Fruits and vegetables intake and bladder cancer risk: a pooled analysis from 11 case-control studies in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) consortium.

PURPOSE: High consumption of fruits and vegetables decrease the risk of bladder cancer (BC). The evidence of specific fruits and vegetables and the BC risk is still limited. METHODS: Fruit and vegetable consumptions in relation to BC risk was examined by pooling individual participant data from case-control studies. Unconditional logistic regression was used to estimate study-specific odds ratio's (ORs) with 95% confidence intervals (CIs) and combined using a random-effects model for intakes of total fruits, total vegetables, and subgroups of fruits and vegetables. RESULTS: A total of 11 case-control studies were included, comprising 5637 BC cases and 10,504 controls. Overall, participants with the highest intakes versus the lowest intakes of fruits in total (OR 0.79; 95% CI 0.68-0.91), citrus fruits (OR 0.81; 95% CI 0.65-0.98), pome fruits (OR 0.76; 95% CI 0.65-0.87), and tropical fruits (OR 0.84; 95% CI 0.73-0.94) reduced the BC risk. Greater consumption of vegetables in total, and specifically shoot vegetables, was associated with decreased BC risk (OR 0.82; 95% CI 0.68-0.96 and OR 0.87; 95% CI 0.78-0.96, respectively). Substantial heterogeneity was observed for the associations between citrus fruits and total vegetables and BC risk. CONCLUSION: This comprehensive study provides compelling evidence that the consumption of fruits overall, citrus fruits, pome fruits and tropical fruits reduce the BC risk. Besides, evidence was found for an inverse association between total vegetables and shoot vegetables intake.

Diabetes Risk Reduction Diet and Colorectal Cancer Risk.

BACKGROUND: Diabetes has been associated with colorectal cancer. We evaluated whether adherence to a diabetes risk reduction diet (DRRD) can favorably influence the risk of colorectal cancer. METHODS: Data came from a multicentric Italian case-control study including 1,953 histologically confirmed colorectal cancer cases and 4,154 hospital controls admitted for acute nonneoplastic diseases. Diet was assessed through a validated and reproducible food frequency questionnaire. The DRRD score was computed assigning higher values for higher consumption of cereal fiber, fruit, coffee, nuts and a higher polyunsaturated/saturated fats ratio and for lower glycemic index and lower consumption of red/processed meat and sweetened beverages and fruit juices. The ORs and the corresponding 95% confidence intervals (CI) of colorectal cancer according to the DRRD score were obtained using logistic regression models adjusting for total energy intake and other major confounders. RESULTS: The DRRD was inversely related to colorectal cancer risk. The ORs of colorectal cancer were 0.77 (95% CI, 0.67-0.89) for the third versus first score tertile (Ptrend < 0.001) and 0.92 (95% CI, 0.87-0.96) for a 3-point increment in the score. Inverse associations were observed for colon and rectal cancers and were consistent in strata of sex, age, and other major covariates. CONCLUSIONS: A higher adherence to a DRRD was inversely associated with colorectal cancer risk. IMPACT: Given the high incidence and mortality rates of colorectal cancer, adherence to a DRRD can have relevant prevention and public health implications.

Aspirin intake and head and neck cancer: A pooled analysis within the INHANCE consortium.

BACKGROUND: Aspirin intake might be inversely associated with head and neck cancer (HNC). Thus, we investigated this relationship within the International Head and Neck Cancer Epidemiology (INHANCE) consortium. METHODS: Four case-control studies within the INHANCE consortium were included (2024 cases, 4196 controls). Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression and subsequently pooled with DerSimonian-Laird random-effects model. Nonlinearity of the relationship between duration of intake and HNC was modeled with fractional polynomials. RESULTS: Aspirin was inversely associated with HNC overall (OR = 0.48; 95% CI: 0.26, 0.91). Results for laryngeal cancer were similar (OR = 0.54; 95% CI: 0.30, 0.96). Analysis on duration of intake confirmed findings for HNC overall, showing also inverse associations for oropharyngeal and laryngeal cancer. CONCLUSIONS: This study suggests that aspirin intake may reduce the risk of HNC, driven mainly by decreases in risk for laryngeal and oropharyngeal cancer.

