[Analysis of predictive factors for non-adherence to organized screening for colorectal and breast cancers in the pre-pandemic period (2018-2019) in Lombardy Region (Northern Italy)]. / Analisi dei fattori predittivi della mancata adesione allo screening organizzato per i tumori del colon retto e della mammella nel periodo pre-pandemico (2018-2019) in Lombardia.

BACKGROUND: according to the International Agency for Cancer Research on Cancer, in 2022, breast cancer is the most common cancer in the Italian population, followed by colorectal cancer. Oncological screenings represent an effective secondary prevention strategy to counteract colorectal and breast cancers, significantly reducing mortality. In Lombardy Region (Northern Italy), screening programmes have been active since 2007, but adherence, especially in specific population subgroups, remains lower than expected. OBJECTIVES: to analyse potential predictors of non-adherence to colorectal and breast cancer screening in the Lombardy Region during the pre-pandemic period of 2018-2019. DESIGN: a retrospective cohort study aimed at investigating the role of sociodemographic variables, health status, and access to the healthcare system on non-adherence to colorectal and breast cancer screening. Statistical analyses were conducted separately by each Agency for Health Protection (ATS). The results of the models were synthesized across the Lombardy region through random-effects meta-analysis. SETTING AND PARTICIPANTS: residents within the territory of each ATS in Lombardy as of 01.01.2018 and aged between 49 and 69 years at the beginning of the follow-up. MAIN OUTCOMES MEASURES: adherence to colorectal and breast cancer screenings. RESULTS: during the study period, across the Lombardy Region, 2,820,138 individuals were eligible to participate in colorectal cancer screening, and 1,357,344 women were eligible to participate in breast cancer screening, with an invitation coverage of 87% and 86%, respectively.For breast cancer screening, older age, cardiopathy, chronic obstructive pulmonary disease (COPD), inflammatory bowel diseases (IBD), autoimmune diseases, and presence of a rare disease are associated with a reduced risk of non-adherence. Conversely, foreign citizenship, oncological diagnosis, transplant, chronic kidney disease/dialysis, diabetes, heart failure, arterial or cerebral vasculopathy, and presence of a neurological diagnosis are associated with significant excess risks of non-participation. For colorectal cancer screening, factors favouring adherence include female gender, older age, cardiopathy, COPD, autoimmune diseases, and having access/utilization of primary care. Non-adherence is associated with foreign citizenship, transplant, chronic kidney disease/dialysis, diabetes, heart failure, arterial or cerebral vasculopathy, IBD, neurological diseases, residence in assisted living facilities, use of integrated home care, and presence of disability. CONCLUSIONS: this is the first study conducted in the Lombardy Region which explores the theme of equity of access to organized screenings. This analysis highlights how sociodemographic determinants, chronic conditions, and access to the healthcare and social healthcare system constitute significant risk factors for non-adherence to screening programmes. Based on the results of this analysis, communication and/or organizational change interventions will be developed to counteract inequalities in access to effective prevention procedures.

Stima dei decessi attribuibili all'inquinamento da NO2, PM10 e PM2,5 nella Città di Milano nel 2019.

