Previous educational and behavioral interventions in type 2 diabetes have produced modest improvements in glycemic control. Future research should refine such interventions and improve methodology.
ObjectivePancreatic ductal adenocarcinoma (PDA) has among the highest stromal fractions of any cancer and this has complicated attempts at expression-based molecular classification. The goal of this work is to profile purified samples of human PDA epithelium and stroma and examine their respective contributions to gene expression in bulk PDA samples.DesignWe used laser capture microdissection (LCM) and RNA sequencing to profile the expression of 60 matched pairs of human PDA malignant epithelium and stroma samples. We then used these data to train a computational model that allowed us to infer tissue composition and generate virtual compartment-specific expression profiles from bulk gene expression cohorts.ResultsOur analysis found significant variation in the tissue composition of pancreatic tumours from different public cohorts. Computational removal of stromal gene expression resulted in the reclassification of some tumours, reconciling functional differences between different cohorts. Furthermore, we established a novel classification signature from a total of 110 purified human PDA stroma samples, finding two groups that differ in the extracellular matrix-associated and immune-associated processes. Lastly, a systematic evaluation of cross-compartment subtypes spanning four patient cohorts indicated partial dependence between epithelial and stromal molecular subtypes.ConclusionOur findings add clarity to the nature and number of molecular subtypes in PDA, expand our understanding of global transcriptional programmes in the stroma and harmonise the results of molecular subtyping efforts across independent cohorts.
Epidemiologic studies of pancreatic cancer risk have reported null or nonsignificant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently. A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow-up. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Compared to individuals with a body mass index (BMI) at baseline between 21-22.9 kg/m 2 , pancreatic cancer risk was 47% higher (95%CI:23-75%) among obese (BMI 30 kg/m 2 ) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR 5 1.30, 95%CI 5 1.09-1.56 comparing BMI 25 kg/m 2 to a BMI between 21 and 22.9 kg/m 2 ). Compared to individuals who were not overweight in early adulthood (BMI < 25 kg/m 2 ) and not obese at baseline (BMI < 30 kg/m 2 ), pancreatic cancer risk was 54% higher (95%CI 5 24-93%) for those who were overweight in early adulthood and obese at baseline. We observed a 40% higher risk among individuals who had gained BMI 10 kg/m 2 between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR 5 1.35 comparing the highest versus lowest quartile, 95%CI 5 1.03-1.78). BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer.
Higher intake of fruits, vegetables, and antioxidants may help protect against oxidative damage, thus lowering cancer and cardiovascular disease risk. This Washington County, Maryland, prospective study examined the association of fruit, vegetable, and antioxidant intake with all-cause, cancer, and cardiovascular disease death. CLUE participants who donated a blood sample in 1974 and 1989 and completed a food frequency questionnaire in 1989 (N = 6,151) were included in the analysis. Participants were followed to date of death or January 1, 2002. Compared with those in the bottom fifth, participants in the highest fifth of fruit and vegetable intake had a lower risk of all-cause (cases = 910; hazard ratio (HR) = 0.63, 95% confidence interval (CI): 0.51, 0.78; p-trend = 0.0004), cancer (cases = 307; HR = 0.65, 95% CI: 0.45, 0.93; p-trend = 0.08), and cardiovascular disease (cases = 225; HR = 0.76, 95% CI: 0.54, 1.06; p-trend = 0.15) mortality. Higher intake of cruciferous vegetables was associated with lower risk of all-cause mortality (HR = 0.74, 95% CI: 0.60, 0.91; p-trend = 0.04). No statistically significant associations were observed between dietary vitamin C, vitamin E, and beta-carotene intake and mortality. Overall, greater intake of fruits and vegetables was associated with lower risk of all-cause, cancer, and cardiovascular disease death. These findings support the general health recommendation to consume multiple servings of fruits and vegetables (5-9/day).
Background: Few risk factors have been implicated in pancreatic cancer etiology. Alcohol has been theorized to promote carcinogenesis. However, epidemiologic studies have reported inconsistent results relating alcohol intake to pancreatic cancer risk. Methods: We conducted a pooled analysis of the primary data from 14 prospective cohort studies. The study sample consisted of 862,664 individuals among whom 2,187 incident pancreatic cancer cases were identified. Study-specific relative risks and 95% confidence intervals were calculated using Cox proportional hazards models and then pooled using a random effects model. Results: A slight positive association with pancreatic cancer risk was observed for alcohol intake (pooled multivariate relative risk, 1.22; 95% confidence interval, 1.03-1.45 comparing z30 to 0 grams/day of alcohol; P value, test for between-studies heterogeneity = 0.80).
Background: Obesity is a worldwide epidemic in children and adolescents. Adult cohort studies have reported an association between higher body mass index (BMI) and increased leukemiarelated mortality; whether a similar effect exists in childhood leukemia remains controversial. Objective: We conducted a meta-analysis to determine whether a higher BMI at diagnosis of pediatric acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) is associated with worse event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR). Design: We searched 4 electronic databases from inception through March 2015 without language restriction and included studies in pediatric ALL or AML (0-21 y of age) reporting BMI as a predictor of survival or relapse. Higher BMI, defined as obese ($95%) or overweight/obese ($85%), was compared with lower BMI [nonoverweight/obese (,85%)]. Summary risk estimates for EFS, OS, and CIR (ALL only) were calculated with random-or fixed-effects models according to tests for between-study heterogeneity. Results: Of 4690 reports identified, 107 full-text articles were evaluated, with 2 additional articles identified via review of citations; 11 articles were eligible for inclusion in this meta-analysis. In ALL, we observed poorer EFS in children with a higher BMI (RR: 1.35; 95% CI: 1.20, 1.51) than in those at a lower BMI. A higher BMI was associated with significantly increased mortality (RR: 1.31; 95% CI: 1.09, 1.58) and a statistically nonsignificant trend toward greater risk of relapse (RR: 1.17; 95% CI: 0.99, 1.38) compared with a lower BMI. In AML, a higher BMI was significantly associated with poorer EFS and OS (RR: 1.36; 95% CI: 1.16, 1.60 and RR: 1.56; 95% CI: 1.32, 1.86, respectively) than was a lower BMI. Conclusion: Higher BMI at diagnosis is associated with poorer survival in children with pediatric ALL or AML.Am J Clin Nutr 2016;103:808-17.
Pancreaticoduodenectomy can be performed safely in select patients 80 years and older. Age alone should not dissuade surgeons from offering patients resection, though elderly patients with pancreatic ductal adenocarcinoma appear to have shorter survival than younger patients with the same disease.
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