Cancer mortality after kidney transplantation: A multicenter cohort study in Italy.

Kidney transplant (KT) recipients are known to be at risk of developing several cancer types; however, cancer mortality in this population is underinvestigated. Our study aimed to assess the risk of cancer death among Italian KT recipients compared to the corresponding general population. A cohort study was conducted among 7373 individuals who underwent KT between 2003 and 2020 in 17 Italian centers. Date and cause of death were retrieved until 31 December 2020. Indirect standardization was used to estimate standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs). Cancer was the most common cause of death among the 7373 KT recipients, constituting 32.4% of all deaths. A 1.8-fold excess mortality (95% CI: 1.59-2.09) was observed for all cancers combined. Lymphomas (SMR = 6.17, 95% CI: 3.81-9.25), kidney cancer (SMR = 5.44, 95% CI: 2.97-8.88) and skin melanoma (SMR = 3.19, 95% CI: 1.03-6.98) showed the highest excess death risks. In addition, SMRs were increased about 1.6 to 3.0 times for cancers of lung, breast, bladder and other hematopoietic and lymphoid tissues. As compared to the general population, relative cancer mortality risk remained significantly elevated in all age groups though it decreased with increasing age. A linear temporal increase in SMR over time was documented for all cancers combined (P < .01). Our study documented significantly higher risks of cancer death in KT recipients than in the corresponding general population. Such results support further investigation into the prevention and early detection of cancer in KT recipients.

SARS-CoV-2 Infection, Vaccination and Risk of Death in People with An Oncological Disease in Northeast Italy.

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.

Variation in Post-Transplant Cancer Incidence among Italian Kidney Transplant Recipients over a 25-Year Period.

This cohort study examined 25-year variations in cancer incidence among 11,418 Italian recipients of kidney transplantation (KT) from 17 Italian centers. Cancer incidence was examined over three periods (1997-2004; 2005-2012; and 2013-2021) by internal (Incidence rate ratio-IRR) and external (standardized incidence ratios-SIR) comparisons. Poisson regression was used to assess trends. Overall, 1646 post-transplant cancers were diagnosed, with incidence rates/1000 person-years ranging from 15.5 in 1997-2004 to 21.0 in 2013-2021. Adjusted IRRs showed a significant reduction in incidence rates across periods for all cancers combined after exclusion of nonmelanoma skin cancers (IRR = 0.90, 95% confidence interval-CI: 0.76-1.07 in 2005-2012; IRR = 0.72, 95% CI: 0.60-0.87 in 2013-2021 vs. 1997-2004; Ptrend < 0.01). In site-specific analyses, however, significant changes in incidence rates were observed only for Kaposi's sarcoma (KS; IRR = 0.37, 95% CI: 0.24-0.57 in 2005-2012; IRR = 0.09, 95% CI: 0.04-0.18 in 2013-2021; Ptrend < 0.01). As compared to the general population, the overall post-transplant cancer risk in KT recipients was elevated, with a decreasing magnitude over time (SIR = 2.54, 95% CI: 2.26-2.85 in 1997-2004; SIR = 1.99, 95% CI: 1.83-2.16 in 2013-2021; Ptrend < 0.01). A decline in SIRs was observed specifically for non-Hodgkin lymphoma and KS, though only the KS trend retained statistical significance after adjustment. In conclusion, apart from KS, no changes in the incidence of other cancers over time were observed among Italian KT recipients.

Intake of prebiotic fibers and the risk of laryngeal cancer: the PrebiotiCa study.

