Idiopathic Pulmonary Fibrosis: What do we Know about the Role of Occupational and Environmental Determinants? A Systematic Literature Review and Meta-Analysis.

The objectives of this systematic review of original articles published up until August 2021 and meta-analyses were to identify the links between occupational and non-occupational environmental exposures, types of occupations and idiopathic pulmonary fibrosis (IPF). Sixteen selected case-control studies were qualified as good level with Newcastle-Ottawa quality assessment scale. Sensitivity analyses highlighted the role of choice of control group, tobacco adjustment and diagnostic tools. Significantly increased risks of IPF were observed (OR (95%CI): for metals (1.42(1.05-1.92)), wood (OR:1.32(1.02-1.71)), and general dust (OR:1.32(1.08-1.63)) exposures. Subgroup analyses found a significantly elevated risk for: hardwood (OR:1.75 (1.13-2.70)), organic dusts (OR:1.72 (1.20-2.46)) and pesticides (OR:2.30 (1.30-4.08)), while no significant change was noted for softwoods and solvents. Smoking adjustments: general dust (1.45 (1.04-2.03)/organic dust (2.5 (1.49-4.22)/metals (1.87 (1.16-3)/wood dust OR: 1.16 (0.86-1.61)/pesticide exposure 2.4 (0.84-6.9) were calculated. Among agricultural workers, the risk was also increased (OR:2.06 (1.02-4.16)). Few environmental data were available and no significant associations detected. Thus, these meta-analyses highlighted the role of some occupational exposures in IPF occurrence. A more accurate and thorough assessment of exposures over the entire working life as well as on the duration and intensity of exposure and complex of multi-pollutant exposure is needed in future research and clinical practice.

Occupational and non-occupational attributable risk of asbestos exposure for malignant pleural mesothelioma.

OBJECTIVES: To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure. METHODS: A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression. RESULTS: A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1 f/mL-year vs. 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10 f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI -33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women. CONCLUSIONS: Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women.

Occupational allergic contact dermatitis and major allergens in France: temporal trends for the period 2001-2010.

BACKGROUND: Occupational allergic contact dermatitis (OACD) is one of the most common occupational skin diseases in developed countries, but data about its temporal trends in incidence remain sparse. OBJECTIVES: The aim of this study is to describe OACD trends in terms of industrial activities and main causal agents in France over the period 2001-2010. MATERIALS AND METHODS: Data were collected from the French National Network of Occupational Disease Vigilance and Prevention (RNV3P, Réseau National de Vigilance et de Prévention des Pathologies Professionnelles). All OACD considered probably or certainly associated with an occupational exposure were included in the study. Trends were examined (i) on annual crude numbers of OACD and (ii) on reported odds ratios of OACD calculated using logistic regression models. RESULTS: Overall, 3738 cases of OACD were reported and the mean age of OACD cases was 35 years, 52% being women. The most frequent occupations were hairdressers, health care workers, cleaning staff and masons. The total number of OACD cases remained stable over the study period, but increases in OACD related to isothiazolinones (P = 0·002), epoxy resins (P = 0·012) and fragrances (P = 0·005) were observed. Conversely, decreases were noted for cement compounds (P = 0·002) and plant products (P = 0·031). These trends highlight specific sectors and exposures at risk of OACD. CONCLUSIONS: Trends in OACD depend on the nature of exposure. Observed decreases were consistent with prevention measures taken during the study period, and the increases observed serve to highlight those areas where preventative efforts need to be made to reduce skin allergies in the workplace.

[The French mesothelioma network from 1998 to 2013]. / Mésothéliome: les dispositifs en place en France « le réseau mésothéliome ¼ 1998-2013.

Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.

[Compensation for occupational diseases after tomodensitometry screening for benign pleuro-pulmonary disease in a multiregional post-occupational medical surveillance program of asbestos-exposed retired workers]. / Déclaration et reconnaissance en maladie professionnelle après dépistage tomodensitométrique de maladies pleuropulmonaires bénignes dans le programme multirégional de surveillance postprofessionnelle de personnes exposées à l'amiante.

