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Background Gastric cancer after Helicobacter pylori (HP) eradication is a crucial clinical challenge today as HP eradication therapy is widely performed. Detecting gastric cancer after HP eradication tends to be difficult with normal white-light endoscopy. In the present study, we aimed to identify easily-evaluated endoscopic findings that indicate the presence of gastric cancer after HP eradication so that endoscopists can consider additional detailed examinations at the site. Methods We analyzed the endoscopic images of 43 patients who underwent endoscopic submucosal dissection for early gastric cancer after HP eradication and 119 patients with an HP eradication history who underwent esophagogastroduodenoscopy for a medical checkup. Endoscopic findings were evaluated according to the Kyoto classification of gastritis (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness) and map-like redness. Results Patients with gastric cancer had significantly higher total Kyoto risk scores; more atrophy, intestinal metaplasia, and diffuse redness; and a significantly higher prevalence of map-like redness compared with those without gastric cancer, in the univariate analyses. We used logistic regression analysis with forward selection based on the likelihood ratio to develop a model using atrophy and diffuse redness. Receiver operating characteristic analysis showed that a score of A2 in the Kyoto classification of gastritis (open-type atrophic pattern in the Kimura–Takemoto classification) was an endoscopic marker for the presence of post-HP-eradication gastric cancer. Conclusions Endoscopic severe gastric mucosal atrophy is useful to screen patients for gastric cancer after HP eradication.

Significance This study directly demonstrates virulence-associated features of Helicobacter suis infection using isolates obtained from human stomachs. H. suis is the second-most-prevalent Helicobacter species in the human stomach, but diagnostic tests for Helicobacter pylori often fail to diagnose H. suis. H. suis does not have orthologs of either cytotoxin-associated gene A (CagA) or vacuolating cytotoxin A (VacA), two major virulence factors in H. pylori, suggesting that the molecular pathogenicity of H. suis and clinical manifestations caused by H. suis infection are different from those caused by H. pylori. This study paves the way for epidemiological research aimed at identifying the causal relationships between H. suis and gastric diseases and developing diagnostic methods., Helicobacter suis, a bacterial species naturally hosted by pigs, can colonize the human stomach in the context of gastric diseases such as gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Because H. suis has been successfully isolated from pigs, but not from humans, evidence linking human H. suis infection to gastric diseases has remained incomplete. In this study, we successfully in vitro cultured H. suis directly from human stomachs. Unlike Helicobacter pylori, the viability of H. suis decreases significantly on neutral pH; therefore, we achieved this using a low-pH medium for transport of gastric biopsies. Ultimately, we isolated H. suis from three patients with gastric diseases, including gastric MALT lymphoma. Successful eradication of H. suis yielded significant improvements in endoscopic and histopathological findings. Oral infection of mice with H. suis clinical isolates elicited gastric and systemic inflammatory responses; in addition, progression of gastric mucosal metaplasia was observed 4 mo postinfection. Because H. suis could be isolated from the stomachs of infected mice, our findings satisfied Koch’s postulates. Although further prospective clinical studies are needed, H. suis, like H. pylori, is likely a gastric pathogen in humans. Furthermore, comparative genomic analysis of H. suis using complete genomes of clinical isolates revealed that the genome of each H. suis isolate contained highly plastic genomic regions encoding putative strain-specific virulence factors, including type IV secretion system–associated genes, and that H. suis isolates from humans and pigs were genetically very similar, suggesting possible pig-to-human transmission.

