Parenteral fish oil lipid emulsion use in adults: a case series and review from an intestinal failure referral center.

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.

Celiac Disease, Gluten Sensitivity, and Diet Management.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.

Outcomes of parenteral nutrition in patients with advanced cancer and malignant bowel obstruction.

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.

Standardizing Randomized Controlled Trials in Celiac Disease: An International Multidisciplinary Appropriateness Study.

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.

Outcomes of parenteral nutrition in patients with advanced cancer and malignant bowel obstruction.

Background: Malignant bowel obstruction (MBO) affects 3-15% 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.

Predictive Model for Positive Video Capsule Endoscopy in Iron Deficiency Anemia.

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.

American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease.

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.

Quality indicators for capsule endoscopy and deep enteroscopy.

BACKGROUND AND AIMS: 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. CONCLUSIONS: 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.

Quality Indicators for Capsule Endoscopy and Deep Enteroscopy.

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.

Gall Bladder Disease and the Risk of Small Bowel Cancer-Results from a Nationwide Swedish Cohort Study.

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.

Superior outcomes with double-balloon enteroscopy for small bowel lesion marking followed by intracorporeal as opposed to extracorporeal resection and reconstruction.

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.

Role of Video Capsule Endoscopy as a Prelude to Deep Enteroscopy.

Video capsule endoscopy and device-assisted enteroscopy are complementary technologies. Capsule endoscopy is a highly acceptable technology with high diagnostic yield that can guide a subsequent enteroscopy approach. This article aims to focus on the role of video capsule endoscopy as a prelude to deep enteroscopy with a focus on the strengths and limitations of either approach.

Long-Term Outcomes With Teduglutide From a Single Center.

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.

Risk of Small Bowel Adenocarcinoma, Adenomas, and Carcinoids in a Nationwide Cohort of Individuals With Celiac Disease.

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.

Association Between Inflammatory Bowel Diseases and Celiac Disease: A Systematic Review and Meta-Analysis.

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.

Celiac Disease and Its Role in the Development of Metabolic Bone Disease.

Celiac disease (CD) is an immune-mediated enteropathy that occurs in genetically susceptible hosts with the ingestion of gluten-containing products. Ongoing gluten consumption leads to intestinal damage, characterized by villous blunting and increased intraepithelial lymphocytes, resulting in malabsorption. Pertinent to the development of bone disease, malabsorption of calcium and vitamin D leads to secondary hyperparathyroidism and metabolic bone disease among individuals with CD. In this article, we review the pathogenesis of CD and the effects of malabsorption on bone health. Imbalances in bone resorption and formation particularly in individuals with CD and persistent disease activity ultimately lead to a state of bone loss and impaired mineralization. Initiation of a gluten-free diet is critical in the management of CD-related metabolic bone disease, demonstrating improvements in bone mineral density within the first year of dietary adherence.