Kazuhiro Mizukami

Aspirin-induced small bowel injuries and the preventive effect of rebamipide

AIM To evaluate the influence of taking low-dose aspirin for 4 wk on small intestinal complications and to examine the preventive effect of rebamipide. METHODS This study was conducted as a single-center, randomized, double-blind, cross-over, placebo-controlled study. Eleven healthy male subjects were enrolled. Each subject underwent video capsule endoscopy after 1 and 4 wk of taking aspirin and omeprazole, along with either rebamipide or placebo therapy. The primary endpoint was to evaluate small bowel damage in healthy subjects before and after taking low-dose aspirin for 4 wk. RESULTS The number of subjects with mucosal breaks (defined as multiple erosions and/or ulcers) were 1 at 1 wk and 1 at 4 wk on the jejunum, and 6 at 1 wk (P = 0.0061) and 7 at 4 wk on the ileum (P = 0.0019). Rebamipide significantly prevented mucosal breaks on the ileum compared with the placebo group (P = 0.0173 at 1 wk and P = 0.0266 at 4 wk). CONCLUSION Longer-term, low-dose aspirin administration induced damage in the small bowel. Rebamipide prevented this damage, and may be a candidate drug for treating aspirin-induced small bowel complications.

Helicobacter pylori Eradication Improves Gastric Atrophy and Intestinal Metaplasia in Long-Term Observation

Background and Aim:Helicobacter pylori has been shown to cause atrophic gastritis and intestinal metaplasia (IM), both of which are precancerous lesions. To clarify the mechanism by which H. pylori eradication prevents gastric cancer, we monitored atrophy and IM improvement in gastric mucosa over a long period after H. pylori eradication. Methods: We monitored 118 patients (72 males, 46 females; mean age 61.3 ± 5.1 years) for a mean of 8.6 years (range 5–13) after successful H. pylori eradication. Biopsy specimens were taken from the greater curvatures of the antrum (A2) and the corpus (B2). Results: Atrophy was significantly decreased in patients with successful H. pylori eradication, both at A2 (from 1.60 ± 0.09 to 1.02 ± 0.08; p < 0.001) and B2 (from 0.71 ± 0.10 to 0.02 ± 0.02; p < 0.001), and IM score was significantly decreased at B2 (from 0.17 ± 0.12 to 0.00 ± 0.00; p < 0.05), but not at A2 (from 0.60 ± 0.11 to 0.43 ± 0.09; p = NS). In patients without successful eradication, however, there were no differences in scores over time. Before eradication, IM score was significantly higher in males than in females, both at A2 (0.81 ± 0.12 vs. 0.25 ± 0.10; p < 0.05) and B2 (0.32 ± 0.08 vs. 0.07 ± 0.04; p < 0.05). Conclusion: We were able to monitor the gastric mucosa for a mean of 8.6 years after H. pylori eradication, the longest period reported to date. Significant improvements in gastric atrophy and IM after H. pylori eradication may decrease the risk of gastric cancer.

Association of helicobacter pylori dupA with the failure of primary eradication.

Goals: To determine whether the presence of dupA Helicobacter pylori (H. pylori) influences the cure rate of primary eradication therapy. Background: Several virulence factors of H. pylori have been reported to affect the efficacy of the eradication rate. However, no study has investigated whether the presence of dupA affects eradication failure. Study: The presence of dupA was evaluated in 142 H. pylori strains isolated from 142 patients with gastrointestinal diseases. Of these patients, 104 received primary eradication therapy for 1 week. The risk factors for eradication failure were determined using univariate and multivariate analyses. Results: Among 142 strains, 44 (31.0%) were dupA positive. There was no association between dupA status and gastroduodenal diseases (P>0.05). The clarithromycin (CLR) resistance rate was generally lower in the dupA-positive than in the dupA-negative group (20.4% vs. 35.7%, P=0.06). However, dupA prevalence was higher in the eradication failure group than in the success group (36.3% vs. 21.9%). Among the CLR-resistant H. pylori infected group, the successful eradication rate was significantly lower in patients infected with dupA-positive H. pylori than dupA-negative H. pylori (P=0.04). In multivariate analysis adjusted for age, sex, and type of disease, not only CLR resistance but also dupA presence was independent risk factors for eradication failure (adjusted odds ratio=3.71; 95% confidence interval,1.07-12.83). Conclusions: Although CLR resistant was more reliable predictor, the presence of dupA may also be an independent risk factor for eradication failure.