BACKGROUND: Underreporting of occupational diseases related to asbestos exposure remains a matter of concern in France. The aim of this study was to evaluate the number of claims for compensation for asbestos-related non-malignant pulmonary or pleural occupational disease in subjects having undergone a chest CT-scan in a multiregional screening programme. METHODS: Among the 5444 voluntary retired asbestos-exposed subjects recruited in four regions between 2003 and 2005 who had undergone a chest CT-scan, the number of claims for compensation for an asbestos-related pulmonary or pleural benign disease was analysed in 2006 and 2010. RESULTS: Following CT-scan screening, 17.2% of participants were acknowledged as presenting with an asbestos-related non-malignant occupational disease, essentially pleural plaques, by the French National Health Insurance fund. Underreporting decreased as duration of follow-up after CT-scan increased. Nevertheless, 4 years after CT-scan, underreporting was still as high as 36% for subjects identified as presenting with pleural plaques. Mean duration between the date of CT-scan and the date of recognition as occupational disease was 7.4 months, shorter in cases where screening was coordinated by specialized centres. CONCLUSION: A plan of action for an easier claiming process for compensation of asbestos-related diseases is desired. This could probably be obtained through improved sensitization of physicians engaged in the follow-up of asbestos-exposed subjects, and by standardization of the interpretation and reporting of asbestos-related abnormalities observed on chest CT-scans.

[The determinants of under-reporting occupational diseases. The case of mesothelioma]. / Les déterminants de la sous-déclaration des maladies professionnelles. Le cas du mésothéliome.

BACKGROUND: Despite widespread press coverage of the harm caused by the asbestos, 40% of mesothelioma patients still do not file claims for compensation as an occupational disease. We aimed at studying elements that influence the administrative procedure of compensation, in particular social classes and instruction level. METHODS: This was a statistical analysis of data from the French national survey program of mesothelioma designed to understand social determinants of reporting occupational illness. Data from a give administrative district were then submitted to a qualitative study using in-depth interviews of patients with suspected mesothelioma. Discourse analysis was then applied to the corpus of information collected. Content analysis grouped the data into themes. RESULTS: The statistical analyses tended to show that the higher the educational level, the less often patients filed claims for their occupational disease. Manual workers asked for compensation for their disease more often than executives. The interviews conducted with suspected mesothelioma patients suggest several factors explaining these findings. The process of reporting an occupational disease is often initiated by the primary care physician who informs the patient about the possible link with a previous occupation, explains the procedure and motivate the patient whose main preoccupation is to fight against the illness, and less so to become recognized as a victim. In this context, the physician plays a fundamental role, independently of the patient's social status. CONCLUSION: Those results throw new light on the complexity of the administrative procedure for reporting occupational diseases in France and highlights possible causes of underdeclaration reporting. Physician awarness of these causes might improve identification of links between occupation and disease and the transmission of adapted information to all concerned patients in order to fight more effectively against the disparities resulting from underreporting.

[A definition of work-related asthma and its social and occupational consequences in adults and teenagers]. / Définition de l'asthme en relation avec le travail et ses conséquences sociales et professionnelles chez l'adulte et l'adolescent.

Work-related asthma (WRA) accounts for 10-25% of all adult asthma. It therefore seems important to raise questions regarding an asthmatic's approach to occupational or job training activities. WRA takes on two forms: work-exacerbated asthma (WEA) and occupational asthma (OA), which encompasses different subtypes of heterogeneous mechanisms. It currently represents a major challenge for occupational medicine in terms of detailed diagnosis, social care, the economic repercussions for workers and employers and, last but not least, social insurance. This review aims to sensitize health care practitioners to the peculiarities of WRA management in routine practice. More specifically, prognosis depends on early diagnosis, medical care and work adjustment measures. WEA and OA are explained in detail in view of identifying causative agents and at-risk occupations and defining adapted medical strategy. Relevant lines of questioning and complementary exams are presented. In addition, the key role of the occupational physician, especially as regards recognition and identification of occupational disease, is underlined, the objective being to facilitate optimal professional and social management. In future studies, the key role of counseling and orientation mechanisms should be highlighted as means of preventing WRA occurrence.

Evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005.

The evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005 was analysed using data derived from the French network of cancer registries (FRANCIM) and the French National Mesothelioma Surveillance Program (PNSM). Mesothelioma proportions in pleural cancers were calculated by diagnosis year in the 1980-2000 period. Our results suggest that the incidences of pleural cancer and mesothelioma levelled off in French men since 2000 and continued to increase in French women. A decrease of the annual pleural cancer incidence average in men was noticed (-3.4% of annual rate of change) between 2000 and 2005. The proportion of pleural cancers that were mesothelioma was unchanged between 1980 and 2003 with an average of 86%. The age standardised incidence rate of pleural mesothelioma remained relatively stable between 1998 and 2005 with a slight falling trend. For women, the age standardised incidence rate of pleural cancers and mesothelioma increased during the period 1998-2005. Additionally, the proportion of pleural cancers that were mesothelioma increased during the same period of time. Finally, the increased trend observed in the incidence of pleural mesothelioma and cancers in women is credibly due to their under diagnosis in the 1980-1997 period. The comparison between the French incidence and the American and British ones shows that the decreasing trend in incidence of mesothelioma and pleural cancers in French men since 2000 is potentially associated with a lower amphibole consumption and by the implementation of safety regulations at work from 1977.

Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare tumour but with increasing incidence and a poor prognosis. In 2008, the European Respiratory Society/European Society of Thoracic Surgeons Task Force brought together experts to propose practical and up-to-dated guidelines on the management of MPM. To obtain an earlier and reliable diagnosis of MPM, the experts recommend performing thoracoscopy, except in cases of pre-operative contraindication or pleural symphysis. The standard staining procedures are insufficient in approximately 10% of cases. Therefore, we propose using specific immunohistochemistry markers on pleural biopsies. In the absence of a uniform, robust and validated staging system, we advice use of the most recent TNM based classification, and propose a three step pre-treatment assessment. Patient's performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM. Other potential parameters should be recorded at baseline and reported in clinical trials. MPM exhibits a high resistance to chemotherapy and only a few patients are candidates for radical surgery. New therapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach should be included in a prospective trial at a specialised centre.

Characterization of particles emitted by incense burning in an experimental house.

The potential health effects of fine and ultrafine particles are of increasing concern. A better understanding of particle characteristics and dispersion behavior is needed. This study aims at characterizing spatial and temporal variations in fine and ultrafine particle dispersion after emission from a model source in an experimental house. Particles emitted by an incense stick burning for 15 min were characterized. Number concentration, specific surface area and mass were measured. Partial chemical analysis of particles was also realized. Near the burning incense stick, the maximum concentration was 25,500 particles/cm(3); the indoor PM(2.5) concentration reached 197 microg/m(3), and the specific surface area concentration was 180 microm(2)/cm(3). The estimated incense smoke density was 1.1 g/cm(3). Time of Flight Aerosol Mass Spectrometer measurements indicated that the organic fraction was predominant in the aerosol mass detected, and other minor components identified were K(+), NO(3)(-), and Cl(-). The combustion of an incense stick in the living room was associated with significant modifications of the concentrations of particles measured in the different rooms of the house. This demonstration of pollution by particle dispersion by a model source of moderate intensity may have significant implications in terms of assessment of indoor exposure to such particles. Practical Implications The particles emitted in a domestic environment by a source of moderate intensity such as burning incense disperse throughout the house, even in rooms with closed doors and in rooms as far away as the next floor. This dispersion has significant implications in terms of evaluating human indoor exposure to fine and ultrafine particles.

Pleural plaques and asbestosis: dose- and time-response relationships based on HRCT data.

Most studies on asbestos-related diseases are based on chest radiographs, and dose-response relationships are still controversial. The aim of this study was to describe the most relevant parameters of asbestos exposure linked to pleural plaques and asbestosis diagnosed by high-resolution computed tomography (HRCT). A large screening programme including systematic HRCT examinations was organised from 2003 to 2005 in France for formerly asbestos-exposed workers. The time since first exposure (TSFE), level, duration and cumulative exposure to asbestos were used in adjusted unconditional logistic regression to model the relationships of the two diseases. Analysis of a population of 5,545 subjects demonstrated that TSFE (p<0.0001) and cumulative exposure (p = 0.02) (or level, depending on the models used), were independently associated with the frequency of pleural plaques. Only cumulative exposure (p<0.0001) or level of exposure (p = 0.02) were significantly associated with asbestosis. All trend tests were significant for these parameters. To date and to our knowledge, this study is the largest programme based on HRCT for the screening of asbestos-exposed subjects. Both time-response and dose-response relationships were demonstrated for pleural plaques, while only dose-response relationships were demonstrated for asbestosis. These parameters must be included in the definition of high-risk populations for HRCT-based screening programmes.

