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Background: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers., Methods: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period., Results: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter., Conclusions: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time., (© 2023 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals LLC.)

Introduction: Exposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy., Method: The cohort study included 12 578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE)., Result: Acceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE., Conclusion: The current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality., Competing Interests: Competing interests: The authors declare that they have no competing interests. The following authors or working group components reported that they served as expert witness in court trials on asbestos related diseases: AA, AB, CM, DM, EM, EO, FB-A, LBi, LMa, LMi, MM, SMe, SS, VP., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: From the beginning of 2020, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) quickly spread worldwide, becoming the main problem for the healthcare systems. Healthcare workers (HCWs) are at higher risk of infection and can be a dangerous vehicle for the spread of the virus. Furthermore, cancer patients (CPs) are a vulnerable population, with an increased risk of developing severe and lethal forms of Coronavirus Disease 19 (COVID-19). Therefore, at the National Cancer Institute of Naples, where only cancer patients are treated, a surveillance program aimed to prevent the hospital access of SARS-CoV-2 positive subjects (HCWs and CPs) was implemented. The study aims to describe the results of the monitoring activity for the SARS-CoV-2 spread among HCWs and CPs, from March 2020 to March 2021., Methods: This surveillance program included a periodic sampling through nasopharyngeal molecular swabs for SARS-CoV-2 (Real-Time Polymerase Chain Reaction, RT-PCR). CPs were submitted to the molecular test at least 48 h before hospital admission. Survival analysis and multiple logistic regression models were performed among HCWs and CPs to assess the main SARS-CoV-2 risk factors., Results: The percentages of HCWs tested with RT-PCR for the detection of SARS-CoV-2, according to the first and the second wave, were 79.7% and 91.7%, respectively, while the percentages for the CPs were 24.6% and 39.6%. SARS-CoV-2 was detected in 20 (1.7%) HCWs of the 1204 subjects tested during the first wave, and in 127 (9.2%) of 1385 subjects tested in the second wave ( p < 0.001); among CPs, the prevalence of patients tested varied from 100 (4.6%) during the first wave to 168 (4.9%) during the second wave ( p = 0.8). The multivariate logistic analysis provided a significant OR for nurses (OR = 2.24, 95% CI 1.23-4.08, p < 0.001) compared to research, administrative staff, and other job titles., Conclusions: Our findings show that the positivity rate between the two waves in the HCWs increased over time but not in the CPs; therefore, the importance of adopting stringent measures to contain the shock wave of SARS-CoV-2 infection in the hospital setting was essential. Among HCWs, nurses are more exposed to contagion and patients who needed continuity in oncological care for diseases other than COVID-19, such as suspected cancer.

COVID-19 pandemic following the outbreak in China and Western Europe, where it finally lost the momentum, is now devastating North and South America. It has not been identified the reason and the molecular mechanisms of the two different patterns of the pulmonary host responses to the virus from a minimal disease in young subjects to a severe distress syndrome (ARDS) in older subjects, particularly those with previous chronic diseases (including diabetes) and cancer. The Management of the Istituto Nazionale Tumori - IRCCS "Fondazione Pascale" in Naples (INT-Pascale), along with all Health professionals decided not to interrupt the treatment of those hospitalized and to continue, even if after a careful triage in order not to allow SARS-CoV-2 positive subjects to access, to take care of cancer patients with serious conditions. Although very few (n = 3) patients developed a symptomatic COVID-19 and required the transfer to a COVID-19 area of the Institute, no patients died during the hospitalization and completed their oncology treatment. Besides monitoring of the patients, all employees of the Institute (physicians, nurses, researchers, lawyers, accountants, gatekeepers, guardians, janitors) have been tested for a possible exposure. Personnel identified as positive, has been promptly subjected to home quarantine and subdued to health surveillance. One severe case of respiratory distress has been reported in a positive employees and one death of a family member. Further steps to home monitoring of COVID-19 clinical course have been taken with the development of remote Wi-Fi connected digital devices for the detection of early signs of respiratory distress, including heart rate and oxygen saturation.In conclusion cancer care has been performed and continued safely also during COVID-19 pandemic and further remote home strategies are in progress to ensure the appropriate monitoring of cancer patients.