BACKGROUND: there is growing evidence that exposure to environmental pollutants affects health, including mortality, chronic diseases, and acute diseases. The World Health Organisation has recently revised downwards the safety thresholds for exposure to environmental pollutants. The City of Milan (CoM) has particularly high levels of pollution; this is due both to the presence of various emission sources and to climatic and orographic conditions. OBJECTIVES: to describe the health effects of exposure to pollutants, measured by deaths due to environmental exposure to NO2, PM10, and PM2.5 in 2019. DESIGN: observational study. Using a pollutant concentration estimation model, annual mean values of NO2, PM10, and PM2.5 were estimated for the CoM in 2019. The number of deaths attributable to each exposure was estimated using risk functions available in the literature; the values recommended by the new World Health Organisation guidelines were used as counterfactual exposure limits. SETTING AND PARTICIPANTS: the population assisted by the Agency for Health Protection of Milan and resident in the CoM on 01.01.2019, aged 30 years or older. The place of residence was georeferenced and the population was followed up until 31.12.2019. Deaths and their causes were obtained from the Causes of Death Registry. MAIN OUTCOME MEASURES: deaths attributable to exposure from non-accidental causes, cardiovascular diseases, respiratory diseases, and lung cancer were estimated. RESULTS: in 2019, the estimated annual average level of NO2 was 36.6 µg/m3, that of PM10 was 24.9 µg/m3, and that of PM2.5 was 22.4 µg/m3, with levels varying across the city area. Concerning exposure to NO2, in 2019 10% of deaths for natural causes were estimated to be attributable to annual mean levels of NO2 above 10 µg/m3. As regard PM2.5, 13% of deaths for natural causes and 18% of deaths from lung cancer were attributable to an annual mean level above 5 µg/m3. The impact of exposure to particulate matter on mortality does not seem to be the same in all the areas of the CoM. CONCLUSIONS: the health impact of exposure to airborne particulate matter in the CoM population is high. It is important that citizens, policy-makers, and stakeholders address this issue, because of its impact on both health and healthcare costs.

The long-term effects of hospitalization on health care expenditures: An empirical analysis for the young-old population in Lombardy.

As the burden of acute care on government budgets is mounting in many countries, documenting the evolution of health costs following patients' hospital admission is essential for assessing overall hospital-related costs. In this paper, we investigate the short- and long-term effects of hospitalization on different types of health care expenditures. We specify and estimate a dynamic DID model using register data of the entire population of individuals aged 50-70 residing in Milan, Italy, over the period 2008-2017. We find evidence of a large and persistent effect of hospitalization on total health care expenditures, with future medical expenses mostly accounted for by inpatient care. Considering all health treatments, the overall effect is sizable and is about twice the cost of a single hospital admission. We show that chronically ill and disabled individuals require greater post-discharge medical assistance, especially for inpatient care, and that cardiovascular and oncological diseases together account for more than half of expenditures on future hospitalizations. Alternative out-of-hospital management practices are discussed as a post-admission cost-containment measure.

[Description of excess of overall and cause-specific mortality in the Agency for Health Protection of the Metropolitan Area of Milan (Lombardy Region, Northern Italy) in 2020]. / Descrizione degli eccessi di mortalità per tutte le cause e specifici per causa nell'ATS di Milano nel 2020.

BACKGROUND: as a result of the SARS-CoV-2 pandemic, a generalised mortality excess was recorded in 2020. However, the mortality for COVID-19 cannot fully explain the observed excesses. The analysis of cause-specific mortality could contribute to estimate the direct and indirect effects of the SARS-CoV-2 outbreak and to the monitoring mortality trends. OBJECTIVES: to describe the impact of the SARS-CoV-2 epidemic in overall and cause-specific mortality in population residing in the Agency for Health Protection (ATS) of Milan. Descriptive analysis of cause-specific mortality within thirty days of SARS-COV-2 infection. DESIGN: descriptive analysis of overall and cause-specific mortality in the ATS of Milan area in 2020 and comparison with a reference period (2015-2019). SETTING AND PARTICIPANTS: overall deaths in ATS of Milan in 2020 were collected, using the Local Registry of Causes of Death, and were classified according to the ICD-10 codes. MAIN OUTCOME MEASURES: total and weekly overall and cause-specific mortality, by age. RESULTS: in 2020, 44,757 deaths for all causes were observed in people residing in the ATS of Milan with percentage change of 35%. The leading cause of death in 2020 were cardiovascular disease and neoplasm; COVID-19 infection was the third cause. An excess of mortality was observed for most of all causes of deaths. Starting from 40-49-year age group, an increase of mortality was observed; the largest increase was observed in the group 70+ years. The largest increases were observed for endocrine, respiratory, and hypertensive diseases. On the contrary, for neoplasm, infectious (not COVID-19) diseases, traffic-related mortality, and cerebrovascular disease and ictus, a decrease of mortality was observed. The greater mortality increase was observed during the first pandemic wave. The leading cause of death after positive swab was COVID-19 infection, with little variation with age class. Other frequent causes of death were respiratory diseases, cardiovascular diseases, and neoplasm. CONCLUSIONS: the study showed a generalised increase for most causes of death; observed mortality trends may indicate delay in access to health care system, in diagnosis and treatment.