[Asbestos-related cancer risk in the presence of asbestosis or pleural plaques]. / Risque de cancer lié à l'amiante en présence d'asbestose ou de plaques pleurales.

INTRODUCTION: The relationships between benign asbestos-related diseases (asbestosis and pleural plaques) and thoracic cancers are still debated. The aim of this paper is to analyse epidemiological data which investigate this topic. STATE OF THE ART: Published studies show that there is a significant relationship between occupational exposure to asbestos and lung cancer risk, even in the absence of abnormalities consistent with asbestos exposure on postero-anterior chest x-ray. In subjects with occupational exposure to asbestos, an increased risk of lung cancer and pleural mesothelioma is observed in subjects with pleural plaques on chest x-ray, in comparison with the general population. In exposed subjects with similar cumulative exposure to asbestos, it is not demonstrated that pleural plaques are associated with an increased risk of lung cancer or pleural mesothelioma. PERSPECTIVES: All the analysed studies are only based on radiographic data. Their results must be confirmed by additional studies including a rigorous evaluation of the cumulative exposure to asbestos and chest CT-scans. CONCLUSION: In the present state of knowledge, isolated pleural plaques do not justify specific medical surveillance, as compared to that required by the mere estimated cumulative exposure to asbestos.

[Psychological impacts of follow up for occupational asbestos exposure. Consequences after compensation for occupational disease in the SPP-A cohort]. / Impact psychologique du suivi post-professionnel amiante à long terme. Quelles conséquences après la déclaration suivie de la reconnaissance d'une maladie professionnelle chez des sujets de la cohorte SPP-A ?

INTRODUCTION: In France, long-term follow-up after occupational exposure to asbestos is recommended. This study looked at the psychological consequences in the longer term following a CT-scan, in particular the impact of having received compensation for an occupational disease. METHODS: As part of an asbestos post-exposure survey study (APExS), volunteers from Normandy were asked to complete self-assessment questionnaires about their psychological condition at different points during follow-up, including a psychological questionnaire before, then 6 months, and finally 18 to 24 months after their chest CT-scan. Information collected from 622 individuals were analyzed based on information provided as to the result of the screening and whether they had received compensation for having an occupational disease. RESULTS: The identification of an occupational disease eligible for compensation is associated with a long term increase in psychological distress. The impact of psychological state during follow-up is greater in men who reported receiving occupational disease compensation. The discovery of an asbestos-related disease during the screening is associated with a negative perception of general health and an increase in psychological distress. CONCLUSION: The receipt of compensation of an occupational disease does not seem to compensate for the negative psychological impact related to the discovery of a disease during the asbestos post-exposure follow-up.

[Evaluation of permanent disability levels in occupational pulmonary diseases]. / Comment évaluer en 2019 les taux d'incapacité permanente des pathologies professionnelles pulmonaires ?

Compensation for occupational pulmonary diseases requires the establishment of guidelines based on standardized and objective criteria, in order to provide compensation that is as fair as possible to patients who suffer from them. A review of the elements necessary for the examination of an individual file was carried out by a working group. It is accepted that respiratory functional exploration is the key element in assessing the level of permanent disability in all of these conditions, with the exception of thoracic malignancies. Guiding scales have been developed for the respiratory impairment of three types of conditions: occupational asthma, thoracic malignancy, and other respiratory diseases. Additional criteria for increasing the permanent disability level are also proposed in order to take into account professional prejudice, in particular the possibility or not of continuing the occupational activity, in the same job or after changing to another. For certain respiratory diseases, a periodic reassessment of the initially attributed permanent disability level is recommended as well as the initial one at the time of definitive cessation of occupational activity.

Anthracofibrosis attributed to mixed mineral dust exposure: report of three cases.

