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Endpoint only comparisons 3. Endpoint only comparisons (with all polyps, all 20 samples) a. Drug normal to polyp b. Placebo normal to polyp 4. Endpoint only excluding polyps < 50% tumor purity a. Drug normal to polyp b. Placebo normal to polyp

Heat map of RNA expression showing all polyps including those with < 50% tumor purity.

Power calculations for experimental design of RNASeq analysis.

Context Synthetic lifting media, OriseTM gel and Eleview®, are increasingly utilized in gastrointestinal endoscopy, but neither comparative features nor pitfalls are well-established. Objective Media histopathology, morphologic mimics, and complications are described, along with helpful stains and endoscopist media preference. Design A 3-year retrospective search was performed. Pan-mucin, amyloid, and infectious disease stains were performed. Endoscopist lifting media preferences were surveyed. Results 123 cases (108 endoscopies, 15 subsequent surgeries) were identified. Orise gel was used in 86 (79.6%), Eleview in 20 (13.9%), and others in 7 (6.5%). Orise gel was histologically identified in 58.1% (n=50) of endoscopic specimens and all 15 resections. Eleview media was not detected histologically. Orise gel mimicked mucin in H&E-stained biopsies, concerning for adenocarcinoma misdiagnosis and/or upstaging, but did not stain for mucin. Acid fast bacterial staining highlights Orise gel for specific and definitive identification. In resections, Orise evolves into an amorphous eosinophilic material, often with exuberant giant-cell reaction and transmural bowel penetration. Polyp formation lead to polypectomy in one patient, and operative lesions concerning for adenocarcinoma resulted in frozen sections in two patients. Orise gel mimics mucin, malignant masses, amyloid, pulse granulomata, elastofibromas, and infectious granulomata. No significant endoscopist media preference was identified. Conclusions Recognition of Orise gel in tissues eliminates multiple pitfalls. Eleview was not detectable, yielded none of the pitfalls seen with Orise gel, and on our survey, has equivalent endoscopist acceptance. In this largest published series to date, Eleview is clearly preferable to Orise gel.

IntroductionAccelerated dose infliximab (IFX) induction is associated with reduced short-term colectomy rate in acute severe ulcerative colitis (ASUC). Data on medium/long-term outcomes of this strategy are limited.AimsEvaluate medium/long-term outcomes in patients receiving IFX induction for ASUC, comparing accelerated dose (AD) and standard dose (SD) induction.MethodsRetrospective study of consecutive patients admitted with corticosteroid-refractory ASUC in four tertiary referral centres within INITIative IBD research network (www.initiativeibd.ie). IFX rescue was given either as SD (weeks 0, 2, 6) or AD (Results145 patients received rescue IFX (AD=58, SD1=32, SD2=55). Disease severity at induction was comparable between AD and SD1 groups; however, SD2 group had less severe disease: median C-reactive protein (CRP) 39, 44 and 20 mg/L for AD, SD1 and SD2 groups, respectively (p=0.026, Kruskal-Wallis); median CRP: albumin ratio was 1.4, 1.8 and 0.6 (p=0.016). Median follow-up for AD, SD1 and SD2 groups was 1.6 (IQR 1.1–3.1), 4.9 (IQR 2.6–5.5) and 1.5 (IQR 0.9–2.3) years. Time to colectomy was shorter in SD1 (log rank p=0.0013); no significant difference in time to colectomy was observed comparing AD and SD2 groups (log rank p=0.32). 123 patients (84%) completed IFX induction and received maintenance therapy. Time to IFX discontinuation was shorter in SD1 (log rank p=0.009).ConclusionTime to colectomy is significantly prolonged with use of AD IFX in selected ASUC patients with more severe disease. Historical use of standard IFX induction for all ASUC patients is associated with inferior long-term outcomes.

