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Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens (1,2). A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte antigen (HLA) HLA-DQ2 or HLA-DQ8 molecules develop inflammatory T-cell and antibody responses against dietary gluten, a protein present in wheat (3). The mechanisms underlying this dysregulated mucosal immune response to a soluble antigen have not been identified. Retinoic acid, a metabolite of vitamin A, has been shown to have a critical role in the induction of intestinal regulatory responses (4-6). Here we find in mice that in conjunction with IL-15, a cytokine greatly upregulated in the gut of coeliac disease patients (3,7), retinoic acid rapidly activates dendritic cells to induce JNK (also known as MAPK8) phosphorylation and release the proinflammatory cytokines IL-12p70 and IL-23. As a result, in a stressed intestinal environment, retinoic acid acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen. Altogether, these findings reveal an unexpected role for retinoic acid and IL-15 in the abrogation of tolerance to dietary antigens., Induction of regulatory intestinal responses to oral antigens prevents the subsequent development of systemic T-helper type-1 ([T.sub.H]1) responses to those antigens, a phenomenon referred to as oral tolerance (2). An [...]

BACKGROUND: Performance parameters for double-balloon enteroscopy (DBE) have not been described. OBJECTIVE: To determine the learning curve for DBE. DESIGN: Prospective cohort study. SETTING: Six U.S. tertiary centers. PATIENTS: A total of 188 subjects undergoing 237 DBE procedures; 130 (69%) with obscure GI bleeding. INTERVENTIONS: Performance parameters from each center's initial 10 cases were compared to the subsequent examinations. MAIN OUTCOME MEASUREMENTS: Exam duration, depth of insertion, and findings on DBE examination. RESULTS: DBE was introduced by mouth in 149 (63%) cases, by rectum in 77 (33%) cases, and through a stoma in 6 (2.5%) patients. The mean (+/-SD) duration was 109.1 +/- 44.6 minutes for the first 10 cases and 92.4 +/- 37.6 minutes for subsequent cases (P = .005) but did not change for rectal DBE procedures. There was no change in mean depth of insertion, but the mean fluoroscopy time declined significantly (P = .025). Diagnostic or therapeutic maneuvers were performed in 64% of cases; DBE led to a diagnosis in 81 (43%) patients. A total of 78% of patients had prior capsule endoscopy (CE) with significant agreement between DBE and CE (kappa = 0.74). One perforation occurred (0.4%). Per-rectal cases failed to reach the small bowel in 24 (31%) cases. LIMITATIONS: All patients did not undergo initial CE. The therapeutic DBE scope was not available for the initial 8 months of the study. CONCLUSIONS: There was a significant decline in overall procedural time and fluoroscopy time after the initial 10 DBE cases. There was no improvement in performance parameters when DBE was performed via the rectal approach despite increased, but limited, operator experience. [ABSTRACT FROM AUTHOR]

Background: Intestinal failure-associated liver disease (IFALD) is a complication of long-term PN use, attributed to the use of ω-6 injectable lipid emulsions (ILE). Fish oil (FO) ILE have been successful in reversing liver injury in neonates. Evidence for pure FO ILE use in adult patients is limited., Methods: Case series of the use of FO lipid emulsions in adults with IFALD from the University of Chicago PN registry. Analysis of medical charts and PN formulations was performed., Results: Three cases of IFALD treated with FO ILE were identified. The first case was a 30-year-old man with short bowel syndrome (SBS), hyperbilirubinemia, and biopsy-proven IFALD. Following a change from a soy lipid emulsion to FO lipid emulsion, his liver tests rapidly improved and remained stable over 202 weeks of use. The second case was a 76-year-old woman with intestinal failure (IF) due to a frozen bowel. A change from a soy ILE to a composite lipid and later to a pure FO ILE did not result in improvement in her liver tests. The third case was a 28-year-old man with SBS and biopsy-proven IFALD. Change to a composite ILE and subsequently FO lipid emulsion resulted in a gradual improvement in liver tests. No clinical essential fatty acid (EFA) deficiencies were identified during treatment., Conclusion: FO ILE may be effective in the treatment of adult patients with cholestatic IFALD. Use is safe with no EFA deficiencies detected in up to 4 years of use., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Malignant bowel obstruction (MBO) affects 3% to 