Tomohiko Shimatani

Comparison of endoscopic findings with symptom assessment systems (FSSG and QUEST) for gastroesophageal reflux disease in Japanese centres

Background and Aim:  We compared endoscopic findings of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), a written questionnaire developed in Japan, to that for the questionnaire for the diagnosis of reflux esophagitis (QUEST) for the diagnosis of reflux esophagitis.

Rabeprazole 10 mg twice daily is superior to 20 mg once daily for night-time gastric acid suppression.

Background : Insufficient acid suppression is one of the main causes of proton pump inhibitor‐refractory gastro‐oesophageal reflux disease.

Validity of endoscopic classification of nonerosive reflux disease

BackgroundMinimal changes, such as erythema without sharp demarcation or whitish turbidity of the lower esophageal mucosa, have recently been used for endoscopic classification of nonerosive reflux disease (NERD) in Japan. This study examined the usefulness of such changes in characterizing the pathophysiology of NERD.MethodsPhysicians specializing in esophageal endoscopy performed endoscopy on 115 patients with NERD. Based on the presence or absence of minimal changes, patients were categorized as displaying NERD with minimal changes (grade M, n = 49) or with no minimal changes or mucosal breaks (grade N, n = 66). Clinical features, quality of life (QOL) scores, and ambulatory 24-h esophageal pH values were compared between groups. Ambulatory 24-h esophageal pH values were monitored in 31 patients (14 grade M and 17 grade N patients) who gave consent out of 115 patients.ResultsIn ambulatory 24-h esophageal pH monitoring, 57.1% (8/14) of grade M patients had pH < 4 more than 4% of the time (abnormal acid reflux) compared with 11.8% (2/17) in the grade N group, a significant difference (P = 0.018). QOL scores did not differ significantly between grades and were significantly lower in both groups compared with the general Japanese population. No significant differences were observed in patient background between the grade M and grade N groups.ConclusionsFrequency of abnormal acid reflux with NERD is higher in patients with minimal changes than in patients without such changes. Minimal changes are most likely attributable to gastric acid reflux.

Effect of omeprazole 10 mg on intragastric pH in three different CYP2C19 genotypes, compared with omeprazole 20 mg and lafutidine 20 mg, a new H2‐receptor antagonist

Background : Omeprazole 10 mg is used as maintenance therapy for gastro‐oesophageal reflux disease, but previous reports have not mentioned the potency of its acid suppression.

Prevalence of Helicobacter pylori infection, endoscopic gastric findings and dyspeptic symptoms among a young Japanese population born in the 1970s

Background:  With the prevalence of Helicobacter pylori (H. pylori) infection rapidly decreasing in Japan, endoscopic findings and dyspeptic symptoms need to be re‐evaluated.

Gastric acidity in patients with follicular gastritis is significantly reduced, but can be normalized after eradication for Helicobacter pylori.

Background.  Follicular gastritis is thought to be caused by Helicobacter pylori infection. However, the pathophysiology of it remains unclear.

Lafutidine, a newly developed antiulcer drug, elevates postprandial intragastric pH and increases plasma calcitonin gene-related peptide and somatostatin concentrations in humans: comparisons with famotidine.

Lafutidine, a newly developed histamine H2-receptor antagonist, inhibits daytime (i.e., postprandial) as well as nighttime gastric acid secretion in clinical studies. It also has gastroprotective activity that particularly affects mucosal blood flow in rats. This study focused on the efficacy of lafutidine on plasma concentrations of gastrointestinal peptides in humans. Six healthy male volunteers aged 23–32 years without Helicobacter pylori infection were orally administered either 10 mg lafutidine, 20 mg famotidine, or water only (control) 30 min after a standard meal (650 kcal). Plasma concentrations of lafutidine and famotidine were highest from 90 to 150 min after administration. Intragastric pH was elevated after both lafutidine and famotidine compared with the control. Plasma concentrations of calcitonin gene-related peptide (CGRP) and somatostatin were significantly increased after lafutidine at 60 and 90 min. We concluded that lafutidine increases plasma concentrations of CGRP and somatostatin in humans, which may result in inhibition of postprandial acid secretion and gastroprotective activity.

