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.

Mesothelioma Risk Among Maritime Workers According to Job Title: Data From the Italian Mesothelioma Register (ReNaM).

The study describes the 466 cases of malignant mesotheliomas (MM) collected by the National Mesothelioma Register (ReNaM) in Italy in the period 1993-2018 relating to subjects with exclusive asbestos exposure in merchant or military navy. The cases among maritime workers represent 1.8% of the total cases with defined exposure registred in the ReNaM, of which 212 cases (45.4%) among merchant maritime workers and 254 cases (54.5%) among navy. The distribution by site of mesothelioma showed 453 (97.2%) MM cases of the pleura, 11 (2.3%) of the peritoneum and 2 (0.4%) of the tunica vaginalis of the testis. With regard to occupational exposure, it was classified as certain in 318 (68.2%) cases, probable in 69 (14.8%) cases and possible in 79 (16.9%) cases. Among the 23 classified jobs, the highest percentages of certain exposures are among naval engineers, motor mechanics, machine captains and sailors. Machine crew accounted for 49.3% of the cases, deck crew for 27.6%. All cases began exposure on board between 1926 and 1988. Seamen were exposed to asbestos while at sea by virtue of living onboard ships and from continual release of asbestos fibers due to the motion of a vessel. Epidemiological surveillance through the ReNaM has allowed us to verify among cases in the maritime, navy and merchant marine sectors, that in the past, subjects were exposed regardless of the ship's department where have provided service therefore all these cases must be considered as occupational diseases.

Mesothelioma Risk among Construction Workers According to Job Title: Data from the Italian Mesothelioma Register.

BACKGROUND: An increased risk of mesothelioma has been reported in various countries for construction workers. The Italian National Mesothelioma Registry, from 1993 to 2018, reported exposure exclusively in the construction sector in 2310 cases. We describe the characteristics of these cases according to job title. METHODS: We converted into 18 groups the original jobs (N=338) as reported by ISTAT codes ('ATECO 91'). The exposure level was attributed at certain, probable and possible in accordance with the qualitative classification of exposure as reported in the Registry guidelines. Descriptive analysis by jobs highlights the total number of subjects for each single job and certain exposure, in descending order, insulator, plumbing, carpenter, mechanic, bricklayer, electrician, machine operator, plasterer, building contractor, painter and labourer. RESULTS: The cases grow for plumbing in the incidence periods 1993-2018, while, as expected, it decreases for insulator. Within each period considered the most numerous cases are always among bricklayers and labourers, these data confirm the prevalence of non-specialised "interchangeable" jobs in Italian construction sector in the past. CONCLUSIONS: Despite the 1992 ban, the construction sector still presents an occupational health prevention challenge, circumstances of exposure to asbestos may still occur due to incomplete compliance with prevention and protection measures.

High temperature, COVID-19, and mortality excess in the 2022 summer: a cohort study on data from Italian surveillances.

We aimed to assess whether the effect of high temperature on mortality differed in COVID-19 survivors and naive. We used data from the summer mortality and COVID-19 surveillances. We found 3.8 % excess risk in 2022 summer, compared to 2015-2019, while 20 % in the last fortnight of July, the period with the highest temperature. The increase in mortality rates during the second fortnight of July was higher among naïve compared to COVID-19 survivors. The time series analysis confirmed the association between temperatures and mortality in naïve people, showing an 8 % excess (95%CI 2 to 13) for a one-degree increase of Thom Discomfort Index while in COVID-19 survivors the effect was almost null with -1 % (95%CI -9 to 9). Our results suggest that the high fatality rate of COVID-19 in fragile people has decreased the proportion of susceptible people who can be affected by the extremely high temperature.

Incidence of malignant mesothelioma and asbestos exposure in the Emilia-Romagna region, Italy.

