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Phenobarbital is not genotoxic, but has been related to promotion of liver cancer (as well as inhibition) in rodents. In October 2012, we carried out a systematic literature search in the Medline database and searched reference lists of retrieved publications. We identified 15 relevant papers. Epidemiological data on epileptics/anticonvulsant use and liver cancer were retrieved from eight reports from seven cohort (record linkage) studies of epileptics, and data on phenobarbital use from a pharmacy-based record linkage investigation of patients treated with phenobarbital (three reports), plus a case–control study nested in one of the cohort studies and including information on phenobarbital use. Of the studies of cancer in epileptics, two showed no excess risk of liver cancer. A long-term (1933–1984) Danish cohort study of epileptics found relative risks (RRs) of 4.7 [95% confidence interval (CI) 3.2–6.8] of liver cancer and of 2.2 (95% CI 1.2–3.5) of biliary tract cancers. Such apparent excess risks could, however, be largely or completely attributed to thorotrast, a contrast medium used in the past in epileptic patients for cerebral angiography. A Finnish cohort study of epileptics obtained an RR of 1.7 (95% CI 1.2–2.4). Such an apparent excess risk, however, was not related to phenobarbital or to any specific anticonvulsant drug. The long-term follow-up of two UK cohorts found some excess risk of liver cancer among severe, but not among mild, epileptics. Some excess risk of liver cancer was also found in cohort studies of patients hospitalized for epilepsy in Sweden and Taiwan, in the absence, however, of association with any specific drugs. A UK General Practice database, comparing epileptics treated with valproate with unexposed ones, found a very low incidence of liver cancer. Of the studies of cancer in patients treated with phenobarbital, a large US pharmacy-based cohort investigation showed no excess risk of liver cancer. In a case–control study, nested in the Danish cohort of epileptics, no association was observed between phenobarbital and liver cancer among patients who had not received thorotrast (RR = 1.0 for liver and 0.8 for biliary tract cancers). Thus, some, although not all, studies reported excess risk of all cancers and liver cancer in severe, but not in milder epileptics. There is no evidence of a specific role of phenobarbital in human liver cancer risk, but data on the topic are limited.

Background: A diagnosis of interstitial lung diseases (ILDs) may include surgical lung biopsy (SLB), which is associated with significant morbidity and mortality and also appreciable costs. Transbronchial lung cryobiopsy (TBLC) is adopting an important role. Objectives: The aim of this study was to compare the diagnostic yield (DY) and safety of TBLC and SLB in a large cohort of patients and to perform a systematic review of the literature as well as a meta-analysis. Methods: We performed a retrospective analysis of 447 cases with ILD undergoing TBLC and/or SLB and a systematic review of the literature (MEDLINE and Embase for all original articles on the DY and safety of TBLC in ILDs up to July 2015). Results: A total of 150 patients underwent SLB and 297 underwent TBLC. The median time of hospitalization was 6.1 days (SLB) and 2.6 days (TBLC; p < 0.0001). Mortality due to adverse events was observed for 2.7% (SLB) and 0.3% (TBLC) of the patients. Pneumothorax was the most common complication after TBLC (20.2%). No severe bleeding was observed. TBLC was diagnostic for 246 patients (82.8%), SLB for 148 patients (98.7%, p = 0.013). A meta-analysis of 15 investigations including 781 patients revealed an overall DY of 0.81 (0.75-0.87); the overall pooled probability of developing a pneumothorax, as retrieved from 15 studies including 994 patients, was 0.06 (95% CI 0.02-0.11). Conclusion: Cryobiopsy is safe and has lower complication and mortality rates compared to SLB. TBLC might, therefore, be considered the first diagnostic approach for obtaining tissue in ILDs, reserving the surgical approach for cases in which TBLC is not diagnostic.