Objective: Italy has been a large user of asbestos and asbestos containing materials until the 1992 ban. We present a pooled cohort study on long-term mortality in exposed workers., Methods: Pool of 43 Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding, glasswork, harbors, insulation and other industries). SMRs were computed by industrial sector for the 1970-2010 period, for the major causes, using reference rates by age, sex, region and calendar period., Results: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Asbestos exposure was estimated at the plant and period levels. Asbestos related mortality was significantly increased. All industrial sectors showed increased mortality from pleural malignancies, and most also from peritoneal and lung cancer and asbestosis, with exposure related trend. Increased mortality was also observed for ovarian cancer and for bladder cancer., Discussion: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. A large increase in mortality from asbestosis was observed.

Objectives: This study was performed with the aim of investigating the temporal patterns and determinants associated with mortality from asbestosis among 21 cohorts of Asbestos-Cement (AC) workers who were heavily exposed to asbestos fibres., Methods: Mortality for asbestosis was analysed for a cohort of 13 076 Italian AC workers (18.1% women). Individual cumulative asbestos exposure index was calculated by factory and period of work weighting by the different composition of asbestos used (crocidolite, amosite, and chrysotile). Two different approaches to analysis, based on Standardized Mortality Ratios (SMRs) and Age-Period-Cohort (APC) models were applied., Results: Among the considered AC facilities, asbestos exposure was extremely high until the end of the 1970s and, due to the long latency, a peak of asbestosis mortality was observed after the 1990s. Mortality for asbestosis reached extremely high SMR values [SMR: males 508, 95% confidence interval (CI): 446-563; females 1027, 95% CI: 771-1336]. SMR increased steeply with the increasing values of cumulative asbestos exposure and with Time Since the First Exposure. APC analysis reported a clear age effect with a mortality peak at 75-80 years; the mortality for asbestosis increased in the last three quintiles of the cumulative exposure; calendar period did not have a significant temporal component while the cohort effect disappeared if we included in the model the cumulative exposure to asbestos., Conclusions: Among heaviest exposed workers, mortality risk for asbestosis began to increase before 50 years of age. Mortality for asbestosis was mainly determined by cumulative exposure to asbestos., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Objectives: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis., Methods: We used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time., Results: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer., Conclusions: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations., Competing Interests: Competing interests: SM served as expert witness for the judge, the public prosecutor and the defendant’s attorneys in court trials regarding asbestos-related diseases. CM and SS served as expert witnesses for the judge and the public prosecutor in court trials regarding asbestos-related diseases. AA, FB-A, PL, EM, LMi, DM and EO served as expert witnesses for the public prosecutor in court trials regarding asbestos-related diseases. LMa conducted negotiations and stipulated contracts representing the Italian Association of Cancer Registries (AIRTUM) for the preparation and publication of specific reports on the epidemiology of tumour pathologies with MSD, Lilly and Sanofi. All other authors declare they have no actual or potential competing financial interests., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos., Methods: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution., Results: Mortality was significantly increased for 'All Causes' and 'All Malignant Neoplasm (MN)', in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%., Conclusions: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.

Objective: Asbestos is a known human carcinogen, with evidence for malignant mesothelioma (MM), cancers of lung, ovary, larynx and possibly other organs. MM rates are predicted to increase with a power of time since first exposure (TSFE), but the possible long-term attenuation of the trend is debated. The asbestos ban enforced in Italy in 1992 gives an opportunity to measure long-term cancer risk in formerly exposed workers., Methods: Pool of 43 previously studied Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding), with mortality follow-up updated to 2010. SMRs were computed for the 1970â€"2010 period, for the major causes, with consideration of duration and TSFE, using reference rates by age, sex, region and calendar period., Results: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Mortality was significantly increased for all deaths (SMR: men: 1.05, 95% CI 1.03 to 1.06; women: 1.17, 95% CI to 1.12 to 1.22), all malignancies combined (SMR: men: 1.17, 95% CI to 1.14 to 1.20; women: 1.33, 95% CI 1.24 to 1.43), pleural and peritoneal malignancies (SMR: men: 13.28 and 4.77, 95% CI 12.24 to 14.37 and 4.00 to 5.64; women: 28.44 and 6.75, 95% CI 23.83 to 33.69 and 4.70 to 9.39), lung (SMR: men: 1.26, 95% CI 1.21 to 1.31; women: 1.43, 95% CI 1.13 to 1.78) and ovarian cancer (SMR=1.38, 95% CI 1.00 to 1.87) and asbestosis (SMR: men: 300.7, 95% CI 270.7 to 333.2; women: 389.6, 95% CI 290.1 to 512.3). Pleural cancer rate increased during the first 40 years of TSFE and reached a plateau after., Discussion: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. Pleural cancer mortality reached a plateau at long TSFE, coherently with recent reports., Competing Interests: Competing interests: The following authors reported that they served as expert witness for the public prosecutor in court trials on asbestos related diseases: CM, EM, DM, EO, SS., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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.

