AGA clinical practice update on the epidemiology, evaluation, and management of exocrine pancreatic insufficiency: expert review

Exocrine pancreatic insufficiency (EPI) is a disorder caused by the failure of the pancreas to deliver a minimum/ threshold level of specific pancreatic digestive enzymes to the intestine, leading to the maldigestion of nutrients and macronutrients, resulting in their variable deficiencies. EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately. There is an urgent need to increase awareness of and treatment for this condition. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to provide Best Practice Advice on the epidemiology, evaluation, and management of EPI.

AGA Clinical Practice Update on the Epidemiology, Evaluation, and Management of Exocrine Pancreatic Insufficiency: Expert Review.

DESCRIPTION: Exocrine pancreatic insufficiency (EPI) is a disorder caused by the failure of the pancreas to deliver a minimum/threshold level of specific pancreatic digestive enzymes to the intestine, leading to the maldigestion of nutrients and macronutrients, resulting in their variable deficiencies. EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately. There is an urgent need to increase awareness of and treatment for this condition. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to provide Best Practice Advice on the epidemiology, evaluation, and management of EPI. METHODS: This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: EPI should be suspected in patients with high-risk clinical conditions, such as chronic pancreatitis, relapsing acute pancreatitis, pancreatic ductal adenocarcinoma, cystic fibrosis, and previous pancreatic surgery. BEST PRACTICE ADVICE 2: EPI should be considered in patients with moderate-risk clinical conditions, such as duodenal diseases, including celiac and Crohn's disease; previous intestinal surgery; longstanding diabetes mellitus; and hypersecretory states (eg, Zollinger-Ellison syndrome). BEST PRACTICE ADVICE 3: Clinical features of EPI include steatorrhea with or without diarrhea, weight loss, bloating, excessive flatulence, fat-soluble vitamin deficiencies, and protein-calorie malnutrition. BEST PRACTICE ADVICE 4: Fecal elastase test is the most appropriate initial test and must be performed on a semi-solid or solid stool specimen. A fecal elastase level <100 µg/g of stool provides good evidence of EPI, and levels of 100-200 µg/g are indeterminate for EPI. BEST PRACTICE ADVICE 5: Fecal elastase testing can be performed while on pancreatic enzyme replacement therapy. BEST PRACTICE ADVICE 6: Fecal fat testing is rarely needed and must be performed when on a high-fat diet. Quantitative testing is generally not practical for routine clinical use. BEST PRACTICE ADVICE 7: Response to a therapeutic trial of pancreatic enzymes is unreliable for EPI diagnosis. BEST PRACTICE ADVICE 8: Cross-sectional imaging methods (computed tomography scan, magnetic resonance imaging, and endoscopic ultrasound) cannot identify EPI, although they play an important role in the diagnosis of benign and malignant pancreatic disease. BEST PRACTICE ADVICE 9: Breath tests and direct pancreatic function tests hold promise, but are not widely available in the United States. BEST PRACTICE ADVICE 10: Once EPI is diagnosed, treatment with pancreatic enzyme replacement therapy (PERT) is required. If EPI is left untreated, it will result in complications related to fat malabsorption and malnutrition, having a negative impact on quality of life. BEST PRACTICE ADVICE 11: PERT formulations are all derived from porcine sources and are equally effective at equivalent doses. There is a need for H2 or proton pump inhibitor therapy with non-enteric-coated preparations. BEST PRACTICE ADVICE 12: PERT should be taken during the meal, with the initial treatment of at least 40,000 USP units of lipase during each meal in adults and one-half of that with snacks. The subsequent dosage can be adjusted based on the meal size and fat content. BEST PRACTICE ADVICE 13: Routine supplementation and monitoring of fat-soluble vitamin levels are appropriate. Dietary modifications include a low-moderate fat diet with frequent smaller meals and avoiding very-low-fat diets. BEST PRACTICE ADVICE 14: Measures of successful treatment with PERT include reduction in steatorrhea and associated gastrointestinal symptoms; a gain of weight, muscle mass, and muscle function; and improvement in fat-soluble vitamin levels. BEST PRACTICE ADVICE 15: EPI should be monitored and baseline measurements of nutritional status should be obtained (body mass index, quality-of-life measure, and fat-soluble vitamin levels). A baseline dual-energy x-ray absorptiometry scan should be obtained and repeated every 1-2 years.

