American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

Nonendoscopic Screening for Barrett's Esophagus and Esophageal Adenocarcinoma in At-Risk Veterans.

INTRODUCTION: Although rates of esophageal adenocarcinoma (EAC) in the United States continue to rise, many patients at risk of disease are not screened. EsoCheck (EC), a nonendoscopic esophageal balloon sampling device coupled with EsoGuard (EG), a DNA-based screening assay, is an US Food and Drug Administration-approved minimally invasive alternative to the traditional screening method of upper endoscopy. The objective of this study was to prospectively determine the diagnostic accuracy, tolerance, and acceptability of the EC/EG test in a screening population. METHODS: We recruited veterans who met the American College of Gastroenterology Guideline criteria for endoscopic Barrett's esophagus (BE) and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center. All study participants completed unsedated EC-guided distal esophageal sampling followed by a sedated esophagogastroduodenoscopy (EGD). Diagnostic yield of the EG assay and EGD was recorded and used in calculation of sensitivity and specificity of EC/EG in prospective screening. The abbreviated Spielberger State-Trait Anxiety Inventory questionnaire was administered before and after completion of EC. Overall tolerance of EC sampling was evaluated on a 10-point Likert scale. RESULTS: Esophageal cancer screening was accepted by 130 of 782 eligible veterans (16.6%), and we analyzed results of those who completed both screening tests (N = 124). Prevalence of BE/EAC among studied veterans was 12.9% (16/124), based on EGD. Sensitivity and specificity of EC/EG for EGD-detected BE/EAC were 92.9% (95% confidence interval [CI] 66.1-99.8) and 72.2% (95% CI 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI 18.6-49.1) and 98.6% (95% CI 92.4-100), respectively. Baseline Spielberger State-Trait Anxiety Inventory-6 scores were reflective of notable levels of anxiety among veterans in the periprocedural setting. The mean postprocedure acceptability score for the EC test was 7.23 (SD 2.45). DISCUSSION: Our data suggest excellent sensitivity and negative predictive value of EC/EG in a screening population of veterans, making this modality a powerful screening tool for BE and EAC.

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.

ACG Clinical Guideline: Diagnosis and Management of Gastrointestinal Subepithelial Lesions.

Subepithelial lesions (SEL) of the GI tract represent a mix of benign and potentially malignant entities including tumors, cysts, or extraluminal structures causing extrinsic compression of the gastrointestinal wall. SEL can occur anywhere along the GI tract and are frequently incidental findings encountered during endoscopy or cross-sectional imaging. This clinical guideline of the American College of Gastroenterology was developed using the Grading of Recommendations Assessment, Development, and Evaluation process and is intended to suggest preferable approaches to a typical patient with a SEL based on the currently available published literature. Among the recommendations, we suggest endoscopic ultrasound (EUS) with tissue acquisition to improve diagnostic accuracy in the identification of solid nonlipomatous SEL and EUS fine-needle biopsy alone or EUS fine-needle aspiration with rapid on-site evaluation sampling of solid SEL. There is insufficient evidence to recommend surveillance vs resection of gastric gastrointestinal stromal tumors (GIST) <2 cm in size. Owing to their malignant potential, we suggest resection of gastric GIST >2 cm and all nongastric GIST. When exercising clinical judgment, particularly when statements are conditional suggestions and/or treatments pose significant risks, health-care providers should incorporate this guideline with patient-specific preferences, medical comorbidities, and overall health status to arrive at a patient-centered approach.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

ACG Clinical Guideline: Gastroparesis.

Gastroparesis is characterized by symptoms suggesting retention of food in the stomach with objective evidence of delayed gastric emptying in the absence of mechanical obstruction in the gastric outflow. This condition is increasingly encountered in clinical practice. These guidelines summarize perspectives on the risk factors, diagnosis, and management of gastroparesis in adults (including dietary, pharmacological, device, and interventions directed at the pylorus), and they represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation process. When the evidence was not appropriate for Grading of Recommendations, Assessment, Development, and Evaluation, we used expert consensus to develop key concept statements. These guidelines should be considered as preferred but are not the only approaches to these conditions.

ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) continues to be among the most common diseases seen by gastroenterologists, surgeons, and primary care physicians. Our understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved. During this time, scrutiny of proton pump inhibitors (PPIs) has increased considerably. Although PPIs remain the medical treatment of choice for GERD, multiple publications have raised questions about adverse events, raising doubts about the safety of long-term use and increasing concern about overprescribing of PPIs. New data regarding the potential for surgical and endoscopic interventions have emerged. In this new document, we provide updated, evidence-based recommendations and practical guidance for the evaluation and management of GERD, including pharmacologic, lifestyle, surgical, and endoscopic management. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to evaluate the evidence and the strength of recommendations. Key concepts and suggestions that as of this writing do not have sufficient evidence to grade are also provided.

ACG Clinical Guidelines: Diagnosis and Management of Achalasia.

