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Although the predominant occupation origin of mesothelioma is well known, determinant factors involved in filing compensation are scarcely investigated. A linkage between incident mesothelioma cases collected by Italian mesothelioma register (ReNaM) and compensation claims and assignment by Italian national insurance Institute (INAIL) has been conducted for cases diagnosed in the period 2010-2015 and occupational exposure to asbestos. Logistic regression models and decision tree models have been used to identify demographic, diagnostic and anamnestic factors significant for filing and receiving compensation. We have included in the analyses 5019 mesothelioma cases, and among them, 3321 (66.2 %) were found in INAIL archives as mesothelioma cases who fil claims for compensation. The modalities of asbestos exposure, sector of working activities and job type are crucial factors. Furthermore, gender, age at diagnosis, area of residence have been found to be significant predictors of probability to fil claims. Relative risks to fil claims were obtained for the above determinants and conditions to maximize the probability to obtain compensation identified. Our findings demonstrate that there is a need to enforce policies for improving awareness of the occupational origin for mesothelioma cases. Stakeholders, occupational health and safety institutions can play an important role for improving the sensitization regarding the rights of compensation benefits, ensuring the equity and the effectiveness of insurance, welfare and public health systems.

The main objective of this study was to analyse the space–time epidemiological differences by sex during the 2009–2020 period in the total mortality recorded among residents in each of the 25 districts of the Genoa municipality, net of the age effect. The analysis was based on official statistical data relating to total mortality and on the resident population. An estimate of the expected deaths was made to calculate the sex-specific age-standardised mortality ratio (SMR). The temporal trends and age-standardized death rates (SDRs) with respect to those of the European population specific to sex and calendar year were identified for each district. Over the entire observation period, the SMR for males ranged from 124.4 (Cornigliano) to 82.0 (Albaro), for females, the values ranged between 133.4 (Cornigliano) and 85.6 (Nervi-Quinto-S. Ilario). Between 2019 and 2020, Genoa recorded an increase in SDR of 24.5%, more pronounced in males (+26.7%) than in females (+22.4%). This epidemiological methodology is replicable and allows to quickly identify spatial, temporal, sex, and age differences in the general mortality within a municipality.

Purpose of the review: More than 50% of all gynaecological cancers can be classified as rare tumours (defined as an annual incidence of

Background In cities suffering from heavy environmental pressure or pollution, it is extremely important to rapidly access municipal demographics that can be used as indicators of population health status. Among those, mortality rates represent the most reliable data as they are officially retained and available to municipality with high level of details, thus allowing epidemiological comparison between different neighborhoods of the city across several years. Our study was aimed at validating and propose as universally applicable approach the use of municipal demographics as first-line tool to rapidly assess population health and drive health policies or urban planning in cities characterized by heavy environmental pressure. The case study of Taranto has been chosen due to the presence of the biggest European steel plant since 1960s resulting in heavy burden on environment and population health. Methods We have performed an ecological study on general mortality data due to all causes, specific by gender, age groups and disaggregated at sub-municipal level (highest data granularity) into neighborhoods from 2011 to 2020 by using official demographics related to all people living in Taranto available at General Registry Office of the municipality. A preliminary analysis comparing data available at Municipality and those provided by the Italian National Institute of Statistics (ISTAT) was performed and confirmed the high level of reliability of the municipal source of data. For comparative analyses, we used Regional demographics and mortality from ISTAT. Indirect age-standardized mortality ratios (SMR; CI 90% and 95%), specific for gender and neighborhoods, were calculated in reference to the city of Taranto and Apulia Region; direct age-standardized and neighborhoods mortality rates were computed on city population. Results The city of Taranto shows relevant inequalities in terms of mortality between the northern neighborhoods, closest to the industrial area (Paolo VI, Tamburi and Citta Vecchia-Borgo), with excess mortality highlighted across 10 years described by SMRs always higher than those of the entire Apulia region, with peaks exceeding 50% between 2015 and 2017 both in women and men. The significant excesses of mortality have increased from 2011 to 2020 and progressively extended across several neighborhoods of Taranto city. Compared to the Apulia region, in the 3 Northern neighborhoods of the city (Paolo VI, Tamburi and Citta Vecchia-Borgo) a total of 1020 excess deaths were recorded from 2011 to 2019 in both males and females (showing statistical significance), with a peak of 68% mortality excess in 2019 for men living in Paolo VI district. Conclusion The use of official mortality data allows a timely, reliable and costless assessment of population health in cities heavily impacted by environmental pollution like Taranto.

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

since 2000s, epidemiological studies conducted by the Italian Ministry of Defence on Italian soldiers sent on a mission abroad showed excess mortality and/or incidence for Hodgkin lymphomas and also a significant reduction of all tumours and of all diseases.this analysis aim to evaluate tumour incidence and overall mortality among Italian soldiers sent on a mission abroad (period 1996-2012; 3,663 cases). This investigation is preliminary to a more complete retrospective study on the cohort of soldiers affected by tumour (No. 6,104 cases) diagnosed in the period 1973-2017 and registered by the Epidemiological Defence Observatory (OED).cohort data were acquired by the Uranium Commission of the Chamber of Deputies (CUC, 2016-2018). For statistical and epidemiological reasons, mainly dictated by the number, completeness, and quality of information concerning patients (or deceased) and the study population. The survey was temporarily limited to male military aged between 20 and 59 during the period 1996-2012 (No. 3,663; 60% of the total). Military from the four Italian defence forces - Air force, Carabinieri, Army, and Navy - were, respectively, divided into two groups: those involved in at least one mission abroad ("missionaries"; No. 874; 24%) and all the others ("non-missionaries"; No. 2,789; 76%). Using the method of indirect rate standardization, the age-standardized incidence ratio comparing missionaries and non-missionaries (SIRm) and comparing missionaries and the general population considered as an external reference (SIR) were calculated, with respective 90% confidence intervals (95%CI). Similarly, the overall mortality risk among missionaries was investigated.considering the population of the non-missionaries, the analysis of tumour incidence (TM) by military forces identified excesses in the missionaries of the Air Force (SIRm: 126.7; 90% CI 107.9-147.9), Carabinieri (SIRm: 152.8; 90%CI 134.0-173.7), and the Army (SIRm: 116.2; 90%CI 108.1-125.6). Taking into account missionaries, there was an excess of risk for specific neoplasia: for hemolymphopoietic system in Carabinieri (SIRm: 150.1; 90%CI 106.0 - 207.1) and in the Army (SIRm: 109.0; 90%CI 93.9-125.9); for Hodgkin lymphoma in Air force (SIRm: 187.7; 90%CI 88.1-352.5), Carabinieri (SIRm: 187.3; 90%CI 87.9-351.8), and the Army (SIRm; 104.5; 90%CI 81.2-132.6); for leukaemia in the Army (SIRm: 142.4; 90%CI 107.5-185.4). Significant risk excesses were also observed in missionaries for stomach, testis, kidney, bladder, and thyroid tumours. On the other hand, for missionaries in the Navy, a statistically significant risk reduction for all tumours emerged (SIRm: 61.1; IC90% 51.0-72.6). Missionaries showed a higher mortality for all causes.this preliminary study confirms the need for an in-depth survey on the health status of Italian soldiers. In particular, the risk for diseases, even non-neoplastic and after 2012, should be investigated in the military over the age of 60, who has a greater risk of incidence and mortality, not only for tumour. All potential disease determinants, both environmental and personal, should also be studied.

