Kiyoshi Ashida

Obesity as a risk factor for GERD in Japan

Background. In Europe and the United States, it is known that obesity, which is increasing, is closely associated with gastroesophageal reflux disease (GERD), but in Japan no definite consensus has been reached on this relationship. Clarification of the relationship between the two is an important issue. Methods. After screening, gastrointestinal endoscopic examinations were conducted on 1813 subjects who were surveyed using a questionnaire in which they recorded body weight, height, weight loss or gain, chief complaints, and underlying disease to prospectively examine the relationship between obesity and GERD. Differences in GERD prevalence and esophageal hiatal hernia prevalence in thin (body mass index less than 18.5 kg/m2), normal (18.5 to 25.0), and obese (greater than 25.0) subjects were examined, and the differences in GERD prevalence in patients with weight loss or gain were also investigated. Results. GERD prevalence was 20.96% in the thin group, 24.42% in the normal group, and 31.86% in the obese group, indicating a significantly higher prevalence in the obese group compared with the other groups. The prevalence of hernia was also significantly higher in the obese group. GERD prevalence in the weight gain group was significantly higher than in the unchanged weight group and weight loss group. Conclusions. Both GERD prevalence and the prevalence of hernia were significantly higher in obese subjects, and the prevalence of GERD in subjects who had gained weight was also significantly higher. From these results, it was concluded that obesity is a risk factor for GERD in Japan.

The demographic characteristics and health-related quality of life in a large cohort of reflux esophagitis patients in Japan with reference to the effect of lansoprazole: the REQUEST study

BackgroundPatients with reflux esophagitis (RE) in Western countries have impaired health-related quality of life (HRQOL). However, few data are available concerning HRQOL in Asian patients with RE.AimTo determine the demographic characteristics, HRQOL, and the impact of lansoprazole treatment in a large cohort of RE patients in Japan.MethodsPatients with RE were enrolled. Lansoprazole was administered for 8 weeks and HRQOL assessed using the SF-8 and a newly developed questionnaire for RE-specific HRQOL (RESQ) at baseline and after 4 and 8 weeks of treatment.ResultsAmong enrolled patients, 2320 patients with the Los Angeles classification grade A to D esophagitis at enrollment to the study were analyzed. A higher proportion of older women was observed (in the group of patients aged ≥60 years, 61.3% were women). Prevalence of obesity was 4.7%. At baseline, HRQOL scores of RE patients were well below the mean for the Japanese general population in all domains of the SF-8. After 8 weeks of treatment with lansoprazole, these scores significantly improved to the levels of the general population (P < 0.01). Scores of RESQ also significantly improved (P < 0.01).ConclusionsDemographically, RE patients in Japan differ from those in Western countries with an increased proportion in older women and lower prevalence of obesity. RE has a marked negative impact on HRQOL, which is significantly improved by treatment with lansoprazole.

Clinical study on the pathophysiology and treatment of PPI-resistant ulcers

We studied the gastric acidity, gastric emptying, and proton pump inhibitor (PPI) plasma levels in 10 patients with PPI-resistant ulcers. The pH 3 holding-time ratio was low in nine of these patients, with an average ratio of only 39%. PPI plasma levels in those patients were also much lower than in those with nonresistant ulcers. Gastric emptying, determined by the acetaminophen method, was reduced in all 10 patients. Therefore, PPI-resistant ulcers appear to result from insufficient inhibition of gastric acidity, with reduced gastric emptying interfering with the absorption of PPIs. In patients with mild reductions in gastric emptying, PPI plasma levels increased after a change from single-unit enteric-coated tablets (omeprazole) to multiunit enteric-coated granules in capsules (lansoprazole). This change in formulation markedly inhibited gastric acidity and led to rapid healing. In patients with moderate reductions in gastric emptying, doubling the dose of lansoprazole was effective. In patients with severely reduced gastric emptying, there appeared to be a limit to the effectiveness of oral administration of PPIs. Changing the formulation and doubling the dose to compensate for reduced gastric emptying are effective approaches in the treatment of patients with PPI-resistant ulcers.

