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Background: Among the various types of basal cell carcinoma, the sclerodermiform variant has a high risk of recurrence and local invasiveness. A systematic description of the dermatoscopic features associated with specific body localization is lacking. Objectives: To describe the clinical and dermoscopic features of sclerodermiform basal cell carcinoma (BCC) according to localization in the body confronting with superficial and nodular types. Methods: Clinical and dermoscopic images of sclerodermiform, nodular and superficial BCCs were retrospectively evaluated to study the location in the various body districts, maximum diameter, clinical appearance of the lesion, features of edges and presence or absence of specific dermatoscopic criteria of BCCs. Results: We examined 291 histopathologically proven BCCs showing that in nodular BCCs, classical arborizing vessels were more frequently found in the body macro‐area (trunk and limbs; n = 46, 97.9%) than in the head/neck area (n = 43, 82.7%); within sclerodermiform BCCs, short arborizing vessels were found more frequently in the head/neck district (n = 35, 49.3%) than in the body (n = 6, 23.1%; P‐value 0.02); within nodular BCCs, multiple blue‐grey dots and globules were more frequently found on the trunk (n = 23, 48.9%) than in the head/neck district (n = 12, 23.1%; P‐value 0.01). In sclerodermiform BCCs, ulceration was found more frequently in the head/neck district (n = 38, 53.5%) than in the body (n = 4, 15.4%; P‐value > 0.01), and in superficial BCCs, ulceration was found more frequently in the head/neck district (n = 5, 38.5%) than in the body (n = 8, 9.8%; P‐value 0.02). Conclusion: Our study shows that superficial BCC are found frequently in the head/neck district dermoscopically characterized by ulceration and arborizing vessels; nodular BCCs are more frequently found in the body than in the head/neck district, and the dermoscopic pattern is characterized by the combination of three features: (i) classical arborizing vessels, (ii) multiple blue‐grey dots and (iii) globules. Instead, sclerodermiform BCC is preferentially located in areas at high–moderate risk of recurrence; if pink‐white areas and/or fine arborizing vessels are seen, clinicians should consider this diagnosis. Furthermore, location‐specific dermatoscopic criteria have been described. [ABSTRACT FROM AUTHOR]

Dermoscopic features of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) have been already described, and however, criteria of these skin cancers, according to different anatomical locations of face and scalp, have not been described before. The most striking results in our study were the prevalence of nodular BCC in fronto-nasal area and sclerosing BCC in peri-auricular area (Table 1). [Extracted from the article]

This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate net survival, cure fraction, time to cure (when 5-year conditional net survival becomes > 95%), cure prevalence (women who will not die of cancer), and already cured (living longer than time to cure). In 2018, 0.4% (121 704) of Italian women were alive after diagnosis of corpus uteri cancer, 0.2% (52 551) after cervical cancer, and 0.2% (52 153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (cure prevalence). Women with gynecological cancers have a residual excess risk of death <5% at 5 years after diagnosis. The cure fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time to cure was ≤10 years for women with gynecological cancers aged <55 years; 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were already cured. These results can contribute to improving follow-up programs for women with gynecological cancers and supporting efforts against discrimination of already cured ones. This article is part of a Special Collection on Gynecological Cancers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Pancreatic cancer risk has been associated with increased serum cholesterol level, which is in turn partially influenced by diet. This study aimed at evaluating the association between pancreatic cancer risk and the adherence to a plant-based cholesterol-lowering diet., Methods: Data were derived from an Italian case-control study including 258 pancreatic cancer patients and 551 controls. The cholesterol-lowering diet score was based on seven components: high intakes of (i) non-cellulosic polysaccharides (a proxy of viscous fibers), (ii) monounsaturated fatty acids, (iii) legumes, and (iv) seeds/corn oils (a proxy of phytosterols); and low intakes of (v) saturated fatty acids, (vi) dietary cholesterol, and (vii) food with a high glycemic index. The score was calculated adding one point for each fulfilled component, thus ranging from zero (no adherence) to seven (complete adherence). The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated through the logistic regression model., Results: Scores 5-7 were associated with reduced cancer risk (OR = 0.30; 95% CI: 0.18-0.52) compared to scores 0-2., Conclusions: Adherence to a plant-based cholesterol-lowering diet was associated with a reduced risk of pancreatic cancer.

