Hiroto Miwa

H. pylori and gastric cancer: the Asian enigma.

The actual distribution of Helicobacter pylori infection and its related diseases in various Asian countries is controversial. Only limited information is available regarding this issue. We discuss the etiological role of H. pylori in gastric cancer through the Asian experience. Seroprevalence of H. pylori infection in asymptomatic subjects and the annual incidence rate of gastric cancer per 100,000 in various Asian countries are summarized from literature reviews and World Health Organization statistics, respectively. There is a large intercountry variation in incidence of gastric cancer and H. pylori seroprevalence among Asian countries. There is a strong link between H. pylori infection and gastric cancer in many countries, such as Japan. By contrast, the prevalence of H. pylori infection is high in some countries, including India and Bangladesh, but low gastric cancer rates have been reported. These disparate observations represent the Asian enigma. Factors that may influence the etiology of gastric cancer include the genetic diversity of the infecting H. pylori strains and differences in the host genetic background in various ethnic groups, including gastric acid secretion and genetic polymorphisms in proinflammatory cytokines. These factors, in addition to environmental factors, such as personal hygiene and dietary habits, reflect the multifactorial etiology of gastric cancer.

Oesophageal hypersensitivity in Japanese patients with non‐erosive gastro‐oesophageal reflux diseases

Background : Visceral hypersensitivity plays a major role in the pathogenesis of non‐erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients.

Impact of rabeprazole, a new proton pump inhibitor, in triple therapy for Helicobacter pylori infection—comparison with omeprazole and lansoprazole

: A recent trend in curative therapy for Helicobacter pylori infection is the so‐called triple therapy, which consists of a proton pump inhibitor (PPI) and two different antimicrobials. Various regimens employing this triple therapy have been reported. However, little is known about the effectiveness of rabeprazole, a recently developed proton pump inhibitor, when used in the triple therapy.

Recurrent Peptic Ulcers in Patients Following Successful Helicobacter pylori Eradication: A Multicenter Study of 4940 Patients

Objective.  Although curative treatment of Helicobacter pylori infection markedly reduces the relapse of peptic ulcers, the details of the ulcers that do recur is not well characterized. The aim of this study is to describe the recurrence rate and specific features of peptic ulcers after cure of H. pylori infection.

Helicobacter pylori DNA in Drinking Water in Japan

Helicobacter pylori has been detected in drinking water in Peru and Sweden, suggesting the possibility of water‐borne transmission. To date there have been few reports of H. pylori being detected in water; one was of the ureA gene of H. pylori in wells and springs in rural Japan. We examined water sampled in or near urban areas of Japan for H. pylori DNA by three assays using the polymerase chain reaction (PCR). Near Tokyo, samples were obtained: 10 of tap water, 6 of well water, 10 of river water, and 10 of sea water. Samples were filtered with membranes with 0.05‐ or 0.22‐μm pores, which bacterial cells are caught by. Bacterial nucleic acids were extracted and purified and the PCR was done to amplify adhesin specific for H. pylori and the ureA gene, if present. Real‐time PCR that measured the yield in terms of fluorescence was done with primers for 16S rRNA. None of the samples of tap, river, or sea water contained adhesin, ureA or 16S rRNA. None of the 6 samples of well water contained adhesin or ureA, but 2 of the 6 samples contained 16S rRNA. Some of the users of the well had had H. pylori infection in the past H. pylori DNA was detected in well water and the users had been infected, so water‐borne transmission via well water may occur even in towns in Japan.

Alteration of histological gastritis after cure of Helicobacter pylori infection

Background : It is still disputed whether gastric atrophy or intestinal metaplasia improves after the cure of Helicobacter pylori infection.

Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up.

Objective. It is proposed that Fusobacterium varium might be one of the elusive pathogenic factors in ulcerative colitis (UC). Our goal was to assess whether an antibiotic combination therapy against F. varium is effective for induction and maintenance of remission of UC. Material and methods. Twenty chronic, active UC patients with F. varium infection were enrolled consecutively and were randomly assigned to receive amoxicillin, tetracycline or metronidazole per os for 2 weeks (treatment group; n=10), or no antibiotics (control group; n=10). F. varium was sensitive to the antibiotics. Symptom assessment, endoscopic and histological evaluations were performed blind before enrollment at 3–5 months and 12–14 months after the treatment. Serum immunoglobulins to F. varium were measured using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical detection of F. varium in biopsy specimens was carried out using the avidin-biotin complex method. Results. The clinical activity, endoscopic and histological scores in the treatment group decreased significantly at 3–5 and 12–14 months after the end of treatment compared with those in the control group (p=0.001–0.036). The remission rate in the treatment group was higher than that in the control group (p=0.037). In addition, the titers of antibody to F. varium and the F. varium density in the mucosa decreased at both the short- and long-term follow-ups in the treatment group (p=0.0002–0.049). No serious drug-related toxicity was observed during the trial. Conclusions. The 2-week antibiotic combination therapy against F. varium was effective and safe in patients with chronic, active ulcerative colitis in this long-term follow-up study.

