Noriyuki Kawami

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.

Variant parameter values—as defined by the Chicago Criteria—produced by ManoScan and a new system with Unisensor catheter

Recently reported normal values for esophageal motility obtained by high‐resolution manometry (HRM) using a system with a Unisensor catheter were significantly different from those obtained by the ManoScan®, which could result in a wrong diagnosis. To clarify whether these differences were due to system or subject differences, we compared the manometric parameter values between ManoScan and a new system with a Unisensor catheter (Starlet) in the same subjects.

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.

Intra-gastric pH following single oral administrations of rabeprazole and esomeprazole: double-blind cross-over comparison

Comparisons between the acid inhibitory effects of rabeprazole and esomeprazole after single oral administration with standard doses have not been previously presented. We examined intra-gastric pH after oral administrations of these two proton pump inhibitors using 24-h pH monitoring. Fifty-four normal volunteers not infected by Helicobacter pylori were investigated. Using a cross-over design, we administered 10 mg of rabeprazole or 20 mg of esomeprazole in 27 at 30 min after supper and in the remaining 27 subjects at 15 min before supper, and performed 24-h pH monitoring. Intra-gastric pH data were nearly identical when the proton pump inhibitors were taken after meals. Even if the data were compared in different CYP2C19 genotypes, rabeprazole and esomeprazole did not show the difference. In poor metabolizer, both of the drugs showed stronger acid inhibition. When taken before meals, intra-gastric pH after esomeprazole administration was slightly but not significantly higher than that observed after rabeprazole administration not only in daytime but also in nighttime period. In conclusion, rabeprazole and esomeprazole were similarly effective when administered after a meal.

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.

Association between reflux esophagitis and/or hiatus hernia and gastric mucosal atrophy level in Japan

Background and Aims:  The mechanisms involved in reflux esophagitis (RE) are mainly esophageal motor dysfunction and abnormal esophageal acid exposure. Therefore the extent of gastric mucosal atrophy (GMA), which is related to gastric acid secretion, is an important factor in the development of RE. The aim of this study was to evaluate the prevalence of RE and hiatus hernia (HH) according to level of GMA.

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.

Mechanisms underlying excessive esophageal acid exposure in patients with gastroesophageal reflux disease

The cause of reflux esophagitis (RE) is excessive esophageal acid exposure. Acid reflux and acid clearance after acid reflux are important factors related to excessive esophageal acid exposure. The main mechanism responsible for acid reflux is transient lower esophageal sphincter relaxation (TLESR), which is LES relaxation not associated with swallowing, and acid reflux caused by low LES pressure is rare. The frequency of TLESR in the postprandial period does not significantly differ between healthy subjects and gastroesophageal reflux disease (GERD) patients; however, the proportion of acid reflux episodes during TLESR is significantly higher in GERD patients. The layer of acid that appears above the dietary layer immediately below the esophagogastric junction (acid pocket) is attracting increasing attention as a cause of the difference in the proportion of acid reflux episodes during TLESR. The proportion of acid reflux episodes during TLESR is significantly higher when the acid pocket is present in the hernia sac than when it is located below the diaphragm. The acid pocket also shows upward migration and reaches the esophageal side of the esophagogastric junction, and the acid pocket itself has been suggested to cause mucosal damage in the lower esophagus. The amplitude and success rate of primary peristalsis decreases with increases in the severity of RE, leading to excessive esophageal acid exposure. Furthermore, the success rate of secondary peristalsis is lower in GERD patients than in healthy subjects.