Tadayoshi Okimoto

Efficacy of triple therapy comprising rabeprazole, amoxicillin and metronidazole for second‐line Helicobacter pylori eradication in Japan, and the influence of metronidazole resistance

Background : The widespread use of eradication therapy for Helicobacter pylori in Japan has led to an increase in antibiotic‐resistant strains and the problem of re‐treatment in cases of eradication failure.

Eradication rates of clarithromycin-resistant Helicobacter pylori using either rabeprazole or lansoprazole plus amoxicillin and clarithromycin

Background : The resistance of Helicobacter pylori to clarithromycin has become one of the primary reasons for eradication failure.

Helicobacter pylori dupA gene is not associated with clinical outcomes in the Japanese population.

The dupA gene of Helicobacter pylori was suggested to be a risk factor for duodenal ulcer but protective against gastric cancer. The present study aimed to re-examine the role of dupA in H. pylori-infected Japanese patients. We found that dupA status was not associated with any gastroduodenal disease, histological score of chronic gastritis or with the extent of interleukin-8 production from gastric cell lines. These results indicate that dupA is unlikely to be a virulence factor of H. pylori in the Japanese population.

Helicobacter pylori infection and gastroduodenal diseases in Vietnam: a cross-sectional, hospital-based study

BackgroundThe rate of H. pylori infection in Vietnam is reportedly high, but the spectrum of H. pylori-associated gastroduodenal diseases has not been systematically investigated. Moreover, despite the similarities of ethnicity and diet, the age-standardized incidence rate of gastric cancer in the northern city of Hanoi is higher than that in the southern city of Ho Chi Minh, but the reason for this phenomenon is unknown. The virulence of Vietnamese H. pylori has also not been investigated in detail.MethodsIndividuals undergoing esophagogastroduodenoscopy were randomly recruited. H. pylori infection status was determined based on the combined results of culture, histology, immunohistochemistry, rapid urine test and serum ELISA. Peptic ulcer (PU) and gastroesophageal reflux disease was diagnosed by endoscopy, and chronic gastritis was determined histologically. H. pylori virulence factors were investigated by PCR and sequencing.ResultsAmong the examined patients, 65.6% were infected with H. pylori. The prevalence of infection was significantly higher in those over 40 years of age than in those aged ≤40. Chronic gastritis was present in all H. pylori-infected individuals, 83.1% of whom had active gastritis, and 85.3% and 14.7% had atrophy and intestinal metaplasia, respectively. PU was present in 21% of infected patients, whereas its incidence was very low in non-infected individuals. The prevalence of PU was significantly higher in Hanoi than in Ho Chi Minh. The prevalence of vacA m1, which has been identified as an independent risk factor for PU in Vietnam, was significantly higher among H. pylori isolates from Hanoi than among those from Ho Chi Minh.ConclusionsH. pylori infection is common in Vietnam and is strongly associated with PU, active gastritis, atrophy and intestinal metaplasia. vacA m1 is associated with an increased risk for PU and might contribute to the difference in the prevalence of PU and gastric cancer between Hanoi and Ho Chi Minh.

Analysis of p53 gene mutations in Helicobacter pylori-associated gastritis mucosa in endoscopic biopsy specimens.

BACKGROUND No previous report has shown the relationship between Helicobacter pylori infection and a direct sequence analysis of p53 gene mutation in a biopsy sample of human gastric mucosa. METHODS A total of 60 endoscopic biopsies samples (21 patients with H. pylori-positive gastritis and 9 patients with H. pylori-negative gastritis), including antral mucosa and corpus mucosa, were used in this study. Direct DNA sequencing of exons 5, 6, 7, and 8 of the p53 gene was performed by the dyedeoxy terminator method. RESULTS Mutations in the p53 gene were identified in non-hot spot codons in exon 7 and 8 in 11 of 21 samples (52.4%) from H. pylori-positive gastritis patients. There was no mutation in H. pylori-negative gastritis patients. CONCLUSIONS This finding shows that H. pylori infection can induce p53 point mutations and appears to be involved in the pathway leading to dysplasia or carcinoma.

