Introduction: Rituximab (RTX), is a monoclonal antibody therapy directed at CD20 positive B lymphocytes, increasingly used in both malignant and autoimmune conditions. RTX therapy may result in hypogammaglobulinemia due to B cell depletion. The gastrointestinal side effects of the therapy are not well described. Here we report the clinical, endoscopic and histologic features of rituximab-associated enteropathy in a single center case series. Methods: Retrospective analysis of medical charts of patients with enteropathy presenting to a tertiary care university hospital between 2008 and 2021 were reviewed. Patients with enteropathy identified using diagnostic codes for: CVID, enteropathy, malabsorption, weight loss and diarrhea. Patients with rituximab use were further characterized. Clinical data, laboratory values, endoscopy and pathology reports were analyzed. Results: Ten patients with enteropathy associated with RTX therapy were identified without other competing etiology. Mean age was 64 years ± 17.4 and 5 (50%) patients were female. Lymphoma 8 (80%) was the most common indication for RTX therapy. Diarrhea and weight loss were the most common clinical presentation. The mean BMI on presentation was 18 kg/m2 with a mean total weight loss of 13.5 kg ± 8.9. Seven (70%) patients were defined as severely malnourished based on clinical criteria. Mean albumin was 3.3 g/dL (3.5-5) and pre-Albumin 16 g/dL (normal >21). Serum levels of IgA, IgM and IgG were below lower limit of normal. Endoscopic appearance of the duodenal mucosa was abnormal in 3/8 cases (37.5%) and 3/5 (60%) cases had decreased plasma cells in the lamina propria with villous atrophy (Figure 1). Seven patients (70%) had a pathologic diagnosis consistent with CVID enteropathy. All of the patients received IVIG therapy (100%) although only 2 had symptomatic improvement. Prednisone (n = 6), budesonide (n = 2), infliximab (n = 2) or vedolizumab (n = 1) did not lead to clinical improvement. Six (60%) required long term parenteral nutrition (PN). Conclusion: RTX is associated with a secondary CVID-like enteropathy with absent/decreased plasma cells in small bowel biopsies. Diarrhea with weight loss and severe malnutrition are common clinical features and patients often require parenteral nutrition. Treatment with IVIG and other immunosuppressive therapies rarely improves GI symptoms. RTX-associated enteropathy should be considered in patients presenting with diarrhea and/or weight loss and history of RTX use.Figure 1.: Small bowel mucosa showing a lack of lamina propria plasma cells (arrows).

In this article, we will examine the role of biopsy in the diagnosis of celiac disease. We will cover the historical place biopsy has held, current practice for diagnosing celiac disease, advancement of serology testing, controversy of a nonbiopsy approach, and future considerations. The relative pitfalls and merits of biopsy and serology testing are covered.

Rituximab (RTX) is a monoclonal anti-CD20 antibody widely used to treat B-cell neoplasms and autoimmune conditions. RTX has recently been linked to an enteropathy characterized by diarrhea, malabsorption, and hypogammaglobulinemia, closely resembling common variable immunodeficiency (CVID) enteropathy. We present the first dedicated histopathologic assessment of RTX-associated CVID-like enteropathy. Study inclusion criteria were the presence of diarrhea, weight loss, or other gastrointestinal symptoms in the setting of current/prior RTX use and associated hypogammaglobulinemia. Twenty-two patients (15 male:7 female; mean age at biopsy/resection, 63.4 years) across 9 tertiary medical centers met inclusion criteria and had small bowel (N = 20) and/or colon (N = 17) specimens (biopsies/resections) available for review; 71.4% of specimens dated from ≤5 years of last RTX dose. Cases were systematically evaluated by gastrointestinal pathologists at each institution. Key histologic features in the small bowel included sparse/absent lamina propria plasma cells (N = 10; 50%), intraepithelial lymphocytosis (N = 12; 60%), villous atrophy (N = 11; 55%), increased crypt apoptotic bodies (N = 6; 30%), and active inflammation (N = 5; 25%). Common features in the colon included sparse/absent plasma cells (N = 7; 41.2%), increased crypt apoptotic bodies (N = 7; 41.2%), active inflammation (N = 5; 29.4%), and intraepithelial lymphocytosis (N = 4; 23.5%). Goblet cell loss was appreciated in small bowel and/or colon specimens from 2 patients. Follow-up biopsies (interval, 2 months to 4 years) were available for 7 patients and largely recapitulated the histology of the index specimens, though 1 patient demonstrated improvement in villous blunting and intraepithelial lymphocytosis. In summary, the histologic spectrum of post-RTX CVID-like enteropathy encompasses lamina propria plasma cell depletion, increased crypt apoptotic bodies, small bowel villous atrophy, and goblet cell loss. While the underlying pathophysiology remains uncertain, the clinicopathologic picture may reflect post-RTX B-cell/plasma cell impairment. Although histologic findings may be subtle and variable, pathologists should be aware of this entity and should seek a history of RTX use in patients whose biopsies exhibit these CVID enteropathy-like features.

