[SENTIERI-ReNaM: Integration of incidence, mortality, and hospitalization: general remarks and a focus on mesothelioma]. / SENTIERI-ReNaM: Integrazione di incidenza, mortalità e ospedalizzazione: considerazioni generali e applicazione al mesotelioma.

The integration of current data sources is now a practice widely used in epidemiology, especially in the environmental field. To better describe the health profile of populations residing in proximity to areas characterized by a "strong environmental pressure", the combined use of multiple indicators (i.e., mortality, hospitalization, cancer incidence) is recommended. To choose an indicator is complex, as indicators should be contextualized and they need to be related to the several issues involved in the studied pathology. This chapter explores the general considerations that are to be addressed both at the time of the study design, during the selection of outcomes and of the proper data sources, and at the time of the discussion of the results, when different and complementary data are compared. A special focus is devoted to the case of mesothelioma.

[SENTIERI-ReNaM: Results]. / SENTIERI-ReNaM: Risultati.

Mesothelioma incidence has been analyzed in National Priority Contaminated Sites (NPCSs) to estimate the health impact of asbestos exposure on resident people. The burden of professional and environmental exposures has been identified through data of the Regional Operational Centres (CORs), made available by the Italian National Mesothelioma Registry (ReNaM). An excess of mesothelioma incidence is confirmed in sites with a known past history of direct use of asbestos, such as Balangero, Casale Monferrato, Broni, Bari-Fibronit, and in coastal areas, where shipyards, harbours and other industries that involved a wide use of asbestos are represented (e.g., Trieste, La Spezia, Venice, and Leghorn). An excess of mesothelioma has been observed in settings where the asbestos is not mentioned as contaminant in the decree that included these sites among NPCSs, such as Cengio and Saliceto in Northern Italy; Falconara Marittima and the Bacino Idrografico Fiume Sacco in the Central Italy; the Litorale Domizio Flegreo and Agro Aversano, Milazzo, and Gela in the Southern Italy. Observed excess in the various NPCSs confirms the large-scale occurrence in contaminated Italian sites of a significant amount of total mesothelioma cases observed at national level. The analysis of occupational risk in epidemiological studies with an ecological design helps in defining the contribution of different factors to the overall risk.

[SENTIERI-ReNaM: Discussion and concluding remarks]. / SENTIERI-ReNaM: Discussione e considerazioni conclusive.

SENTIERI-ReNaM Project analysed the incidence of malignant mesothelioma (MM) for the period 2000-2011 in 39 National Priority Contaminated Sites (NPCSs), and assessed the overall impact of mesothelioma in different types of NPCSs. In the study period, 2,683 incident cases of malignant mesothelioma were recorded: 1,998 males (74.5%), 685 females (25.5%). Excluding cases with non attributable exposure and those non interviewed, exposure was identified in 1,926 cases (70% of all cases): 1,541 males (occupational exposure: 1,414; environmental exposure: 82), 385 females (occupational exposure: 103; environmental exposure: 141). Women experienced mainly environmental and domestic exposures to asbestos. Standard Incidence Ratio (SIR) excesses were observed in men in 27 out of 39 NPCSs and defects in the remaining 12; in women, 20 NPCSs showed SIR excesses, defects in 15; in 4 NPCSs no MM cases occurred among female population. The highest rates were found in NPCSs with asbestos-cement plants (Broni and Casale Monferrato), respectively, 98 per 100,000 per year and 68.6 in men, 72.1 and 45.8 in women. Excluding these two sites, the highest incidence rates were found in the group with harbours and shipyards, where the rates were, respectively, 13.2 among men and 2.5 among women. The results of this report will be communicated to national and local institutions, as well as to NPCSs resident populations.

[A comparative analysis between regional mesothelioma registries and cancer registries: results of the ReNaM-AIRTUM project]. / Confronto fra registri specializzati e registri tumori di popolazione: i risultati del progetto ReNaM-AIRTUM.

