Journal of Gastroenterology最新文献

Objectives: Sedation is increasingly essential for gastrointestinal endoscopy. Remimazolam, an ultra-short-acting benzodiazepine, has a shorter pharmacokinetic half-life than midazolam. The aim of this study was to determine whether remimazolam provides superior procedural sedation in Japanese patients.

Methods: The cohort of this prospective, multicenter, randomized, single-blind controlled trial comprised adults (18-80 years) scheduled for sedated upper gastrointestinal endoscopy. Participants were randomized to remimazolam and midazolam groups. The primary outcome was the proportion of ambulatory patients 5 min after endoscopy. Secondary outcomes were successful pre-procedure sedation (Modified Observer's Assessment of Alertness/Sedation ≤ 4), dose of sedative to achieve sedation, time to ambulation, and adverse events.

Results: From October 2024 to January 2025, 40 patients were enrolled. After excluding two outliers 38 were analyzed (remimazolam, n = 20; midazolam, n = 18). Ambulation at 5 min occurred in 85.0% (17/20) of the remimazolam versus 0.0% (0/18) of the midazolam group (p < 0.0001). Mean time from procedure end to walking was 4.25 min (range 0.0-10.0) for remimazolam and 35.56 min (10.0-60.0) for midazolam (p < 0.0001). Pre-procedure sedation was successful (MOAA/S ≤ 4) in 100% of both groups. Mean doses to achieve sedation were 4.30 mg (3.0-7.0) for remimazolam and 3.11 mg (2.0-5.0) for midazolam (p = 0.003). Hypoxemia occurred in 5.0% of the remimazolam and 33.3% of the midazolam group (p = 0.038).

Conclusions: In upper gastrointestinal endoscopy, remimazolam achieved markedly faster recovery and a lower incidence of hypoxemia than midazolam. Rates of achieving target sedation were equivalent. These findings indicate remimazolam is an effective and potentially safer sedative option for Japanese patients undergoing endoscopy.

Trial registration: This research was registered with the Japan Registry of Clinical Trials (trial number jRCTs071240062) on September 26, 2024.

Background: Mismatch repair (MMR) testing is recommended for all colorectal cancer (CRC) patients, but this assay necessitates the involvement of specialized institutions and is time-consuming. This study aims to develop a deep learning model for MMR prediction using macroscopic images to provide a rapid and cost-free screening tool.

Methods: This diagnostic study enrolled 809 CRC patients who underwent surgical resection without neoadjuvant therapy at Peking University Third Hospital (from January 2020 to July 2025). Macroscopic images of surgical specimens were captured immediately after resection. MMR status was confirmed by postoperative immunohistochemical staining for MMR proteins (MLH1, MSH2, MSH6, and PMS2). Deep learning models were developed by a two-step approach: automated lesion segmentation using DeepLabV3 + , followed by MMR classification using vision transformer (ViT). MMR prediction performance was mainly evaluated utilizing area under the curve (AUC). Gradient-weighted Class Activation Mapping (Grad-CAM) appraisal and principal component analysis (PCA) were performed to assess the explainability of the model.

Results: The proposed model achieved an average AUC of 0.896 (95% CI, 0.763-0.959) on internal test and 0.860 (95% CI, 0.644-0.921) on independent test for MMR prediction. High NPVs of 0.987 (95% CI, 0.928-0.999) and 0.978 (95% CI, 0.925-0.994) were observed in internal and independent testing, respectively, using a threshold of 0.323. Grad-CAM analysis and PCA demonstrated that the deep-learning model was of explainability.

Conclusions: The new deep-learning model accurately identified MMR status using macroscopic specimen images and showed potential for MMR screening among CRC patients, particularly in a rapid-response scenario.

Background: Owing to the rarity of metastatic tumors in the small bowel, their clinicopathological features, and prognostic factors remain poorly understood. This study aimed to clarify the clinicopathological features and factors associated with the prognosis of patients with small bowel metastasis from other organs in Japan.

Methods: We retrospectively examined 253 patients who were histopathologically diagnosed with small bowel metastases between January 2008 and December 2017 at multiple institutions in Japan. We identified the clinicopathological features of the condition and determined the factors associated with the prognosis of these patients.

Results: Obstructive symptoms were the most frequent clinical presentations (39% abdominal pain and 18% vomiting), while gastrointestinal bleeding was observed in 27% of patients. The diagnostic modalities included enteroscopy (33%), balloon-assisted enteroscopy (30%), and capsule endoscopy (13%). The most common primary tumor was lung cancer (38%), followed by colorectal cancer (18%), gastric cancer (9%), and malignant melanoma (6%). Surgical intervention, including tumor resection or bypass surgery, was performed in 79% of patients. The cumulative survival rates of patients at 12, 24, and 60 months were 49%, 36%, and 22%, respectively. Multivariate analysis identified surgery as a significant factor for improving overall survival (HR = 0.56, 95% CI 0.35-0.89, p = 0.01).

Conclusions: The lung cancer is the most frequent primary tumor of metastatic tumors in the small bowel. Surgical intervention was associated with improved survival outcomes.

Background: The prognosis and recurrence patterns of early-diagnosed pancreatic ductal adenocarcinoma (PDAC), particularly following surgical resection, remain unclear.

Methods: This multicenter retrospective study analyzed patients who underwent surgical resection for PDAC between 2005 and 2023. Patients were categorized according to pathological stages 0, I, and II. Recurrence patterns and survival outcomes were compared among the three groups. Multivariate analysis was performed to identify independent risk factors for remnant pancreatic recurrence, including early-stage disease, postoperative follow-up of more than 5 years, and receipt of adjuvant chemotherapy.