PURPOSE: To evaluate whether the intake of specific fibers with prebiotic activity, e.g., inulin-type fructans (ITFs), fructo-oligosaccharides (FOSs), and galacto-oligosaccharides (GOSs), is associated with laryngeal cancer risk. METHODS: Within the PrebiotiCa study, we used data from a case-control study (Italy, 1992-2009) with 689 incident, histologically confirmed laryngeal cancer cases and 1605 controls. Six prebiotic molecules (ITFs, nystose [FOS], kestose [FOS], 1F-ß-fructofuranosylnystose [FOS], raffinose [GOS] and stachyose [GOS]) were quantified in various foods via ad hoc conducted laboratory analyses. Subjects' prebiotic fiber intake was calculated by multiplying food frequency questionnaire intake by the prebiotic content of each food item. The odds ratios (OR) of laryngeal cancer for prebiotic fiber intake were calculated using logistic regression models, including, among others, terms for tobacco, alcohol, and total energy intake. RESULTS: The intakes of kestose, raffinose and stachyose were inversely associated with laryngeal cancer, with ORs for the highest versus the lowest quartile of 0.70 (95% confidence interval, CI 0.50-0.99) for kestose, 0.65 (95% CI 0.45-0.93) for raffinose and 0.61 (95% CI 0.45-0.83) for stachyose. ITFs, nystose and 1F-ß-fructofuranosylnystose were not associated with laryngeal cancer risk. Current smokers and heavy drinkers with medium-low intakes of such prebiotic fibers had, respectively, an over 15-fold increased risk versus never smokers with medium-high intakes and a five to sevenfold increased risk versus never/moderate drinkers with medium-high intakes. CONCLUSION: Although disentangling the effects of the various components of fiber-rich foods is complex, our results support a favorable role of selected prebiotic fibers on laryngeal cancers risk.

The use of PSA testing over more than 20 years: A population-based study in North-Eastern Italy.

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.

Vaccination against SARS-CoV-2 and risk of hospital admission and death among infected cancer patients: A population-based study in northern Italy.

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.

Association of prebiotic fiber intake with colorectal cancer risk: the PrebiotiCa study.

PURPOSE: To evaluate the association between the intake of specific fibers with prebiotic activity, namely inulin-type fructans (ITFs), fructooligosaccharides (FOSs) and galactooligosaccharides (GOSs), and colorectal cancer risk. METHODS: Within the PrebiotiCa study, we used data from a multicentric case-control study conducted in Italy and including 1953 incident, histologically confirmed, colorectal cancer patients and 4154 hospital controls. The amount of six prebiotic molecules [ITFs, nystose (FOS), kestose (FOS), 1F-ß-fructofuranosylnystose (FOS), raffinose (GOS) and stachyose (GOS)] in a variety of foods was quantified via laboratory analyses. Subjects' prebiotic fiber intake was estimated by multiplying food frequency questionnaire intake by the prebiotic content of each food item. The odds ratios (OR) of colorectal cancer for quintiles of intakes were derived from logistic regression models including terms for major confounders and total energy intake. RESULTS: GOSs intake was inversely associated with colorectal cancer risk. The OR for the highest versus the lowest quintile of intake were 0.73 (95% confidence interval, CI 0.58-0.92) for raffinose and 0.64 (95% CI 0.53-0.77) for stachyose, with significant inverse trends across quintiles. No association was found with total ITFs and FOSs. The association with stachyose was stronger for colon (continuous OR = 0.74, 95% CI 0.66-0.83) than rectal cancer (OR = 0.89, 95% CI 0.79-1.02). CONCLUSION: Colorectal cancer risk was inversely associated with the intake of dietary GOSs, but not ITFs and FOSs.

Increased kidney disease mortality among people with AIDS versus the general population: a population-based cohort study in Italy, 2006-2018.

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.

Risk of Cancer in Connective Tissue Diseases in Northeastern Italy over 15 Years.

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.

Mortality of people with AIDS in Italy: comparison of AIDS surveillance and multiple cause-of-death registries.