Background Consensus guidelines from the European Crohns and Colitis Organisation conclude that optimizing quality of care in inflammatory bowel disease [IBD] involves information and education. However, there is no standardized patient education programme in IBD and education varies from centre to centre. Aim To assess patients' education needs in IBD to facilitate design of a patient education programme. Methods We created focus groups of 12 patients with IBD and used qualitative analysis to generate hypotheses. We then developed a quantitative questionnaire which was disseminated to 327 IBD patients attending three different centres. Five patients declined to participate and thus 322 patients (159 [49%] male, 180 [58%] Crohn's disease, median age 38 years and disease duration 7 years) were included. Results Patients were most keen to receive education on medications, 'what to expect in future', living with IBD and diet. They wanted to receive this information from specialist doctors or nurses and believed it could improve their quality of life. Though the internet was the preferred source of general information [i.e. planning holidays], it was the least preferred source of IBD education. While there was a trend for females to prefer peer education, family history of IBD was the only statistically significant factor associated with information preferences. Conclusion This is a patient-centred, mixed methodology study on patient education in IBD. Patients' preferences for education include components such as what to expect and diet and patients seem to distrust the internet as an IBD information source. International validation would be valuable to create a consensus education programme.

Background and Aims The American Society for Gastrointestinal Endoscopy (ASGE) advanced endoscopy fellowship (AEF) match offers a structured application process for AEF training in the United States. Our aim was to describe recent trends in AEF match, trainee experience, and postfellowship employment. Methods ASGE AEF match data from 2012 to 2020 were reviewed. Online surveys were sent to advanced endoscopy trainees in 2019 and 2020 to explore their perceptions about AEF training and postfellowship jobs. Results Data for 2020 showed 19% of matched applicants were women, 55% foreign medical graduates, and 17.5% U.S. visa holders. The number of AEF match applicants increased by 15.6% (90 in 2012 to 104 in 2020) and number of AEF programs increased by 23.5% (51 in 2012 to 63 in 2020). The average applicant match rate was 57% (range, 52.8%-60.6%) and position match rate 87.9% (range, 79.1%-94.6%). Ninety-one percent of trainees (n = 58) rated the quality of their training as very good/excellent; 75% of trainees participated in >300 ERCPs and 64.1% in >300 EUS cases. Seventy percent of trainees reported that advanced endoscopic procedures comprised ≤50% of their procedure volume in their first job, and 71.9% believed it was not easy to find a job after fellowship; however, 97% believed they would make the same decision to pursue AEF training again. Conclusions There has been a steady increase in the number of advanced endoscopy applicants and training positions over recent years. Most graduating fellows reported 50% or less of their upcoming clinical practice would involve advanced endoscopic procedures. Future studies are needed to further clarify employment opportunities and personnel needs for advanced endoscopists.

Biliary tract cancers (BTC) including, cholangiocarcinoma (CC) and gallbladder cancer (GBC), are rare and highly fatal malignancies. The etiology and inherited susceptibility of both malignancies are poorly understood. We quantified the risk of BTC in first-degree (FDR), second-degree (SDR), and first cousin (FC) relatives of individuals with BTC, stratified by tumor subsite. BTC diagnosed between 1980 and 2011 were identified from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. Age- and gender-matched BTC-free controls were selected to form the comparison group for determining BTC risk in relatives using Cox regression analysis. Of the 1302 index patients diagnosed with BTC, 550 (42.2 %) were located in the gallbladder and 752 (57.8 %) were cholangiocarcinomas. There was no elevated risk of BTC (all subsites combined) in FDRs (HR 0.94, 95 % CI 0.29–3.0), SDRs (HR 0.25, 95 % CI 0.06–1.03), and FCs (HR 0.96, 95 % CI 0.61–1.51) of BTC cases compared to cancer-free controls. Similarly, no increased familial risk of GBC or CC was found in relatives of BTC patients stratified by tumor subsite compared to relatives of controls. Relatives of BTC patients are not at an increased risk of GBC or CC in a statewide population. This suggests that biliary tract cancer risk is not associated with a familial predisposition and may be mitigated more strongly by environmental modifiers.

Background Patients with familial adenomatous polyposis (FAP) frequently undergo colectomy to reduce the 70 to 90% lifetime risk of colorectal cancer. After risk-reducing colectomy, duodenal cancer and complications from duodenal surgeries are the main cause of morbidity. Our objective was to prospectively describe the duodenal and gastric polyp phenotype in a cohort of 150 FAP patients undergoing pre-screening for a chemoprevention trial and analyze variables that may affect recommendations for surveillance. Methods Individuals with a diagnosis of FAP underwent prospective esophagogastroduodenoscopy using a uniform system of mapping of size and number of duodenal polyps for a 10 cm segment. Gastric polyps were recorded as the total number. Results The distribution of the count and sum diameter of duodenal polyps were statistically different in two genotype groups, those with APC mutations associated with classic FAP had a greater count (median 17) and sum diameter of polyps (median 32 mm) than those with APC mutations associated with attenuated FAP (median count 4 and median sum diameter of 7 mm) (p