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., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: The number and projections of cancer survivors are necessary to meet the healthcare needs of patients, while data on cure prevalence, that is, the percentage of patients who will not die of cancer by time since diagnosis, are lacking., Materials and Methods: Data from Italian cancer registries (duration of registration ranged from 9 to 40 years, with a median of 22 years) covering 47% of the population were used to calculate the limited-duration prevalence, the complete prevalence in 2018, projections to 2030, and cure prevalence, by cancer type, sex, age, and time since diagnosis., Results: A total of 3 347 809 people were alive in Italy in 2018 after a cancer diagnosis, corresponding to 5.6% of the resident population. They will increase by 1.5% per year to 4 012 376 in 2030, corresponding to 6.9% of the resident population, 7.6% of women and ∼22% after age 75 years. In 2030, more than one-half of all prevalent cases (2 million) will have been diagnosed by ≥10 years. Those with breast (1.05 million), prostate (0.56 million), or colorectal cancers (0.47 million) will be 52% of all prevalent patients. Cure prevalence was 86% for all patients alive in 2018 (87% for patients with breast cancer and 99% for patients with thyroid or testicular cancer), increasing with time since diagnosis to 93% for patients alive after 5 years and 96% after 10 years. Among patients who survived at least 5 years, the excess risk of death (1 - cure prevalence) was <5% for patients with most cancer types except for those with cancers of the breast (8.3%), lung (11.1%), kidney (13.2%), and bladder (15.5%)., Conclusions: Study findings encourage the implementation of evidence-based policies aimed at improving long-term clinical follow-up and rehabilitation of people living after cancer diagnosis throughout the course of the disease. Updated estimates of complete prevalence are important to enhance data-driven cancer control planning., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Gastric cancer (GC) incidence has been decreasing over the last decades; however, there are uncertainties in trends and proportional distribution of the diffuse type., Methods: GC incidence data were extracted from the population-based Friuli Venezia Giulia Cancer Registry. GC types (diffuse vs. others) were compared in relation to age at diagnosis, calendar years, and sexes., Results: Between 1995 and 2021, diffuse GC accounted for 10.2% of all GCs. The proportion was greater among individuals aged <45 years, 34.0% in women and 25.7% in men. An increasing proportion over time was observed, in particular in women (from 9.9% in 1995-2000 to 14.10% during 2011-2021). In the last decade (2011-2021), a decreasedincidence of all GC was observed, reaching an age-standardized rate (world standard) of 1.4/100,000 for men and 1.2/100,000 for women. Rates of diffuse GC were 0.3/100,000 in younger population., Conclusion: Although the overall GC incidence is decreasing, the percentage of diffuse GC is increasing in the younger population, particularly in women. Reasons for the increased proportion of diffuse-type GC within younger women remain uncertain, possibly related to the decreased exposure to risk factors for other GC histotypes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.

A study was conducted to assess the fraction of female breast cancer (BC) deaths attributable to alcohol consumption in Italy. National mortality data for the period 2015-2019 were used along with national estimates of women from the general population exposed to moderate (11-20 gr/day) or heavy (>20 gr/day) alcohol consumption. From 2015 to 2019, 2918 (4.6%) out of 63,428 BC| deaths were attributable to alcohol consumption, including 1269 deaths (2.0%) caused by moderate consumption. Study findings could help stakeholders to prioritize programs aimed at reducing alcohol consumption, and to improve ways to effectively communicate alcohol-related health risks, including moderate consumption., Competing Interests: Declaration of competing interest All Authors declare that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

People with a history of cancer have a higher risk of death when infected with SARS-CoV-2. COVID-19 vaccines in cancer patients proved safe and effective, even if efficacy may be lower than in the general population. In this population-based study, we compare the risk of dying of cancer patients diagnosed with COVID-19 in 2021, vaccinated or non-vaccinated against SARS-CoV-2 and residing in Friuli Venezia Giulia or in the province of Reggio Emilia. An amount of 800 deaths occurred among 6583 patients; the risk of death was more than three times higher among unvaccinated compared to vaccinated ones [HR 3.4; 95% CI 2.9-4.1]. The excess risk of death was stronger in those aged 70-79 years [HR 4.6; 95% CI 3.2-6.8], in patients with diagnosis made <1 year [HR 8.5; 95% CI 7.3-10.5] and in all cancer sites, including hematological malignancies. The study results indicate that vaccination against SARS-CoV-2 infection is a necessary tool to be included in the complex of oncological therapies aimed at reducing the risk of death., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships construed as a potential conflict of interest.