Predictive Factors Associated with the Success of Pneumatic Dilatation in Japanese Patients with Primary Achalasia: A Study Using High-Resolution Manometry

Background/Aims: A new classification of achalasia using high-resolution manometry (HRM) has recently been suggested. Pneumatic dilatation (PD) is a common treatment for primary achalasia. The usefulness of the new classification and HRM for the treatment and follow-up of patients after PD is unknown. The aim of this study was to evaluate the PD effectiveness and the predictive factors of success in Japanese patients with achalasia using HRM and the new classification of achalasia. Methods: Twenty-five patients were diagnosed with primary achalasia using HRM and treated by PD in our hospital. We evaluated symptom scores and esophageal manometry 6 and 12 months after the first PD. Results: After the first PD treatment, remission occurred in 24 out of 25 (96.0%) patients at 6 months and in 19 out of 25 (76.0%) patients at 12 months. With the new classification of achalasia, the success rates were 83.3, 80.0 and 50% for types I, II and III, respectively, 12 months after PD. The median age of the successful group was significantly greater than that of the failure group (47.1 vs. 37.0 years, p <0.05). The median residual lower esophageal sphincter (LES) pressure 6 months after PD in the successful group was significantly lower than that of the failure group (9.0 vs. 15.5 mm Hg, p <0.05). Conclusion: Good predictors of PD success were old age (>40 years) and residual LES pressures less than 15 mm Hg 6 months after PD.

Influence of cure of Helicobacter pylori infection on gastric acidity and gastroesophageal reflux: study by 24-h pH monitoring in patients with gastric or duodenal ulcer.

BackgroundWhether or not the eradication of Helicobacter pylori is a risk factor for reflux esophagitis (RE) is a question at issue. To find an answer, it is necessary to clarify the influence of H. pylori eradication on the mechanism of RE.MethodsThe authors investigated the influence of H. pylori eradication on gastric acidity and gastroesophageal reflux in ten gastric ulcer (GU) patients and ten duodenal ulcer (DU) patients by 24-h simultaneous determination of pH in the stomach and esophagus.ResultsThough the results indicated enhanced gastric acidity in GU patients at night after H. pylori eradication, no such influence was observed in DU patients. No significant changes in gastroesophageal reflux occurred in GU or DU patients before and after H. pylori eradication. RE after H. pylori eradication occurred in only one patient, with GU. This patient had several risk factors for RE, such as obesity, male sex, and dietary habits to add to the increase in gastric acidity at night that occurred after H. pylori eradication. No increase in gastroesophageal reflux occurred in any DU patients or in the other GU patients that demonstrated enhanced gastric acidity at night after H. pylori eradication.ConclusionsThe cure of H. pylori infection does not, by itself, cause RE in patients who have few other risk factors for RE.

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.

Comparison of PPIs and H2-receptor antagonists plus prokinetics for dysmotility-like dyspepsia

AIM To compare efficacy of proton pump inhibitors (PPIs) with H(2)-receptor antagonists (H(2)RAs) plus prokinetics (Proks) for dysmotility-like symptoms in functional dyspepsia (FD). METHODS Subjects were randomized to receive open-label treatment with either rabeprazole 10 mg od (n = 57) or famotidine 10 mg bid plus mosapride 5 mg tid (n = 57) for 4 wk. The primary efficacy endpoint was change (%) from baseline in total dysmotility-like dyspepsia symptom score. The secondary efficacy endpoint was patient satisfaction with treatment. RESULTS The improvement in dysmotility-like dyspepsia symptom score on day 28 was significantly greater in the rabeprazole group (22.5% ± 29.2% of baseline) than the famotidine + mosapride group (53.2% ± 58.6% of baseline, P < 0.0001). The superior benefit of rabeprazole treatment after 28 d was consistent regardless of Helicobacter pylori status. Significantly more subjects in the rabeprazole group were satisfied or very satisfied with treatment on day 28 than in the famotidine + mosapride group (87.7% vs 59.6%, P = 0.0012). Rabeprazole therapy was the only significant predictor of treatment response (P < 0.0001), defined as a total symptom score improvement ≥ 50%. CONCLUSION PPI monotherapy improves dysmotility-like symptoms significantly better than H(2)RAs plus Proks, and should be the treatment of first choice for Japanese FD.