OBJECTIVE: To investigate the carcinogenicity of styrene by reanalysing data from a previous international cohort study of workers in the reinforced plastics industry. METHODS: Mortality from cancers of prior interest was analysed with more detailed consideration of exposure-response relations and an updated classification of leukaemias and lymphomas in data from a previous international cohort study of 37 021 reinforced plastics workers exposed to airborne styrene. RESULTS: Increased mortality from non-Hodgkin's lymphoma (NHL) was associated with the mean level of exposure to styrene in air (relative risk (RR) 2.31, 95% CI 1.29 to 4.12 per 100 ppm), but not with cumulative styrene exposure. Similar associations with mean exposure were observed for the oesophagus (RR 2.44, 95% CI 1.11 to 5.36 per 100 ppm) and pancreas (RR 1.89, 95% CI 1.17 to 3.09). Oesophageal cancer mortality was also associated with cumulative styrene exposure lagged 20 years (RR 1.16, 95% CI 1.03 to 1.31). No other cancer, including lung cancer, was associated with any indicator of styrene exposure. CONCLUSION: This reanalysis does not substantially change the conclusions of the original study with respect to NHL or lung cancer but new evidence concerning cancers of the oesophagus and pancreas merits further investigation.

Rare cancers epidemiology is better known compared to the other rare diseases. Thanks to the long history of the European population-based cancer registries and to the EUROCARE huge database, the burden of rare cancers has been estimated the European (EU28) population. A considerable fraction of all cancers is represented by rare cancers (24%). They are a heterogeneous group of diseases, but they share similar problems: uncertainty of diagnosis, lack of therapies, poor research opportunities, difficulties in clinical trials, lack of expertise and of centres of reference. This paper analyses the major epidemiological indicators of frequency (incidence and prevalence) and outcome (5-year survival) of all rare cancers combined and of selected rare cancers that will be in depth treated in this monographic issue. Source of the results is the RARECAREnet search tool, a database publicly available. Disparities both in incidence and survival, and consequently in prevalence of rare cancers were reported across European countries. Major differences were shown in outcome: 5-year relative survival for all rare cancers together, adjusted by age and case-mix, varied from 55% or more (Italy, Germany, Belgium and Iceland) and less than 40% (Bulgaria, Lithuania and Slovakia). Similarly, for all the analyzed rare cancers, a large survival gap was observed between the Eastern and the Nordic and Central European regions. Dramatic geographical variations were assessed for curable cancers like testicular and non epithelial ovarian cancers. Geographical difference in the annual age-adjusted incidence rates for all rare cancers together varied between >140 per 100,000 (Italy, Scotland, France, Germany, and Switzerland) and

Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network.

Patients with soft tissue sarcoma (STS) experienced better outcomes when treated according to existing clinical practice guidelines either at reference institution or dedicated treatment networks. Despite increasing evidence supporting referral to sarcoma specialised units, up to half of patients are not managed according to guidelines, particularly those in the early stage of their disease requiring surgery. Also, criteria to certify expertise of institutions, such as the treatment volume, are debated and health authorities have only recently started identification of these centres and creation of treatment networks in Europe as well as in several countries. This process have important implications for both patient outcomes and innovation of existing treatment strategies through clinical research, making improvement of clinical pathways a priority for health care authorities. This article will discuss issues with management of patients with STS, such as pathological diagnosis and adherence to guidelines, and the definition of referral centres and networks will be illustrated along with existing experiences and population-based data.

Germ-cell tumours (GCT) of the testis and penile squamous cell carcinoma (PeSCC) are a rare and a very rare uro-genital cancers, respectively. Both tumours are well defined entities in terms of management, where specific recommendations - in the form of continuously up-to-dated guide lines- are provided. Impact of these tumour is relevant. Testicular GCT affects young, healthy men at the beginning of their adult life. PeSCC affects older men, but a proportion of these patients are young and the personal consequences of the disease may be devastating. Deviation from recommended management may be a reason of a significant prognostic worsening, as proper treatment favourably impacts on these tumours, dramatically on GCT and significantly on PeSCC. RARECAREnet data may permit to analyse how survivals may vary according to geographical areas, histology and age, leading to assume that non-homogeneous health-care resources may impact the cure and definitive outcomes. In support of this hypothesis, some epidemiologic datasets and clinical findings would indicate that survival may improve when appropriate treatments are delivered, linked to a different accessibility to the best health institutions, as a consequence of geographical, cultural and economic barriers. Finally, strong clues based on epidemiological and clinical data support the hypothesis that treatment delivered at reference centres or under the aegis of a qualified multi-institutional network is associated with a better prognosis of patients with these malignancies. The ERN EURACAN represents the best current European effort to answer this clinical need.