Background: Helicobacter suis, a bacterial species naturally hosted by pigs, can colonize the human stomach in the context of gastric diseases, such as gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Because H. suis has been successfully isolated from pigs, but not from humans, evidence linking human H. suis infection to gastric diseases has remained incomplete. The aim of this study is to elucidate the pathogenicity of H. suis by genetic characterization and through animals infected with H. suis isolated from human stomachs. Methods: H. suis from human gastric biopsies was isolated as previously described in pigs, with modifications. Mice were orally infected with H. suis for 4 months, and then pathogenesis was analyzed. Whole-genome analysis of H. suis isolates was performed by short-read and long-read sequencing, and their genomes were subjected to comparative analysis. Findings: H. suis was successfully isolated from three patients with gastric diseases, including gastric MALT lymphoma. Successful eradication of H. suis yielded significant improvements in endoscopic and histopathological findings in all patients. H. suis infection in mice using clinical isolates elicited gastric and systemic inflammatory responses, and H. suis could be isolated from the stomachs of infected mice. Therefore, according to Koch’s postulates, these findings demonstrate that H. suis is a human gastric pathogen. Genomic analysis revealed high similarity between isolates from humans and pigs, suggesting possible horizonal transmission of H. suis. Interpretation: This is the first study to directly demonstrate virulence-associated features of H. suis infection using isolates obtained from human stomachs. Since H. suis would have been missed by routine diagnostic tests for Helicobacter pylori, large-scale epidemiological research on H. suis is needed to identify causal relationships with gastric diseases and develop novel diagnostic methods. Funding: MEXT/JSPS KAKENHI Grant numbers JP19H03474 for (HM) and JP20K08365 for (KT), and AMED Grant Numbers JP20fk0108148 (ER) and JP20fk0108133 (MS). Conflict of Interest: ER has received research funding from GlaxoSmithKline, outside the submitted work. All other authors declare no competing interests. Ethical Approval: Ethical approvals were obtained from all participating hospitals and the National Institute of Infectious Diseases (NIID). Written informed consent was obtained from all participants.

Objective: Guidelines on the management of antithrombotic therapy for endoscopic procedures vary among countries. Differences in the management of antithrombotic agents for endoscopic procedures between Western and Eastern countries have already been reported. However, no study has investigated the differences among Asian countries. The aim of this study was to examine the differences in the etiology of gastrointestinal bleeding and management of antithrombotic agents during endoscopic procedures between Japan and other Asian countries (OAC). Methods: Questionnaires regarding gastrointestinal bleeding in clinical practice and management of antithrombotic agents during endoscopy were distributed to members of the International Gastroenterology Consensus Symposium Study Group. We analyzed the questionnaire answers and compared the results between Japan and OAC. Results: The cause of and treatment methods for gastrointestinal bleeding differed between Japan and OAC. In Japan, the trend was to continue drugs at the time of biopsy and endoscopic therapy. Even in cases of discontinuation, the drug withdrawal period was as short as p = 0.016). Conclusion: Due to differences in guidelines and complications associated with discontinuation of drugs, the antithrombotic withdrawal period in Japan tended to be shorter than that in OAC.

Background: Gastrointestinal endoscopy and Helicobacter pylori(H. pylori) eradication therapy are commonly performed even among the elderly population. The aim of this study was to understand the way endoscopists viewed the application of endoscopy and H. pylori eradication in the elderly of East Asian countries. Methods: Self-administered questionnaires containing 13 questions on endoscopy and H. pylori eradication in the elderly were distributed to major institutions in Japan, South Korea, China, Indonesia, and the Philippines. Results: Two hundred and fifteen endoscopists (111 in Japan, 39 in China, 24 in Korea, 21 in Indonesia, and 20 in the Philippines) participated in this study. In the institutions where these endoscopists were associated, around 50% of patients undergoing endoscopy were above the age of 60 years. The participating endoscopists indicated that the necessity of screening esophagogastroduodenoscopy and colonoscopy was lower in populations aged over 81 than the other age groups. They hesitated to perform therapeutic endoscopy, such as endoscopic submucosal dissection or endoscopic retrograde cholangiopancreatography, more often in patients over 85. They also hesitated to perform H. pylori eradication in patients aged over 81, especially in Japan. Conclusion: Endoscopists had significantly different attitudes regarding the indications for screening or therapeutic endoscopy and H. pylori eradication therapy in younger and elderly populations in East Asian countries.

We herein report a case of simultaneous amebic colitis and cytomegalovirus (CMV) enteritis in an HIV-infected patient. The patient was a 40-year-old man who developed bloody stool and diarrhea. We diagnosed him with severe amebic colitis associated with HIV infection and administered metronidazole. While his symptoms began to improve, the patient then developed CMV enteritis. We administered ganciclovir, and his symptoms improved. However, despite control of the infection, stenosis of the descending colon caused intestinal obstruction, and colostomy was performed. This case shows the importance of considering the possibility of simultaneous infection when gastrointestinal symptoms appear in people infected with HIV.

