Osamu Handa

Background: Helicobacter pylori infection is a primary cause of gastric cancer. Although eradication therapy in adulthood suppresses carcinogenesis, its efficacy is limited due to the progression of advanced gastric mucosal atrophy before eradication. Implementing a “screen‐and‐treat” strategy during adolescence represents a promising approach to prevent advanced atrophy and subsequent gastric cancer. Methods: This prospective cohort study included first‐year high school students in Kyoto Prefecture, Japan, from 2015 to 2023. Screening was performed using a primary urine H. pylori antibody test, followed by a secondary stool antigen test for confirmation. Confirmed positive individuals were referred to designated medical institutions for 7‐day eradication therapy. The primary therapeutic regimen was shifted from rabeprazole, amoxicillin, and clarithromycin (PAC) in 2015 to rabeprazole, amoxicillin, and metronidazole (PAM) from 2016 onward. Clostridium butyricum MIYAIRI 588 strain (CBM588) was co‐administered starting in 2017. Eradication success was verified via a stool antigen test at least 8 weeks post‐treatment. Results: A total of 50,031 students were targeted over the 9‐year period, with an overall consent rate ranging from 59.9% to 83.9%. The confirmed H. pylori infection rate declined from 4.7% in 2015 to 1.5% in 2023. The medical consultation rate among positive screenees exhibited a declining trend, peaking at 84.6% (2015) and dropping to 15.8% (2023), despite a temporary increase in 2019 (65.9%). The eradication success rate significantly improved from 76.5% with the PAC regimen (2015) to over 93.8% with the PAM regimen (2016 onward), exceeding 96.0% after the addition of CBM588. No serious adverse events were reported throughout the study period. Conclusions: The prospective adolescent screen‐and‐treat program demonstrated a significant decrease in H. pylori infection rates among first‐year high school students over the decade. While the safety and efficacy of the PAM‐based eradication regimen were verified, declining medical consultation rates present a continuous challenge for public health implementation.

Background: The Japanese Society for Helicobacter Research (JSHR) published the fifth edition of the guidelines for the management of Helicobacter pylori ( H. pylori ) infection in 2024 in Japanese language. Methods: This edition of JSHR guidelines was first developed in accordance with the Minds Clinical Practice Guideline and Grading of Recommendations Assessment, Development, and Evaluation system. This was published after inviting public comments and external evaluations. Consensus on clinical questions (CQs) was achieved using the modified Delphi method. Results: There was no change in the basic policy that all H. pylori infectious diseases are indications for eradication. Nucleic acid amplification was added to the diagnostic methods. Effects of proton-pump inhibitors (PPIs) on diagnostic tests were updated. The superiority of potassium-competitive acid blockers to PPIs in 1-week triple therapy with amoxicillin and clarithromycin has been shown. A flowchart for eradication therapy was provided for use in real-world settings. For gastric cancer prevention, eradication in earlier age is recommended. The most appropriate test and treatment strategies for adolescents are also described. Some CQs concerning gastric cancer prevention were identified, although evidence level was insufficient to make recommendations based on clinical importance. Conclusion: The revised guidelines facilitate the appropriate management of H. pylori infection and gastric cancer prevention.

Introduction: The incidence of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is increasing rapidly worldwide. Although multiple advanced therapies are now available, selecting the optimal treatment remains challenging due to the expanding options and diverse healthcare systems. Methods: We conducted a questionnaire survey among physicians in nine Asian countries prior to the 18th International Gastrointestinal Consensus Symposium (IGICS) to assess the current status of advanced therapies for IBD. The survey included questions regarding therapeutic agent selection, biomarkers, and imaging modalities for monitoring. Results: Of the 210 respondents, 173 physicians treating IBD were analyzed. Anti-TNFα antibodies remain the most commonly selected advanced therapy for both UC and CD. Elderly patients with UC were more likely to receive anti-α4β7-integrin antibodies or anti-IL-12/23p40 monoclonal antibodies, reflecting safety considerations. Janus kinase inhibitors were used more frequently as a second-line option in severe cases. Comorbidities, drug costs, and lifestyle factors also influenced treatment choice. CRP is the most common biomarker used for monitoring, and endoscopy is the most frequently used imaging modality. Conclusion: This questionnaire survey revealed the current status of advanced therapies for IBD in nine Asian countries and regions. Region-specific evidence-based algorithms for selecting advanced therapies for IBD should be established.

Background/Objectives: This study aimed to identify specific endoscopic findings associated with the development of GC following successful H. pylori eradication. Methods: This prospective multicenter observational study included patients who underwent annual surveillance endoscopy after successful H. pylori eradication therapy between September 2013 and June 2019. Endoscopic findings were evaluated one year after eradication therapy and analyzed using the Kyoto Classification of Gastritis to identify factors associated with GC development. Results: A total of 465 patients were included, including 49 patients with GC and 416 patients without GC. At the initial endoscopic assessment (median, 0.96 years post-eradication), emergence of map-like redness and invisible regular arrangement of collecting venule (RAC) as independent predictors of GC (map-like redness: hazard ratio [HR], 2.561; 95% confidence interval [CI], 1.362–4.572; p = 0.003; invisible RAC: HR, 3.131; 95% CI, 1.078–9.091; p = 0.036). Patients with map-like redness or invisible RAC showed a significantly higher incidence of GC than those without map-like redness or invisible RAC (p < 0.001 and p < 0.001, respectively). Notably, map-like redness and visible RAC appeared in 13% and 28.4% of cases within the first year after eradication, respectively. Conclusions: Map-like redness and invisible RAC were identified as independent predictors of GC following H. pylori eradication and may serve as early predictive indicators, appearing within one year of successful eradication. This finding underscores the importance of early surveillance endoscopy in identifying patients at elevated risk for GC.

The gut microbiota plays an important role in the development of colorectal tumors. However, the underlying mechanisms remain unclear. In this study, we examined the effects of fecal microbiota transplantation (FMT) on azoxymethane (AOM)-induced colorectal tumors in obese mice. We divided the study subjects into the following five groups: high-fat diet (HFD), normal diet (ND), ND+exercise (Ex), HFD+FMT from ND-alone donor (HFD+FMT(ND alone)), and HFD+FMT from ND+Ex donor (HFD+FMT(ND+Ex)). The Ex group performed treadmill exercise for 15 weeks. Thereafter, fecal and colonic mucus samples were extracted for microbiome analysis. The deoxyribonucleic acid sample was collected from the feces and colonic mucosa, and V3–V4 amplicon sequencing analysis of the 16S rRNA gene was performed using MiSeq. The number of polyps was significantly lower in the ND (6.0 ± 1.6) and ND+Ex (1.8 ± 1.3) groups than in the HFD group (11.4 ± 1.5). The ND+Ex group had significantly fewer polyps than the ND group. The HFD+FMT(ND alone) (5.2 ± 0.8) and HFD+FMT(ND+Ex) (2.8 ± 2.6) groups also had significantly fewer polyps than the HFD group. The IL-15 mRNA levels in the colonic tissues were significantly higher in the HFD+FMT(ND alone) group than in the ND group. Fecal ω-muricholic acid concentrations were significantly higher in the HFD+FMT(ND alone) group than in the ND group and in the HFD+FMT(ND+Ex) group than in the ND+Ex group. The ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of Lacyobacillaceae than the HFD group. In the FMT group, Erysipelotrichaceae and Tannerellaceae were significantly less abundant. Compared with the HFD group, the ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of Muribaculaceae and a significantly higher abundance of Lactobacillaceae and Rikenellaceae in common among the ND and ND+Ex groups. The common and significantly less common species were Bacteroidaceae in the FMT group and Lactobacillaceae and Rikenellaceae in the ND alone and ND+Ex groups. Bacteroidaceae and Lachnospiraceae were significantly less common in the FMT group. We found that FMT inhibited AOM-induced colorectal tumorigenesis in obese mice. Furthermore, the fecal concentrations of short-chain fatty acids, bile acids, microbiota, and mucosa-associated microbiota differed between the FMT and diet/EX groups, suggesting that the inhibitory effect of FMT on colorectal tumorigenesis may be due to mechanisms different from those of ND alone and ND+Ex.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by esophageal dysfunction and eosinophilic inflammation of the esophageal mucosa. In this study, we investigated the bacterial flora in saliva and esophageal mucus in patients with EoE and examined the relationship between EoE disease activity and mucosal cytokine expression, involving patients with active and inactive EoE (A-EoE and I-EoE, respectively). A-EoE was defined as a peak eosinophil count > 15/high-power field, according to the 2025 consensus guidelines. Saliva samples were collected from patients before the endoscopic examination. Brushing samples were collected from the distal esophagus of patients with EoE during endoscopic procedures. The degree of EoE inflammation was assessed using the EoE endoscopic reference score (EREFS). The samples were profiled using the Illumina MiSeq platform. The V3–V4 regions of the 16S rRNA gene (460 bp) were amplified using tailed PCR. Fifty-nine patients were enrolled, including eight with I-EoE, seventeen with A-EoE, and twenty-eight non-EoE controls. Major bacterial genera such as Streptococcus, Prevotella, Veillonella, and Haemophilus were detected in both the oral cavity and esophagus. Compared with the control group, the active EoE group had significantly more Prevotella spp. in the saliva and esophageal mucosa. Conversely, significantly fewer Neisseria spp. were found in the saliva and Streptococcus spp. in the esophageal mucosa of patients with active EoE. The EREFS of EoE and Streptococcus were inversely correlated. This study elucidated the characteristics of bacterial flora in the saliva and esophageal mucosa of patients with EoE.

Introduction: Eosinophilic gastrointestinal disease (EGID) is divided into eosinophilic esophagitis (EoE) and non-eosinophilic esophagitis eosinophilic gastrointestinal disease (non-EoE-EGID), based on the involved gastrointestinal organs. The present survey was performed to provide an overview of the current status of the epidemiology, diagnosis, and treatment of EGID in Asia. Methods: Responses to the questionnaire were obtained from 228 doctors at various institutions in eight Asian countries. The questionnaire consisted of 52 questions on EoE and non-EoE EGID. Results: Responses to questionnaire were obtained from 228 doctors from eight countries. The most common participation facilities were university hospitals, followed by public hospitals, private hospitals, and private clinics. 1–10 were the most frequent patients per year in each institution for both EoE and non-EoE-EGID. The 30s and 40s are common age groups for both EoE and non-EoE-EGID. Although endoscopic findings vary among countries, 15 or more eosinophil infiltrations in high-power fields as a diagnostic criterion are used in all countries for EoE. As treatments, the prescription rates of Proton pump inhibitor, diet, topical and systemic steroids, and biologics were similar among the eight countries in EoE. Non-EoE-EGID showed a similar trend to EoE in epidemiology, symptoms, diagnosis, and treatment. Conclusion: The questionnaire survey partially revealed the current status of the epidemiology, symptoms, diagnosis, and treatment of EGID in Asian countries.

Background/Objectives: 5-Aminosalicylic acid (5-ASA) is a first-line therapy for ulcerative colitis (UC). This study examined the mucosa-associated microbiota (MAM) in UC patients, distinguishing between those who were 5-ASA tolerant and intolerant. Methods: Brushing samples were collected from the sigmoid and ileal end of patients with UC during endoscopic procedures. The samples were profiled by using the Illumina MiSeq platform. The V3–V4 regions of the 16S rRNA gene (460 bp) were amplified by using tailed PCR. Results: A total of 15 patients with 5-ASA intolerance, 38 patients with 5-ASA tolerance, and 19 healthy controls were recruited in this study. The α-diversity indices were remarkably different among the three groups in the ileum mucosa but not in the sigmoid colon. In the ileum mucosa, Alistipes, Ruminococcaceae, and Odoribacter were less abundant in the 5-ASA-intolerant group than in the control and 5-ASA-tolerant groups. On the contrary, Merdibacter, Brevundimonas, and Porphyromonas were more abundant in the 5-ASA-intolerant group than in other groups. Conclusions: The present study showed that the changes in MAM were characterized by a decrease in mucoprotective bacteria rather than an increase in harmful bacteria.

The only reliable factor that reduces the risk of colorectal carcinogenesis is physical activity. However, the underlying mechanisms remain unclear. In this study, we examined the effects of physical activity against gut microbiota, including mucosa-associated microbiota (MAM) on azoxymethane-induced colorectal tumors in obese mice. We divided the subjects into four groups: normal diet (ND), high-fat diet (HFD), ND + exercise (Ex), and HFD + Ex groups. The Ex group performed treadmill exercise for 20 weeks. Thereafter, fecal and colonic mucus samples were extracted for microbiota analysis. DNA was collected from feces and colonic mucosa, and V3–V4 amplicon sequencing analysis of the 16SrRNA gene was performed using MiSeq. The HFD group had significantly more colonic polyps than the ND group (ND 6.5 ± 1.3, HFD 11.4 ± 1.5, p < 0.001), and the addition of Ex suppressed the number of colonic polyps in ND and HFD groups (ND 6.5 ± 1.3, ND + Ex 2.8 ± 2.5, p < 0.05). The HFD group showed significantly lower concentrations of succinic, acetic, butyric, and propionic acids (mg/g) in feces, compared with the ND group (succinic acid HFD 0.59, ND 0.17; acetic acid HFD 0.63, ND 2.41; propionic acid HFD 0.10, ND 0.47; and N-butyric acid HFD 0.31, ND 0.93). In the case of ND, succinic acid and butyric acid tended to decrease with Ex (succinic acid ND 0.17, ND + Ex 0.12; N-butyric acid ND 0.93, ND + Ex 0.74 0.74). Succinic acid, acetic acid, butyric acid, and propionic acid levels in feces were significantly lower in the HFD group than in the ND group; in both feces and mucus samples, Butyricicoccus and Lactobacillus levels were significantly lower in the HFD group. Akkermansia was significantly increased in ND + Ex and HFD + Ex groups. Diet and exercise affected the number of colorectal tumors. Furthermore, diet and exercise alter intestinal MAM, which may be involved in colorectal tumor development.

Background/Aims: Intestinal strictures represent an important serious complication of Crohn’s disease. Shear wave elastography is a promising noninvasive ultrasound technique for assessing tissue stiffness. This study aimed to evaluate stiffness in the areas of intestinal stricture in patients with Crohn’s disease using shear wave elastography and the changes in stiffness after biologics. Materials and Methods: We enrolled 21 Crohn’s disease patients having intestinal stricture. The patients consisted of 3 groups, which were the infliximab naïve (n = 6) group, the ustekinumab naïve (n = 8), and the bio-switch from infliximab to ustekinumab (n = 7) group. Bowell wall thickness was examined by ultrasound sonography, and the stiffness of Crohn’s disease stricture lesions was evaluated using Shear wave speed before and 1 year after anti-tumor necrosis factor-alpha antibody infliximab, anti-interleukin 12/23 antibody ustekinumab, and bio-switch from infliximab to ustekinumab. Results: Bowell wall thickness was significantly improved after infliximab, ustekinumab, and the bio-switch. However, shear wave speed indices only in the ustekinumab group significantly decreased after treatment (P = .028), but not in the other group. Conclusions: Shear wave elastography might be a useful method to evaluate stiffness in the areas of intestinal stricture in patients with Crohn’s disease treated with biologics. However, a prospective randomized study evaluating the development of obstruction after biological treatment is needed to validate the study findings.