Finkelstein1 invited physicians and researchers interested in mesothelioma to investigate on past usage of talcum powders by affected people. In Italy, asbestos contamination in talc for industrial use has been documented,2 and, as he underlines tremolite contamination at low levels of cosmetic and pharmaceutical talc has been reported in USA by Blount3 and Gordon and colleagues.4 In the Italian National Mesothelioma Register (ReNaM), the analysis of intensive exposure to talc has been evaluated with respect to occupational and environmental history. The catalogue of possible asbestos exposure circumstances (a tool for the interviewers) reports the potential presence of industrial talcs in quarries or mines working activities, in leather tanning and in rubber industries. The use of intensive cosmetic talc for personal use is evaluated by means of a structured questionnaire,5 as reported in the ReNaM guidelines (see https://www.inail.it/cs/internet/docs/all-linee-guida-renam.pdf%3Fsection=attivita, p82, p98, in Italian). In our paper regarding gender differences in mesothelioma epidemiology,6 we have presented figures referring to 21 463 MM cases detected by ReNaM with a diagnosis between 1993 and 2012. Among female case list (6087 cases), 4374 cases (71.9%) have been interviewed for defining exposure. During the interview, 30 MM female cases referred an intensive use of talc in the context of occupational or life habits. For five of them, the regional centre has identified an exposure to asbestos due to intensive talc use, classifying such modality of exposure as ‘leisure activities’ (see ReNaM guidelines5). For the remaining 25 cases, an occupational exposure to asbestos in other working (or familiar or environmental) circumstances has been identified and coded. Registry data such as those provided by ReNaM cannot provide estimates of the mesothelioma risk associated with any particular exposure circumstance. We plan to include talc exposure at work and cosmetic talc usage in the analyses of a case–control study on pleural mesothelioma currently under way. A specific survey to compare and discuss how the modalities of exposure to talc have been evaluated in patients with mesothelioma in countries where epidemiological surveillance systems are active could improve knowledge and support prevention policies.

The management of patients with mesothelioma and thymic malignancy requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. Access to innovative strategies represents a major challenge, as there is a lack of funding for clinical research in rare cancers and their rarity precludes the design of robust clinical trials that could lead to specific approval of drugs. In this context, patient-centered initiatives, such as the establishment of dedicated networks, are warranted. International societies, such as IMIG (International Mesothelioma Interest Group) and ITMIG (International Thymic Malignancy Interest Group) provide infrastructure for global collaboration, and there are many advantages to having strong regional groups working on the same issues. There may be regional differences in risk factors, susceptibility, management and outcomes. The ability to address questions both regionally as well as globally is ideal to develop a full understanding of mesothelioma and thymic malignancies. In Europe, through the integration of national networks with EURACAN, the collaboration with academic societies and international groups, the development of networks in thoracic oncology provides multiplex integration of clinical care and research, ultimately ensuring equal access to high quality care to all patients, with the opportunity of conducting high level clinical and translational research projects.

Head and neck cancer (HNC) is a rare disease that can affect different sites and is characterized by variable incidence and 5-year survival rates across Europe. Multiple factors need to be considered when choosing the most appropriate treatment for HNC patients, such as age, comorbidities, social issues, and especially whether to prefer surgery or radiation-based protocols. Given the complexity of this scenario, the creation of a highly specialized multidisciplinary team is recommended to guarantee the best oncological outcome and prevent or adequately treat any adverse effect. Data from literature suggest that the multidisciplinary team-based approach is beneficial for HNC patients and lead to improved survival rates. This result is likely due to improved diagnostic and staging accuracy, a more efficacious therapeutic approach and enhanced communication across disciplines. Despite the benefit of MTD, it must be noted that this approach requires considerable time, effort and financial resources and is usually more frequent in highly organized and high-volume centers. Literature data on clinical research suggest that patients treated in high-accrual centers report better treatment outcomes compared to patients treated in low-volume centers, where a lower radiotherapy-compliance and worst overall survival have been reported. There is general agreement that treatment of rare cancers such as HNC should be concentrated in high volume, specialized and multidisciplinary centers. In order to achieve this goal, the creation of international collaboration network is fundamental. The European Reference Networks for example aim to create an international virtual advisory board, whose objectives are the exchange of expertise, training, clinical collaboration and the reduction of disparities and enhancement of rationalize migration across Europe. The purpose of our work is to review all aspects and challenges in and outside this network setting planned for the management of HNC patients.

In the "Epikit study" [1], P. Piscitelli with 27 co-authors from 20 scientific institutions estimated the absolute number of hospital admissions for newly diagnosed cancer in people aged 0-19 in Italian provinces and regions in 2007-2011.[...].

Background: Cancer Registries (CRs) remain the gold standard for providing official epidemiological estimations. However, due to CRs’ partial population coverage, hospitalization records might represent a valuable tool to provide additional information on cancer occurrence and expenditures at national/regional level for research purposes. The Epidemiology of Cancer in Italy (EPIKIT) study group has been built up, within the framework of the Civic Observers for Health and Environment: Initiative of Responsibility and Sustainability (COHEIRS) project under the auspices of the Europe for Citizens Program, to assess population health indicators. Objective: To assess the burden of all cancers in Italian children and adults. Methods: We analyzed National Hospitalization Records from 2001 to 2011. Based on social security numbers (anonymously treated), we have excluded from our analyses all re-hospitalizations of the same patients (n = 1,878,109) over the entire 11-year period in order to minimize the overlap between prevalent and incident cancer cases. To be more conservative, only data concerning the last five years (2007–2011) have been taken into account for final analyses. The absolute number of hospitalizations and standardized hospitalization rates (SHR) were computed for each Italian province by sex and age-groups (0–19 and 20–49). Results: The EPIKIT database included a total of 4,113,169 first hospital admissions due to main diagnoses of all tumors. The annual average number of hospital admissions due to cancer in Italy has been computed in 2362 and 43,141 hospitalizations in pediatric patients (0–19 years old) and adults (20–49 years old), respectively. Women accounted for the majority of cancer cases in adults aged 20–49. As expected, the big city of Rome presented the highest average annual number of pediatric cancers (n = 392, SHR = 9.9), followed by Naples (n = 378; SHR = 9.9) and Milan (n = 212; SHR = 7.3). However, when we look at SHR, minor cities (i.e., Imperia, Isernia and others) presented values >10 per 100,000, with only 10 or 20 cases per year. Similar figures are shown also for young adults aged 20–49. Conclusions: In addition to SHR, the absolute number of incident cancer cases represents a crucial piece of information for planning adequate healthcare services and assessing social alarm phenomena. Our findings call for specific risk assessment programs at local level (involving CRs) to search for causal relations with environmental exposures.