BACKGROUND: The aim of this study is to describe the incidence of malignant mesothelioma (MM) and asbestos exposure in an Italian region in the period 1996-June 2021. METHODS: The study included cases with microscopic confirmation and those with instrumental confirmation. For each case, information on sex, age, tumour site, morphology and date of diagnosis was collected, along with details of exposure to asbestos. RESULTS: 3,097 cases of MM (2,233 males and 864 females) were registered: 90.8% with microscopic confirmation. A total of 2,840 cases involved the pleura (92%), 230 cases the peritoneum (7%), and a small number of cases the pericardium and testis (9 and 18, respectively). Most cases (78.0%) occurred after 65 years of age, while only 1.5% concerned individuals with age < 45 years. The standardized incidence rate for the entire period (adjusted to the 2000 Italian standard population and calculated per 100,000 person-years) was equal to 3.9 in males and 1.4 in females, and the trend showed an increase with age in both sexes. Concerning asbestos exposure, 79.7% of cases were exposed (86.7% males and 60.1% females). In 70.3%, exposure was occupational (83.4% males and 33.2% females), while 20.7% of females and 0.8% of males had familial exposure. Building construction, rolling stock manufacture/repair and metalworking were the most prevalent economic activities associated with occupational exposure. CONCLUSIONS: This study offers an overview of MM in an Italian region characterized by high incidence and high exposure due to its particular production activities.

Excess risk of subsequent malignant neoplasms in adolescent and young adult cancer survivors: Results from the first Italian population-based cohort.

BACKGROUND: Evidence about late effects in adolescent and young adult (AYA) cancer survivors is scarce. This study assessed the risk of subsequent malignant neoplasms (SMNs) to identify the most common SMNs to be considered in follow-up care. METHODS: Population-based cancer registries retrospectively identified first primary tumors (between 1976 and 2013) and SMNs in AYAs (15-39 years old at their cancer diagnosis). AYA cancer survivors were those alive at least 5 years after their first cancer diagnosis. The excess risk of SMNs was measured as standardized incidence ratios (SIRs) and absolute excess risk together with the cumulative incidence of SMNs. RESULTS: The cohort included 67,692 AYA cancer survivors. The excess risk of developing any SMN (SIR, 1.6; 95% confidence interval, 1.5-1.7) was 60%. The excess risk of SMNs was significantly high for survivors of lymphomas; cancers of the breast, thyroid, female genital tract, digestive organs, gonads, and urinary tract; and melanomas. The cumulative incidence of all SMNs in AYA cancer survivors within 25 years of their first cancer diagnosis was approximately 10%. Subsequent tumors contributing to approximately 60% of all SMNs were breast cancer, colorectal cancer, corpus uteri cancer, and ovarian cancer in females and colorectal cancer, bladder cancer, prostate cancer, lung cancer, and lymphomas in males. CONCLUSIONS: These results highlight the need to personalize follow-up strategies for AYA cancer survivors.

Treatment patterns among patients with malignant pleural mesothelioma: An Italian, population-based nationwide study.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. Centralization of rare cancer in dedicated centers is recommended to ensure expertise, multidisciplinarity and access to innovation. In Italy, expert centers for MPM have not been identified in all regions. We aimed to describe the treatment patterns among MPM patients across different Italian regions and to identify factors associated with the treatment patterns across the regions. METHODS: We performed an observational study on a random sample of 2026 MPM patients diagnosed in 2003-2008. We included 26 population-based registries covering 70% of the Italian population. To identify factors associated with treatment patterns, across the different regions, we fitted a multinomial logistic regression model adjusted by age, sex, stage, histology and hospital with thoracic surgical department. RESULTS: MPM patients mostly received chemotherapy alone (41%) or no cancer-directed therapy (36%) especially the older patients. The first course of treatment for MPM patients differed across regions. Patients from Piedmont, Liguria and Campania were more likely to receive no cancer-directed therapy; those living in Tuscany and Sicily were more likely to get surgery; patients from Marche and Lazio were more likely to receive chemotherapy. These differences were not explained by age, sex, stage, histology and availability of a thoracic surgery department. CONCLUSIONS: There is limited expertise available and lack of a network able to maximize the expertise available may contribute to explaining the results of our study. Our findings support the need to ensure the appropriate care of all MPM patients in reorganizing the health care services. KEY POINTS: Significant findings of the study: MPM patients mostly received chemotherapy alone or no cancer-directed therapy especially the older patients. The first course of treatment for MPM patients differed across Italian regions. WHAT THIS STUDY ADDS: Differences in MPM clinical management are not explained by the age, stage, histology nor by the availability of a thoracic surgery department. Limited expertise for MPM contribute to explaining the unequal access to appropriate care for MPM patients in Italy.