Achalasia is an esophageal motility disorder characterized by aberrant peristalsis and insufficient relaxation of the lower esophageal sphincter. Patients most commonly present with dysphagia to solids and liquids, regurgitation, and occasional chest pain with or without weight loss. High-resolution manometry has identified 3 subtypes of achalasia distinguished by pressurization and contraction patterns. Endoscopic findings of retained saliva with puckering of the gastroesophageal junction or esophagram findings of a dilated esophagus with bird beaking are important diagnostic clues. In this American College of Gastroenterology guideline, we used the Grading of Recommendations Assessment, Development and Evaluation process to provide clinical guidance on how best to diagnose and treat patients with achalasia.

Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis.

BACKGROUND & AIMS: Gluteofemoral obesity (determined by measurement of subcutaneous fat in the hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces the risk of Barrett's esophagus (BE), a premalignant lesion associated with abdominal obesity. METHODS: We collected data from non-Hispanic white participants in 8 studies in the Barrett's and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n = 1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using individual participant data and multivariable logistic regression and combined using a random-effects meta-analysis. RESULTS: We found an inverse relationship between hip circumference and BE (OR per 5-cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was statistically significant only among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with a decreased risk of BE. Increasing waist circumference was associated with an increased risk of BE in the mutually adjusted population-based and GERD control models. CONCLUSIONS: Although abdominal obesity is associated with an increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men.

Associations of Serum Adiponectin and Leptin With Barrett's Esophagus.

BACKGROUND & AIMS: Central adiposity is a risk factor for Barrett's esophagus (BE). Serum levels of adiponectin and leptin are deregulated in obese states and are implicated as putative mediators in the pathophysiology of esophageal columnar metaplasia. We describe associations between serum adiponectin and leptin levels with BE. METHODS: Patients were recruited prospectively for a case-control study. Fasting serum levels of adiponectin and leptin were measured in 135 patients with BE and compared with 2 separate control groups: 133 subjects with gastroesophageal reflux disease (GERD) and 1157 colon screening controls. RESULTS: Multivariate analyses adjusted for age, race, and waist-to-hip ratio showed that patients within the highest tertile of serum adiponectin level had decreased odds of BE compared with screening colonoscopy controls (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.22-0.80). This effect was more pronounced in men (OR, 0.35; 95% CI, 0.17-0.74) compared with women (OR, 0.71; 95% CI, 0.17-3.03). In comparisons of BE cases with GERD controls, subjects within the highest tertile of serum adiponectin level showed decreased odds of BE (OR, 0.65; 95% CI, 0.31-1.36), however, this was not statistically significant. Patients in the highest tertile of serum leptin level did not have a significantly increased risk of BE in comparison with GERD (OR, 1.32; 95% CI, 0.61-2.88) or screening colonoscopy controls (OR, 1.57; 95% CI, 0.82-3.04) in analyses including both sexes. Based on sex-specific analyses, sex did not significantly alter the association of leptin with odds of BE. CONCLUSIONS: Serum adiponectin was associated inversely with BE and this effect was more pronounced in men, whereas serum leptin showed no evidence of association with BE in comparisons with multiple control groups. The exact mechanism, if any, by which these adipokines promote metaplasia in the esophagus needs to be explored further.

Association of Serum Levels of Adipokines and Insulin With Risk of Barrett's Esophagus: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Metabolically active visceral fat may be associated with esophageal inflammation, metaplasia, and neoplasia. We performed a meta-analysis to evaluate the association of serum adipokines and insulin with Barrett's esophagus (BE). METHODS: We performed a systematic search of multiple electronic databases, through April 2015, to identify all studies reporting associations between leptin, adiponectin, insulin, insulin resistance, and risk of BE in adults. Comparing the highest study-specific category with the reference category for each hormone, we estimated the summary adjusted odds ratio (aOR) and 95% confidence intervals (CI), using a random effects model. RESULTS: We identified 9 observational studies (10 independent cohorts; 1432 patients with BE total, and 3550 control subjects). Meta-analysis revealed that high serum level of leptin was associated with 2-fold higher risk of BE (BE cases vs population control subjects in 5 studies: aOR, 2.23; 95% CI, 1.31-3.78; I(2), 59%). Total serum level of adiponectin was not associated with BE (BE cases vs population control subjects in 5 studies: aOR, 0.79; 95% CI, 0.46-1.34; I(2), 65%), although 1 study observed decreased risk of BE with increased level of low-molecular-weight adiponectin. High serum level of insulin was associated with increased risk of BE (BE cases vs population control subjects in 3 studies: aOR, 1.74; 95% CI, 1.14-2.65; I(2), 0), whereas insulin resistance was not associated with increased risk of BE (BE cases vs gastroesophageal reflux disease control subjects in 2 studies: aOR, 0.98; 95% CI, 0.42-2.30; I(2), 64%). CONCLUSIONS: Increased serum levels of leptin and insulin are associated with increased risk of BE, compared with population control subjects. In contrast, increased total serum levels of adiponectin and insulin do not seem to modify BE risk. Well-designed longitudinal studies of incident BE are needed to clarify existing associations of serum adipokines and insulin with BE.

Development of a program to train physician extenders to perform transnasal esophagoscopy and screen for Barrett's esophagus.