The recent finding of asbestos fibres in drinking water (up to 700.000 fibres/litres) in Tuscany (Central Italy) leads to concerns about health risks in exposed communities. Exposure to asbestos has been linked with cancer at several levels of the gastrointestinal tract, and it has been documented, in an animal model, a direct cytotoxic effect of asbestos fibres on the ileum. It has been recently described a possible link between asbestos and intrahepatic cholangiocarcinoma, and asbestos fibres have been detected in humans in histological samples from colon cancer and in gallbladder bile. Taken together, these findings suggest the possibility of an enterohepatic translocation of asbestos fibres, alternative to lymphatic translocation from lungs. In animal models, asbestos fibres ingested with drinking water act as a co-carcinogen in the presence of benzo(a) pyrene and, according to the International Agency for Research on Cancer (IARC ), there is evidence pointing to a causal effect of ingested asbestos on gastric and colorectal cancer. The risk seems to be proportional to the concentration of ingested fibres, to the extent of individual water consumption, to exposure timing, and to the possible exposure to other toxics (i.e., benzo(a)pyrene). Furthermore, the exposure to asbestos by ingestion could explain the epidemiological finding of mesothelioma in subjects certainly unexposed by inhalation. In conclusion, several findings suggest that health risks from asbestos could not exclusively derive from inhalation of fibres. Health hazards might also be present after ingestion, mainly after daily ingestion of drinking water for long periods. In Italy, a systemic assessment of the presence of asbestos fibres in drinking water is still lacking, although asbestos-coated pipelines are widely diffused and still operating. Despite the fact that the existence of a threshold level for health risks linked to the presence of asbestos in drinking water is still under debate, the precautionary principle should impose all possible efforts in order to revise health policies concerning this topic, and a systematic monitoring of drinking water to quantify the presence of asbestos is certainly needed in all regions. Further epidemiological studies aimed to the identification of exposed communities and to an adequate health risk assessment in their specific geographical areas are urgently needed.

Introduction Due to the strong causal association with asbestos fibres, the distribution of incident malignant mesothelioma (MM) cases over time and space likely reflect different kinds of asbestos exposures occurring in the past, as previously demonstrated in several studies. Starting from the data of a disease-specific national registry, namely the Italian mesothelioma registry (ReNaM), a geographic cluster analysis was integrated with information about exposure, either occupational or non occupational, in order to trace patterns of asbestos exposure in Italy. Methods A total of 15,322 incident cases of all-site MM, recorded by ReNaM in the period 1993 to 2008 were analysed, corresponding to 11,852 occupational, residential and familial histories reconstructed by interview. Observed cases were mapped based on the municipality of residence at diagnosis and age-specific rates of the area where municipality was located was used to calculate expected cases. A Bayesian hierarchical model was applied to identify municipality clusters and each cluster was characterised by type and source of asbestos exposure of cases. Results Thirty-two clusters of MM were mapped. Asbestos manufacturing industries and shipbuilding and repair facilities were the more common sources of asbestos exposure, but other activity sectors, such as non-asbestos textile, metal engineering and construction had a relevant contribution in some clusters. Environmental asbestos exposure was detected more frequently in clusters with an asbestos cement industry or a natural source of asbestos-like fibres. Differences by gender among clusters were attributable to environmental fraction but also to high female employment in selected activity sectors, such as textile industry. Discussion This study while indirectly confirming the role of specific natural or industrial sources of asbestos exposure for mesothelioma risk, highlights the great public health implications of spatial tracing of asbestos exposure for risk prevention, health surveillance and welfare policies.

This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities.Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data.In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity.One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population.

Protocols and results of case-control studies, pooled- and meta-analyses on the relationship between mobile phone use and risk of head tumours are critically analysed, and for each study strict elements necessary for evaluating its reliability are identified and applied (see Methods). In studies funded by public bodies, blind protocols give positive results revealing cause-effect relationships between long-term latency or use of mobile phones (cellulars and cordless) and statistically significant increases of ipsilateral risk of brain gliomas and acoustic neuromas, with biological plausibility. In studies funded or co-funded by the cellphone companies non-blind protocols give overall negative results with systematic underestimation of risk; however, also in these studies a statistically significant increase in risk of ipsilateral brain gliomas, acoustic neuromas, and parotid gland tumours is quite common when only subjects with at least 10 years of latency or exposure to mobile phones (only cellulars) are considered. Informed precautionary measures are therefore recommended as a step towards reducing risk of head tumours, especially for young people and those making intense use of cellular and cordless phones.

