Impact of Bile Acid Diarrhea in Patients With Diarrhea-Predominant Irritable Bowel Syndrome on Symptoms and Quality of Life.

BACKGROUND & AIMS: Bile acid diarrhea (BAD) affects approximately a quarter of patients with irritable bowel syndrome with diarrhea (IBS-D). We aimed to compare the demographics, bowel and somatic symptoms, and quality of life of patients with IBS-D, with or without BAD. METHODS: On one occasion, patients with IBS-D (positive for Rome III criteria) completed the following questionnaires: bowel disease questionnaire, Hospital Anxiety and Depression inventory, general quality of life (Symptom Checklist-90), and IBS-specific quality of life. A fasting serum C4 level higher than 52.5 ng/mL was used as a biomarker for BAD. Statistical analysis included a multiple variable logistic model to identify strong predictors of BAD in IBS-D. RESULTS: Among 219 patients (79% female) with IBS-D, 44 had BAD; the BAD group was significantly older and had a higher body mass index than the patients without BAD. Patients with BAD had more severe bowel dysfunction and impact on IBS-specific quality of life (need of toilet proximity) compared with patients with IBS-D without BAD. Patients with BAD were more likely than other IBS-D groups to receive antidiarrheals, bile acid binders, and antacid secretory agents. The severity of diarrhea and need of toilet proximity were predictors of BAD in IBS-D (P < .01). Patients with BAD were more likely to have a depression score higher than 8 on the Hospital Anxiety and Depression inventory. CONCLUSIONS: There is a greater impact on bowel and somatic symptoms and quality of life in IBS-D with BAD compared with IBS-D without BAD. Screening for BAD in IBS-D is especially relevant, with more severe and frequent diarrhea along with urgency.

Secretin effects on gastric functions, hormones and symptoms in functional dyspepsia and health: randomized crossover trial.

Abnormal gastric accommodation (GA) and gastric emptying contribute to pathophysiology in functional dyspepsia (FD). Secretin is a key regulator of GA in animal studies. Our aim was to study the effects of secretin on gastric motility, satiation, postprandial symptoms, and key hormones. We performed two double-blind, randomized, saline-controlled crossover trials in 10 healthy volunteers and 10 patients with FD by Rome IV criteria. We used measured GA (by validated SPECT method) after a 111In radiolabeled Ensure 300-mL meal and quantified gastric emptying for 30 min by scintigraphy. Satiation was measured by volume to fullness (VTF) and maximum tolerated volume (MTV) on an Ensure nutrient drink test and postprandial symptoms 30 min post-MTV. Fasting and postprandial GLP-1, GIP, and HPP were measured. The ages and sex distribution of healthy controls and patients with FD were similar. Compared with placebo, secretin delayed gastric emptying at 30 min in both health [-11% (-16, -4), P = 0.004]; and FD [-8% (-9, 0), P = 0.03]. Satiation (VTF and MTV), GA, and plasma levels of GLP-1, GIP, and HPP did not differ between treatment arms in health or FD. On ANCOVA analysis (adjusting for age and sex), secretin did not consistently increase postprandial symptoms in health or FD. Secretin delayed gastric emptying in both health and FD without significantly altering GA, VTF, or MTV or selected hormones. Thus, secretin receptor activation may provide a novel therapeutic mechanism for patients with FD and rapid gastric emptying.NEW & NOTEWORTHY The naturally occurring hormone secretin retards gastric emptying of solids without deleteriously affecting gastric accommodation, satiation, other upper gastrointestinal hormones, or postprandial symptoms. Given these findings, a subset of patients with rapid gastric emptying (e.g., the estimated 20% of patients with functional dyspepsia) could be candidates for treatments that stimulate a secretin receptor such as sacubitril, which inhibits neprilysin, an enzyme that degrades secretin.

Pretest and Post-test Probabilities of Diagnoses of Rectal Evacuation Disorders Based on Symptoms, Rectal Exam, and Basic Tests: a Systematic Review.

