Explore the vast range of titles available.

Pancreatic cancer (PC) is a lethal malignancy that lacks specific diagnostic markers. The present study explores the diagnostic potential of the most differentially overexpressed secretory mucin MUC5AC alone and in combination with CA19-9 using multi-center training and validation sets. The expression of MUC5AC in benign pancreatic pathologies, PC precursor lesions, primary PC tissues and metastatic lesions was evaluated by immunohistochemistry. Circulating MUC5AC levels were measured using sandwich ELISA assay developed in-house, and CA19-9 was measured using radioimmunoassay. A combined training set (n=346) was used to evaluate the diagnostic (n=241) and predictive (n=105, total samples 201 from pre- and post-surgical and chemotherapy set) significance of MUC5AC. Results were further validated with a pre-defined cut-off value using independent sets from the Mayo Clinic (n=94) and the University of Pittsburgh Medical Center (n=321). Tissue expression analyses indicated the de novo expression of MUC5AC in pancreatic intraepithelial precursor lesions 1A (PanIN1A); the expression was maintained through all stages of progression to invasive adenocarcinoma. The median circulating MUC5AC levels in patients with resectable early-stage PC (EPC) (stage 1/2; 67.2 ng/ml, IQR: 23.9-382.1) and unresectable late-stage PC (LPC) (stage 3/4; 389.7 ng/ml, IQR: 87.7-948.6) were significantly higher compared with (P-value ≤0.0001) benign controls (BC) (7.2 ng/ml, IQR: 0.4-26.5) and (P-value ≤0.0001) chronic pancreatitis (CP) controls (8.4 ng/ml, IQR: 1.5-19.2). In the diagnostic training set (n=241), MUC5AC efficiently differentiated EPC from healthy controls (HC) (83%/80% sensitive (SN)/specific (SP)), BC (67%/87% SN/SP), and CP (83%/77% SN/SP). Independent validation sets from the Mayo Clinic and UPMC confirmed the diagnostic potential of MUC5AC to differentiate EPC from BC (68%/73%; 65%/83%) and CP (68%/79%; 65%/72%). Furthermore, MUC5AC and CA19-9 combination significantly improved (p-value < 0.001) the diagnostic accuracy for differentiating resectable cases from controls. MUC5AC is a valuable diagnostic biomarker, either alone or in combination with CA19-9, to differentiate PC from CP and benign controls.

Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cyst fluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND). From an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs. Of 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs (TBX15, BMP3) achieved sensitivity and specificity above 90%. Discrimination was significantly better by this CF-MDM panel than by mutant KRAS or carcinoembryonic antigen, with areas under the receiver operating characteristic curve of 0.93 (95% confidence interval: 0.86-0.99), 0.71 (0.57-0.85), and 0.72 (0.60-0.84), respectively. Cutoffs for the MDM panel applied to an independent CF validation set (31 cases, 56 controls) yielded similarly high discrimination, areas under the receiver operating characteristic curve = 0.86 (95% confidence interval: 0.77-0.94, P = 0.2). Novel MDMs discovered and validated in tissue accurately identify PCLs harboring HGD/PC. A panel of 2 MDMs assayed in CF yielded results with potential to enhance current risk prediction algorithms. Prospective studies are indicated to optimize and further evaluate CF-MDMs for clinical use.

INTRODUCTION:Patients with Celiac disease (CD) are at increased risk of infections, as evidenced by increased prevalence of tuberculosis, influenza, and sepsis. Alterations in immunity and microbiota can contribute to this predisposition. Although the prevalence of Clostridium difficile infection (CDI) continues to increase in the US, there is little data on the association and outcomes in patients with CD. The aim of this study was to assess inpatient prevalence, outcomes and resource utilization of patients with CD and CDI in the US in the past decade.METHODS:Retrospective cohort study using the NIS 2007 to 2016. All patients with CD were included using ICD9-10CM codes. Cohorts were stratified for CDI coexistence. None were excluded. The primary outcome was determining the association of CD with CDI. Secondary outcomes were determining the CDI inpatient prevalence trend in the CD patients, as well as mortality, morbidity, length of hospital stay (LOS), total hospital charges and costs, which were adjusted for inflation using the Consumer Price Index. Multivariate regression was used to adjust for age, gender, income in patient zip code, Charlson Comorbidity Index, hospital region, location, size and teaching status.RESULTS:A total of 337,201 patients with CD were identified, of which 5,500 had associated CDI. Mean age was 55 years and 71% were female. The inpatient prevalence of CDI in patients with CD increased from 0.9/100,000 admissions in 2007 to 1.65/100,000 admissions in 2016. Patients with CD displayed increased adjusted odds (aOR:1.56, P < 0.01) of coexisting CDI compared to patients without CD. Patients with CD had lower odds of mortality, ICU, shock, multiorgan failure, hospital costs, charges, and LOS but increased odds of requiring TPN compared to the general population admitted population with CDI.CONCLUSION:Patients with CD had higher odds of CDI compared to non-CD patients, which could be attributed to CD-related gut mucosal integrity, immunological or microbiome alterations. The inpatient prevalence of CDI in patients with CD increased from 2007 to 2016. This may be a reflection of the general increase of CDI cases in the inpatient population and with improved CD diagnostic modalities. Patients with CD and CDI did show decreased morbidity/mortality and resource utilization, suggesting that the clinical course is less severe. Further studies should further assess the gut immunological and microbiome changes in CD to clarify potential factors associated with CDI.Table 1.Adjusted means and odds ratio for the evaluated parameters comparing patients with CDI and CD compared to patients with CDI without CD. a=adjusted.

