Cholangiocarcinoma and Occupational Exposure to Asbestos: Insights From the Italian Pooled Cohort Study.

BACKGROUND: Recent studies supported the association between occupational exposure to asbestos and risk of cholangiocarcinoma (CC). Aim of the present study is to investigate this association using an update of mortality data from the Italian pooled asbestos cohort study and to test record linkage to Cancer Registries to distinguish between hepatocellular carcinoma (HCC) and intrahepatic/extrahepatic forms of CC. METHODS: The update of a large cohort study pooling 52 Italian industrial cohorts of workers formerly exposed to asbestos was carried out. Causes of death were coded according to ICD. Linkage was carried out for those subjects who died for liver or bile duct cancer with data on histological subtype provided by Cancer Registries. RESULTS: 47 cohorts took part in the study (57,227 subjects). We identified 639 causes of death for liver and bile duct cancer in the 44 cohorts covered by Cancer Registry. Of these 639, 240 cases were linked to Cancer Registry, namely 14 CC, 83 HCC, 117 cases with unspecified histology, 25 other carcinomas, and one case of cirrhosis (likely precancerous condition). Of the 14 CC, 12 occurred in 2010-2019, two in 2000-2009, and none before 2000. CONCLUSION: Further studies are needed to explore the association between occupational exposure to asbestos and CC. Record linkage was hampered due to incomplete coverage of the study areas and periods by Cancer Registries. The identification of CC among unspecific histology cases is fundamental to establish more effective and targeted liver cancer screening strategies.

Cause specific mortality in an Italian pool of asbestos workers cohorts.

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.

The Epidemiological Surveillance of Mesothelioma Mortality in Italy as a Tool for the Prevention of Asbestos Exposure.

As part of a surveillance plan active since the early 1990s, this study evaluates malignant mesothelioma (MM) mortality for the time-window 2010-2019 in Italy, a country that banned asbestos in 1992. National and regional mortality rates for MM, and municipal standardized mortality ratios (all mesotheliomas, pleural (MPM) and peritoneal (MPeM)), by gender and age group were calculated. A municipal clustering analysis was also performed. There were 15,446 deaths from MM (11,161 males, 3.8 × 100,000; 4285 females, 1.1 × 100,000), of which 12,496 were MPM and 661 were MPeM. In the study period, 266 people ≤50 years died from MM. A slightly decreasing rate among males since 2014 was observed. The areas at major risk hosted asbestos-cement plants, asbestos mines (chrysotile in Balangero), shipyards, petrochemical and chemical plants, and refineries. Female mortality excesses particularly were found in municipalities with a fluoro-edenite-contaminated mine (Biancavilla) and textile facilities. Excesses were also found in a region with the presence of natural asbestos fibres and in males living in two small islands. The Italian National Prevention Plan stated recommendations to eliminate asbestos exposures and to implement health surveillance and healthcare for people exposed to asbestos.

The health impact of hazardous waste landfills and illegal dumps contaminated sites: An epidemiological study at ecological level in Italian Region.

Background and aim: The implementation of idoneous management of hazardous waste, in contrast to illegal practices, is one of the environment and health priorities of the WHO. The aim of the present study, based on a collaborative agreement between the Italian National Health Institute and a Prosecution Office located in Naples North, was to evaluate the health effects of illegal landfills and burning of urban and hazardous waste in the territory of the Prosecution Office. Methods: The municipalities included in the study territory were investigated with respect to the regional population. Regression analyses were performed in the study area between four classes of an environmental municipal indicator of waste risk (MRI) previously defined, computing the relative risks (RRs) in 2-4 MRI classes, with respect to the first MRI class (the least impacted). The prevalence of reproductive outcomes and cause-specific mortality and hospitalization were analyzed in the general population and in the 0-19-year-old population using SAS software. Results: An increase of mortality and hospitalization risk in both the genders of the whole area, with respect to regional population, were found for overall all cancer cases, cancer of the stomach, the liver, the lung and the kidney, and ischemic heart diseases. An increase of mortality for leukemias in the 0-19-year-old population and in hospitalization risk for certain conditions originating in the perinatal period were observed. Correlation between MRI and the risk of mortality from breast tumors in women (MRI class 2: RR = 1.06; MRI class 3: RR = 1.15; MRI class 4: RR = 1.11) and between MRI and the risk of hospitalization from testis tumors (MRI class 2: RR = 1.25; MRI class 3: RR = 1.31; MRI class 4: RR = 1.32) were found. The hospitalization risk from breast tumors and asthma exceeded significantly in both genders of three and four MRI classes. Among the 0-19-year-old population, correlation between MRI and hospitalization from leukemias (MRI class 2: RR = 1.48; MRI class 3: RR = 1.60; MRI class 4: RR = 1.41) and between MRI and the prevalence of preterm birth (MRI class 2: RR = 1.17; MRI class 3: RR = 1.08; MRI class 4: RR = 1.25) were found. Conclusion: A correlation between health outcomes and the environmental pressure by uncontrolled waste sites was found. Notwithstanding the limitation of the study, the results promote implementing the actions of environmental remediation and the prosecution of illegal practices.

[SENTIERI Project: a systematic review on the association between sources of environmental exposure in contaminated sites and health outcomes]. / Progetto SENTIERI: revisione della letteratura scientifica sull'associazione tra fonti di esposizione ambientale in siti contaminati ed esiti di salute.