BACKGROUND & AIMS: There is controversy over the utility of symptoms, examination, and tests for diagnosis of rectal evacuation disorders (REDs) or slow-transit constipation (STC). We aimed to ascertain the pooled prevalence, sensitivity, specificity, and likelihood ratios for clinical parameters to determine pretest and post-test probabilities of diagnoses of RED and STC without RED. METHODS: We searched the MEDLINE and PUBMED databases since 1999 for studies that used binary data to calculate sensitivity, specificity, and likelihood ratios to determine the diagnostic utility of history, symptoms, and tests for RED and STC. RED and STC were defined based on confirmation by at least 1 objective anorectal test or colonic transit test. Controls had normal test results based on the specific protocol in each study. RESULTS: We reviewed 100 articles; 63 studies of RED and 61 studies of STC met the inclusion criteria. Among 3364 patients with chronic constipation, objective tests demonstrated RED alone, 27.2%; normal transit constipation alone, 37.2%; STC alone, 19.0%; and RED with STC, 16.6%. To diagnose RED, discriminant features were urinary symptoms (specificity, 100%; likelihood ratio, above 10; 58 patients), less than 2 findings of dyssynergia in a digital rectal exam (sensitivity, 83.2%; negative likelihood ratio, 0.2; 462 patients) and rectoanal pressure gradient below -40 mm Hg with high anal pressure during straining (specificity, 100%; likelihood ratio, above 10; 101 patients). The features most strongly associated with STC alone were call to stool (specificity, 91.5%; likelihood ratio, 10.5; 75 patients) and absence of abdominal distension, fullness, or bloating (sensitivity, 92.9%; negative likelihood ratio, 0.1; 93 patients). CONCLUSIONS: In a systematic review, we found specific symptoms, lack of dyssynergia in a digital rectal exam, and findings on anorectal manometry to be highly informative and critical in evaluation of RED and STC.

Colonic Manifestations and Complications Are Relatively Under-Reported in Systemic Sclerosis: A Systematic Review.

OBJECTIVES: Although systemic sclerosis (SSc) is known to affect the gastrointestinal (GI) tract, most of the literature focuses on esophageal, small intestinal, or anorectal manifestations. There have been no reviews focused on large bowel SSc complications in over 30 years. The aim of this study is to perform a systematic review of colonic manifestations and complications of SSc. METHODS: An experienced librarian conducted a search of databases, including English and Spanish articles. The search used keywords including "systemic sclerosis," "scleroderma," and "colon." A systematic review was performed using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Case reports/series were screened for validity by adapting from criteria published elsewhere. RESULTS: Of 1,890 articles, 74 met selection criteria. Fifty-nine of the 77 articles were case reports/series. The most common article topics on colonic SSc complications were constipation/dysmotility (15), colonic volvulus (8), inflammatory bowel disease (7), microscopic colitis (6), megacolon (6), and telangiectasia (6). Colonic manifestations constituted 24% of articles on GI complications of SSc. There were a total of 85 cases (84% women, with a median age of onset of colon complication of 52 years). Limited cutaneous SSc phenotype (65.6%) was more common than diffuse (26.2%). Patients frequently had poor outcomes with high mortality related to colonic complications (27%). Recent studies explore contemporary topics such as the microbiome in SSc and prucalopride for chronic constipation in SSc. DISCUSSION: Colonic complications comprise a large proportion of the published reports on GI symptoms afflicting patients with SSc and require raised diagnostic suspicion and deliberate action to avoid potentially serious complications including death.

Characterization of Upper Gastrointestinal Symptoms, Gastric Motor Functions, and Associations in Patients with Diabetes at a Referral Center.

