Pietro Gino Barbieri

Survival of peritoneal malignant mesothelioma in Italy: a population-based study.

In some population‐based studies, a shorter median survival was observed in peritoneal as compared with pleural, malignant mesothelioma, but in others, longer median survival times or higher proportions of long‐term survivors were reported. Statistical instability could have caused these differences. We analyzed survival in peritoneal mesothelioma in a large and unselected population‐based case series. Cases (338) registered from 1990 to 2001 by 9 Italian regional mesothelioma registries contributing to the network of the National Mesothelioma Registry were followed until December 31, 2005. Univariate (Kaplan‐Meier) and multivariate (Cox proportional hazards regression) analyses of survival were performed according to selected individual characteristics, including limited treatment information in a subset of 194 cases. The results were compared with those obtained in a parallel study on pleural mesothelioma cases. Epithelioid histotype, younger age at diagnosis and, to a lesser degree, gender (women), and being diagnosed in a hospital with a thoracic surgery unit positively and significantly affected survival. The effect of treatment was positive but not statistically significant. No trend in the risk of death according to calendar period of diagnosis was present. Peritoneal mesothelioma cases had shorter median survival time than pleural cases, but a larger proportion of long‐term survivors. Survival patterns after peritoneal and pleural mesothelioma differed markedly. Treatment was not associated with a statistically significant improvement in survival, but our study included cases first diagnosed before the introduction of the most recent therapeutic approaches. This provides a large historical comparison for future studies on survival trends at the population level.

Asbestos Fibre Burden in the Lungs of Patients with Mesothelioma Who Lived Near Asbestos-Cement Factories

BACKGROUND Epidemics of malignant mesothelioma are occurring among inhabitants of Casale Monferrato and Bari never employed in the local asbestos-cement (AC) factories. The mesothelioma risk increased with proximity of residence to both plants. OBJECTIVES To provide information on the intensity of environmental asbestos exposure, in the general population living around these factories, through the evaluation of the lung fibre burden in mesothelioma patients. METHODS We analysed by a scanning electron microscope equipped with X-ray microanalysis wet (formalin-fixed) lung tissue samples from eight mesothelioma patients who lived in Casale Monferrato or Bari and underwent surgery. Their occupational and residential history was obtained during face-to-face interviews. Semi-quantitative and quantitative indices of cumulative environmental exposure to asbestos were computed, based on residential distance from the AC plants and duration of stay. RESULTS The lung fibre burden ranged from 110 000 to 4 300 000 fibres per gram of dry lung (f/g) and was >1 000 000 f/g in three subjects. In four cases, only amphibole fibres were detected. Environmental exposures had ceased at least 10 years before samples were taken. No patient had other definite or probable asbestos exposures. A linear relationship was observed between the lung fibre burden and all three indices of environmental cumulative exposure to asbestos. CONCLUSIONS Environmental exposure to a mixture of asbestos fibres may lead to a high lung fibre burden of amphiboles years after exposure cessation. The epidemiological evidence of an increased mesothelioma risk for the general population of Casale Monferrato and Bari, associated with asbestos contamination of the living environment, is corroborated.

Effects of combined therapies on the survival of pleural mesothelioma patients treated in Brescia, 1982-2006

AIMS AND BACKGROUND During the 1990s, the traditional unimodal treatments (surgery, radiotherapy, chemotherapy, immunotherapy) for malignant pleural mesothelioma started to be combined in bimodal or multimodal strategies. However, recent population-based analyses of the survival of patients with malignant pleural mesothelioma indicate that even these treatments have not led to significant improvements in prognosis, which remains very poor. The present study assessed the survival of patients given combined treatments and multimodal therapies in a specialized hospital department. METHODS The study population comprised 530 patients diagnosed with malignant pleural mesothelioma from 1982 to 2006: 343 of them were residents in the province of Brescia (Lombardy, Northern Italy) and 187 were residents outside the province, with a follow-up to 31 December 2009. Kaplan-Meier survival analyses and Cox proportional risks model were used to test sex, age at diagnosis, histological type and treatments, as prognostic factors. RESULTS The estimated median survival for the whole group of patients was 317 days (257 for residents and 398 for non-residents), and respectively 310 and 340 days in the groups diagnosed in the periods 1982-2000 and 2001-2006. Multivariate analysis confirmed that the prognosis was better for younger patients and cases of epithelioid type malignant pleural mesothelioma, whereas for patients receiving any single treatment the prognosis was not significantly better than for those given palliative care alone. However, patients receiving combined treatments or the multimodality approach had significantly longer median survival and the relative risk of death was respectively 0.57 and 0.61 compared to untreated patients (or those only given symptomatic therapy). CONCLUSIONS This is the first study in Italy to assess the effectiveness of different treatment approaches in a significant number of patients treated in one hospital. Further studies are needed to confirm the improvement in prognosis - even if modest--on larger numbers of patients and taking into account the different stages of the disease.

