Marina Musti

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.

An electronic nose distinguishes exhaled breath of patients with Malignant Pleural Mesothelioma from controls

BACKGROUND Malignant Pleural Mesothelioma (MPM) is a tumour of the surface cells of the pleura that is highly aggressive and mainly caused by asbestos exposure. Electronic noses capture the spectrum of exhaled volatile organic compounds (VOCs) providing a composite biomarker profile (breathprint). OBJECTIVE We tested the hypothesis that an electronic nose can discriminate exhaled air of patients with MPM from subjects with a similar long-term professional exposure to asbestos without MPM and from healthy controls. METHODS 13 patients with a histology confirmed diagnosis of MPM (age 60.9±12.2 year), 13 subjects with certified, long-term professional asbestos exposure (age 67.2±9.8), and 13 healthy subjects without asbestos exposure (age 52.2±16.2) participated in a cross-sectional study. Exhaled breath was collected by a previously described method and sampled by an electronic nose (Cyranose 320). Breathprints were analyzed by canonical discriminant analysis on principal component reduction. Cross-validated accuracy (CVA) was calculated. RESULTS Breathprints from patients with MPM were separated from subjects with asbestos exposure (CVA: 80.8%, sensitivity 92.3%, specificity 85.7%). MPM was also distinguished from healthy controls (CVA: 84.6%). Repeated measurements confirmed these results. CONCLUSIONS Molecular pattern recognition of exhaled breath can correctly distinguish patients with MPM from subjects with similar occupational asbestos exposure without MPM and from healthy controls. This suggests that breathprints obtained by electronic nose have diagnostic potential for MPM.

Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register.

Due to the large scale use of asbestos (more than 3.5 million tons produced or imported until its definitive banning in 1992), a specific national surveillance system of mesothelioma incident cases is active in Italy, with direct and individual anamnestic etiological investigation. In the period between 1993 and 2004, a case‐list of 8,868 pleural MM was recorded by the Italian National Register (ReNaM) and the modalities of exposure to asbestos fibres have been investigated for 6,603 of them. Standardized incidence rates are 3.49 (per 100,000 inhabitants) for men and 1.25 for women, with a wide regional variability. Occupational asbestos exposure was in 69.3% of interviewed subjects (N = 4,577 cases), while 4.4% was due to cohabitation with someone (generally, the husband) occupationally exposed, 4.7% by environmental exposure from living near a contamination source and 1.6% during a leisure activity. In the male group, 81.5% of interviewed subjects exhibit an occupational exposure. In the exposed workers, the median year of first exposure was 1957, and mean latency was 43.7 years. The analysis of exposures by industrial sector focuses on a decreasing trend for those traditionally signaled as “at risk” (asbestos‐cement industry, shipbuilding and repair and railway carriages maintenance) and an increasing trend for the building construction sector. The systematic mesothelioma surveillance system is relevant for the prevention of the disease and for supporting an efficient compensation system. The existing experience on all‐too‐predictable asbestos effects should be transferred to developing countries where asbestos use is spreading.

Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival.

Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival

A cluster of familial malignant mesothelioma with del(9p) as the sole chromosomal anomaly

We describe a family of three sisters affected by malignant mesothelioma (MM) (2 pleural and 1 peritoneal) and one brother affected by pleural plaques. All members of the family had been subjected to previous asbestos exposure of environmental-residential type. For 13 years, from 1951 to 1964, their housing was provided by the fathers employer, an asbestos cement factory, and the factory warehouse was on the ground floor of the building they lived in. DNA extracted from paraffin-embedded MM samples was used to search for chromosomal alterations by a comparative genomic hybridization (CGH) method. In two cases, a loss at 9p was found to be the only change. The loss at 9p is a frequent event in malignant mesothelioma and the fact that this anomaly was diagnosed in two sisters as the only alteration suggests that this region may be the site of one or more oncosuppressor genes that could play an important role in the development of MM and in inducing greater genetic susceptibility to the carcinogenic effects of asbestos.

Non-occupational exposure to asbestos and malignant mesothelioma in the Italian National Registry of Mesotheliomas

Background Malignant mesotheliomas are strictly related to asbestos, but in a proportion of cases no exposure can be recalled. Published estimates of this proportion have important variations. Historical and geographical differences in the fraction of cancer due to any given exposure are to be expected, but incomplete identification of non-occupational exposures may have played a role. Methods To assess the role of non-occupational exposures in causing malignant mesotheliomas in Italy, the exposures of cases registered by the national mesothelioma registry (ReNaM) were examined. ReNaM started in 1993 in five regions and currently covers 98% of the Italian population. Information on occupational and non-occupational exposures of cases is collected whenever possible. Results From 1993 to 2001 ReNaM registered 5173 malignant mesothelioma cases, and exposures were assessed in 3552 of them. 144 and 150 cases with exposures limited to environmental (living in the neighbourhood of an industrial or natural source of asbestos) or familial (living with a person occupationally exposed to asbestos) circumstances, respectively, were identified, accounting for 8.3% of all cases. Conclusions Geographical variations in the proportion of cases due to non-occupational exposures may be explained by the past distribution of asbestos-using industries.