Age-period-cohort effects in utilization of diagnostic procedures leading to incidental colorectal cancer detection.

BACKGROUND AND AIM: Despite the overall decrease in colorectal cancer (CRC) incidence, a small but constant rise has been recently observed in people younger than 50 years across several countries. This phenomenon can be explained by environmental or lifestyle factors, but it may also be partially justified by an increasing tendency in younger cohorts to undertake diagnostic procedures that may lead to CRC incidental diagnosis. METHODS: We performed an age-period-cohort analysis on 1 815 694 diagnostic procedures undertook by the population of the City of Milan, served by the Agency for Health Protection of Milan, between 1999 and 2018. We considered all instances of colonoscopy, rectoscopy, fecal occult blood test (FOBT) and ultrasonography. We stratified by gender, nationality and quintile of socioeconomic deprivation. RESULTS: Incidence of utilization rose with age for all procedures but rectoscopy; there was a marked increase from 2005 to 2010 for FOBT and colonoscopy. A strong all-procedures cohort effect was observed, greater for FOBT and colonoscopy. A steady increase of diagnostic procedures utilization started in cohorts born in the late 1950s, with a relative effect rising from 0.91 [95% confidence interval (CI) 0.90-0.92] for the 1950 cohort to 5.03 (95% CI, 4.58-5.48) for the 1990 one. CONCLUSION: We found a growing tendency in younger cohorts to undertake diagnostic procedures, explainable by inappropriate access to endoscopic procedures, that can lead to an incidental diagnosis of CRC. This finding may at least partially explain the observed rising incidence of early-onset CRC.

Administrative healthcare data to predict performance status in lung cancer patients.

The dataset includes 4488 patients diagnosed with lung cancer (ICD-O 3[3], C33-C34) between 2010-2012 and 2016-2018 in the territory of the Agency for Health Protection (ATS) of Milan, Italy, and selected from its population cancer registry on the basis of availability of the following information: performance status (PS), age, sex, and stage at diagnosis. The dataset includes also the following variables, extracted from the health databases of the ATS and linked to the variables derived from the cancer registry through deterministic record linkage on a unique key (tax code): Charlson comorbidity index, presence of chronic obstructive pulmonary disease, number of hospitalizations, outpatient visits, emergency accesses and prescribed drugs in the previous year, and dispensed durable medical equipment in the previous three years. The dataset was used to develop a logistic prediction model for PS, dichotomized as 'poor' (ECOG, 3-5) and 'good' (ECOG, 0-2), on the basis of all other variables in the dataset. The prediction model was developed on a 50% random subsample of the described dataset (development dataset, n = 2,244) and validated on the remaining half. The area under the curve (AUC) of the model in the development and validation samples were 0.76 and 0.73, respectively. The developed model was used to predict 'good' vs. 'poor' PS in a sample of patients with advanced lung cancer, from the same registry and years, for which the information was not available. Researchers using registry data, or electronic claims, to perform studies of oncologic therapy effectiveness for lung cancer could use the reported coefficients to predict PS value, dichotomized as 'good' or 'poor'.

Immune checkpoint inhibitors at any treatment line in advanced NSCLC: Real-world overall survival in a large Italian cohort.