Anthracofibrosis, defined as bronchial luminal narrowing with black pigmentation of the overlying mucosa, has been attributed to tuberculosis. Three patients with anthracofibrosis without mycobacterial infection are described who had previous occupational exposure to mixed dusts. CT scans showed calcified hilar lymph nodes in two patients. Surgical biopsy in one patient and autopsy in another revealed fibrotic lymph nodes with black pigmentation. Mineralogical analysis by transmission electron microscopy of pulmonary, hilar and/or bronchial samples found high levels of particle retention, raised percentages of free crystalline silica and mica in two patients, and free crystalline silica, kaolin and other silicates in the third. No evidence of any other contributory factor was found, suggesting that mixed mineral dust was the most probable cause. These observations suggest that exposure to mixed mineral dust should be added to the aetiology of anthracofibrosis.

[Etiology, epidemiology, biology. Occupational respiratory cancers]. / Cancers respiratoires professionnels.

Lung cancer and pleural mesothelioma are the most common occupational cancers. Recent epidemiological studies have estimated that the fraction attributable to occupational factors varies from 13 to 29% for lung cancer in men and is about 85% for pleural mesothelioma in men. Previous occupational exposure to asbestos is the most common occupational exposure in these cancers. Mesothelioma immediately leads the clinician to look for past asbestos exposure. In contrast, the search for an occupational exposure that should be routine in all cases of lung cancer, is generally more difficult because of the number of occupational aetiological factors and the absence of criteria that allow distinction of an occupational cancer from a tobacco related one. Therefore attention should be paid to the identification of occupational exposure in order to set up primary prevention programmes to prevent exposure still present in the working environment and, on the other hand, to identify the subjects entitled to the acknowledgement of occupational disease and/or to obtain the compensation available to asbestos victims.

[Occupational respiratory cancers]. / Cancers respiratoires professionnels.

Lung cancer and pleural mesothelioma are the most common occupational cancers. Recent epidemiological studies have estimated that the fraction attributable to occupational factors varies from 13 to 29% for lung cancer in men and is about 85% for pleural mesothelioma in men. Previous occupational exposure to asbestos is the most common occupational exposure in these cancers. Mesothelioma immediately leads the clinician to look for past asbestos exposure. In contrast, the search for an occupational exposure that should be routine in all cases of lung cancer, is generally more difficult because of the number of occupational aetiological factors and the absence of criteria that allow distinction of an occupational cancer from a tobacco related one. Therefore attention should be paid to the identification of occupational exposure in order to set up primary prevention programmes to prevent exposure still present in the working environment and, on the other hand, to identify the subjects entitled to the acknowledgement of occupational disease and/or to obtain the compensation available to asbestos victims.

New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center.

