Katsuhiro Mabe

Newly Developed Antibiotic Combination Therapy for Ulcerative Colitis: A Double-Blind Placebo-Controlled Multicenter Trial

OBJECTIVES:Fusobacterium varium may contribute to ulcerative colitis (UC). We conducted a double-blind placebo-controlled multicenter trial to determine whether antibiotic combination therapy induces and/or maintains remission of active UC.METHODS:Patients with chronic mild-to-severe relapsing UC were randomly assigned to oral amoxicillin 1500 mg/day, tetracycline 1500 mg/day, and metronidazole 750 mg/day, vs. placebo, for 2 weeks, and then followed up. The primary study end point was clinical response (Mayo score at 3 months after treatment completion) and secondary end points were clinical and endoscopic score improvements at 12 months. Anti-F. varium antibodies were measured by enzyme-linked immunosorbent assay.RESULTS:Treatment and placebo groups each had 105 subjects. At the primary end point, response rates were significantly greater with antibiotics than with placebo (44.8 vs. 22.8%, P=0.0011). Endoscopic scores significantly improved at 3 months (P=0.002 vs. placebo). Remission rates were 19.0% (antibiotics) vs. 15.8% (placebo) at 3 months (P=0.59). At the secondary end point, response rates were significantly greater with antibiotics than with placebo (49.5 vs. 21.8%, respectively, P<0.0001). Endoscopic scores were significantly improved at 12 months after antibiotic treatment (P=0.002 vs. placebo). Remission rates had improved to 26.7% with antibiotics vs. 14.9% for placebo, at 12 months (P=0.041). F. varium antibody titers decreased in responders but not in nonresponders, and more in the antibiotic than in the placebo group. More pretreatment steroid-dependent UC patients discontinued corticosteroids after treatment completion (6 months: 28.6 vs. 11.8%, respectively, P=0.046; 9 months: 34.7 vs. 13.7%, respectively, P=0.019; and 12 months: 34.7 vs. 13.7%, respectively, P=0.019). These effects were greater in the subanalysis of the active group (Mayo scores of 6–12) than in that of total cases (0–12). No serious drug-related toxicities occurred.CONCLUSIONS:The 2-week triple antibiotic therapy produced improvement, remission, and steroid withdrawal in active UC more effectively than a placebo.

Urease-positive bacteria in the stomach induce a false-positive reaction in a urea breath test for diagnosis of Helicobacter pylori infection

This study investigated the influence of urease-positive non-Helicobacter pylori bacteria on the results of a urea breath test (UBT) to evaluate the diagnostic utility of a UBT using film-coated [(13)C]urea tablets. The UBT was performed in 102 patients treated with a proton pump inhibitor and antibiotics for the eradication of H. pylori. Urease-producing bacteria other than H. pylori were isolated and identified from the oral cavity and stomach. In 4/102 patients, the UBT gave false-positive results. These false-positive results were found to be caused by the presence of urease-positive bacteria in the oral cavity and stomach. Five bacterial species with urease activity (Proteus mirabilis, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter cloacae and Staphylococcus aureus) were subsequently isolated from the oral cavity and/or stomach. As there was no correlation between the in vitro urease activity of urease-positive non-H. pylori bacteria and the UBT value, and all of the patients with a false-positive UBT result were suffering from atrophic gastritis, it is possible that the false-positive results in the UBT were a result of colonization of urease-positive bacteria and gastric hypochlorhydric conditions. Thus, for the diagnosis of H. pylori infection using a UBT, the influence of stomach bacteria must be considered when interpreting the results.

Prevalence of Helicobacter pylori Infection by Birth Year and Geographic Area in Japan

Helicobacter pylori (H. pylori)‐related diseases are responsible for a tremendous amount of morbidity and mortality in Japan. We estimated the prevalence of H. pylori infection by sex, birth year, and geographic area among Japanese adults.

Frequency of Helicobacter pylori-Negative Gastric Cancer and Gastric Mucosal Atrophy in a Japanese Endoscopic Submucosal Dissection Series Including Histological, Endoscopic and Serological Atrophy

Background: The definition of Helicobacter pylori-negative gastric cancer depends on the accuracy of diagnosis of H. pylori infection. The aim of this study was to determine the frequency of H. pylori-negative gastric cancer and to clarify relationships with histological atrophy, endoscopic atrophy, and serological atrophy. Methods: A total of 240 early gastric cancers were included in this study. The status of H. pylori infection was determined from the rapid urease test, 13C-urea breath test, H. pylori culture, histopathological examination and examination of IgG antibodies. In H. pylori-negative gastric cancer, histological atrophy and intestinal metaplasia, endoscopic atrophy and serological atrophy were assessed by pepsinogen. Results: The rate of H. pylori infection was 77.9% and 19 patients (7.9%) had a history of eradication. 34 patients (14.2%) were diagnosed with H. pylori-negative gastric cancer using diagnostic tools of H. pylori. However, most of the patients with H. pylori-negative gastric cancer had histological atrophy and intestinal metaplasia. Only 1 gastric cancer (0.42%) occurred in the mucosa without histological atrophy, endoscopic atrophy or serological atrophy. Conclusion: Early gastric cancers in the Japanese endoscopic submucosal dissection series were strongly related to current or past infection with H. pylori and to gastric mucosal atrophy.