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.

This study aims at investigating, in asbestos exposed workers, the time trend of their risk of mesothelioma and of other neoplasm after very long latency and after the cessation of asbestos exposure. We pooled a large number of Italian cohorts of asbestos workers and updated mortality follow-up. The pool of data for statistical analyses includes 51,988 workers, of which 6,058 women: 54.2% was alive at follow-up, 42.6% was dead, and 2.8%was lost. Cause of death is known for 94.3%: 2,548 deaths from lung cancer, 748 frompleural cancer, 173 fromperitoneal cancer, and 434 from asbestosis. An exposure index is being developed to compare the different cohorts. Data analysis is in progress. This study will have the size for analysing not only time trends in mesothelioma, but also the occurrence of rarer diseases and cancer specific mortality in women.

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.

Background: An epidemic of asbestos-related disease is ongoing in most industrialized countries, mainly attributable to past occupational exposure but partly due to environmental exposure. In this perspective, the incidence of pleural mesothelioma close to a former asbestos-cement plant in a national contaminated site was estimated., Methods: The census-tracts interested by atmospheric dispersion of facilities in the contaminated site were identified. Two subareas with different estimated environmental asbestos impact were distinguished. An ecological study at micro-geographic level was performed. The standardized incidence ratios (SIR) for study area and the two subareas, in comparison with region and municipality were computed. The standardized incidence rate ratio (IRR) between the two subareas was computed., Results: Mesothelioma incidence in the study area was increased: 46 cases were observed with respect to 22.23 expected (SIR: 2.02). The increase was confirmed in analysis considering only the subjects without an occupationally exposure to asbestos: 19 cases among men (SIR = 2.48; 95% CI: 1.49-3.88); 11 case among women (SIR = 1.34; 95% CI: 0.67-2.40). The IRR between the two subareas is less than one in overall population considering all age-classes and of 3 fold (IRR = 3.14, 95% CI: 0.65-9.17) in the age-classes below 55 years., Conclusions: The findings indicate an increased incidence of pleural mesothelioma in the neighbourhood of asbestos-cement plant, and a possible etiological contribution of asbestos environmental exposure in detected risks.

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.

Malignant pleural mesothelioma is a fatal malignancy linked to asbestos exposure. The main challenge for mesothelioma treatment is to go beyond the drug resistance, in particular against cisplatin (CDDP), one of the most used chemotherapeutic drug. 3-O-methylfunicone (OMF) is a metabolite produced by the fungus Penicillium pinophilum; its antiproliferative properties have been previously studied in vitro. Particularly, OMF is able to inhibit mesothelioma cell motility. To improve the effects of CDDP by-passing the resistance of mesothelioma cells to this drug, in the present study we investigated the combined treatment of OMF with CDDP respectively in an established mesothelioma cell line (NCI) and primary mesothelioma cells (Mest). As compared to the effect of single treatments, the combination of OMF and CDDP resulted in a stronger inhibition of NCI and Mest cell proliferation. OMF combination with CDDP was also able to affect the migratory ability of NCI and Mest cells by down-regulating αv and β5 expression and reducing metalloproteinase 2 (MMP-2) production. In addition, this association was effective in modulating VEGF gene expression. This finding highlights the possibility to use OMF and CDDP together to regulate angiogenesis and tumour progression in mesothelioma.

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., (Copyright © 2011 UICC.)

