Kazuhiko Uchiyama

Background: Minimally invasive treatments for superficial pharyngeal cancer including transoral videolaryngoscopic surgery (TOVS) and endoscopic submucosal dissection (ESD) have become more widespread as minimally invasive treatments; however, no reports have compared these treatment methods. Methods: We retrospectively investigated consecutive patients with superficial hypopharyngeal squamous cell carcinoma who underwent ESD or TOVS between January 2013 and December 2024. Results: A total of 60 lesions in 55 patients were included in the ESD and TOVS groups. The en bloc resection rate was 100% in both groups. The R0 resection rate in the ESD group showed a nonsignificant trend toward being higher than that in the TOVS group (58.1% vs. 34.5%; p = 0.077). No significant differences were observed in the 3‐year overall survival (OS) rates between the TOVS and ESD groups (93.8% vs. 81.3%; p = 0.330). The 3‐year cumulative incidence of local recurrence was 13.6% in the TOVS group and 5.9% in the ESD group ( p = 0.241). In an exploratory univariate analysis, tumor thickness ≥ 1000 μm was significantly associated with lymph node metastasis ( p = 0.017). Conclusions: Clinical outcomes in patients with superficial hypopharyngeal cancer were not significantly different between ESD and TOVS. Although the cumulative incidence of local recurrence was numerically lower after ESD than after TOVS, the difference was not statistically significant. Both procedures may represent feasible minimally invasive treatment options for selected patients.

Endoscopic closure of mucosal defects after colorectal endoscopic submucosal dissection (ESD) has been increasingly adopted to prevent adverse events. Various devices and techniques, including conventional clips, clips with various technical tips, clip with line, clip with device, special clips, and suturing devices, have been developed, achieving high rates of complete closure (approximately 95% on average), although procedure times and technical complexity vary considerably. Among 14 eligible comparative studies, including randomized controlled trials and retrospective studies published up to April 2026, a meta-analysis was performed to evaluate the efficacy of complete closure after colorectal ESD in preventing delayed bleeding (DB), delayed perforation (DP), and post-ESD coagulation syndrome (PECS). For DB, pooled analysis demonstrated that complete endoscopic closure was significantly associated with a reduced risk of DB (odds ratio [OR]: 0.77, 95% confidence interval [CI]: 0.60–0.97, p = 0.030, I² = 53.6%). In contrast, no significant differences were observed between the closure and non-closure groups for DP (OR: 0.60, 95% CI: 0.23–1.55, p = 0.290, I² = 0.0%) or PECS (OR: 0.94, 95% CI: 0.65–1.38, p = 0.765, I² = 56.6%). In a literature review, reported risk factors for DB include lesion size >50 mm, an ASA score of III or IV, antithrombotic therapy, age ≥75 years, and rectal location. Severe fibrosis and prolonged ESD procedure time have been reported as risk factors for DP, whereas female sex, age ≥70 years, right-sided colon, and lesion size >24 mm have been associated with PECS. Overall, various closure devices and techniques achieve high technical success rates after colorectal ESD. Complete closure appears beneficial for reducing DB, particularly in high-risk patients, whereas its efficacy for preventing DP and PECS remains uncertain. Further studies are warranted.