Background and Aim Helicobacter pylori (H. pylori) infection is a strong risk factor for the development of gastric cancer. In 2013, the Japanese government approved H. pylori eradication therapy in patients with chronic gastritis as well as peptic ulcer. However, the continuing decline in eradication rates for first-line H. pylori eradication therapies is an urgent problem. In this study, we investigated changes in the first-line eradication rate from 2001 to 2010. Methods Eradication rates for 7-day triple therapy [proton pump inhibitor (rabeprazole 20 mg, lansoprazole 60 mg, or omeprazole 40 mg) + amoxicillin 1500 mg + clarithromycin (CAM) 400 or 800 mg, daily] were collated from 14 hospitals in the Tokyo metropolitan area. The urea breath test was used for the evaluation of eradication. The cut-off value was less than 2.5%. Results The yearly eradication rates (intention to treat/per protocol) were 78.5/79.5% (2001, n = 242), 71.2%/72.9% (2002, n = 208), 67.8%/70.5% (2003, n = 183), 75.6%/84.6% (2004, n = 131), 56.4%/70.5% (2005, n = 114), 70.5%/75.8% (2006, n = 271), 67.4%/82.0% (2007,n = 135), 64.0%/76.3% (2008, n = 261), 60.5%/74.3% (2009, n = 329), and 66.5%/78.8% (2010, n = 370), respectively. Examination of eradication rates according to CAM dosage revealed an eradication rate of 65.6% (383/584) for CAM 400 mg daily, and 68.5% (1124/1642) for CAM 800 mg daily, with no significant difference seen between dosages. Conclusion In recent years, eradication rates for first-line triple therapy have obviously decreased, but no noticeable decrease has occurred after 2001.

Background: Diagnostic and therapeutic strategies in inflammatory bowel disease (IBD) vary among countries in terms of availability of modalities, affordability of health care resource, health care policy and cultural background. This may be the case in different countries in Eastern Asia. The aim of this study was to determine and understand the differences in diagnostic and therapeutic strategies of IBD between Japan and the rest of Asian countries (ROA). Methods: Questionnaires with regard to clinical practice in IBD were distributed to members of the International Gastroenterology Consensus Symposium Study Group. The responders were allowed to select multiple items for each question, as multiple modalities are frequently utilized in the diagnosis and the management of IBD. Dependency and independency of selected items for each question were evaluated by the Bayesian network analysis. Results: The selected diagnostic modalities were not very different between Japan and ROA, except for those related to small bowel investigations. Balloon-assisted enteroscopy and small bowel follow through are frequently used in Japan, while CT/MR enterography is popular in ROA. Therapeutic modalities for IBD depend on availability of such modalities in clinical practice. As far as modalities commonly available in both regions are concerned, there seemed to be similarity in the selection of each therapeutic modality. However, evaluation of dependency of separate therapeutic modalities by Bayesian network analysis disclosed some difference in therapeutic strategies between Japan and ROA. Conclusion: Although selected modalities showed some similarity, Bayesian network analysis elicited certain differences in the clinical approaches combining multiple modalities in various aspects of IBD between Japan and ROA.

Background: The environment surrounding Helicobacter pylori eradication treatment is dramatically changing. Recently, vonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), was introduced onto the market in 2015. The aging of Japan’s demographic structure is becoming pronounced. In this study, we examined the trend of the eradication rate of H. pylori in the metropolitan area and examined factors concerning successful eradication. Methods: We collected data from 20 hospitals in the Tokyo metropolitan area on patients who received first-line eradication therapy with a proton-pump inhibitor (PPI)/P-CAB, amoxicillin, and clarithromycin for 1 week and second-line eradication therapy with a PPI/P-CAB, amoxicillin, and metronidazole for 1 week from 2013 to 2018. The annual eradication rate and associated factors for successful eradication were analyzed. Results: We collected data of 4097 and 3572 patients in the first- and second-line eradication therapies, respectively. The eradication rate decreased from 2013 to 2014 and increased again from 2015 to 2018 with the first-line therapy [the eradication rates in 2013, 2014, 2015, 2016, 2017 and 2018 were 71.8%, 63.7%, 78.5%, 84.6%, 89.7 and 90.1%, respectively, in the per protocol (PP)]. The second-line eradication rates were 90.0%, 82.6%, 88.8%, 87.5%, 91.8% and 90.1% in 2013, 2014, 2015, 2016, 2017 and 2018, respectively, in PP. Vonoprazan was an independent factor for successful eradication in not only first-line, but also second-line eradication. Age over 75 years was an independent factor for eradication failure in both first- and second-line eradication therapies. Conclusion: The eradication rate improved from 2015 to 2018 with the first-line therapy because of the introduction of vonoprazan in the market. The eradication rates with first- and second-line regimens in elderly patients were lower than those in younger patients.