High Degree of Practice Variability in Colonic Dysplasia Surveillance for Patients With Inflammatory Bowel Disease.

Dysplasia surveillance practice varies widely among high-volume inflammatory bowel disease providers. We surveyed high-volume inflammatory bowel disease providers about practice patterns to detect dysplasia. Regular use of dye-based chromoendoscopy was reported by 20%, virtual chromoendoscopy by 27%, and random biopsies by 58%.

Utility of FDG PET/CT in assessing bowel inflammation.

PURPOSE: To develop a methodology for the quantification of gastrointestinal (GI) inflammation as indicated by 2-deoxy-2-(18F)fluoro-D-glucose (FDG) uptake on positron-emissions tomography/computed tomography (PET/CT) imaging. This is intended to investigate the feasibility of using standard uptake value (SUV) levels to assess levels of GI inflammation in humans. METHODS: 131 participants were injected with a weight-controlled dose of FDG 180 minutes prior to PET/CT scanning. Operator-guided software was used to segment the GI tract and perform (SUV) calculations. Regions of interest (ROIs) were created using CT images and stacked to create three dimensional volumes of interest (VOIs). These VOIs defined 6 sections of the GI tract: esophagus, stomach, descending colon, ascending and transverse colon, bowel below the ilium and small bowel above the ilium. RESULTS: This study found a significant correlation between age and average FDG uptake (avg-SUV) of the GI tract (P=.0003) with the esophagus showing the highest significance. Correlations were found between avg-SUV of the sigmoid segment and the group average (P<.0001), and between the descending colon VOI and the group (P<.0001). Intra-operator reproducibility over 3 trials showed a coefficient of variation (CV) of .63%. Inter-operator CV over 5 randomly selected patients was 5.6% over the entire GI tract. CONCLUSION: This study shows that FDG-PET/CT imaging is a promising technique for quantifying bowel inflammation, despite the fact that age related inflammation may not be of clinical utility. The fact that we were able to detect these subtle changes indicates this as an avenue for potential future investigation.

Development of a narrow-band imaging classification to reduce the need for routine biopsies of gastric polyps.

BACKGROUND: Most incidental gastric polyps identified during upper endoscopy are considered low-risk. However, current guidelines recommend sampling all gastric polyps for histopathologic analysis. We aimed to devise a simple narrow-band imaging (NBI) classification to reduce the need for routine biopsies of low-risk gastric polyps. METHODS: Pairs of NBI and white-light images were collected from 73 gastric polyps for which concurrent histopathologic diagnosis was available. A diagnostic accuracy cohort study was performed. Two blinded endoscopists independently analysed NBI features of each polyp for color, vessel pattern, surface pattern, and any combinations thereof to develop a classification scheme to differentiate low-risk polyps (fundic-gland or hyperplastic) from high-risk polyps (adenomatous or adenocarcinoma) and fundic-gland polyps (FGPs) from non-FGPs. RESULTS: An isolated lacy vessel pattern and a homogenous absence of surface pattern successfully differentiated low-risk from high-risk gastric polyps. Combining both descriptors into a single algorithm resulted in a negative predictive value (NPV) of 100% [95% confidence interval (CI): 100%-100%], positive predictive value (PPV) of 13.7% (95% CI: 2.6-24.8), sensitivity of 100% (95% CI: 100%-100%), and specificity of 53.7% (95% CI: 45.3%-62.0%) for high-risk polyps. This would reduce the number of polyps requiring biopsy by 50%, while still capturing all high-risk polyps. Regarding FGPs, using a rule not to biopsy polyps with isolated lacy vessels resulted in a 94.9% NPV (95% CI: 89.2%-100%), 63.2% PPV (95% CI: 47.2%-79.2%), 94.8% sensitivity (95% CI: 89.5%-100%), and 63.6% specificity (95% CI: 51.3%-76.0%) for non-FGPs. CONCLUSION: In this derivation cohort study, NBI is helpful for differentiating between high-risk and low-risk gastric polyps, thereby reducing the need for routine sampling of low-risk polyps. These results need to be validated in a separate test population.