Objectives The epidemiology of extrapleural malignant mesothelioma is rarely discussed and the risk of misdiagnosis and the very low incidence complicate the picture. This study presents data on extrapleural malignant mesothelioma from the Italian National Mesothelioma Register (ReNaM). Methods ReNaM works on a regional basis, searching for cases and interviewing subjects to investigate asbestos exposure. Classification and code criteria for certainty of diagnosis and exposure modalities are set by national guidelines. Between 1993 and 2004, 681 cases were collected. Incidence measures and exposure data refer to the ReNaM database. Age-standardised rates were estimated by the direct method using the Italian resident population in 2001. Correlations between the incidence of pleural and non-pleural malignant mesothelioma for the 103 Italian provinces were analysed. Results Standardised incidence rates (Italy, 2004, per million inhabitants) were 2.1 and 1.2 cases for the peritoneal site (in men and women, respectively), 0.2 cases for the tunica vaginalis testis, and 0.1 in the pericardial site, varying widely in different parts of the country. Mean age at diagnosis for all extrapleural malignant mesothelioma cases was 64.4 years and the men/women ratio was 1.57:1. Median latency was over 40 years for all extrapleural sites combined. The correlation between pleural and peritoneal mesothelioma was 0.71 (Pearson’s r coefficient, p

A median survival time of about 9 months is generally reported among malignant pleural mesothelioma cases. Recently, better results in terms of survival and performance status have been reported in clinical trials that included highly selected patients. We describe the survival of pleural mesothelioma patients and the factors predictive of survival in an unselected, population-based setting. Pleural mesothelioma cases (4,100) registered from 1990 to 2001 by 9 Italian regional mesothelioma registries contributing to the network of the National Mesothelioma Registry were followed until December 31, 2005. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards regression) analyses of survival were carried out according to selected individual characteristics, including limited information on treatment in a subset of 578 cases. The median survival time was 9.8 months (95% confidence interval: 9.4-10.1). In multivariate analysis, younger age at diagnosis and epithelioid histotype were associated with significantly reduced hazard ratios. Positive effects of gender (women) and being diagnosed in a hospital with a thoracic surgery unit were of border-line statistical significance. No association with calendar period of diagnosis or asbestos exposure was present. Treatment was not associated with a statistically significant improvement in survival. This is the largest population-based study on survival in patients with pleural mesothelioma to date. Age and morphology were the main prognostic factors. Results regarding the effect of treatment were disappointing but may be useful to assess the future impact, at the population level, of recently introduced therapies.

Fish contain n-3 polyunsaturated fatty acids, principally eicosapentaenoic acid and docosahexaenoic acid, which are known to interfere with the body's inflammatory response and may be of benefit in chronic inflammatory conditions.We studied the relation between the dietary intake of n-3 fatty acids and chronic obstructive pulmonary disease (COPD) in 8960 current or former smokers participating in a population-based study of artheroscierosis. Intake of fatty acids was estimated with a dietary questionnaire. The presence of COPD was assessed by a questionnaire on respiratory symptoms and by spirometry. Three case definitions of COPD were used: symptoms of chronic bronchitis (667 subjects), physician-diagnosed emphysema reported by the subject (185 subjects), and spirometrically detected COPD (197 subjects).After control for pack-years of smoking, age, sex, race, height, weight, energy intake, and educational level docosahexaenoic acid was inversely related to the ris of COPD in a quantity-dependent fashion. The adjusted odds ratio for the highest quartile was 0.66 for chronic bronchitis (95 percent confidence interval, 0.52 to 0.85; P0.001 for linear trend across the range of intake value), 0.31 for physician-diagnosed emphysema (95 percent confidence interval, 0.18 to 0.52; P for liner trend, 0.003), and 0.50 for spirometrically detected COPD (95 percent confidence interval, 0.32 to 0.79; P for linear trend, 0.007).A high dietary intake of n-3 fatty acids may protect cigarette smokers against COPD.

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

The aim of this retrospective cohort study was to determine if the workers of an Electric Arc Furnace (EAF), which recycles scrap, had higher mortality and morbidity due to possible exposure to pollutants at work. EAFs do not run on coke ovens. In EAFs 40 % of the particulate matter (PM) is made up of PM 2.5. The foundry dust contained iron, aluminum, zinc, manganese, lead, chromium, nickel, cadmium, mercury, arsenic, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls and dioxins. Mortality study: a cohort of 331 exposed workers (6731 person-years) was studied from 19/03/1979 to 31/12/2009 (mean follow up 20.7 years). The group of exposed workers was compared to the general population and to a small control group of 32 workers from the same company. Morbidity study: rates of exemption from health fee for the seven major diseases of 235 exposed workers were compared to the rates of exemption in the Province of Trento. Mortality study: an excess mortality was found in the exposed workers as compared to the general population (SMR 1.13; 95 % CI: 0.76–1.62; 29 deaths) and to the internal group (RR 2.34; 95 % CI: 0.39–95.7). The mortality rate was increased for all tumours (SMR 1.36; 95 % CI: 0.75–2.29; 14 cases), for lung cancer (SMR 3.35; 95 % CI 1.45–6.60; 8 cases), for ischemic heart disease (SMR 1.27; 95 % CI: 0.35–3.26; 4 cases), for chronic liver disease (SMR 1.16; 95 % CI: 0.14–4.20; 2 cases) and for injury and poisoning (SMR 1.32; 95 % CI: 0.48–2.88; 6 cases). Morbidity study: there was a statistically significant increase of diabetes, rheumatoid arthritis, hypertension and cardiovascular diseases in exposed workers. With the limitations of this relatively small cohort, we found a statistically significant increase of diabetes, cardiovascular diseases and deaths due to lung cancer in exposed workers. These findings cannot be explained by PAH exposure alone; metal particulates are the most important pollutants in the working area of EAFs. A reliable method for measuring metal PM in tissues is urgently needed for exposure assessment. This study underlines the necessity to maximize the standards of security toward foundry dusts/diffuse emission. Further studies on EAF’s are needed to confirm our findings and to increase statistical power.

In spite of claiming primary prevention as their aim, studies of potential occupational and environmental health hazards that are funded either directly or indirectly by industry are likely to have negative results. The authors present three common scenarios in which faulty design of epidemiologic studies skews results, and list 15 study design flaws that lead to results that are dangerously misleading with regard to both the evaluation and the improvement of public health.