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.

Analysis of virulence factors of Helicobacter pylori isolated from a Vietnamese population

BackgroundThe incidence of gastric cancer differs among countries in Asia, and it has been suggested that virulence factors associated with Helicobacter pylori are partly responsible. The aim of this study was to investigate several genetic factors regarded as virulence or molecular epidemiologic markers in H. pylori isolates from Vietnamese subjects.ResultsThe cagA, vacA and cag right-end junction genotypes of 103 H. pylori strains from Vietnam (54 from Hanoi and 49 from Ho Chi Minh) were determined by PCR and sequencing. Three types of deletion in the region located upstream of the cagA Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region were identified: the 39-bp deletion type, the 18-bp deletion type, and the no-deletion type. The majority of strains studied (77%; 80/103) had the 18-bp deletion irrespective of geographical location in the country or clinical outcome. All of the 39-bp and 18-bp deletion-type strains possessed the East Asian type cagA repeat region. The type II cag right-end junction genotype was predominant (84%). The vacA m1 genotype was significantly more common in strains isolated in Hanoi, where the incidence of gastric cancer is higher, than in strains from Ho Chi Minh.ConclusionPre-EPIYA-region typing of the cagA gene could provide a new genetic marker of H. pylori genomic diversity. Our data support the hypothesis that vacA m1 is closely associated with gastric carcinogenesis.

Guidelines for the management of Helicobacter pylori infection in Japan: current status and future prospects

In the years that followed the issuance in 2000 of the Guidelines for the Management of Helicobacter pylori Infection in Japan by the Japanese Society for Helicobacter Research (JSHR), a number of major issues arose, including the emergence of H. pylori strains resistant to clarithromycin as part of primary eradication therapy, and this led to the Guidelines being revised by the JSHR in 2003. While the JSHR aimed in the 2000 Guidelines to prepare clinicians for the task ahead in view of H. pylori eradication therapy becoming available, the JSHR went a step further in the 2003 Guidelines to include more evidence-based recommendations to address clinical and institutional challenges and issues of interest in the management of H. pylori infection in Japan. Thus, a number of diseases were upgraded to either class A or B indications for H. pylori eradication, including mucosa-associated lymphoid tissue lymphoma (class A), and after endoscopic mucosal resection for early gastric cancer, atrophic gastritis, and gastric hyperplastic polyp (all class B), with further diseases such as extragastric disease also included as class C indications requiring further examination. Concern was expressed over reliance on a single diagnostic test for H. pylori infection, which is in place due to institutional constraints. Metronidazole was also recommended for use in the place of clarithromycin as part of a second-line eradication regimen in light of increasing clarithromycin resistance, although metronidazole remains to be approved for health insurance coverage. Finally, areas requiring further clinical research and endeavors, including establishment of second-line eradication therapy, were also proposed in the 2003 Guidelines to point the way for the future.

Eradication of Helicobacter pylori reduced the immunohistochemical detection of p53 and MDM2 in gastric mucosa

Background:  Although Helicobacter pylori has been regarded as a pathogen of gastric cancer, the mechanism by which H. pylori is involved in gastric carcinogenesis remains unknown. To clarify the role of H. pylori in carcinogenesis, the expression of tumor suppressor p53 and its regulator multiple double minute 2 (MDM2) in gastric mucosa were examined before and after H. pylori eradication.

Is the Recurrence of Helicobacter pylori Infection After Eradication Therapy Resultant from Recrudescence or Reinfection, in Japan

Background. Reinfection of Helicobacter pylori after eradication is rare in developed countries but most often occurs within 1 year. In the present study, we attempted to differentiate between reinfection and recrudescence of H. pylori strains between 6 months and 6 years after successful eradication in Japan, a country with a high prevalence of H. pylori infection.