Cure indicators and prevalence by stage at diagnosis for breast and colorectal cancer patients: A population-based study in Italy.

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5-year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III-IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III-IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow-up in the years after diagnosis, thus avoiding patients' discrimination.

How many Italian cancer patients are eligible for, and may respond to, Italian Medicines Agency-approved immune checkpoint inhibitors?

INTRODUCTION: This cross-sectional study was aimed at estimating the number of Italian incident cancer patients in 2020 eligible for, and respondent to, immune checkpoint inhibitors (ICI). METHODS: The study is based on publicly available data: the ICI approved until August 2022 by the Italian Medicines Agency (AIFA) with their specific indications and overall observed responses, rther details can be found in the Online Supplementary Materi cancer incidence estimates at 2020 and observed cancer deaths, and published papers with estimates on the frequency of different cancer stage/histology/markers etc. corresponding to AIFA authorizations. RESULTS: In the analyzed period, a total of seven ICI were authorized in Italy for 20 cancer types. The estimated number of ICI-eligible patients in 2020 was 48,400, 14.3% of those tumors (including skin epitheliomas) that may fit AIFA-indications, and 10.5% of all the incident malignant tumors, including skin epitheliomas. The number of patients who may benefit from ICI therapy was 24,052, 49.7% of the ICI-eligible ones, or 5.2% of the overall estimated incident cancers in 2020. CONCLUSIONS: In conclusion, although the number of ICI-eligible patients is a relatively small proportion of the yearly burden of cancers, about half of them may respond to ICI-treatment.

The descriptive epidemiology of melanoma in Italy has changed - for the better.

A recent research project using data from a total of 40 cancer registries has provided new epidemiologic insights into the results of efforts for melanoma control in Italy between the 1990s and the last decade. In this article, the authors present a summary and a commentary of their findings. Incidence increased significantly throughout the study period in both sexes. However, the rates showed a stabilization or a decrease in men and women aged below 35 years. The risk of disease increased for successive cohorts born until 1973 (women) and 1975 (men) while subsequently tending to decline. The trend towards decreasing tumor thickness and increasing survival has continued, but a novel favorable prognostic factor has emerged since 2013 for patients - particularly for males - with thick melanoma, most likely represented by molecular targeted therapies and immune checkpoint inhibitors. Due to this, the survival gap between males and females has been filled out. In the meanwhile, and despite the incidence increase, dermatologists have not lowered their threshold to perform skin biopsy. Skin biopsy rate has increased because of the increasingly greater volume of dermatologic office visits, but the proportion of skin biopsies out of dermatologic office visits has remained constant. In summary, an important breakthrough in melanoma control in Italy has taken place. Effective interventions have been implemented across the full scope of care, which involve many large local populations - virtually the whole national population. The strategies adopted during the last three decades represent a valuable basis for further steps ahead in melanoma control in Italy.

Exposure to low levels of hydrogen sulphide and its impact on chronic obstructive pulmonary disease and lung function in the geothermal area of Mt. Amiata in Italy: The cross-sectional InVETTA study.

BACKGROUND: The geothermal power plants for electricity production currently active in Italy are all located in Mt. Amiata area in the Tuscany region. A cross-sectional survey was conducted in the framework of the regional project "InVETTA-Biomonitoring Survey and Epidemiological Evaluations for the Protection of Health in the Amiata Territories", using objective measures of lung function to investigate the role of hydrogen sulphide (H2S) in affecting the respiratory health of the population living in this area. METHODS: 2018 adults aged 18-70 were enrolled during 2017-2019. Home and workplace addresses of participants were geocoded. Dispersion modelling was used to evaluate the spatial variability of exposure to H2S from the geothermal power plants' emissions. We estimated average long-term historical exposure to H2S and more recent exposure indicators. Chronic Obstructive Pulmonary Disease (COPD) was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Multivariable logistic regressions were performed to investigate associations between outcome and exposure. RESULTS: Our findings did not showed any evidence of an association between increasing H2S exposure and lung function impairments. Some risk reductions were observed: a -32.8% (p = 0.003) for FEV1<80% and a -51.7% (p = 0.001) risk decrease for FVC<80% were associated with interquartile increase (13.8 µg/m3) of H2S levels. CONCLUSION: Our study provides no evidence that chronic exposure to low levels of H2S is associated with decrements in pulmonary function, suggesting that ambient H2S exposure may benefit lung function.