OBJECTIVES: To estimate the average treatment effect of immune checkpoint inhibitors in any line of treatment in a 2016-2018 population-based cohort of patients with advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: The cohort, and information on the tumor, were derived from the cancer registry of the Agency for Health Protection of Milan, Italy. Inclusion criteria were adult age, microscopically confirmed NSCLC, stage IIIB or IV at diagnosis, and having received at least one line of treatment. Treatment with all licensed anti PD-1/PD-L1 inhibitors was derived from inpatients and outpatients' pharmaceutical databases of the ATS and vital status at 31 December 2019 from the health registry office of the Lombardy region. We investigated, with a causal approach, the relationship between survival and anti PD-1/PD-L1 treatment at any line constructing a directed acyclic graph and fitting a Marginal Structural Cox Model (MSCM). RESULTS: Of 1673 subjects, 324 received anti PD-1/PD-L1 at any treatment line. Overall, one-year survival was 61.1% (95 %CI, 55.6-66.2%) in the group treated with anti PD-1/PD-L1 at any line and 31.1% (95 %CI, 28.6-33.5%) among not treated. One-year hazard ratio (HR) of death for not treated vs. treated was 2.15 (95 %CI, 1.91-2.41), decreasing to 1.23 (95 %CI, 1.03-1.46) at two years and reaching one in the third year. CONCLUSION: In un unselected population-based cohort with advanced lung cancer, treatment with anti PD-1/PD-L1 at any line lowered the hazard of death up to two-years from date of diagnosis, confirming the efficacy of immunotherapy outside clinical trials.

Association Between Smoking And Cancers Among Women: Results From The FRiCaM Multisite Cohort Study.

Background: Smoking is one of the leading causes of death worldwide, and it is strongly associated with several human cancers. However, the differential effects of cigarette smoke on the development and progression of different types of cancer remain unclear, and related data are limited. Methods: In this longitudinal cohort study conducted among 75,324 women aged 41-76 years, we aimed to evaluate the effect of exposure to tobacco smoke on cancer development. The participants completed a questionnaire assessing socio-demographic characteristics, anthropometric measures, health status, and lifestyle habits, including smoking and dietary habits; Cox proportional hazards regression modelling was used to evaluate the association between smoking and 21 different types of cancer. Results: After a 15-year follow-up, we identified 9,487 cases of cancer through record linkage with the Cancer Registry of Milan. Smoking was found to be positively associated with all neoplasms, with a Hazard Ratio (HR) of 1.10 (95% Confidence Interval (CI), 1.04-1.16). Regarding the specific types, we found the following associations: cancer of the oral cavity HR = 2.63 ( 95% CI 1.72-4.01]), oesophagus HR = 3.09 (95% CI 1.37-6.96), stomach HR = 1.52 (95% CI 1.10-2.11), pancreas HR = 1.69 (95% CI 1.29-2.21), larynx HR= 34.81 (95% CI 8.07-150.14), lung HR = 8.48 (95% CI 7.09-10.14), cervix uteri HR = 2.51 (95% CI 1.38-4.57), and bladder and urinary tract HR = 5.67 ( 95% CI 3.96-8.14); lymphoma HR = 1.37 (95% CI 1.03-1.83); and colorectal cancer HR = 1.30 (95% CI 1.11-1.51). Conclusions: Our results thus demonstrate how smoke exposure increases the risk of several types of cancer. Considering the increasing prevalence of smoking among women, our results highlight the need to prioritize the development of anti-smoking campaigns targeted at women in order to contrast the evident gender inequality with respect to healthcare.

Development of a multivariable model predicting mortality risk from comorbidities in an Italian cohort of 18,286 confirmed COVID-19 cases aged 40 years or older.