15% of all cancer patients. In patients with advanced cancer and inoperable MBO, the average survival varies between four to nine weeks. Parenteral nutrition (PN) may improve survival in specific patient populations with malignant bowel obstruction., Aims: This retrospective, single-center cohort study aimed to review individual patient outcomes on PN in the setting of advanced cancer with a diagnosis of MBO and identify clinical and laboratory markers predictive of short- and long-term survival to further highlight patients that would benefit from PN in the setting of an inoperable MBO., Results: In a retrospective analysis of 68 patients receiving PN for inoperable MBO, the median survival was 142 (IQR: 63.3-239.5) days. Patients experienced a median number of two hospital readmissions (range: 0-10) and spent a median of 29 days (range: 0-105) in the hospital after starting PN. Eighteen (26.5%) patients developed a catheter-related bloodstream infection (CRBSI). A diagnosis of appendiceal cancer was identified as a predictive marker of improved survival (HR: 0.53, 95% CI: 0.29-0.92, p = 0.023)., Conclusions: The use of PN in the context of end-of-life cancer care is a practice that necessitates improvement. Recognizing the outcomes and patient experiences of PN utilization is essential to physicians and patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Bleeding from the gastrointestinal tract can contribute to the development of iron deficiency anemia (IDA) among individuals without another obvious source of bleeding. In order to identify patients most likely to benefit from examination of the small bowel, our aim was to create a risk score for positive video capsule endoscopy (VCE) in IDA utilizing a multicenter collection of studies., Methods: We performed a retrospective multicenter study utilizing VCE studies performed for an indication of IDA between 1/1/2005 and 7/31/2018. VCE findings were graded based on the P0-P2 grading system. The primary outcome of interest was a positive (P2) VCE. Data were analyzed with Student's t test for continuous variables and the Fisher's exact test for categorical variables. Logistic regression was used to identify independent associations with positive VCE., Results: In total, 765 VCE procedures were included with 355 (46.5%) male subjects and a median age of 63.2 (SD 15.3) years. One hundred ninety studies (24.8%) were positive (P2) for small bowel bleeding. Four variables associated with positive VCE which were incorporated into a point scoring system: (+) 1 for age ≥ 66 years, active smoking and cardiac arrythmia and (-) 1 for preceding hemoglobin level ≥ 8.5. The risk probabilities for positive VCE-assigned scores - 1, 0, 1, and 2 + were 12.3% (95% CI 7.3-17.3%), 20% (14.9-25.1%), 34.8% (28.6-41%), and 39% (30-47.8%)., Conclusion: In order to improve the diagnostic yield of capsule examinations, risk factors should be applied to clinical decision-making. We created a risk score for positive VCE in IDA, including the risk factors of age, smoking, history of cardiac arrythmia, and preceding hemoglobin level., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This guideline presents an update to the 2013 American College of Gastroenterology Guideline on the Diagnosis and Management of Celiac Disease with updated recommendations for the evaluation and management of patients with celiac disease (CD). CD is defined as a permanent immune-mediated response to gluten present in wheat, barley, and rye. CD has a wide spectrum of clinical manifestations that resemble a multisystemic disorder rather than an isolated intestinal disease, and is characterized by small bowel injury and the presence of specific antibodies. Detection of CD-specific antibodies (e.g., tissue transglutaminase) in the serum is very helpful for the initial screening of patients with suspicion of CD. Intestinal biopsy is required in most patients to confirm the diagnosis. A nonbiopsy strategy for the diagnosis of CD in selected children is suggested and discussed in detail. Current treatment for CD requires strict adherence to a gluten-free diet (GFD) and lifelong medical follow-up. Most patients have excellent clinical response to a GFD. Nonresponsive CD is defined by persistent or recurrent symptoms despite being on a GFD. These patients require a systematic workup to rule out specific conditions that may cause persistent or recurrent symptoms, especially unintentional gluten contamination. Refractory CD is a rare cause of nonresponsive CD often associated with poor prognosis., (Copyright © 2022 by The American College of Gastroenterology.)