The pharmacodynamic effect of omeprazole 10 mg and 20 mg once daily in patients with nonerosive reflux disease in Japan

BackgroundTo evaluate the pharmacodynamic effect, efficacy, and safety of omeprazole 10 mg and 20 mg once daily in patients with nonerosive reflux disease (NERD) in Japan.MethodsA total of 37 patients were randomized to omeprazole 10 mg or omeprazole 20 mg once daily for 4 weeks. Eligible patients had a history of moderate-to-severe heartburn for 2 days or more per week during the last 1 month or longer prior to the study screening, grade M or grade N on Hoshiharas modification of the Los Angeles classification (i.e., no sign of mucosal break on esophagogastroduodenoscopy), and heartburn episodes for 2 days or more per week during the last week of the observation period while taking antacids. Ambulatory 24-h intraesophageal pH was monitored on the day before treatment and on the last day of treatment. The occurrence of a heartburn episode was recorded during pH monitoring. The primary endpoint was the change in the percentage of time with intraesophageal pH < 4 during the 24-h period before and after omeprazole treatment.ResultsBoth omeprazole 10 mg and omeprazole 20 mg once daily reduced the percentage of time with intraesophageal pH < 4. The percentage reduction in time with intraesophageal pH < 4 after treatment with omeprazole was associated with a reduced number of heartburn episodes. Patients with grade M or grade N esophagus had similar pH profiles and NERD characteristics (e.g., pH holding time, symptom index) and comparable responses to omeprazole. No serious, drug-related adverse events were reported.ConclusionsOmeprazole 10 mg or 20 mg reduces the percentage of time with intraesophageal pH < 4, is efficacious, and is well tolerated in patients with NERD in Japan, regardless of the patients endoscopic classification.

Efficacy of a Low-Dose Omeprazole-Based Triple-Therapy Regimen for Helicobacter pylori Eradication Independent of Cytochrome P450 Genotype : The Japanese MACH Study.

AbstractObjectives: To investigate the efficacies of two different triple-therapy regimens (standard versus low doses), and the influence of cytochrome P450 enzyme (CYP) genetic polymorphism on these efficacies, in Japanese patients undergoing Helicobacter pylori eradication treatment. Methods: All patients received 1 week of triple therapy. Patients in group A (low-dose regimen) received omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day; patients in group B (standard-dose regimen) received omeprazole 40 mg/day + amoxicillin 2000 mg/day + clarithromycin 1000 mg/day. Results: A total of 225 patients (113 in group A and 112 in group B) were randomised to one of the two triple-therapy regimens. The eradication rates were 78.8% (89/113 patients; 95% CI 70.1, 85.9) in group A and 83.0% (93/112 patients; 95% CI 74.8, 89.5) in group B. Genetic polymorphism of CYP2C19, a major metabolic enzyme of omeprazole, did not affect eradication rates, while susceptibility to clarithromycin greatly affected the success of eradication. The cumulative ulcer relapse rate at 24 weeks after endoscopically documented ulcer healing (30 weeks after completion of the drug regimen) was 8.3% for group A and 12.5% for group B (log rank test: p = 0.6248). However, comparison of the cumulative relapse rate of 6.7% in patients after successful H. pylori eradication with the relapse rate of 27.3% in those who failed H. pylori eradication revealed a significant difference in the remission-time curve (log rank test: p = 0.0047). This finding suggested the existence of a relationship between H. pylori eradication failure and ulcer relapse. Both drug regimens were well tolerated. Endoscopically proven reflux esophagitis developed in about 10% of patients after eradication, but was not clinically significant. Conclusions: One week of triple therapy with a low-dose regimen provides adequate H. pylori eradication in Japanese patients. CYP genetic polymorphism is of minimal clinical significance with both triple-therapy regimens.

Improvement in gastric histology following Helicobacter pylori eradication therapy in Japanese peptic ulcer patients.

We aimed to determine if successful or failed eradication of Helicobacter pylori with triple therapy causes any difference in gastric mucosal histology. Japanese H. pylori-positive patients with a healed peptic ulcer received high (n = 112) or low (n = 113) doses of triple therapy (omeprazole, amoxicillin and clarithromycin) for 1 week. Biopsies from the greater curvature of the central antrum and upper corpus were taken 6 weeks and 30 weeks after treatment completion, and gastric mucosal histology compared between successful (n = 171) and failed (n = 34) eradication groups. Morphological variables of gastritis were graded according to the updated Sydney System. Successful eradication therapy was defined as improvement in inflammation, neutrophil activity and atrophy; failed eradication therapy as improvement in inflammation and neutrophil activity only. Gastric mucosal atrophy gradually improved (in addition to improvements in inflammation and neutrophil activity) with successful eradication of H. pylori infection. Conclusions: Improvements in atrophy, inflammation and neutrophil activity were confirmed histopathologically following successful H. pylori eradication therapy, but improvements in inflammation and neutrophil activity were also seen after failed eradication therapy. No improvement in metaplasia was observed, irrespective of the success or failure of treatment. Since atrophy is known to be involved in the aetiology of gastric cancer, H. pylori eradication might prevent development of gastric cancer.