OBJECTIVES: to develop a risk prediction model for 30-day mortality from COVID­19 in an Italian cohort aged 40 years or older. DESIGN: a population-based retrospective cohort study on prospectively collected data was conducted. SETTING AND PARTICIPANTS: the cohort included all swab positive cases aged 40 years older (No. 18,286) among residents in the territory of the Milan's Agency for Health Protection (ATS-MI) up to 27.04.2020. Data on comorbidities were obtained from the ATS administrative database of chronic conditions. MAIN OUTCOME MEASURES: to predict 30-day mortality risk, a multivariable logistic regression model, including age, gender, and the selected conditions, was developed following the TRIPOD guidelines. Discrimination and calibration of the model were assessed. RESULTS: after age and gender, the most important predictors of 30-day mortality were diabetes, tumour in first-line treatment, chronic heart failure, and complicated diabetes. The bootstrap-validated c-index was 0.78, which suggests that this model is useful in predicting death after COVID-19 infection in swab positive cases. The model had good discrimination (Brier score 0.13) and was well calibrated (Index of prediction accuracy of 14.8%). CONCLUSIONS: a risk prediction model for 30-day mortality in a large COVID-19 cohort aged 40 years or older was developed. In a new epidemic wave, it would help to define groups at different risk and to identify high-risk subjects to target for specific prevention and therapeutic strategies.

Strategy to identify priority groups for COVID-19 vaccination: A population based cohort study.

BACKGROUND: Evidence from COVID-19 outbreak shows that individuals with specific chronic diseases are at higher risk of severe prognosis after infection. Public health authorities are developing vaccination programmes with priorities that minimize the risk of mortality and severe events in individuals and communities. We propose an evidence-based strategy that targets the frailest subjects whose timely vaccination is likely to minimize future deaths and preserve the resilience of the health service by preventing infections. METHODS: The cohort includes 146,087 cases with COVID-19 diagnosed in 2020 in Milan (3.49 million inhabitants). Individual level data on 42 chronic diseases and vital status updated as of January 21, 2021, were available in administrative data. Analyses were performed in three sub-cohorts of age (16-64, 65-79 and 80+ years) and comorbidities affecting mortality were selected by means of LASSO cross-validated conditional logistic regression. Simplified models based on previous results identified high-risk categories worth targeting with highest priority. Results adjusted by age and gender, were reported in terms of odds ratios and 95%CI. RESULTS: The final models include as predictors of mortality (7,667 deaths, 5.2%) 10, 12, and 5 chronic diseases, respectively. The older age categories shared, as risk factors, chronic renal failure, chronic heart failure, cerebrovascular disease, Parkinson disease and psychiatric diseases. In the younger age category, predictors included neoplasm, organ transplantation and psychiatric conditions. Results were consistent with those obtained on mortality at 60 days from diagnosis (6,968 deaths). CONCLUSION: This approach defines a two-level stratification for priorities in the vaccination that can easily be applied by health authorities, eventually adapted to local results in terms of number and types of comorbidities, and rapidly updated with current data. After the early phase of vaccination, data on effectiveness and safety will give the opportunity to revise prioritization and discuss the future approach in the remaining population.

Population-based incidence and prevalence of inflammatory bowel diseases in Milan (Northern Italy), and estimates for Italy.

OBJECTIVE: A reliable measure of the burden of inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are essential to monitor their epidemiology and plan appropriate health services. METHODS: This is a population-based study carried out in the Milan Agency for Health Protection. Incident and prevalent cases were identified according to specific codes in hospital discharges and copayment exemptions. Age-standardized incidence rates were computed for 2015-2018 and yearly rates from 2010 to 2018, as well as annual prevalence and prevalence on 31 December 2018. Incidence and prevalence estimates for Italy were also produced. RESULTS: During 2015-2018, 3434 citizens had an IBD diagnosis, 2154 (62.7%) ulcerative colitis and 1.280 (37.3%) Crohn's disease. Age-adjusted incidence rates were 15.3 [95% confidence interval (CI), 14.7-16.0] for ulcerative colitis and 9.4 (8.9-9.9) for Crohn's disease. Incidence was stable during 2010-2018 for both diseases. On 31 December 2018, there were 15 141 prevalent patients, corresponding to a proportion of 442.3 every 100 000 inhabitants/year (95% CI, 435.6-449.8). Prevalence proportion has increased to around +10% per year from 2010 to 2018. Projections for Italy assessed the burden of IBD in more than 15 000 new cases/year (55% ulcerative colitis) and around 260 000 prevalent cases (62% ulcerative colitis). CONCLUSIONS: The exploitation of administrative data provides reliable and up-to-date measures of the burden of disease. Incidence of IBDs is stable while prevalence notably grows. The burden of IBDs and the consequent need for care and follow-up is going to increase in the future.