Complete prevalence and indicators of cancer cure: enhanced methods and validation in Italian population-based cancer registries.

Objectives: To describe the procedures to derive complete prevalence and several indicators of cancer cure from population-based cancer registries. Materials and methods: Cancer registry data (47% of the Italian population) were used to calculate limited duration prevalence for 62 cancer types by sex and registry. The incidence and survival models, needed to calculate the completeness index (R) and complete prevalence, were evaluated by likelihood ratio tests and by visual comparison. A sensitivity analysis was conducted to explore the effect on the complete prevalence of using different R indexes. Mixture cure models were used to estimate net survival (NS); life expectancy of fatal (LEF) cases; cure fraction (CF); time to cure (TTC); cure prevalence, prevalent patients who were not at risk of dying as a result of cancer; and already cured patients, those living longer than TTC at a specific point in time. CF was also compared with long-term NS since, for patients diagnosed after a certain age, CF (representing asymptotical values of NS) is reached far beyond the patient's life expectancy. Results: For the most frequent cancer types, the Weibull survival model stratified by sex and age showed a very good fit with observed survival. For men diagnosed with any cancer type at age 65-74 years, CF was 41%, while the NS was 49% until age 100 and 50% until age 90. In women, similar differences emerged for patients with any cancer type or with breast cancer. Among patients alive in 2018 with colorectal cancer at age 55-64 years, 48% were already cured (had reached their specific TTC), while the cure prevalence (lifelong probability to be cured from cancer) was 89%. Cure prevalence became 97.5% (2.5% will die because of their neoplasm) for patients alive >5 years after diagnosis. Conclusions: This study represents an addition to the current knowledge on the topic providing a detailed description of available indicators of prevalence and cancer cure, highlighting the links among them, and illustrating their interpretation. Indicators may be relevant for patients and clinical practice; they are unambiguously defined, measurable, and reproducible in different countries where population-based cancer registries are active.

Trends in Net Survival from Vulvar Squamous Cell Carcinoma in Italy (1990-2015).

(1) Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990-2001 to 81.9% in 2009-2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70-79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003-2015 versus 1990-2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level.

Female breast cancer subtypes in the Romagna Unit of the Emilia-Romagna cancer registry, and estimated incident cases by subtypes and age in Italy in 2020.

PURPOSE: The aim of this study was to estimate the Italian burden of incident breast cancer (BC) by subtypes, according to the distribution of hormonal receptor (HR) status and expression of human epidermal growth factor 2 (HER2). METHODS: Female breast cancers incidence in the Romagna Unit of the Emilia-Romagna registry (n. 10,711) were grouped into: HR+ /HER2-, HR+ /HER2+ , HR-/HER2+ , HR-/HER2- and missing, and by age: < 50, 50-69 and 70+ years. Data were compared with other published Italian population-bases series before using them for national estimates. We used national and regional numbers of expected breast cancers published by the Italian network of cancer registries considering the age- and geographic-specific variation of the Italian population. RESULTS: Overall, 70.7% of incident BC cases are expected to be HR+ /HER2-, 8.5% HR+ /HER2+ , 7.5% HR-/HER2-, 4.1% HR-/HER2+ and 9.3% missing. The global ranking is similar across age-groups but with age-specific differences. The proportion of missing was around 3-times lower than in the other Italian published population-based series and similar to the SEER one. In Italy, are estimated 38,841 HR+ /HER2- breast cancer cases, 4665 HR+ /HER2+ , 4098 HR-/HER2-, 2281 HR-/HER2+ , and 5092 not specified. Numbers by age-group were provided. CONCLUSIONS: The present estimates relied on high-quality population-based data and provide a clinically relevant information on the burden of breast cancer subtypes. These data will support the planning of therapy needs for oncologists, decision-makers, and all other stakeholders.