Adolescent and Young Adult Cancer Survivors: Design and Characteristics of the First Nationwide Population-Based Cohort in Italy.

Purpose: Adolescent and young adult (AYA, 15-39 years) cancer survivors (alive at least 5 years after cancer diagnosis) are less studied than younger and older cancer survivors and research on their late effects is limited. To facilitate research on long-term outcomes of AYA cancer survivors, we established, in Italy, a population-based AYA cancer survivors' cohort. This article describes the study design and main characteristics of this cohort. Methods: The cohort derives from population-based cancer registries (CRs). Each CR identified AYA cancer patients retrospectively. Treatment for first primary cancer and all health events from diagnosis to death can be traced through linkage with available health databases, such as hospital discharge records (HDRs), mortality files, and outpatient and pharmaceutical databases. Results: Thirty-four CRs participated to the cohort which overall includes 93,291 AYAs with cancer and 67,692 cancer survivors. First primary cancer distribution in AYA cancer survivors differs by sex and age groups because of the different cancer types diagnosed in AYAs. Almost 78% of AYA cancer survivors have HDRs and 14.8% also pharmaceutical and outpatient databases. Conclusion: This cohort will be used to study, for the first time in Italy, the pattern and excess risk of late effects in AYA cancer survivors. HDRs, outpatient and pharmaceutical databases will be used to define primary treatment to assess its impact on AYA cancer survivors' late effects. This cohort exploiting data sources already available at CRs, minimize the data collection effort and it will contribute to assess the feasibility of using administrative database to study cancer survivors' late effects.

The effects of improving the mesothelioma surveillance network on sensitivity, timeliness in reporting and asbestos exposure assessment.

BACKGROUND: In Italy, Mesothelioma Registries (MRs) have been established by law for the epidemiological surveillance of occupational cancers. MRs collect information about asbestos exposure of incident cases, through interviews. In the Emilia-Romagna region, MR was implemented in 1996 and extended its network of health professionals who report suspected mesothelioma in 2001 and 2007. OBJECTIVES: This study evaluated the impact of the extension of the network on MR sensitivity and timeliness. METHODS: Mesothelioma cases were analysed in three subsequent periods: 1996-2001 (before any network extension), 2002-2007 (after first extension) and 2008-2014 (after second extension). Sensitivity was evaluated by the proportion of cases directly reported by the network out of the total number of incident cases; reporting and interview timeliness were assessed by median times between diagnosis and, respectively, reporting and interview. Pleural mesothelioma reporting timeliness was also evaluated by use of quantile regression models, stratified by diagnostic certainty and adjusted by sex and age. RESULTS: Sensitivity increased from 79.4% (1996-2001), to 89.0% (2002-2007) and to 91.4% (2008-2013). For mesothelioma with diagnostic certainty, we recorded considerably reduced reporting times from the 50th percentile on, whereas for uncertain mesothelioma relevant reductions were observed also in the lower percentiles. A reduced time to interview was observed too, which was more significant for uncertain cases. The proportion of patients directly interviewed increased from 33.5% (1996-2001), to 39.1% (2002-2007), to 49.5% (2008-2014). CONCLUSIONS: The extended network improved the MR sensitivity and allowed shorter reporting and interview times and more frequent patient interviews, thus improving accuracy of exposure definition.