Clinicopathological analysis of early-stage gastric cancers detected after successful eradication of Helicobacter pylori.

Background and Aims:  The results of a randomized controlled study and meta‐analysis study have recently proved that Helicobacter pylori eradication has a preventive effect against the development of metachronous and primary gastric cancer. However, gastric cancer is sometimes detected after successful eradication. There is a lack of study about gastric cancers in eradicated patients. To clarify the characteristics of gastric cancers detected after H. pylori eradication, we analyzed the clinicopathological features of these cancers.

Endoscopic resection (endoscopic mucosal resection/ endoscopic submucosal dissection) for superficial esophageal squamous cell carcinoma: current status of various techniques.

Endoscopic resection (ER) has been widely accepted as an effective and minimally invasive treatment for patients with superficial esophageal squamous cell carcinoma (SCC). Techniques of conventional endoscopic mucosal resection (EMR) were first developed for ER. There are three representative methods of conventional EMR: endoscopic esophageal mucosal resection (EEMR)‐tube method, EMR using a cap‐fitted endoscope (EMRC) method and two‐channel EMR method. In the past decade, techniques of endoscopic submucosal dissection (ESD) have become established as standard methods of ER. ESD allows en bloc resection of a lesion, irrespective of the size and shape of the lesion. Recently, results of retrospective cohort studies confirming that ESD is superior to EMR as a curative treatment for superficial esophageal SCC have been reported. Representative knives that are now frequently used in esophageal ESD include Hook knife, Triangle tip knife, IT knife nano, Flush knife‐BT, Dual knife, SB knife, and so on. Although there are various knives developed for ESD, the basic techniques for safe and effective ESD are the same.

Efficacy of omeprazole, famotidine, mosapride and teprenone in patients with upper gastrointestinal symptoms: an omeprazole-controlled randomized study (J-FOCUS)

BackgroundIn Japan, treatment guidelines are lacking for patients with upper gastrointestinal symptoms. We aimed to compare the efficacy of different drugs for the treatment of uninvestigated upper gastrointestinal symptoms.MethodsThis was a randomized, open-label, parallel-group multicenter study. Helicobacter pylori-negative, endoscopically uninvestigated patients ≥ 20 years of age with upper gastrointestinal symptoms of at least moderate severity (Global Overall Symptom score [GOS] ≥ 4 on a 7-point Likert scale) were randomized to treatment with omeprazole (10 mg once daily), famotidine (10 mg twice daily), mosapride (5 mg three times daily) or teprenone (50 mg three times daily). The primary endpoint was sufficient relief of upper gastrointestinal symptoms after 4 weeks of treatment (GOS ≤ 2). UMIN clinical trial registration number: UMIN000005399.ResultsOf 471 randomized patients, 454 were included in the full analysis set. After 4 weeks of treatment, sufficient symptom relief was achieved by 66.9% of patients in the omeprazole group, compared with 41.0%, 36.3% and 32.3% in the famotidine, mosapride and teprenone groups, respectively (all, p < 0.001 vs omeprazole). There were no treatment-related adverse events.ConclusionsThe favorable efficacy and safety profiles of omeprazole in relieving uninvestigated upper gastrointestinal symptoms support its use as first-line treatment in this patient group in Japan. Patients who show no improvement in symptoms despite PPI use, and those with alarm symptoms (such as vomiting, GI bleeding or acute weight loss) should receive further investigation, including prompt referral for endoscopy.Trial registrationUMIN000005399.

Strategies for eliminating death from gastric cancer in Japan

In Japan, efforts have been directed toward improving the detection of early gastric cancer by double contrast radiography and endoscopy, since early cancer has a good prognosis, resulting in Japan having the world’s best diagnostic system for early gastric cancer. The 5-year survival rate of gastric cancer patients in Japan is much higher than in Western countries by the development of endoscopic treatment for early gastric cancer. In February 2013, Japanese national health insurance cover for H. pylori eradication therapy was expanded to patients with H. pylori-associated gastritis, a type of chronic gastritis. H. pylori-associated gastritis causes gastric and duodenal ulcers and gastric polyps, therefore, providing treatment for this gastritis is likely to substantially decrease the prevalence of both gastric and duodenal ulcer and gastric cancer. Patients with gastritis are tested for H. pylori infection and those who are positive receive eradication therapy followed by periodic endoscopic surveillance. If such an approach is pursued further in Japan, gastric cancer deaths will show a dramatic decline after 10–20 years.

Helicobacter pylori Eradication to Eliminate Gastric Cancer: The Japanese Strategy

Helicobacter pylori eradication therapy for chronic gastritis achieved world-first coverage by the Japanese national health insurance scheme in 2013, making a dramatic decrease of gastric cancer-related deaths more realistic. Combining H pylori eradication therapy with endoscopic surveillance can prevent the development of gastric cancer. Even if it develops, most patients are likely to be diagnosed at an early stage, possibly resulting in fewer gastric cancer deaths. Success with the elimination of gastric cancer in Japan could lead other countries with a high incidence to consider a similar strategy, suggesting the potential for elimination of gastric cancer around the world.

Nationwide survey of Helicobacter pylori treatment for children and adolescents in Japan

To prevent gastric cancer, a test‐and‐treat strategy for Helicobacter pylori has been proposed. This retrospective study assessed the clinical features, efficacy and safety of treatment for H. pylori infection in children and adolescents.