BACKGROUND: the epidemiological surveillance programme carried out in the Italian Contaminated Sites (SENTIERI Project) is based on an a priori evaluation of the epidemiological evidence of a causal association between environmental exposures and health outcomes. OBJECTIVES: to produce an updated review of the epidemiological evidence (January 2009-May 2020) on the association between environmental exposures and health outcomes predefined and published by the SENTIERI working group. METHODS: a systematic review was conducted on MEDLINE, EMBASE, and Web of Science. Additional searches were conducted on the websites of relevant organizations. The sources of environmental exposure considered were the ones included in SENTIERI Projects (chemicals, petrochemicals and refineries, steel plants, power plants, port area, waste, mines and source of asbestos). RESULTS: a total of 16,817 records were identified and, after the screening process, 14 systematic reviews were identified: two IARC Monograph, two WHO Reports, one WHO/UNEP Report, and 15 observational studies. Living in proximity of contaminated sites was associated with specific diseases (mortality or incidence), with a high heterogeneity across environmental sources. For some exposures, data suggests a gender differential effect for some causes of disease. CONCLUSIONS: compared to a previous evidence evaluation, this systematic review shows a higher number of diseases associated with residential exposure to some contaminated sites (petrochemical facilities, waste, mines, and sources of asbestos). According to the results of this review, the a priori evidence evaluation was updated and used to interpret the epidemiological data of the Sixth SENTIERI Project Report.

[SENTIERI - Epidemiological Study of Residents in National Priority Contaminated Sites. Sixth Report]. / SENTIERI - Studio epidemiologico nazionale dei territori e degli insediamenti esposti a rischio da inquinamento. Sesto Rapporto.

