Mototsugu Kato

Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial

BACKGROUND The relation between Helicobacter pylori infection and gastric cancer has been proven in epidemiological studies and animal experiments. Our aim was to investigate the prophylactic effect of H pylori eradication on the development of metachronous gastric carcinoma after endoscopic resection for early gastric cancer. METHODS In this multi-centre, open-label, randomised controlled trial, 544 patients with early gastric cancer, either newly diagnosed and planning to have endoscopic treatment or in post-resection follow-up after endoscopic treatment, were randomly assigned to receive an H pylori eradication regimen (n=272) or control (n=272). Randomisation was done by a computer-generated randomisation list and was stratified by whether the patient was newly diagnosed or post-resection. Patients in the eradication group received lansoprazole 30 mg twice daily, amoxicillin 750 mg twice daily, and clarithromycin 200 mg twice daily for a week; those in the control group received standard care, but no treatment for H pylori. Patients were examined endoscopically at 6, 12, 24, and 36 months after allocation. The primary endpoint was diagnosis of new carcinoma at another site in the stomach. Analyses were by intention to treat. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000001169. FINDINGS At 3-year follow-up, metachronous gastric carcinoma had developed in nine patients in the eradication group and 24 in the control group. In the full intention-to-treat population, including all patients irrespective of length of follow-up (272 patients in each group), the odds ratio for metachronous gastric carcinoma was 0.353 (95% CI 0.161-0.775; p=0.009); in the modified intention-to-treat population, including patients with at least one post-randomisation assessment of tumour status and adjusting for loss to follow-up (255 patients in the eradication group, 250 in the control group), the hazard ratio for metachronous gastric carcinoma was 0.339 (95% CI 0.157-0.729; p=0.003). In the eradication group, 19 (7%) patients had diarrhoea and 32 (12%) had soft stools. INTERPRETATION Prophylactic eradication of H pylori after endoscopic resection of early gastric cancer should be used to prevent the development of metachronous gastric carcinoma. FUNDING Hiroshima Cancer Seminar Foundation.

Guidelines for the Management of Helicobacter pylori Infection in Japan: 2009 Revised Edition

Background:  Over the past few years, the profile of Helicobacter pylori infection has changed in Japan. In particular, the relationship between H. pylori and gastric cancer has been demonstrated more clearly. Accordingly, the committee of the Japanese Society for Helicobacter Research has revised the guidelines for diagnosis and treatment of H. pylori infection in Japan.

Possible role of Helicobacter pylori infection in early gastric cancer development.

Background. Gastric cancer is the most frequently diagnosed malignancy in Japan. The possible relationship between Helicobacter pylori infection and gastric cancer in Japan was evaluated.

Atrophic Gastritis and Intestinal Metaplasia in Japan: Results of a Large Multicenter Study

This study evaluated the relationship between Helicobacter pylori infection, atrophic gastritis and intestinal metaplasia in Japan.

What Role Does Helicobacter pylori Play in Gastric Cancer

Several lines of evidence support an association between Helicobacter pylori infection and gastric cancer. The natural history of H. pylori-associated gastritis is inexorable progression ultimately leading to gastric atrophy. In general, this process requires between 20 and 40 years to complete. Atrophic gastritis is widely considered to be a precursor lesion of the intestinal type of gastric cancer. Moreover, areas with a high prevalence of H. pylori infection also have a high prevalence of gastric cancer. Strong evidence from three prospective studies shows the risk of gastric cancer to be increased fourfold in H. pylori-positive persons. Several retrospective studies have also confirmed that H. pylori infection is associated with development of gastric cancer, especially in the younger generation, early gastric cancer, and noncardiac gastric cancer. H. pylori alone is not likely responsible for gastric cancer. Rather, it may provide a suitable environment, including chronic gastritis and intestinal metaplasia, for neoplastic change. Recognition of an association between H. pylori infection and gastric cancer has led to a major shift in emphasis on the cause of the disease. Research into H. pylori has focused attention on the importance of chronic inflammation and impaired host defense mechanisms as factors in the development of gastric cancer. H. pylori infection leads to changes in many factors that are important to the pathogenesis of gastric cancer, including vitamin C content of gastric juice, reactive oxygen metabolites, and epithelial cell proliferation. Eradication of the organism may reverse these changes. Therefore, eradication of H. pylori in infected persons might be a route to preventing gastric cancer, although many questions still remain as to the effectiveness of this strategy.

A Multicenter, Double‐Blind Study on Triple Therapy with Lansoprazole, Amoxicillin and Clarithromycin for Eradication of Helicobacter pylori in Japanese Peptic Ulcer Patients

Two triple therapies with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of Helicobacter pylori were studied in multicenter, double‐blind fashion to evaluate the eradication rate of H. pylori and safety of eradiation treatment in Japanese patients with H. pylori‐positive active gastric ulcers or duodenal ulcers.