The etiology of eosinophilic esophagitis (EoE) is not well understood. It has been proposed that eosinophils migrate to the esophagus in response to various ingested and inhaled allergens. Recent reports in children found an increased proportion of cases of EoE during months with higher outdoor aeroallergens. To our knowledge, this has not been evaluated in adults. We aimed to determine whether there is a seasonal distribution in the number of newly diagnosed cases of EoE in an adult population. We conducted a retrospective review of consecutive adult cases newly diagnosed with EoE in 1 year. Cases were grouped based on the index month when the diagnosis was made at endoscopy. To test the consistency of the observations, a second cohort of consecutive cases of similar sample size diagnosed at a different period in time was also analyzed. In total, 41 patients were diagnosed with EoE at our center during the study period, providing an annual prevalence of 0.98%. More cases were diagnosed with EoE during the months of April and May than any other month (P<0.001). When patients were grouped seasonally, there was a significant increase of EoE cases in spring and summer months (n=28) when compared with the fall and winter months (n=13) (P=0.019). Analysis of the second cohort of cases (n=37) from 2002 to 2006 confirmed a similar seasonal diagnostic pattern for EoE during the outdoor seasons. Our data demonstrate that EoE has a seasonal prevalence in adults. The seasonal variation pattern found in newly diagnosed EoE cases in adults supports the potential role of aeroallergens in the pathogenesis of EoE.

We evaluated risk factors for residual neoplasia on first follow-up endoscopy after colonic endoscopic mucosal resections (EMRs). This retrospective study in a high-volume EMR tertiary-referral center examined EMRs on 423 colonic lesions in 313 patients. Residual neoplasia at first follow-up endoscopy was present following 12% of colonic EMRs. Single-variable analysis showed evidence of an increased risk of residual neoplasia for larger polyps, polyps without a lifting sign, and polyps removed piecemeal. In multivariable analysis, only use of the piecemeal method was independently associated with residual neoplasia. Additional procedures are needed to complete resection in more than 1 in 10 colonic EMRs. Residual neoplasia occurs more often with piecemeal resection. Close surveillance after EMR and the use of newer methods to further reduce residual neoplasia are needed.

IntroductionBariatric surgery (BSx) leads to weight loss and causes alterations in gastrointestinal and pancreatic peptides. This raises questions on acute pancreatitis (AP) occurrence and outcomes in this cohort of patients. We aim to assess mortality, morbidity, and resource utilization of AP in patients with BSx.MethodsObservational retrospective cohort study (2012–2016) with propensity score match. Patients with a principal diagnostic ICD9-10CM code for AP were included. Stratification for the coexistence of history of BSx was performed. The primary outcome was mortality. Secondary outcomes were morbidity, resource utilization, length of hospital stay (LOS), total hospital charges, and costs.ResultsOut of 920,615 AP patients, 15,345 had undergone BSx. After propensity matching, 8220 patients with BSx had AP. The mortality for AP was 0.42 (p < 0.01) and for biliary AP 0.29 (< 0.04) in the history of BSx group compared to patients without BSx history. Acute kidney insufficiency (AKI), shock, ICU, multiorgan failure, ERCP, costs, charges, and LOS were all lower for patients with AP who had history of BSx. Patients with biliary AP showed even lower odds of AKI, ICU, multiorgan failure, costs, charges, and LOS, but higher odds of cholecystectomy.ConclusionPatients with AP with history of BSx have lower mortality, morbidity, and resource utilization. This may be due to post-surgical alterations in pancreatic and gastrointestinal functions including hormonal and anatomical changes. Interestingly, patients with biliary AP and BSx had even lower odds of mortality and morbidity than patients with non-biliary AP, suggesting an added benefit with milder disease course.