Objective: To summarize the geographical and temporal variations in incidence of pleural mesothelioma in Europe, using the extensive data available from European general cancer registries, and consider these in light of recent trends in asbestos extraction, use and import in European countries. Material and methods: The data were extracted from the European Cancer Incidence and Mortality database (EUROCIM). The inclusion criteria was acceptance in Volume VII of Cancer Incidence in Five Continents. Truncated age-standardized rates per 100,000 for the ages 40–74 were used to summarise recent geographical variations. Standardized rate ratios and 95% confidence intervals for the periods 1986–1990 and 1991–1995 were compared to assess geographical variations in risk. To investigate changes in the magnitude of most recent trends, regression models fitted to the latest available 10-year period (1988–1997) were compared with trends in the previous decade. Fitted rates in younger (40–64) and older adults (65–74) in the most recent period were also compared. Results: There was a great deal of geographical variation in the risk of mesothelioma, annual rates ranging from around 8 per 100,000 in Scotland, England and The Netherlands, to lower than 1 per 100,000 in Spain (0.96), Estonia (0.85), Poland (0.85) and Yugoslavia, Vojvodina (0.56) among men. The rank of the rates for women was similar to that observed for men, although rates were considerably lower. Between 1978 and 1987, rates in men significantly increased in all countries (excepting Denmark). In the following 10 years, there was a deceleration in trend, and a significant increase was detectable only in England and France. In addition, the magnitude of recent trends in younger men was generally lower than those estimated for older men, in both national and regional cancer registry settings. Conclusions: While mesothelioma incidence rates are still rising in Europe, a deceleration has started in some countries. A decrease may begin in the next few years in certain European populations considering the deceleration of observed trends in mesothelioma and asbestos exposure, as well as the recent ban on its use.

We recently conducted a re-analysis [Gennaro et al. 2000] of two independent studies among oil refineries workers: an Italian cohort study [Gennaro et al., 1994,1995] and a Canadian case-control study [Finkelstein, 1996]. In the re-analysis we reported that maintenance workers (MW) experienced an asbestos-attributable risk (AR) of 96-100% for mesothelioma; the same subgroup of workers showed an asbestos AR for lung cancer of 49.2 (95% Confidence Interval (CI) = 26.4-72.4) in the Italian cohort study and an AR of 42.2 (95% CI=10.8-82.6) in the Canadian study. White collar workers (WCW), likely unexposed to asbestos, were considered the internal referent population in the Italian cohort study, while other workers were the comparison group in the Canadian study.

Epidemiological data should support policy makers in their decisions. Misjudgments in data interpretation can justify the preservation of the existing situation and the lack of decision about health and environment safeguard. In the SENTIERI study on Italian polluted sites, women mortality results significantly lower than the regional mean in 11 sites in 44. The authors of this paper think that these data depend on the different impact of pollution on the population of a site, as witnessed by the cases of Brindisi and Manfredonia (Southern Italy). It is now necessary to conduct studies at suburban level integrating mortality data with other available health data.

Introduction In this short essay, we would like to address a severe divergence observed in Italy between Life Expectancy (LE) and Healthy Life Expectancy (Healthy LE) and a unique trend of worsening in Healthy LE, compared to the other European countries. Both issues emerge in recent data by EUROSTAT Report. Methods The analysis used by the authors of the EUROSTAT report is based on Sullivan method which combines 2 type of variables: mortality and morbidity data. Results While several European countries started to deal with comparable data about LE since 1960, in Italy, analogous data were available for the first time in EUROSTAT Report only in 1985. In Italy, in the period 1985-2008, there was a good progressive increase in L.E., following the best European values. Nevertheless, while until 2004 Italy was among the European best countries in terms of both LE and Healthy LE at birth, four years later in 2008 there was a shocking loss of 10 years of Healthy LE at birth in newborn girls. In the process, they lost their 2-years previous advantage with respect to males (the latter lost only 6 years of Healthy LE, in the same time span). Looking at healthy LE at age 65 in respect to 2004, Italian women in 2008 could expect to live healthy only about 7 years (as much as men) versus the almost 15 years of the European best values (14 years for men). Conclusions It is legitimate to wonder why no one official comment has been produced as a reaction after the first year of spectacular decline in Healthy Life Years in Italy: in counter-tendency with European values, from 2004 to 2008 there is a clear evidence of a 10 years drop in Healthy LE among newborn girls. The problem has not been taken into consideration even when the situation clearly appeared to worsen in the following years, dropping 4-6 more years for males and females in 2006 (for newborn babies); two more years of healthy life expectancy have been lost between 2006 and 2007 for each gender. One more year of Healthy Life Expectancy is lost in 2008. And data have not been made available any more, since then, from Italy.

BACKGROUND Fish contain n-3 polyunsaturated fatty acids, principally eicosapentaenoic acid and docosahexaenoic acid, which are known to interfere with the body's inflammatory response and may be of benefit in chronic inflammatory conditions. METHODS We studied the relation between the dietary intake of n-3 fatty acids and chronic obstructive pulmonary disease (COPD) in 8960 current or former smokers participating in a population-based study of atherosclerosis. Intake of fatty acids was estimated with a dietary questionnaire. The presence of COPD was assessed by a questionnaire on respiratory symptoms and by spirometry. Three case definitions of COPD were used: symptoms of chronic bronchitis (667 subjects), physician-diagnosed emphysema reported by the subject (185 subjects), and spirometrically detected COPD (197 subjects). RESULTS After control for pack-years of smoking, age, sex, race, height, weight, energy intake, and educational level, the combined intake of eicosapentaenoic acid and docosahexaenoic acid was inversely related to the risk of COPD in a quantity-dependent fashion. The adjusted odds ratio for the highest quartile of intake as compared with the lowest quartile was 0.66 for chronic bronchitis (95 percent confidence interval, 0.52 to 0.85; P < 0.001 for linear trend across the range of intake values), 0.31 for physician-diagnosed emphysema (95 percent confidence interval, 0.18 to 0.52; P for linear trend, 0.003), and 0.50 for spirometrically detected COPD (95 percent confidence interval, 0.32 to 0.79; P for linear trend, 0.007). CONCLUSIONS A high dietary intake of n-3 fatty acids may protect cigarette smokers against COPD.