Indicators of guideline-concordant care in lung cancer defined with a modified Delphi method and piloted in a cohort of over 5,800 cases.

BACKGROUND: To identify indicators of guideline-concordant care in lung cancer, to implement such indicators with cancer registry data linked to health databases, and to pilot them in a cohort of patients from the cancer registry of the Milan Province. METHODS: Thirty-four indicators were selected by revision of main guidelines by cancer epidemiologists, and then evaluated by a multidisciplinary panel of clinicians involved in lung cancer care and working on the pathway of lung cancer diagnosis and treatment in the Lombardy region, Italy. With a modified Delphi method, they assessed for each indicator the content validity as a quality measure of the care pathway, the degree of modifiability from the health professional, and the relevance to the health professional. Feasibility was assessed using the cancer registry and the routine health records of the Lombardy region. Feasible indicators were then calculated in the cohort of lung cancer patients diagnosed in 2007-2012 derived from the cancer registry of the Milan Province. Criterion validity was assessed reviewing clinical records of a random sample of 114 patients (threshold for acceptable discordance ≤20%). Finally, reliability was evaluated at the provider level. RESULTS: Initially, 34 indicators were proposed for evaluation in the first Delphi round. Of the finally 22 selected indicators, 3 were not feasible because the required information was actually not available. The remaining 19 were calculated on the pilot cohort. After assessment of criterion validity (3 eliminated), 16 indicators were retained in the final set and evaluated for reliability. CONCLUSION: The developed and piloted set of indicators is now available to implement and monitor, over time, quality initiatives for lung cancer care in the studied health system.

The Economic Impact of Rectal Cancer: A Population-Based Study in Italy

Costs of cancer care are increasing worldwide, and sustainability of cancer burden is critical. In this study, the economic impact of rectal cancer on the Italian healthcare system, measured as public healthcare expenditure related to investigation and treatment of rectal cancer patients is estimated. A cross-sectional cohort of 9358 rectal cancer patients is linked, on an individual basis, to claims associated to rectal cancer diagnosis and treatments. Costs refer mainly to years 2010-2011 and are estimated by phase of care, as healthcare needs vary along the care pathway: diagnostic procedures are mainly provided in the first year, surveillance procedures are addressed to chronically ill patients, and end-of-life procedures are given in the terminal status. Clinical approaches and corresponding costs are specific by cancer type and vary by phase of care, stage at diagnosis, and age. Surgery is undertaken by the great majority of patients. Thus, hospitalization is the main cost driver. The evidence produced can be used to improve planning and allocation of healthcare resources. In particular, early diagnosis of rectal cancer is a gain in healthcare budget. Policies raising spreading of and adherence to screening plans, above all when addressed to people living in Southern Italy, should be strongly encouraged.

Paraneoplastic Neurological Syndromes: Study of Prevalence in a Province of the Lombardy Region, Italy.