INTRODUCTION ADN OBJECTIVES: The Sixth Report presents the results of the "SENTIERI Project: implementation of the permanent epidemiological surveillance system of populations residing in Italian Sites of Remediation Interest", promoted and financed by the Italian Ministry of Health (Centre for Disease Control and Prevention - CCM Project 2018). The aim of this study is to update the mortality and hospitalization analyses concerning the 6,227,531 inhabitants (10.4% of the Italian population) residing in 46 contaminated sites (39 of national interest and 7 of regional interest). The sites include 316 municipalities distributed as follows: 15 in the North-East (20.3% of the investigated population); 104 in the North-West (12% of the investigated population), 32 in the Centre (12.6% of the investigated population), 165 in the South and Islands (55.5% of the investigated population). Analyses were carried out on the paediatric-adolescent (1,128,396 residents) and youth (665,284 residents) population, and a study on congenital anomalies (CA) was carried out at sites covered by congenital malformation registers. Accompanying the epidemiological assessments, site-specific socioeconomic conditions were examined and an overall estimate of excess risk for populations residing at contaminated sites was drawn up. By means of a systematic review of the scientific literature, the epidemiological evidence on causal links between sources of environmental exposure and health effects was updated to identify pathologies of a priori interest. METHODOLOGY: In the 46 sites included in the SENTIERI Project, mortality (time window: 2013-2017) and hospital admissions (time window: 2014-2018) of the general population of all ages, divided by gender, and of the paediatric-adolescent (0-1 year, 0-14 years, 0-19 years), youth (20-29 years), and overall (0-29 years) age groups, divided by gender, were analysed. In 21 sites, CA diagnosed within the first year of life were studied. Standardised mortality ratios (SMR) and hospitalization ratios (SHR) were calculated with reference to the rates in the regions to which the sites belong. The reference population was calculated net of residents in the sites. CA were studied by calculating the prevalence per 10,000 births and the ratio, multiplied by 100, between the cases observed at the site and those expected on the basis of the prevalences observed in the reference area (region or sub-regional area of belonging, according to the geographical coverage of the registry). The socioeconomic condition studied in the 46 sites is based on the convergence of three deprivation indicators with respect to the reference region: deprivation index at municipal level, deprivation index at census section level, premature mortality indicator (age range 30-69 years) for chronic non-communicable diseases. For the estimation of excess risk for the entire study population, meta-analysis of the mortality and hospitalization risk estimates for each site was carried out and the number of excess deaths estimated for the sites as a whole. The epidemiological evidence was updated through a systematic literature review (January 2009-May 2020), following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was carried out on the search engines MEDLINE, EMBASE and Web of Science; the quality of the studies included in the review was assessed using the AMSTAR 2 checklist for systematic reviews and the NewCastle-Ottawa Scale for observational studies in the case of cohort and case-control studies and a modified version thereof for ecological and cross-sectional studies. The update was based on the selection of 14 systematic reviews, 15 primary studies, 6 monographs/reports from international scientific organisations on health effects due to the presence of environmental exposure sources. RESULTS: Mortality. The a priori causes of interest that occur most frequently in excess are, in descending order: malignant lung cancer, malignant mesothelioma of the pleura, malignant bladder cancer, respiratory diseases, non-Hodgkin lymphomas, malignant liver cancer, all malignant tumours, malignant colorectal cancer, malignant stomach cancer, total mesotheliomas, malignant breast cancer, and asbestosis. Hospitalization. The a priori causes of interest that occur most frequently in excess are represented in descending order by: respiratory diseases, malignant lung cancer, malignant tumours of the pleura, malignant bladder cancer, malignant breast cancer, malignant liver cancer, asthma, malignant colorectal cancer, all malignant tumours, malignant stomach cancer, non-Hodgkin's lymphomas, acute respiratory diseases, leukaemias. The differences observed between mortality and hospitalization can be attributed to the intrinsic characteristics of the diseases (higher or lower lethality, gender differences in incidence), lifestyles, and occupational phenomena. Age classes. Excesses of general mortality were observed in the first year of life at the Manfredonia, Basso Bacino Fiume Chienti, Litorale Domizio Flegreo and Agro Aversano sites; in the 0-1 year and 0-19 year age groups at Casale Monferrato; in the paediatric age group at Serravalle Scrivia and at the Trento Nord site; in the 0-19 year age group at Sassuolo Scandiano; in the young age group (0-29 years) at the two municipalities of Cerchiara and Cassano (Crotone-Cassano-Cerchiara site). With regard to hospitalization due to natural causes, risk excesses in both genders are found in the first year of life in 35% of the sites (Porto Torres industrial areas, Bari-Fibronit, Basso bacino fiume Chienti, Bolzano, Crotone-Cassano-Cerchiara, Cerro al Lambro, Bologna ETR large repair workshop, Gela, Manfredonia, Massa Carrara, Pioltello Rodano, Pitelli, Priolo, Sesto San Giovanni, Trento Nord, and Trieste). These same sites, with the addition of Casale Monferrato, Cengio e Saliceto, Serravalle Scrivia, and Sulcis-Iglesiente-Guspinese (total: 43% of sites), show excesses for all natural causes, in both genders, even in the paediatric-adolescent age group (0-19 years). Among young adults (20-29 years), the analyses show excesses of hospitalization for all natural causes in both genders in the Bolzano, Crotone-Cassano-Cerchiara, Gela, Manfredonia, Pitelli, Priolo, and Sulcis-Iglesiente-Guspinese sites. Among young women only, excesses for all natural causes are also found in Brescia Caffaro, Brindisi, Broni, Casale Monferrato, Crotone-Cassano-Cerchiara, Falconara Marittima, Fidenza, and Massa Carrara. Congenital anomalies. In the 21 sites investigated for CA, 10,126 cases of CA, validated by participating registers, were analysed out of 304,620 resident births. Genital CA is the subgroup for which the greatest number of excesses was observed (in 6 out of 21 sites). The available evidence does not allow a causal link to be established between the excesses observed for specific subgroups of ACs and exposure to industrial sources, but the results suggest further action. The interpretation of the results appears, in fact, particularly complex as the scientific literature on the association between exposure to industrial sources and AC is very limited. Socioeconomic status. The sites in which the indicators converge to show the presence of fragility are: Litorale Vesuviano area, Val Basento industrial areas, Basso Bacino fiume Chienti, Biancavilla, Crotone-Cassano-Cerchiara, Litorale Domizio Flegreo and Agro Aversano, Livorno, Massa Carrara, Trieste. Global impact. Over the period 2013-2017, an estimated 8,342 excess deaths (CI90% 1,875-14,809) or approximately 1,668 excess cases/year, 4,353 excess deaths among males (CI90% 334-8,372) and 3,989 among females (CI90% -1,122;9,101). The pooled excess risk of general mortality is 2% in both genders (pooled SMR 1.02; CI90% 1.00-1.04). The proportion of excess deaths to total observed deaths is almost constant over time, rising from 2.5% in 1995-2002 to 2.6% in 2013-2017. The number of deaths in absolute value is also very similar between the periods analysed. Deaths from all malignant tumours contribute the most by accounting for 56% of the observed excesses, the excess risk of mortality from malignant tumours across all sites, compared to the reference populations, is 4% in the male population (pooled SMR 1.04; CI90% 1.01-1.06) and 3% among the female population (pooled SMR 1.03; CI90% 1.01-1.05). Hospitalization (2014-2018) in the 46 sites as a whole was in excess of 3% for all causes, in both genders, for all major disease groups (males: SHR pooled 1.03; CI90% 1.01-1.04 - females: SHR pooled 1.03; CI90% 1.01-1.05). The results for the pooled estimates at the 46 sites on the general population, both with regard to mortality and hospitalization, are consistent in indicating excess risk in both genders for all the diseases considered and, in particular, for all malignancies. A total of 1,409 paediatric-adolescent deaths and 999 young adult deaths were observed, and the pooled analysis of mortality across the 46 sites showed no critical issues, with pooled estimates for all causes, perinatal morbid conditions and all malignancies falling short of expectations. The analysis of hospitalizations, on the other hand, showed an excess risk of 8% (males: SHR pooled 1.08; CI90% 1.03-1.13 - females: SHR pooled 1.08; CI90% 1.03-1.14) for all causes in the first year of life, and in paediatric-adolescent and juvenile age of 3-4% among males (age 0-19 years: SHR pooled 1.04; CI90% 1.02-1.06 - age 20-29 years: SHR pooled 1.03; CI90% 1.00-1.05) and 5% among females (in both age groups; SHR pooled 1.05; CI90% 1.02-1.08). The pooled analysis of mortality for the a priori identified diseases reported excesses for specific diseases in the group of sites with sources of exposure associated with them. Mortality from total mesotheliomas is three times higher at sites with asbestos present (males:pooled SMR 3.02; CI90% 2.18-3.87 - females: pooled SMR 3.61; CI90% 2.33-4.88) and that from pleural mesotheliomas more than two times higher at the group of sites with asbestos and port areas (males: pooled SMR 2.47; CI90% 1.94-3.00 - females: pooled SMR 2.43; CI90% 1.67-3.19). Lung cancer was in excess by 6% among males (pooled SMR 1.06; CI90% 1.03-1.10) and 7% among females (pooled SMR 1.07; CI90% 1.00-1.13). In addition, there are excess mortalities for colorectal cancer at sites with chemical plants, by 4 % among males (SMR pooled 1.04; CI90% 1.01-1.08) and 3 % among females (SMR pooled 1.03; CI90% 1.00-1.07) and for bladder cancer among the male population of sites with landfills (+6 %: SMR pooled 1.06; CI90% 1.02-1.11). Among the diseases of a priori interest, stomach and soft tissue cancers are at fault as a cause of death among all the sites considered. LITERATURE REVIEW: The update of the epidemiological evidence underlying the Sixth SENTIERI Report has highlighted in the general population a possible association, previously undiscovered, between certain diseases and residence near petrochemical and steel plants, landfills, coal mines and asbestos sources. CONCLUSIONS AND PERSPECTIVES: Despite the fact that this is an ecological study, and the excesses of pathologies with multifactorial aetiology can never be mechanically attributed solely to the environmental pressure factors that exist or existed in the areas studied, the ability to identify the excesses found in the contaminated sites investigated by the SENTIERI Project confirms the validity of this method of assessing the site-specific health profile, based on the use of epidemiological evidence to identify pathologies of interest a priori. In interpreting the data and lending robustness to what has been observed, comparison with the results obtained in previous Reports is essential. The global estimates give an overall picture that shows excess mortality and hospitalization in these populations compared to the rest of the population, and show how, for specific pathologies, comparable effects are produced at sites with similar contamination characteristics. The themes developed in the in-depth chapters broaden the vision and understanding of the complex interactions between environment and health, describe the possibilities offered by new ways of communicating the results, and confirm the modernity of a Project that began way back in 2006, and that could be grafted onto the objectives of the National Recovery and Resilience Plan within the framework of the Operational Programme Health, Environment, Biodiversity and Climate.