BackgroundIntestinal failure-associated liver disease (IFALD) is a complication of long-term PN use, attributed to the use of omega-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.MethodsCase 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.ResultsThree 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.ConclusionFO 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.

Celiac disease is a common chronic inflammatory condition of the small bowel triggered by gluten in wheat, rye and barley in the diet. Non-celiac gluten sensitivity presents with symptoms similar to celiac disease with the ingestion of gluten or other components of wheat. In this article, we review challenges presented by a gluten free diet for the treatment of both disorders. Wheat is ubiquitous in the diet and medications/products. A registered dietitian is mandatory for patient education on the gluten free diet. Naturally gluten free foods provide a healthy diet for those with celiac disease. Whole grains labelled gluten free, including oats, are encouraged in the diet as refined grains may be deficient in fiber, protein, and micronutrients, particularly folate. Gluten contamination is the most common cause of persistent symptoms in celiac disease though shared equipment of food preparation may not be as large a problem as suspected. Most with celiac disease on a gluten free diet will fully recover and gain weight that poses a problem for those overweight to start. The gluten free diet may have a negative impact on quality of life for both celiac patients and their families. Those with hypervigilance of the gluten free diet and avoidance of dining out have the lowest quality of life. The gluten free diet is currently the only effective treatment for celiac disease. A registered dietitian is needed to educate patients on the complexity of the gluten free diet with a goal of healthy eating, maintaining a healthy weight, and avoiding disordered eating or diet hypervigilance; key to a good quality of life.

Rubio-Tapia, Alberto MD1; Hill, Ivor D. MD, FACG2; Semrad, Carol MD, FAG3; Kelly, Ciarán P. MD, FACG4; Greer, Katarina B. MD, MS Epi5; Limketkai, Berkeley N. MD, PhD, FACG6; Lebwohl, Benjamin MD, MS7 Author Information

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. 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. In total, 765 VCE procedures were included with 355 (46.5

Rubio-Tapia, Alberto MD1; Greer, Katarina B. MD, MS2; Limketkai, Berkeley N. MD, PhD, FACG3; Hill, Ivor D. MD4; Semrad, Carol MD5; Kelly, Ciarán P. MD6; Lebwohl, Benjamin MD, MS7 Author Information

Rubio-Tapia, Alberto MD1; Greer, Katarina B. MD, MS2; Limketkai, Berkeley MD, PhD3; Hill, Ivor D. MD4; Semrad, Carol MD5; Kelly, Ciarán P. MD6; Lebwohl, Benjamin MD, MS7 Author Information