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 and Objectives: Bowel bubble formation during colonoscopy can impair mucosal visualization and reduce procedural efficiency. However, its clinical significance remains incompletely characterized. This study aimed to evaluate the prevalence of severe bowel bubbles in the proximal colon and their impact on colonoscopic quality in patients undergoing bowel preparation with oral sulfate solution (OSS), using either a same-day regimen (SAR) with 480 mL OSS or a split-day regimen (SPR) with 960 mL OSS. Methods: This retrospective study was conducted between October 2024 and December 2025 across two affiliated institutions. Patients who underwent colonoscopy with OSS-based bowel preparation were included. SAR was used for screening, symptomatic evaluation, and surveillance colonoscopy. SPR was applied exclusively to patients with a prior history of sodium picosulfate-related abdominal pain or inadequate bowel preparation with SAR. Sodium picosulfate was prescribed on the day before colonoscopy in the SAR group and a low-residual diet was administered in both the SAR and SPR groups. The prevalence of severe bubbles in the proximal colon was evaluated, and their impact on colonoscopic quality was examined. Results: A total of 176 SAR cases and 51 SPR cases were analyzed. The rate of severe bubbles in the proximal colon was identical between both regimens (17.6%). Compared with cases without severe bubbles, those with severe bubbles had significantly longer cecal insertion times (median [IQR]: 7.0 [5.0–10.0] vs. 9.0 [7.0–13.0] min, p = 0.018) and total procedure time (20.0 [16.0–25.0] vs. 24.0 [19.0–30.0] min, p = 0.024). Preparation-to-colonoscopy time was also longer in cases with severe bubbles (5.0 [4.0–5.5] vs. 5.0 [5.0–6.0] h, p = 0.041). Adenoma detection rates were 73.2% in cases without severe bubbles and 67.5% in those with severe bubbles (p = 0.571). Conclusions: Severe bowel bubble formation tended to be associated with longer cecal insertion and total procedure times, and was more frequently observed with a longer preparation-to-colonoscopy interval.

Background: This retrospective study aimed to verify the efficacy of endoscopic submucosal dissection (ESD) using a scissor‐type knife for early gastric cancer (EGC). Methods: The patients who underwent ESD for EGC between April 2014 and March 2022 were enrolled. The primary endpoint of this study was to assess the efficacy of a scissor‐type knife by comparing the self‐completion rate of trainees between gastric ESD performed using a scissor‐type knife (ESD‐SC) and nonscissor devices (ESD‐NS). Results: Of the 903 lesions, 485 and 418 underwent ESD‐SC and ESD‐NS, respectively. The self‐completion rate of trainees was significantly higher for ESD‐SC than for ESD‐NS (50.3 and 33.0%, respectively; p < 0.001). The procedure time was also significantly shorter for ESD‐SC (50.0 vs. 66.5 min, respectively; p < 0.001). Intraoperative perforation rate was not significantly different (0.6% for ESD‐SC and 1.4% for ESD‐NS, respectively). In multivariate analyses, tumor located in the lower third of the stomach (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.46–2.55, p < 0.001), tumor size ≤ 20 mm (OR 3.32, 95% CI 2.20–5.00, p < 0.001), and a scissor‐type knife (OR 2.22, 95% CI 1.67–2.94, p < 0.001) were factors related to the self‐completion rate of trainees for gastric ESD. Conclusions: A scissor‐type knife was associated with higher self‐completion rates and shorter procedure times among trainees. Further prospective studies are needed to validate its clinical utility in ESD training.

Introduction: Improvement of small intestinal lesions is essential for achieving favorable long-term outcomes in patients with Crohn’s disease (CD); however, evidence regarding the efficacy of biologics for small bowel involvement remains limited. Risankizumab (RZB), a selective interleukin-23 (IL-23) p19 inhibitor, has shown efficacy in large randomized trials; however, data on its effect on small intestinal inflammation are limited. This study aimed to evaluate the real-world effectiveness of RZB on small intestinal lesions using balloon-assisted enteroscopy. Methods: We conducted a retrospective study of patients with CD who received RZB between July 2023 and January 2025. Clinical activity was assessed using the Harvey-Bradshaw Index (HBI), and serum biomarkers (albumin, C-reactive protein, and hemoglobin) were measured longitudinally. Endoscopic activity was evaluated using the Simple Endoscopic Score for CD (SES-CD) before treatment and at 28 weeks after treatment; paired endoscopic assessment was available in 16 patients. Results: A total of 23 patients met the inclusion criteria. At baseline, 10 patients had clinically active disease (HBI ≥4), and 13 were in clinical remission (HBI ≤3). In the active group, HBI and C-reactive protein levels decreased after treatment, whereas hemoglobin and albumin concentrations increased during follow-up (HBI: p < 0.01; CRP: p < 0.05; hemoglobin: p < 0.05; albumin: p < 0.05). Among the 16 patients who underwent paired endoscopic evaluation, both total and ileal SES-CD scores decreased after 28 weeks of RZB therapy, demonstrating mucosal improvement in the terminal ileum (total SES-CD: p < 0.0001; ileal SES-CD: p = 0.0001). Notably, several patients who showed inadequate response to ustekinumab (UST) also exhibited endoscopic improvement after RZB treatment. Conclusions: RZB was effective in improving clinical and endoscopic disease activities, including terminal ileal lesions, even in patients who were previously refractory to UST. Given the prognostic importance of small bowel inflammation, these findings highlight the potential of selective IL-23p19 inhibition as a valuable therapeutic option for patients with small bowel-dominant CD.