Background: The aim of this study was to quantify the long-term clinical outcomes for individuals receiving teduglutide for short-bowel syndrome (SBS)., Methods: A single-center, retrospective study was performed for individuals commencing use of teduglutide between March 2013 and May 2019., Results: Eighteen patients were included in the final analysis, among which the median duration of teduglutide administration was 3.2 (range, 0.6-6.2) years. Twelve of 16 (75%) patients at 12 months, 10 of 13 (76.9%) at 24 months, 7 of 10 (70%) at 36 months, and 3 of 3 (100%) at 60 months had a response to teduglutide therapy, defined as a >20% reduction in parenteral support (PS) requirement. Among responders at 12, 24, and 36 months, the presence of a colon-in-continuity, an ileocecal valve, a response at 3 months, the length of small bowel, nor the baseline volume affected response to therapy (P > .05 for all comparisons). Five (28%) patients were able to achieve freedom from PS, among which all had a history of Crohn's disease with loss of the ileocecal valve and among which 3 had a colon-in-continuity. Four of the 5 patients discontinued PS by 6 months of teduglutide therapy., Conclusions: In a real-world experience, teduglutide therapy results in rapid and sustained reductions in PS. Larger postmarketing studies will be required to reliably predict response to treatment and the factors associated with enteral autonomy., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Background & Aims: The incidence of small bowel cancers is increasing. Associations have been made between celiac disease (CD) and small bowel cancers, but there have been no detailed studies of large cohorts., Methods: Through the nationwide Epidemiology Strengthened by Histopathology Reports in Sweden cohort study, we retrieved data from Sweden's 28 pathology departments on all individuals who received a diagnosis of CD from 1965 through 2017. Individuals with CD, defined as duodenal or jejunal villous atrophy (stage 3 Marsh score), were matched with as many as 5 randomly selected reference individuals from the general population. We used stratified Cox regression to calculate hazard ratios (HRs) for small bowel adenocarcinoma, adenomas, and carcinoids., Results: During a median follow-up of 11 years, we identified 48,119 individuals with CD (patients) and 239,249 reference individuals. Beginning at 1 year after a diagnosis of CD, 29 patients (0.06%) received a diagnosis of small bowel adenocarcinoma vs 45 reference individuals (0.02%), 7 patients received a diagnosis of carcinoids vs 31 reference individuals, and 48 patients received a diagnosis of adenomas vs 50 reference individuals. Corresponding HRs were small bowel adenocarcinoma 3.05 (95% confidence interval [CI], 1.86-4.99), carcinoids 0.59 (95% CI, 0.16-2.10), and adenomas 5.73 (95% CI, 3.70-8.88). HRs were independent of sex and age. Overall, there was 1 extra case of small bowel adenocarcinoma in every 2944 patients with CD followed for 10 years. There was an inverse association between mucosal healing risk of future small bowel adenocarcinoma (HR, 0.18; 95% CI, 0.02-1.61), although the HR failed to attain statistical significance., Conclusions: In an analysis of a nationwide pathology database in Sweden, we found the absolute risk of small bowel adenocarcinoma is low in individuals with CD. However, risks of small bowel adenocarcinoma and adenomas (but not carcinoids) are significantly increased in people with CD compared to people without this disease., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: There is controversy over the association between celiac disease (CeD) and inflammatory bowel diseases (IBD). We performed a systematic review and meta-analysis to assess evidence for an association between CeD and IBD., Methods: We searched databases including MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL, DARE, and SIGLE through June 25, 2019 for studies assessing the risk of CeD in patients with IBD, and IBD in patients with CeD, compared with controls of any type. We used the Newcastle-Ottawa Scale to evaluate the risk of bias and GRADE to assess the certainty of the evidence., Results: We identified 9791 studies and included 65 studies in our analysis. Moderate certainty evidence found an increased risk of CeD in patients with IBD vs controls (risk ratio [RR] 3.96; 95% confidence interval [CI] 2.23-7.02) and increased risk of IBD in patients with CeD vs controls (RR 9.88; 95% CI 4.03-24.21). There was low-certainty evidence for the risk of anti-Saccharomyces antibodies, a serologic marker of IBD, in patients with CeD vs controls (RR 6.22; 95% CI 2.44-15.84). There was low-certainty evidence for no difference in risk of HLA-DQ2 or DQ8 in patients with IBD vs controls (RR 1.04; 95% CI 0.42-2.56), and very low-certainty evidence for an increased risk of anti-tissue transglutaminase in patients with IBD vs controls (RR 1.52; 95% CI 0.52-4.40). Patients with IBD had a slight decrease in risk of anti-endomysial antibodies vs controls (RR 0.70; 95% CI 0.18-2.74), but these results are uncertain., Conclusions: In a systematic review and meta-analysis, we found an increased risk of IBD in patients with CeD and increased risk of CeD in patients with IBD, compared with other patient populations. High-quality prospective cohort studies are needed to assess the risk of CeD-specific and IBD-specific biomarkers in patients with IBD and CeD., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Celiac disease is a common inflammatory disease triggered by dietary gluten in genetically susceptible individuals. The strongest and best-characterized genetic susceptibilities in celiac disease are class II human leukocyte antigen (HLA) genes known as HLA-DQ2 and DQ8. HLA genetic testing is available through a number of commercial and academic laboratories and is used in the evaluation of celiac disease and to identify at-risk family members. Importantly, HLA genetic testing has a high negative predictive value for celiac disease, but a low positive predictive value. Therefore, for a practicing clinician, it is important to understand when to order HLA genetic testing, what test to order, and how to interpret the result. This review provides a practical primer on HLA genetics in celiac disease.