Levels and determinants of urinary and blood metals in the geothermal area of Mt. Amiata in Tuscany (Italy).

Natural sources and anthropogenic activities are responsible for the widespread presence of heavy metals in the environment in the volcanic and geothermal area of Mt. Amiata (Tuscany, Italy). This study evaluates the extent of the population exposure to metals and describes the major individual and environmental determinants. A human biomonitoring survey was carried out to determine the concentrations of arsenic (As), mercury (Hg), thallium (Tl), antimony (Sb), cadmium (Cd), nickel (Ni), chromium (Cr), cobalt (Co), vanadium (V), and manganese (Mn). The associations between socio-demographics, lifestyle, diet, environmental exposure, and metal concentrations were evaluated using multiple log-linear regression models, adjusted for urinary creatinine. A total of 2034 urine and blood samples were collected. Adjusted geometric averages were higher in women (except for blood Hg) and younger subjects (except for Tl and Cd). Smoking was associated with Cd, As, and V. Some dietary habits (rice, fish, and wine consumption) were associated with As, Hg, Co, and Ni. Amalgam dental fillings and contact lenses were associated with Hg levels, piercing with As, Co, and Ni. Among environmental determinants, urinary As levels were higher in subjects using the aqueduct water for drinking/cooking. The consumption of locally grown fruits and vegetables was associated with Hg, Tl, and Co. Exposure to geothermal plant emissions was associated only with Tl.

Patient presentation, skin biopsy utilization and cutaneous malignant melanoma incidence and mortality in northern Italy: Trends and correlations.

BACKGROUND: The global increase in incidence of cutaneous malignant melanoma (CMM) occurring in the past decades has been partly attributed to increased diagnostic scrutiny of early lesions, with a potential phenomenon of overdiagnosis. The reported positive linear relation between skin biopsy rate and incidence of early CMM is compatible with this hypothesis. OBJECTIVES: We explored the ecological association between the trends in annual dermatologic office visit rates, skin biopsy rates, incidence rates of in situ and invasive CMM by tumour thickness category, and CMM mortality rates in the Emilia-Romagna Region (northern Italy). METHODS: Four cancer registries covering a population of 2,696,000 provided CMM incidence data for the years 2003-2017. Dermatologic office visit rates and skin biopsy rates were calculated using the Regional outpatient care database. All rates were age-standardized. Trends were described with the estimated average annual per cent change (EAAPC). Correlations were tested with the Spearman correlation coefficient. RESULTS: Incidence increased significantly. The increase was steeper for in situ CMM (EAAPC: men, 10.2; women, 6.9) followed by CMM <0.8 mm thick (9.1; 5.2), but the rates grew significantly for most subgroups of CMMs ≥0.8 mm thick. Mortality decreased significantly among women (-2.3) and non-significantly among men. For dermatologic office visit rate and skin biopsy rate the EAAPC were, respectively, 1.7 and 1.8 for men and 1.2 and 0.9 for women. Annual dermatologic office visit rate correlated with skin biopsy rate in both sexes. However, the proportion of skin biopsies out of dermatologic office visits was constant across the years (range: men, 0.182-0.216; women, 0.157-0.191). CONCLUSIONS: In Italy, the increasing CMM incidence trend is, at least in part, genuine. Overdiagnosis-if any-is due to an increased patient presentation at dermatologic offices and not to a lower dermatologic threshold to perform biopsy.

[Update of survival of cancer patients in Italy: geographical comparisons and focus on patients with cancers targeted by screening programmes, childhood cancers, and smoking-associated cancers]. / Aggiornamento della sopravvivenza dei pazienti con tumore in Italia: confronti geografici e focus su pazienti con tumori oggetto di screening, pediatrici e associati al fumo.