Background In Japan, the eradication rate of first-line therapy for Helicobacter pylori (H. pylori) with a proton pump inhibitor (PPI), amoxicillin (AMPC) and clarithromycin (CAM) has been decreasing because of a high prevalence of CAM resistance. A possible decrease of the eradication rate for second-line therapy with a PPI, AMPC and metronidazole (MNZ) is of concern. The aim of this study is to assess the trends in second-line eradication therapy for H. pylori in Japan. Materials and Methods We accumulated data retrospectively on patients administered second-line eradication therapy for Helicobacter pylori with a PPI, AMPC, and MNZ for 1 week after failure of first-line eradication therapy with a PPI, AMPC and CAM at 15 facilities in the Tokyo metropolitan area in Japan from 2007 to 2011. Trends for second-line eradication rates in modified intention-to-treat (ITT) analyses were investigated. Second-line eradication rates were categorized by three PPIs (rabeprazole (RPZ), lansoprazole (LPZ) or omeprazole (OMZ)) and evaluated. Results We accumulated data on 1373 patients. The overall second-line eradication rate was 92.4%. Second-line eradication rates in 2007, 2008, 2009, 2010 and 2011 were 97.7, 90.6, 94.5, 91.8 and 91.8%, respectively, with no significant trends revealed. Second-line eradication rates categorized by three PPIs for the entire 5-year period were 91.6, 93.4 and 92.4% (RPZ, LPZ and OPZ, respectively) with no significant differences among the three PPIs. Conclusions From 2007 to 2011, there were no significant trends in the second-line eradication rates and the rates remained consistently high. From the viewpoint of high prevalence of CAM resistance in Japan, triple therapy with PPI, AMPC and MNZ may be a better strategy for first-line therapy compared to triple therapy with PPI, AMPC and CAM.

Antibiotic associated diarrhea due to human intestinal microbiota abnormalities is a side effect of H. pylori eradication therapy. We examined intestinal microbiota changes during H. pylori eradication therapy and the preventive effect of CBM588 as a probiotic agent. Nineteen patients with gastro-duodenal ulcer were randomly divided into three groups: group A (without probiotics), group B (with regular doses of CBM588) and group C (with double doses of CBM588). The incidence of diarrhea and soft stools during H. pylori eradication therapy was 43% in group A and 14% in group B, while none of the patients in group C reported diarrhea or soft stools. Both bacterial counts and detection rates of bifidobacteria and/or obligate anaerobe were decreased by eradication therapy. However, bacterial counts of obligate anaerobes in group C were significantly higher than in group A (P < 0.05). Additionally, during eradication therapy C. difficile toxin A was detected in both group A and group B but not in group C. In conclusion, these results indicate that H. pylori eradication therapy induces antibiotic associated diarrhea due to abnormalities in intestinal microbiota and/or C. difficile. However, these side effects might be prevented by probiotics.

The mechanism for gastric epithelial cellular apoptosis by both H. pylori and NSAIDs remains unknown. Normal gastric epithelial cells, collected from rabbit stomach, were cultured with viable H. pylori and/or an acetylsalicylic acid for 24 hr as an in vitro model of gastric epithelial cell injury. The Fas antigen expression rate in the gastric epithelial cells was measured using a FACScan. In group E, in which H. pylori inoculation of epithelial cells was followed by treatment with an NSAID, the rate of Fas antigen expression was significantly higher than the rate observed after treatment with either H. pylori or NSAID alone. Despite the fact that drug treatment alone did not significantly increase the Fas expression rate vs control cells. The results suggest that H. pylori and NSAID induce gastric cell injury as apoptosis via the Fas antigen pathway in a synergistic manner and that this effect is particularly strong when NSAID treatment follows H. pylori infection.