Addition of Metronidazole to Rabeprazole-Amoxicillin-Clarithromycin Regimen for Helicobacter pylori Infection Provides an Excellent Cure Rate with Five-Day Therapy

Background. New triple therapy for eradication of Helicobacter pylori based on a proton pump inhibitor (PPI) provides a cure rate of approximately 90% with few adverse effects. Recently, a PPI‐based quadruple therapy, which consists of a PPI plus bismuth‐based triple therapy for 7 days, has been studied, and a sufficient eradication rate has been achieved. However, a shorter duration results in improved compliance. In this study, newly developed short‐term, simple twice‐daily quadruple therapy consisting of rabeprazole, amoxicillin, clarithromycin, and metronidazole (RACM) was compared with a PPI‐based triple‐therapy regimen for eradication of H. pylori.

Efficacy of reduced dosage of rabeprazole in PPI/AC therapy for Helicobacter pylori infection. Comparison of 20 and 40 mg rabeprazole with 60 mg lansoprazole.

Proton pump inhibitor (PPI)- based triple therapy has been a recent trend for treatment of Helicobacter pylori infection, with the PPI–amoxicillin–clarithromycin (PPI/AC) regimen being one of the most popular. We have reported the effectiveness of PPI/AC regimens in the Japanese population and have demonstrated that the effectiveness of 40 mg rabeprazole, a recently developed PPI, is similar to that of 40 mg of omeprazole and 60 mg of lansoprazole when used in combination with amoxicillin and clarithromycin. In this study, we focused on whether 20 mg of rabeprazole is effective in our patient population by comparing that dosage with 40 mg of rabeprazole and 60 mg of lansoprazole. In all, 308 H. pylori-infected patients [236 men and 72 women; age (mean ± sem) 49.3 ± 0.6 years] with peptic ulcer disease (N = 270) or nonulcer dyspepsia (N = 38) were randomly assigned to one of three different PPI/AC regimens for seven days: LAC (N = 104), consisting of lansoprazole 30 mg twice a day, amoxicillin 500 mg three times a day, and clarithromycin 200 mg twice a day; RAC (N = 104), consisting of rabeprazole 20 mg twice a day, amoxicillin 500 mg three times a day, and clarithromycin 200 mg twice a day; and the R1/2AC regimen (N = 100), which included rabeprazole 10 mg twice a day, amoxicillin 500 mg three times a day, and clarithromycin 200 mg twice a day. Cure of the infection was determined by the [13C]urea breath test one month after completion of the treatment. Intention-to-treat based and per-protocol based cure rates for the LAC, RAC, and R1/2AC regimens were 82.7 (95% CI, 74–89) and 88.7% (81–94), 85.6 (77–92) and 89.8% (82–95), and 87.0 (79–93) and 89.7% (82–95), respectively. Although adverse effects were reported by 20.3% of the patients, these affected compliance in only five patients in the RAC and LAC regimens and none in the R1/2AC group. Overall complete compliance was achieved in 94.7% of interviewed patients. In conclusion, the effectiveness of the PPI/AC regimen with 20 mg of rabeprazole is comparable with and even safer than that of 40 mg of rabeprazole and 60 mg of lansoprazole in our patient population.

Strategy for retreatment of therapeutic failure of eradication of Helicobacter pylori infection

A proton pump inhibitor (PPI)‐based triple therapy consisting of a PPI, amoxicillin (A) and clarithromycin (C) or metronidazole (M) provides an eradication rate ranging from 80 to 90%. However, there have been few controlled studies with regard to the most effective regimen to re‐treat patients after failure of the first‐line therapy. Accordingly, we retrospectively reviewed our experiences and compared regimens with different combinations of antimicrobials to determine the optimal retreatment regimen.