INTRODUCTION: The 2015 WHO classification of tumors categorized malignant mesothelioma into epithelioid, biphasic (BMM), and sarcomatoid (SMM) for prognostic relevance and treatment decisions. The survival of BMM is suspected to correlate with the amount of the sarcomatoid component. The criteria for a sarcomatoid component and the interobserver variability between pathologists for identifying this component are not well described. In ambiguous cases, a "transitional" (TMM) subtype has been proposed but was not accepted as a specific subtype in the 2015 WHO classification. The aims of this study were to evaluate the interobserver agreement in the diagnosis of BMM, to determine the nature and the significance of TMM subtype, and to relate the percentage of sarcomatoid component with survival. The value of staining for BRCA-1-associated protein (BAP1) and CDKN2A(p16) fluorescence in situ hybridization (FISH) were also assessed with respect to each of the tumoral components. METHODS: The study was conducted by the International Mesothelioma Panel supported by the French National Cancer Institute, the network of rare cancer (EURACAN) and in collaboration with the International Association for the Study of Lung Cancer (IASLC). The patient cases include a random group of 42 surgical biopsy samples diagnosed as BMM with evaluation of SMM component by the French Panel of MESOPATH experts was selected from the total series of 971 BMM cases collected from 1998 to 2016. Fourteen international pathologists with expertise in mesothelioma reviewed digitally scanned slides (hematoxylin and eosin - stained and pan-cytokeratin) without knowledge of prior diagnosis or outcome. Cases with at least 7 of 14 pathologists recognizing TMM features were selected as a TMM group. Demographic, clinical, histopathologic, treatment, and follow-up data were retrieved from the MESOBANK database. BAP1 (clone C-4) loss and CDKN2A(p16) homozygous deletion (HD) were assessed by immunohistochemistry (IHC) and FISH, respectively. Kappa statistics were applied for interobserver agreement and multivariate analysis with Cox regression adjusted for age and gender was performed for survival analysis. RESULTS: The 14 panelists recorded a total of 544 diagnoses. The interobserver correlation was moderate (weighted Kappa = 0.45). Of the cases originally classified as BMM by MESOPATH, the reviewers agreed in 71% of cases (385 of 544 opinions), with cases classified as pure epithelioid in 17% (93 of 544), and pure sarcomatoid in 12% (66 of 544 opinions). Diagnosis of BMM was made on morphology or IHC alone in 23% of the cases and with additional assessment of IHC in 77% (402 of 544). The median overall survival (OS) of the 42 BMM cases was 8 months. The OS for BMM was significantly different from SMM and epithelioid malignant mesothelioma (p < 0.0001). In BMM, a sarcomatoid component of less than 80% correlated with a better survival (p = 0.02). There was a significant difference in survival between BMM with TMM showing a median survival at 6 months compared to 12 months for those without TMM (p < 0.0001). BAP1 loss was observed in 50% (21 of 42) of the total cases and in both components in 26%. We also compared the TMM group to that of more aggressive patterns of epithelioid subtypes of mesothelioma (solid and pleomorphic of our large MESOPATH cohort). The curve of transitional type was persistently close to the OS curve of the sarcomatoid component. The group of sarcomatoid, transitional, and pleomorphic mesothelioma were very close to each other. We then considered the contribution of BAP1 immunostaining and loss of CDKN2A(p16) by FISH. BAP1 loss was observed in 50% (21 of 41) of the total cases and in both component in 27% of the cases (11 of 41). There was no significant difference in BAP1 loss between the TMM and non-TMM groups. HD CDKN2A(p16) was detected in 74% of the total cases with no significant difference between the TMM and non-TMM groups. In multivariate analysis, TMM morphology was an indicator of poor prognosis with a hazard ratio = 3.2; 95% confidence interval: 1.6 - 8.0; and p = 0.003 even when compared to the presence of HD CDKN2A(p16) on sarcomatoid component (hazard ratio = 4.5; 95% confidence interval: 1.2 - 16.3, p = 0.02). CONCLUSIONS: The interobserver concordance among the international mesothelioma and French mesothelioma panel suggests clinical utility for an updated definition of biphasic mesothelioma that allows better stratification of patients into risk groups for treatment decisions, systemic anticancer therapy, or selection for surgery or palliation. We also have shown the usefulness of FISH detection of CDKN2A(p16) HD compared to BAP1 loss on the spindle cell component for the separation in ambiguous cases between benign florid stromal reaction from true sarcomatoid component of biphasic mesothelioma. Taken together our results further validate the concept of transitional pattern as a poor prognostic indicator.

Computed tomography findings in urban transportation workers with low cumulative asbestos exposure.

OBJECTIVE: To assess the frequency of computed tomography (CT) scan pleural and interstitial changes in a population of urban transportation workers with low cumulative exposure to asbestos, and to measure inter-reader agreement. DESIGN: A total of 269 male volunteers (mean age 54.0 +/- 2.3 years, mean estimated cumulative exposure index 1.7 +/- 2.3 fibres/ml-years), underwent a CT scan which was read independently by three experienced readers, with further consensus reading in case of pleural or parenchymal abnormalities. Inter-reader agreement was assessed by means of Kappa statistic. RESULTS: On consensus reading, four subjects had interstitial opacities, three had diffuse pleural thickening and 26 (9.7%) had pleural plaques that were unilateral in 65% of cases and < or =2 mm thick in 54% of cases. No correlation was observed between pleural plaques and latency, duration of exposure or cumulative exposure. The inter-reader agreement for the detection of pleural abnormalities was fair. CONCLUSION: In this relatively young population with low cumulative exposure to asbestos, the prevalence of pleural abnormalities was low. These abnormalities were very limited in thickness and extent, leading to marked inter-reader variability and making it difficult to assess their relationship to asbestos exposure.