The major cause of chemotherapy failure in patients with chronic gastritis and peptic ulcers caused by Helicobacter pylori is clarithromycin (CAM) resistance due to a mutation in the 23S rRNA gene. This study describes a non-invasive and accurate method for the detection of mixed CAM-resistant and -susceptible H. pylori by sequencing of the H. pylori 23S rRNA gene. Faeces were crushed with beads and the 23S rRNA gene was amplified using a nested PCR on the extracted DNA. Mutation analysis of this gene using this method showed that 20.4 % of patients carried mixed CAM-susceptible (wild type) and -resistant (A2142G or A2143G mutant) H. pylori. Furthermore, it was found that 66.6 % of patients who had been treated unsuccessfully carried one of these mutations in the 23S rRNA gene (including the mixed type), whilst standard culture detected CAM-resistant isolates in only 22.2 % of patients with unsuccessful treatment. These data suggest that, for successful therapy, the diagnosis method described here would more accurately detect CAM-resistant H. pylori, including mixed infections.

After official acceptance of eradication therapy for Helicobacter pylori infected peptic ulcer disease in 2000, this treatment has been generalized as ulcer therapy in Japan. In 2003 the consensus statement of the Japanese Society for Helicobacter Research (JSHR) for Helicobacter pylori infection was presented. According to this statement MALT lymphoma was recommended to treat H. pylori infection because of the efficacy of its out come. Atrophic gastritis was also advised to treat H. pylori infection for the purpose of preventing gastric cancer development. The extra alimentary disease such as idiopathic thrombocytopenic purpura was still under evaluation. In diagnostic method the importance of drug susceptibility test is rising because of the increase of drug resistant H. pylori strain in Japan. The false positive case of urea breath test, the accuracy of new Japanese original serology tests and the stool antigen test are also under investigation. The standard regimen of H. pylori eradication therapy in Japan is proton pomp inhibitor (PPI) + amoxicilin (AMPC) + clarithromycin (CAM). The problem of this regimen is the decrease of eradication rate. The reason of this trend might be increase of CAM resistant strain. JSHR recommended a rescue regimen as PPI + AMPC + metronidazole for the patient whose first eradication therapy was unsuccessful result. The eradication of this second line regimen was reported as about 90%.

Background. Previous reports revealed no resistant strains of amoxicillin (AMPC), which is usually used in eradication therapy for H. pylori infection. However, the frequency and evolution of natural AMPC-resistant strains in the Japanese population remains unknown. Aim. To assess the prevalence of H. pylori resistance against AMPC in the Tokyo area, a collection of 648 H. pylori strains isolated from patients with GI diseases from 1985 to 2003 was tested for their sensitivity to AMPC. Methods. The susceptibility of the strains was assessed by determination of the minimal inhibitory concentration (MIC) using the E-test and/or the Dry-plate method. The susceptibility breakpoints of AMPC for H. pylori were: sensitive (AMPC-S); MIC 1. Results. No AMPC-R strains were detected in the strains isolated between 1985 and 1996, while the rate of resistance was determined to be 1.1%, 2.1%, 5.4%, 5.6%, 0%, 8.8%, and 1.5% every year, respectively, from 1997 to 2003. The percentage of AMPC-I strains increased from 2000 to 2003. The total eradication rate of H. pylori in the patients who received triple therapy containing AMPC was 81.4% (214/263). Classified as above, the rates of AMPC-S, AMPC-I, and AMPC-R were 84.6%, 77.8%, 25%, respectively. Conclusion. H. pylori resistance to AMPC is still rare in Japan, although the percentage of AMPC-I strains has increased over the last 4 years. The frequency of isolation of strains showing true resistance to AMPC may increase in the future, along with an increase in the frequency of isolation of AMPC-I strains.