Introduction: A small bowel source is suspected when evaluation of overt gastrointestinal (GI) bleeding with upper and lower endoscopy is negative. Video capsule endoscopy (VCE) is the recommended next diagnostic test for small bowel bleeding sources. However, clinical or endoscopic predictive factors for small bowel bleeding in the setting of an overt bleeding presentation are unknown. We aimed to define predictive factors for positive VCE among individuals presenting with overt bleeding and a suspected small bowel source., Methods: We included consecutive inpatient VCE performed between September 1, 2012 to September 1, 2015 for melena or hematochezia at two tertiary centers. All patients had EGD and colonoscopy performed prior to VCE. Patient demographics, medication use, and endoscopic findings were retrospectively recorded. VCE findings were graded based on the P0-P2 grading system. The primary outcome of interest was a positive (P2) VCE. The secondary outcome of interest was the performance of a therapeutic intervention. Data were analyzed with the Fisher exact test for dichotomous variables and logistic regression., Results: Two hundred forty-three VCE were reviewed, and 117 were included in the final analysis. A positive VCE (P2) was identified in 35 (29.9%) cases. In univariate analysis, a positive VCE was inversely associated with presence of diverticula on preceding colonoscopy (OR: 0.44, 95% CI: 0.2-0.99), while identification of blood on terminal ileal examination was associated with a positive VCE (OR: 5.18, 95% CI: 1.51-17.76). In multivariate analysis, only blood identified on terminal ileal examination remained a significant risk factor for positive VCE (OR: 6.13, 95% CI: 1.57-23.81). Blood on terminal ileal examination was also predictive of therapeutic intervention in both univariate (OR: 4.46, 95% CI: 1.3-15.2) and multivariate analysis (OR: 5.04, 95% CI: 1.25-20.32)., Conclusion: Among patients presenting with overt bleeding but negative upper and lower endoscopy, the presence of blood on examination of the terminal ileum is strongly associated with a small bowel bleeding source as well as with small bowel therapeutic intervention. Presence of diverticula on colonoscopy is inversely associated with a positive VCE and therapeutic intervention in univariate analysis., Competing Interests: The authors have declared that no competing interests exist.

Background & Aims: Patients with celiac disease should maintain a gluten-free diet (GFD), excluding wheat, rye, and barley. Oats might increase the nutritional value of a GFD, but their inclusion is controversial. We performed a systematic review and meta-analysis to evaluate the safety of oats as part of a GFD in patients with celiac disease., Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases for clinical trials and observational studies of the effects of including oats in GFD of patients with celiac disease. The studies reported patients' symptoms, results from serology tests, and findings from histologic analyses. We used the GRADE approach to assess the quality of evidence., Results: We identified 433 studies; 28 were eligible for analysis. Of these, 6 were randomized and 2 were not randomized controlled trials comprising a total of 661 patients-the remaining studies were observational. All randomized controlled trials used pure/uncontaminated oats. Oat consumption for 12 months did not affect symptoms (standardized mean difference: reduction in symptom scores in patients who did and did not consume oats, -0.22; 95% CI, -0.56 to 0.13; P = .22), histologic scores (relative risk for histologic findings in patients who consumed oats, 0.24; 95% CI, 0.01-4.8; P = .35), intraepithelial lymphocyte counts (standardized mean difference, 0.21; 95% CI, reduction of 1.44 to increase in 1.86), or results from serologic tests. Subgroup analyses of adults vs children did not reveal differences. The overall quality of evidence was low., Conclusions: In a systematic review and meta-analysis, we found no evidence that addition of oats to a GFD affects symptoms, histology, immunity, or serologic features of patients with celiac disease. However, there were few studies for many endpoints, as well as limited geographic distribution and low quality of evidence. Rigorous double-blind, placebo-controlled, randomized controlled trials, using commonly available oats sourced from different regions, are needed., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Eicosanoids are inflammatory mediators that play a key but incompletely understood role in linking the innate and adaptive immune systems. Here, we show that cytotoxic effector T cells (CTLs) are capable of both producing and responding to cysteinyl leukotrienes (CystLTs), allowing for the killing of target cells in a T cell receptor-independent manner. This process is dependent on the natural killer receptor NKG2D and exposure to IL-15, a cytokine induced in distressed tissues. IL-15 and NKG2D signaling drives the up-regulation of key enzymes implicated in the synthesis of CystLTs, as well as the expression of CystLT receptors, suggesting a positive feedback loop. Finally, although the CystLT pathway has been previously linked to various allergic disorders, we provide unexpected evidence for its involvement in the pathogenesis of celiac disease (CD), a T helper 1 cell-mediated enteropathy induced by gluten. These findings provide new insights into the cytolytic signaling pathway of NKG2D and the pathogenesis of organ-specific immune disorders. Furthermore, they suggest that the blockade of CystLT receptors may represent a potent therapeutic target for CD or potentially other autoimmune disorders in which NKG2D has been implicated., (© 2015 Tang et al.)