Histological characteristics of gastric mucosa prior to Helicobacter pylori eradication may predict gastric cancer

Abstract Objective. Although Helicobacter pylori (H. pylori) eradication has been shown to inhibit gastric cancer, it does not completely suppress it. Therefore, risk factors of gastric cancer development following H. pylori eradication were examined. Material and methods. A total of 2355 patients (1501 males and 824 females) underwent successful eradication of H. pylori. Endoscopic atrophy, histological gastritis, atrophy, intestinal metaplasia (IM), and operative link for gastritis assessment (OLGA) staging were subsequently evaluated. Results. Following eradication, 33/2355 patients (25 males and 8 females) developed gastric cancer. Compared to a nongastric cancer group that was matched according to gender and age, the incidence of endoscopic atrophy (3.52 ± 1.45 vs. 4.85 ± 1.18, p < 0.001), histological atrophy at the greater curvature of the antrum (1.42 ± 0.80 vs. 1.95 ± 0.86, p = 0.0059), inflammation (2.05 ± 0.59 vs. 2.33 ± 0.66, p = 0.031), IM at the greater curvature of the corpus (0.06 ± 0.30 vs. 0.24 ± 0.54, p = 0.029), the ratio of OLGA-stage 0–II/III, IV (13/8 vs. 55/11, p = 0.038) were significantly higher for the gastric cancer group. Multivariate analysis also showed the highest odds ratio (6.26, 95% confidence interval or CI, 1.28–30.60, p = 0.023) for IM at the greater curvature of the corpus. Conclusions. Severe endoscopical atrophy, OLGA staging, histological atrophy at the antrum, inflammation, and particularly IM at the corpus, were identified as risk factors for gastric cancer development following H. pylori eradication. Therefore, eradication should be performed before these predictors develop.

Impact of Helicobacter pylori CagA diversity on gastric mucosal damage: An immunohistochemical study of East-Asian-type CagA

Background and Aims:  Recently, we successfully produced an anti‐East‐Asian‐type CagA‐specific antibody called α‐EAS Ab, which is specifically immunoreactive only with East‐Asian‐type CagA but not Western‐type CagA. In this study, the correlations between Helicobacter pylori CagA protein diversity and gastric mucosal condition was investigated using immunohistochemical staining with α‐EAS Ab in Japan.

Comparison of the efficacy of irsogladine maleate and famotidine for the healing of gastric ulcers after Helicobacter pylori eradication therapy: a randomized, controlled, prospective study.

Abstract Objective. Helicobacter pylori eradication therapy alone cannot heal gastric ulcers in Japanese patients. Irsogladine has previously been shown to accelerate the healing of gastric ulcers after H. pylori eradication therapy. And we previously reported that histamine H2 receptor antagonists inhibit gastric ulcer relapse after H. pylori eradication therapy. We therefore compared the efficacy of irsogladine with famotidine as appropriate treatments for ulcers after eradication therapy. Methods. Gastric ulcer patients with H. pylori infection (n = 119) were randomized to treatment with irsogladine 4 mg/day (n = 60) or famotidine 40 mg/day (n = 59) following 1-week H. pylori eradication therapy. After treatment, assessments of gastric ulcer healing were performed. Results. The ulcer healing rates in patients receiving irsogladine and famotidine were 85.2% (46/54) and 79.6% (43/54), respectively, and were not significantly different (p = 0.4484). In the famotidine group, the healing rate was significantly lower in patients who drink alcohol than in those who do not (60.0% vs. 91.2%; p = 0.0119). However, in the irsogladine group the healing rate did not differ between patients who drink alcohol and those who do not. Furthermore, the healing rate in smokers was significantly higher in the irsogladine group (88.0%) than in the famotidine group (59.1%) (p = 0.0233). Conclusions. Irsogladine and famotidine are both acceptable in treatment after H. pylori eradication therapy in gastric ulcer patients. Findings also suggest that irsogladine is more beneficial than famotidine in patients who drink alcohol and smoke.