[Methodological approaches to evaluate the over-time mortality in SENTIERI epidemiological surveillance system: a focus on cohort analyses]. / Approcci metodologici per valutare l'andamento della mortalità nel lungo periodo nel sistema di sorveglianza SENTIERI: focus sull'analisi di coorte.

The SENTIERI Project analyses the health profile of the populations residing in Italian national priority contaminated sites in specific calendar periods using a cross-sectional approach. An aspect that has not been evaluated so far is the analysis over a long period, for understanding the changes in health profiles over time and studying them also in function of the changes occurred in the territories. This article studies temporal trends by birth cohort and calendar period for overall mortality and lung cancer mortality from 1980 to 2018, separately for men and women, for three sites: Priolo (Sicily Region, Southern Italy), Pitelli (Liguria Region, Northern Italy), and Terni-Papigno (Umbria Region, Central Italy). A method for selecting the temporal model that best fits the data is then proposed. General mortality presents complex temporal profiles when considering cumulative risks, and usually the most important temporal axis is the birth cohort for cumulative SMRs (i.e., after adjusting for trends in the reference population). For lung cancer, the most important time axis is the birth cohort and the age-cohort model is the most appropriate, in particular for men of Priolo and Terni.

[The concept map of SENTIERI Project: a communication interactive digital tool of the national epidemiological surveillance system of Italian contaminated sites]. / La mappa concettuale: uno strumento digitale interattivo per la comunicazione del sistema di sorveglianza epidemiologica SENTIERI nei siti contaminati.

This paper describes the development and the envisioned use of concept maps in the framework of the SENTIERI communication strategies as an information and scientific communication tool applied to epidemiological surveillance in contaminated sites. The concept map of SENTIERI 2019-2022 was designed and implemented to foster access to complex scientific information ensuring usability of the contents and communication with the various stakeholders. The concept map aims to promote environmental health literacy in contaminated sites. The methodology adopted to create the map includes the following phases: 1. choice of a dynamic focus question; 2. selection of the representative terms of the addressed topics; 3. elaboration of the glossary of the selected terms; 4. representation of the links among the selected terms; 5. identification of the significant propositions that make explicit the meaning of each link. Online access to the map is guaranteed by the Mindomo software. The use of the concept map promotes active learning of the topics that characterize SENTIERI 2019-2022 through knowledge paths chosen because of the specific interests and learning purposes. The concept map derives from the integration of specific approaches of the epidemiological discipline with those of the social sciences and offers the possibility of developing site-specific maps through the interactions with local actors and the integration of elements related to emerging problems as well as institutional and local interests.

[Global evaluation of the mortality and hospitalization in the Italian contaminated sites included in the SENTIERI project]. / Stime globali della mortalità e ospedalizzazione nei siti contaminati italiani inclusi nel progetto SENTIERI.

Since 2006, epidemiological surveillance of populations living in Italian contaminated sites has been ongoing (SENTIERI Project). Updated global estimates of mortality (2013-2017) and hospitalization (2014-2018) are reported. The excess deaths (observed-expected) for the main groups of diseases were calculated for all the 46 sites together. Through a random-effect meta-analysis of the standardized mortality and hospitalization rates (SMR/SHR), the pooled SMR/SHR for all the sites and their groupings were estimated. In the 46 sites, 8,342 exceeding deaths (1,668/year) were estimated, 4,353 in males and 3,989 in females, resulting in an excess risk of 2% in both genders. The risk of hospitalization for all causes was in excess of 3%. These excesses are mainly attributable to malignant tumours. In subgroups of sites, exceeding SMRs were observed for all mesotheliomas and pleural mesotheliomas, lung and colorectal cancers in both genders. SHR for all causes were observed in excess in the first year of life (+8%), in the group 0-19 and 20-29 years (+3-5%); no excesses of mortality were observed in the group 0-29 years.

Mortality rates from asbestos-related diseases in Italy during the first year of the COVID-19 pandemic.