Studies of 13C-urea breath test for diagnosis of Helicobacter pylori infection in Japan

Abstract: In recent years Helicobacter pylori infection has been implicated in the etiology of a variety of upper gastrointestinal diseases. The aim of this multi-center trial was to search for the cut-off value of the simple 13C-urea breath test (13C-UBT) for diagnosis of H. pylori infection, and to examine the sensitivity and specificity of 13C-UBT for culture, the rapid urease test (CLO test), histology, and serological tests. Two hundred and forty-eight patients participated in this study after giving their informed consent. Endoscopic biopsy specimens were taken from gastric antrum and corpus for culture (190 patients), CLO test (222 patients), and histology (98 patients). A serological test was carried out for all patients. H. pylori infection was established when culture was positive or more than two of the tests, histology, CLO test, and serological test, were positive, and non-infection status was established when the all tests more than two tests were negative. After baseline breath samples were taken, the patients (who had fasted) were given 100 mg of 13C-urea in 100 ml water while sitting; they washed out the mouth with water. They were then placed in the left lateral decubitus position for 5 min, and additional breath samples were taken 10, 20, 30, 45, and 60 min after urea administration, with patients in the sitting position. One hundred and sixty-five of the 248 patients were infected, 48 were not infected, and H. pylori infection status was not evaluated in 35 by endoscopic and serological tests. Breath samples at 20 min were employed to determine the cut-off value. Using the receiver operating characteristic (ROC) curve, we determined the cut-off value for a positive UBT at 2.5 Δ‰. The sensitivities of UBT for culture, CLO test, histology, and serological test were 98.4%, 98.6%, 100.0%, and 92.5%, and the specificities were 78.8%, 82.5%, 83.3%, and 87.3%, respectively. The cut-off value of 13C-UBT for the diagnosis of H. pylori infection was 2.5 Δ‰; this test is a simple and non-invasive method for the diagnosis of this infection and has high sensitivity and specificity.

Changing Antimicrobial Susceptibility Epidemiology of Helicobacter pylori Strains in Japan between 2002 and 2005

ABSTRACT Surveillance of Helicobacter pylori antimicrobial susceptibility reflecting the general population in Japan is limited. The antimicrobial susceptibilities of 3,707 H. pylori strains isolated from gastric mucosa samples of previously untreated patients diagnosed with gastroduodenal diseases at 36 medical facilities located throughout Japan between October 2002 and September 2005 were evaluated. Using an agar dilution method for antimicrobial susceptibility testing of H. pylori, the MIC distributions and trends during the study period for clarithromycin, amoxicillin, and metronidazole were studied. While the MIC50 and MIC90 for clarithromycin did not change during the 3-year period, the MIC80 showed a 128-fold increase. Furthermore, the rate of resistance increased yearly from 18.9% (2002 to 2003) to 21.1% (2003 to 2004) and 27.7% (2004 to 2005). With a resistance rate of 19.2% among males compared to 27.0% among females, a significant gender difference was observed (P < 0.0001). Our study shows that in Japan, there is an evolving trend towards increased resistance to clarithromycin with geographical and gender differences as well as between clinical disease conditions. No significant changes in resistance were observed for amoxicillin and metronidazole during the period. While the benefit of H. pylori antimicrobial susceptibility testing has been debated in Japan, current empirical regimens are not based on susceptibility data representative of the general population. The development of an effective H. pylori eradication regimen in Japan will require continued resistance surveillance as well as a better understanding of the epidemiology of resistance.

Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment

Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment have been produced by the Japan Gastroenterological Endoscopy Society in collaboration with the Japan Circulation Society, the Japanese Society of Neurology, the Japan Stroke Society, the Japanese Society on Thrombosis and Hemostasis and the Japan Diabetes Society. Previous guidelines from the Japan Gastroenterological Endoscopy Society have focused primarily on prevention of hemorrhage after gastroenterological endoscopy as a result of continuation ofantithrombotic therapy, without considering the associated risk of thrombosis. The new edition of the guidelines includes discussions of gastroenterological hemorrhage associated with continuation of antithrombotic therapy, as well as thromboembolism associated with withdrawal of antithrombotic therapy.

The Relationship Between Consumption of Antimicrobial Agents and the Prevalence of Primary Helicobacter pylori Resistance

Background. Primary and acquired resistance to the antimicrobial agents is a primary reason for the failure of Helicobacter pylori eradication therapies. We assessed the primary antibiotic resistance rates of H. pylori to three different antibiotics and its relationship due to the annual antibiotic consumption in Japan during the period prior to approval of anti‐H. pylori therapy in Japan.