Rationale: Early PEG tube dislodgement (defined < 7 days from placement) has significant morbidity and mortality. Our aim was to study its incidence and prevention strategies. Methods: Medical charts were reviewed in patients who underwent PEG placement at a tertiary care hospital from 2018 to 2021. Those with a second PEG within a week from initial placement were further studied. This was a quality improvement study exempt from IRB approval Results: There were 586 patients identified with PEG tube placements. The number of placements significantly increased from 2018 to 2022. Five (0.8%) patients had early PEG tube dislodgments; all had impaired mentation and self-pulled the tube. The median time from placement to dislodgment was 1 (SD±3.4) day, 2 occurred within 2 hours of placement. Incidence increased from 2019 (no cases) to 2022 [1/100 (1%) in 2020; 1/163 (0.6%) in 2021; 3/164 (1.8%) in 2022]. All patients were managed conservatively. Orders to prevent tube dislodgement were placed in less than 50% of patients. A PEG tube was re-placed in all 5 patients. All with re-placed tubes had orders placed for hand restraints and abdominal binders and were monitored for adherence. One patient had a second early PEG dislodgment. All 5 patients had delayed discharge. There were no deaths. Image: Conclusion: We report an increasing incidence of early dislodgement in hospitalized patients with impaired mentation. This may be due to a change in practice with earlier placements in high risk patients or a breakdown in education, communication, and beside care on preventive measures. Quality improvement measures include cautious selection of tube placement in those with impaired mentation, specific pre and post procedure order sets to include hand restraints and abdominal binder with close monitoring for adherence. Disclosure of Interest: None declared

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.

BACKGROUND & AIMS:There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking. METHODS:A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes. Two RCT designs were considered, representing the following distinct clinical scenarios for which pharmacotherapy may be used: trials incorporating a gluten challenge to simulate exposure; and trials evaluating reversal of histologic changes, despite attempted adherence to a gluten-free diet. Each statement was rated as appropriate, uncertain, or inappropriate, using a 9-point Likert scale. RESULTS:For trials evaluating prevention of relapse after gluten challenge, participants adherent to a gluten-free diet for 12 months or more with normal or near-normal-sized villi should be enrolled. Gluten challenge should be FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) free, and efficacy evaluated using histology with a secondary patient-reported outcome measure. For trials evaluating reversal of villus atrophy, the panel voted it appropriate to enroll participants with a baseline villus height to crypt depth ratio ≤2 and measure efficacy using a primary histologic end point. Guidance for measuring histologic, endoscopic, and patient-reported outcomes in adult and pediatric patients with CeD are provided, along with recommendations regarding the merits and limitations of different end points. CONCLUSIONS:We developed standardized recommendations for clinical trial design, eligibility criteria, outcome measures, gluten challenge, and disease evaluations for RCTs in patients with CeD.

INTRODUCTION: Capsule endoscopy (CE) and deep enteroscopy (DE) can be useful for diagnosing and treating suspected small-bowel disease. Guidelines and detailed recommendations exist for the use of CE/DE, but comprehensive quality indicators are lacking. The goal of this task force was to develop quality indicators for appropriate use of CE/DE by using a modified RAND/UCLA Appropriateness Method. METHODS: An expert panel of 7 gastroenterologists with diverse practice experience was assembled to identify quality indicators. A literature review was conducted to develop a list of proposed quality indicators applicable to preprocedure, intraprocedure, and postprocedure periods. The panelists reviewed the literature; identified and modified proposed quality indicators; rated them on the basis of scientific evidence, validity, and necessity; and determined proposed performance targets. Agreement and consensus with the proposed indicators were verified using the RAND/UCLA Appropriateness Method. RESULTS: The voting procedure to prioritize metrics emphasized selecting measures to improve quality and overall patient care. Panelists rated indicators on the perceived appropriateness and necessity for clinical practice. After voting and discussion, 2 quality indicators ranked as inappropriate or uncertain were excluded. Each quality indicator was categorized by measure type, performance target, and summary of evidence. The task force identified 13 quality indicators for CE and DE. DISCUSSION: Comprehensive quality indicators have not existed for CE or DE. The task force identified quality indicators that can be incorporated into clinical practice. The panel also addressed existing knowledge gaps and posed research questions to better inform future research and quality guidelines for these procedures.