Background and Aim: The association between vascular cell adhesion molecule‐1 (VCAM‐1) expression and intestinal mucosal inflammation and between VCAM‐1 expression and the clinical course in patients with ulcerative colitis (UC) remains unclear. Therefore, we investigated not only the association between mucosal VCAM‐1 expression and mucosal inflammation but also its association with subsequent relapse in UC patients with clinical remission.Methods: Fifty‐eight patients with UC in clinical remission and 16 patients in clinical active who visited Kyoto Prefectural University of Medicine for a 2‐year follow‐up period were included. VCAM‐1 expression was compared between patients who subsequently relapsed and those who remained in remission, and it was examined in relation to endoscopic findings, histological activity, and cytokine expression. We also investigated the expression of mucosal addressin cell adhesion molecule‐1 (MAdCAM‐1).Results: VCAM‐1 was associated with clinical disease activity and endoscopic severity and was significantly elevated in histologically active mucosa compared with inactive mucosa. VCAM‐1 expression co‐localized with MAdCAM‐1 in the mucosal and submucosal microvessels of the colon and was significantly higher in the relapse group than in the remission group. Similar results were observed for MAdCAM‐1 expression. VCAM‐1 expression levels were also closely correlated with those of several other cytokines.Conclusions: VCAM‐1 expression in the colonic mucosa of patients with UC is associated with mucosal inflammation and subsequent relapse. These results suggest that VCAM‐1 may serve as a marker for relapse and therapeutic effectiveness in UC, and that treatment targeting α4 integrin is efficient and rational.

Introduction: Biopsy-specimen examination is the gold standard for the preoperative histological diagnosis of early gastric cancer (EGC). However, few studies have compared the diagnostic accuracies of biopsy and magnifying endoscopy with narrow-band imaging or blue laser imaging (ME-NBI/BLI). Thus, we compared the diagnostic accuracy of biopsy specimens and ME-NBI/BLI to evaluate whether ME-NBI/BLI is a feasible preoperative diagnostic tool for EGC. Methods: This retrospective single-center study enrolled 185 patients who underwent gastric endoscopic submucosal dissection (ESD) between January and December 2018. The sensitivity and positive predictive value (PPV) of the histological diagnosis of ME-NBI/BLI and biopsy were evaluated. Logistic regression analysis was used to assess the risk factors for the misdiagnosis of biopsy specimens and ME-NBI/BLI. Results: In total, 158 patients with EGC were analyzed. Sensitivities of biopsy and ME-NBI/BLI were 1 and 0 for adenomas (p = 0.333), 0.693 and 0.971 for differentiated adenocarcinomas (p < 0.001), and 0.688 and 0.625 for undifferentiated adenocarcinomas (p > 0.999), respectively. PPVs of biopsy and ME-NBI/BLI were 0.077 and 0 for adenomas (p > 0.999), 0.960 and 0.958 for differentiated adenocarcinomas (p > 0.999), and 0.750 and 0.750 for undifferentiated adenocarcinomas (p > 0.999), respectively. The underdiagnosis rate for differentiated adenocarcinomas was significantly higher in biopsy examination than in ME-NBI/BLI (27.9% vs. 0%, respectively, p < 0.001). Conclusion: ME-NBI/BLI had a higher sensitivity than biopsy examination for the preoperative diagnosis of differentiated adenocarcinomas. Therefore, performing ME-NBI/BLI for these lesions may be preferable regardless of their diagnosis as noncancerous lesions from biopsy specimens.