OBJECTIVES: to update the Italian estimates of survival for patients with a paediatric cancer, tobacco smoke-associated cancers, and cancers targeted by screening; to assess geographical differences. DESIGN: population-based descriptive study. SETTING AND PARTICIPANTS: incident cancer cases diagnosed in 2010-2014, with follow-up to 2018, from 17 Italian cancer registries (covering 31% of the national population; 43% of the population residing in the North-Centre of the country and 8% of the population living in the South and Islands). MAIN OUTCOME MEASURES: age-standardized 5-year net survival (NS) by cancer site or type, sex, age, and geographical area. RESULTS: NS of patients aged ≥15 years with breast, prostate, colorectal, and lung cancers was higher in the North-Centre than in the South and Islands. The overall survival of people diagnosed with cancer in childhood (0-14 years) was 84.3%, with similar values among the geographical macro-areas and between males and females. Women with breast cancer within the current target age of the screening programmes and those in the younger age groups (45-49 years) show similar survival values; the same is true for women with colorectal cancer. In both cases, survival decreased in the age groups after the age of cessation of screening programmes. Survival of patients with tobacco smoke-associated cancers varies according to cancer site (from 11.1% for patients with pancreatic cancer to 79.7% for those with bladder cancer). For most cancer sites, women have higher survival than men. CONCLUSIONS: for adults, a geographical survival gap persists. The results may contribute to the debate on extending the target age for screening programmes and to support initiatives to encourage tobacco smoking cessation even after cancer diagnosis. For patients who receive a cancer diagnosis in childhood, survival similar to highest values internationally.

The importance of mitosis ≥2 in selecting patients with T1 cutaneous melanomas for sentinel lymph node biopsy.

The 8th Edition of the American Joint Committee on Cancer (AJCC) Staging Manual removed the mitotic rate (MR) as a staging criterion for T1 melanomas, thus leading to a debate on sentinel lymph node biopsy (SLNB) in thin melanomas. This study investigates whether MR plays a role in selecting patients with T1 melanoma for SLNB. We analyzed clinical and histological data from the Florence Melanoma & Skin Cancer Unit database for 313 patients with a single thin melanoma who had undergone SLNB. We determined sentinel lymph node (SLN) positivity percentages in T1 melanomas according to the AJCC 8th Edition focusing on MR. Of the 313 T1 patients, 108 had MR = 0, 127 had MR = 1 and 78 had MR ≥2. The overall SLN positivity rate was 8.6%, (5.6% with MR = 0, 6.3% with MR = 1 and 16.7% with MR ≥2). The SLNB positivity rate in T1b melanomas was 12.1%, (8.5% with MR = 0, 5.7% with MR = 1 and 24.4% with MR ≥2), whereas in T1a melanomas it was 5.8%, (3.3% with MR = 0, 6.8% with MR = 1 and 8.1% with MR ≥2). In a logistic regression analysis, MR ≥2 had an odds ratio of almost three in comparison with MR = 0/1 also adjusting for thickness. Thus, MR ≥2 significantly predicted SLN metastases in T1 melanomas. Of those patients with positive SLN, 37% were classified as T1a according to the AJCC 8th edition. These findings underline the importance of MR ≥2 in selecting patients with T1 cutaneous melanomas for SLNB.

The relative contribution of the decreasing trend in tumour thickness to the 2010s increase in net survival from cutaneous malignant melanoma in Italy: a population-based investigation.