Background and aim: Patients with interstitial lung diseases, including asbestosis, showed high susceptibility to the SARS-CoV-2 virus and a high risk of severe COVID-19 symptoms. Italy, highly impacted by asbestos-related diseases, in 2020 was among the European countries with the highest number of COVID-19 cases. The mortality related to malignant mesotheliomas and asbestosis in 2020 and its relationship with COVID-19 in Italy are investigated. Methods: All death certificates involving malignant mesotheliomas or asbestosis in 2010-2020 and those involving COVID-19 in 2020 were retrieved from the National Registry of Causes of Death. Annual mortality rates and rate ratios (RRs) of 2020 and 2010-2014 compared to 2015-2019 were calculated. The association between malignant pleural mesothelioma (MPM) and asbestosis with COVID-19 in deceased adults ≥80 years old was evaluated through a logistic regression analysis (odds ratios: ORs), using MPM and asbestosis deaths COVID-19-free as the reference group. The hospitalization for asbestosis in 2010-2020, based on National Hospital Discharge Database, was analyzed. Results: In 2020, 746,343 people died; out of them, 1,348 involved MPM and 286 involved asbestosis. Compared to the period 2015-2019, the mortality involving the two diseases decreased in age groups below 80 years; meanwhile, an increasing trend was observed in subjects aged 80 years and older, with a relative mortality risks of 1.10 for MPM and 1.17 for asbestosis. In subjects aged ≥80 years, deaths with COVID-19 were less likely to have MPM in both genders (men: OR = 0.22; women: OR = 0.44), while no departure was observed for asbestosis. A decrease in hospitalization in 2020 with respect to those in 2010-2019 in all age groups, both considering asbestosis as the primary or secondary diagnosis, was observed. Conclusions: The increasing mortality involving asbestosis and, even if of slight entity, MPM, observed in people aged over 80 years during the 1st year of the COVID-19 pandemic, aligned in part with the previous temporal trend, could be due to several factors. Although no positive association with COVID-19 mortality was observed, the decrease in hospitalizations for asbestosis among individuals aged over 80 years, coupled with the increase in deaths, highlights the importance of enhancing home-based assistance during the pandemic periods for vulnerable patients with asbestos-related conditions.

Spatial Analysis of Shared Risk Factors between Pleural and Ovarian Cancer Mortality in Lombardy (Italy).

BACKGROUND: Asbestos exposure is a recognized risk factor for ovarian cancer and malignant mesothelioma. There are reports in the literature of geographical ecological associations between the occurrence of these two diseases. Our aim was to further explore this association by applying advanced Bayesian techniques to a large population (10 million people). METHODS: We specified a series of Bayesian hierarchical shared models to the bivariate spatial distribution of ovarian and pleural cancer mortality by municipality in the Lombardy Region (Italy) in 2000-2018. RESULTS: Pleural cancer showed a strongly clustered spatial distribution, while ovarian cancer showed a less structured spatial pattern. The most supported Bayesian models by predictive accuracy (widely applicable or Watanabe-Akaike information criterion, WAIC) provided evidence of a shared component between the two diseases. Among five municipalities with significant high standardized mortality ratios of ovarian cancer, three also had high pleural cancer rates. Wide uncertainty was present when addressing the risk of ovarian cancer associated with pleural cancer in areas at low background risk of ovarian cancer. CONCLUSIONS: We found evidence of a shared risk factor between ovarian and pleural cancer at the small geographical level. The impact of the shared risk factor can be relevant and can go unnoticed when the prevalence of other risk factors for ovarian cancer is low. Bayesian modelling provides useful information to tailor epidemiological surveillance.

Burden of Mortality from Asbestos-Related Diseases in Italy.

Asbestos is one of the major worldwide occupational carcinogens. The global burden of asbestos-related diseases (ARDs) was estimated around 231,000 cases/year. Italy was one of the main European asbestos producers until the 1992 ban. The WHO recommended national programs, including epidemiological surveillance, to eliminate ARDs. The present paper shows the estimate of the burden of mortality from ARDs in Italy, established for the first time. National standardized rates of mortality from mesothelioma and asbestosis and their temporal trends, based on the National Institute of Statistics database, were computed. Deaths from lung cancer attributable to asbestos exposure were estimated using population-based case-control studies. Asbestos-related lung and ovarian cancer deaths attributable to occupational exposure were estimated, considering the Italian occupational cohort studies. In the 2010-2016 period, 4400 deaths/year attributable to asbestos were estimated: 1515 from mesothelioma, 58 from asbestosis, 2830 from lung and 16 from ovarian cancers. The estimates based on occupational cohorts showed that each year 271 deaths from mesothelioma, 302 from lung cancer and 16 from ovarian cancer were attributable to occupational asbestos exposure in industrial sectors with high asbestos levels. The important health impact of asbestos in Italy, 10-25 years after the ban, was highlighted. These results suggest the need for appropriate interventions in terms of prevention, health care and social security at the local level and could contribute to the global estimate of ARDs.

Ecological meta-analytic study of kidney disease in Italian contaminated sites.

