Digestion最新文献

Introduction: Early use of biologics improves outcomes for Crohn's disease (CD). Evidence now indicates that initiating therapy within 6 months of diagnosis - the "very early" window - may yield additional benefits over the traditional ≤2-year target. We therefore compared 1-year outcomes after very early (<6 months) versus early (6-24 months) biologic initiation in routine practice.

Methods: In this retrospective cohort (March 2018 to June 2025), biologic-naïve adults with CD and ≥52 weeks of follow-up were stratified by time from diagnosis to first biologic: very early (<6 months) or early (6-24 months). The primary endpoint was steroid-free clinical remission at week 52. Multivariate logistic regression identified variables independently associated with remission.

Results: Ninety-six patients were analyzed (very early = 52; early = 44). Baseline characteristics were comparable except for a higher proportion of corticosteroid use in the very early group (67.3% vs. 43.2%; p = 0.018). At week 52, very early initiation was associated with a lower mean CD Activity Index (64.82 ± 6.79 vs. 96.10 ± 13.03; p = 0.038) and a higher steroid-free clinical remission rate (71.2% vs. 45.5%; p = 0.011). Concomitant corticosteroid use fell to 11.4% in the very early group versus 30.6% in the early group (p = 0.033). Very early initiation remained the strongest independent predictor of steroid-free remission (adjusted OR 3.537, 95% CI: 1.417-8.824; p = 0.007).

Conclusions: Initiating biologic therapy within 6 months of CD diagnosis significantly increases 1-year steroid-free clinical remission and reduces corticosteroid dependence compared with initiation at 6-24 months. These real-world data support adopting a standardized "very early" biologic treatment strategy to optimize clinical outcomes in newly diagnosed, biologic-naïve CD.

Introduction: Sedation protocols for balloon-assisted enteroscopy (BAE) are not yet standardized. The aim of this study was to compare the efficacy and safety between continuous infusion and intermittent bolus administration of midazolam for sedation during BAE. The study hypothesis was that continuous infusion would provide a greater proportion of time under conscious sedation than would intermittent bolus administration.

Methods: We conducted a multicenter, prospective, double-blind, randomized controlled trial at 15 institutions of the National Hospital Organization in Japan. Patients scheduled for diagnostic or therapeutic BAE were randomly assigned to receive continuous infusion or intermittent bolus administration of intravenous midazolam. The primary endpoint was the proportion of time under conscious sedation, defined as a Ramsay Sedation Scale score of 3-4. Secondary endpoints included body movements causing procedure interruption, endoscopist and patient satisfaction, total drug dosage, adverse events, and termination of the procedure.

Results: Of 76 enrolled patients (39 continuous infusion group, 37 intermittent bolus group), one from each group discontinued before treatment, leaving 74 patients (38 continuous group, 36 intermittent bolus group) for analysis. The proportion of time under conscious sedation was comparable between groups (mean ± SD: 0.637 ± 0.315 vs. 0.609 ± 0.272, p = 0.721). However, the continuous infusion group showed a lower incidence of body movements causing procedure interruption (7.9% vs. 25.0%, p = 0.091). The total midazolam dose was higher in the continuous infusion group, whereas the incidence of adverse events was comparable between the two groups.

Conclusion: Continuous infusion of midazolam did not demonstrate superiority over intermittent bolus administration with regard to the proportion of time under conscious sedation. However, continuous infusion suppressed body movements during BAE without increasing adverse events; thus, it could be one of the feasible sedation options for BAE in clinical practice.

Introduction: Vonoprazan (VPZ) therapy has become one of the standard treatments for gastroesophageal reflux disease (GERD). When GERD symptoms persist despite the maintenance dose therapy (10 mg daily), dose escalation to 20 mg daily is generally recommended. This study aims to clarify the proper timing and predictors for dose escalation of VPZ therapy in patients with refractory GERD treated with the maintenance dose.

Methods: This retrospective observational study included 257 patients with symptomatic GERD. Data from medical records, including endoscopic findings and Izumo scale scores, were analyzed.

Results: The mean follow-up period was 3.3 years. Throughout the follow-up period, VPZ dose escalation (from 10 to 20 mg daily) was required in 56 of 257 patients (22%). Kaplan-Meier analysis showed cumulative dose-escalation-free rates at 6 months, 1 year, and 2 years were 87%, 81%, and 78%, respectively. Predictive factors for VPZ dose escalation were analyzed using a Cox proportional-hazards regression model. Multivariate analysis revealed that pre-existing epigastric pain was a significant positive predictor for dose escalation, whereas pre-existing constipation was identified as a significant negative predictor. Kaplan-Meier analysis indicated that the 1-year dose-escalation-free rates were 69% in patients with epigastric pain compared to 88% in those without (p = 0.001). GERD symptom scores showed a significant improvement 1 month after dose escalation.

Conclusion: The incidence of refractory GERD requiring VPZ dose escalation is relatively low. Epigastric pain prior to VPZ initiation independently predicts the need for dose escalation. VPZ dose escalation effectively improves GERD symptoms.

