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.

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.

[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.

[The contaminated sites in the SENTIERI Project: an update of legislative, contamination, and sources of environmental exposure aspects in Italy]. / I siti contaminati del Progetto SENTIERI: aggiornamenti legislativi, caratteristiche della contaminazione e fonti di esposizione ambientale.

In Italy, the problem of contaminated sites was introduced for the first time at a regulatory level with the 'Ronchi Decree' No. 22 of 1997. Subsequently, the regulations that defined most of the contaminated Sites of National Interest (SINs) were Law No. 426 of 09.12.1998 and Law no. 179 of 31.07.2002. Today, the reference directive is the Legislative Decree 152/2006 'Consolidated Environmental Act', which in Part IV, Title V 'Remediation of contaminated sites', dictates the administrative and technical procedures for the remediation of contaminated sites. Over time, there have been numerous regulatory updates that have changed the selection criteria for the SINs, leading some of these to be downgraded to Sites of Regional Interest (SIRs). The SINs in their entirety are managed by the Italian Ministry of the Environment, today called 'of the Ecological Transition', while the pass to the competence of the territorially concerned Regions SIRs regarding the verification and eventual remediation operations. Currently, in Italy there are 42 SINs and 17 SIRs. All the information derived from the various environmental regulations and that found in the context of the remediation procedures made it possible to define the exposure of the population residing in the areas adjacent to the SINs and SIRs as well as the elaboration of sheets containing all the site-specific information.

[From the selection of priority pollutants to the analysis of health data in the SENTIERI Project]. / Dalla selezione degli inquinanti prioritari alla lettura dei dati sanitari nel Progetto SENTIERI.

OBJECTIVES: evaluation of mortality and hospitalization of residents in five Italian National Priority Contaminated Sites, studied in the SENTIERI Project, for those pathologies which, on the basis of the assessments of international agencies and bodies, are known to have an aetiological connection with exposure to specific environmental pollutants. DESIGN: ecological study. SETTING AND PARTICIOANTS: resident population in the sites of Trieste and Piombino (steel plants), and Falconara, Livorno, and the industrial area of Milazzo (petrochemical plants and/or refineries). Data extracted from the Sixth SENTIERI Report. MAIN OUTCOME MEASURES: mortality (2013-2017) and hospitalization (2014-2018) for associated causes by exposure to specific pollutants detected in the soil and water matrices. RESULTS: the results obtained do not show common patterns between the excesses found in Trieste and Piombino Sites (steel plants) nor among Livorno, Falconara, and Milazzo (petrochemicals and/or refineries). Livorno and Trieste sites, having a larger population, show the greatest number of excesses. CONCLUSIONS: the proposed approach can be a useful tool, in addition to others, for the study of the health profile of residents in contaminated sites, being also the basis for aetiological epidemiological studies.

[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.

[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.

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.

[Environmental justice promotion in industrially contaminated sites]. / Promozione della giustizia ambientale nei siti industriali contaminati.

The communities residing close to industrially contaminated sites are often affected by several fragilities, particularly of a socioeconomic nature. The disadvantaged conditions have often resulted from their marginalization in the decision-making related to the industrialization processes and may persist even when action is taken to limit the harmful consequences for the natural and social environment. Exposure to contaminants and the resulting health risks often regard socioeconomic deprived communities or the most disadvantaged subgroups, generating conditions of environmental injustice. This paper reports the results of a multidisciplinary reflection focusing on the Italian context. It describes how the national epidemiological surveillance system of communities residing close to industrially contaminated sites (named SENTIERI) and local epidemiological surveillance systems can be implemented to document local conditions of distributive injustice (inequalities in harmful exposures and consequent health risks). Furthermore, it analyses the mechanisms for generating and maintaining marginalities that prevent local communities from participating in decision-making processes (procedural injustice). Finally, after having identified and described the dimensions of community capacity, which concern both to the understanding of the adverse effects of environmental contamination and to the capability of promoting interventions against environmental injustices, it proposes an environmental justice promotion approach that starts from mapping the dimensions of community capacity as a premise to the identification of interventions for community empowerment.

[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.

[SENTIERI-ReNaM: Rationale and objectives]. / SENTIERI-ReNaM: Razionale e obiettivi.

The purpose of the SENTIERI-ReNaM Project is to analyse the incidence of mesothelioma in Italian National Priority Contaminated Sites (NPCSs) in order to estimate the health impact of asbestos on resident populations, disentangling the role of occupational and environmental exposures. SENTIERI Project has provided the relevant information on geographic and demographic structure of NPCSs and on existing sources of contamination. The Italian National Mesothelioma Registry (ReNaM), that covers the whole country through its Regional Operational Centres (CORs), has made available the procedures for estimating the incidence of mesothelioma in NPCSs and for assessing occupational and environmental asbestos exposure of the individual cases. The synergy between these two epidemiological surveillance systems lay also the ground for communication programmes with the affected communities.

[SENTIERI-ReNaM: Materials and methods]. / SENTIERI-ReNaM: Materiali e metodi.

In the framework of SENTIERI Project, this study is aimed to identify excess risks of malignant mesothelioma (MM) in Italian National Priority Contaminated Sites (NPCSs) included in the national environmental remediation programme and to discuss the results by means of data available from the Italian National Mesothelioma Registry (ReNaM). Re- NaM has a regional structure with Regional Operational Centres (CORs) in charge of identifying mesothelioma incident cases and defining the asbestos exposure modalities thought an individual questionnaire. Starting from the 44 NPCSs selected in SENTIERI Project, we excluded Calabria and Sardinia Regions from the analyses (3 NPCSs). Furthermore, for 2 sites (Emarese in Valle d'Aosta and Tito in Basilicata) no incident MM cases have been detected in the considered period. Incident cases of MM and Standardized Incidence Ratios (SIR), with corresponding 90% confidence intervals, have been estimated in each NPCS, for both gender, in the period 2000-2011. Age-standardized rates of Italian geographical macro-areas (North- East, North-West, Centre, South and Islands) have been used to estimate expected cases. For every analyzed site, the occupational and non-occupational asbestos exposure modalities are discussed.