INTRODUCTION: Environmental heavy metals exposure has been associated with kidney disease. There is also some evidence that exposure to solvents may be a risk factor for kidney disease. We estimated the risk of hospitalization for kidney diseases (ICD-9 580-586) and chronic kidney disease (CDK, ICD-9 585) in residents in thirty-four Italian National Priority Contaminated Sites (NPCSs) polluted by heavy metals. METHODS: Random-effects model meta-analyses of SHR (Standard Hospitalization Ratio) computed for each NPCS was performed for all the NPCSs together, and separately, according to the presence/absence of selected industrial activities (petrochemical/refinery and steel plants), and the presence/absence of solvents contamination. RESULTS: Pooled SHRs of overall NPCSs were in excess in both genders. Statistically significant excesses were found for CKD in both genders, and for kidney diseases in females, residing in NPCSs with the combined presence of heavy metals and solvents contamination. The pooled SHRs for CKD and kidney diseases were not statistically significant in excess in NPCSs with petrochemical/refinery and steel plants, and only petrochemical/refinery plants. CONCLUSIONS: The results are suggestive of a possible kidney disease risk in population living in the above-mentioned NPCSs. Epidemiological surveillance and remediation actions in these areas are recommended.

Early mortality from malignant mesothelioma in Italy as a proxy of environmental exposure to asbestos in children.

Malignant mesothelioma (MM) is a rare neoplasm caused by asbestos. Mortality from MM in ≤50 years old people, considering the long latency, is likely related to asbestos exposure in childhood. Mortality from MM (C45, ICD10 code) is described among ≤50 years (ys) old people in Italy, in 2003-2016. National and regional Standardized Rates (SRs) were computed by age-class. The North-South trend of regional SRs, increasing in >50ys age-class, showed a flat cline in ≤50ys old people. Municipal Standardized Mortality Ratios (SMRs) were computed, with respect to regional figures, for ≤50 ys old population. In Italy, 487 people ≤50 ys old died from MM, in 2003-2016 (2.5% of all MM deaths), corresponding to 35/year. The highest SMRs were observed in Northern Regions, the most industrialized areas. Exceeding SMRs were found in 10 municipalities where former asbestos-cement plants, shipyards, and a quarry contaminated by fluoro-edenite fibres were present. Early mortality from MM, proxy of childhood environmental asbestos exposure, deserves particular concern.

A Geographic Information System-Based Indicator of Waste Risk to Investigate the Health Impact of Landfills and Uncontrolled Dumping Sites.

Uncontrolled and poor waste management practices are widespread. The global health impact of hazardous waste exposure is controversial, but the excess of some diseases appears to be consistent. The Geographic Information System (GIS, ESRI Inc., Rome, Italy) method used to estimate the waste risk exposure, in an area with many illegal waste dumps and burning sites, is described. A GIS geodatabase (ESRI ArcGIS format) of waste sites' data was built. A municipal GIS-based indicator of waste risk (Municipal Risk Index: MRI) has been computed, based on type and quantity of waste, typology of waste disposal, known or potential environmental contamination by waste and population living near waste sites. 2767 waste sites were present in an area 426 km2 large. 38% of the population lived near one or more waste sites (100 m). Illegal/uncontrolled waste dumps, including waste burning areas, constituted about 90% of all sites. The 38 investigated municipalities were categorized into 4 classes of MRI. The GIS approach identified a widespread impact of waste sites and the municipalities likely to be most exposed. The highest score of the MRI included the municipalities with the most illegal hazardous waste dumps and burning sites. The GIS-geodatabase provided information to contrast and to prosecute illegal waste trafficking and mismanagements.

Residential proximity to an industrial incinerator and risk of soft-tissue sarcoma, 1999-2014.

BACKGROUND: exposure to dioxins has been associated with an increased risk of soft-tissue sarcoma (STS). In a study relating to 1989-1998, a significant excess of STS was found in the population living within a 2-kilometre radius of an industrial incinerator located inside a Mantua industrial site. In the years 1974-1991, the incinerator burned hazardous chlorine-containing waste that resulted in the emission of dioxins. After 1991, it was exclusively fed with organic synthetic products not containing chlorine. OBJECTIVES: the aim of this case-control study was to estimate the STS risk, for 1999-2014, in the population living in four Mantua districts located in the proximity of the industrial incinerator, compared to subjects resident in the remaining parts of Mantua province, regarded as non-exposed. METHODS: the cases analysed were subjects with a first-incident diagnosis of STS between 1999 and 2014 resident at diagnosis in Mantua Province. Cases were selected using the 2013 criteria from the WHO classification. Cases of Kaposi sarcoma, PEComas and STS occurring in a previously irradiated field were excluded. For each case of soft-tissue sarcoma, four controls were randomly selected from all individuals resident in Mantua Province included in the Regional Health Service database in the years of incidence of each case (calendar year), and individually matched for gender and year of birth. Residential and occupational history (for employment in an oil refinery, and petrochemical and chemical plants) was reconstructed for all study subjects (cases and controls) since 1961. Subjects were considered exposed if they had lived in the four Mantua districts most affected by the incinerator emissions, on the basis of an atmospheric dispersion model and a dioxins biomonitoring survey. Four analyses were performed according to variously defined residential time windows. Odds ratios and corresponding 95% confidence intervals (95%CI) were calculated using conditional regression models adjusted for occupational history. RESULTS: 391 cases (203 males and 188 females) and 1,564 controls were included. The number of exposed cases and controls in the four analyses were 8 and 55, 8 and 60, 15 and 68, and 15 and 73, respectively. An increased STS risk was not observed in any of the analyses. CONCLUSIONS: in this study, no increased risk of STS was observed in subjects who had lived, in the study's time window, in the Mantua districts most affected by the incinerator emissions. The most likely interpretation of the present finding is a real STS risk reduction for subjects resident in the most recent decades in the Mantua districts most affected by the incinerator emissions, due to the cessation of burning chlorine-containing waste in the incinerator, development of some remediation plans, and implementation of new industrial procedures.