Paraneoplastic neurological syndromes (PNSs) are a heterogeneous group of rare immune-mediated diseases associated with cancer. The aim of this study was to investigate the prevalence of PNSs in the province of Brescia. PNS prevalence was calculated using the Lombardy regional hospital admission records from 1998 to 2003. We used the website "Epidemiologic and Economic Atlas of Hospital Activities in Lombardy" and the "International Statistical Classification of Diseases and Related Health Problems". In the province of Brescia, we found 54 cases of PNSs, 29 with subacute neuropathies, five with paraneoplastic cerebellar degeneration and 20 with encephalomyelitis. Peripheral nervous system diseases were the most frequent neurological disorders. In Lombardy, the number of PNS patients admitted was 322 (133 with encephalomyelitis, 21 with paraneoplastic cerebellar degeneration, 166 with polyneuropathies and two with optic degeneration). In Lombardy, the prevalence of PNSs was 25 in 100,000 hospital admissions and 5.92 in 100,000 for the Lombardy population. Our results show a discrete presence of PNS patients in the province of Brescia and in the Lombardy region as a whole.

Patterns of care and cost profiles of women with breast cancer in Italy: EPICOST study based on real world data.

OBJECTIVES: To estimate total direct health care costs associated to diagnosis and treatment of women with breast cancer in Italy, and to investigate their distribution by service type according to the disease pathway and patient characteristics. METHODS: Data on patients provided by population-based Cancer Registries are linked at individual level with data on health-care services and corresponding claims from administrative databases. A combination of cross-sectional approach and a threephase of care decomposition model with initial, continuing and final phases-of-care defined according to time occurred since diagnosis and disease outcome is adopted. Direct estimation of cancer-related costs is obtained. RESULTS: Study cohort included 49,272 patients, 15.2% were in the initial phase absorbing 42% of resources, 79.7% in the continuing phase absorbing 44% of resources and 5.1% in the final phase absorbing 14% of resources. Hospitalization was the most important cost driver, accounting for over 55% of the total costs. CONCLUSIONS: This paper represents the first attempt in Italy to estimate the economic burden of cancer at population level taking into account the entire disease pathway and using multiple current health care databases. The evidence produced by the study can be used to better plan resources allocation. The model proposed is replicable to countries with individual health care information on services and claims.

Latent composite indicators for evaluating adherence to guidelines in patients with a colorectal cancer diagnosis.

Evidence-based guidelines for the correct management of cancer patients are developed on the idea that timely care can improve health prognoses and quality of life.The aim of this paper is to evaluate the adherence of clinical pathways to clinical guidelines provided at the hospital level, for colorectal cancer care.By using a retrospective observational study, we proposed a method for associating each patient to a healthcare provider and modeling adherence as a latent construct governed by a set of 10 influential indicators. These indicators measure the adherence to specific guidelines for diagnosis, surgical treatment, chemotherapy, and follow-up. The model used was that of the item response theory (IRT). When evaluating providers, the IRT allows for a comparison of indicators in terms of their discriminating ability and difficulty, and in terms of their adherence to guidelines. The IRT results were compared with non-latent methods: numerator-based weight and denominator-based weight.A strong degree of coherence of the indicators in measuring adherence, and a high level of overall agreement between latent and non-latent methods were noted. The IRT approach demonstrated similar providers' evaluations between endoscopy and histological assessment indicators. The greatest discriminating ability among providers could be attributed to all diagnostic exams, while the lowest was associated with follow-up endoscopies. The most difficult indicator to achieve was fecal occult blood test, while follow-up imaging was the easiest.In a decision-making framework, valuable indications can be derived from the use of IRT models rather than weighting methods. Using IRTs, we were able to highlight the principal indicators in terms of strength of discrimination, and to isolate those that merely duplicated information.

Cancer incidence and congenital anomalies evaluation in the contaminated sites of Sesto San Giovanni - the SENTIERI Project.