Objective: To describe the practice of prostate-specific antigen (PSA) testing over more than 20 years in Friuli Venezia Giulia (FVG), North-Eastern Italy., Methods: A population-based, ecological study was conducted using information derived from regional administrative health-related databases. Data on PSA and prostate biopsies performed on resident men aged ⩾45 years from 1998 to 2019 were retrieved. PSA and biopsy rates were calculated as the number of men who had at least one such procedure in each calendar year over the mean resident male population of the same year. Temporal trends were analyzed using joinpoint regression (annual percentage change -APC)., Results: A total of 2,502,670 PSA were made between 1998 to 2019 in men aged ⩾45 years. The number of PSA steadily increased from 51,055 in 1998-1999 to 134,504 in 2010-2011, then dropped to 122,080 in 2018-2019. Significant changes in the slopes of PSA rates emerged in 2002 and 2009: the largest increase occurred during 1998-2002 (APC 18.4), followed by a smaller increase in 2002-2009 (APC 3.4) and a subsequent reduction (APC -2.5). Similar patterns emerged for all ages, but the decrease since 2009 was smaller for men aged ⩾65 years. An upward trend emerged in biopsy rate from 1998 to 2001 (APC 13.0), followed by a smaller increase until 2007 (APC 5.7) and a subsequent decrease. Biopsies as percentage of PSA decreased from 3.2% to 2.2%, particularly in those aged ⩾75 years., Conclusions: Although overall declining PSA rates have been observed in FVG since 2009, rates remained higher in the ⩾65-year-old group than in the 45-64-year-old group.

Objective: A decrease in the use of radioactive iodine (RAI) treatment for thyroid cancer has been described in the last decade in the US following subsequent updates of the American Thyroid Association guidelines. By contrast, population-based data from European countries are lacking. The study aims to assess the frequency and long-term trends in the use of RAI in Italy., Methods: From the Italian national hospital discharge database, the proportion of RAI treatment after total thyroidectomy with thyroid cancer diagnosis has been assessed by sex and age class during 2001-2018., Results: Throughout the whole study period, RAI was performed after 58% of 149,419 total thyroidectomies. The use of RAI was higher for men and younger patients; it peaked in 2007 (64% in women and 68% in men) and declined thereafter (2018: 46% in women and 53% in men), with a similar pattern observed across all ages and areas., Conclusion: National data show that in Italy trends in RAI treatment paraleled those observed in the US. Further monitoring of the use of RAI is warranted in Italy, as elsewhere, to assess the impact of international guidelines on real-life clinical management of thyroid cancer.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Toffolutti, Guzzinati, De Paoli, Francisci, De Angelis, Crocetti, Botta, Rossi, Mallone, Zorzi, Manneschi, Bidoli, Ravaioli, Cuccaro, Migliore, Puppo, Ferrante, Gasparotti, Gambino, Carrozzi, Stracci, Michiara, Cavallo, Mazzucco, Fusco, Ballotari, Sampietro, Ferretti, Mangone, Rizzello, Mian, Cascone, Boschetti, Galasso, Piras, Pesce, Bella, Seghini, Fanetti, Pinna, Serraino, Dal Maso and AIRTUM Working Group.)

(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.