Background: Mucosal healing is necessary to maintain the long-term remission of ulcerative colitis (UC). Currently, the gold standard for assessing mucosal healing is endoscopic diagnosis. The Mayo Endoscopic Subscore (MES) is the most commonly used index for evaluating endoscopic mucosal healing; however, a certain number of patients may experience relapse during the clinical course of the disease, even at MES 0, where the mucosa appears to be in a state of healing. Therefore, the usefulness of image-enhanced endoscopy, such as narrow-band imaging, linked color imaging, autofluorescence imaging, red dichromatic imaging, texture and color enhancement imaging, and i-Scan, has been increasingly reported in recent years for the diagnosis of complete mucosal healing without recurrence. The importance of histological healing has also been emphasized in recent years. The three main histological scoring systems currently used are the Geboes score, Nancy Histological Index, and Robarts Histologic Index. When combined with MES, these histological assessments have been reported to considerably predict UC relapse. However, the relevance of diagnosing histological activity in patients with MES 0 and endoscopically confirmed mucosal healing remains debatable. Cytokines play an important role in UC pathogenesis, as evidenced by the effectiveness of biologics and small molecules that target specific cytokines in treating refractory cases. Therefore, the concept of “molecular healing” has recently been proposed to describe the regulation of cytokine profiles during mucosal healing in patients with UC. Summary: Specific mucosal cytokine expression correlates with endoscopic severity, predicts UC relapse, and indicates the therapeutic efficacy of biologics. This highlights the growing interest in understanding UC pathogenesis based on cytokine expression. Defining mucosal healing in UC based on mucosal cytokine expression is expected to evolve as a next-generation diagnostic approach. Key Messages: Therefore, accurate diagnosis of mucosal healing in patients with UC is essential. In this review, we describe mucosal healing from the perspective of mucosal gene expression, which has recently gained attention alongside advances in conventional endoscopic and histological diagnostics.

Background: Ulcerative colitis (UC) is a chronic inflammatory disease of unknown cause, for which no curative treatments have been developed. Cytokines play an important role in the pathogenesis of UC, and therapies targeting specific cytokines have been successful in treating refractory UC. The purpose of this study was to measure mucosal cytokines in UC and identify those that contribute to nonrelapsing mucosal healing (MH) diagnosed by endoscopy. Methods: This prospective, observational study included 163 patients with UC. The mucosa was evaluated by the Mayo Endoscopic Subscore (MES) and linked color imaging (LCI) at the time of endoscopy, and cytokine mRNA expression in biopsy tissue taken from the same site was quantified by real-time PCR and compared with endoscopic findings. The relationship between cytokine mRNA expression and endoscopic findings was investigated. Results: Cytokines such as IFNγ, IL-1β, IL-8, IL-17A, and IL-23 were significantly elevated in proportion to endoscopic severity of MES and LCI classification. Interestingly, we found differences in the expression of cytokines (eg, IL-22 and IL-33) between MES and LCI classification according to disease severity. Additionally, pathway analysis based on RNA sequencing comparing LCI-A and LCI-B in patients diagnosed as MES 0 revealed that IL-5 and IL-6 are involved in the finer differences in endoscopic mucosal redness. Conclusions: This study is the first to report the correlation between mucosal cytokine expression and the pathogenesis of MH in UC and supports the contribution of specific cytokines as molecular markers of MH or in the pathogenesis of MH in UC.