Legislative decree No. 81/2008 in the article n. 244 states that ISPESL, now INAIL, realizes a register of occupational cancers with low etiological fraction by means of a data collection method based exclusively on voluntary reports by GPs, healthcare and social security agencies (ReNaLOC) and a surveillance cancer monitoring system (OCCAM) based on linkage of routinely available data (cancer registries, hospital discharge records, Italian Social Security archives). ReNaLOC has produced a partial picture of the situation, it includes 1.584 cases as of June 2011. With OCCAM many situations of known risks were identified and others are worthy to be deepen.

The objective of this paper is to investigate mortality among 1247 male asbestos-cement workers employed in an asbestos-cement plant located in Naples. The cohort included 1247 men hired between 1950 and 1986. The follow-up began on January 1st 1965. The vital status and causes of death were ascertained up to December 31 2005. Cause-specific mortality rates of the Campania Region population were used as reference. Relative risks were estimated using Standardized Mortality Ratios (SMRs), and the confidence intervals were calculated at a 95% level (95% CI). A significant increase in mortality was observed for respiratory disease (81 deaths; SMR = 187; 95% CI = 149- 233), particularly for pneumoconiosis (42 deaths; SMR = 13 313; 95% CI = 9595-17 996) of which 41 deaths for asbestosis (SMR = 43 385; 95% CI = 31 134-58 857), for pleural cancer (24 deaths; SMR = 2617; 95% CI = 1677-3893), for lung cancer (84 deaths; SMR=153; 95% CI = 122-189) and for peritoneal cancer (9 deaths; SMR = 1985; 95% CI = 908-3769). Non-significant increases were also observed for rectum cancer (6 deaths; SMR = 157; 95% CI = 58-342). In conclusion, consistently with other mortality studies on asbestos-cement workers performed in different countries, an increased mortality from asbestosis, lung cancer, pleural and peritoneal mesothelioma was detected in the present cohort.

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.

Objectives: 3-O-methylfunicone (OMF), a secondary metabolite produced by Penicillium pinophilum, affects cell proliferation and motility in a variety of human solid tumours. The aim of this study was to demonstrate whether OMF has the ability to arrest cell division and motility, in a human mesothelioma cell line. Malignant mesothelioma is an aggressive cancer that does not respond to standard therapies the cells of which are considered to be highly resistant to apoptosis., Material and Methods: Cell motility and invasion were measured using a modified Boyden chamber. Gene expression was examined by RT-PCR, while ERK1/2 was investigated by Western blot analysis. All experiments were also performed on primary cultures of mesothelial cells., Results: The present study shows that OMF inhibited motility of the NCI mesothelioma cell line by modulating ERK signalling activity, and affected alphaVbeta5 integrin and MMP-2 expression, inducing marked downregulation at both mRNA and protein levels. Substantial downregulation of VEGF gene expression was also demonstrated. These effects were not observed in normal mesothelial cell cultures., Conclusion: OMF may have potential as a naturally derived anti-tumour drug for treatment of mesothelioma.

Malignant mesothelioma (MM) is a rare, highly aggressive tumor that arises from the surface serosal cells (pleural, peritoneal and pericardial cavities). Epidemiological and clinical data show that there is an association between asbestos exposure and MM development, even if the exact mechanism whereby asbestos induces MM is unknown. The continuing identification and elucidation of the molecular defects involved in mesothelioma pathogenesis and progression should lead to better disease control and greater therapeutic options in the near future. Goal of this article is to summarize the most recent advances in molecular pathogenesis of mesothelioma with particular emphasis on genes that could be considered as biomarkers or therapeutic targets and discuss possible clinical implications of these findings.

Background: The goal of our study was to molecularly dissect mesothelioma tumour pathways by mean of microarray technologies in order to identify new tumour biomarkers that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets., Methodology: We performed Affymetrix HGU133A plus 2.0 microarray analysis, containing probes for about 39,000 human transcripts, comparing 9 human pleural mesotheliomas with 4 normal pleural specimens. Stringent statistical feature selection detected a set of differentially expressed genes that have been further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes, never associated before to mesotheliom that could be involved in tumour progression. Notable is the identification of MMP-14, a member of matrix metalloproteinase family. In a cohort of 70 mesothelioma patients, we found by a multivariate Cox regression analysis, that the only parameter influencing overall survival was expression of MMP14. The calculated relative risk of death in MM patients with low MMP14 expression was significantly lower than patients with high MMp14 expression (P = 0.002)., Conclusions: Based on the results provided, this molecule could be viewed as a new and effective therapeutic target to test for the cure of mesothelioma.