Background: Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma (AHLM/LMM) may be very difficult to diagnose at an early stage., Objectives: To quantify the predictive value of dermoscopic and reflectance confocal microscopy (RCM) features for AHLM/LMM., Methods: Dermoscopic and RCM images of histopathologically diagnosed AHLM/LMM, amelanotic/hypomelanotic benign lesions (AHBL), and amelanotic/hypomelanotic basal and squamous cell carcinomas (AHBCC/AHSCC) of the head and neck from consecutive patients were retrospectively collected and blindly evaluated by three observers to assess presence or absence of dermoscopic and RCM criteria., Results: Overall, 224 lesions in 216 patients including LM/LMM (n = 55, 24.6%), AHBL (n = 107, 47.8%) and AHBCC/AHSCC (n = 62, 27.7%) were analysed. Multivariable analysis showed that milky-red areas (OR = 5.46; 95% CI: 1.51-19.75), peripheral light brown structureless areas (OR = 19.10; 4.45-81.96), linear irregular vessels (OR = 5.44; 1.45-20.40), and asymmetric pigmented follicles (OR = 14.45; 2.77-75.44) at dermoscopy, and ≥3 atypical cells in five fields (OR = 10.12; 3.00-34.12) and focal follicular localization of atypical cells at dermo-epidermal junction (DEJ) (OR = 10.48; 1.10-99.81) at RCM were significantly independent diagnostic factors for AHLM/LMM vs. AHBL. In comparison with AHBCC/AHSCC, peripheral light brown structureless area (OR = 7.11; 1.53-32.96), pseudonetwork around hair follicles (OR = 16.69; 2.73-102.07), and annular granular structures (OR = 42.36; 3.51-511.16) at dermoscopy and large dendritic (OR = 6.86; 3.15-38.28) and round pagetoid cells (OR = 26.78; 3.15-227.98) at RCM led to a significantly increased risk of diagnosing AHLM/LMM., Conclusions: Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma may have the same dermoscopic features of AHM on other body sites, such as milky red areas, peripheral light brown structureless areas and linear irregular vessels. These features, asymmetric pigmented follicles and at RCM ≥ 3 atypical cells in five fields and focal follicular extension of atypical cells at DEJ may help in recognizing AHLM/LMM even when LM conventional features (e.g., obliteration of hair follicles under dermoscopy and large pagetoid cells under RCM) are absent or present only in very small areas of the lesion., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: The risks of hospital admission for COVID-19-related conditions and all-cause death of SARS-CoV-2 infected cancer patients were investigated according to vaccination status., Methods: A population-based cohort study was carried out on 9754 infected cancer patients enrolled from January 1, 2021 to June 30, 2022. Subdistribution hazard ratio (SHRs) or hazard ratios (HRs) with 95 % confidence intervals (CI), adjusted for sex, age, comorbidity index, and time since cancer incidence, were computed to assess the risk of COVID-19 hospital admission or death of unvaccinated vs. patients with at least one dose of vaccine (i.e., vaccinated)., Results: 2485 unvaccinated patients (25.5 %) were at a 2.57 elevated risk of hospital admission (95 % CI: 2.13-2.87) and at a 3.50 elevated risk of death (95 % CI: 3.19-3.85), as compared to vaccinated patients. Significantly elevated hospitalizations and death risks emerged for both sexes, across all age groups and time elapsed since cancer diagnosis. For unvaccinated patients, SHRs for hospitalization were particularly elevated in those with solid tumors (SHR = 2.69 vs. 1.66 in patients with hematologic tumors) while HRs for the risk of death were homogeneously distributed. As compared to boosted patients, SHRs for hospitalization and HRs for death increased with decreasing number of doses., Conclusions: Study findings stress the importance of SARS-CoV-2 vaccines to reduce hospital admission and death risk in cancer patients., Competing Interests: Declaration of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to assess whether an excess mortality related to kidney and other urinary tract diseases exists among Italian people with AIDS (PWA), as compared with the general population without AIDS (non-PWA)., Design: Population-based, retrospective cohort study., Setting and Participants: We conducted a nationwide study including 9481 Italian PWA, aged 15-74 years, reported to the National AIDS Registry between 2006 and 2018., Methods: Vital status and causes of death were retrieved by record linkage with the National Register of Causes of Death up to 2018. Excess mortality for PWA versus non-PWA was estimated through sex-standardised and age-standardised mortality ratios (SMRs) with corresponding 95% CIs., Results: Among 2613 deceased PWA, 262 (10.0%) reported at least one urinary tract disease at death, including 254 (9.7%) non-cancer diseases-mostly renal failures (225 cases, 8.6%)-and 9 cancers (0.3%). The overall SMR for non-cancer urinary tract diseases was 15.3 (95% CI 13.4 to 17.3) with statistically significant SMRs for acute (SMR=22.3, 95% CI 18.0 to 27.4), chronic (SMR=8.4, 95% CI 6.0 to 11.3), and unspecified renal failure (SMR=13.8, 95% CI 11.2 to 16.8). No statistically significant excess mortality was detected for urinary tract cancers (SMR=1.7, 95% CI 0.8 to 3.3). The SMRs were particularly elevated among PWA aged <50 years, injecting drug users, or those with the first HIV-positive test >6 months before AIDS diagnosis., Conclusions: The excess mortality related to non-cancer kidney and other urinary tract diseases reported among PWA highlights the importance of implementing the recommendation for screening, diagnosis and management of such conditions among this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Objective: To evaluate cancer risk among individuals with connective tissue disease (CTD) in Friuli Venezia Giulia, northern Italy., Methods: A population-based cohort study was conducted based on data from health records available in the regional healthcare database. Demographic characteristics, hospital discharges, exemption from medical charges, drug prescriptions, were individually matched with data from the population-based cancer registry. Cancer risk was assessed in people diagnosed with the following diseases: systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), systemic sclerosis (SSc), polymyositis (PM), and dermatomyositis (DM)., Results: In all, 2504 patients were followed for a total of 18,006 person-years (median follow-up: 6.8 years). After 5 and 10 years of follow-up, the cumulative cancer incidence was 2.6% and 8.5%, respectively. The most common cancers were breast ( n = 34), lung ( n = 24), colon-rectum-anus ( n = 20), and non-Hodgkin lymphomas (NHL) ( n = 20). Overall, no excess cancer risk was noted (SIR = 0.87), whereas the number of observed NHL cases was more than two-fold significantly higher than expected (SIR = 2.52). The subgroup analysis showed a higher risk of NHL among SS patients (SIR = 3.84) and SLE patients (SIR = 2.69). Conversely, the study population showed a decreased risk for breast cancers (SIR = 0.61) and corpus uteri (SIR = 0.21)., Conclusions: The incidence of NHL was higher among patients with SS and SLE. Careful surveillance for hematological malignancies in these patients is recommended., Competing Interests: The authors declare no conflict of interest.

