The epidemiological surveillance of malignant mesothelioma in Italy (1993-2015): methods, findings, and research perspectives.

BACKGROUND: as a legacy of the large asbestos consumption until the definitive ban in 1992, Italy had to tackle a real epidemic of asbestos related diseases. The Italian National Registry of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with a regional structure. Aims, assignments and territorial network of ReNaM are described, as well as data collection, recording and coding procedures. OBJECTIVES: to describe the Italian epidemiological surveillance system of mesothelioma incidence, to provide updated data about occurrence of malignant mesothelioma in Italy, and to discuss goals, attainments, and expectations of registering occupational cancer. DESIGN: analysis of data by malignant mesothelioma incident cases surveillance system. SETTING AND PARTICIPANTS: Italy, network of regional surveillance system, all Italian regions. MAIN OUTCOME MEASURES: a Regional Operating Centre (COR) is currently established in all the Italian regions, actively searching incident malignant mesothelioma cases from health care institutions. Occupational history, lifestyle habits, and residential history are obtained using a standardized questionnaire, administered to the subject or to the next of kin by a trained interviewer. The extent of dataset, epidemiological parameters, and occupations involved are reported updated at 31.12.2016, and standardized incidence rates are calculated. RESULTS: at December 2016, ReNaM has collected 27,356 malignant mesothelioma cases, referring to the period of incidence between 1993 and 2015. The modalities of exposure to asbestos have been investigated for 21,387 (78%) and an occupational exposure has been defined for around 70% of defined cases (14,818). CONCLUSIONS: the Italian experience shows that epidemiological systematic surveillance of asbestos related diseases incidence has a key importance for assessing and monitoring the public health impact of occupational and/or environmental hazards, programming preventive interventions, including remediation plans and information campaigns, and supporting the efficiency of insurance and welfare system. Monitoring the incidence of malignant mesothelioma through a specialized cancer registry is essential to follow-up the health effects of changing modalities and extent of occupational exposures over years and of environmental contamination. Such consolidated surveillance system is recommended also for occupational cancers with low aetiological fraction.

[Health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy)]. / Impatto sulla salute delle fibre di amianto presenti in affioramenti naturali nell'area del Pollino (Basilicata).

OBJECTIVES: to estimate the health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy). DESIGN: geographic mortality, hospitalization, and incidence study. Setting and participant s: population resident in 12 Municipalities of Mount Pollino area with naturally occurring asbestos fibres. MAIN OUTCOME MEASURES: standardized mortality ratio (SMR) and standardized hospitalization rate (SHR) for asbestos-related diseases; standardized incidence ratio (SIR) for mesotheliomas. Result s: in the area of Mount Pollino, where asbestos fibres naturally occur, especially in the sub-area in which fibres are close to dwellings and settlements, it was observed: • a significant excess of mesothelioma incidence (SIR: 208; CI95% 111-355; 13 observed); • a non-significant excess of hospitalization for malignant pleural neoplasms (SHR: 176; CI95% 93-335; 9 observed); • a significant excess for mortality and hospitalization for pneumoconiosis (SMR: 534; CI95% 345-824; 20 observed - SHR: 245; CI95% 149-405; 15 observed); • a significant excess for hospitalization (SHR: 852; CI95% 290-2,506; 3 observed) for asbestosis. CONCLUSION: it is necessary to continue environmental monitoring and environmental remediation in the area with higher asbestos exposure. It is suggested to implement a permanent process of epidemiological surveillance in this same area. A communication plan with local administrators, general practitioners, school teachers, media, and the resident population at large should be realized.

The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure.

INTRODUCTION: The epidemiology of gender differences for mesothelioma incidence has been rarely discussed in national case lists. In Italy an epidemiological surveillance system (ReNaM) is working by the means of a national register. METHODS: Incident malignant mesothelioma (MM) cases in the period 1993 to 2012 were retrieved from ReNaM. Gender ratio by age class, period of diagnosis, diagnostic certainty, morphology and modalities of asbestos exposure has been analysed using exact tests for proportion. Economic activity sectors, jobs and territorial distribution of mesothelioma cases in women have been described and discussed. To perform international comparative analyses, the gender ratio of mesothelioma deaths was calculated by country from the WHO database and the correlation with the mortality rates estimated. RESULTS: In the period of study a case list of 21 463 MMs has been registered and the modalities of asbestos exposure have been investigated for 16 458 (76.7%) of them. The gender ratio (F/M) was 0.38 and 0.70 (0.14 and 0.30 for occupationally exposed subjects only) for pleural and peritoneal cases respectively. Occupational exposures for female MM cases occurred in the chemical and plastic industry, and mainly in the non-asbestos textile sector. Gender ratio proved to be inversely correlated with mortality rate among countries. CONCLUSIONS: The consistent proportion of mesothelioma cases in women in Italy is mainly due to the relevant role of non-occupational asbestos exposures and the historical presence of the female workforce in several industrial settings. Enhancing the awareness of mesothelioma aetiology in women could support the effectiveness of welfare system and prevention policies.