The Impact of Lifestyle Modification on the Health-Related Quality of Life of Patients With Reflux Esophagitis Receiving Treatment With a Proton Pump Inhibitor

OBJECTIVES:Although lifestyle modification involving diet, exercise, cessation of smoking, etc. is generally advised for patients with reflux esophagitis (RE), few data that show its clinical benefits are available. We analyzed whether lifestyle modification improves health-related quality of life (HRQOL) in Japanese patients with RE receiving the proton pump inhibitor (PPI) lansoprazole as a post hoc analysis of an observational study that investigated the effect of lansoprazole on HRQOL.METHODS:Patients with RE received lansoprazole for 8 weeks. HRQOL was assessed using the 8-Item Short-Form Health Survey (SF-8) and RE-specific HRQOL questionnaires at baseline and after 4 and 8 weeks of treatment. Physical and mental component summaries (PCS, MCS) and RE-specific summary (RES) scores were calculated.RESULTS:Of the 8,757 patients analyzed, 40.8% were advised regarding new lifestyle at the start of lansoprazole treatment (Group A), 33.3% were advised to continue the lifestyle as advised previously (Group B), and 25.9% did not receive any advice (Group C). The change in PCS from baseline at week 8 for Group A was 5.7±8.1, and this was significantly greater (P<0.001) than the increases achieved in Groups B (4.3±7.5) and C (4.0±7.6). The changes in MCS and RES were also significantly greater in Group A than in the other groups. The changes in HRQOL scores from baseline were significantly greater in Group A than in the other groups, irrespective of baseline patient characteristics.CONCLUSIONS:Lifestyle modification may be clinically beneficial in terms of improving HRQOL in Japanese patients with RE who are receiving treatment with a PPI.

Suppressive action of lansoprazole on gastric acidity and its clinical effect in patients with gastric ulcers : comparison with famotidine

We studied the action on acid secretion of lansoprazole compared with famotidine by 24-h intragastric pH monitoring, evaluated its clinical effects prospectively, and assessed the importance of acid inhibition in gastric ulcer patients. Twenty symptomatic patients with active gastric ulcers diagnosed by endoscopy were assigned to a lansoprazole (LAN) group (lansoprazole 30 mg q.d., n = 10) or a famotidine (FAM) group (famotidine 20 mg b.i.d., n= 10). There were no differences between the groups in pretreatment pH profiles or background factors such as age, sex, smoking, previous ulcer therapy, ulcer site, or Helicobacter pylori infection. The FAM group showed a continuous increase in intragastric pH during the night, with low pH values except for a transient increase associated with food intake during the day. However, the LAN group showed a more neutral pH throughout the day, with pH-3 holding time ratios of 99.0% for 24 h, 98.3% at night, and 99.8% during the day, compared with 68.0, 76.5, and 59.4%, respectively, in the FAM group. The healing rate was also higher in the LAN group. We conclude that inhibition of gastric acidity is important in ulcer therapy and that lansoprazole is superior to famotidine in promoting ulcer healing.

Tu1055 TAK-438 Versus Lansoprazole 15 mg for Secondary Prevention of Peptic Ulcers Associated With Low-Dose Aspirin Therapy: Results of a Phase 3 Trial

Background and Aims: Gastroesophageal reflux is considered to cause sleep disturbance, while proton pump inhibitor (PPI) administration is reported to improve insomnia associated with gastroesophageal reflux disease (GERD). The majority of patients with gastroesophageal reflux are asymptomatic and a significant number with erosive esophagitis are also reported to be asymptomatic. Therefore, PPIs may improve sleep disturbance not only for symptomatic GERD patients, but also individuals without reflux symptoms if asymptomatic reflux is an important factor to cause insomnia. We examined whether PPI administration has a therapeutic effect for improving insomnia in patients without reflux symptoms in the same manner as patients with reflux symptoms. Methods: We performed a randomized multicenter doubleblind placebo-controlled trial using 176 patients with insomnia regardless of the presence of reflux symptoms. The patients were divided into those administered omeprazole (20 mg) or a placebo for 14 days. Four self-reporting questionnaires, QOLRAD-J(Japanese translation of Quality of Life in Reflux and Dyspepsia questionnaire), PSQI(Pittsburg Sleep Quality Index) , ESS (Epworth Sleepiness Scale), and a sleep diary, were used for evaluating GERDrelated quality of life and sleep disturbance. Results:We evaluated 171 patients with insomnia, of whom 69 had typical reflux symptoms. Omeprazole improved GERD-related quality of life and insomnia significantly better than the placebo in patients with reflux symptoms. On the other hand, the therapeutic effects of omeprazole and the placebo were not different in patients without reflux symptoms.(Table) Conclusion: Our results showed that PPI administration is effective only for insomnia in patients with reflux symptoms. Effects of omeprazole and placebo on reflux and sleep indices in patients with heartburn and/or acid regurgitation