OBJECTIVES: to assess the agreement on row data and incidence rates between regional mesothelioma registries (CORs) and population cancer registries (CRs) in Italy, and to contribute in harmonizing the procedures used in identifying the date of incidence and the morphology of mesothelioma cases. SETTING E PARTICIPANTS: the mesothelioma cases registered by 19 CRs and by 9 out of 19 CORs were included in the study. Some CORs were not able to participate in the study, because there were no active CRs in their areas. MAIN OUTCOME MEASURES: agreement on cases defined as mesotheliomas by the two types of registries; Cohen's k was used for the evaluation of the agreement on morphology on specific mesothelioma (ICD-O-3 90513-90533) and mesothelioma not otherwise specified (NOS) (ICD-O-3 90503); instead, Odds Ratio was calculated to evaluate the direction of the discrepancy. Difference among incidence rates were calculated using data collected by the two types of registries. It was also made a comparison between dates of incidence. RESULTS: the comparison among the registered data by the two different types of registry showed a high concordance (>80%), especially in the areas where there is a continuous exchange of data. Only in a few areas a lower concordance was observed. The agreement between specific and non-specific morphology showed a fairly wide range and lower values than the calculation of the positive agreement. CORs used the specific morphology (ICD-O-3 90503-90533) with higher frequency compared to CRs. The CRs incidence standardized rates are higher when only cases defined as «certain ¼ by ReNaM are considered; on the opposite the CORs rates are higher when all cases defined as «certain, probable and possible¼ are considered. CONCLUSIONS: the study permitted to compare and bring out the different procedures used in identifying the date of incidence of cases and morphology definition. This represents a first step of a cooperative discussion process among the involved registries: the working group hope it will end with the implementation of shared guidelines.

Incidence of pleural mesothelioma in a community exposed to fibres with fluoro-edenitic composition in Biancavilla (Sicily, Italy).

INTRODUCTION: Amphibolic fibres with fluoro-edenitic composition characterize Biancavilla soil, including the major quarry from which building materials have been extensively extracted. These fibres induce mesothelioma in experimental animals and their in vitro biological action is similar to that of crocidolite. MATERIALS AND METHODS: Malignant mesothelioma case series and incidence were examined to evaluate the disease burden on Biancavilla inhabitants. RESULTS: The incidence of pleural mesothelioma in Biancavilla is steadily higher than in the Sicilian Region, risk estimates are more elevated in women than in men, the most affected age class is constituted by subjects aged less than 50. DISCUSSION AND CONCLUSIONS: Environmental exposure to fibres with fluoro-edenitic composition appears to be causally related to the elevated mesothelioma occurrence in Biancavilla. In this frame, environmental clean-up is the main goal to be pursued in public health terms. A contribution of scientific research to public health decision making with respect to priority setting for environmental clean-up can derive from some further selected epidemiological investigations.

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.

[Considerations on the need for cooperation between Italian Association of Cancer Registries (AIRTUM) and the Italian National Mesothelioma Registry (RENAM)]. / Un contributo per una fattiva collaborazione fra AIRTUM e RENAM.

UNLABELLED: A pilot study comparing mesothelioma registries and population-based cancer registries of two Italian regions, Sicilia and Toscana, shows a good agreement on total number of registered incident cases. However, and in spite of the use of the same clinical sources of data, discrepancies were detected because of different criteria applied in collecting and classifying the relevant information on diagnoses. The development of common guidelines on the definition of mesothelioma case is a challenge for the Italian National Mesothelioma Registry (RENAM) and for the Italian Association of Cancer Registries (AIRTUM). The calendar period covered by the study was 1998- 2005 for Sicily and 1988-2005 for Tuscan. KEYWORDS: cancer registries, mesothelioma, guidelines.

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.

[Mortality from asbestos-related causes and incidence of pleural mesothelioma among former asbestos cement workers in San Filippo del Mela (Sicily)]. / Mortalità per cause asbesto-correlate e incidenza del mesotelioma fra i lavoratori del cemento-amianto di San Filippo del Mela (Messina).