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

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

[SENTIERI-ReNaM: Burden of disease from mesothelioma in national priority contaminated sites in Italy]. / SENTIERI-ReNaM: Valutazione globale del carico di mesotelioma.

BACKGROUND: in Italy, National Priority Contaminated Sites (NPCSs) are defined as of concern for remediation; most of them are sites with a long-lasting industrial activity. OBJECTIVE: the study aims to estimate the burden of disease from mesothelioma in NPCSs. DESIGN: mesothelioma incidence in the period 2000-2011 was estimated for the populations residing in the 39 Italian NPCSs. Data were taken from the Italian National Mesothelioma Registry (ReNaM). NPCSs were ranked into risk groups (RGs) on the basis of the presence of the following asbestos-exposing activities: 1. asbestos-cement plants; 2. asbestos mines; 3. harbours with shipyards; 4. illegal dumping sites containing asbestos; 5. petrochemicals and/or refineries, and/or steel plants; 6. chemical plants and/or landfills without explicit mention of asbestos. For the population residing in each NPCS, crude rates per 100,000 per year and number of observed minus expected cases (Obs-Exp) by gender were computed. Expected cases were calculated using the age-class rates of a reference population (the geographical macroarea of every NPCS). For every RG, the meta-analytic estimate of the attributable proportion (AP), i.e., the proportion of cases attributable to the local context, was computed, being the AP for each NPCS expressed as (Obs-Exp/Obs) x100. RESULTS: the total number of mesothelioma cases estimated in the considered period of 12 years is 2,741 (2,048 males, 693 females). The total number of Obs-Exp cases was 1,531 (1,178 in males, 353 in females). In males, crude rate ranges from 71.5 in the RG1 to 3.0 in RG4, while in females it ranges from 48.4 in RG1 to 0.6 in RG4. In males, AP in RGs from 1 to 3 is over 65%, in RG4 is 59%, in RG5 is 30%, in RG6 is -14%. AP in females gradually drops from 95% in RG1 to -64% in RG6. CONCLUSIONS: the burden of mesothelioma in populations residing in NPCSs is high, with an AP gradient consistent with the a priori RG. This burden impacts on females in a different way: rates are lower than male ones; AP is similar to male ones in the RGs 1 and 3.

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

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

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

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

Reference rates for cohort studies in Italy: an essential tool in occupational and residential cohort studies. / Aggiornamento dei tassi di mortalità in Italia, strumento fondamentale per la conduzione di studi di coorte occupazionali e residenziali.

The cohort study aims to test the hypothesis of an association between specific exposure/s and adverse health outcomes. The cohorts include the subjects who experience the exposure/s and are followed up over time to ascertain the health outcomes. This contribution presents the database for the analysis of mortality studies which is made available for public institutions carrying out cohort studies in Italy. The rates were computed from official mortality data from ISTAT. The database contains 141 causes or groups of causes for the years 1970-2012 ensuring correspondence with subsequent editions of ICD (International Classification of Diseases) VIII, IX and X.

[Index contaminants and target organs]. / Inquinanti indice e organi bersaglio.

SENTIERI Project evaluates the health impact of environmental exposures on residential population of National Priority Contaminated Sites (NPCSs). It takes into account a priori etiological hypotheses, based on the epidemiological evidence of an association between those exposures and selected diseases or causes of death. Building on the previous chapter, this one acts as a blueprint for future causal inferences based on scientific evidence relating to the health effects of exposure to specific pollutants present in the sites. In order to select the relevant pollutants, we make use of data concerning soil, aquifers, the food chain and the atmosphere. For each pollutant, we indicate cancer site and target organs, for non-neoplastic diseases, based on scientific assessment by international Agencies. We have chosen to focus on two sites: Brescia-Caffaro and Priolo. This method may conceivably be used by SENTIERI in the future to carry out more specific studies and provides the basis for a systematic analysis of contaminated sites.

[SENTIERI Project: rationale and objectives]. / Razionale e obiettivi del Progetto SENTIERI.

The Istituto Superiore di Sanità (National Institute of Health-ISS), in partnership with a network of Italian national and regional scientific institutions, initiated the SENTIERI Project (Epidemiological Study of Residents in Italian Contaminated Sites-NPCSs), the objectives, methods and initial results of which were published by Epidemiologia & Prevenzione in 2010 and 2011. In the course of 2013, some of the SENTIERI Project findings were published in international scientific journals, and the "SENTIERI approach" was among those sanctioned by the World Health Organization to conduct an initial description of the health status of residents of contaminated sites. The present Report, set up jointly by ISS and the Italian Network of Cancer Registries (AIRTUM), as anticipated in the 2011 Report, aims to provide, for each of the 18 National Priority Contaminated Sites included in the SENTIERI Project where the Italian Association of Cancer Registries is active, a mortality update to 2010, analyses of cancer incidence (1996-2005 in 17 NPCSs) and of hospital discharges (2005-2010), as is explained in detail in Chapter 2, pertaining to the project's materials and methods. The results of the analyses for each NPCS are presented in Chapter 3, while Chapter 4 includes a critical appraisal, a discussion of the methodological approach and a series of concluding remarks. The second section of the Report takes an in-depth look at important issues of public health and scientific research in contaminated sites. This Report represents an important step towards implementing a permanent epidemiological surveillance system in Italy's contaminated sites, the ultimate goal of the SENTIERI Project.