Background and Aims: Inflammatory bowel diseases (IBDs) are heterogeneous disorders with complex aetiology. Quantitative genetic studies suggest that only a small proportion of the disease variance observed in IBD is accounted for by genetic variation, indicating a potential role for differential epigenetic regulation in disease aetiology. The aim of this study was to assess genome-wide DNA methylation changes specifically associated with ulcerative colitis (UC), Crohn’s disease (CD) and IBD activity. Methods: DNA methylation was quantified in peripheral blood mononuclear cells (PBMCs) from 149 IBD cases (61 UC, 88 CD) and 39 controls using the Infinium HumanMethylation450 BeadChip. Technical and functional validation was performed using pyrosequencing and the real-time polymerase chain reaction. Cross-tissue replication of the top differentially methylated positions (DMPs) was tested in colonic mucosa tissue samples obtained from paediatric IBD cases and controls. Results: A total of 3196 probes were differentially methylated between CD cases and controls, while 1481 probes were differentially methylated between UC cases and controls. There was considerable (45%) overlap between UC and CD DMPs. The top-ranked IBD-associated PBMC differentially methylated region (promoter region of TRIM39-RPP2 ) was also significantly hypomethylated in colonic mucosa from paediatric UC patients. In addition, we confirmed TRAF6 hypermethylation using pyrosequencing and found reduced TRAF6 gene expression in PBMCs of IBD patients. Conclusions: Our data provide new insights into differential epigenetic regulation of genes and molecular pathways, which may contribute to the pathogenesis and activity of IBD.

AIMS To determine whether specific magnetic resonance enterography (MRE) findings can predict outcome following commencement of antitumor necrosis factor (aTNF) in small bowel Crohn's disease (CD) PATIENTS AND METHODS: This was a single-centre retrospective study of patients with CD who commenced aTNF (infliximab or adalimumab) between 2007 and 2013. Patients who had an MRE within 6 months before commencing aTNF were included. The primary end-point was the need for CD-related surgery. The secondary end-points were time to surgery and time to treatment failure. The relationship between these end-points, clinical variables and specific MRE findings were studied. RESULTS Four hundred and eighteen patients commenced aTNF for CD during the study period. Seventy-five patients had an MRE within 6 months before commencing aTNF (30 infliximab; 45 adalimumab). The median time from MRE to commencing aTNF was 43 days (IQR 19.5-87 days). Eighteen of 75 (24%) had surgery during a median follow-up of 16.7 months (IQR 9.0-30.1 months). Patients with small bowel stenosis (SBS) on MRE were at a significantly higher risk of requiring surgery: 12/18 (66.7%) versus 6/57 (10.5%) (P

To identify gene expression biomarkers and pathways targeted by sulindac and erlotinib given in a chemoprevention trial with a significant decrease in duodenal polyp burden at 6 months (P < 0.001) in familial adenomatous polyposis (FAP) patients, we biopsied normal and polyp duodenal tissues from patients on drug versus placebo and analyzed the RNA expression. RNA sequencing was performed on biopsies from the duodenum of FAP patients obtained at baseline and 6-month endpoint endoscopy. Ten FAP patients on placebo and 10 on sulindac and erlotinib were selected for analysis. Purity of biopsied polyp tissue was calculated from RNA expression data. RNAs differentially expressed between endpoint polyp and paired baseline normal were determined for each group and mapped to biological pathways. Key genes in candidate pathways were further validated by quantitative RT-PCR. RNA expression analyses of endpoint polyp compared with paired baseline normal for patients on placebo and drug show that pathways activated in polyp growth and proliferation are blocked by this drug combination. Directly comparing polyp gene expression between patients on drug and placebo also identified innate immune response genes (IL12 and IFNγ) preferentially expressed in patients on drug. Gene expression analyses from tissue obtained at endpoint of the trial demonstrated inhibition of the cancer pathways COX2/PGE2, EGFR, and WNT. These findings provide molecular evidence that the drug combination of sulindac and erlotinib reached the intended tissue and was on target for the predicted pathways. Furthermore, activation of innate immune pathways from patients on drug may have contributed to polyp regression. Cancer Prev Res; 11(1); 4–15. ©2017 AACR. See related editorial by Shureiqi, p. 1