Background Whether or not there is a relationship between use of mobile phones (analogue and digital cellulars, and cordless) and head tumour risk (brain tumours, acoustic neuromas, and salivary gland tumours) is still a matter of debate; progress requires a critical analysis of the methodological elements necessary for an impartial evaluation of contradictory studies. Methods A close examination of the protocols and results from all case-control and cohort studies, pooled- and meta-analyses on head tumour risk for mobile phone users was carried out, and for each study the elements necessary for evaluating its reliability were identified. In addition, new meta-analyses of the literature data were undertaken. These were limited to subjects with mobile phone latency time compatible with the progression of the examined tumours, and with analysis of the laterality of head tumour localisation corresponding to the habitual laterality of mobile phone use. Results Blind protocols, free from errors, bias, and financial conditioning factors, give positive results that reveal a cause-effect relationship between long-term mobile phone use or latency and statistically significant increase of ipsilateral head tumour risk, with biological plausibility. Non-blind protocols, which instead are affected by errors, bias, and financial conditioning factors, give negative results with systematic underestimate of such risk. However, also in these studies a statistically significant increase in risk of ipsilateral head tumours is quite common after more than 10 years of mobile phone use or latency. The meta-analyses, our included, examining only data on ipsilateral tumours in subjects using mobile phones since or for at least 10 years, show large and statistically significant increases in risk of ipsilateral brain gliomas and acoustic neuromas. Conclusions Our analysis of the literature studies and of the results from meta-analyses of the significant data alone shows an almost doubling of the risk of head tumours induced by long-term mobile phone use or latency.

Background Malignant mesotheliomas are strictly related to asbestos, but in a proportion of cases no exposure can be recalled. Published estimates of this proportion have important variations. Historical and geographical differences in the fraction of cancer due to any given exposure are to be expected, but incomplete identification of non-occupational exposures may have played a role. Methods To assess the role of non-occupational exposures in causing malignant mesotheliomas in Italy, the exposures of cases registered by the national mesothelioma registry (ReNaM) were examined. ReNaM started in 1993 in five regions and currently covers 98% of the Italian population. Information on occupational and non-occupational exposures of cases is collected whenever possible. Results From 1993 to 2001 ReNaM registered 5173 malignant mesothelioma cases, and exposures were assessed in 3552 of them. 144 and 150 cases with exposures limited to environmental (living in the neighbourhood of an industrial or natural source of asbestos) or familial (living with a person occupationally exposed to asbestos) circumstances, respectively, were identified, accounting for 8.3% of all cases. Conclusions Geographical variations in the proportion of cases due to non-occupational exposures may be explained by the past distribution of asbestos-using industries.

Epidemiology is a public health oriented discipline and is aimed to detect the spatial, temporal, social and causal distribution of diseases in the human population, in order to promote timely and effective preventive solutions. This paper highlights some gold standard of the epidemiological method and suggests some considerations for a critical comprehension of epidemiological studies, in particular those that deny or minimize the existence of public health risks. This paper will focus on some crucial elements such as definition, attribution, misclassification and underestimation of the harmful exposures caused by a multitude of factors, undervaluation of the possible interactions among harmful agents (even when law limits are respected), selection of exposed populations, insufficient number of studied diseases, importance of the right comparisons between similar groups when the reference population is used, disproportion between shortness of follow-up in respect with long latency period of the studied diseases, including cancer. This paper also observes that many epidemiologists carry out confirmative studies rather than exploratory ones, and they end to both underestimate and underevaluate the multiplicity of the causal associations in favour of a reductive and a critical approach to the statistics which, in final analysis, wants to replace epidemiology. It points out, moreover, that neglecting primary prevention as well as precautionary principles in the interpretation of public health studies, arises the suspicion of professional limitation or strong conflict of interests (business bias). Epidemiology is naturally oriented to both primary prevention and public health defense, and today, more than ever before, for many reasons, among which the overwhelming market power that is first and foremost the cause of the general increase of populations affected by avoidable pathologies, a systematic, correct and timely application of this precious discipline seems to be urgent to us. In conclusion, we would suggest that some technical-scientific and institutional initiatives should overcome the intrinsic limits of the current aetiological researches. The rigorous adhesion of epidemiology to its scientific method appears to be absolutely necessary in order to enforce the Italian constitutional principle which states that health defence is a fundamental right of each individual and a concern for the whole community.

In some population-based studies, a shorter median survival was observed in peritoneal as compared with pleural, malignant mesothelioma, but in others, longer median survival times or higher proportions of long-term survivors were reported. Statistical instability could have caused these differences. We analyzed survival in peritoneal mesothelioma in a large and unselected population-based case series. Cases (338) registered from 1990 to 2001 by 9 Italian regional mesothelioma registries contributing to the network of the National Mesothelioma Registry were followed until December 31, 2005. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards regression) analyses of survival were performed according to selected individual characteristics, including limited treatment information in a subset of 194 cases. The results were compared with those obtained in a parallel study on pleural mesothelioma cases. Epithelioid histotype, younger age at diagnosis and, to a lesser degree, gender (women), and being diagnosed in a hospital with a thoracic surgery unit positively and significantly affected survival. The effect of treatment was positive but not statistically significant. No trend in the risk of death according to calendar period of diagnosis was present. Peritoneal mesothelioma cases had shorter median survival time than pleural cases, but a larger proportion of long-term survivors. Survival patterns after peritoneal and pleural mesothelioma differed markedly. Treatment was not associated with a statistically significant improvement in survival, but our study included cases first diagnosed before the introduction of the most recent therapeutic approaches. This provides a large historical comparison for future studies on survival trends at the population level.