Background: The human embryonic lethal abnormal vision (ELAV)-like protein HuR is a messenger RNA (mRNA)-binding protein that controls the stability of certain transcripts, including cyclooxygenase2 (COX-2)., Methods: To investigate a possible contribution of dysregulation of mRNA stability to the progression of cancer and to COX-2 over expression in mesothelioma, the authors studied expression of COX-2 and HuR in 5 mesothelioma cell lines (MSTO, NCI, Ist-Mes1, Ist-Mes2, and MPP89) and in a group of 29 human mesothelioma specimens that were characterized previously for COX-2 expression., Results: All 5 cell lines expressed HuR, whereas COX-2 was not detectable in MSTO or NCI cells. Treatment with cytokines induced a shift in systolic HuR protein levels in MPP89 and Ist-Mes2 cells that was accompanied by an increase in the expression of COX-2 mRNA and protein. In Ist-Mes1 cells, cytokine stimulation did not cause the passage of HuR from nucleus to cytoplasm, and the synthesis of COX-2 did not increase. In tumor tissues, immunohistochemistry revealed a positive, statistically significant correlation between high COX-2 expression and cytoplasmic localization of HuR (P = .016). Moreover, on univariate analysis, overall survival was found to be influenced strongly by cytoplasmic HuR localization (P = .004)., Conclusions: The current results suggested that HuR plays a role in tumor progression in mesothelioma and that COX-2 may be a target of its activity in neoplastic cells. Together, these observations indicate that strategies aiming toward the modulation of HuR may have a potential clinical benefit in mesothelioma.

Aims: The objective of our study was to analyze the potential prognostic value of the expression of the serine protease HtrA1 and of EGFR in 70 malignant mesotheliomas., Materials & Methods: Immunohistochemistry was used to determine the expression of HtrA1 and EGFR. Univariate and multivariate analyses were used to correlate expression of these molecular factors in combination with available clinicopathologic data to patient survival., Results: A positive, statistically significant relationship has been recorded between HtrA1 expression level and survival (p < 0.0001). By contrast, a negative relationship has been identified between EGFR expression and survival (p = 0.02). Moreover, extension of the tumor (T) and involvement of lymph nodes (N) advanced status (p = 0.001 and 0.002, respectively), as well as the sarcomatoid histotype (p = 0.005), correlated significantly with poor survival. Finally, by a multivariate Cox regression analysis, the only immunohistochemical parameter that resulted to influence overall survival was HtrA1 (p = 0.0001). Interestingly, the prognostic value of HtrA1 expression was completely independent from EGFR expression (p < 0.0001)., Conclusion: This is the first study of the relationship between HtrA1 expression and survival of mesothelioma patients. The data obtained strongly indicate the utilization of HtrA1 expression as a prognostic parameter for mesothelioma and suggest this serine protease as a possible molecular target for the treatment of malignant mesotheliomas.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently shown to exert significant anti-tumoral activity in combination with cisplatin (CDDP) on mesothelioma cells. However, the mechanisms through which NSAIDs regulate the cell cycle as well as the signal pathways involved in the growth inhibition, remain unclear. In the present study, using two mesothelioma cell lines, MSTO-211H and NCI-H2452, we have investigated the influence of piroxicam alone and in association with CDDP on proliferation, cell cycle regulation and apoptosis. In both cell lines a significant effect on cell growth inhibition, respect to the control, was observed with all the drugs tested. Moreover, treatment with piroxicam or CDDP alone altered the cell cycle phase distribution as well as the expression of some cell cycle regulatory proteins in both cell lines. These effects were increased, even if in a not completely overlapping manner, after treatment with the association of piroxicam and CDDP. In particular, the two drugs in NCI cell line had a synergistic effect on apoptosis, probably through activation of caspase 8 and caspase 9, while the most evident targets among the cell cycle regulators were cyclin D1 and p21waf1. These results suggest that the association of piroxicam and CDDP specifically triggers cell cycle regulation and apoptosis in different mesothelioma cell lines and may hold promise in the treatment of mesothelioma.