Background: The incidence of thyroid disease is generally increasing, and it is subject to major geographic variability, between and within countries. Moreover, the incidence rates and the proportion of overdiagnosis for thyroid cancer in Italy are among the highest worldwide. This study aimed to estimate population-based frequency and trends of thyroidectomies in Italy by type of surgical procedure (total/partial), indication (tumors/other conditions), sex, age, and geographical region. Materials and Methods: Age-standardized rates (ASRs) of thyroidectomies were estimated from 2001 to 2018 using the national hospital discharges database. Results: In Italy, ASRs of thyroidectomies were nearly 100 per 100,000 women in 2002-2004 and decreased to 71 per 100,000 women in 2018. No corresponding variation was shown in men (ASR 27 per 100,000 men) in the overall period. A more than twofold difference between Italian regions emerged in both sexes. The proportion of total thyroidectomies (on the sum of total and partial thyroidectomies) in the examined period increased from 78% to 86% in women and from 72% to 81% in men. Thyroidectomies for goiter and nonmalignant conditions decreased consistently throughout the period (from 81 per 100,000 women in 2002 to 49 in 2018 and from 22 to 16 per 100,000 men), while thyroidectomies for tumors increased until 2013-2014 up to 24 per 100,000 women (9 per 100,000 men) and remained essentially stable thereafter. Conclusions: The decrease in thyroidectomies for nonmalignant diseases since early 2000s in Italy may derive from the decrease of goiter prevalence, possibly as a consequence of the reduction of iodine deficiency and the adoption of conservative treatments. In a context of overdiagnosis of thyroid cancer, recent trends have suggested a decline in the diagnostic pressure with a decrease in geographic difference. Our results showed the need and also the possibility to implement more conservative surgical approaches to thyroid diseases, as recommended by international guidelines.

The impact of specific risk factors for SARS-CoV-2 infection spread was investigated among the 215 municipalities in north-eastern Italy. SARS-CoV-2 incidence was gathered fortnightly since April 1, 2020 (21 consecutive periods) to depict three indicators of virus spreading from hierarchical Bayesian maps. Eight explanatory features of the municipalities were obtained from official databases (urbanicity, population density, active population on total, hosting schools or nursing homes, proportion of commuting workers or students, and percent of > 75 years population on total). Multivariate Odds Ratios (ORs), and corresponding 95% Confidence Intervals (CIs), quantified the associations between municipality features and virus spreading. The municipalities hosting nursing homes showed an excess of positive tested cases (OR = 2.61, ever versus never, 95% CI 1.37;4.98), and displayed repeated significant excesses: OR = 5.43, 3-4 times versus 0 (95% CI 1.98;14.87) and OR = 6.10, > 5 times versus 0 (95% CI 1.60;23.30). Municipalities with an active population > 50% were linked to a unique statistical excess of cases (OR = 3.06, 1 time versus 0, 95% CI 1.43;6.57) and were inversely related to repeated statistically significant excesses (OR = 0.25, > 5 times versus 0; 95% CI 0.06;0.98). We highlighted specific municipality features that give clues about SARS-CoV-2 prevention., (© 2022. The Author(s).)