Malignant mesothelioma due to non-occupational asbestos exposure from the Italian national surveillance system (ReNaM): epidemiology and public health issues

Introduction Italy produced and imported a large amount of raw asbestos, up to the ban in 1992, with a peak in the period between 1976 and 1980 at about 160 000 tons/year. The National Register of Mesotheliomas (ReNaM, “Registro Nazionale dei Mesoteliomi” in Italian), a surveillance system of mesothelioma incidence, has been active since 2002, operating through a regional structure. Methods The Operating Regional Center (COR) actively researches cases and defines asbestos exposure on the basis of national guidelines. Diagnostic, demographic and exposure characteristics of non-occupationally exposed cases are analysed and described with respect to occupationally exposed cases. Results Standardised incidence rates for pleural mesothelioma in 2008 were 3.84 (per 100 000) for men and 1.45 for women, respectively. Among the 15 845 mesothelioma cases registered between 1993 and 2008, exposure to asbestos fibres was investigated for 12 065 individuals (76.1%), identifying 530 (4.4%) with familial exposure (they lived with an occupationally exposed cohabitant), 514 (4.3%) with environmental exposure to asbestos (they lived near sources of asbestos pollution and were never occupationally exposed) and 188 (1.6%) exposed through hobby-related or other leisure activities. Clusters of cases due to environmental exposure are mainly related to the presence of asbestos-cement industry plants (Casale Monferrato, Broni, Bari), to shipbuilding and repair activities (Monfalcone, Trieste, La Spezia, Genova) and soil contamination (Biancavilla in Sicily). Conclusions Asbestos pollution outside the workplace contributes significantly to the burden of asbestos-related diseases, suggesting the need to prevent exposures and to discuss how to deal with compensation rights for malignant mesothelioma cases induced by non-occupational exposure to asbestos.

Epidemiological patterns of asbestos exposure and spatial clusters of incident cases of malignant mesothelioma from the Italian national registry

BackgroundPrevious ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM).MethodsIn the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews. Observed cases were assigned to the municipality of residence at the time of diagnosis and compared to those expected based on the age-specific rates of the respective geographical area. A spatial cluster analysis was performed for each area applying a Bayesian hierarchical model. Information about modalities and economic sectors of asbestos exposure was analyzed for each cluster.ResultsThirty-two clusters of malignant mesothelioma were identified and characterized using the exposure data. Asbestos cement manufacturing industries and shipbuilding and repair facilities represented the main sources of asbestos exposure, but a major contribution to asbestos exposure was also provided by sectors with no direct use of asbestos, such as non-asbestos textile industries, metal engineering and construction. A high proportion of cases with environmental exposure was found in clusters where asbestos cement plants were located or a natural source of asbestos (or asbestos-like) fibers was identifiable. Differences in type and sources of exposure can also explain the varying percentage of cases occurring in women among clusters.ConclusionsOur study demonstrates shared exposure patterns in territorial clusters of malignant mesothelioma due to single or multiple industrial sources, with major implications for public health policies, health surveillance, compensation procedures and site remediation programs.

Comparative genomic hybridisation in malignant deciduoid mesothelioma

Background: Malignant deciduoid mesothelioma is a rare variant of epithelioid mesothelioma. This tumour generally has poor prognosis, and can be asbestos related. Aim: To identify peculiar genetic changes responsible for critical phases in pathogenesis of malignant deciduoid mesothelioma and their prognostic relevance. Methods: Comparative genomic hybridisation was carried out in six cases of malignant pleural deciduoid mesothelioma, four sporadic and two familial. All cases were found to be asbestos related. Four patients died during follow-up and the mean survival was 29.5 (SD 14.2, range 12–43) months. Results: Genetic abnormalities were found in all the tumour tissues, the most frequent being chromosomal gains at 1p, 12q, 17, 8q, 19 and 20 and losses at 13q, 6q and 9p. Survival was found to be longer in those patients who presented a smaller number of losses (⩽2) in the tumorous chromosomes. Conclusions: Although numerous genetic changes are presented by deciduoid mesotheliomas, certain chromosomal regions are preferentially affected. The clinical outcome for this mesothelioma subtype is predicted by the number of losses.

Seroprevalence of Q-fever, brucellosis and leptospirosis in farmers and agricultural workers in Bari, southern Italy

To establish the seroprevalence of antibodies to C. burnetii, Leptospira and Brucella in subjects at risk of exposure, 128 workers exposed to farm animals and 280 healthy blood donors were studied. Antibodies to C. burnetii, Leptospira and Brucel- la were determined by indirect immunofluorescence assay, by microagglutination test (MAT) and by standard tube agglutination test, respectively. Of subjects exposed to farm animals 73.4% were positive for anti C. burnetii IgG (titer ≥ 20) compared to 13.6% of control subjects (p < 0.0001). The seroprevalence was found mainly among the veterinar- ians (100%) and the animal breeding workers (84%). The trend of percentage of positiv- ity to antibodies to C. burnetii is significant only in the group of workers ≥ 70 years, when adjusted for sex and occupation. None of the subjects examined had antibodies to Leptospira and Brucella. Further improvements in the occupational hygiene of the work environment is advisable.