Introduction Fertility after cancer represents a growing clinical concern. This study assessed childbearing outcomes among women diagnosed with cancer during reproductive age between 2012 and 2017 in Lombardy, the largest region in Italy. Material and Methods Women aged 15–45 years with a primary diagnosis of cancer recorded in hospital discharge records from regional healthcare databases were selected. Each woman diagnosed with cancer was matched with up to five cancer‐free women of the same age at diagnosis. The cumulative probability of childbirth up to December 31, 2022 was estimated using the Kalbfleisch–Prentice cumulative incidence function estimator. Cox regression models were used to estimate the cause‐specific hazard ratios (HRs) and the 95% confidence intervals (CIs) of childbirth according to the cancer diagnosis. Furthermore, in the group of cancer survivors, exposure to antineoplastic treatment was considered and included in the model as a time‐dependent covariate. Finally, a log‐binomial regression model was used to assess the association between antineoplastic therapy and medically assisted reproduction. Results A total of 13,877 women were diagnosed with cancer at reproductive age during the study period (1.16 per 1000 person‐years). The cumulative probability of childbirth was lower among women diagnosed with cancer compared to cancer‐free women across all age groups: 31.4% vs 32.2% (p = 0.02) among those diagnosed under 30, 13.3% vs 22.7% (p < 0.01) among those aged 30–39, and 0.8% vs 1.6% (p < 0.01) among those aged 40 and over. The corresponding HRs were 0.93 (95% CI: 0.83–1.05), 0.58 (95% CI: 0.53–0.64), and 0.52 (95% CI: 0.40–0.68). When analyses were stratified by time since diagnosis, the reduced probability among cancer survivors was confirmed to be significant only within the first 5 years after diagnosis, also for younger individuals. Antineoplastic treatment was associated with a reduced probability of subsequent birth (HR = 0.46, 95% CI: 0.39–0.52). Moreover, the therapy was positively associated with medically assisted reproduction (RR = 1.71, 95% CI: 1.14–2.56). Conclusions The probability of childbearing was reduced within the first 5 years of diagnosis, regardless of the patient's age. A more pronounced reduction was observed in women diagnosed after the age of 30. Age and antineoplastic therapy were key factors in determining childbearing in women diagnosed with cancer. Compared to cancer‐free women, the probability of childbearing within 5 years of a cancer diagnosis was reduced, particularly among those diagnosed over the age of 30. Age at diagnosis and antineoplastic treatment were key factors, with treatment also increasing the use of assisted reproduction.

Purpose: We investigated risk factors for colorectal cancer in early-onset cancers, to provide quantitative estimates for major selected risk factors. Methods: We analyzed data from three Italian and Swiss case–control studies conducted between 1985 and 2009, including 329 colorectal cancer cases and 1,361 controls aged ≤45 years. We computed odds ratios (ORs) from unconditional logistic regression models, adjusted for major confounding factors. Results: The OR of young-onset colorectal cancer was 4.50 for family history of colorectal cancer in first-degree relatives, the association being higher in subjects with affected siblings (OR 11.68) than parents (OR 3.75). The ORs of young-onset colorectal cancer were 1.56 for ≥14 drinks/week of alcohol, 1.56 for the highest tertile of processed meat, 0.40 for vegetables, 0.75 for fruit, and 0.78 for fish intake. Among micronutrients, the ORs were 0.52 for β-carotene, 0.68 for vitamin C, 0.38 for vitamin E, and 0.59 for folate. No significant associations emerged for physical activity, overweight, and diabetes. Conclusions: This study—the largest on young-onset colorectal cancer—confirms that several recognized risk factors for colorectal cancer are also relevant determinants of young-onset colorectal cancer. Family history of colorectal cancer in particular is a stronger risk factor in young subjects, as compared to middle age and elderly ones.