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., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Cutaneous melanoma (CM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CM in several Italian centers, which are part of the Clinical National Melanoma Registry (CNMR)., Methods: Melanoma-specific survival and overall survival were calculated. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors., Results: The median follow-up time was 36 months (range 1.2-185.1). 787 CM were included in the analysis with completed information about therapies. All types of immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by anti-PD-1 (HR=0.25), globally immunotherapy was significantly associated with improved survival, either for anti-CTLA4 monotherapy or combined with anti-PD-1 (HR=0.47 and 0.26, respectively) and BRAFI+MEKI (HR=0.62)., Conclusions: The nivolumab/pembrolizumab in combination of ipilimumab and the addition of ant-MEK to the BRAFi can be considered the best therapies to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment., Competing Interests: PA has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Array, Merck Serono, Pierre-Fabre, Incyte, Medimmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Oncosec, Pfizer. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Array and travel support from MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Crispo, Corradin, Giulioni, Vecchiato, Del Fiore, Queirolo, Spagnolo, Vanella, Caracò, Tosti, Pennacchioli, Giudice, Nacchiero, Quaglino, Ribero, Giordano, Marussi, Barruscotti, Guida, De Giorgi, Occelli, Grosso, Cairo, Gatti, Massa, Atzori, Calvani, Fabrizio, Mastrangelo, Toffolutti, Celentano, Budroni, Gandini, Rossi, Testori, Palmieri, Ascierto and the Clinical National Melanoma Registry Study Group at the Italian Melanoma Intergroup.)

Background: Hepatitis C virus (HCV) infection represents a global health issue with severe implications on morbidity and mortality. This study aimed to evaluate the impact of HCV infection on all-cause, liver-related, and non-liver-related mortality in a population living in an area with a high prevalence of HCV infection before the advent of Direct-Acting Antiviral (DAA) therapies, and to identify factors associated with cause-specific mortality among HCV-infected individuals., Methods: We conducted a cohort study on 4492 individuals enrolled between 2003 and 2006 in a population-based seroprevalence survey on viral hepatitis infections in the province of Naples, southern Italy. Study participants provided serum for antibodies to HCV (anti-HCV) and HCV RNA testing. Information on vital status to December 2017 and cause of death were retrieved through record-linkage with the mortality database. Hazard ratios (HRs) for cause-specific mortality and 95% confidence intervals (CIs) were estimated using Fine-Grey regression models., Results: Out of 626 deceased people, 20 (3.2%) died from non-natural causes, 56 (8.9%) from liver-related conditions, 550 (87.9%) from non-liver-related causes. Anti-HCV positive people were at higher risk of death from all causes (HR = 1.38, 95% CI: 1.12-1.70) and liver-related causes (HR = 5.90, 95% CI: 3.00-11.59) than anti-HCV negative ones. Individuals with chronic HCV infection reported an elevated risk of death due to liver-related conditions (HR = 6.61, 95% CI: 3.29-13.27) and to any cause (HR = 1.51, 95% CI: 1.18-1.94). The death risk of anti-HCV seropositive people with negative HCV RNA was similar to that of anti-HCV seronegative ones. Among anti-HCV positive people, liver-related mortality was associated with a high FIB-4 index score (HR = 39.96, 95% CI: 4.73-337.54)., Conclusions: These findings show the detrimental impact of HCV infection on all-cause mortality and, particularly, liver-related mortality. This effect emerged among individuals with chronic infection while those with cleared infection had the same risk of uninfected ones. These results underline the need to identify through screening all people with chronic HCV infection notably in areas with a high prevalence of HCV infection, and promptly provide them with DAAs treatment to achieve progressive HCV elimination and reduce HCV-related mortality.