Endoscopic Management of Complex Lesions in Patients With Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated dysplastic lesions. Surveil-lance colonoscopy with endoscopic imaging techniques such as chromoendoscopy has been suggested. However, complex dysplastic lesions of larger size, challenging location behind folds, and nonpolypoid morphology defy standard polypectomy techniques and require advanced management with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). When technically feasible for visible dysplasia with distinct margins, these endoscopic procedures have replaced the traditional approach of surgical management. Recent guidelines support careful endoscopic inspection of the colonic mucosa with high-definition colonoscopes and the application of imaging techniques such as chromoendoscopy to enhance lesion detection and characterization as well as to help determine whether endoscopic management is an effective alternative to colectomy. Endoscopic resection techniques such as EMR and ESD have become key modalities in the management of endoscopically resectable dysplasia in patients with IBD.

Biosimilars in Inflammatory Bowel Disease.

Over the past 2 decades, biological therapy with monoclonal antibodies targeting tumor necrosis factor-α has become a cornerstone of treatment of patients with inflammatory bowel disease. Although clinically effective, the biological therapies remain expensive, and their availability and utilization have been at times limited due to their high costs. Biosimilars are biological products similar to but not identical to the original biological agent or "reference biologic," also called "originator biologic." It is hoped that the use of biosimilars might enable these agents to become more available and, thus, decrease further expenditures related to the use of the original reference agents such as infliximab and adalimumab. In this study, we review the currently available evidence and shortcomings of these data supporting the use of biosimilars for the treatment of patients with inflammatory bowel disease, including their efficacy and safety as related to initiating therapy with biosimilar agents or switching between reference and biosimilar biologic agents.

Confocal Laser Endomicroscopy in the Evaluation of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, can be effectively monitored with the use of endoscopy. The additional application of small field imaging technology such as confocal laser endomicroscopy CLE during ongoing endoscopic evaluation has led to real-time visualization of mucosal abnormalities and thus in vivo histology. The endomicroscopy (CLE) can improve IBD endoscopic evaluation by identifying seemingly normal-appearing mucosa, assessing the function of the intestinal barrier of the epithelium and vascular permeability, and by characterizing any mucosal lesions, including dysplastic lesions. CLE used during conventional endoscopy could especially facilitate the evaluation of mucosal healing in IBD. In addition, future developments in molecular imaging in IBD may optimize therapeutic approaches by identifying mucosal targets for therapy and determining the reasons for lack of response to specific therapy or subsequent loss of the response.

A User-Friendly Prediction Tool to Identify Colectomy Risk in Patients With Ulcerative Colitis.

BACKGROUND: Many patients with ulcerative colitis (UC) fear the potential side effects of immunosuppressive therapies. However, those with medically refractory disease often require total proctocolectomy (TPC) with a permanent ostomy or pouch, which may reduce quality of life. Prior studies have identified TPC predictors; however, no clinically useful prognostic tools exist to guide shared therapeutic decision-making. We therefore sought to develop a prediction tool of future TPC risk in UC patients. METHODS: In this retrospective study, clinic charts of UC patients were reviewed from January 1, 2017, to December 31, 2017. Cases had TPC performed for refractory UC after January 1, 2008. Controls had no prior UC surgery. Clinical data were assessed 1-12 months preceding TPC or clinic visit for cases and controls, respectively. We randomly selected two-thirds of patients to develop a TPC prediction model using multivariable logistic regression. One-third was reserved for model validation. RESULTS: We identified 115 cases and 325 controls. TPC predictors included albumin, 9-point Mayo score >5, Mayo endoscopic subscore >1, and corticosteroid use within 6 months. The areas under the receiver operating characteristic curve for the multivariable model were 0.94 (95% confidence interval [CI], 0.92-0.95) and 0.92 (95% CI, 0.89-0.95) for the test and validation cohorts, respectively. The validation cohort demonstrated a significant difference in calculated probability distributions between patients who did and did not have TPC (P < 0.01). We incorporated our model into a web-based application to allow convenient calculation of a patient's TPC risk. CONCLUSIONS: We created a user-friendly tool to assess TPC risk in UC. Prospective assessment will determine its utility for shared therapeutic decision-making.