BACKGROUND & AIMS: Screening for Barrett's esophagus (BE) and esophageal adenocarcinoma is not recommended because it was not found to be cost effective. However, physician extenders (PEs) are able to perform unsedated procedures; their involvement might reduce the costs of BE screening. We examined the feasibility of training PEs to independently perform transnasal esophagoscopy (TNE) and screen patients for BE and measured their learning curve. METHODS: Two PEs at a Veterans Affairs (VA) medical center underwent a structured didactic training program and observed nasopharyngoscopies before performing TNE under the supervision of attending endoscopists. Individual technical and cognitive components of TNE were rated on a 9-point structured scale. Learning curves were constructed using cumulative summation. Once the PEs were judged to be technically competent, each PE performed 10 independent videotaped TNEs, which were graded. RESULTS: Both PEs identified anatomic landmarks after 18 consecutive procedures. PE1 and PE2 performed satisfactory nasal intubations after 20 and 25 procedures and esophageal intubations after 29 and 35 procedures, respectively. They acquired overall competence after supervised training on 43 and 47 procedures, respectively. CONCLUSIONS: We developed a program at a VA medical center to train PEs to perform TNE to screen for BE. The PEs were able to perform TNE and recognize esophageal landmarks independently after a modest number of supervised procedures.

Comparative acceptability of transnasal esophagoscopy and esophageal capsule esophagoscopy: a randomized, controlled trial in veterans.

BACKGROUND: EGD screening for Barrett's esophagus (BE) is costly, with insufficient evidence to support its effectiveness. OBJECTIVE: To compare acceptance and tolerability of 2 novel, office-based, endoscopic screening techniques done on nonsedated patients. DESIGN: Randomized block study design with allocation concealment. SETTING: Outpatient clinic setting at a Veterans Affairs medical center. PATIENTS: A total of 184 veterans with or without GERD symptoms. INTERVENTIONS: Transnasal esophagoscopy (TNE) or esophageal capsule esophagoscopy (ECE). MAIN OUTCOME MEASUREMENTS: Acceptance and tolerability of TNE and ECE and effectiveness of BE screening. RESULTS: Esophageal screening was accepted by 184 of 1210 (15.2%) veterans. The majority were men (96%) and African American (58%), with a mean (± standard deviation) age of 58.9 (± 8.1) years. Five TNE participants (5%) and 2 ECE participants (2%) refused the assigned procedure after randomization (P = .25). Eleven patients (12.6%) randomized to TNE crossed the minimal clinically important threshold for overall procedure tolerability, as opposed to no patients randomized to ECE (P = .001). Effectiveness of BE screening was not significantly different in both procedures (TNE vs ECE = 3.2% vs 5.4%; P = .47). Overall, BE was present in 8 of 75 white participants (10.6%) and in 0 of 107 African American participants (P < .001). LIMITATIONS: The general veteran population may not reflect the screening population for BE. CONCLUSION: Despite a small proportion of veterans expressing interest in esophageal screening, both TNE and ECE were feasible in the outpatient clinic setting and were accepted by >95% of participants who did express an interest. Screening was effective only in white participants. Moderate differences in tolerability between TNE and ECE notwithstanding, cost considerations along with availability of equipment and trained personnel should guide the modality to be used for BE screening.

Association of insulin and insulin-like growth factors with Barrett's oesophagus.

BACKGROUND: It is postulated that high serum levels of insulin and insulin growth factor 1 (IGF-1) mediate obesity-associated carcinogenesis. The relationship of insulin, IGF-1 and IGF binding proteins (IGFBP) with Barrett's oesophagus (BO) has not been well examined. METHODS: Serum levels of insulin and IGFBPs in patients with BO were compared with two separate control groups: subjects with gastro-oesophageal reflux disease (GORD) and screening colonoscopy controls. Fasting insulin, IGF-1 and IGFBPs were assayed in the serum of BO cases (n = 135), GORD (n = 135) and screening colonoscopy (n = 932) controls recruited prospectively at two academic hospitals. Logistic regression was used to estimate the risk of BO. RESULTS: Patients in the highest tertile of serum insulin levels had an increased risk of BO compared with colonoscopy controls (adjusted OR 2.02, 95% CI 1.15 to 3.54) but not compared with GORD controls (adjusted OR 1.55, 95% CI 0.76 to 3.15). Serum IGF-1 levels in the highest tertile were associated with an increased risk of BO (adjusted OR 4.05, 95% CI 2.01 to 8.17) compared with the screening colonoscopy control group but were not significantly different from the GORD control group (adjusted OR 0.57, 95% CI 0.27 to 1.17). IGFBP-1 levels in the highest tertile were inversely associated with a risk of BO in comparison with the screening colonoscopy controls (adjusted OR 0.11, 95% CI 0.05 to 0.24) but were not significantly different from the GORD control group (adjusted OR 1.04, 95% CI 0.49 to 2.16). IGFBP-3 levels in the highest tertile were inversely associated with the risk of BO compared with the GORD controls (OR 0.36, 95% CI 0.16 to 0.81) and also when compared with the colonoscopy controls (OR 0.40, 95% CI 0.20 to 0.79). CONCLUSIONS: These results provide support for the hypothesis that the insulin/IGF signalling pathways have a role in the development of BO.