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ABSTRACTObjectives:The aim of the present study was to investigate the natural history of chronic pancreatitis (CP); patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared.Methods:Demographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables.Results:Alcohol was a risk in 53% of adults and 1% of children (P < 0.0001); tobacco in 50% of adults and 7% of children (P < 0.0001). Obstructive factors were more common in children (29% vs 19% in adults, P = 0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, P = 0.107). Diabetes was more common in adults than children (36% vs 4% respectively, P < 0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2‐CO) were compared with INSPPIRE subjects. These 2 cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2‐CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2‐CO vs 1% INSPPIRE cohorts, P = 0.011).Conclusions:Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.

Goal: To investigate associations of prediagnosis and postdiagnosis use of statins and metformin on overall survival of patients with diabetes who later developed HCC. Background: Statins and metformin have received considerable interest as potential chemopreventive agents against hepatocellular carcinoma (HCC) development in individuals with type 2 diabetes mellitus (T2DM); however, their impact on overall survival of patients with T2DM who later develop HCC (diabetic HCC patients) is unclear. Study: Data on 2499 elderly diabetic HCC patients obtained from the SEER-Medicare program (2009 to 2013) were analyzed. Patients were categorized based on use of statins only, metformin only, both, or neither (reference for all comparisons). The patients were further categorized based on: (1) metformin dose: ≤1500 or >1500 mg/d; (2) statins functional form: hydrophilic (pravastatin and rosuvastatin) or lipophilic (atorvastatin, fluvastatin, lovastatin, and simvastatin); (3) statins potency: high (atorvastatin, rosuvastatin, and simvastatin) or low (fluvastatin, lovastatin, and pravastatin); and (4) individual statins type. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. Results: Prediagnosis use of metformin dose ≤1500 mg/d was associated with lower risk of death after HCC diagnosis in patients with T2DM (HR, 0.72; 95% CI, 0.58-0.91), adjusting for postdiagnosis metformin dose, diabetes severity, Charlson comorbidity index, tumor characteristics, and other relevant factors. No association was found for prediagnosis metformin dose >1500 mg/d or postdiagnosis metformin use. Further, no association was found for either prediagnosis or postdiagnosis statins use. Conclusions: Prediagnosis use of metformin dose ≤1500 mg/d is associated with longer overall survival of elderly diabetic HCC patients.

Background: Efforts to improve prescription of oral anticoagulation (OAC) drugs in patients with atrial fibrillation have had limited success in improving guideline adherence. Methods: We evaluated adherence to the American College of Cardiology/American Heart Association performance measures for OAC in eligible patients with a CHA 2 DS 2 -VASc score ≥2 and trends in prescription over time in the American Heart Association’s Get With The Guidelines–AFIB (atrial fibrillation) registry. Adjusted associations with in-hospital outcomes were also determined. The cohort included 33 235 patients with a CHA 2 DS 2 -VASc score ≥2 who were admitted for atrial fibrillation and were enrolled at 115 sites between January 1, 2013, and September 31, 2017. Results: The median (25th, 75th percentile) age was 73 years (65, 81 years); 51% were female; and the median (25th, 75th percentile) CHA 2 DS 2 -VASc score was 4 (3, 5). At admission, 16 206 (59.5%) of 27 221 patients with a previous diagnosis of atrial fibrillation were taking OAC agents, and OAC drug use at admission was associated with a lower adjusted odds of in-hospital ischemic stroke (odds ratio, 0.38; 95% CI, 0.24–0.59; P <0.0001). At discharge, prescription of OAC in eligible patients (no contraindications) was 93.5% (n=25 499 of 27 270). In a sensitivity analysis, when excluding only strict contraindications (4.6%, n=1497 of 32 806), OAC prescription at discharge was 80.3%. OAC prescription at discharge was higher in those aged ≤75 years, men, those with heart failure, those with previous atrial fibrillation ablation, and those with rhythm control ( P <0.0001 for all). OAC use was lowest in Hispanic patients (90.2%, P <0.0001). Prescription of OAC at discharge in eligible patients improved over time from 79.9% to 96.6% ( P <0.0001). Conclusions: Among hospitals participating in the GWTG-AFIB quality improvement program, OAC prescription at discharge in eligible guideline-indicated patients increased significantly and improved consistently over time. These data confirm that high-level adherence to guideline-recommended stroke prevention is achievable.