BACKGROUND: The long-term increase in survival from cutaneous malignant melanoma (CMM) is generally attributed to the decreasing trend in tumour thickness, the single most important prognostic factor. OBJECTIVES: To determine the relative contribution of decreased tumour thickness to the favourable trend in survival from CMM in Italy. METHODS: Eleven local cancer registries covering a population of 8 056 608 (13.4% of the Italian population in 2010) provided records for people with primary CMM registered between 2003 and 2017. Age-standardized 5-year net survival was calculated. Multivariate analysis of 5-year net survival was undertaken by calculating the relative excess risk (RER) of death. The relative contribution of the decrease in tumour thickness to the RER of death was evaluated using a forward stepwise flexible parametric survival model including the available prognostic factors. RESULTS: Over the study period, tumour thickness was inversely associated with 5-year net survival and multivariate RER in both sexes. The median thickness was 0.90 mm in 2003-2007, 0.85 mm in 2008-2012 and 0.75 mm in 2013-2017 among male patients, and 0.78 mm, 0.77 mm and 0.68 mm among female patients, respectively. The 5-year net survival was 86.8%, 89.2% and 93.2% in male patients, and 91.4%, 92.0% and 93.4% in female patients, respectively. In 2013-2017, male patients exhibited the same survival as female patients despite having thicker lesions. For them, the increasing survival trend was more pronounced with increasing thickness, and the inclusion of thickness in the forward stepwise model made the RER in 2013-2017 vs. 2003-2007 increase from 0.64 [95% confidence interval (CI) 0.51-0.80] to 0.70 (95% CI 0.57-0.86). This indicates that the thickness trend accounted for less than 20% of the survival increase. For female patients, the results were not significant but, with multiple imputation of missing thickness values, the RER rose from 0.74 (95% CI 0.58-0.93) to 0.82 (95% CI 0.66-1.02) in 2013-2017. CONCLUSIONS: For male patients in particular, decrease in tumour thickness accounted for a small part of the improvement in survival observed in 2013-2017. The introduction of targeted therapies and immune checkpoint inhibitors in 2013 is most likely to account for the remaining improvement.

Effectiveness and Safety of Non-Vitamin K Oral Anticoagulants in Non-Valvular Atrial Fibrillation Patients: Results of A Real-World Study in a Metropolitan Area of Northern Italy.

BACKGROUND: New oral anticoagulant agents (NOACs) are valid alternatives for vitamin K antagonists (VKA) in patients with non-valvular atrial fibrillation (NVAF) for stroke prevention. In clinical practice, NOACs users may differ from patients enrolled in clinical trials in age or comorbidities, and thus it is a critical issue to evaluate the effectiveness and safety of NOACs in the real-world. Accordingly, we assessed two-year overall mortality and hospital admissions for myocardial infarction, stroke or bleeding in patients with NVAF users of NOACs compared to warfarin-treated patients. METHODS: This is a population-based retrospective new user active comparator study. All atrial fibrillation patients who were naïve and not switcher users of oral anticoagulants from January 2017 to December 2019 were included (n = 8543). Data were obtained from the electronic health records of the Milan Agency for Health Protection, Italy. Two-year risks for overall mortality, myocardial infarction, stroke and bleeding were computed using Cox models. Age, sex, number of comorbidities, use of platelet aggregation inhibitors and Proton pump inhibitors and area of residence were used as confounding factors. We also controlled by indication bias-weighting NOACs and warfarin users based on the weights computed by a Kernel propensity score. RESULTS: For all NOACs, we found a decrease in the risks compared with warfarin for mortality (from -25% to -49%), hospitalization for myocardial infarction (from -16% to -27%, statistically significant for apixaban, edoxaban and rivaroxaban) and ischemic stroke (from -23% to -41%, significant for dabigatran and apixaban). The risk of bleeding was decreased for rivaroxaban (-33%) and numerically but not significantly for the other NOACs. CONCLUSIONS: After two years of follow-up, in comparison with warfarin, NOACs users showed a significant reduction of overall mortality (all NOACs), hospital admission for myocardial infarction (apixaban and edoxaban), ischemic stroke (dabigatran) and bleeding (rivaroxaban).

Variation of Cancer Incidence between and within GRELL Countries.