AIMS: To assess whether the use of multiple cause-of-death data could improve reporting of AIDS mortality in Italy. METHOD: Population-based, record-linkage study, on 3,975,431 deaths recorded in the National Registry of Causes of Death (RCoD) and 4,530 deaths recorded in the National AIDS Registry (RAIDS), during 2006-2012. RESULTS: The record-linkage identified 3,646 AIDS-related deaths present in both registries, 884 deaths in the RAIDS without mention of HIV/AIDS in the RCoD, and 3,796 deaths in the RCoD with mention of HIV/AIDS that were not present in the RAIDS. In the latter, in-depth analysis of multiple cause-of-death allowed the identification of 1,484 deaths that were AIDS-related. On these results, we estimated 6,014 deceased people with AIDS. Of them, 14.7% (884) were not present in the RCoD and 24.7% (1,484) derived from the RCoD only. CONCLUSIONS: The integration of different nationwide registries allowed a more comprehensive estimate of the impact of AIDS-associated mortality in Italy.

Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients.

Liver transplanted (LT) patients for hepatocellular carcinoma (LT-HCC) or for other causes (LT-no-HCC) may develop post-transplantation malignancies. Although immune activation and senescence are frequently implicated in cancer development, no data is available on their possible role as biomarkers predictive of tumor onset in this setting. A total of 116 patients were investigated: the 45 LT-HCC patients were older than the 71 LT-non-HCC (p=0.011), but comparable for sex, HCV, HBV infection and immunosuppressive treatment. At baseline, the numbers of activated and senescent-like circulating cells were significantly higher in LT-HCC patients than in LT-no-HCC ones. After a median follow-up of 26.8 months, 6 post-transplant malignancies (PTM) occurred: 4 in LT-HCC (8.9%) and 2 in LT-no-HCC (2.8%) patients. Overall, subjects with high percentages of activated and exhausted T and B cells at baseline were at higher risk of PTM. Notably, within the LT-HCC group, a higher percentage of senescence-like T cells was also associated with cancer development. Moreover, patients with PTM had higher telomere erosion and higher levels of circulating PAMPs (16S rDNA) and DAMPs (mtDNA) when compared with matched patients without PTM. Overall, these findings suggest that immune activation and exhaustion may be useful to predict the risk of PTM occurrence, regardless of the cause of transplantation. In LT-HCC, T-cell senescence represents an additional risk factor for tumor onset.

Prevalence and determinants of quitting smoking after cancer diagnosis: a prospective cohort study.

OBJECTIVE: To describe smoking behaviours of patients with incident cancer attending an Italian cancer centre and to examine changes in their smoking habits within 12 months from cancer diagnosis, evaluating determinants of smoking cessation. METHODS: A hospital-based prospective cohort included patients hospitalized in an Italian cancer centre (2016-2018). Patients were mostly female (74%) and included a limited proportion of aerodigestive cancers (7%). Face-to-face interviews were performed during hospital stay to gather information on patient characteristics and smoking history. Changes in smoking habits were assessed through telephone interviews at 3, at 6, and at 12 months after cancer diagnosis. RESULTS: Among 1011 enrolled patients, 222 (22%) were current smokers at cancer diagnosis. Smoking prevalence was high in male patients (30%), in patients <50 years old (28%), in those with aerodigestive cancers (50%), and in those diagnosed at advanced stages (26%). Among current smokers at cancer diagnosis, 38% quit smoking after 12 months, 26% reduced intensity, and 36% did not modify smoking habits. Smoking cessation was associated with chemotherapy and, although not statistically significant, with female sex, older age, and advanced cancer stage. Patients with gastrointestinal, breast, or genitourinary cancer and those treated with surgery were less likely to quit smoking. CONCLUSIONS: Our results highlighted that 62% of smoking patients with cancer did not quit the habit. Smoking cessation programs targeted to patients with cancer need intensification, particularly for those who may underestimate smoking effects after diagnosis.