Introduction: Small bowel bleeding poses a clinical challenge in patients with vascular lesions. Bleeding recurrence after endoscopic therapy is high and medical therapies have limited efficacy. In those with left ventricular assist devices (LVADs), the use of angiotensin converting enzyme inhibitors (ACEi) has been associated with a reduced rate of gastrointestinal bleeding. Conversely, the antiplatelet effects of ACEi have been described thought due to their effects in decreasing platelet aggregation. Our aim was to determine whether ACEi or angiotensin receptor blocker (ARB) therapy had an impact on the rate of positive VCE small bowel findings in those with iron deficiency anemia (IDA). Methods: Data was collected from consecutive inpatient and outpatient VCE examinations performed between January 1, 2009 to March 1, 2018 at a single U.S. tertiary medical center performed for IDA. VCE studies were excluded in those with incomplete small bowel examinations (9) or technical failure (1). Patient demographics, laboratory values, medication use and endoscopic findings were recorded. VCE findings were based on the P0-P2 grading system. The primary outcome of interest was a positive (P2) VCE. Data were analyzed using Wilcoxon rank-sum test for continuous variables and Fischer’s exact test for dichotomous variables. Bivariate logistic regression was performed to identify independent factors predictive of positive VCE. Results: Eighty-two VCE were included in the final analysis. Median age was 67.6 (IQR: 57.1-75.5) years and 38 (46.3%) patients were male. Thirty-seven (45.1%) VCE examinations were positive with the most common finding of angiectasia in 21 (55.3%). Risk factors for positive VCE are listed in Table 1. In univariate analysis, ACEi therapy associated with both positive VCE (P=0.014) and the presence of angiectasia (P=0.021), whereas ARB therapy did not associate with positive VCE. ACEi findings remained significant in bivariate analysis after controlling for cardiac and pulmonary comorbidities. Conclusion: In this single center study the presence of ACEi use was associated with small bowel and/or stomach angiectasias on VCE in univariate analysis and when controlled for cardiac and pulmonary risk factors. Further studies are required to determine the mechanistic impact of ACEi on gastrointestinal bleeding risk such as the reduction in von Willebrand factor or factors that affect platelet aggregation. Table 1. - Univariate predictors of positive video capsule endoscopy in iron deficiency anemia Negative VCE (n = 45) Positive VCE (n =37) P-value Age, years, mean (SD) 63.6 (15.8) 68.6 (9.3) 0.303 Male sex, n (%) 21 (46.7) 17 (46) 1 White race, n (%) 22 (48.9) 20 (54.1) 0.223 Active smoking, n (%) 6 (14) 11 (29.7) 0.105 Outpatient location, n (%) 31 (68.9) 21 (56.8) 0.357 Chronic kidney disease, n (%) 10 (22.2) 13 (35.1) 0.224 Chronic liver disease, n (%) 3 (6.7) 4 (10.8) 0.696 Congestive heart failure, n (%) 10 (22.2) 13 (35.1) 0.224 Diabetes mellitus, n (%) 15 (33.3) 15 (40.5) 0.645 Cardiac valvular disease, n (%) 7 (15.6) 6 (16.2) 1 Coronary artery disease, n (%) 14 (31.1) 14 (37.8) 0.641 Cardiac arrhythmia, n (%) 10 (22.2) 18 (48.7) 0.019 Chronic lung disease, n (%) 10 (22.2) 13 (35.1) 0.224 Left ventricular assist device, n (%) 2 (4.4) 2 (5.4) 1 Blood transfusion in the preceding 4 weeks, n (%) 17 (37.8) 16 (43.2) 0.656 Aspirin, n (%) 20 (44.4) 14 (37.8) 0.654 Thienopyridine, n (%) 3 (6.7) 2 (5.4) 1 Coumadin, n (%) 1 (2.2) 5 (13.5) 0.086 SSRI/SNRI, n (%) 7 (15.6) 9 (24.3) 0.404 ACEi 7 (15.6) 15 (40.5) 0.014 ARB 9 (20) 7 (18.9) 1 Hemoglobin, g/dL1 9.9 (1.7) 9.2 (2.3) 0.216 Platelets, 109/L1 225.4 (67.5) 208.6 (84.9) 0.202 BUN, mg/dL1 21.9 (13.1) 26.7 (22) 0.869 Creatinine, mg/dL1 1.3 (0.5) 1.9 (1.5) 0.197 Ferritin, ng/mL,1 128 (259) 39.6 (28.7) 0.966 Percent saturation, %1 14.8 (15.1) 13.7 (15.4) 0.76