There has been an increase in the incidence of esophageal adenocarcinoma in the USA since the 1970s. The goal of screening and surveillance endoscopy for Barrett’s esophagus was to identify and then subsequently treat the patients who are at the highest risk for the development of esophageal adenocarcinoma. In general, the American GI societies, including the American Gastroenterological Society (AGA), American College of Gastroenterology (ACG), and American Society for Gastrointestinal Endoscopy (ASGE), are in agreement with screening guidelines for Barrett’s esophagus. Screening should be considered for patients at higher risk for the development of esophageal cancer, and endoscopic screening has not been advocated for the general population. Non-dysplastic Barrett’s esophagus is most often followed with surveillance endoscopy and biopsies every 3–5 years. Since non-dysplastic Barrett’s esophagus has a low risk of progression to esophageal adenocarcinoma, endoscopic treatment is not generally recommended. Endoscopic treatment with ablative therapy, mechanical therapy, or combination of both is recommended for patients with Barrett’s esophagus with confirmed low-grade dysplasia, high-grade dysplasia, and intramucosal carcinoma. After complete eradication of both intestinal metaplasia and dysplasia, patients should continue to have endoscopic surveillance to monitor for recurrence of disease.

Objectives Elemental diets have not been studied in adults with eosinophilic esophagitis (EoE). The goal of this trial was to assess the efficacy of an elemental diet in adults with EoE. Methods A total of 18 adults with EoE were given an elemental diet for 4 weeks, or just 2 weeks if their response was complete. Symptoms and histologic findings, based on biweekly biopsies, were monitored. Six subjects were rebiopsied 2-7 days after resuming a normal diet. Results After therapy, esophageal tissue eosinophil content decreased from 54 to 10 per maximal high power field (P=0.0006). There was complete or nearly complete response (≤10 eosinophils) in 72% of subjects. Mast cell content, parabasal layer thickness, and endoscopic furrows and exudates also significantly decreased. Of the 29 qualified subjects, 11 (38%) failed to adhere to the diet. Several subjects had significant weight loss. Symptoms and endoscopic fixed strictures did not improve. After the subjects resumed a normal diet, the eosinophil content increased substantially in 3-7 days. Conclusions While symptoms did not improve and dietary compliance was problematic, there was substantial histologic improvement after 4 weeks on the elemental diet. EoE in adults is substantially triggered by foods.

Importance Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful. Objective To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP. Design, Setting, and Participants Double-blind, randomized, placebo-controlled trial, enrolling 92 participants with FAP, conducted from July 2010 through June 2014 at Huntsman Cancer Institute in Salt Lake City, Utah. Interventions Participants with FAP were randomized to sulindac (150 mg) twice daily and erlotinib (75 mg) daily (n = 46) vs placebo (n = 46) for 6 months. Main Outcomes and Measures The total number and diameter of polyps in the proximal duodenum were mapped at baseline and 6 months. The primary outcome was change in total polyp burden at 6 months. Polyp burden was calculated as the sum of the diameters of polyps. The secondary outcomes were change in total duodenal polyp count, change in duodenal polyp burden or count stratified by genotype and initial polyp burden, and percentage of change from baseline in duodenal polyp burden. Results Ninety-two participants (mean age, 41 years [range, 24-55]; women, 56 [61%]) were randomized when the trial was stopped prematurely by recommendation of the external data and safety monitoring board because the second preplanned interim analysis met the prespecified stopping rule for superiority. Over 6 months, the median duodenal polyp burden in the sulindac-erlotinib group decreased from 29.0 mm to 19.5 mm (median change, −8.5 mm), and in the placebo group increased from 23.0 mm to 31.0 mm (median change, 8.0 mm), for a net difference of −19.0 mm (95% CI, −32.0 to −10.9; P P P Conclusions and Relevance Among participants with FAP, the use of sulindac and erlotinib compared with placebo resulted in a lower duodenal polyp burden after 6 months. Adverse events may limit the use of these medications at the doses used in this study. Further research is necessary to evaluate these preliminary findings in a larger study population with longer follow-up to determine whether the observed effects will result in improved clinical outcomes. Trial Registration clinicaltrials.gov Identifier:NCT01187901

Cannulation and sphincterotomy are two of the most fundamental techniques required to perform ERCP successfully. Both of these techniques have evolved over the years and have been the subject of intense scrutiny. Modern cannulation and sphincterotomy techniques are designed to maximize efficiency and minimize harm to the patient. This chapter reviews basic and advanced techniques for cannulation and sphincterotomy.

