Hirohito Sano

Defective triggering of secondary peristalsis in patients with non‐erosive reflux disease

Background and Aim:  The pathophysiology of non‐erosive reflux disease is poorly understood. Triggering of secondary peristalsis is impaired in patients with erosive esophagitis but data in patients with non‐erosive reflux disease are lacking. The aim of this study was to evaluate the difference in esophageal motility between patients with non‐erosive reflux disease and healthy subjects.

Efficacy of Vonoprazan for Proton Pump Inhibitor-Resistant Reflux Esophagitis

Background: Vonoprazan (VPZ) is a novel potassium-competitive acid blocker that may be clinically beneficial for proton pump inhibitor (PPI)-resistant reflux esophagitis (RE). The aim of this study was to investigate the efficacies of VPZ therapy at 20 mg for 4 weeks in patients with PPI-resistant RE and VPZ maintenance therapy at 10 mg for 8 weeks in patients who have been successfully treated. Methods: Subjects comprised 24 patients with PPI-resistant RE (Los Angeles classification grade A/B/C/D: 3/7/11/3). After confirming PPI-resistant RE by endoscopy, 20 mg VPZ was administered. Endoscopy was performed 4 weeks after the initiation of VPZ. Symptoms were evaluated using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG). Maintenance therapy with 10 mg VPZ was performed and endoscopy was conducted after 8 weeks. Results: In 21 (87.5%) out of 24 patients, esophageal mucosal breaks were successfully treated by 20 mg VPZ. The median FSSG score was significantly lower on days 1-7, 14, and 28 after the initiation of VPZ than before its administration. Maintenance therapy with 10 mg VPZ prevented the relapse of esophageal mucosal breaks in 16 (76.2%) out of 21 patients. Conclusion: VPZ was effective for most patients with PPI-resistant RE.

Characteristics of symptomatic reflux episodes in patients with non-erosive reflux disease who have a positive symptom index on proton pump inhibitor therapy.

Background and Aim: The reason that some reflux episodes evoke symptoms is poorly understood, therefore the aim of this study is to assess the determinants of reflux perception in patients with non-erosive reflux disease (NERD) on proton pump inhibitor (PPI) therapy. Methods: Ten NERD patients with persistent symptoms, despite double-dose PPI therapy, were included in this study. All patients had a positive symptom index (SI), which was determined by ambulatory 24-hour combined impedance-pH monitoring. Reflux episodes were identified and classified as acid, weakly acidic or weakly alkaline reflux and were considered symptomatic if patients recorded a symptom within 5 min after a reflux episode. Results: A total of 954 liquid reflux episodes were detected, including 135 (14.2%) acid, 782 (82.0%) weakly acidic, and 37 (3.9%) weakly alkaline. Overall, 59 (6.2%) reflux episodes were symptomatic and the majority (88.1%) of symptomatic reflux episodes were weakly acidic reflux. When reflux episodes were confined to the distal esophagus, there were very few reflux symptoms. Proximal reflux is significantly more likely to be associated with reflux symptoms, irrespective of the acidity of the refluxate or the duration of proximal reflux episodes. Conclusions: In NERD patients who have a positive SI on double-dose PPI therapy, the high proximal extent of refluxate is a major factor associated with reflux perception.

The appearance of rosette-like esophageal folds (“esophageal rosette”) in the lower esophagus after a deep inspiration is a characteristic endoscopic finding of primary achalasia

BackgroundIn healthy subjects who inspire deeply the lower esophagus usually opens, and the esophageal palisade vessels (EPVs) become visible. However, in patients with achalasia, the full extent of the EPVs does not become visible and, in addition, rosette-like esophageal folds appear in the lower esophagus. The aim of this study was to investigate whether or not these changes at the lower esophagus are characteristic findings of achalasia.MethodsA total of 34 patients with achalasia and no esophageal dilatation following deep inspiration were compared with 34 sex- and age-matched control subjects. Following a deep inspiration, the lower esophagus of all study cohorts was evaluated on (1) whether or not the full extent of the EPVs was visible, (2) whether or not rosette-like esophageal folds appeared in the lower esophagus, and (3) whether or not there were any gastric lesions.ResultsOne patient had secondary achalasia, and the remaining 33 patients had primary achalasia. In the control subjects, the full extent of the EPVs was clearly visible after a deep inspiration, and no esophageal folds appeared in the lower esophagus. In contrast, in the achalasia patients, EPVs were not observed in all patients after a deep inspiration, and rosette-like esophageal folds appeared in 33 of the 34 patients.ConclusionAfter a deep inspiration, the non-visibility of the EPVs and the appearance of rosette-like esophageal folds at the lower esophagus, which we have called “esophageal rosette”, are characteristic endoscopic findings of primary achalasia.

Mechanisms of acid reflux and how refluxed Acid extends proximally in patients with non-erosive reflux disease.

Background/Aims: The mechanisms that cause acid reflux in patients with non-erosive reflux disease (NERD), including those that determine how acid extends proximally, are not yet clear. Methods: Concurrent esophageal manometry and pH monitoring were performed for 3 h after a meal in 13 patients with NERD, 12 with mild reflux esophagitis (RE), and 13 healthy subjects (HS). Results: Transient lower esophageal sphincter (LES) relaxation (TLESR) was the major mechanism of acid reflux in all three groups. LES pressure did not differ between the groups. At 2 cm above the LES, there were no differences between the three groups in the number of TLESR-related acid reflux episodes, rate of TLESRs and rate of acid reflux during TLESR. However, at 7 cm above the LES, the rate of acid reflux during TLESRs was significantly higher in patients with NERD (mean ± SEM 42.3 ± 4.8) than in those with mild RE (28.0 ± 3.8) and HS (10.8 ± 2.5). Conclusions: TLESRs are the sole motor events underlying acid reflux episodes in patients with NERD. Acid extends proximally more readily in patients with NERD than in HS and those with mild RE.

