Andrews, Christopher N.

Summary Background Medications can affect gastrointestinal tract motility. However, their effects on oesophageal motility in particular are often not as widely known or may be underestimated. Aim To review the effect of existing medication use on high‐resolution oesophageal manometry (HRM) in a ‘real‐world’ setting. Methods Adult patients with upper gut symptoms and normal endoscopy or imaging who had HRM over a 22‐month period were analysed. Achalasia and major disorders of peristalsis were excluded. All medications taken within 24 hours of the procedure were prospectively recorded and compared with HRM results, controlling for age, gender and proton pump inhibitor use. Results A total of 502 patients (323 female, mean age 51) were recruited. Of these, 41.2% had normal oesophageal HRM, while 41.4% had ineffective oesophageal motility (IOM) and 7.6% had oesophagogastric junction outflow obstruction (OGJOO). Serotonin/norepinephrine reuptake inhibitors (SNRI) and opioids were associated with significantly higher resting lower oesophageal sphincter pressure. Benzodiazepines and opioids were associated with elevated integrated relaxation pressure. SNRI and inhaled beta‐agonists were associated with increased distal contractile index, whereas calcium channel blockers were associated with a lower distal contractile index. Odds ratio of being on anticholinergics was higher in IOM patients vs normal (3.6, CI 1.2‐10.8). Odds ratio for anticholinergics, inhaled beta‐agonists, anticonvulsants, SNRIs and opioids (trend) were all > 3 for OGJOO patients vs normal. Conclusion Many medication classes are associated with abnormal HRM variables and diagnoses such as OGJOO and IOM; some of these associations are probably causal. These possible links should be taken into consideration during manometry interpretation.

Abstract Background While motility disorders may evolve over time, there is scant guidance around the role of repeat high-resolution esophageal manometry (HRM). Given the invasive nature of HRM and the implications on financial cost and patient discomfort, it is obvious that the emphasis should be on minimizing unnecessary repeat examinations. However, there are no recommendations around indications or timing of repeat HRM. Aims We aimed to determine the outcomes in patients who underwent repeat manometry and look for predictors of progression to achalasia or major motility disorder. Methods Consecutive reports from HRM studies performed between Aug 2013 – May 2017 were retrospectively analyzed. All patients with ≥ 2 HRM studies were included. Studies without a Chicago classification diagnosis were excluded. Chi-squared analysis was performed to determine if initial HRM diagnosis was associated with change in diagnosis on follow-up HRM. Initial and follow-up manometric parameters were compared with paired T-tests. Binary logistic regression analysis was performed to look for predictors of progression to achalasia or major motility disorder. Results 134 patients underwent ≥ 2 HRM studies. Initial diagnoses were IEM (45 patients [33.6%], EGJOO (34 [25.4%], absent peristalsis (18 [13.4%], achalasia (11 [8.2%], DES (4 [3.0%]), and JH (3 [2.2%]; 29 (14.2%) of patients had a normal HRM. 109 (81.3%) patients underwent 2 HRM, 18 (13.4%) 3 HRM, 4 (3%) 4 HRM, and 3 (2.2%) 5 HRM. The final follow-up HRM occurred after a median 496 [80 – 1823] days. 72 (53.7%) of patients had no change from their initial diagnosis. Patients with an initial diagnosis of DES were significantly more likely to have a change in diagnosis on the final follow-up (3 normal:1 IEM) (p = .043). No other classes reached significance. Patients with IEM had a significantly higher mean DCI (395.1 [0 - 3248] vs 790.8 [0 – 10715.0], p = .006) and IRP (4.5 [-10.4 – 14.2] vs [6.6 [-6.2 – 21.0], p = .017) on their follow-up HRM. 4 patients without achalasia (3 EGJOO:1 IEM) on their index HRM had a diagnosis of achalasia on their final HRM. The median IRP in non-achalasia patients with a diagnosis of achalasia on final HRM (22.3 [8.4 – 30.7] was significantly higher than those without a diagnosis of achalasia on final HRM (6.6 [-10.4 – 39.8]) (p = .013); however no manometric criteria or initial HRM diagnoses predicted progression to achalasia or major motility disorder on binary logistic regression analysis. Conclusions In most patients, repeat manometry did not change the manometric diagnosis. Patients with DES were significantly likely to have their diagnosis change with repeat HRM, and most of these patients had normalization of their HRM. Manometric parameters in IEM appear to improve over time. This finding could reflect interval therapy, or shed some light on the natural history of this disease. Funding Agencies None

Objective Antireflux surgery can be proposed in patients with GORD, especially when proton pump inhibitor (PPI) use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for antireflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for antireflux surgery. Design We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous. Results Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with oesophagitis Los Angeles (LA) grade B or higher and patients with Barrett’s oesophagus are good candidates for antireflux surgery. An endoscopy prior to antireflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short oesophagus. Oesophageal manometry is mandatory to rule out major motility disorders. Finally, oesophageal pH (±impedance) monitoring of PPI is mandatory to select patients for antireflux surgery, if endoscopy is negative for unequivocal reflux oesophagitis. Conclusion With the ICARUS guidelines, we generated key recommendations for selection of patients for antireflux surgery.

