Bharucha, Adil E.

Abstract Background This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high‐resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. Methods Twenty‐nine working group members (clinicians/academics in the field of gastroenterology, coloproctology, and gastrointestinal physiology) were invited to six face‐to‐face and three remote meetings to derive consensus between 2014 and 2018. Key recommendations The IAPWG protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia. Conclusions and Inferences This framework introduces the IAPWG protocol and the London classification for disorders of anorectal function based on objective physiological measurement. The use of a common language to describe results of diagnostic tests, standard operating procedures, and a consensus classification system is designed to bring much‐needed standardization to these techniques.

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.

Abstract This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus. Up to 50% of patients with type 1 and type 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13C breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i.e., mild to moderate indigestion, with or without a mild delay in GE) or gastroparesis, which is a syndrome characterized by moderate to severe upper gastrointestinal symptoms and delayed GE that suggest, but are not accompanied by, gastric outlet obstruction. Gastroparesis can markedly impair quality of life, and up to 50% of patients have significant anxiety and/or depression. Often the distinction between dyspepsia and gastroparesis is based on clinical judgement rather than established criteria. Hyperglycemia, autonomic neuropathy, and enteric neuromuscular inflammation and injury are implicated in the pathogenesis of delayed GE. Alternatively, there are limited data to suggest that delayed GE may affect glycemic control. The management of diabetic gastroparesis is guided by the severity of symptoms, the magnitude of delayed GE, and the nutritional status. Initial options include dietary modifications, supplemental oral nutrition, and antiemetic and prokinetic medications. Patients with more severe symptoms may require a venting gastrostomy or jejunostomy and/or gastric electrical stimulation. Promising newer therapeutic approaches include ghrelin receptor agonists and selective 5-hydroxytryptamine receptor agonists.

AbstractBackgroundOur aim is to explain the lack of clarity in the ways in which anxiety and depression, which are common in defecatory disorders (DD), may contribute to the disorder. In this study, we evaluate the effects of mental stress and relaxation on anal pressures and the mechanisms thereof.MethodsIn 38 healthy women and 36 DD patients, rectoanal pressures were assessed at rest and during mental stressors (ie, word‐color conflict [Stroop] and mental arithmetic tests) and mental relaxation, before and after randomization to placebo or the adrenergic α1‐antagonist alfuzosin.Key ResultsDuring the baseline Stroop test, the anal pressure increased by 6 ± 13 mm Hg (mean ± SD, P = 0.004) in healthy women and 9 ± 10 mm Hg (P = 0.0001) in constipated women. During mental arithmetic, the anal pressure increased in healthy (4 ± 8 mm Hg, P = 0.002) and constipated women (5 ± 9 mm Hg, P = 0.004). After relaxation, anal pressure declined (P = 0.0004) by 3 ± 4 mm Hg in DD patients but not in controls. Alfuzosin reduced (P = 0.0001) anal resting pressure (by 31 ± 19 mm Hg) vs placebo (16 ± 18 mm Hg). However, during the postdrug Stroop test, anal pressure increased (P = 0.0001) in participants who received alfuzosin but not placebo.Conclusions & InferencesIn healthy controls and DD patients, mental stressors likely increased anal pressure by contracting the internal anal sphincter; relaxation reduced anal pressure in DD patients. Alfuzosin reduced anal resting pressure but did not block the Stroop‐mediated contractile response, which suggests that this response is not entirely mediated by adrenergic α1 receptors.

