Citations

INTRODUCTION: There is still controversy surrounding the use of symptoms, history, and tests for diagnosis of rectal evacuation disorders (RED) and slow transit constipation (STC). We performed a comprehensive literature-based analysis to ascertain pooled prevalence, sensitivity (SN), specificity (SP), and likelihood ratios (LR) for clinical parameters to determine pre- and post-test probabilities of diagnosing RED and STC without RED. METHODS: Using MEDLINE and PUBMED, we examined systematic and clinical reviews, meta-analyses, primers, guidelines, and consensus statements since 1999 to determine the diagnostic utility of history, symptoms, and testing for RED and STC. Studies were included if binary data were available to assess true/false positives or negatives to pool and calculate SN/SP/LR. Given there are no “gold standard” diagnostic criteria for RED or STC, designation of “true” RED or STC was based on confirmation by at least one objective anorectal or colonic transit test. Controls varied across studies; all had normal anorectal and/or transit tests by the specific protocol used in each study. We assessed STC alone (associated with normal anorectal testing). RESULTS: We reviewed 97 articles involving studies from many different countries, and 63 articles for RED and 61 articles for STC met inclusion/exclusion criteria. The prevalence of disease phenotypes among 4160 patients with chronic constipation based on objective testing was RED alone 23.3%, normal transit constipation (NTC) alone 31.9%, STC alone 16.2%, and RED + STC 14.3%. To diagnose RED (Figure 1, Table 1), the most clinically significant symptoms included hard/lumpy stools (+LR 269.6, n = 1583) and urinary symptoms (100% specificity, n = 58). The strongest digital rectal exam (DRE) findings were poor anal relaxation (+LR 5.3, n = 529) or increased anal squeeze (+LR 8.4, n = 395). The most predictive anorectal tests were balloon expulsion time >120 s (+LR 5.5, n = 551) and rectoanal pressure gradient < −40 mmHg with high anal pressure on straining on anorectal manometry (100% specificity, n = 101). For STC alone, the most predictive symptom was a call to stool (+LR 10.5, n = 75). Patients without abdominal distension/fullness/bloating were less likely to have RED (−LR 0.2, n = 324) or STC alone (−LR 0.2, n = 93). CONCLUSION: Symptom assessments and DREs are critical in the evaluation for RED and STC. RED is highly prevalent in patients presenting with chronic idiopathic constipation.

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.

The overall objectives of this review are to summarize actionable biomarkers for organic etiology of lower functional gastrointestinal disorders (FGIDs) that lead to individualized treatment for their FGIDs and to assess the pipeline for novel approaches to the management of constipation, diarrhea, and chronic abdominal pain in lower FGIDs. The new approaches to therapy include ion exchangers/transporters for functional constipation (sodium-glucose cotransporter 1, Na+/H+ exchanger 3, and solute carrier family 26 member 3 inhibitors), bile acid modulators for constipation such as ileal bile acid transporter inhibitors and fibroblast growth factor 19 analog for functional constipation, and bile acid sequestrants or farnesoid X receptor agonists for functional diarrhea. Treatment for chronic abdominal pain remains an unmet need in patients with lower FGIDs, and promising novel approaches include delayed-release linaclotide, nonclassical opioid visceral analgesics, and selective cannabinoid receptor agonists. The role of probiotics, fecal microbial transplantation, and possible future microbiome therapies is discussed.

AbstractBackgroundNon‐ulcer dyspepsia (NUD) is a heterogeneous disorder, which is characterized by upper gastrointestinal symptoms and sensorimotor disturbances, including abnormal gastric emptying (GE) and increased intestinal chemosensitivity, and associated with greater plasma glucagon‐like peptide‐1 (GLP‐1) levels during duodenal lipid infusion. However, the relationship(s) between these disturbances and daily symptoms in NUD is variable. We hypothesize that abnormal GE and symptoms during a GE study and during duodenal lipid infusion are associated with the severity of daily symptoms and that GLP‐1 mediates symptoms during duodenal lipid infusion in NUD.MethodsGastric emptying of solids, symptoms during the GE study and duodenal lipid infusion, and daily gastrointestinal symptoms (2 week diary) were measured in 24 healthy controls and 40 NUD patients. During duodenal lipid infusion, participants received the GLP‐1 antagonist exendin 9‐39 or placebo.Key ResultsIn controls and patients, GE of solids was normal in 75% and 75%, delayed in 8% and 12.5%, or rapid in 17% and 12.5%, respectively. No controls but 26 patients (65%) had severe symptoms during the GE study. During lipid infusion, gastrointestinal symptoms were greater (P = .001) in patients and not affected by exendin. Symptoms during GE study and lipid infusion accounted for respectively 62% and 37% of variance in daily symptom severity.ConclusionsIn NUD, symptoms during a GE study and to a lesser extent during lipid infusion explain the variance in daily symptoms. Intestinal chemosensitivity is not reduced by GLP‐1 antagonist. Assessment of symptoms during a GE study may provide a useful biomarker for NUD in research and clinical practice.

Summary Background Due to the paucity of targeted therapy for irritable bowel syndrome (IBS), many patients turn to dietary modifications for symptom management. The combination of five subgroups of poorly absorbed and rapidly fermented carbohydrates—fructans, galacto‐oligosaccharides, lactose, excess fructose and polyols—are thought to trigger gastrointestinal symptoms and are referred to collectively as “FODMAPs”. Aims To examine the biological plausibility and mechanisms by which foods high in specific FODMAP subgroups cause symptoms, and to use this information to explore the possibility of targeting select dietary components to allow for a more personalised approach to dietary adjustment Methods Recent literature was analysed via search databases including Medline, PubMed and Scopus. Results Lactose, fructans and galacto‐oligosaccharides have strong biologic plausibility for symptom generation due to lack of hydrolases resulting in distention from osmosis and rapid fermentation. However, excess fructose and polyols may only cause symptoms in specific individuals when consumed in high doses, but this remains to be established. There is evidence to suggest that certain patient characteristics such as ethnicity may predict response to lactose, but differentiation of other subgroups is difficult prior to dietary manipulation. Conclusions While some clear mechanisms of action for symptom generation have been established, further research is needed to understand which patients will respond to specific FODMAP subgroup restriction. We suggest that clinicians consider in some patients a tailored, personalised “bottom‐up” approach to the low‐FODMAP diet, such as dietary restriction relevant to the patients’ ethnicity, symptom profile and usual dietary intake.

A reduction in intestinal barrier function is currently believed to play an important role in pathogenesis of many diseases, as it facilitates passage of injurious factors such as lipopolysaccharide, peptidoglycan, whole bacteria, and other toxins to traverse the barrier to damage the intestine or enter the portal circulation. Currently available evidence in animal models and in vitro systems has shown that certain dietary interventions can be used to reinforce the intestinal barrier to prevent the development of disease. The relevance of these studies to human health is unknown. Herein, we define the components of the intestinal barrier, review available modalities to assess its structure and function in humans, and review the available evidence in model systems or perturbations in humans that diet can be used to fortify intestinal barrier function. Acknowledging the technical challenges and the present gaps in knowledge, we provide a conceptual framework by which evidence could be developed to support the notion that diet can reinforce human intestinal barrier function to restore normal function and potentially reduce the risk for disease. Such evidence would provide information on the development of healthier diets and serve to provide a framework by which federal agencies such as the US Food and Drug Administration can evaluate evidence linking diet with normal human structure/function claims focused on reducing risk of disease in the general public.