Occupational cohort study of asbestos-cement workers in a contaminated site in Sicily (Italy).

OBJECTIVES: to analyse the asbestos-related diseases risk among the former workers of Sacelit asbestos-cement plant, operating in San Filippo del Mela (Sicily: 1958- 1993). DESIGN: cohort study. SETTING AND PARTICIPANTS: 228 subjects were employed in Sacelit from 1958 to 1993. Due to the available observation periods, the analyses of the different outcomes were performed for the subjects alive at the beginning of the respective follow up periods: mortality (1986-2018) was analysed for 204 subjects (177 men, 27 women), hospitalization (2001-2016) for 164 workers (139 men, 25 women) and the incidence of mesothelioma (1998-2016) was estimated for 178 subjects (153 men, 25 women). MAIN OUTCOMES MEASURES: mortality (Standardized Mortality Ratio: SMR) and hospitalization (Standardized Hospitalization Ratio: SHR) from specific diseases were analysed. Incidence (Standardized Incidence Ratio: SIR) of mesothelioma cases was detected, also. SMR (1986-2014), SHR (2001-2016) and SIR (1998-2016), with 95% Confidence Intervals, were computed with respect to the regional rates, with STATA11. RESULTS: in the men cohort, mortality from lung (17 cases, SMR 2.83) and pleural cancers (5 cases, SMR 30) and from asbestosis (15 cases, SMR 1,930) was in excess. The risk of hospitalization was in excess, in both genders, from lung cancer (men: 6 cases, SHR 4.1; women: 2 cases, SHR 8.6) and asbestosis (men: 17 cases, SHR 1,304; women: 6 cases, SHR 2,455). The incidence of mesothelioma was in excess in men (5 cases, SIR 23.9); no female cases of mesothelioma were observed. CONCLUSIONS: a high occurrence of asbestos-related diseases in the cohort, particularly among men, was observed. The excess of hospitalization from asbestosis and lung cancer was highlighted also in women. The prosecution of the on-going health surveillance plan is particularly appropriated.

[Effects of Asbestos on Human Health. Document of the Italian Epidemiological Association (AIE)]. / Effetti dell'amianto sulla salute. Documento dell'Associazione Italiana di Epiemiologia (AIE).

OBJECTIVES: the Italian Epidemiological Association (AIE) intends to formulate assessments and recommendations on the most relevant and critical aspects in the preparation, conduct, and interpretation of epidemiological investigations on the health effects of exposure to asbestos and asbestos-like fibres. DESIGN, SETTING, AND PARTICIPANTS: the document was prepared by a working group of AIE associates, with a broad curriculum of epidemiological investigations, starting from the evaluation of scientific evidence, and was subsequently evaluated by the AIE governing body. RESULTS: the topics covered included: • consumption and presence of asbestos; • association between asbestos exposure and disease; • epidemiological surveillance of asbestos related diseases in Italy; • risk function for asbestos related diseases; • increased risk and anticipation of the disease; • interaction between asbestos and other carcinogens; • diagnosis in epidemiological studies; • assessment of exposure to asbestos; • epidemiological evidence on asbestos related diseases. CONCLUSIONS: the document ends with a summary of the conclusions of scientific research shared by AIE, with reflection on the methodology to be followed for the application at individual level of the results of epidemiological studies, and the proposal of themes on which to direct research.

Serum levels of polychlorinated biphenyls and risk of non-Hodgkin lymphoma: A hospital-based case-control study.

Polychlorinated biphenyls (PCB) have been classified by the International Agency for Research on Cancer (IARC) in Group 1 as carcinogenic to human, based on sufficient evidence in humans of an increased risk of cutaneous malignant melanoma and limited evidence for non-Hodgkin lymphoma (NHL). However present findings on the association of PCB exposure and NHL are still controversial. This study examined the relationship between PCB serum levels and risk of NHL in a Northern Italy area (Brescia province), where a chemical factory produced PCBs from 1938 to 1984, causing human contamination. A case-control study of 215 NHL patients and 215 control subjects was conducted. Cases and controls were assayed for serum levels of 33 PCB congeners. No associations were found between risk of NHL and serum levels of total PCBs (OR = 0.51; 95% CI: 0.25-1.04 for highest vs lowest quartile) or specific PCB congeners. The study confirmed a strong association of NHL with HCV infection (OR = 3.60; 95% CI: 1.30-10.02). This case-control study does not support the hypothesis of an association between current serum levels of PCBs and NHL development in the general population.

[SENTIERI: Epidemiological Study of Residents in National Priority Contaminated Sites. Fifth Report]. / SENTIERI: Studio epidemiologico nazionale dei territori e degli insediamenti esposti a rischio da inquinamento. Quinto Rapporto.