Residual fibre lung burden among patients with pleural mesothelioma who have been occupationally exposed to asbestos

Objectives To evaluate the lungs asbestos fibres concentration in participants with malignant pleural mesothelioma (MPM) who have been occupationally exposed. Methods The lung samples were obtained from pleuropneumonectomies or autopsies of 271 male MPMs. The lung samples were examined through scanning electron microscopy. Retrospective assessment was used to assess for asbestos exposure. This study includes 248 MPMs with an occupational exposure defined as either ‘definite’ or ‘probable’ or ‘possible’. Results The participants had finished working in asbestos exposure conditions more than 20 years ago (on average 26.1±11.0 years). The fibre burden resulted with a geometric mean equal to 2.0 (95% CI 1.6 to 2.4) million fibres per gram of dry lung tissue. The burden was higher among participants employed in asbestos textiles industry and in shipyards with insulation material, if compared with construction workers or non-asbestos textile workers or participants working in chemicals or as auto mechanics. 91.3% of MPMs had a detectable amount of amphibole fibres. A strong lung clearance capability was evident among workers exposed to chrysotile fibres. Owing to that, the 1997 Helsinki Criteria for occupational exposure were reached in <35% of cases among participant working in construction, in metallurgical industry, in chemical or textile industry and among those performing brake repair activities. Conclusions The MPM cases are now occurring in Italy in participants who ceased occupational asbestos exposure decades before the analysis. A large majority still shows a residual content of amphibole fibres, but given the lung clearance capability, attribution to occupational exposure cannot rely only on fibres detection.

On the diagnosis of malignant pleural mesothelioma: A necropsy-based study of 171 cases (1997–2016)

Background: Malignant pleural mesothelioma (MPM) diagnosis is known to be difficult. We report on the diagnostic elements available in life in an MPM necropsy case series and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices. Methods: We reviewed pathologic and clinical records of an unselected series of autopsies (1977–2016) in patients with MPM employed in the Monfalcone shipyards or living with shipyard workers. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings, with and without immunophenotyping. Results: Data on 171 cases were available: for 169, autopsy confirmed the MPM diagnosis. In life, 119 cases had histologic confirmation of diagnosis, whereas 7 were negative; all cases without immunophenotypization were autoptic MPMs. Cytology alone had been positive in 18 autoptic MPM cases, negative in 14. Radiologic imaging alone had been positive in another 16, negative in 11. In the 2 cases not confirmed at autopsy, MPM had been suspected by chest computed tomography only. Bilateral pleural plaques were found in 144 and histologic evidence of asbestosis in 62 cases. Conclusions: Autopsies confirmed 169/171 cases, including cases that would not be considered as certain based on diagnosis in life. Radiologic imaging, cytologic examination of pleural effusions, or both combined had low sensitivity but high positive predictive value: when they are positive, proceeding to thoracoscopy should be justified. MPM has been correctly diagnosed even without immunohistochemistry. The prevalence of pleural plaques and asbestosis was high due to severity of asbestos exposures in these cases.

0362 Risk of pleural mm and residual asbestos burden in the lung: a retrospective case-control study

Introduction Results of Malignant Pleural Mesothelioma (MPM) occurrence (mortality and incidence) by cumulative exposure dose clearly showed a proportional relation of MPM risk with dose, confirmed among studies by fibre burden. We evaluated the association between residual fibre content and MPM risk by circumstance of asbestos exposure. Methods and materials Lung samples obtained from pleuro-pneumonectomies or autopsies (349 MPMs, and 41 controls) among subjects investigated for probability and circumstance of asbestos exposure were examined through Scanning Electron Microscopy; 291 cases had an occupational asbestos exposure, 38 MPMs a non-occupational exposure (familiar or environmental), whereas among 20 MPM an asbestos exposure was not identified. The MPM risk was evaluated by means of Odds Ratio (OR). Results The residual asbestos fibre burden was higher among MPMs occupationally exposed (Geometric Mean:2.10 Million fibres/gram of dried tissue; 95% CI:1.5–2.58) in comparison with non-occupational (GM:0.66 Mff/gdt; 95% CI:0.47–0.95) or with unknown exposures (GM:0.59 Mff/gdt; 95% CI:0.34–1.03) and controls (GM:0.26 Mff/gdt; 95% CI:0.20–0.34). Among occupationally exposed, the MPM risk increased according to the asbestos fibre burden reaching an OR of 36.8 (95%CI:11.9–113.5) for concentrations higher than 1 Mff/g dt, compared to the reference level (<0.25 Mff/gdt). Higher ORs were observed at any concentration of amphibole fibres in comparison those for chrysotile fibres. Conclusions The MPM risk was strongly associated to the residual asbestos fibre lung burden. The MPM risk due to non-occupational exposure shows a magnitude comparable with that with unknown asbestos exposures. The residual lung burden of chrysotile is strongly influenced by clearance and time since exposures ceased.