442 Background: Neutrophil to lymphocyte ratio (NLR) has been used as an inflammation-based prognostic marker for various malignancies. The aim of our study was to determine whether NLR can independently predict the overall survival in patients with metastatic gallbladder cancer (GBC). Methods: We identified patients diagnosed with GBC who were treated at Mayo Clinic between the years 2000 and 2016. Patients who had nonmetastatic GBC were excluded along with the patients who did not have data for neutrophils and lymphocytes. Optimal cutoff point for NLR was identified by plotting martingale residuals against NLR and patients were divided into two groups, ≥ 5 or < 5. Demographic, follow-up data and outcomes were collected by retrospective review of electronic medical records. Fisher’s exact test was used to compare categorical variables, while The Mann- Whitney U test was used to compare continuous variables. Kaplan-Meier curves were plotted for NLR ≥ 5 and NLR < 5 and overall survival (OS) between the two groups were compared using log rank test. Multivariate survival analysis was performed using Cox-proportional hazard regression. Results: A total of 231 patients met our inclusion criteria, of which, 138 (60%) had NLR < 5 and 93 (40%) had NLR ≥ 5. Patients with NLR ≥ 5 were more likely to be older and have poor performance score, lower albumin level, higher alkaline phosphatase level, and higher platelet count. There were no significant differences noted in gender, race and administration of chemotherapy between the two groups. In univariate analysis, patients with NLR ≥ 5 at presentation had a significantly worse OS compared to those with NLR < 5 (Median survival: 3.6 vs. 8.8 months, p < 0.001). In multivariate analysis, adjusting for age, ECOG status, albumin, ALP, AST, ALT, bilirubin, platelet count and administration of chemotherapy, NLR of ≥ 5 was associated with a worse OS compared to NLR < 5 (HR: 1.70, 95% CI:1.20 – 2.39. p < 0.05). Conclusions: Our study demonstrates that NLR ≥ 5 is an independent predictor of poor prognosis in patients with metastatic gallbladder cancer.

433 Background: Current staging systems for gallbladder cancer (GBC) are inadequate, as they are based on surgical pathology, and therefore are not relevant for unresectable patients and patients undergoing neoadjuvant chemotherapy. Methods: Patients with a confirmed diagnosis of GBC who were seen at Mayo Clinic between the years 2000 and 2016 were included in this analysis. Data on demographic and tumor characteristics and outcomes were collected by retrospective review of electronic medical records. A model predictive of overall survival was developed using Cox proportional hazard regression analysis. Harrel’s C-statistic was calculated to evaluate the predictive accuracy of the model and compared with the TNM staging system. Results: A total of 523 patients were included in the final analysis, with a median age of diagnosis of 68 years. The median duration of follow up of the entire cohort was 12 months. In multivariate analysis, factors predictive of poorer overall survival were: ages 65-74 years (HR : 1.80, 95% CI: 1.33–2.43) and ages 75+ years (HR: 2.93, 95% CI: 2.12–4.06) compared to age <55 years; tumor size ≥ 5 cm by imaging (HR: 1.24, 95% CI: 1.01–1.55); nodal involvement by imaging (HR:1.61, 95% CI: 1.23–2.10); involvement of distant organs by imaging (HR: 2.85, 95% CI: 2.16–3.75); ECOG performance score of 2 or higher (HR: 1.78, 95% CI: 1.36–2.32) compared to ECOG 0-1; albumin level <3.5 g/dL (HR: 1.40, 95% CI: 1.08–1.81); and alkaline Phosphatase level ≥ 200 IU/L (HR: 1.49, 95% CI: 1.21–1.84). Using these seven predictive factors of survival we created a four-tier staging system. The median survivals of Stages I, II, III and IV created in our novel system were 64, 34, 20 and 7 months with corresponding hazard ratios of 1, 1.5, 2.5 and 8.5 respectively. The C-statistic for this novel staging system was 0.68 compared to C-statistic of 0.69 for the TNM staging system, indicating similar performance in predicting survival. Conclusions: We have created a novel clinically-based staging system for patients with GBC based on nonoperative information at the time of diagnosis which performs on par with the current surgical pathology based TNM staging system.

243 Background: The risk factors for gallbladder cancer (GBC) are poorly understood and preventive therapeutic options have not been identified. The use of aspirin (ASA) and/or statin has been associated with reduced risk of several gastrointestinal cancers. In this study, we explore if the use of ASA or statin is associated with a reduced risk of GBC. Methods: We identified patients with GBC diagnosed between the years 2000 and 2016 at Mayo Clinic. We identified matched controls in 2:1 fashion for age, gender and country of residence from patients who underwent cholecystectomy at Mayo Clinic. We collected information on co-morbidities and use of statins or ASA by retrospective chart review. We compared baseline characteristics between cases and controls using Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables. We used binomial logistic regression to calculate the odds ratio (OR) and 95% confidence intervals (CI) to estimate the association of ASA or statin use with GBC. The logistic regression model included history of cholelithiasis, diabetes, hypercholesterolemia (HCL), hypertension (HTN), hyperthyroidism, hypothyroidism, primary sclerosing cholangitis (PSC), inflammatory bowel disease (IBD), cirrhosis and statin or ASA use as covariates. Results: 633 cases and 1,266 controls were included in our final analysis. The median age at diagnosis of cases and controls was 67 years. The control group had a significantly (p < 0.05) higher proportion of patients with cholelithiasis, HCL, HTN, hypothyroidism and liver cirrhosis compared to the cases. The case group,contrarily, had a significantly higher proportion of patients with PSC and IBD. In univariate analysis, ASA (OR: 0.41; 95% CI: 0.33-0.52) or statin (OR: 0.48; 95% CI: 0.38-0.60) use was associated with a lower risk of GBC (p < 0.001). However, in multivariate analysis, ASA use was associated with a lower risk of GBC (OR: 0.52; 95% CI: 0.41-0.67, p < 0.001) whereas statin use was not (OR: 0.76; 95% CI: 0.56-1.03, p = 0.08). Conclusions: Our study demonstrates that aspirin use is associated with a reduced risk of GBC, whereas statin use is not. Further studies on GBC are needed to confirm these results and to elucidate mechanisms that explain the risk reduction with aspirin.