Background & Aims: The mechanisms of tissue destruction during progression of celiac disease are poorly defined. It is not clear how tissue stress and adaptive immunity contribute to the activation of intraepithelial cytotoxic T cells and the development of villous atrophy. We analyzed epithelial cells and intraepithelial cytotoxic T cells in family members of patients with celiac disease, who were without any signs of adaptive antigluten immunity, and in potential celiac disease patients, who have antibodies against tissue transglutaminase 2 in the absence of villous atrophy., Methods: We collected blood and intestinal biopsy specimens from 268 patients at tertiary medical centers in the United States and Italy from 2004 to 2012. All subjects had normal small intestinal histology. Study groups included healthy individuals with no family history of celiac disease or antibodies against tissue transglutaminase 2 (controls), healthy family members of patients with celiac disease, and potential celiac disease patients. Intraepithelial cytotoxic T cells were isolated and levels of inhibitory and activating natural killer (NK) cells were measured by flow cytometry. Levels of heat shock protein (HSP) and interleukin 15 were measured by immunohistochemistry, and ultrastructural alterations in intestinal epithelial cells (IECs) were assessed by electron microscopy., Results: IECs from subjects with a family history of celiac disease, but not from subjects who already had immunity to gluten, expressed higher levels of HS27, HSP70, and interleukin-15 than controls; their IECs also had ultrastructural alterations. Intraepithelial cytotoxic T cells from relatives of patients with celiac disease expressed higher levels of activating NK receptors than cells from controls, although at lower levels than patients with active celiac disease, and without loss of inhibitory receptors for NK cells. Intraepithelial cytotoxic T cells from potential celiac disease patients failed to up-regulate activating NK receptors., Conclusions: A significant subset of healthy family members of patients with celiac disease with normal intestinal architecture had epithelial alterations, detectable by immunohistochemistry and electron microscopy. The adaptive immune response to gluten appears to act in synergy with epithelial stress to allow intraepithelial cytotoxic T cells to kill epithelial cells and induce villous atrophy in patients with active celiac disease., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Double-balloon enteroscopy (DBE) is effective in visualizing the small bowel to perform biopsy sampling and interventions. Few studies have evaluated the utility of DBE in patients with known or suspected Crohn's disease (CD)., Objective: To evaluate the use of DBE in the diagnosis and impact on patient management in known and suspected CD and to compare capsule endoscopy (CE) with DBE findings., Design: Retrospective study from August 2004 to August 2009 of DBE procedures., Setting: Five academic, tertiary U.S. centers., Patients: Patients with known or suspected CD., Main Outcome Measures: Diagnostic yield, impact on patient management, and comparison of DBE to CE findings in patients with known and suspected CD., Results: We analyzed 98 DBE procedures performed in 81 patients (38 with known CD and 43 with suspected CD). For patients with CD, common indications were abdominal pain and bleeding/anemia. The diagnostic yield was 87% (33/38 patients). The impact on subsequent management decisions was 82% (31/38). Common indications for DBE in patients with suspected CD were abnormal CE or other imaging. The diagnostic yield was 79% (34/43 patients). The impact on subsequent management decisions was 77% (33/43). In 17% of patients (14/81), DBE failed to reach the target lesion. There was 1 perforation, 3 strictures dilated, and 1 of 2 retained capsules recovered. When CE was followed by DBE, 46% of lesions were confirmed on DBE., Limitations: Retrospective analysis, imperfect criterion standard., Conclusions: DBE is an effective technique for assessment of the small bowel in known and suspected CD and affects management. Failure to reach target areas with DBE is not uncommon, and perforations can occur. There is poor correlation between