Objectives The epidemiological trends contributing to increasing acute pancreatitis (AP) hospitalizations remain unknown. We sought to analyze etiological factors and outcomes of increasing AP-hospitalizations. Methods Utilizing the Nationwide Inpatient Sample, retrospective analyses of adult (≥18 years) inpatient admissions with a primary diagnosis of AP (total N: 2,016,045) were performed. Patient hospitalizations from 2009–2012 were compared to those from 2002–2005. Results Compared to 2002–2005, there was a 13.2% (p<0.001) increase in AP-admissions in 2009–2012. Multivariate analysis adjusted for “time-period”, patient and hospital demographics, AP-etiologies, and disease associations, demonstrated an increase in the odds of associated-chronic pancreatitis (CP) (2002–2005: odds ratio [OR] 32.04, 95% confidence interval [CI] 30.51–33.64; 2009–2012: OR 35.02, 95% CI 33.94–36.14); while associated odds of gallstones (2002–2005: OR 36.37, 95% CI 35.32–37.46; 2009–2012: OR 29.85, 95% CI 29.09–30.64) decreased. Compared to 2002–2005, the AP-related mortality decreased in 2009–2012 (1.62% to 0.79%, p<0.001) and was lower in AP with associated-CP (0.65% to 0.26%; p<0.001) compared to AP without-CP. Conclusion In the preceding decade, AP-hospitalizations are increasing but associated mortality is declining. Associated-CP has emerged as a leading contributor for AP-related hospitalizations. Further research is needed to identify novel interventions to prevent disease progression of AP.

Morbid obesity negatively influences inpatient hospitalization and is associated with adverse clinical outcomes, including mortality, organ failure, and health-care resource utilization. These observations and the increasing global prevalence of obesity justify ongoing efforts to understand the role of obesity-induced inflammation in the pathogenesis and management of AP.

BackgroundA significant challenge to overcome in pancreatic ductal adenocarcinoma (PDAC) is the profound systemic immunosuppression that renders this disease non-responsive to immunotherapy. Our supporting data provide evidence that CD200, a regulator of myeloid cell activity, is expressed in the PDAC microenvironment. Additionally, myeloid-derived suppressor cells (MDSC) isolated from patients with PDAC express elevated levels of the CD200 receptor (CD200R). Thus, we hypothesize that CD200 expression in the PDAC microenvironment limits responses to immunotherapy by promoting expansion and activity of MDSC.MethodsImmunofluorescent staining was used to determine expression of CD200 in murine and human PDAC tissue. Flow cytometry was utilized to test for CD200R expression by immune populations in patient blood samples. In vivo antibody blocking of CD200 was conducted in subcutaneous MT-5 tumor-bearing mice and in a genetically engineered PDAC model (KPC-Brca2 mice). Peripheral blood mononuclear cells (PBMC) from patients with PDAC were analyzed by single-cell RNA sequencing. MDSC expansion assays were completed using healthy donor PBMC stimulated with IL-6/GM-CSF in the presence of recombinant CD200 protein.ResultsWe found expression of CD200 by human pancreatic cell lines (BxPC3, MiaPaca2, and PANC-1) as well as on primary epithelial pancreatic tumor cells and smooth muscle actin+ stromal cells. CD200R expression was found to be elevated on CD11b+CD33+HLA-DRlo/− MDSC immune populations from patients with PDAC (p=0.0106). Higher expression levels of CD200R were observed in CD15+ MDSC compared with CD14+ MDSC (p<0.001). In vivo studies demonstrated that CD200 antibody blockade limited tumor progression in MT-5 subcutaneous tumor-bearing and in KPC-Brca2 mice (p<0.05). The percentage of intratumoral MDSC was significantly reduced in anti-CD200 treated mice compared with controls. Additionally, in vivo blockade of CD200 can also significantly enhance the efficacy of PD-1 checkpoint antibodies compared with single antibody therapies (p<0.05). Single-cell RNA sequencing of PBMC from patients revealed that CD200R+ MDSC expressed genes involved in cytokine signaling and MDSC expansion. Further, in vitro cytokine-driven expansion and the suppressive activity of human MDSC was enhanced when cocultured with recombinant CD200 protein.ConclusionsThese results indicate that CD200 expression in the PDAC microenvironment may regulate MDSC expansion and that targeting CD200 may enhance activity of checkpoint immunotherapy.