The success of any Endoscopic retrograde cholangiopancreatography (ERCP) is dependent on achieving successful cannulation of the desired duct via the desired route. Proper cannulation technique is critical for achieving procedure success and minimizing complications. The goal of this review is to discuss endoscopic techniques devices to help achieve successful cannulation, to detail multiple methods to assist with difficult cannulation, and to describe special circumstances that may be encountered. The manuscript will place an emphasis on cannulation techniques, while focusing on minimizing overall complications and a reduction in the incidence and severity of post-ERCP pancreatitis.

Importance Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for colorectal polyps and cancer. A combination of sulindac and erlotinib led to a 71% reduction in duodenal polyp burden in a phase 2 trial. Objective To evaluate effect of sulindac and erlotinib on colorectal adenoma regression in patients with FAP. Design, Setting, and Participants Prespecified secondary analysis for colorectal adenoma regression was carried out using data from a double-blind, randomized, placebo-controlled trial, enrolling 92 patients with FAP, conducted from July 2010 to June 2014 in Salt Lake City, Utah. Interventions Patients were randomized to sulindac, 150 mg twice daily, and erlotinib, 75 mg daily (n = 46), vs placebo (n = 46) for 6 months. Main Outcomes and Measurements The total number of polyps in the intact colorectum, ileal pouch anal anastomosis, or ileo-rectum were recorded at baseline and 6 months. The primary outcomes were change in total colorectal polyp count and percentage change in colorectal polyps, following 6 months of treatment. Results Eighty-two randomized patients (mean [SD] age, 40 [13] years; 49 [60%] women) had colorectal polyp count data available for this secondary analysis: 22 with intact colon, 44 with ileal pouch anal anastomosis and 16 with ileo-rectal anastomosis; 41 patients received sulindac/erlotinib and 41 placebo. The total colorectal polyp count was significantly different between the placebo and sulindac-erlotinib group at 6 months in patients with net percentage change of 69.4% in those with an intact colorectum compared with placebo (95% CI, 28.8%-109.2%;P = .009). Conclusion and Relevance In this double-blind, placebo-controlled, randomized trial we showed that combination treatment with sulindac and erlotinib compared with placebo resulted in significantly lower colorectal polyp burden after 6 months of treatment. There was a reduction in polyp burden in both those with an entire colorectum and those with only a rectal pouch or rectum. Trial Registration clinicaltrials.gov Identifier:NCT01187901

The objective of this trial was to test the effect of a combination of COX and EGFR inhibition on duodenal adenoma progression in patients with familial adenomatous polyposis (FAP). FAP is caused by mutations in the APC gene and is characterized by the development of hundreds of colorectal adenomas and colorectal cancer. FAP patients are also at increased risk for duodenal neoplasia with a ∼10% lifetime risk of duodenal carcinoma. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful. Preclinical data has illustrated that a combination of cyclooxygenase (COX) and epidermal growth factor (EGFR) inhibition diminishes small intestinal adenoma development by 87% in mice with germline Apc mutations. Therefore, we conducted a double blind, randomized, placebo-controlled trial in which FAP patients received combination therapy with 150 mg sulindac twice per day and 75 mg erlotinib daily or placebo for 6 months (NCT01187901). The total number and diameter of polyps in a 10cm segment of the proximal duodenum were mapped at baseline and 6 months. The primary outcome was change in total polyp burden, calculated as the sum of the diameters of polyps. We also evaluated RNA expression in duodenal tissue and polyps at endpoint from 10 patients on drug and 10 patients on placebo by RNA sequencing. Seventy-three randomized patients were included in the intention to treat analysis. Over six months, the median change in total duodenal polyp burden was an increase of 8.0 mm from baseline burden in the placebo group (23.0 to 31.0 mm) and the median change in the sulindac-erlotinib group was a decrease of 8.5 mm (29.0 to 19.5 mm). The estimated net difference in change between the two groups was -19.0 mm (95% CI: -32.0, -10.9; P Part of this abstract was presented as part of a preliminary presentation. Citation Format: Deborah W. Neklason, Don A. Delker, Kenneth M. Boucher, Priyanka Kanth, Kathryn Byrne, Philip Bernard, Wade Samowitz, Michelle W. Done, Therese Berry, Lisa Pappas, Laurel Smith, Danielle Sample, Rian Davis, Matthew K. Topham, Randall W. Burt, Scott K. Kuwada, N Jewel Samadder. Regression of duodenal neoplasia in familial adenomatous polyposis patients using COX and EGFR inhibition: A randomized placebo-controlled trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-074.