Introduction: Hepatitis C virus (HCV) infection affects about 170 million people worldwide. HCV is responsible for both hepatitis and extra-hepatic manifestations. Chronic infection has been shown to develop in about 70% of cases, and it can progress to cirrhosis or hepatocellular carcinoma. Ten percent of HCV patients may develop extra-hepatic manifestations, including mixed cryoglobulinemia (MC) and non-Hodgkin lymphomas (NHL). Cryoglobulinemic vasculitis (CV) varies, ranging from mild-moderate clinical symptoms (purpura on the legs, asthenia and arthralgias) and chronic hepatitis to severe symptoms (ulcers on the legs, peripheral neuropathy, glomerulonephritis, low-grade NHL to life threatening complications (rapid progressive glomerulonephritis, gastrointestinal vasculitis, acute hyper-viscosity)., Evidence Acquisition: CV is associated with significant morbidity and mortality. Some studies have shown kidney involvement, cirrhosis, central nervous system involvement, and heart involvement as unfavorable prognostic factors. Many studies have demonstrated that, after antiviral therapy, CV can disappear along with HCV. After the introduction of the new direct antiviral agents (DAAs), the combination of pegylated interferon and ribavirin has been abandoned., Evidence Synthesis: Several studies on new DAAs have reported remarkable 90% to 100% HCV eradication rates, regardless of genotype. Treatment with DAAs has comparable efficacy on viral eradication in CV patients but definite clinical improvements of vasculitis can be observed only in half the patients., Conclusions: In patients with mild to moderate CV disease, DAAs therapy should be used as first line approach. In patients with severe vasculitis, DAAs therapy and a second-line treatment with RTX with or without aphaeresis are a required.

The CDKN1B gene, encoding for the CDK inhibitor p27 kip1 , is mutated in defined human cancer subtypes, including breast, prostate carcinomas and small intestine neuroendocrine tumors. Lessons learned from small intestine neuroendocrine tumors suggest that CDKN1B mutations could be subclonal, raising the question of whether a deeper sequencing approach could lead to the identification of higher numbers of patients with mutations. Here, we addressed this question and analyzed human cancer biopsies from breast (n = 396), ovarian (n = 110) and head and neck squamous carcinoma (n = 202) patients, using an ultra-deep sequencing approach. Notwithstanding this effort, the mutation rate of CDKN1B remained substantially aligned with values from the literature, showing that essentially only hormone receptor-positive breast cancer displayed CDKN1B mutations in a relevant number of cases (3%). However, the analysis of copy number variation showed that another fraction of luminal breast cancer displayed loss (8%) or gain (6%) of the CDKN1B gene, further reinforcing the idea that the function of p27 kip1 is important in this type of tumor. Intriguingly, an enrichment for CDKN1B alterations was found in samples from premenopausal luminal breast cancer patients (n = 227, 4%) and in circulating cell-free DNA from metastatic luminal breast cancer patients (n = 59, 8.5%), suggesting that CDKN1B alterations could correlate with tumor aggressiveness and/or occur later during disease progression. Notably, many of the identified somatic mutations resulted in p27 kip1 protein truncation, leading to loss of most of the protein or of its C-terminal domain. Using a gene-editing approach in a luminal breast cancer cell line, MCF-7, we observed that the expression of p27 kip1 truncating mutants that lose the C-terminal domains failed to rescue most of the phenotypes induced by CDKN1B gene knockout, indicating that the functions retained by the C-terminal portion are critical for its role as an oncosuppressor, at least in luminal breast cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland., (© 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.)

Despite the considerable number of studies investigating the Mediterranean diet in prostate cancer (PCa) etiology, very few focused on cancer survival. We assessed the pre-diagnostic diet and physical activity in a cohort of 777 men with PCa diagnosed between 1995 and 2002 in north-eastern Italy; adherence to the Mediterranean diet was evaluated through the Mediterranean Diet Score (MDS). Hazard ratios (HR) of death with confidence intervals (CI) were estimated using the Cox model, adjusting for potential confounders. During 10 years of follow-up, 208 patients (26.8%) died, 75 (9.7%) due to PCa. Patients reporting MDS ≥ 5 showed a higher overall survival than those with MDS < 5 (HR = 0.74; 95% CI: 0.56-0.99). Although high physical activity was not significantly associated with overall survival (HR = 0.79; 95% CI: 0.59-1.07), the HR for all-cause death was the lowest (HR = 0.58; 95% CI: 0.38-0.90) for men reporting MDS ≥ 5 and high physical activity compared to those reporting MDS < 5 and low/moderate physical activity. No association emerged for PCa specific survival. Study findings support the beneficial impact of pre-diagnostic adherence to the Mediterranean diet and physical activity on overall survival; they are mainly driven by risk reduction in non-prostate cancer mortality, which however accounts for about 80% of death in men with PCa.

