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Context.—: Pleural mesothelioma is a rare cancer with an often-challenging diagnosis because of its potential to be a great mimicker of many other tumors. Among them, primary lung and breast cancers are the 2 main causes of pleural metastasis. The development and application of targeted therapeutic agents have made it even more important to achieve an accurate diagnosis. In this setting, international guidelines have recommended the use of 2 positive and 2 negative immunohistochemical biomarkers., Objectives.—: To define the most highly specific and sensitive minimum set of antibodies for routine practice to use for the separation of epithelioid malignant mesothelioma from lung and breast metastasis and to determine the most relevant expression cutoff., Design.—: To provide information at different levels of expression of 16 mesothelial and epithelial biomarkers, we performed a systematic review of articles published between 1979 and 2017, and we compared those data to results from the Mesothelioma Telepathology Network (MESOPATH) of the standardized panel used in routine practice database since 1998., Results.—: Our results indicate that the following panel of markers-calretinin (poly)/thyroid transcription factor 1 (TTF-1; clone 8G7G3/1) and calretinin (poly)/estrogen receptor-α (ER-α; clone EP1)-should be recommended; ultimately, based on the MESOPATH database, we highlight their relevance which are the most sensitive and specific panel useful to the differential diagnosis at 10% cutoff., Conclusions.—: Highlighted by their relevance in the large cohort reported, we recommend 2 useful panels to the differential diagnosis at 10% cutoff. more...

Background: Peritoneal malignant mesothelioma is a rare disease for which few population-based studies are available. The aim of this study was to describe the evolution of the incidence and survival of peritoneal malignant mesothelioma in France between 1989 and 2015, using data derived from the French network of cancer registries., Methods: Age world-standardized incidence rates and overall survival were calculated using data from 16 French cancer registries. Log-linear Poisson regression analysis was used to estimate the average annual percentage change in incidence rates. Overall survival was performed using age-adjusted Cox proportional hazards model., Results: In French men, the incidence has increased quietly over the reporting period from 0.07 to 0.10 with a maximum of 0.16 per 100,000 persons-years in 2001-2003. For women, the increase in incidence has been lower than for men over the period 1989-2015, ranging from 0.04 to 0.11. A better prognosis was associated with a diagnosis made after 2000 (HR = 1.76; p = 0.013), the epithelioid histological type (p = 0.003), and the fact of being a woman, which has a 5-year risk of death half that of men (HR = 0.55; p = 0.001), regardless of age, diagnosis period or histology., Conclusion: Our results are similar to those currently available for other countries. In France, peritoneal mesothelioma remains a rare and fatal cancer with a small increase in the incidence rate since 1989 and a median survival of 1 year; it seemed to develop equally in women and men over this period of time., (Copyright © 2019 Elsevier Ltd. All rights reserved.) more...

Objective: The aim of our study was to estimate the incidence of digestive cancers within a cohort of asbestos-exposed workers., Methods: Our study was based on a cohort of 2024 participants occupationally exposed to asbestos. The incidence of digestive cancers was calculated from 1 January 1978 to 31 December 2009 and compared with levels among the local general population using Standardised Incidence Ratios (SIRs). Asbestos exposure was assessed using the company's job-exposure matrix., Results: 119 cases of digestive cancer were observed within our cohort, for an expected number of 77 (SIR=1.54 (1.28 to 1.85)). A significantly elevated incidence was observed for peritoneal mesothelioma, particularly in women. Significantly elevated incidences were also observed among men for: all digestive cancers, even when excluding peritoneal mesothelioma (SIR=1.50 (1.23 to 1.82)), oesophageal cancer (SIR=1.67 (1.08 to 2.47)) and liver cancer (SIR=1.85 (1.09 to 2.92)). Concerning colorectal cancer, a significant excess of risk was observed for men with exposure duration above 25 years (SIR=1.75 (1.05 to 2.73))., Conclusions: Our results are in favour of a link between long-duration asbestos exposure and colorectal cancer in men. They also suggest a relationship between asbestos exposure and cancer of the oesophagus in men. Finally, our results suggest a possible association with small intestine and liver cancers in men., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.) more...

Given the interest in defining biomarkers of asbestos exposure and to provide insights into asbestos-related and cell-specific mechanisms of neoplasia, the identification of gene alterations in asbestos-related cancers can help to a better understanding of exposure risk. To understand the aetiology of asbestos-induced malignancies and to increase our knowledge of mesothelial carcinogenesis, we compared genetic alterations in relevant cancer genes between lung cancer, induced by asbestos and tobacco smoke, and malignant pleural mesothelioma (MPM), a cancer related to asbestos, but not to tobacco smoke. TP53, KRAS, EGFR and NF2 gene alteration analyses were performed in 100 non-small cell lung cancer (NSCLC) patients, 50 asbestos-exposed and 50 unexposed patients, matched for age, gender, histology and smoking habits. Detailed assessment of asbestos exposure was based on both specific questionnaires and asbestos body quantification in lung tissue. Genetic analyses were also performed in 34 MPM patients. TP53, EGFR and KRAS mutations were found in NSCLC with no link with asbestos exposure. NF2 was only altered in MPM. Significant enhancement of TP53 G:C to T:A transversions was found in NSCLC from asbestos-exposed patients when compared with unexposed patients (P = 0.037). Interestingly, TP53 polymorphisms in intron 7 (rs12947788 and rs12951053) were more frequently identified in asbestos-exposed NSCLC (P = 0.046) and MPM patients than in unexposed patients (P < 0.001 and P = 0.012, respectively). These results emphasise distinct genetic alterations between asbestos-related thoracic tumours, but identify common potential susceptibility factors, i.e. single nucleotide polymorphisms in intron 7 of TP53. While genetic changes in NSCLC are dominated by the effects of tobacco smoke, the increase of transversions in TP53 gene is consistent with a synergistic effect of asbestos. These results may help to define cell-dependent mechanisms of action of asbestos and identify susceptibility factors to asbestos. more...