Variation in cancer incidence between countries and groups of countries has been well studied. However cancer incidence is linked to risk factors that may vary within countries, and may subsist in localized geographic areas. In this study we investigated between- and within-country variation in the incidence of all cancers combined for countries belonging to the Group for Cancer Epidemiology and Registration in Latin Language Countries (GRELL). We hypothesized that investigation at the micro-level (circumscribed regions and local cancer registry areas) would reveal incidence variations not evident at the macro level and allow identification of cancer incidence hotspots for research, public health, and to fight social inequalities. Data for all cancers diagnosed in 2008-2012 were extracted from Cancer Incidence in Five Continents, Vol XI. Incidence variation within a country or region was quantified as r/R, defined as the difference between the highest and lowest incidence rates for cancer registries within a country/region (r), divided by the incidence rate for the entire country/region × 100. We found that the area with the highest male incidence had an ASRw 4.3 times higher than the area with the lowest incidence. The area with the highest female incidence had an ASRw 3.3 times higher than the area with the lowest incidence. Areas with the highest male ASRws were Azores (Portugal), Florianopolis (Brazil), Metropolitan France, north Spain, Belgium, and north-west and north-east Italy. Areas with the highest female ASRws were Florianopolis (Brazil), Belgium, north-west Italy, north-east Italy, central Italy, Switzerland and Metropolitan France. Our analysis has shown that cancer incidence varies markedly across GRELL countries but also within several countries: the presence of several areas with high cancer incidence suggests the presence of area-specific risk factors that deserve further investigation.

Risk of thyroid as a first or second primary cancer. A population-based study in Italy, 1998-2012.

BACKGROUND: The number of patients living after a cancer diagnosis is increasing, especially after thyroid cancer (TC). This study aims at evaluating both the risk of a second primary cancer (SPC) in TC patients and the risk of TC as a SPC. METHODS: We analyzed two population-based cohorts of individuals with TC or other neoplasms diagnosed between 1998 and 2012, in 28 Italian areas covered by population-based cancer registries. Standardized incidence ratios (SIRs) of SPC were stratified by sex, age, and time since first cancer. RESULTS: A total of 38,535 TC patients and 1,329,624 patients with other primary cancers were included. The overall SIR was 1.16 (95% CI: 1.12-1.21) for SPC in TC patients, though no increase was shown for people with follicular (1.06) and medullary (0.95) TC. SPC with significantly increased SIRs was bone/soft tissue (2.0), breast (1.2), prostate (1.4), kidney (2.2), and hemolymphopoietic (1.4) cancers. The overall SIR for TC as a SPC was 1.49 (95% CI: 1.42-1.55), similar for all TC subtypes, and it was significantly increased for people diagnosed with head and neck (2.1), colon-rectum (1.4), lung (1.8), melanoma (2.0), bone/soft tissue (2.8), breast (1.3), corpus uteri (1.4), prostate (1.5), kidney (3.2), central nervous system (2.3), and hemolymphopoietic (1.8) cancers. CONCLUSIONS: The increased risk of TC after many other neoplasms and of few SPC after TC questions the best way to follow-up cancer patients, avoiding overdiagnosis and overtreatment for TC and, possibly, for other malignancies.

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.

Mid-term trends and recent birth-cohort-dependent changes in incidence rates of cutaneous malignant melanoma in Italy.

In Oceania, North America and north-western Europe, after decades of increase, cutaneous malignant melanoma (CMM) rates began to stabilise or decline before 2000. Anecdotal evidence suggests that the reversal of the incidence trend is extending to southern Europe. To obtain a formal confirmation, this nationwide study from Italy investigated the incidence trends by birth cohort. Twenty-one local cancer registries covering a population of 15 814 455 provided incidence data for primary CMM registered between 1994 and 2013. Trends in age-standardised rates were analysed using joinpoint regression models and age-period-cohort models. Age-standardised incidence showed a consistent increase throughout the period (estimated annual percent change, 3.6 [95% confidence interval, 3.2-4.0] among men and 2.5 [2.0-3.1] among women). This pattern was confirmed by a sensitivity analysis with removal of low-risk populations of southern Italy. The rates, however, showed a stabilisation or a decrease in men and women aged below 35. Using the cohort of 1949-the median cohort with respect to the number of cases for both genders-as a reference, the incidence rate ratio increased for successive cohorts born until 1973 (women) and 1975 (men), and subsequently tended to decline. For the most recent cohorts in both genders, the risk of disease returned to the level of the cohort of 1949. The changes observed in the latest generations can be interpreted as the earliest manifestations of a birth-cohort-dependent incidence decrease. Our study adds to previous data indicating that the reversal of the long-term upward incidence trend of CMM is extending to southern Europe.