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.

Introduction: Systemic sclerosis (SSc) causes esophageal motility disorders. However, esophageal symptom severity often does not correlate with the physiological findings of high-resolution manometry (HRM) in patients with SSc. Esophageal hypervigilance and visceral anxiety play a relevant role in symptom perception in patients with gastroesophageal reflux disease and esophageal motility disorders. Therefore, the present study examined the effects of anxiety and hypervigilance, along with HRM findings, on esophageal symptom severity in patients with SSc.

Methods: We reviewed the clinical data of consecutive patients with SSc who underwent HRM and were assessed using the esophageal hypervigilance and anxiety scale (EHAS) at our hospital between January 2022 and February 2025. Predictors for the Eckardt symptom score (ESS) and gastroesophageal reflux disease questionnaire (GerdQ) were investigated.

Results: This study included 51 patients with SSc. Significant differences were observed in EHAS scores between patients with ESS >3 and those with ESS ≤3 (34.0 [24.0-42.0] vs. 13.0 [1.0-24.0], p = 0.003), but not in HRM findings. The EHAS score accounted for 38.2% of the variance in the ESS score. Significant differences were also observed in the EHAS score between patients with GerdQ ≥8 and those with GerdQ <8 (26.0 [14.3-32.5] vs. 13.0 [0-22.0], p = 0.011). The combined factors of the EHAS score and absent contractility accounted for 17.3% of the variance in the GerdQ score.

Conclusion: Esophageal hypervigilance and anxiety may be involved in esophageal symptom severity, particularly dysphagia severity, in patients with SSc. Further studies involving interventions targeting these conditions, such as cognitive behavioral therapy, are warranted.

Background: Barrett's esophagus (BE) is a recognized precursor to esophageal adenocarcinoma (EAC), yet its endoscopic diagnosis remains inconsistent worldwide. This review summarizes current challenges and recent advancements in the endoscopic diagnosis of BE, including updates from international consensus statements and emerging technologies such as image-enhanced endoscopy (IEE) and artificial intelligence (AI).

Summary: This narrative review integrated international guidelines, multicenter studies, expert consensuses, including the Kyoto International Consensus and Asian Barrett Consortium data, and recent trials of diagnostic imaging and quality indicators (QIs) regarding BE surveillance.

Key messages: Discrepancies in defining the gastroesophageal junction (GEJ) - notably between palisade vessels and gastric folds - contribute to the global variability of the BE diagnosis. The Kyoto International Consensus recommends using the distal end of the palisade vessels as a more stable and histologically consistent landmark. Additionally, the Prague C & M criteria offer a standardized approach to measuring the BE length; however, limitations for ultra-short-segment BE exist. IEE modalities such as linked color imaging and red dichromatic imaging enhance GEJ visualization, whereas AI systems have the potential for automated BE classification. QIs such as the neoplasia detection rate, inspection time, and adherence to biopsy protocols have been proposed to improve diagnostic consistency and outcomes. Standardizing the endoscopic definition of BE and adopting quality-based surveillance strategies are essential to improving detection and reducing variability. Incorporating IEE- and AI-based tools into routine practice may support a more reliable and efficient diagnostic pathway for BE, thus facilitating early EAC detection and prevention worldwide.

Introduction: Non-ampullary duodenal epithelial tumors with a gastrointestinal mixed phenotype (mixed-type NADETs) have not been thoroughly analyzed. We aimed to elucidate the clinicopathological and endoscopic characteristics of mixed-type NADETs.

Methods: A total of 229 NADETs from 218 patients collected from February 2010 to December 2023 were analyzed. Based on immunohistochemistry for MUC5AC, MUC6, MUC2, and CD10, the NADETs were classified into gastric phenotype (GP), gastric predominant mixed phenotype (GPP), intestinal predominant mixed phenotype (IPP), and intestinal phenotype (IP).

Results: Among the 229 NADETs, there were 20, 22, 69, and 118 lesions classified as GP, GPP, IPP, and IP, respectively. Tumor location (first/second/third) was GP = 13/7/0, GPP = 12/8/2, IPP = 13/52/4, and IP = 16/94/8 (p < 0.01). Mean tumor sizes of GP, GPP, IPP, and IP were 14.7/18.5/10.9/10.3 mm (p < 0.01), respectively. The ratio of category 4/5 by Vienna classification was 50.0, 68.2, 13.0, and 2.5% (p < 0.01), respectively. In the comparisons between GP vs. GPP and IP vs. IPP, white opaque substance was significantly less frequently observed in GP than in GPP (p < 0.05), the ratio of category 4/5 was significantly higher in IPP than in IP (p < 0.01), but no significant differences were observed in tumor location, coloration, macroscopic type, and endoscopic findings including magnifying endoscopy with narrow-band imaging.

Conclusion: Mixed-type NADETs (GPP and IPP) exhibited similar endoscopic and clinicopathological characteristics to their predominant phenotypes, and may have a higher malignant potential than the pure phenotypes.