Background and aims: Small bowel cancer is a rare but rising malignancy. The etiology is poorly understood and there is a need for large-scale studies. Gallbladder disease (GBD), inducing localized inflammation, has been suggested to increase small bowel cancer risk. Methods: We retrieved nationwide data from Sweden’s 28 pathology departments on all adults (age 20–79) with pathology-confirmed GBD diagnosed in 1965–2017. In total 156,390 GBD patients were matched with up to 5 matched comparators from the general population and follow-up started one year after GBD diagnosis. We used stratified Cox regression to calculate hazard ratios (HRs) for small bowel adenocarcinoma, adenomas, and carcinoids. Results: During a median follow-up of 12 years, we identified 92 small bowel adenocarcinomas, 132 adenomas, and 81 carcinoid tumors in the GBD cohort. Corresponding incidence rates were 4.8, 6.9, and 4.2 per 100,000 person-years (PY), compared to 3.2, 3.2, and 1.8 in matched comparators. The adjusted HR was 1.42 (95% CI = 1.08–1.87) for small bowel adenocarcinoma, 1.79 (95% CI = 1.41–2.27) for adenoma, and 2.07 (95% CI = 1.52–2.81) for carcinoid. The excess cancer risk was most pronounced during the first year of follow-up for adenocarcinomas and during the first six years for adenomas while for carcinoids the HR peaked 10–15 years after start of follow-up. Conclusions: In this nationwide cohort study, GBD was associated with an increased risk of small bowel cancer. The excess risk of small bowel adenocarcinoma was mainly seen during the first years of follow-up while small bowel carcinoid risk peaked 11–16 years after GBD diagnosis.

Background Double-balloon enteroscopy (DBE) is used for the diagnosis and therapy of small bowel disease. Endoscopic sampling and marking small bowel lesions destined for surgery permit intracorporeal resection and reconstruction (IRR), thereby facilitating a complete minimally invasive technique. There are limited data that compare outcomes of IRR to conventional extracorporeal resection and reconstruction (ERR). The purpose of this study was to evaluate the surgical outcomes of patients undergoing pre-operative DBE for lesion marking followed by laparoscopic IRR compared to those undergoing ERR. Methods A retrospective chart review was performed on patients who underwent DBE followed by small bowel resection from 2006 to 2017 at a single tertiary care medical center. IRR was defined as laparoscopic inspection to identify the lesion (previously marked by DBE or by laparoscopic-assisted DBE) followed by intra-abdominal bowel resection and anastomosis with specimen extraction via minimal extension of a laparoscopic port site. ERR was defined as extracorporeal resection and/or reconstruction performed via a conventional or mini-laparotomy abdominal incision. Results A total of 82 patients met inclusion criteria and were reviewed. Thirty-two patients (39%) had ERR and 50 patients (61%) had IRR. The most common indications for DBE were small bowel bleeding (76%) and small bowel mass or thickening on prior imaging studies (16%). Successful DBE was higher in the IRR group when compared to the ERR group, but not significantly different (90% vs 75%, p-value 0.07). Patients who underwent IRR had faster bowel function recovery (2 vs 4 days, p < 0.01), shorter time to discharge (3 vs 7 days, p < 0.01), and fewer post-operative complications (10 vs 18; p < 0.01), when compared to the ERR group. Conclusion DBE successfully facilitated laparoscopic small bowel IRR and this approach was associated with faster return of bowel function, shorter recovery time, and decreased morbidity when compared to ERR.