Clinical differences of Helicobacter pylori infection in children.

Helicobacter pylori infection is widely spread all over the world. The prevalence of H. pylori infection in the world varies and depends on numerous factors such as age, ethnicity, geographical and socioeconomic status. Humans have been in a symbiotic relationship with this bacterium for thousands of years. However 10-20% of people infected with H. pylori are likely to develop gastroduodenal diseases such as peptic ulcer disease, iron deficiency anemia, gastric mucosal atrophy, metaplasia, dysplasia, MALT lymphoma, or gastric adenocarcinoma. Most of these diseases develop as the infection progresses and they are likely to occur later in life among the elderly. In the following years, the use of modern molecular techniques has led to the discovery of new Helicobacter strains and their genotypic differentiation. Newly discovered Helicobacter microorganisms can colonize human gastrointestinal tract and bile ducts. This article summarizes the distinct features of H. pylori infection in children including its prevalence, clinical manifestation, indications for treatment and recommended schemes of eradication.

Editorial: Endoscopic Scoring Systems in Crohn's Disease for Evaluation of Responsiveness to Treatment: Are we Ready for the Prime Time of Endoscopic Assessment?

There are currently two validated endoscopic indices for evaluation of Crohn's disease (CD), the Crohn's disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn's disease (SES-CD). The study by Khanna et al. evaluated the responsiveness of the SES-CD and CDEIS using data from a trial of adalimumab. The study used appropriate statistical methods to quantify responsiveness of the indices as assessed by blinded central readers. The SES-CD demonstrated numerically greater responsiveness to a treatment of known efficacy, suggestive that the SES-CD is more efficient outcome measure than the CDEIS. Removal of stenosis as an index item and adjusting for observed segments did not improve responsiveness. In the future, the implementation of the SES-CD into daily clinical practice may become a practical tool used by gastroenterologists when caring for patients with Crohn's disease. Further studies analyzing the responsiveness of the indices in combination with clinical and patients' driven outcomes are expected prior to the indices' use in "prime time".

The Role of Chromoendoscopy in Evaluating Colorectal Dysplasia.

Chromoendoscopy pertains to image-enhanced endoscopic techniques such as dye-based chromoendoscopy and electronic chromoendoscopy using narrow-band imaging, flexible spectral imaging color enhancement, and i-scan. Dye-based chromoendoscopy has been demonstrated to improve colorectal dysplasia detection in high-risk patients with long-term inflammatory bowel disease, and electronic chromoendoscopy techniques have been shown to improve characterization of diminutive colorectal lesions, allowing for optical diagnosis during a colonoscopy examination. This article reviews endoscopic imaging using chromoendoscopy techniques for colorectal dysplasia evaluation.

Endomicroscopy and Molecular Tools to Evaluate Inflammatory Bowel Disease.

Endoscopy is an essential tool for effective care of patients with inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis. The newest endoscopic small-field imaging technologies with confocal endomicroscopy have allowed real-time imaging of gastrointestinal mucosal during ongoing endoscopic evaluation and in vivo histology. Thus, endomicroscopy has a potential to further enhance the endoscopic evaluation of IBD. Advances in molecular in vivo imaging in IBD may be used not only to better understand the pathophysiology of IBD but also to guide optimized therapy and thus to allow a personalized, new approach to the IBD management.