CE and DBE., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: MiroCam, a capsule endoscope, uses a novel transmission technology, electric-field propagation, which uses the human body as a conduction medium for data transmission., Objective: To compare the ability of the MiroCam (MC) and PillCam (PC) to identify sources of obscure GI bleeding (OGIB)., Design: Prospective, multicenter, comparative study., Setting: Six academic hospitals., Patients: A total of 105 patients with OGIB., Intervention: Patients ingested both the MC and PC capsules sequentially in a randomized fashion., Main Outcome Measurements: Concordance of rates in identifying a source of OGIB, operational times, and rates of complete small-bowel examination., Results: Data analysis resulted in 43 (48%) "abnormal" cases identifying a source of OGIB by either capsule. Twenty-four cases (55.8%) were positive by both capsules. There was negative agreement in 46 of 58 cases (79.3%). The κ index was 0.547 (χ(2) = 1.32; P = .36). In 12 cases, MC positively identified a source that was not seen on PC, whereas in 7 cases, PC positively identified a source that was not seen on MC. MC had a 5.6% higher rate of detecting small-bowel lesions (P = .54). MC captured images at 3 frames per second for 11.1 hours, and PC captured images at 2 frames per second for 7.8 hours (P < .0001). Complete small-bowel examination was achieved in 93.3% for MC and 84.3% for PC (P = .10)., Limitations: Readers were not blinded to the particular capsule they were reading., Conclusion: A positive diagnostic finding for OGIB was identified by either capsule in 48% of cases. The concordance rate between the 2 capsules was comparable to that of prior studies in identifying sources of small-bowel bleeding. The longer operational time of the MC may result in higher rates of complete small-bowel examination, which may, in turn, translate into a higher rate of detecting small-bowel lesions. (, Clinical Trial Registration Number: NCT00878982.)., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Hypothesis: Laparoscopic diverting ileostomy should help define whether a severe, obscure gastrointestinal hemorrhage is in the upper or lower gastrointestinal tract in preparation for subtotal resection without increasing risk of patient morbidity and mortality., Design: Case reports., Setting: University hospital., Patients: Patient 1 is an 83-year-old woman. Patient 2 is a 75-year-old woman. Both were admitted to the hospital for massive gastrointestinal hemorrhage, which required multiple blood transfusions. Extensive workup revealed multiple diverticula in the small and large intestines without identification of any source of active bleeding in either patient., Intervention: Laparoscopic exploration of the abdominal cavity was performed. The terminal ileum at the ileocecal valve was identified and, 5 cm proximal to the ileocecal valve, the small bowel was transected. The distal end staple line was secured in end-to-side fashion to the proximal end, and the proximal end was brought out as an end ileostomy. Patients were then observed for bleeding into the ostomy bag or in the rectum., Main Outcome Measure: Localization of the source of bleeding as upper or lower, occurrence of surgical complications, and clinical outcome., Results: No intraoperative complications occurred in either patient. Patient 1 had significant bleeding into her ileostomy bag on postoperative day 1. She was taken back to the operating room for empirical small bowel resection. She was discharged, had no further bleeding, and underwent closure of the ileostomy 2 months later. The postoperative course of patient 2 was complicated by a small parastomal abscess that resolved with percutaneous drainage and antibiotics. Patient 2 returned on postoperative day 22 with bleeding in the rectum. She was taken to the operating room for laparoscopic total colectomy with ileosigmoid anastomosis and ileostomy closure. Both patients recovered uneventfully and had no recurrent bleeding., Conclusions: Our experience with these 2 patients suggests that in cases in which the risk of blind resection appears ill-advised, laparoscopic compartmentalization of the small bowel from the colon via end ileostomy may be safely performed.