Results: A total of 349 patients were included: 51 with stage 0, 77 with stage I, and 221 with stage II PDAC. The 5-year overall survival rates were 87%, 71%, and 49% for patients with stage 0, I, and II PDAC, respectively. Remnant pancreatic recurrence was observed in 10% of patients with stage 0 PDAC and 18% of patients with stage I PDAC, compared with 5% of those with stage II PDAC. Recurrence was significantly more frequent in stage I (P < 0.001) and tended to be higher in stage 0 (P = 0.062) than in stage II. Multivariate analysis identified pathological stage 0-I and postoperative follow-up of > 5 years as independent risk factors for remnant pancreatic recurrence.

Conclusions: Patients with early-stage PDAC exhibit a higher risk of remnant pancreatic recurrence than those with stage II disease. These findings underscore the importance of long-term pancreas-focused surveillance in early-stage PDAC to enable timely detection of late recurrence and potentially improve patients outcomes.

Background: Long-term effects of direct-acting antiviral (DAA) on hepatic reserve and prognosis in hepatitis C virus (HCV)-related decompensated cirrhosis remain unclear.

Methods: Ninety-four patients from a follow-up study of the Japanese phase 3 trial of DAA treatment for decompensated cirrhosis were included.

Results: Twelve, seventy-seven, and ten percent of patients had Child-Pugh class A/B/C, respectively. The sustained virologic response (SVR) rate was 93.6%. The proportion of Child-Pugh A patients was 21% at end of treatment (EOT), and 40%, 42%, 49%, 40% at 24 weeks, 1 year, 3 years, and 5 years after EOT, respectively. A significant breakpoint for Child-Pugh class improvement to A was observed between 24 weeks and 1 year after EOT. The proportions of patients with albumin levels > 3.5 g/dl increased from 11% (baseline) to 39% (5 years after EOT), and significant breakpoint for this improvement was observed between 12 and 24 weeks after EOT. During the 4.8 years from EOT, 19 patients died, and 1 underwent liver transplantation (LT). The five-year LT-free survival rate was 74.7%. Multivariate analysis identified virologic response and Child-Pugh class at 12 weeks after EOT as significant LT-free survival predictors. The four-year LT-free survival rates were 91.5% for SVR patients and 33.3% for virologic failure patients.

Conclusions: In HCV-related decompensated cirrhosis, 5 year LT-free survival rate after DAA was 74.7%, and viral clearance and post-treatment Child-Pugh class were associated with long-term prognosis. Child-Pugh class improved until 24 weeks after EOT, but little change was observed thereafter, which was closely associated with albumin levels.

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with limited treatment options and a poor prognosis. Although immune checkpoint inhibitor (ICI)-based chemotherapy has recently been introduced as a first-line treatment, clinical responses remain highly variable. Currently, no reliable molecular biomarkers are available to predict the therapeutic efficacy of ICC.

Methods: We conducted a retrospective, multicenter cohort study of 25 patients with unresectable ICC treated with gemcitabine, cisplatin, and durvalumab (GCD therapy) between September 2022 and August 2024. Comprehensive genomic profiling was performed in 19 patients (76%) to identify genomic alterations. In selected cases, spatial transcriptomic analysis using the Xenium platform was employed to characterize tumor-immune spatial dynamics.

Results: The median progression-free survival (PFS) was 7.8 months (95% CI: 3.6-10.6), and the median overall survival (OS) was 11.1 months (95% CI: 6.9-18.6). Among genomic alterations, TP53 mutation was the only independent predictor of shorter PFS in multivariate analysis (HR: 4.20; p = 0.036). TP53-mutant tumors were associated with significantly shorter PFS (p = 0.011) and a trend toward worse OS (p = 0.051). Spatial transcriptomic profiling revealed a distinct immunosuppressive microenvironment in TP53-mutated tumors marked by poor CD8⁺ T-cell infiltration, enrichment of CD109⁺ tumor-associated macrophages, and downregulation of antigen-presentation genes TAP1 and TAP2.

Conclusions: This study is the first to identify TP53 mutation as a biomarker of resistance to ICI-based therapy in ICC, and to uncover its immune-evasive phenotype using spatial profiling. These findings provide mechanistic insight into immune evasion and support the development of TP53-guided immunotherapeutic strategies in ICC.

Background: This study aimed to evaluate whether laparoscopic splenectomy and azygoportal disconnection (LSD) can promote decompensated cirrhotic portal hypertension (CPH) patients to achieve recompensation as defined by Baveno VII.

Methods: This retrospective study reviewed clinical records and follow-up data of decompensated CPH patients diagnosed with gastroesophageal variceal bleeding (GEVB) and hypersplenism at our hepatobiliary center from 2013 to 2023. According to treatment strategy, patients were categorized into the LSD arm or the endoscopic therapy (ET) arm. Post-treatment liver function, incidence of decompensation events, recompensation, and overall survival were analyzed across the two arms. Furthermore, the mediating effect of LSD on survival through recompensation was analyzed.

Results: This study enrolled 568 eligible patients, with 300 undergoing LSD and 268 receiving ET. Most patients in both groups showed varying degrees of liver function improvement post-treatment. Overall, 307 patients (54.05%) met the Baveno VII criteria for recompensation. More patients achieved recompensation among those treated with LSD as opposed to ET (73.0% VS. 32.8%, OR = 4.569; 95% CI 3.088-6.760; P < 0.001). Mediation assessment indicated that recompensation accounted for 43.3%, 32.4%, and 16.4% of the effect of LSD on mortality at 3, 5, and 8 years, respectively. Furthermore, younger patients were more likely to achieve recompensation after LSD.

Conclusions: LSD was found to significantly promote recompensation and extend survival in decompensated cirrhosis patients with CPH bleeding and hypersplenism.