OBJECTIVES: Our aim was to characterize upper gastrointestinal (UGI) symptoms and associations in individuals with diabetes mellitus (DM) who had undergone evaluation of gastric emptying (GE) and accommodation (GA) at a referral center. METHODS: From the Mayo Clinic Rochester electronic medical records of adults with diabetes types 1 and 2 (DM1 and DM2) evaluated between January 1997 and December 2015, we extracted demographics, UGI symptoms, current medications, treatments for diabetes, GE solids by scintigraphy, GA by single photon emission computed tomography (SPECT), and diabetes complications. We compared subgroups with delayed (GE at 2 h <25% or GE at 4 h <75%), rapid (GE at 1 h > 35%), and normal GE, as well as reduced (<428 mL) and normal GA. RESULTS: We reviewed 108 patients (60.2% females, median age 49.0 years). Overall, 71.3% had DM2; one-third of these were insulin dependent and had fairly well-controlled diabetes (median HbA1c 6.7% (IQR 6.2; 7.9)). Manifestations of diabetic triopathy (peripheral neuropathy, nephropathy, and retinopathy) were uncommon at presentation with UGI symptoms. Nausea was the most common symptom (80.6%). There were single or combined GE (total 56%: rapid in 37%, slow in 19%) and GA (total 39%) abnormalities; there was normal GA and GE in 28%; 40.3% of the DM2 patients had accelerated GE at 1 h. GE at 1 h is associated with nausea/vomiting, and fasting gastric volume is associated with bloating. CONCLUSIONS: Among referred diabetic patients with UGI symptoms, GE and GA testing identifies potential targets for individualizing treatment and avoidance of empirical trials for the 28% with no disturbance of GE and GA.

Efficacy of Over-the-Scope Clips in Management of High-Risk Gastrointestinal Bleeding.

BACKGROUND & AIMS: Standard endoscopic therapies do not control bleeding or produce complications in as many as 20% of patients with nonvariceal gastrointestinal bleeding. Most bleeding comes from ulcers with characteristics such as high-risk vascular territories and/or large vessels. We evaluated the efficacy of using over-the-scope clips (OTSCs) as primary or rescue therapy for patients with bleeding from lesions that have a high risk for adverse outcomes. METHODS: We performed a retrospective analysis of data from 67 patients with gastrointestinal bleeding from high-risk lesions who were treated with OTSCs as primary (n = 49) or rescue therapy (n = 18) at a quaternary center, from December 2011 through February 2015. The definition of high-risk lesions was lesions that were situated in the area of a major artery and larger than 2 mm in diameter and/or a deep penetrating, excavated, fibrotic ulcer with high-risk stigmata, in which a perforation could not be ruled out or thermal therapy would cause perforation, or lesions that could not be treated by standard endoscopy. Clinical severity was determined based on the Rockall score and a modified Blatchford score. Our primary outcome was the incidence of rebleeding within 30 days after OTSC placement. We assessed risk factors for rebleeding using univariate hazard models followed by multivariable analysis. RESULTS: Of the 67 patients, 47 (70.1%) remained free of rebleeding at 30 days after OTSC placement. We found no difference in the proportion of patients with rebleeding who received primary or rescue therapy (hazard ratio, 0.639; 95% confidence interval, 0.084-4.860; P = .6653). Only 9 rebleeding events were linked clearly to OTSCs and required intervention, indicating an OTSC success rate of 81.3%. We found no significant associations between rebleeding and clinical scores. However, on multivariable analysis, patients with coronary artery disease had a higher risk of rebleeding after OTSC independent of international normalized ratio and antiplatelet use (hazard ratio, 7.30; P = .0002). CONCLUSIONS: In a retrospective analysis of 67 patients with bleeding from high-risk gastrointestinal lesions, we found OTSCs to prevent rebleeding in more than 80% of cases. In the past, these lesions were treated with surgical or radiologic interventions. Patients with coronary artery disease have an increased risk of rebleeding after OTSCs, suggesting the need for escalated therapies.

Randomised study: effects of the 5-HT4 receptor agonist felcisetrag vs placebo on gut transit in patients with gastroparesis.