OBJECTIVES: Prokinetics are recommended for the treatment of functional dyspepsia (FD) but systematic reviews give conflicting results on the efficacy of these agents. We have therefore conducted an updated systematic review to support the 2017 joint ACG/CAG dyspepsia guidelines. METHODS: Electronic databases, including MEDLINE, EMBASE, and CENTRAL, were searched until September 2017 for randomized controlled trials (RCTs) comparing either prokinetics and placebo or two types of prokinetics to improve FD symptoms. The primary outcome was absence or improvement of dyspeptic symptoms at the end of treatment. Double-blind eligibility assessment and data extraction was performed. Pooled risk ratios of symptoms persisting or adverse events occurring, and standardized mean difference of quality-of-life (QoL) scores with 95% CI, using a random effects model, were calculated. Quality of evidence was assessed using GRADE. RESULTS: The search identified 1388 citations; 38 studies in 35 papers were included. Of these, 29 trials comparing prokinetics with placebo were found. There was a statistically significant effect of prokinetic treatment in reducing global symptoms of FD (RR 0.81, 95% CI 0.74 to 0.89; I 2 91%; NNT 7), regardless of FD subtype or ethnicity. When comparing two types of prokinetic, the most commonly used comparator was domperidone. There was no difference in reducing global symptoms (RR 0.94, 95% CI 0.83 to 1.07). QoL was not improved with prokinetic treatment. The adverse events with individual prokinetics were not different from placebo, except for cisapride. The GRADE assessment rated the quality of the evidence in each outcome as very low. CONCLUSIONS: From the current evidence, prokinetics may be effective for the treatment in all subtypes of FD, with very low quality of evidence. There was no difference between prokinetics for dyspeptic symptom improvement. High-quality RCTs with large sample sizes of FD patients are needed to verify the efficacy of prokinetics.

Not so long ago, physicians construed the irritable bowel syndrome (IBS) as being a neurotic trait: it was all in the head. Today most clinicians believe that the main abnormality lies in the brain (and spinal cord), which reacts abnormally to stimuli from the gut. Recent studies are identifying a basis for these neural changes - low grade inflammation in the gut - which may play a key role in IBS.

BACKGROUND: It is not clear if starting intravenous proton pump inhibitors (IV PPI) before endoscopic therapy provides additional benefit over starting it afterward in patients with high-risk ulcer stigmata of peptic ulcer disease.METHODS: All patients who received IV pantoprazole bolus and infusion and underwent endoscopy in six Canadian hospitals over 20 months were reviewed. Only patients with high-risk ulcer stigmata (arterial bleeding, oozing, nonbleeding visible vessel or adherent clot) were included. Patients receiving IV PPI before endoscopy (before group) were compared with those who received it after endoscopy (after group) with respect to endoscopic findings and, secondarily, to patient demographics and clinical outcomes.RESULTS: The demographics and baseline characteristics of the before group (n=57) and the after group (n=109) were similar. The before group was more likely to have had IV PPI started outside of daytime hours, and median time to endoscopy in patients admitted with upper gastrointestinal bleeding was 24 h (interquartile range 9.5 to 35) in the before group and 11.3 h (interquartile range 3.7 to 17.2) in the after group ( P<0.0001). At the time of endoscopy, 33% of patients in the before group had actively bleeding lesions (Forrest 1a or 1b) compared with 54% in the after group (P=0.01), but there were no significant differences in rebleeding, surgical rates, intensive care unit admission or death between the groups.CONCLUSION: IV PPI infusions before endoscopy may lower the proportion of actively bleeding peptic ulcer lesions at endoscopy, but this finding does not appear to affect rates of rebleeding, surgery or death.

Abstract Background Acetylcholinesterase inhibitors ( ACI s), e.g., neostigmine, are known to increase upper and lower gastrointestinal ( GI ) motility and are used to treat acute colonic pseudoobstruction. However, their effects on gastroduodenal motility in humans are poorly understood. Our hypotheses were that, in patients with suspected GI motility disorders, neostigmine increases gastric and small intestinal motor activity, and these effects are greater in patients with cardiovagal neuropathy, reflecting denervation sensitivity. Methods In this open label study, the effects of neostigmine (1 mg intravenously) on gastroduodenal motor activity recorded with manometry were assessed in 28 patients with a suspected GI motility disorder. Cardiovagal function was assessed with the heart rate response to deep breathing and GI transit by scintigraphy. Key Results The final diagnoses were gastroparesis (6 patients), gastroparesis with intestinal neuropathy (3 patients), intestinal neuropathy or pseudoobstruction (5 patients), functional dyspepsia (6 patients), chronic abdominal pain (3 patients), mechanical small intestinal obstruction (3 patients), and pelvic floor dysfunction (2 patients). Neostigmine increased both antral and intestinal phasic pressure activity ( p < 0.001). Neostigmine increased antral and intestinal pressure activity in 81% and 50% of patients with reduced postprandial antral and intestinal contractile responses to meal, respectively. The antroduodenal pressure response to neostigmine was not higher in patients with cardiovagal dysfunction. Conclusions & Inferences Neostigmine increased antral and intestinal motor activity in patients with hypomotility, including intestinal dysmotility. These responses to neostigmine were not greater in patients with cardiovagal dysfunction. The use of longer‐acting ACI s for treating antroduodenal dysmotility warrant further study.