Background Several studies considered the relation between long-term exposure to particulate matter (PM) and total mortality, as well as mortality from cardiovascular and respiratory diseases. Our aim was to provide a comprehensive review of European epidemiological studies on the issue. Methods We searched the Medline database for epidemiological studies on air pollution and health outcomes published between January 2002 and December 2007. We also examined the reference lists of individual papers and reviews. Two independent reviewers classified the studies according to type of air pollutant, duration of exposure and health outcome considered. Among European investigations that examined long-term PM exposure we found 4 cohort studies (considering total and cardiopulmonary mortality), 1 case-control study (considering mortality from myocardial infarction), and 4 ecologic studies (2 studies considering total and cardiopulmonary mortality and 2 studies focused on cardiovascular mortality). Results Measurement indicators of PM exposure used in European studies, including PM10, PM2.5, total suspended particulate and black smoke, were heterogeneous. This notwithstanding, in all analytic studies total mortality was directly associated with long-term exposure to PM. The excesses in mortality were mainly due to cardiovascular and respiratory causes. Three out of 4 ecologic studies found significant direct associations between PM indexes and mortality. Conclusion European studies on long-term exposure to PM indicate a direct association with mortality, particularly from cardiovascular and respiratory diseases.

Background Gastric cancer (GC) incidence is declining heterogeneously worldwide. We aimed to calculate updated mortality trends for GC. Methods We investigated time trends for selected countries using the World Health Organization database. We computed age‐standardized mortality rates (ASMR) per 100,000 persons over the 1990–2019 period. We reported rates for the 2010–2014 and 2015–19 calendar periods, and the corresponding percent changes. We used joinpoint regression analysis to identify changes in the slope of mortality trends, and predict the number of deaths and rates for 2025. We also reported 2008–2012 incidence rates of cardia and noncardia GC. Results Mortality trends from GC have been favorable since 1990 for all countries analyzed and the European Union (EU 27), in both sexes and all ages. GC mortality is predicted to decline in all countries for both sexes, except for French and US women aged 35–64 years, and Canadian men aged 35–64. The highest proportions of cardia GC were observed in Northern and Central Europe while the lowest ones in Southern and Eastern Europe. Elsewhere, the highest proportions were registered in countries with low incidence and mortality rates, whereas high‐mortality countries showed lower proportions of cardia GC. Conclusion Observed and predicted GC mortality trends declined in most countries in both sexes, with few exceptions, likely due to the control of GC risk factors, in particular Hp infection. Age‐standardized mortality rates from gastric cancer per 100,000, 2015‐2019, in men and women in selected countries

Background Pregnancy associated cancer (PAC) may lead to adverse obstetric and neonatal outcomes. This study aims to assess the association between PACs and adverse perinatal outcomes [i.e. labor induction, iatrogenic delivery, preterm birth, small for gestational age (SGA) newborn, low Apgar score, major malformations, perinatal mortality] in Lombardy, Northern Italy. Methods This population-based historic cohort study used the certificate of delivery assistance and the regional healthcare utilization databases of Lombardy Region to identify beneficiaries of National Health Service who delivered between 2008 and 2017. PACs were defined through oncological ICD-9-CM codes reported in the hospital discharge forms. Each woman with PAC was matched to four women randomly selected from those cancer-free (1:4). Log-binomial regression models were fitted to estimate crude and adjusted prevalence ratio (aPR) and the corresponding 95% confidence interval (CI) of each perinatal outcome among PAC and cancer-free women. Results Out of the 657,968 deliveries, 831 PACs were identified (1.26 per 1000). PAC diagnosed during pregnancy was positively associated with labor induction or planned delivery (aPR=1.80, 95% CI: 1.57–2.07), cesarean section (aPR=1.78, 95% CI: 1.49–2.11) and premature birth (aPR=6.34, 95% CI: 4.59–8.75). No association with obstetric outcomes was found among PAC diagnosed in the post-pregnancy. No association of PAC, neither during pregnancy nor in post-pregnancy was found for SGA (aPR=0.71, 95% CI: 0.36–1.35 and aPR=1.04, 95% CI: 0.78–1.39, respectively), but newborn among PAC women had a lower birth weight ( p -value< 0.001). Newborns of women with PAC diagnosed during pregnancy had a higher risk of borderline significance of a low Apgar score (aPR=2.65, 95% CI: 0.96–7.33) as compared to cancer-free women. Conclusion PAC, especially when diagnosed during pregnancy, is associated with iatrogenic preterm delivery, compromising some neonatal heath indicators.