The omentum is a sheet-like tissue attached to the greater curvature of the stomach and contains secondary lymphoid organs called milky spots. The omentum has been used for its healing potential for over 100 years by transposing the omental pedicle to injured organs (omental transposition), but the mechanism by which omentum helps the healing process of damaged tissues is not well understood. Omental transposition promotes expansion of pancreatic islets, hepatocytes, embryonic kidney, and neurons. Omental cells (OCs) can be activated by foreign bodies in vivo. Once activated, they become a rich source for growth factors and express pluripotent stem cell markers. Moreover, OCs become engrafted in injured tissues suggesting that they might function as stem cells. Omentum consists of a variety of phenotypically and functionally distinctive cells. To understand the mechanism of tissue repair support by the omentum in more detail, we analyzed the cell subsets derived from the omentum on immune and inflammatory responses. Our data demonstrate that the omentum contains at least two groups of cells that support tissue repair, immunomodulatory myeloid derived suppressor cells and omnipotent stem cells that are indistinguishable from mesenchymal stem cells. Based on these data, we propose that the omentum is a designated organ for tissue repair and healing in response to foreign invasion and tissue damage.

Background Tolerance to collagen structures has been shown to inhibit the progression of autoimmune scleroderma and rheumatoid arthritis. More recently, tolerance induction to collagen type V (colV) in experimental models of lung transplantation was shown to ameliorate the complex pathology known as "chronic rejection." The link between colV autoimmunity and progressive graft dysfunction and subsequent development of bronchiolitis obliterans syndrome (BOS) has been established in human lung transplant recipients. We hypothesized that intravenous injection of colV inhibits development of lung fibrosis in a bleomycin-induced lung injury mouse model. Methods Experimental animals were injected intravenously with saline or colV 10 days before intratracheal instillation of bleomycin. Pulmonary inflammation was monitored and quantified for the presence of cells in the bronchoalveolar lavage (BAL) fluid by flow cytometry and histology of lung tissue. Results ColV–pre-treated animals showed a significant reduction in lung inflammation compared with non-treated animals, according to histology and morphometry. The number of inflammatory cells in the BAL fluid was significantly reduced and associated with a lower proportion of γδ T cells and CD4 + T cells in the colV–pre-treated group. Matrix metalloproteinase-2 and -9 (MMP-2 and -9; also known as gelatinase A and gelatinase B, respectively) levels in the BAL fluid were significantly reduced in colV–pre-treated mice compared with the non-treated mice. In addition, intravenous injection of colV was associated with a significant reduction in the relative expression of interleukin (IL)-6, IL-17 and IL-22 in cells present in BAL fluid at 7 and 14 days after bleomycin instillation. Conclusions Pre-treatment by intravenous injection of colV inhibits bleomycin-induced pulmonary fibrosis by inhibiting IL-6 and IL-17 production. Fibrosis treatment in this context therefore should target induction of colV tolerance and Th17 development.

Introduction: Malignant masquerade describes the scenario in which an operation is performed for what is presumed to be a malignant condition but for which final histopathology is benign. The aim of this studywas to investigate the incidence and importance ofmasquerade in a contemporary pancreatoduodenectomy (PD) series. Methods: Under IRB approval, a retrospective review of a prospectively collected database of patients at a tertiary care institution who underwent PD from 2000 to 2014 was performed. Final histopathology was compared to the final pre-operative diagnosis. The investigatory pathways of these patients were then evaluated. Results: 894 patients underwent PD during the study period and 61 had a benign final histopathology when a malignant origin was presumed. 56 (92%) had a biopsy or cytology performed with 15 showing atypia and an additional 9 suggestive of carcinoma. 24 patients had pre-malignant pathologies (IPMN, Duodenal & ampullary adenomas), and 15 with head pancreatic masses had a final diagnosis of chronic pancreatitis. The remaining 22 patients had a variety of conditions with no malignant potential. 17 of the 22 were symptomatic, the commonest being jaundice [n=13]. Suspicious radiology was present in all cases with a mass [n=16] and/or stricture [n=13], and 8 had concerning cytology. All patients with incidental lesions had endoscopic evaluation with cytological assessment. There was a single post-operative mortality. Conclusion: Despite modern imaging and endoscopic ultrasound, some patients still undergo resection for benign conditions without malignant potential. However for these patients PD is an acceptable approach when concern for malignancy remains despite thorough evaluation.