Melanoma survival with Classification and Regression Trees Analysis: a complement for the communication of prognosis to patients.

BACKGROUND: Prognostic factors in cutaneous melanoma are commonly evaluated by the Cox proportional hazard model. However, the interpretation of the effect of multiple variables is not straightforward. Classification and Regression Trees Analysis (CART), which allows a more friendly data evaluation, could be a valid integration of the message from Cox model. METHODS: The CART algorithm splits up data, creating a "tree" of groups of patients with different profiles for the risk of death. Results are easy to interpret in clinical practice. A total of 2692 patients with invasive cutaneous melanoma registered in Romagna (northern Italy) between 1993-2012 and followed-up until the end of 2013 were included. The Cox model and CART analysis were applied to sex, patient age, histological subtype, Breslow's tumor thickness, ulceration, site of disease, and Clark level. RESULTS: The CART analysis identified 15 categories which were collapsed into five classes with statistically different survival. The best prognostic group (10-year observed survival, 99.1%) included subjects with Breslow thickness ≤0.78 mm and age 16-81 years. The worst prognostic group (10-year observed survival, 35.8%) comprised subjects with thickness ≥3.75 mm and age 16-96 years. According to the Cox model, patient age, histological subtype, Breslow thickness, ulceration, and site of disease had a significant independent prognostic value. CONCLUSIONS: CART and Cox models provided consistent results. CART seemed friendlier in its interpretation and it could facilitate the communication of risk.

T-PEC: a novel test for the elicited production of clitic pronouns in Italian. Preliminary data.

The study presented in this article aims at investigating the clinical usefulness of a novel test, called T-PEC, for the diagnosis of Developmental Language Disorder in Italian preschool children. The instrument exploits the production of clitic pronouns, in particular third person direct object clitics (3PDO-CL), as a clinical marker for the disorder. Psychometric properties and normative data were computed on a sample of 70 children ranging in age from 4.6 to 5.8 years: 22 children diagnosed as language-impaired by expert clinicians according to international guidelines, and 48 typically developing peers. The statistical analysis of the collected data revealed good internal consistency (Cronbach's α = 0.86) and confirmed the effectiveness of the T-PEC test in distinguishing typically developing and DLD children, especially when the latter showed morphosyntactic deficits (AUC = 79.9%). Its high accuracy, combined with the rapidity and easiness of its administration, makes the T-PEC test suitable for use in clinical settings.

Cancer cure for 32 cancer types: results from the EUROCARE-5 study.

BACKGROUND: Few studies have estimated the probability of being cured for cancer patients. This study aims to estimate population-based indicators of cancer cure in Europe by type, sex, age and period. METHODS: 7.2 million cancer patients (42 population-based cancer registries in 17 European countries) diagnosed at ages 15-74 years in 1990-2007 with follow-up to 2008 were selected from the EUROCARE-5 dataset. Mixture-cure models were used to estimate: (i) life expectancy of fatal cases (LEF); (ii) cure fraction (CF) as proportion of patients with same death rates as the general population; (iii) time to cure (TTC) as time to reach 5-year conditional relative survival (CRS) >95%. RESULTS: LEF ranged from 10 years for chronic lymphocytic leukaemia patients to <6 months for those with liver, pancreas, brain, gallbladder and lung cancers. It was 7.7 years for patients with prostate cancer at age 65-74 years and >5 years for women with breast cancer. The CF was 94% for testis, 87% for thyroid cancer in women and 70% in men, 86% for skin melanoma in women and 76% in men, 66% for breast, 63% for prostate and <10% for liver, lung and pancreatic cancers. TTC was <5 years for testis and thyroid cancer patients diagnosed below age 55 years, and <10 years for stomach, colorectal, corpus uteri and melanoma patients of all ages. For breast and prostate cancers, a small excess (CRS < 95%) remained for at least 15 years. CONCLUSIONS: Estimates from this analysis should help to reduce unneeded medicalization and costs. They represent an opportunity to improve patients' quality of life.