PurposeTo 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.MethodsWithin 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-β-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.ResultsThe 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-β-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.ConclusionAlthough 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.

Although physical activity (PA) has been recognized as a favourable factor in the prevention of various diseases, including certain forms of cancer, the relationship between PA and gastric cancer (GC) is not yet fully understood. This study aims to provide data from a pooled analysis of case-control studies within the Stomach cancer Pooling (StoP) Project to estimate the association between leisure-time PA and the occurrence of GC. Six case-control studies from StoP project collected data on leisure-time PA, for a total of 2,343 cases and 8,614 controls. Subjects were classified into three leisure-time PA categories, either none/low, intermediate or high, based on study-specific tertiles. We used a two-stage approach. Firstly, we applied multivariable logistic regression models to obtain study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) then, we used a random-effect models to obtain pooled effect estimates. We performed stratified analyses according to demographic, lifestyle and clinical covariates. The meta-analysis showed ORs of GC with no significant differences between intermediate vs low and high vs low PA level (OR 1.05 [95%CI 0.76-1.45]; OR 1.23 [95%CI 0.78-1.94], respectively). GC risk estimates did not strongly differ across strata of selected covariates except for age ≤ 55 years old (high vs low level: OR 0.72 [95%CI 0.55-0.94]) and for control population-based studies (high vs low level: OR 0.79 [95%CI 0.68-0.93]). No association was found between leisure time PA and GC, apart from a slight suggestion of decreased risk below age 55 and in control population-based studies. These results may reflect specific characteristics of GC at a younger age, or the presence of a cohort effect mediating and interacting with socioeconomic determinants of GC The different distribution of PA levels among hospitalized controls could have led to an underestimated effect of PA on GC risk.

Background A diagnosis of cancer during pregnancy or within one year after the end of pregnancy is a major clinical and public health issue. The current study aimed at estimating the incidence of pregnancy-associated cancer (PAC) and assessing whether the risk of abortion is increased in women diagnosed with cancer. Methods This population-based cohort study used the regional healthcare utilization (HCU) databases of Lombardy, the largest region in Italy, to identify the women who delivered between 2010 and 2020. PAC were identified by oncological ICD-9-CM codes reported in the hospital discharge forms. We computed the ratio of PAC cases to the total number of pregnancies. Following a diagnosis of PAC, the prevalence ratio (PR) of abortion and the corresponding 95% confidence interval (CI), was estimated using a log-binomial model adjusted for maternal age. Results During the study period, 926 women who gave birth (1.29 cases per 1000 births) and 341 women who had an abortion (1.52 cases per 1000 abortions) were diagnosed with PAC. Regardless of the outcome of pregnancy, the risk of PAC increased with increasing age. The rate of PAC was initially lower among births, but it came very close to the rate of PAC among abortions in the last two calendar years. The proportion of abortions among women with PAC gradually decreased from 27.7% in 2010–2012 to 18.5% in 2019–2020 ( p -value < 0.001). Overall, a diagnosis of PAC was related to an approximately 10% increased risk of abortion (PR = 1.11, 95%CI:1.01–1.22). However, no association was observed in 2019–2020 (PR = 0.87, 95%CI:0.65–1.17). Considering only diagnoses made during the first trimester of pregnancy, the risk of abortion was about 2.5 times higher (PR = 2.53, 95%CI:2.05–3.11) and the risk of induced abortion was almost 4 times higher (PR = 3.71, 95%CI:2.82–4.90). Conclusion In this population the risk of abortion was about 10% higher in women with PAC than in women without PAC. However, this association tended to decrease in more recent calendar periods. This trend seemed to be influenced more by spontaneous than by induced abortions.