Objectives Pancreatic ductal adenocarcinoma (PDAC) is often accompanied by weight loss. We sought to characterize factors associated with weight loss and observed nutritional interventions, as well as define the effect of weight loss on survival. Methods Consecutive subjects diagnosed with PDAC (n = 123) were retrospectively evaluated. Univariate analysis was used to compare subjects with and without substantial (>5%) weight loss. Multivariate logistic regression was performed to identify factors associated with weight loss, and survival analyses were performed Kaplan-Meier curves and Cox survival models. Results Substantial weight loss at diagnosis was present in 71.5% of subjects, and was independently associated with higher baseline body mass index, longer symptom duration, and increased tumor size. Recommendations for nutrition consultation and pancreatic enzyme replacement therapy occurred in 27.6% and 36.9% of subjects, respectively. Weight loss (>5%) was not associated with worse survival on multivariate analysis (hazard ratio (HR) 1.32, 95% CI, 0.76–2.30), unless a higher threshold (>10%) was used (HR 1.77, 95% CI, 1.09–2.87). Conclusions Despite the high prevalence of weight loss at PDAC diagnosis, there are low observed rates of nutritional interventions. Weight loss based on current criteria for cancer cachexia is not associated with poor survival in PDAC.

Guidelines recommend genetic testing of patients with 10 or more cumulative adenomatous polyps. However, little is known about the utility of these tests-especially for older patients. We aimed to determine the prevalence of pathogenic mutations in patients with multiple colorectal polyps, stratified by age. METHODS: We performed a cross-sectional study of patients with 10 or more colorectal polyps who underwent multigene panel testing (MGPT) from March 2012 through December 2016 (n [ 3789). Demographic, clinical and family history data were obtained from test requisition forms and accompanying clinic notes, pedigrees, and pathology reports. Subjects were stratified based on reported polyp histology. Primary outcomes of interest were gene mutations associated with adenomatous polyposis, hamartomatous polyposis, and non-polyposis colorectal cancer syndromes. RESULTS: Based on MGPT, the prevalence of mutations in adenomatous polyposis genes decreased with increasing age in all polyp count groups in the adenoma cohort (P < .001 for 10-19, 20-99, and 100 or more polyps). The prevalence of mutations in all genes of interest also decreased with increasing age but remained above 5% in all age and polyp cohorts. Increased age at testing was associated with a significantly lower risk of a mutation in any gene of interest with multivariate analysis. In the hamartoma cohort, the prevalence of mutations in hamartomatous polyposis genes was high regardless of polyp count (40% with 10-19 polyps, 72.1% with 20-99 polyps, and 50% with 100 or more polyps). CONCLUSION: Our findings support continued genetic testing of patients with 10 or more polyps including adenomas and/or hamartomas. MGPT that includes analysis of polyposis and non-polyposis colorectal cancer genes should be considered for these patients given the high proportion with mutations (above 5%) in all age groups.

Analysis of national level data demonstrates that morbidly obese patients have an increased CRC surgery peri-operative mortality with higher prevalence of co-morbidities, surgical complications, and more health care resource utilization. Future research efforts should concentrate on ameliorating these outcomes in morbidly obese patients.

Same-admission CCY should be considered in patients with biliary AP when feasible. This national appraisal recognizes modifiable risk factors to reduce readmission in biliary AP and reinforces adherence to major society guidelines.

Objectives To evaluate national health care use and costs for pediatric acute pancreatitis. Study design The Kids’ Inpatient Database for 2006, 2009, and 2012 was queried for patients with a principal diagnosis of acute pancreatitis. Cases were grouped by age: preschool (<5 years of age), school age (5–14 years of age), and adolescents (>14 years of age). Results A total of 27 983 discharges for acute pancreatitis were found. The number of admissions increased with age: young n = 1279, middle n = 8012, and older n = 18 692. Duration of stay was highest in preschool children (median, 3.47 days; IQR, 2.01–7.35), compared with school age (median, 3.22 days; IQR, 1.81–5.63) and adolescents (median, 2.87 days; IQR, 1.61–4.81; P < .001). The median cost of hospitalization varied with age: $6726 for preschoolers, $5400 for school-aged children, and $5889 for adolescents (P < .001). Acute pancreatitis–associated diagnoses varied by age. The presence of gallstone pancreatitis, alcohol, and hypertriglyceridemia was more common among older children compared with younger children (P < .001). There was an increasing trend in acute pancreatitis, chronic pancreatitis, and obesity for the 2 older age groups (P < .001). Conclusion Admission of children for acute pancreatitis constitutes a significant healthcare burden, with a rising number of admissions with age. However, the cost and duration of stay per admission are highest in young children.