AbstractBackgroundDuring proctography, rectal emptying is visually estimated by the reduction in rectal area. The correlation between changes in rectal area, which is a surrogate measure of volume, is unclear. Our aims were to compare the change in rectal area and volume during magnetic resonance (MR) proctography and to compare these parameters with rectal balloon expulsion time (BET).MethodsIn 49 healthy and 46 constipated participants, we measured BET and rectal area and volume with a software program before and after participants expelled rectal gel during proctography.Key ResultsAll participants completed both tests; six healthy and 17 constipated patients had a prolonged (>60 seconds) BET. During evacuation, the reduction in rectal area and volume was lower in participants with an abnormal than a normal BET (P < 0.01). The reduction in rectal area and volume were strongly correlated (r = 0.93, P < 0.001) and equivalent for identifying participants with abnormal BET. Among participants with less evacuation, the reduction in rectal area underestimated the reduction in rectal volume. A rectocele larger than 2 cm was observed in eight of 18 (44%) participants in whom the difference between change in volume and area was ˃10% but only 14 of 77 (18%) participants in whom the difference was ≤10% (P = 0.03).ConclusionsMeasured with MR proctography, the rectal area is reasonably accurate for quantifying rectal emptying and equivalent to rectal volume for distinguishing between normal and abnormal BET. When evacuation is reduced, the change in rectal area may underestimate the change in rectal volume.

AbstractBackgroundHigh‐resolution manometry (HRM) is used to measure rectoanal pressures in defecatory disorders and fecal incontinence. This study sought to define normal values for rectoanal HRM, ascertain the effects of age and BMI on rectoanal pressures, and compare pressures in asymptomatic women with normal and prolonged balloon expulsion time (BET).MethodsHigh‐resolution manometry pressures and BET were measured in 163 asymptomatic healthy participants. Women (96) and men (47) with normal BET were used to estimate normal values and the effects of age/BMI on pressures using a Medtronic 4.2‐mm‐diameter rectoanal catheter.Key ResultsAge is associated with lower resting pressure, higher rectal pressure during evacuation, and a higher rectoanal gradient during evacuation in women and men. In women, the BET is also inversely correlated with age while the BMI is correlated with a higher threshold volume for discomfort and a longer BET. The anal squeeze pressure increment, squeeze duration, and HPZ length are higher in men than women. The rectoanal gradient during evacuation is also lower (ie, more negative) in asymptomatic women with an abnormal than a normal BET.Conclusions & InferencesThese findings provide an expanded database of normal values for anorectal HRM in men and women. Age and sex affect anal resting and squeeze pressures, respectively; rectal pressure during evacuation is also higher in older people. Less than 15% of asymptomatic people have BET >60 seconds, which is associated with manometry features of impaired evacuation.

AbstractBackgroundColonic functions (ie, absorption of fluids and electrolytes, digestion of selected nutrients, harbor for microbes, and elimination of excreta) necessitate complex patterns of storage and transit. Indeed, colonic transit accounts for a major part of the mouth‐to‐anus transit time. Colonic transit assessments are useful for understanding the pathophysiology of disease, the pharmacodynamic effects of new medications and to diagnose slow transit constipation. Currently, radiopaque markers, scintigraphy, and a colonic pH‐pressure capsule are used to measure overall colonic transit. Radioopaque markers, scintigraphy, and the electromagnetic capsule, which is a newer technique, also evaluate regional colonic transit. The pH‐pressure capsule also measures colonic pressures. Magnetic resonance imaging and a radio‐frequency identification‐based device are evolving methods for assessing colonic transit.PurposeThis mini‐review, which accompanies a study evaluating the assessment of colon transit with the electromagnetic capsule, evaluates and compares existing and evolving methods for evaluating colonic transit in humans (Neurogastroenterol Motil. 2018; in press). In addition to overall and regional colonic transit, the electromagnetic capsule evaluates colonic motor patterns without radiation exposure. These patterns are summarized by analyzing the characteristics (ie, distance and velocity) of discrete antegrade and retrograde capsule movements as they travel in the colon. However, the electromagnetic capsule does not measure pressure or colonic wall movement (ie, contractions). The motor patterns identified by this capsule should be compared with motor patterns identified with manometry. The next challenge is to harness different techniques to evaluate the relationships between colonic pressures and transit or, even better, the trifecta of colonic contractions, pressure events, and transit.