OBJECTIVES: The present paper estimates the burden of asbestos-related disease among asbestos-cement production workers of the Sacelit plant that operated in San Filippo del Mela (Province of Messina) from 1958 through 1993. SETTING AND PARTICIPANTS: The cohort was enumerated by the local committee of formerly exposed workers, with whom a collaboration was set up. The cohort includes 198 subjects with complete individual anagraphic information, out of 231 previous workers identified by the committee. A record-linkage with the Sicilian centre of the National mesothelioma registry enabled estimation of mesothelioma incidence for the years 1998-2008. Standardised proportionate mortality (SPMR) for asbestos-related causes was computed for the years 1986-2009. Sicilian Region constituted the reference population. The rationale for using SPMR rather than standardized mortality ratio (SMR) was a consequence for the lack of company files from which to obtain dates of start and termination of employment, and thus to compute person-years of observation, following the guidelines of the international scientific literature. RESULTS: Standardised incidence ratio (SIR) for mesothelioma in the overall cohort was 251 (4 observed, 0.02 expected). Proportionate mortality analysis among male subjects showed significant increases for pneumoconiosis (SPMR 80.1, 5 observed), lung cancer (SPMR 2.81, 10 observed) and pleural neoplasms (SPMR 19.4, 2 observed). CONCLUSIONS: Notwithstanding limitations in cohort reconstruction, for which the proportion of eligible subjects was 87.5% of those detected by the local committee, and the lack of information on duration of employment, it was possible to estimate a significant increase of the incidence of pleural mesothelioma with respect to Sicilian population. Also mortality from asbestos-related causes was in excess with respect to the regional reference population.

Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register.

OBJECTIVES: The epidemiology of extrapleural malignant mesothelioma is rarely discussed and the risk of misdiagnosis and the very low incidence complicate the picture. This study presents data on extrapleural malignant mesothelioma from the Italian National Mesothelioma Register (ReNaM). METHODS: ReNaM works on a regional basis, searching for cases and interviewing subjects to investigate asbestos exposure. Classification and code criteria for certainty of diagnosis and exposure modalities are set by national guidelines. Between 1993 and 2004, 681 cases were collected. Incidence measures and exposure data refer to the ReNaM database. Age-standardised rates were estimated by the direct method using the Italian resident population in 2001. Correlations between the incidence of pleural and non-pleural malignant mesothelioma for the 103 Italian provinces were analysed. RESULTS: Standardised incidence rates (Italy, 2004, per million inhabitants) were 2.1 and 1.2 cases for the peritoneal site (in men and women, respectively), 0.2 cases for the tunica vaginalis testis, and 0.1 in the pericardial site, varying widely in different parts of the country. Mean age at diagnosis for all extrapleural malignant mesothelioma cases was 64.4 years and the men/women ratio was 1.57:1. Median latency was over 40 years for all extrapleural sites combined. The correlation between pleural and peritoneal mesothelioma was 0.71 (Pearson's r coefficient, p<0.001). Modalities of exposure to asbestos fibres were investigated for 392 cases. CONCLUSIONS: The rarity of the disease, the low specificity of diagnosis and difficulties in identifying the modalities of asbestos exposure call for caution in discussing aetiological factors other than asbestos.

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

A median survival time of about 9 months is generally reported among malignant pleural mesothelioma cases. Recently, better results in terms of survival and performance status have been reported in clinical trials that included highly selected patients. We describe the survival of pleural mesothelioma patients and the factors predictive of survival in an unselected, population-based setting. Pleural mesothelioma cases (4,100) 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 carried out according to selected individual characteristics, including limited information on treatment in a subset of 578 cases. The median survival time was 9.8 months (95% confidence interval: 9.4-10.1). In multivariate analysis, younger age at diagnosis and epithelioid histotype were associated with significantly reduced hazard ratios. Positive effects of gender (women) and being diagnosed in a hospital with a thoracic surgery unit were of border-line statistical significance. No association with calendar period of diagnosis or asbestos exposure was present. Treatment was not associated with a statistically significant improvement in survival. This is the largest population-based study on survival in patients with pleural mesothelioma to date. Age and morphology were the main prognostic factors. Results regarding the effect of treatment were disappointing but may be useful to assess the future impact, at the population level, of recently introduced therapies.

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.