Glycemic Changes and Weight Loss Precede Pancreatic Ductal Adenocarcinoma by up to 3 Years in a Diverse Population.

BACKGROUND & AIMS: Elevations in fasting blood glucose are observed prior to the development of pancreatic ductal adenocarcinoma (PDAC). Our aim was to describe glycemic and weight changes that occur prior to PDAC diagnosis in a diverse population. METHODS: We conducted a case-control study comparing patients with PDAC with matched controls between January 2011 and November 2019 at a tertiary care institution. Normally distributed variables were compared using t tests, and the Wilcoxon rank sum test was used for non-normally distributed variables; logistic regression was used to estimate odds of PDAC based on changes over time in hemoglobin A1c (HbA1c) and body mass index (BMI), controlling for appropriate confounders. RESULTS: A total of 4626 patients met inclusion criteria: 1542 cases and 3084 controls; the median age was 69.3 years, and 2487 (53.8%) were male; 751 cases (48.7%) were non-Hispanic white. In the 3 years prior to diagnosis, HbA1c was higher in patients with PDAC compared with controls (P ≤ .02 for all); a similar trend was seen for glucose values. BMI was greater for patients with PDAC for all study periods, except 0 to 6 months prior to cancer diagnosis when BMI was lower (P < .01 for all). The change in BMI (ΔBMI) of cases at 1 year and 6 months before diagnosis was -0.59 and -1.21 when compared with -0.08 and 0.03 for controls (P < .01 for both). Multivariable logistic regression demonstrated that HbA1c slope (adjusted odds ratio, 1.33; 95% confidence interval, 1.01-1.76) and BMI slope (adjusted odds ratio, 0.75; 95% confidence interval, 0.65-0.87) were predictors of PDAC. CONCLUSION: Glycemic elevations and weight loss predate PDAC diagnosis. These metabolic changes may suggest an underlying PDAC.

Elevated hemoglobin A1c is associated with the presence of pancreatic cysts in a high-risk pancreatic surveillance program.

BACKGROUND: Emerging evidence demonstrates that surveillance of individuals at high-risk (HRIs) of developing pancreatic adenocarcinoma allows for identification and treatment of resectable tumors with improved survival. Population-based data suggest that hyperglycemia may be present up to three years before the development of pancreatic cancer. We investigated whether elevated hemoglobin A1c (HbA1c) is associated with the development of pancreatic cysts in a pancreatic surveillance program. METHODS: We performed a retrospective study of HRIs who underwent pancreatic surveillance at a single institution between May 2013 and March 2019, according to published criteria. We collected demographic information, clinical data including HbA1c, and imaging results. We compared data using univariable and multivariable analyses. Our primary outcome was the presence of pancreatic cysts on initial surveillance in patients with elevated HbA1c. RESULTS: Ninety-eight patients underwent surveillance imaging via EUS or MRCP and seventy-four patients met inclusion criteria. Thirty patients were found to have cysts on initial imaging. Older age (p < 0.01) and HbA1c in the prediabetic range or higher (p = 0.01) were associated with the presence of cysts or solid lesions on univariable analysis. After controlling for confounders, age (aOR 9.08, 95% CI 2.29-36.10), and HbA1c > 5.7% (aOR 5.82, 95% CI 1.50-22.54) remained associated with presence of cysts and solid lesions in HRIs. In patients with cysts or solid lesions there was a strong association between increased age and elevated HbA1c (p < 0.01). CONCLUSION: HRIs with elevated HbA1c were more likely to have pancreatic cysts compared to individuals with lower HbA1c on initial imaging in a pancreatic surveillance program. These findings may help tailor the surveillance protocols for those at increased risk of developing pancreatic adenocarcinoma.

CDH1 pathogenic variants and cancer risk in an unselected patient population.

CDH1 pathogenic variants confer a markedly elevated lifetime risk of developing diffuse gastric cancer (DGC) and lobular breast cancer (LBC). The aim of this study was to evaluate the prevalence and clinical impact of CDH1 pathogenic variants in the unselected and ancestrally diverse BioMe Biobank. We evaluated exome sequence data from 30,223 adult BioMe participants to identify CDH1 positive individuals, defined as those harboring a variant previously classified as pathogenic or likely pathogenic or a predicted loss-of-function variant in CDH1. We reviewed electronic health records and BioMe enrollment surveys for personal and family history of malignancy and evidence of prior clinical genetic testing. Using a genomics-first approach, we identified 6 CDH1 positive individuals in BioMe (~ 1 in 5000). CDH1 positive individuals had a median age of 42 years (range 35-62 years), all were non-European by self-report, and one was female. None had evidence of either a personal or family history of DGC or LBC. Our findings suggest a low risk of DGC and LBC in unselected patients harboring a pathogenic variant in CDH1. Knowledge of CDH1-related cancer risk in individuals with no personal or family history may better inform surveillance and prophylactic measures.

Beta-blockers have no impact on survival in pancreatic ductal adenocarcinoma prior to cancer diagnosis.

Previous studies have suggested that ß-adrenergic signaling may regulate the growth of various cancers. The aim of our study is to investigate the association between the incidental use of beta-blockers for various conditions on the overall survival of patients with pancreatic ductal adenocarcinoma (PDAC). Patients with histologically-confirmed PDAC between 2007 and 2011 were extracted from Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database. Kaplan Meier and multivariable Cox Proportional-Hazard models were used to examine the association between beta-blocker usage before diagnosis and overall survival adjusting for appropriate confounders. As an additional analysis we also examined continuous beta-blocker use before and after diagnosis. From 2007 to 2011, 13,731 patients were diagnosed with PDAC. Of these, 7130 patients had Medicare Part D coverage in the 6-month period before diagnosis, with 2564 (36%) of these patients using beta-blockers in this period. Patients receiving beta-blockers had a mean survival time of 5.1 months compared to 6 months for non-users (p < 0.01). In multivariable analysis, beta-blockers usage was not associated with improved survival (Hazard Ratio (HR) 1.04, 95%, Confidence Interval (CI) 0.98-1.1, p = 0.2). When patients were stratified by conditions with indications for beta-blocker usage, such as hypertension, coronary artery disease and cardiac arrhythmia, differences in survival were insignificant compared to non-users in all groups (p > 0.05). After stratification by receptor selectivity, this lack of association with survival persisted (p > 0.05 for all). As a subgroup analysis, looking at patients with continuous Medicare Part D coverage who used beta-blockers in the 6-month period before and after cancer diagnosis, we identified 7085 patients, of which 1750 (24.7%) had continuous beta blocker use. In multivariable analysis, continuous beta-blockers usage was associated with improved survival (Hazard Ratio (HR) 0.86, 95%, Confidence Interval (CI) 0.8-0.9, p < 0.01). Beta-blocker usage before diagnosis does not confer a survival advantage in patients with PDAC, though continuous use before and after diagnosis did confer a survival advantage. Prospective studies into the mechanism for this advantage are needed.

Vitamin D Deficiency is Common in Patients with Ulcerative Colitis After Total Proctocolectomy with Ileal Pouch Anal Anastomosis.

In a retrospective study of 412 patients with ulcerative colitis who underwent total proctocolectomy with ileal pouch anal anastomosis and had subsequent pouchoscopy, low 25-hydroxyvitamin D was common and was not significantly associated with age, sex, ethnicity, or precolectomy medication use.