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.

BACKGROUND: Previous 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). METHODS: In 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. RESULTS: Thirty-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. CONCLUSIONS: Our 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.

[Epidemiologic surveillance of mesothelioma for the prevention of asbestos exposure also in non-traditional settings]. / Sorveglianza epidemiologica dei mesoteliomi per la prevenzione dell'esposizione ad amianto anche in attività non tradizionalmente coinvolte.

OBJECTIVE: To show how malignant mesothelioma (MM) surveillance not only identifies settings of exposure representing past industrial history, but it may also detect conditions of current exposure relevant for the prevention, if the wide spectrum of asbestos uses is considered. DESIGN: Active search of MM cases and exposure assessment at individual level through a questionnaire; identification of exposure circumstances relevant for prevention. SETTING AND PARTICIPANTS: Italy, all the Regions where a Regional Operating Centre (COR) is established to identify all MM cases diagnosed in the population and analyze their occupational, residential, household and environmental histories. Period of diagnosis: 1993-2008. MAIN OUTCOME MEASURES: Descriptive analysis of MM cases and of asbestos exposures. RESULTS: ReNaM includes 15,845 cases of MM diagnosed between 1993 and 2008.The male/female ratio is 2.5. Mean age at diagnosis is 69 years. Pleural MMs represent 93% of all cases. Exposures have been investigated in 12,065 cases (76%). The median latency time is 46 years. In addition to clusters of MM cases in activities well known to entail asbestos use, different current exposure circumstances requiring intervention have been evidenced. CONCLUSIONS: On the basis of this experience, epidemiological surveillance of all occupational cancers should be implemented to foster synergies with the compensation system and the Local Health Authorities' occupational safety and health services, as required by the Italian Legislative Decree N. 81/2008.

Governance of preventive Health Intervention and On time Verification of its Efficiency: the GIOVE Study.

OBJECTIVES: The GIOVE Study was aimed to the achievement of allocative efficiency of the budget allocated to the prevention of human papillomavirus (HPV)-induced diseases. An ex-ante determination of the most efficient allocation of resources between screening and multicohort quadrivalent immunisation programmes was followed by the ex-post assessment of the allocative efficiency actually achieved after a 12-month period. DESIGN: A bound optimisation model was developed to determine the ex-ante allocative efficiency of resources. The alternatives compared were the screening programme alone and the quadrivalent immunisation with access to screening. A sensitivity analysis was carried out to assess the uncertainty associated with the main inputs of the model. Subsequently, a cohort of girls with a complete recorded vaccination history were enrolled in an observational retrospective study for 18 months to ensure full compliance with the recommended schedule of vaccination (0, 2, 6 months) within a 12-month time horizon. SETTING: Basilicata region, in the south of Italy. PARTICIPANTS: 12 848 girls aged 12, 15, 18 or 25 years. INTERVENTION: Immunisation with quadrivalent anti-HPV vaccine. OUTCOME MEASURES: The vaccination coverage rate was considered to be the indicator of the best achievable benefit, given the budgetary constraints. RESULTS: Assuming a vaccine price of €100 per dose, a vaccination coverage rate of 59.6% was required for the most effective allocation of resources. The optimal rate of coverage was initially in favour of the multicohort strategy of vaccination against HPV (72.8%±2%). When the price paid for the quadrivalent vaccine dropped to €85 per dose, the most efficient coverage rate (69.5%) shifted closer to the immunisation rate actually achieved during the 12-month observation period. CONCLUSIONS: The bound optimisation model demonstrated to be a useful approach to the ex-ante allocation and the ex-post assessment of the resources allocated to the implementation of a multicohort quadrivalent anti-HPV vaccination programme.

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.

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.