BACKGROUND & AIMS: Interferon gamma (IFNγ) responses and distinct CD8+ T cell transcriptional signatures can be linked to clinical manifestations of inflammatory bowl disease (IBD). CD39 is an ectonucleotidase and is typically associated with CD4+ T regulatory memory cells, which have the capacity to generate immunosuppressive adenosine. However, immunomodulatory effects of CD39 expression on CD8+ T cells, as in IBD, remain unknown. METHODS:CD39+CD8+ T cells were purified from peripheral blood (PB) and lamina propria (LP) of patients with Crohn's disease. Phenotypic features and functions of CD39+CD8+ T cells were assessed by flow cytometry and immunoblotting. RESULTS: CD39 expressing CD8+ T cells of patients with Crohn's disease are IFNγ-producing cells, and exhibited type 1 CD8+ T cell (Tc1) properties. CD3 and CD28-mediated synergistic stimulation of CD8+ T cells augment CD39 expression, boost reactive oxygen species (ROS) generation, and increase IFNγ production. CD39+CD8+ T cells preferentially express CD28, and exhibit robust ROS-JNK/NFkB signals and IFNγ production. Decreases in ROSmediated by inhibitors of NADPH oxidases (NOX) or knockdown of gp91phox (NOX2) in CD8+ T cells abrogate effects of TCR ligation, and decrease both CD39 expression and IFNγ production. Curiously, CD39+CD8+ T cells inhibit IFNγ production by CD39-CD8+ T cells via generation of adenosine, which is operational via the paracrine expression of Adenosine 2A (ADORA2A) receptor. CONCLUSIONS: CD8+ Tc1 cells express CD39, which is further boosted by cell activation and ROS, which in turn limit IFNg responses by these cells. Strategies to regulate ROS signal cascades and adenosine-mediated effects might have therapeutic potential in the treatment of Crohn's disease.

Critical to realizing increasing benefits of enteral nutrition are techniques for feeding tube placement. Feeding tubes can be placed by bedside, endoscopic, fluoroscopic, and surgical methods. This review encompasses noteworthy studies on endoscopic approaches to enteral feeding published from January 2005 to the present.Studies involving placement of nasoenteric feeding tubes include description of new methods for endoscopic nasoenteric feeding tube placement using a push technique with a stiffened tube, a modification of the 'drag and pull' method using a distal suture tie, and placement using an ultrathin transnasal endoscopic technique compared with fluoroscopic placement. Recent studies involving percutaneous endoscopic gastrostomy tube placement have demonstrated equivalent outcomes of endoscopic and fluoroscopic approaches, description of unsedated placement using transnasal technique, and risk of percutaneous endoscopic gastrostomy site metastasis in head and neck cancer patients. Studies on percutaneous jejunal feeding tubes demonstrate: high complication rate and short functional duration of percutaneous endoscopic gastrojejunostomy and reported outcomes of direct percutaneous endoscopic jejunostomy placement.Enteral nutrition access can be obtained by a variety of methods depending on local expertise and resources. Endoscopic approaches have equivalent or better outcomes than other methods; however, these methods may still have limitations and distinct complications.

Eosinophilic Esophagitis (EE) is an emerging cause of esophageal food impaction (EFI) not accounted for in previous studies. We sought to determine the causes of EFI in a recent cohort with recognition of EE. A retrospective chart review of all patients with EFI during the past 5 years was performed. Etiology was determined by endoscopy report, pathology results, and follow-up studies. A total of 85 EFIs occurred, in 79 patients (55 men, 30 women, age 18-100). The most common etiologies of EFI were Schatzki's ring (n = 18), peptic stricture (n = 18), EE (n = 9), esophagitis (n = 9), and no underlying diagnosis (n = 20). EE was significantly more frequent in men (P.025) and those50 years old (P.025). There was a significant difference in the age at which men (median age = 44) and women (median age = 71) present with EFI (P.001). The etiology of EFI differs significantly by age and gender. This information may be useful in evaluation and management of EFI.