Background: Barrett's esophagus (BE)-related neoplasia remains less prevalent in Japan than in Western countries; however, its incidence is steadily rising. While multimodal treatment - typically endoscopic resection (ER) followed by ablation - is the standard of care, ER alone remains the primary treatment strategy in Japan. With advances in endoscopic techniques, endoscopic submucosal dissection (ESD) has become the mainstay for managing BE-related neoplasia. This review outlines the current Japanese approach, focusing on indications, preoperative assessment, treatment outcomes, and post-resection surveillance practices within the Japanese clinical context.

Summary: Accurate endoscopic assessment, including the use of magnifying endoscopy with image-enhanced modalities, is central to Japanese practice due to the importance of complete resection of neoplasia in the absence of ablative therapy. While data on BE-related neoplasia remain relatively limited in Japan, several multicenter studies have demonstrated favorable outcomes for ESD in terms of resection quality, safety, and long-term survival, particularly in low-risk patients. However, challenges remain, including the lack of standardized surveillance protocols and considerable heterogeneity in clinical practice across institutions. The establishment of unified clinical pathways and evidence-based strategies will be essential to address the increasing burden of BE-related neoplasia in Japan.

Key messages: The incidence of BE and esophageal adenocarcinoma is increasing in Japan, although still significantly lower than in Western countries. Unlike the Western standard of combining ER with radiofrequency ablation (RFA), Japanese practice relies primarily on ESD as the main curative modality. RFA is not widely available in Japan, leading to a reliance on complete resection and more aggressive ER strategies. Surveillance strategies remain inconsistent, largely due to the lower disease prevalence and limited Japan-specific clinical evidence.

Background: Barrett's esophagus (BE) is the replacement of normal squamous epithelium in the distal esophagus by columnar epithelium. The prognosis of esophageal adenocarcinoma depends largely on the stage at diagnosis. Advances in endoscopic imaging and quality standards have significantly improved the early detection of BE-associated neoplasia. This review summarizes current classification systems, sampling protocols, and adjunct tools for diagnosing early neoplasia in BE in Western practice.

Summary: In Western practice, the diagnosis of BE relies on consensus criteria requiring endoscopic evidence and histopathological confirmation of columnar epithelium proximal to the gastroesophageal junction. However, there are discrepancies regarding the minimum BE extent and the necessity of intestinal metaplasia for diagnosis. Detecting early neoplasia in BE is challenging due to the flat and subtle nature of dysplastic lesions. High-definition white-light endoscopy (HD-WLE) is the standard modality for BE surveillance and is used to assess for characteristic features of neoplasia, including nodularity, surface irregularity, color changes, and demarcated areas. Image-enhancing techniques - such as virtual chromoendoscopy (e.g., narrow-band imaging [NBI], texture and color enhancement imaging [TXI], blue light imaging [BLI], linked color imaging [LCI]), and acetic acid chromoendoscopy - have improved dysplasia detection when applied alongside validated classification systems. Despite technological advances, random four-quadrant biopsies (4QBs) remain the standard for dysplasia detection. Estimating lesion depth is based primarily on HD-WLE, with limited contribution from chromoendoscopy and ancillary imaging techniques (i.e., endoscopic ultrasound [EUS], confocal laser endomicroscopy, optical coherence tomography).

Key messages: Early Barrett's neoplasia is challenging to detect. HD-WLE and image-enhancing techniques improve visualization, but random 4QBs remain central to the diagnostic process. Lesion depth is primarily assessed using endoscopic features and, to a limited extent, ancillary techniques.

Background: Barrett's esophagus (BE) is becoming increasingly prevalent in both Western countries and Japan. Early diagnosis of Barrett's neoplasia remains challenging. Traditionally, the Seattle protocol, a four-quadrant random biopsy method, has been recommended in Western guidelines. However, this approach has several limitations, including sampling errors, poor adherence, and a high procedural burden. Therefore, magnifying endoscopy has gained attention as a valuable tool for detecting and characterizing neoplastic lesions in patients with BE.

Summary: This review outlines historical and current developments in magnifying endoscopic classification systems for BE, with a focus on narrow-band imaging (NBI) and acetic acid chromoendoscopy in both Western countries and Japan. Although various NBI-based classifications have been proposed, their complexity and poor reproducibility have limited their widespread clinical adoption. Recently, simplified and standardized classification systems, including the Barrett's International NBI Group classification in the West and the Japan Esophageal Society-Barrett's esophagus classification in Japan, have been introduced. These systems adopt a binary framework, categorizing mucosal and vascular patterns as "regular" (non-neoplastic) or "irregular" (neoplastic). They are easy to apply and have demonstrated high diagnostic accuracy and substantial interobserver agreement. Further simplification and practical refinement are required for broader clinical implementation.

Key messages: Compared with other gastrointestinal cancers, the magnifying endoscopic diagnosis of Barrett's neoplasia remains technically demanding. However, based on a growing body of evidence, endoscopists should be encouraged to actively challenge this area. Continued efforts to simplify and validate the classification systems are essential for their widespread clinical use in BE surveillance.