Efficacy of rebamipide for low-dose aspirin-related gastrointestinal symptoms.

Gastrointestinal symptoms are a problematic issue for patients who take low-dose aspirin for long time. We conducted a pilot study to investigate the efficacy of combination therapy with proton pump inhibitor and rebamipide. This was a prospective, randomized, double-blind, placebo-controlled cross-over study. All the subjects received aspirin 100 mg and omeprazole 20 mg. The subjects were divided into two groups and received either rebamipide 300 mg or placebo, which was prescribed for 4 weeks. The subjects were instructed to record their gastrointestinal symptom rating scale before the study and 1 and 4 weeks after beginning the protocol. These scores of the groups were compared before and after the treatment to evaluate the severity of their symptoms and the number of symptom items present in each group. For the subjects receiving rebamipide, the total prevalence of lower gastrointestinal symptoms was significantly different from the placebo group (p=0.0093) at week 4. No troublesome symptoms were observed in the rebamipide group. Inconclusion, the administration of rebamipide prevented the occurrence of troublesome symptoms, especially lower gastrointestinal symptoms, in patients taking aspirin and omeprazole. Rebamipide is a candidate drug for combination therapy with proton pump inhibitors to prevent low-dose aspirin-induced gastrointestinal symptoms.

Evaluation of esophageal function in patients with gastroesophageal reflux disease using transnasal endoscopy

Background and Aims:  To investigate the utility of a new method of carrying out esophageal manometry using a narrow gauge manometry catheter via a transnasal endoscope.

Evaluation of selective cyclooxygenase‐2 inhibitor‐induced small bowel injury: Randomized cross‐over study compared with loxoprofen in healthy subjects

Non‐steroidal anti‐inflammatory drugs have the potential to injure the mucosa of the upper digestive tract and small bowel, whereas celecoxib (a selective cyclooxygenase‐2 inhibitor) has less influence on the entire digestive tract mucosa. The present study was conducted to compare the extents of small bowel mucosal injury induced by celecoxib and loxoprofen (the most frequently used non‐steroidal anti‐inflammatory drugs in Japan).

Helicobacter pylori and NSAID-induced gastric ulcer in a Japanese population

A recent meta-analysis by Huang et al. clarified that Helicobacter pylori infection and nonsteroidal antiinflammatory drugs (NSAIDs) are important factors for peptic ulcer. The results showed that the risk for ulcer in NSAID(+)/H. pylori(+) patients was 61.1 fold higher when compared with NSAID(−)/H. pylori(−) patients. Some gastric ulcers detected in patients on NSAID therapy may actually be caused by H. pylori, but it is difficult to differentiate NSAID-induced gastric ulcer from H. pylori-induced gastric ulcer. Several studies have investigated the effects of H. pylori eradication on ulcer healing. One study reported that H. pylori eradication actually lowered the healing rate of gastric ulcers. Because there have been no studies finding that H. pylori eradication facilitates healing, H. pylori eradication is not recommended for NSAID users. Concerning the efficacy of H. pylori eradication in the prevention of NSAID-induced gastric ulcer, a meta-analysis concluded that among all patients on NSAID therapy, H. pylori eradication lowered the prevalence of ulcer, which was particularly marked in NSAID-naïve patients. When compared with those of proton pump inhibitors (PPIs), the preventative effects of H. pylori eradication were inferior. In Japan, national health insurance does not cover procedures that prevent or lower the risk for NSAID-induced ulcer. When administering NSAID to patients with risk factors, it is desirable to administer antiulcer agents.