Objectives: to study the cumulative incidence, the demographics and health conditions of the population tested for COVID-19, and to map the evolving distribution of individual cases in the population of the Friuli Venezia Giulia Region (North-Eastern Italy)., Design: population-based observational study based on a record linkage procedure of databases included in the electronic health information system of the Friuli Venezia Giulia Region., Setting and Participants: the study group consisted of individuals who resided in the Friuli Venezia Giulia Region and who underwent COVID-19 testing from 01.03 to 24.04.2020. The study group was identified from the laboratory database, which contains all the microbiological testing performed in regional facilities. Tested people were categorized into positive or negative cases, based on test results., Main Outcome Measures: probability of being tested for and cumulative incidence of COVID-19., Results: the cumulative probability of being tested for COVID-19 was 278/10,000 inhabitants, while the cumulative incidence was 22 cases/10,000. Out of 33,853 tested people, 2,744 (8.1%) turned out to be positive for COVID-19. Women were tested more often than men (337 vs 216/10,000), and they showed a higher incidence of infection than men (25 and 19 infected cases/10,000 residents, respectively). Both cumulative incidence and cumulative probability of being tested were higher in the elderly population. About 25% of infected people was hosted in retirement homes and 9% was represented by healthcare workers. Thirty seven percent of positive cases had hypertension, 15% cardiologic diseases, while diabetes and cancer characterized 11.7% and 10% of the infected population, respectively. The geographic distribution of positive cases showed a faster spread of the infection in the city of Trieste, an urban area with the highest regional population density., Conclusions: the COVID-19 pandemic did not hit the Friuli Venezia Giulia Region as hard as other Northern Italian Regions. In the early phase, as documented in this study, the COVID-19 pandemic particularly affected women and elderly people, especially those living in retirement homes in Trieste.

The cancer risk of patients with inflammatory bowel diseases (IBD) has not been well documented in southern Europe. This study aimed to evaluate the overall pattern of cancer risk among patients with IBD in Friuli Venezia Giulia, northeastern Italy. A population-based cohort study was performed through a record linkage between local healthcare databases and the cancer registry (1995-2013). We identified 3664 IBD patients aged 18-84 years, including 2358 with ulcerative colitis (UC) and 1306 with Crohn's disease (CD). Sex- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were used to compare the cancer incidence of IBD patients with the general population. The cumulative cancer risk among IBD patients reached about 10% after 10 years of follow-up. A total of 246 cancers occurred among UC patients (SIR = 1.05, 95% CI: 0.92-1.19), and 141 among CD patients (SIR = 1.20, 95% CI: 1.01-1.41). As compared with the general population, no increased risk of colorectal cancers was observed for either UC or CD patients, whereas the risk of anal cancer was significantly elevated among UC patients (SIR = 6.03, 95% CI: 1.24-17.60). Increased risks were seen for specific extra-intestinal cancers, including corpus uteri (SIR = 2.67, 95% CI: 1.07-5.50) and kidney (SIR = 2.06, 95% CI: 1.03-3.69) among UC patients; thyroid (SIR = 5.58, 95% CI: 2.41-11.00) and skin non-melanoma (SIR = 1.86, 95% CI: 1.32-2.55) among CD patients. This population-based study showed that both UC and CD patients had a colorectal cancer risk similar to that of the general population. However, they were at a higher risk of developing certain extra-intestinal cancer types. Although detection biases cannot be excluded, the study findings pointed to a role of long-standing exposures to immunosuppressive therapies, underlying disease status, as well as the interactions with lifestyle factors. Our findings lent additional support to the need for monitoring the cancer burden in this at-risk population., Competing Interests: The authors have declared that no competing interests exist.

Objective: The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged <50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy., Method: Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models., Results: Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945., Conclusions: The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones., Competing Interests: Declaration of competing interest The authors have no competing interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)