The impact of cancer on the risk of death with a functioning graft of Italian kidney transplant recipients.

This study assessed the impact of cancer on the risk of death with a functioning graft of kidney transplant (KT) recipients, as compared to corresponding recipients without cancer. A matched cohort study was conducted using data from a cohort of 13 245 individuals who had undergone KT in 17 Italian centers (1997-2017). Cases were defined as subjects diagnosed with any cancer after KT. For each case, two controls matched by gender, age, and year at KT were randomly selected from cohort members who were cancer-free at the time of diagnosis of the index case. Overall, 292 (20.5%) deaths with a functioning graft were recorded among 1425 cases and 238 (8.4%) among 2850 controls. KT recipients with cancer had a greater risk of death with a functioning graft (hazard ratio, HR = 3.31) than their respective controls. This pattern was consistent over a broad range of cancer types, including non-Hodgkin lymphoma (HR = 33.09), lung (HR = 20.51), breast (HR = 8.80), colon-rectum (HR = 3.51), and kidney (HR = 2.38). The survival gap was observed throughout the entire follow-up period, though the effect was more marked within 1 year from cancer diagnosis. These results call for close posttransplant surveillance to detect cancers at earlier stages when treatments are more effective in improving survival.

Hepatitis C virus infection and risk of liver-related and non-liver-related deaths: a population-based cohort study in Naples, southern Italy.

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.

Hepatocellular carcinoma and the risk of de novo malignancies after liver transplantation - a multicenter cohort study.

Patients with hepatocellular carcinoma (HCC) are at high risk of second primary malignancies. As HCC has become the leading indication of liver transplant (LT), the aim of this study was to investigate whether the presence of HCC before LT could influence the onset of de novo malignancies (DNM). A cohort study was conducted on 2653 LT recipients. Hazard ratios (HR) of DNM development for patients transplanted for HCC (HCC patients) were compared with those of patients without any previous malignancy (non-HCC patients). All models were adjusted for sex, age, calendar year at transplant, and liver disease etiology. Throughout 17 903 person-years, 6.6% of HCC patients and 7.4% of non-HCC patients developed DNM (202 cases). The median time from LT to first DNM diagnosis was shorter for solid tumors in HCC patients (2.7 vs 4.5 years for HCC and non-HCC patients, respectively, P < 0.01). HCC patients were at a higher risk of bladder cancer and skin melanoma. There were no differences in cumulative DNM-specific mortality by HCC status. This study suggests that primary HCC could be a risk factor for DNM in LT recipients, allowing for risk stratification and screening individualization.

Risk of intestinal and extra-intestinal cancers in patients with inflammatory bowel diseases: A population-based cohort study in northeastern Italy.

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.

Worldwide Age at Onset of Female Breast Cancer: A 25-Year Population-Based Cancer Registry Study.

A higher frequency of early onset female breast cancers (BC) has been observed in low/middle income countries than in high income countries. We quantified the role of population ageing to this pattern using data from all population-based cancer registries (CRs) worldwide. Patients' median age at BC onset and that of the general population were extracted for CRs listed in volumes VI (1983-1987 years) through XI (2008-2012 years) of Cancer Incidence in Five Continents. Their association was assessed at cross-sectional level by linear regression model and longitudinally considering 25-year ageing of the population in long-standing CRs listed at the beginning and at the end of the study. During 2008-2012, each one-year increase of population ageing was associated with a nearly ½ year increase of age at BC diagnosis. Population demographics explained forty-two percent of the age variance for BC. In 1983-1987, long-standing CRs with a median age at BC below age 61.8 years showed an increase of age at BC after 25-years. Worldwide, age at BC diagnosis essentially reflected the median age of the population. Changes in BC detection methodology likely lessened this association. Nevertheless, the elevated absolute number of BCs in young populations deserves strategies of BC prevention.