Effects of Aging and Acid Reflux on Esophageal Motility

Backgrounds: It is generally thought that esophageal motility decreases with age; however, a decrease in esophageal motility may also be caused by esophagitis. The aim of this study is to investigate the effects of aging and acid reflux on esophageal motility. Methods: 40 young (under 45) healthy subjects (HS), 40 elderly (over 65) HS, and 40 elderly (over 65) patients with mild reflux esophagitis (RE), underwent esophageal high-resolution manometry (HRM). Lower esophageal sphincter pressure (LESP), primary peristalsis (PP), and secondary peristalsis (SP) were evaluated. Results: There was no difference in the LESP and also in the success rate of PP between young and elderly HS or between elderly HS and RE. There was no difference in the distal contractile integral (DCI) of PP and SP between the young and elderly HS, but in the elderly RE, it was significantly lower than in the elderly HS. There was no difference in the success rate of SP between elderly HS and RE, but in elderly HS it was significantly lower than in young HS. Conclusions: Aging may cause a decrease in the success rate of SP, and acid reflux itself may cause a decrease of the DCI in PP and SP.

Pathogenesis of Double-Dose Proton Pump Inhibitor-Resistant Non-Erosive Reflux Disease, and Mechanism of Reflux Symptoms and Gastric Acid Secretion-Suppressive Effect in the Presence or Absence of Helicobacter pylori Infection

Background: Various mechanisms have been suggested to be responsible for contributing to the occurrence of proton pump inhibitor (PPI)-resistant non-erosive reflux disease (NERD). The aims of this study were to clarify the pathogenesis of PPI-resistant NERD. Methods: Fifty-three patients with NERD, who had persistent reflux symptoms despite taking double-dose PPI, were included in this study. After excluding eosinophilic esophagitis (EoE) and primary esophageal motility disorder, esophageal impedance-pH monitoring was carried out. In symptom index (SI)-positive patients, the mechanism of SI positivity and the percent time with intragastric pH >4 were investigated according to the presence or absence of Helicobacter pylori infection. Results: One of the 53 patients had EoE, and 4 had primary esophageal motility disorder. Twenty-three and 2 patients were SI-positive for liquid and gas-only reflux respectively. Of 17 SI-positive, H. pylori-negative patients, 5 were SI-positive for acid reflux, whereas all of the H. pylori-positive patients were SI-positive for non-acid reflux. The percent time with intragastric pH >4 was significantly lower in the H. pylori-negative patients than in the H. pylori-positive patients. Conclusions: The pathogenesis of double-dose PPI-resistant NERD was identified in 57%. In some of H. pylori-negative patients, acid-related symptoms were observed. However, in H. pylori-positive patients, these symptoms were excluded by taking double-dose PPI.

Erratum to: Effects of acotiamide on esophageal motility in healthy subjects: a randomized, double-blind, placebo-controlled crossover study

Background Acotiamide is a new drug that exhibits prokinetic activity by enhancing the release of acetylcholine. However, its effects on esophageal motility currently remain unknown. Therefore, we herein investigated the effects of acotiamide on esophageal motility in healthy, asymptomatic subjects.

Tu1787 Primary Peristalsis and Esophagigastric Junction (EGJ) Pressure, Following a Transient Lower Esophageal Sphincter Relaxation (TLESR), Are Accompanied by a Forceful Contraction

Background: A TLESR is a major mechanism of acid reflux in healthy subjects and patients with reflux esophagitis and we have noticed that the amplitude of primary peristalsis and EGJ pressure, following a TLESR, is accompanied by a forceful contraction, when compared with before a TLESR. The aim of this study is to investigate whether or not primary peristalsis and EGJ pressure, when accompanied by a forceful contraction and following a TLESR, is a characteristic finding of a TLESR. Methods: 10 healthy subjects underwent esophageal high-resolution manometry with a 21-lumen perfused assembly, which monitored pressure in the pharynx, the upper esophageal sphincter, the esophageal body, LES and the proximal stomach. The EGJ was evaluated using ten side holes, spaced at 1-cm intervals. Recordings were then taken, in the sitting position, for 1 hour after a meal (692 kcal, 33 % fat). A TLESR is defined as previously described. Data were analyzed, using Trace! Software (Dr. G.S Hebbard, The Royal Melbourne Hospital, Australia). The contractile integral (CI) of the distal esophageal segment (D-CI: volume of the domain above 20 mmHg), excluding the EGJ segment, was measured both before and after a TLESR, and the CI of the EGJ (EGJCI) (volume of the domain above 0 mmHg), was measured for 8 seconds after primary peristalsis reached the EGJ, both before and after a TLESR. Results: 56 TLESRs were measured during the study. The D-CI (1603 mmHg s cm (1177-2120), median (interquartile range)) following a TLESR was significantly greater than before a TLESR (484 (323-1079)) and more than a 50% increase of D-CI in 35 (62.5%) of the 56 TLESRs was observed. The EGJCI (790 (465-1009)) following a TLESR was significantly greater than before a TLESR (238 (186-308)) and more than a 50% increase in the EGJ-CI in 48 (85.7%) of the 56 TLESRs was observed. Conclusions: The D-CI and the EGJ-CI following a TLESR, were significantly greater than before a TLESR and this tendency was evident in the EGJ-CI, although it can, at times, be difficult to evaluate a TLESR. If the focus is on a forceful contraction of primary peristalsis or on the EGJ, it may be easier to detect and evaluate a TLESR.