BACKGROUND: Gastroparesis is defined by delayed gastric emptying with associated symptoms in the absence of mechanical obstruction. AIM: To evaluate pharmacokinetics and pharmacodynamics of felcisetrag, a highly selective 5-HT4 receptor agonist, on total gut transit in patients with documented delayed gastric emptying of solids. METHODS: Single-centre, placebo-controlled study of 36 participants receiving placebo, 0.1mg, 0.3mg or 1.0mg of felcisetrag I.V. infusion, daily, for 3 days. At baseline, each participant completed a 4h, 99m Tc-egg meal (300 kcal, 30% fat) gastric emptying test. Following infusion (Day 2), gastric, small bowel and colonic transit of solids were measured over 48h (same meal plus 111 In-charcoal delivered in methacrylate-coated capsule). Samples were collected for pharmacokinetics. The primary endpoint was gastric emptying T1/2 . Statistical analysis used baseline parameters as covariates (ANCOVA). RESULTS: Patients (22 idiopathic, 14 diabetic gastroparesis) were randomised to felcisetrag (0.1 mg, n = 10; 0.3 mg, n = 9; 1.0 mg, n = 7) or placebo (n = 10). Compared to placebo, felcisetrag significantly accelerated gastric emptying T1/2 , colonic filling at 6h, and 10% small bowel transit time (overall P < 0.01; all three doses individually Bonferroni corrected P < 0.05) for all three measurements. Ascending colon emptying (T1/2 ) was significantly accelerated (all doses), and colonic transit at 48 hours was accelerated with 0.1 mg and 0.3 mg felcisetrag compared to placebo. Pharmacokinetic results were dose proportional. Felcisetrag was well tolerated with no clinically significant findings from clinical laboratory, vital signs or ECG. CONCLUSION: I.V. felcisetrag significantly accelerated gastric, small bowel and colonic transit in patients with gastroparesis, and should be further evaluated for short-term treatment of gastric and intestinal motility disorders. ClinicalTrials.gov #NCT03281577.

Refractory Constipation: How to Evaluate and Treat.

Patients are often referred for treatment of refractory constipation that may result from uncontrolled underlying disease or ineffective treatment. This article reviews clinical testing in patients with refractory constipation, differentiating subtypes of primary chronic idiopathic constipation, and common pitfalls in assessment of refractory chronic constipation. The constipation may also be refractory because of significant associated diseases affecting the colon and resulting in slow transit constipation. The choice of therapy is best guided by the subtype. Management of refractory constipation requires correct diagnosis and individualized treatment, which may rarely include conservative surgery (loop ileostomy).

Gastric accommodation measurements by single photon emission computed tomography and two-dimensional scintigraphy in diabetic patients with upper gastrointestinal symptoms.

OBJECTIVE: To compare estimates of gastric accommodation (GA) with single photon emission computed tomography (SPECT) to measurements based on intragastric meal distribution immediately post-meal ingestion (IMD0 ). METHODS: We evaluated 108 diabetics with upper gastrointestinal (UGI) symptoms who had undergone gastric emptying of solids (GE) by scintigraphy and GA measurements by SPECT. Immediately after ingestion of a 99m Tc-labeled egg meal (time 0), we estimated IMD0 as radioactive counts or area of the proximal half of the stomach on two-dimensional images. Gastric volume (GV) during fasting and after 300 mL Ensure® was measured by SPECT to quantify accommodation volume (AV) or postprandial to fasting volume ratio (GVR). From the measured proximal gastric area, we estimated the volume of proximal stomach (4/3 × π × r3 ). We performed regression analyses to assess relationships between IMD0 and GA (AV) and GVR. RESULTS: There was a significant correlation between area and radioactivity counts in the proximal stomach (r = 0.67, P < 0.001); however, there was considerable interpersonal variation [bias 0.20 (95% CI -0.07, 0.47)]. There were no significant correlations between total GV or AV or VR by SPECT and measurements using IMD0 : proximal gastric counts, area, and estimated volume as continuous variables of dichotomized patient groups, based on published cutoff values. There were no significant differences in total gastric area or the IMD0 parameters (% area or % radioactive counts) between those with and without UGI symptoms except for fullness and satiety. CONCLUSIONS: Intragastric meal distribution immediately post-meal ingestion is not significantly correlated with GA measurement by SPECT.