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

Health effects of occupational exposures are frequently evaluated by comparing the mortality of a whole cohort of workers with that of the general population. This study design may be affected by two major biases: a dilution effect (DE), due to the inclusion of unexposed subjects in the study cohort, and a comparison bias (CB), due to the different distribution of risk factors in the reference population. A theoretical model of the joint effect of DE and CB is proposed. Their impact was evaluated in two actual cohorts, selecting specific causes of death based on a priori hypotheses of an association. A linear relationship between the risk estimates and the two biases was found after applying either direct or indirect standardization to adjust for confounding. In the two cohorts, higher risks in exposed workers emerged only after adjusting for DE and CB. Cohort studies without an internal referent group may provide unreliable results.

To evaluate the health conditions (period 1986-2003) of the residents in Cornigliano, a district of Genoa (Italy), exposed to air pollution produced by a steel plant with coke-ovens.Three epidemiological investigations were performed: on all mortality causes; on tumors incidence; on hospitalizations for respiratory diseases. The studies are based on the Regional Mortality Registry, the Ligurian Tumor Registry and the regional hospital discharge records. We calculated both the standardized mortality (SMR) and incidence (SIR) ratios with 95% confidence limits, and we have compared the hospitalization rates in two Cornigliano subareas with different pollution levels; the "rest of Genoa" represents the general reference.In Cornigliano the total mortality is statistically higher among males (SMR 123; n. 1684) and females (SMR 148; n. 2160); in particular all tumours, prostate, brain and emolymphopoietic system were significantly higher among males, while colon-rectum and NOS intestine tumours were higher among females. SMRs were statistically higher in both genders for degenerative illnesses of the nervous central system, brain circulatory disorders and liver cirrhosis; only in males for respiratory tract illnesses and in females for myocardial heart attacks. The incidence has increased to a statistically significant extent among males for all cancer sites (SIR 110; n. 821), and for larynx, brain and emolymphopoietic system tumours. Hospitalizations for respiratory illnesses appear to be higher in the most polluted area among males (age 0-14), and decreased after closing the coke-oven plant (2002).Results of these studies suggest that air pollution in Cornigliano may have a role on populations health conditions.

The authors investigated the relationship between asbestos exposure and respiratory cancer mortality among maintenance workers and other blue-collar workers at an Italian oil refinery. The cohort contained 931 men, 29,511 person-years, and 489 deaths. Poisson regression analysis using white-collar workers as an internal referent group provided relative risk estimates (RRs) for main causes of death, adjusted for age, age at hiring, calendar period, length of exposure, and latency. Among maintenance workers, RRs for all tumors (RR = 1.50), digestive system cancers (RR = 1.41), lung cancers (RR = 1.53), and nonmalignant respiratory diseases (RR = 1.71) were significantly increased (p < 0.05); no significant excess was found for all causes and among maintenance (RR = 1.12) and other blue-collar workers (RR = 1.01). Results confirm the increased risk of death from respiratory diseases and cancer among maintenance workers exposed to asbestos, whereas other smoking-related diseases (circulatory system) were not statistically different among groups.

A truncated left-censored and right-censored lognormal model has been validated for representing pleural mesothelioma survival times in the range 5-200 weeks for data subsets grouped by age for males, 40-49, 50-59, 60-69, 70-79 and 80+ years and for all ages combined for females. The cases available for study were from Europe and USA and totalled 5580. This is larger than any other pleural mesothelioma cohort accrued for study. The methodology describes the computation of reference baseline probabilities, 5-200 weeks, which can be used in clinical trials to assess results of future promising treatment methods. This study is an extension of previous lognormal modelling by Mould et al (2002 Phys. Med. Biol. 47 3893-924) to predict long-term cancer survival from short-term data where the proportion cured is denoted by C and the uncured proportion, which can be represented by a lognormal, by (1 - C). Pleural mesothelioma is a special case when C = 0.

Objectives: To investigate cancer risk in dockyard workers exposed to carbon black. Methods: Cancer incidence was ascertained among 2101 longshoremen employed at the dockyard of Genova, Italy They were categorized a priori as exposed to low, moderate, and high level of carbon black dust. Incidence rates for the male population of the City of Genova were used to compute standardized incidence ratios (SIR). Results: A positive exposure–response relation with carbon black exposure was detected only for bladder cancer (SIR = 204, 95%CI = 112–343, in highly exposed workers). Increased incidence of pleural mesothelioma (SIR = 751, 95%CI = 302–1547) and melanoma (SIR = 288, 95%CI = 125–2168) were detected. Conclusion: Exposure to carbon black experinced by dockyard workers was associated with a two-fold increased risk of bladder cancer.

To summarize the geographical and temporal variations in incidence of pleural mesothelioma in Europe, using the extensive data available from European general cancer registries, and consider these in light of recent trends in asbestos extraction, use and import in European countries.The data were extracted from the European Cancer Incidence and Mortality database (EUROCIM). The inclusion criteria was acceptance in Volume VII of Cancer Incidence in Five Continents. Truncated age-standardized rates per 100,000 for the ages 40-74 were used to summarise recent geographical variations. Standardized rate ratios and 95% confidence intervals for the periods 1986-1990 and 1991-1995 were compared to assess geographical variations in risk. To investigate changes in the magnitude of most recent trends, regression models fitted to the latest available 10-year period (1988-1997) were compared with trends in the previous decade. Fitted rates in younger (40-64) and older adults (65-74) in the most recent period were also compared.There was a great deal of geographical variation in the risk of mesothelioma, annual rates ranging from around 8 per 100,000 in Scotland, England and The Netherlands, to lower than 1 per 100,000 in Spain (0.96), Estonia (0.85), Poland (0.85) and Yugoslavia, Vojvodina (0.56) among men. The rank of the rates for women was similar to that observed for men, although rates were considerably lower. Between 1978 and 1987, rates in men significantly increased in all countries (excepting Denmark). In the following 10 years, there was a deceleration in trend, and a significant increase was detectable only in England and France. In addition, the magnitude of recent trends in younger men was generally lower than those estimated for older men, in both national and regional cancer registry settings.While mesothelioma incidence rates are still rising in Europe, a deceleration has started in some countries. A decrease may begin in the next few years in certain European populations considering the deceleration of observed trends in mesothelioma and asbestos exposure, as well as the recent ban on its use.