INTRODUCTION AND OBJECTIVES: This volume provides an update of the health status of the populations living in the National Priority Contaminated Sites (NPCSs) included in the SENTIERI Project. This update is part of an epidemiological surveillance programme carried out in NPCSs, promoted by the Italian Ministry of Health as a further step of a project started in 2006, when the health status of residents in contaminated sites was first addressed within the National Strategic Program "Environment and Health". The Report focuses on five health outcomes: mortality, cancer incidence, hospital discharges, congenital anomalies, and children, adolescents and young adults' health. A key element of SENTIERI project is the a priori evaluation of the epidemiological evidence of a causal association between the considered cause of disease and the exposure. When an a priori evidence is identified, it is given a greater importance in the comment of the study findings. METHODS: The present update of the SENTIERI Project concerns 45 NPCSs including in all 319 Italian Municipalities (out of over 8,000 Municipalities), with an overall population of 5,900,000 inhabitants at the 2011 Italian Census. Standardized Mortality Ratios (SMRs) and Standardized Hospitalization Ratios (SHRs), referring to a time window of 2006-2013, were computed for all the 45 NPCSs, using as a reference the corresponding mortality and hospitalization rates of the Regions where each NCPS is located. Standardized Incidence Ratios (SIRs) were computed by the Italian Association of Cancer Registries (AIRTUM) for the 22 NPCSs served by a Cancer Registry. AIRTUM covers about 56% of Italy, with partly different time-windows. SIRs have been estimated using as reference population the 4 macroareas in which Italy is divided (North-West, North-East, Centre, South). Prevalence of congenital anomalies was computed for 15 NPCSs. RESULTS: An all-cause excess of 5,267 and 6,725 deaths was observed, respectively, in men and women; the cancer death excess was of 3,375 in men and 1,910 in women. It was estimated an excess of cancer incidence of 1,220 case in men and 1,425 in women over a five-year time window. With regard to the diseases with an a priori environmental aetiological validity, an excess for malignant mesothelioma, lung, colon, and gastric cancer, and for non-malignant respiratory diseases was observed. Cancer excess mainly affected NPCSs with presence of chemical and petrochemical plants, oil refineries, and dumping hazardous wastes. An excess of non-malignant respiratory disease was also detected in NPCSs in which steel industries and thermoelectric plants were present. An excess of mesothelioma was observed in NPCSs characterized by presence of asbestos and fluoro-edenite; it was also observed where the presence of asbestos was not reported in the legislative national decrees which define the NPCS areas. It is worth noting that, even if the presence of asbestos is not reported in many NPCSs legislative decrees, petrochemical plants and steel industries, for instance, are often characterized by the presence of a large amount of this mineral that, in the past, was extensively used as an insulating material. For the first time, the present Report includes a focus on the health status of children and adolescents (1,160,000 subjects, aged 0-19 years), and young adults (660,000 subjects, aged 20-29 years). Among infants (0-1 year), an excess of 7,000 hospitalizations was observed, 2,000 of which due to conditions of perinatal origin. In the age class 0-14, an excess of 22,000 hospitalizations for all causes was observed; 4,000 of them were due to acute respiratory diseases, and 2,000 to asthma. Data on cancer incidence for subjects aged 0-24 years were derived from general population cancer registries for twenty NPCSs, and from children cancer registries (age group: 0-19 years) for six NPCSs; 666 cases where diagnosed in the age group 0-24 years, corresponding to an excess of 9%. The main contributions to this excess are from soft tissue sarcomas in children (aged 0-14 years), acute myeloid leukaemia in children (aged 0-14 years) and in the age group 0-29 years, non-Hodgkin lymphoma and testicular cancer in young adults (aged 20-29 years). In seven out of 15 NPCSs, an excess prevalence rate of overall congenital anomalies at birth was observed. Congenital anomalies excesses included the following sites: genital organs, heart, limbs, nervous system, digestive system, and urinary system. CONCLUSIONS: The main findings of SENTIERI Project have been the detection of excesses for the diseases which showed an a priori epidemiological evidence of a causal association with the environmental exposures specific for each considered NPCS. These observations are valuable within public health, because they contribute to priority health promotion activities. Looking ahead, the health benefits of an improved environmental quality might be appreciated in terms of reduction of the occurrence of adverse health effects attributable to each Site major pollutant agents. Due to the methodological approach of the present study, it was not possible to adjust for several confounding factors reported to be risk factors for the studied diseases (e.g., smoking, alcohol consumption, obesity). Even if excesses of mortality, hospitalization, cancer incidence, and prevalence of congenital anomalies were found in several NPCSs, the study design and the multifactorial aetiology of the considered diseases do not permit, for all of them, to draw conclusions in terms of causal links with environmental contamination. Moreover, it must be taken into consideration that economic factors and the availability of health services may also play a relevant role in a diseases outcome. A few observations regarding some methodological limitations of SENTIERI Project should be made. There is not a uniform environmental characterisation of the studied NPCSs in term of quality and detection of the pollutants, because this information is present in different databases which at present are not adequately connected. Moreover, the recognition of a contaminated site as a National Priority Site is based on soil and groundwater pollution, and the available information on air quality is currently sparse and not homogenous. Another limitation, in term of statistical power, is the small population size of many NPCSs and the low frequency of several health outcomes. A special caution must be paid in data interpretation when considering the correspondence between the contaminated areas and the municipality boundaries, as they do not always coincide perfectly: in some cases, a small municipality with a large industrial site, while in other settings only a part of the municipality is exposed to the sources of pollution. Furthermore, all available health information systems are currently accessible at municipality level. The real breakthrough is essentially comprised of the development and fostering of a networking system involving all local health authorities and regional environmental protection agencies operating in the areas under study. The possibility to integrate the geographic approach of SENTIERI Project with a set of ad hoc analytic epidemiological investigations, such as residential cohort studies, case control studies, children health surveys, biomonitoring surveys, and with socioepidemiological studies, might greatly contribute to the identification of health priorities for environmental remediation activities. Finally, as discussed in the last section of the report, there is a need to adopt, in each NPCS, a two-way oriented communication plan involving public health authorities, scientific community, and resident population, taking into account that the history, the cultural frame and the network of relationships specific of each local context play a major role in the risk perception perspective.