The Italian Institute for Environmental Protection and Research defines national priority contaminated sites (NPCSs) as land where hazardous substances are likely to pose a risk to human health. SENTIERI was the first national project evaluating the health status of residents in NPCSs. We have extended, for the site of Sesto San Giovanni, the evaluation to cancer incidence and congenital anomalies (CAs). We have found an overall significant negative association between living in the NPCS and overall cancer incidence in all ages and no association in paediatric, adolescent and young adults' population. We have found an excess risk for bladder cancer, leukaemia, lymphoid leukaemia and chronic lymphocytic leukaemia in men and for lung and breast cancer in women. For the paediatric and adolescent population, we have found an excess in embryonic tumours. Total CAs were not different from expected, while we have found excesses regarding ear, face and neck, digestive system and chromosomal defects.

Changes in life expectancy for cancer patients over time since diagnosis.

The aims of this study were to provide life expectancy (LE) estimates of cancer patients at diagnosis and LE changes over time since diagnosis to describe the impact of cancer during patients' entire lives. Cancer patients' LE was calculated by standard period life table methodology using the relative survival of Italian patients diagnosed in population-based cancer registries in 1985-2011 with follow-up to 2013. Data were smoothed using a polynomial model and years of life lost (YLL) were calculated as the difference between patients' LE and that of the age- and sex-matched general population. The YLL at diagnosis was highest at the youngest age at diagnosis, steadily decreasing thereafter. For patients diagnosed at age 45 years, the YLL was above 20 for lung and ovarian cancers and below 6 for thyroid cancer in women and melanoma in men. LE progressively increased in patients surviving the first years, decreasing thereafter, to approach that of the general population. YLL in the long run mainly depends on attained age. Providing quantitative data is essential to better define clinical follow-up and plan health care resource allocation. These results help assess when the excess risk of death from tumour becomes negligible in cancer survivors.

Early-onset colorectal cancer in young individuals.

Treatment of young adults with colorectal cancer (CRC) represents an unmet clinical need, especially as diagnosis in this population might lead to the greatest loss of years of life. Since 1994, CRC incidence in individuals younger than 50 years has been increasing by 2% per year. The surge in CRC incidence in young adults is particularly alarming as the overall CRC frequency has been decreasing. Early-onset CRC are characterized by a more advanced stage at diagnosis, poorer cell differentiation, higher prevalence of signet ring cell histology, and left colon-sided location of the primary tumor. Among EO-CRC, approximately 30% of patients are affected by tumors harboring mutations causing hereditary cancer predisposing syndromes, and 20% have familial CRC. Most notably, the remaining 50% of EO-CRC patients have neither hereditary syndromes nor familial CRC, thus representing a formidable challenge for research. In this review article we summarize epidemiology, clinical and molecular features, heredity and outcome of treatments of EO-CRC, and provide considerations for future perspectives.

Risk factors for breast cancer in a cohort of mammographic screening program: a nested case-control study within the FRiCaM study.

Breast cancer is the most common cancer diagnosis and the leading cause of cancer death among women in the world, and differences across populations indicate a role of hormonal, reproductive and lifestyle factors. This study is based on a cohort of 78,050 women invited to undergo a mammogram by Local Health Authority of Milan, between 2003 and 2007. We carried out a nested case-control study including all the 3303 incident breast cancer cases diagnosed up to 2015, and 9909 controls matched by age and year of enrollment. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using logistic regression models. The ORs were 0.88 (95% CI: 0.78-0.98) for an age at menarche ≥14 years and 1.39 (95% CI: 1.07-1.81) for an age of 30 years or older at first pregnancy. Body mass index (BMI) was positively associated with breast cancer risk in women older than 50 years (OR = 1.89, 95% CI: 1.54-2.31, for BMI≥30 vs. <20), while the association tended to be inverse in younger women. A high mammographic density increased breast cancer risk (OR = 2.61, 95% CI: 2.02-3.38 for density >75% vs. adipose tissue). The ORs were 1.67 (95% CI: 1.47-1.89) and 2.04 (95% CI: 1.38-3.00) for one first-degree relative and two or more relatives affected by breast cancer, respectively. Our study confirms the role of major recognized risk factors for breast cancer in our population and provides the basis for a stratification of the participants in the mammographic screening according to different levels of risk.