Ravi, Karthik

SummaryBackgroundEstimation of the prevalence of oesophageal narrowing and its clinical relevance in patients with oesophageal eosinophilia is probably underestimated by endoscopy.AimsTo determine the sensitivity and specificity of oesophagogastroduodenoscopy (EGD) for oesophageal narrowing when compared to a structured oesophagram.MethodsWe conducted a retrospective chart review at Mayo Clinic, Rochester of adult patients with eosinophilic oesophageal infiltration of >15 eosinophils/hpf with symptomatic dysphagia, who underwent a structured barium oesophagram. The sensitivity and specificity of EGD were evaluated against the gold standard of oesophagram. Demographic and multiple clinical factors were evaluated as potential predictors of oesophageal narrowing.ResultsOf the 58 patients identified, 34 (58.6%) had a narrowed oesophageal diameter (<21 mm). EGD had poor sensitivity (14.7%, 95% CI 5.0–31.1%) for detection of a narrowed oesophagus and only modest specificity (79.2%, 95% CI 57.8–92.9%). Even at a cut‐off diameter of EDmax ≤ 15 mm, EGD had a sensitivity of only 25.0% (95% CI 5.5–57.2%) for narrowed oesophagus. A history of >5 food impaction episodes, endoscopic rings, and female sex were the best predictors of oesophageal narrowing. 86% (6/7) patients with persistent dysphagia despite remission of histological eosinophilia responded to oesophageal dilation all of whom had radiological oesophageal narrowing and 71% of whom had no perceived oesophageal narrowing at EGD.ConclusionsSymptomatic oesophageal narrowing identified by barium oesophagography is common and under‐recognised at endoscopy in patients with oesophageal eosinophilia.

Although in vitro studies show that muscarinic M3receptors primarily mediate the effects of acetylcholine on gastrointestinal contractility, the muscarinic receptor subtypes regulating gastrointestinal motor activity and transit in humans in vivo are unclear. We hypothesized that muscarinic M3-specific but not nonspecific receptor antagonists would delay gastrointestinal and colonic transit in humans. In this parallel-group study, gastric emptying, small intestinal transit, and colonic transit were assessed by scintigraphy on days 4- 6 in 72 healthy subjects (49 women) who received placebo ( n = 16), the M3antagonist darifenacin ER [7.5 mg ( n = 20) or 15 mg daily ( n = 17)], or the nonspecific antagonist tolterodine [4 mg daily ( n = 19)] for 6 days. Bowel habits were recorded by daily diaries. Both doses of darifenacin substantially delayed [ P < 0.01 vs. placebo (for both doses), P < 0.01 vs. tolterodine (for 15 mg)] small intestinal transit, i.e., colonic filling at 6 h (placebo [59.6 ± 6.4%, mean ± SE], 7.5 mg ER [34.4 ± 6.1%], 15 mg ER [20.4 ± 6.3%)]. Darifenacin (15 mg) also delayed ( P < 0.01 vs. placebo and tolterodine) half-time for ascending colonic emptying [placebo (12.0 ± 1.5 h), 7.5 mg (18.6 ± 1.9 h), 15 mg (22.9 ± 2.6 h)] and colonic transit (geometric center) at 24 [placebo (2.8 ± 0.2), 7.5 mg (2.4 ± 0.2), 15 mg (1.9 ± 0.2)] but not 48 h. Darifenacin did not affect gastric emptying and tolterodine did not affect bowel habits or gastrointestinal transit. With muscarinic antagonists used at clinically approved doses, these findings demonstrate that muscarinic M3receptors regulate small intestinal and colonic transit in humans; colonic effects are more pronounced in the right than left colon. At doses that affect small and large intestinal transit, M3antagonists do not affect gastric emptying in humans. The efficacy of darifenacin in diarrhea-predominant irritable bowel syndrome should be evaluated.