Background & Aims: Double balloon enteroscopy (DBE) was introduced into the US in 2004. Potential complications include perforation, pancreatitis, and gastrointestinal bleeding. Prevalence and risk factors for complications have not been described in a US population., Methods: We conducted a retrospective study of DBE complications in 9 US centers. We obtained detailed information for each complication including patient history, maneuvers performed during the DBE, and presence of altered surgical anatomy., Results: We collected data from 2478 DBE examinations performed from 2004 to 2008. The dataset included 1691 (68%) anterograde DBE, 722 (29%) retrograde DBE (including 5 per-stomal DBEs), and 65 (3%) DBE-facilitated endoscopic retrograde cholangiopancreatography ERCP cases. There were a total of 22 (0.9%) major complications including perforation in 11 (0.4%), pancreatitis in 6 (0.2%), and bleeding in 4 (0.2%) patients. One of 6 cases of pancreatitis occurred post retrograde DBE. Perforations occurred in 3/1691 (0.2%) anterograde examinations and 8/719 (1.1%) retrograde DBEs (P = .004). Eight (73%) perforations occurred during diagnostic DBE examinations. Four of 8 retrograde DBE perforations occurred in patients with prior ileoanal or ileocolonic anastomoses. In the subset of 219 examinations performed in patients with surgically altered anatomy, perforations occurred in 7 (3%), including 1/159 (0.6%) anterograde DBE examinations, 6/60 (10%) retrograde DBEs, and 1 of 5 (20%) peristomal DBE examinations (P < .005 compared with patients without surgically altered anatomy)., Conclusions: DBE is associated with a higher complication rate compared with standard endoscopic procedures. The perforation rate was significantly elevated in patients with altered surgical anatomy undergoing diagnostic retrograde DBE examinations.

Background: Small bowel mass lesions (SBML) are a relatively common cause of obscure gastrointestinal bleeding (OGIB). Their detection has been limited by the inability to endoscopically examine the entire small intestine. This has changed with the introduction of capsule endoscopy (CE) and double balloon enteroscopy (DBE) into clinical practice., Study Aim: To evaluate the detection of SBML by DBE and CE in patients with OGIB who were found to have SBML by DBE and underwent both procedures., Methods: A retrospective review of a prospectively collected database of all patients undergoing DBE for OGIB at seven North American tertiary centers was performed. Those patients who were found to have SBML as a cause of their OGIB were further analyzed., Results: During an 18 month period, 183 patients underwent DBE for OGIB. A small bowel mass lesion was identified in 18 patients. Of these, 15 patients had prior CE. Capsule endoscopy identified the mass lesion in five patients; fresh luminal blood with no underlying lesion in seven patients, and non-specific erythema in three patients. Capsule endoscopy failed to identify all four cases of primary small bowel adenocarcinoma., Conclusions: Double balloon enteroscopy detects small bowel mass lesions responsible for OGIB that are missed by CE. Additional endoscopic evaluation of the small bowel by DBE or intraoperative enteroscopy should be performed in patients with ongoing OGIB and negative or non-specific findings on CE.

Background: Because of postoperative complications, patients who have undergone Roux-en-Y gastric bypass (RYGB) for weight loss may require radiographic investigation of the pancreaticobiliary limb or enteral feeding. Gastrostomy-tube placement into the excluded stomach for these indications is typically performed surgically or via fluoroscopic or US guidance; PEG has not been reported as being performed for this purpose. Successful examination of the excluded stomach after RYGB has been reported when using double-balloon enteroscopy (DBE)., Objective: To perform PEG in the excluded stomach by using DBE., Design: Retrospective review., Setting: Single, North American tertiary-care center., Patients: Individuals with postoperative complications after RYGB that requires radiographic examination of the excluded stomach and the pancreaticobiliary limb, or enteral feeding., Interventions: Performance of PEG within the excluded stomach by using DBE., Main Outcome Measurements: Ability to perform PEG-procedure-related complications and resultant management changes., Results: PEG was successfully performed by using DBE in 3 of 4 patients with postoperative complications after RYGB. In 2 of the cases, the results of radiographic studies performed with contrast administration through the gastrostomy tube led to significant operative management changes. In the third case, preoperative enteral nutrition was provided by using a gastrostomy tube. PEG placement was not possible in the fourth case because of the lack of abdominal transillumination. Major complications were not observed., Limitations: Small sample size, single-center experience., Conclusions: PEG placement in the excluded stomach after RYGB by using DBE was safe, technically feasible, and led to management changes in patients in whom it was performed. This procedure should be added to the growing list of indications for DBE.

Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon gamma-producing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases.