Akira Horiuchi

Background and Aim: In Japan, gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) account for nearly all fatal upper gastrointestinal malignancies. A unified model that simultaneously predicts the incidence of these two cancers could help optimize endoscopic screening and postindex surveillance strategies. Methods: We conducted a retrospective multicenter cohort study of 33 422 individuals who underwent screening esophagogastroduodenoscopy (EGD) at 17 health check‐up institutions across Japan. Clinical and endoscopic data from the index EGD were used to develop a 5‐year risk prediction model for GC or ESCC. Significant predictors were identified using Cox regression, and a scoring system (J‐GESS score) was constructed by scaling β coefficients. Model performance was evaluated using the 5‐year inverse probability of censoring weighted (IPCW) Brier score, calibration, and c indices. Internal validation used bootstrap resampling (500 iterations) to obtain optimism‐corrected estimates. Decision curve analysis (DCA) assessed clinical utility at 5 years. Results: At 5 years, the IPCW‐estimated cumulative incidence of GC or ESCC was 0.84% (234 events). Independent predictors included older age, male sex, ever smoking, and endoscopic gastric mucosal atrophy. The model showed good calibration at 5 years (calibration‐in‐the‐large 0.005; slope 1.055; identical after optimism correction) and robust discrimination (Harrell's c index 0.81; Uno's 5‐year c index 0.81). DCA demonstrated positive net benefit across clinically relevant thresholds. Conclusion: Using routinely collected health check‐up data, we developed a unified, practical, and internally validated 5‐year prediction model for GC and ESCC. The J‐GESS score enables effective risk stratification and may inform postindex endoscopic surveillance and screening interval optimization in Japan.

The heterogeneity of ulcerative colitis (UC) results in variable biological responses. Although anti-tumor necrosis factor (anti-TNF) agents remain a cornerstone of therapy, 30-40% of patients experience primary non-response, which is often linked to persistent activation of the interleukin-23 (IL-23) pathway. There is increasing evidence that the IL-23-Th17-neutrophil axis plays a central role in mucosal inflammation and treatment resistance. Phase II and III trials of selective IL-23 inhibitors for UC have demonstrated high rates of endoscopic and histologic remission, with safety profiles comparable to those of anti-TNF agents. These agents have demonstrated efficacy in various patient subgroups, including those with a history of anti-TNF failure. This supports their potential as effective alternatives to existing biologics. Based on these data, we propose a multimodal framework for personalized treatment selection that integrates three diagnostic pillars: (1) noninvasive biomarkers, such as serum leucine-rich alpha-2 glycoprotein and fecal calprotectin, to differentiate between systemic and mucosal inflammation, (2) the Mayo Endoscopic Subscore to guide therapeutic intensity, and (3) quantitative histopathology, specifically the Komagane subclassification of Geboes Grade 3, to identify IL-23-Th17-dominant activity. This integrative approach may enable predicting biologic responses, risk stratification, and the individualized use of selective IL-23 inhibitors. We propose this strategy as a model for generating hypotheses for future personalized medicine studies in UC.

Background: Older patients with inflammatory bowel disease (IBD) often have multimorbidity and functional vulnerability, which increases the risk of in-hospital complications. This study examined whether frailty at admission is associated with hospital-associated geriatric complications in this population. Methods: This retrospective cohort study was conducted using a nationwide hospital-based claims database in Japan. Patients aged ≥ 60 years hospitalized with ulcerative colitis or Crohn’s disease between February 2014 and September 2025 were identified. Frailty was assessed using the Hospital Frailty Risk Score (HFRS ≥ 5). The primary outcome was hospital-associated complications in older people (HAC-OP), which is a composite of functional decline, incontinence, delirium, pressure injury, and falls/fractures. The risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using modified Poisson regression. Results: Among 3,905 hospitalizations, 1,220 (31.2%) patients were classified as frail. Overall, 6.7% of hospitalizations were complicated by at least one HAC-OP, with a higher incidence in patients with frailty than in non-frail patients (10.7% vs. 4.8%). Frailty was associated with HAC-OP (adjusted RR 1.74, 95% CI 1.36–2.21), functional decline (adjusted RR 1.54, 95% CI 1.12–2.11), and delirium (adjusted RR 2.50, 95% CI 1.66–3.76). Results were robust in sensitivity analyses using multiple imputation, additional adjustment for length of stay. Conclusions: In hospitalized older patients with IBD, frailty at admission was associated with hospital-associated geriatric complications, particularly delirium and functional decline. The HFRS may be a useful tool for identifying patients at higher risk, and future studies should evaluate whether frailty-targeted interventions can reduce these complications.

This case series reports three patients with active ulcerative colitis (UC) successfully treated with mirikizumab, a selective IL-23p19 monoclonal antibody. Mirikizumab was initiated based on both clinical presentation and a histopathological marker—high neutrophilic infiltration of the colonic epithelium classified as Geboes Grade 3.2—which reflects an IL-23/Th17-driven inflammatory phenotype. The cases included: an elderly man with acute severe pancolitis and primary nonresponse to infliximab; a middle-aged woman with steroid-dependent left-sided UC and inadequate response to adalimumab and ustekinumab; and a young biologic-naïve woman with steroid-refractory UC and bowel urgency. All three patients demonstrated high epithelial neutrophilic infiltration (Geboes Grade 3.2). These cases demonstrate the potential utility of histology-guided biologic selection and support Geboes Grade 3.2 as a candidate predictive biomarker for IL-23 inhibitor response in UC.

Background: The growing number of ulcerative colitis (UC) treatments has complicated the selection process. We hypothesized that the degree of epithelial neutrophilic infiltration, which is a hallmark of interleukin-23 (IL-23) pathway activation, could guide personalized therapy. Methods: This single-center, prospective study included 42 patients with active UC who were treated between July 2024 and September 2025. The study was registered (NCT 06626165) on 20 July 2024. Prior to treatment, all patients underwent colonoscopy with biopsy. Using a refined subclassification of the Geboes histopathology score, patients were stratified into two groups based on the percentage of crypts with neutrophilic infiltration: Grade ≥ 3.2 and Grade < 3.2. The primary outcome was clinical remission at four weeks. The secondary outcome was endoscopic remission at six months. Results: Of the 42 patients, 22 were classified as Grade ≥ 3.2, and 20 were classified as Grade < 3.2. Baseline clinical and endoscopic characteristics were similar between the two groups. All 22 patients in the Grade ≥ 3.2 group treated with mirikizumab achieved clinical remission within four weeks. Nineteen (86%) of the twenty-two patients achieved endoscopic remission within six months. All 20 patients in the Grade < 3.2 group who received vedolizumab (16) or upadacitinib (4) achieved clinical remission within the same timeframe. Both treatment strategies led to a statistically significant reduction in the inflammatory biomarker leucine-rich alpha-2-glycoprotein (LRG) (p < 0.001). Conclusions: Our findings suggest that UC patients with advanced epithelial neutrophil infiltration (Geboes Grade ≥ 3.2) may have a disease that is predominantly driven by the IL-23 pathway, making them potential candidates for selective IL-23p19 inhibitors. This histopathology-driven approach appears to be a useful strategy for tailoring treatment to patients with active UC, though further validation is required.

Background: Interleukin (IL)-23 exerts its effects by activating Th17 cells, resulting in high neutrophilic infiltration in the colonic mucosal epithelium. We have developed a scoring method for refining the Geboes score Grade 3 to identify active ulcerative colitis (UC) patients with high epithelial neutrophilic infiltration (Geboes Grade 3.2 or 3.3). Methods: Colonoscopy and histology findings were assessed using the Mayo endoscopic subscore (MES) and the Geboes score Grade 3. The percentage of crypts with neutrophilic infiltration, which was calculated as the number of crypts with neutrophilic infiltration/total crypts in a glass slide, was used to subclassify the Geboes score Grade 3 into Grades 3.0, 3.1, 3.2, and 3.3. Results: This scoring method was then applied to 30 enrolled patients (20 men; median age: 46 years), yielding the following distribution: Geboes Grade 3.0 in six (20%) patients, Grade 3.1 in seven (23%) patients, Grade 3.2 in sixteen (53%) patients, and Grade 3.3 in one (3%) patient. Of the 18 UC patients with MES 2, 5 (28%) were classified as Grade 3.1 and 12 (67%) were classified as Grade 3.2. One of the IL-23 antagonists, mirikizumab treatment, resulted in clinical and endoscopic improvements in 10 active UC patients who were classified as Geboes score ≥ 3.2. Conclusions: We developed a novel Geboes score Grade 3 scoring method and applied it to 30 patients; approximately 60% were classified as Grade 3.2 or higher. This method may help to identify UC patients who are likely to respond effectively to IL-23 antagonists.

Objectives: We prospectively investigated the risk of colonoscopy‐related bleeding in relation to antithrombotic treatment. Methods: This prospective, observational, single‐center cohort study (NCT02594813) enrolled consecutive patients who underwent colonoscopy, including the removal of colorectal polyps, regardless of the continuation of antithrombotic treatment. The primary outcome measure was delayed bleeding in the patients who underwent a hot snare polypectomy and/or endoscopic mucosal resection in addition to a cold snare polypectomy (CSP) and required endoscopic treatment ≤2 weeks after the procedure. Secondary outcomes were immediate bleeding and the number of hemostatic clips used during the procedure. Results: From January 2019 to December 2023 at our institution, 1562 (mean age 75 years) and 15,769 (mean age, 64 years) patients underwent colonoscopy with or without antithrombotic treatment, respectively. Immediate bleeding following the removal of colorectal polyps, regardless of the polypectomy technique, occurred in 173 (33.86%) of the 511 patients with antithrombotic treatment, which was significantly more frequent than in 439 (9.44%) of the 4651 patients without antithrombotic treatment ( p < 0.001). On the other hand, there was no significant difference in delayed bleeding after CSP between the two groups (0.41% vs. 0.11%, p = 0.15). However, the incidence of delayed bleeding following polypectomy was significantly higher in patients receiving antithrombotic treatment compared to those without it (seven of 511 [1.37%] vs. 12 of 4651 [0.26%], p = 0.0016). Conclusions: The risk of delayed bleeding after colonoscopy with removal of colorectal polyps was low despite continuation of antithrombotic therapy. www.clinicaltrials.gov (NCT02594813).

(1) Background: Interleukin (IL)-23 exerts its effects by activating Th17 cells, resulting in high neutrophilic infiltration in the colonic mucosal epithelium. We have developed a scoring method for refining Geboes score Grade 3 to identify active ulcerative colitis (UC) patients with high epithelial neutrophilic infiltration (Geboes Grade 3.2 or 3.3). (2) Methods: Colonoscopy and histology findings were assessed using the Mayo Endoscopic Subscore (MES) and Geboes Grade 3. The percentage of crypts with neutrophilic infiltration, calculated as the number of crypts with neutrophilic infiltration/total crypts in a glass slide, was used to subclassify Geboes score Grade 3 into Grades 3.0, 3.1, 3.2 and 3.3. (3) Results: This scoring method was then applied to 30 enrolled patients (20 males; median age 46 years), yielding a distribution of Geboes Grade 3.0 in 6 (20%), 3.1 in 7 (23%), 3.2 in 16 (53%) and 3.3 in 1 (3%) patient(s). Of the 18 UC patients with MES 2, 5 (28%) had Grade 3.1 and 12 (67%) had Grade 3.2. (4) Conclusions: we have developed a novel Geboes score Grade 3 scoring method and applied it to 30 patients: approximately 60% had Grade 3.2 or higher. This method may help to identify UC patients likely to respond effectively to IL-23 antagonists.

Objectives: We compared the frequency of post‐polypectomy bleeding or injured submucosal arteries between cold snare polypectomy (CSP) and endoscopic mucosal resection (EMR) for nonpedunculated colorectal polyps.Methods: This was a prospective, randomized, single‐center study. Patients who underwent CSP or EMR for 10–19‐mm nonpedunculated polyps were enrolled in CSP and EMR groups, and we compared the patient and polyp characteristics, the number of clips used, clinical outcomes, adverse events, and pathological features of the resected polyps between these groups. The primary outcome was the presence of injured arteries in the submucosal layer of the resected polyps examined histologically. The secondary outcomes were immediate bleeding and delayed bleeding.Results: Fifty‐three patients with 60 eligible polyps were enrolled. The numbers of polyps/patients were 30/26 in the CSP group and 30/27 in the EMR group. The patient and polyp characteristics were similar between the groups. The total number of hemostatic clips used for hemostasis or prophylactic clipping was significantly greater in the EMR group compared to the CSP group (78 vs. 10, p < 0.001). The frequency of immediate bleeding after CSP was similar to that after EMR [6.7% (2/30) vs. 13% (4/30), p = 0.39]. Delayed bleeding did not occur in either group. The presence of injured submucosal arteries after CSP was significantly less frequent than that after EMR: 10% (3/30) versus 67% (20/30), p < 0.001.Conclusions: In the resection of 10–19‐mm nonpedunculated colorectal polyps, CSP may decrease post‐polypectomy bleeding without prophylactic clipping compared to EMR as it results in fewer injured submucosal arteries. www.clinicaltrials.gov (NCT05930041).

The ideal texture of pureed diets to prevent aspiration pneumonia remains unclear. The aim of this study was to evaluate the effectiveness of a pureed diet with either a gelling agent or a xanthan gum-based thickener to prevent pharyngeal residues in patients with dysphagia. We retrospectively analyzed a randomized, crossover trial of pureed rice with either a gelling agent or a xanthan gum-based thickener in patients with dysphagia. The enrolled patients were classified into mild and moderate-to-severe dysphagia groups. The primary outcome measure was degree of need for cyclic ingestion using test jelly for pharyngeal residuals (cyclic ingestion score). The secondary outcome was the patient’s sense of material remaining in the throat following swallowing. Sixty-two patients (58% men; mean age 83 ± 9 years) with dysphagia were included. They were classified into mild dysphagia (n = 26) and moderate-to-severe dysphagia (n = 36) groups. In the moderate-to-severe dysphagia group, pharyngeal residuals were significantly less likely with pureed diets using a gelling agent than with those using a xanthan gum-based thickener, with respective median cyclic ingestion scores (range) of 1 (0–4) vs. 2.5 (0–4) (p = 0.001). There was no significant difference in pharyngeal residuals between the pureed diets in the mild dysphagia group. The multivariate analysis identified gelling agent as an important factor significantly associated with less pharyngeal residual after swallowing of pureed diet in patients with moderate-to-severe dysphagia. Pureed diets thickened by a gelling agent decrease pharyngeal residues in patients with moderate-to-severe dysphagia and may reduce risk of aspiration pneumonia.