Background: The association between pleural plaques and pleural mesothelioma remains controversial. The present study was designed to examine the association between pleural plaques on computed tomography (CT) scan and the risk of pleural mesothelioma in a follow-up study of asbestos-exposed workers., Methods: Retired or unemployed workers previously occupationally exposed to asbestos were invited to participate in a screening program for asbestos-related diseases, including CT scan, organized between October 2003 and December 2005 in four regions in France. Randomized, independent, double reading of CT scans by a panel of seven chest radiologists focused on benign asbestos-related abnormalities. A 7-year follow-up study was conducted in the 5287 male subjects for whom chest CT scan was available. Annual determination of the number of subjects eligible for free medical care because of pleural mesothelioma was carried out. Diagnosis certification was obtained from the French mesothelioma panel of pathologists. Survival regression based on the Cox model was used to estimate the risk of pleural mesothelioma associated with pleural plaques, with age as the main time variable and time-varying exposure variables, namely duration of exposure, time since first exposure, and cumulative exposure index to asbestos. All statistical tests were two-sided., Results: A total of 17 incident cases of pleural mesothelioma were diagnosed. A statistically significant association was observed between mesothelioma and pleural plaques (unadjusted hazard ratio (HR) = 8.9, 95% confidence interval [CI] = 3.0 to 26.5; adjusted HR = 6.8, 95% CI = 2.2 to 21.4 after adjustment for time since first exposure and cumulative exposure index to asbestos)., Conclusion: The presence of pleural plaques may be an independent risk factor for pleural mesothelioma. more...

Background: The aim of this study was to determine the rates of compensation awarded to patients presenting with pleural mesothelioma and factors linked to such compensation in France., Methods: The study population consisted of 2,407 patients presenting with pleural mesothelioma, recorded by the National Mesothelioma Surveillance Programme between January 1, 1999 and December 31, 2009. Analysis of claims for recognition as "occupational disease" (OD) and claims for compensation by the Compensation Fund for Asbestos Victims (FIVA) were analyzed., Results: Approximately 30% of subjects presenting with pleural mesothelioma, affiliated to the General National Health Insurance fund, neither sought recognition as an OD nor claimed for FIVA compensation. Gender, age at diagnosis, type of health insurance, and socio-professional category influence the likelihood of patients presenting with mesothelioma seeking compensation for this disease., Conclusions: Results show an under-compensation of pleural mesothelioma as OD and by the FIVA in France., (Copyright © 2012 Wiley Periodicals, Inc.) more...

As long as the value of screening for cancers related to asbestos is not proven in the population at risk, the medical benefits of follow-up post-professional exposure remain uncertain and the only justification is to answer the questions of anxious retired workers concerning the consequences of their past-exposure and to provide compensation for any abnormalities that are demonstrated. In this country, to answer the questions posed in the title of this contribution in the case of pathologies related to asbestos, it is necessary, after verifying the fact and the level of exposure, to identify the pleural or pulmonary fibrosis and, above all, the pleural plaques, which constitute the essential lesions currently screened for. Thoracic CT scanning without contrast is the examination of choice to achieve this objective. There are, however, two significant problems. On one hand there is a high incidence of pulmonary micronodules, the necessary surveillance of which requires subsequent scans, leading to increased irradiation and anxiety. On the other hand the diagnostic uncertainty concerning discrete lesions is a source of confusion for the persons followed-up. There are, at present, neither scientific criteria to determine the optimum frequency of examination nor any arguments for replacing the pragmatic proposals of the consensus conference of 1999. It is important, therefore, to provide a medical assessment appropriate to the symptoms and anxiety expressed by a person previously exposed to asbestos. Overall it is necessary to question the benefit to the exposed person, in terms of quality of life, of a regular search for lesions that would usually be asymptomatic if not identified. Would it not be more judicious and more equitable to compensate persons whose past-exposure is sufficient to increase significantly their risk of cancer independently of the presence of benign abnormalities., (Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.) more...

Background Although the role of asbestos in the genesis of mesothelioma and primary bronchopulmonary cancers has been established, results from studies focusing on the relationship between occupational exposure to asbestos and digestive cancer remain contradictory. Aim To determine whether occupational asbestos exposure increases the incidence of digestive cancers. Methods Our study was a retrospective morbidity study based on 2024 subjects occupationally exposed to asbestos. The incidence of digestive cancer was calculated from 1st January 1978 to 31st December 2004 and compared with levels among the local general population using Standardized Incidence Ratios. Asbestos exposure was assessed using the company’s job exposure matrix. Results Eighty-five cases of digestive cancer were observed within our cohort, for an expected number of 66.90 (SIR = 1.27 [1.01; 1.57]). A significantly elevated incidence, particularly notable among women, was observed for peritoneal mesothelioma, independently of exposure levels. A significantly elevated incidence was also noted among men for cancer of small intestine and oesophagus, for cumulative exposure indexes for asbestos above 80 fibres/mL × years. A significantly elevated incidence of cancer of the small intestine was also observed among men having been exposed to asbestos for periods in excess of 25 years and for mean exposure levels in excess of 4 fibres/mL. Conclusions This study suggests the existence of a relationship between exposure to asbestos and cancer of the small intestine and of the oesophagus in men. [ABSTRACT FROM AUTHOR] more...