[Epidemiological surveillance of malignant mesothelioma cases in Italy: incidence and asbestos exposure figures by the Italian mesothelioma registry (ReNaM)]. / La sorveglianza epidemiologica del mesotelioma maligno in Italia: dati d'incidenza ed esposizione ad amianto del Registro nazionale dei mesoteliomi (ReNaM).

The Study describes the epidemiological surveillance of mesothelioma cases carried out by the Italian mesothelioma register (ReNaM). A Regional Operating Centre (COR) is present in nearly all Italian regions (17 out of 20) and it collects malignant mesothelioma cases and investigate the modalities of asbestos exposure by using a structured questionnaire. The register produces malignant mesothelioma incidence measures and analyses of the modalities of the asbestos exposure. The standardized incidence rate of malignant mesothelioma in 2001 was 2.98 (in 100,000 inhabitants) among men and 0.98 among women; a professional (certain, probable, possible) exposure has been detected in 67.4% of defined cases. In addition to the conventional sectors (shipbuilding, railways repair and demolition, asbestos-cement production), also textile, building, transport, chemical and glass industries, petroleum and sugar refineries, electricity production and distribution plants are getting involved. Despite the absence of some regions completing the national coverage and the non homogeneity in collecting and coding data, the epidemiological surveillance of malignant mesothelioma carried out by ReNaM is an important tool for the scientific knowledge and the prevention of asbestos-related diseases.

Analysis of latency time and its determinants in asbestos related malignant mesothelioma cases of the Italian register.

Italy was an important producer of raw asbestos until 1992 (when it was banned) and it is now experiencing severe public health consequences due to large-scale industrial use of asbestos in shipbuilding and repair, asbestos-cement production, railways, buildings, chemicals and many other industrial sectors. Latency of malignant mesothelioma generally shows a large variability and the relationship with the modality of asbestos exposure is still not fully clarified. We present an analysis of latency period among the case list collected by the Italian mesothelioma register (ReNaM) in the period of diagnosis 1993-2001 (2544 malignant mesothelioma (MM) cases with asbestos exposure history). Exposure is assessed retrospectively by interview. Statistical univariate analyses were performed to estimate median and variability measures of latency time by anatomical site, gender and diagnosis period. The role of diagnostic confidence level, the morphology of the tumour and the modalities of asbestos exposure were verified in a regression multivariate model. We found a median latency period of 44.6 years increasing in recent years with a linear trend. Anatomical site, gender and morphology were not relevant for MM latency time whereas a shorter latency period was documented among occupationally exposed subjects (43 years) with respect to environmentally and household exposed ones (48 years).

[Consensus Conference "Health surveillance of resident population exposed to tremolite in Local Health Unit 3 territory Lagonegro, PZ". Rome 22-23 February 2005]. / Consensus Conference "Sorveglianza sanitaria delle popolazioni esposte a fibre di tremolite nel territorio della ASL 3 Lagonegro-PZ". Roma 22-23 febbraio 2005.

Herein is reported the health surveillance document agreed upon during the Consensus Conference held in Rome at the Istituto Superiore di Sanità last year. The aim of the consensus conference was to define guidelines for epidemiologic and health surveillance of the resident population in the area of the Basilicata region exposed to tremolite pollution (Local Health Unit 3 territory Lagonegro, PZ). The health surveillance program for residents and the nested epidemiologic study evaluates for each resident willing to participate, individual exposure with a personal dosimeter, as well as the prevalence of obstructive, restrictive or mixed pulmonary functional patterns, searching for fiber and asbestos bodies in induced-sputum, the prevalence of non malignant asbestos disturbances related to pleural anomalies and, last but not least, provides information on risks and sensitization, advising on personal behaviour that could reduce the risks.

[Pleural mesothelioma and environmental exposure to mineral fibres: the case of a rural area in the Basilicata region, Italy]. / Mesotelioma pleurico ed esposizione ambientale a fibre minerali: il caso di un'area rurale in Basilicata.

The main aspects of the sites characterized by environmental exposure to mineral asbestiform fibres are described. Several adverse health effects including high incidence of pleural mesothelioma are reported. The average concentration of airborne fibres is generally low but it rises significantly in association with mechanical disturb of materials with fibres. Multiple sources of exposure have been identified, fibres can be found in the soil and in many materials locally used, mainly in buildings. Three mesothelioma cases were observed in a small rural area of the Basilicata region (Italy). Two of them had a possible occupational exposure to asbestos, the third had a proved environmental exposure to tremolite. This fibre, found in the area, is the same observed in two of the three biological samples analysed.