Campania Mesothelioma Register was established in 2002; its purpose is to record every case of malignant mesothelioma that occurs in the registered population of Campania. Its aim is to identify new dangerous asbestos sources, by giving patients a questionnaire about their working and living habits. The questionnaire used is by National Mesothelioma Register (ReNaM). Analyzing carefully the answers to the questionnaire, it is possible to classify patients' exposure with a code given by ReNaM. By means of a recognition identification network, COR Campania identified 492 cases of malignant mesothelioma (pleura, pericardium, peritoneum and tunica vaginalis of the testis) diagnosed between 1996-2007. The analysis of the ReNaM questionnaire confirms a prevalence of professional exposures (71%), however unknown exposures (15%) also play an important role. The economic sector that determined the greatest number of professional exposures are Construction (17.5%), Industrial Metalwork (13.13%), Railway Car (9.3%), Vehicle production and maintenance (8.16%), Ship building (7.5%).

41 malignant mesothelioma cases were reported between January 2000 and April 2007 in the province of Salerno. The small town of Pellezzano, near Salerno, has more cases than any other urban centre in the province; five mesothelioma cases (three male and two female) in Pellezzano (population 9,171 in 1991) means a standardized incidence rate of 32.7 males and 21.8 females per 100.000 inhabitants. That's very alarming, considering that in Italy mesothelioma standardized incidence rate per 100.000 inhabitants is 2,98 for males and 0,98 for females. Campania Mesothelioma Register aims to investigate which kind of exposure caused this abnormal incidence rate. All five patients answered the questionnaire and a team of doctors performed an on-the-spot investigation. The studies verified the existence of two kind of asbestos exposure, professional (Cotton Manufacture, Construction, Foundry) and environmental (cement-asbestos pre-fabricated since 1980 earthquake), that have to be analyzed further.

Aim: The purpose of the present paper is to describe the geographical distribution at municipality level of mortality from malignant pleural neoplasms in the Campania Region, along with the distribution of former asbestos-exposed workers. A GIS (Geographical Information System) application has been developed to integrate exposure and mortality data., Study Design: The number of asbestos workers by municipality has been estimated by merging data provided by the National Institute for Insurance against Occupational Accidents (INAIL), the Ministry of Labour and an association of formerly exposed workers (AUSER Flegrea). The number of deaths from malignant pleural neoplasms by municipality has been derived from published studies regarding two consecutive periods: 1988-1994 and 1995-1997., Results: In the first period most deaths occurred in areas with a high number of formerly exposed asbestos workers, whilst in the second period mesothelioma mortality increased extending to other areas without registered exposed workers., Conclusion: This finding may be attributable to the presence of atypical occupational exposures, not reported by the current information systems, or to environmental, non occupational exposure patterns.

From the comparative appraisal, an area is identified for the period 1995-1997, corresponding to the so-called inner zones, in which the "ex novo" emersion of consisting cluster of mesotheliomas is recorded. Such data are analyzed for a possible correlation with professional and/or extra professional causes.

The new legislation on the labor market (Biagi Law, Ministerial Decree approved by the Council of Ministers on 06.06.2003) introduces new contractual profiles imprinted to the criterion of maximum mobility and flexibility. This new legislation does not appear equipped from a parallel legislation that guarantees occupational safety and the protection of the new professional figures.

Cause specific mortality was investigated in a cohort of insulators employed by a company which operated in various parts of Italy. Follow-up covered the years 1960-1996. The cohort, which included 893 subjects, was derived from company files of relatively poor quality, which resulted in a high rate of lost to follow-up (10.1%) and of deaths with unknown cause (12.4%). The mortality experience of the cohort was contrasted with that of the Italian population. Overall mortality (SMR 141, 90% CI 118-167, 97 observed), and cancer mortality (SMR 165, 90% CI 123-216, 38 observed) were significantly increased. Among neoplasms, significant increases were observed for lung cancer (SMR 202, 90% CI 124-311, 15 observed), pleural neoplasms (SMR 2667, CI 90% 911-6103, 4 observed), and peritoneal neoplasms (SMR 1853, 90% CI 329-5832, 2 observed). The excess mortality for lung cancer was especially pronounced in subjects with latency time longer than ten years (SMR 237.1, 90% CI 140-377, 13 observed).