Therapeutic Advances in Gastroenterology最新文献

Background: Pancreatic cancer is a common and lethal malignancy, with the two primary subtypes being pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (pNET). Accurate diagnosis and effective treatment are crucial. Hyperspectral imaging (HSI) is a novel optical diagnostic technology that can capture spectral features inaccessible by traditional imaging techniques. With the aid of artificial intelligence (AI), HSI can provide richer information.

Objectives: This study aims to develop a convolutional neural network (CNN) based on HSI to assist in the diagnosis of liquid-based cytology (LBC) specimens of PDAC and pNET obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).

Design: We designed a deep learning model using HSI data to differentiate between PDAC and pNET specimens. The CNN model was developed and evaluated using a dataset of LBC slides.

Methods: During the EUS-FNA procedure, we prepared LBC slides of PDAC and pNET specimens. These slides were scanned using HSI technology to acquire both spectral and spatial information. We employed a modified ResNet18 model to analyze this information and perform classifications. In addition, we used attribute-guided factorization visualization (AGF-visualization) to visualize the CNN's decision-making process.

Results: Based on samples from 59 patients, 2014 HSI images were acquired. The spectral curves of PDAC and pNET cells exhibited recognizable differences in the wavelength range of 520-600 nm. Our modified ResNet18 model processes images at approximately 9 images/s and achieves a sensitivity of 90.80%, a specificity of 94.68%, and an accuracy rate of 92.82% (area under the receiver operating characteristic curve = 0.9721). AGF-visualization confirmed that our CNN model classifies based on the features of the tumor cell nucleus.

Conclusion: Our HSI-CNN model accurately differentiates PDAC and pNET in EUS-FNA specimens, aiding pathologists in diagnosis and reducing their workload.

Background: Non-variceal gastrointestinal bleeding (NVGIB) is a critical situation and needs immediate resuscitation therapy. Hemostatic powder (HP) is an effective way to achieve hemostasis.

Objectives: This study compares the outcomes of HP and conventional therapies (CT) for NVGIB patients.

Design: Systematic review and meta-analysis of randomized controlled trials (RCTs).

Data sources and methods: We searched PubMed, Scopus, and other medical databases up to August 2024. This meta-analysis includes studies that reported data on rebleeding, hemostasis, and hospital stays. Using a random-effect model, we analyzed the odds ratios (OR) of the outcomes between the HP and CT groups.

Results: Nine RCTs meeting the inclusion criteria were included in this study, comprising data from 796 patients. HP demonstrated a statistically significant advantage in achieving hemostasis compared to CT, with an OR of 2.73 (95% confidence interval (CI): 1.09-6.80; p = 0.03). However, no significant differences (p > 0.05) were observed in rebleeding rates (OR: 0.73; 95% CI: 0.36-1.47) or length of hospital stay (mean difference: 1.38 days; 95% CI: -1.18 to 3.93). Secondary outcomes, including mortality, surgical intervention requirements, blood transfusion needs, intensive care unit admissions, transfusion units, and procedure time, also showed no significant disparities between groups. Subgroup analyses based on bleeding etiology revealed enhanced efficacy of HP in cases of tumor-related bleeding.

Conclusion: Both HP and CT effectively manage NVGIB with similar rebleeding rates, but HP demonstrates superior immediate hemostasis, offering a critical advantage in acute bleeding control.

Meta-analysis registration: This systematic review and meta-analysis was registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/) with registration number CRD42024523237.

Background: Large common bile duct stones (CBDSs) often require endoscopic papillary large balloon dilation (EPLBD) for removal. However, stone removal is sometimes insufficient when EPLBD is performed using conventional devices such as balloon catheters, basket catheters, and mechanical lithotripsy. Adjunctive electrohydraulic lithotripsy (EHL) is suggested to be useful for large CBDSs that cannot be removed by conventional approach.

Objectives: The present study aimed to identify pre-procedural predictors for the need for EHL.

Design: A retrospective, single-center observational study.

Methods: Patients with CBDSs ⩾10 mm in diameter who underwent EPLBD or EHL between December 2017 and March 2025 were included. Clinical factors associated with the need for EHL in EPLBD to remove large CBDSs were analyzed by multivariate logistic regression. Receiver operating characteristic (ROC) curve analysis was performed to determine the predictive value of the independent risk factors.

Results: A total of 2881 patients underwent endoscopic retrograde cholangiopancreatography during the study period, 163 patients were included in this study. Among them, CBDS removal with EPLBD could be achieved with conventional devices in 123 patients, while 40 patients required EHL. Multivariate analysis suggested that independent risk factors for the need for EHL in EPLBD to remove CBDSs were a larger maximum bile duct diameter and a higher stone-to-distal bile duct diameter (SD) ratio. In ROC analysis, the SD ratio had the highest area under the curve of 0.82 (95% confidence interval, 0.75-0.89) with an optimal cut-off value of 1.17. The sensitivity, specificity, positive predictive value, and negative predictive value at this cutoff were 0.95, 0.51, 0.39, and 0.97, respectively.

Conclusion: A higher SD ratio was shown to be a potential independent risk factor for the need for EHL in EPLBD for large CBDSs. Patients with a SD ratio ⩾1.17 may be more likely to require additional treatment. These findings are exploratory and require validation in future studies to confirm their robustness and support their generalizability.

Background: Endoscopic retrograde appendicitis therapy (ERAT) has emerged as a minimally invasive approach to treating appendicitis.

Objectives: This study aimed to assess the long-term safety and efficacy of ERAT and to develop a model predicting 1‑year appendicitis recurrence in patients with acute appendicitis, to guide clinical decision-making.

Design: This is a multicenter retrospective study. Consecutive patients were referred to the three participating centers.

Methods: A retrospective analysis was conducted on clinical data from 435 patients with acute appendicitis who underwent ERAT at three hospitals between October 2017 and October 2024. Twenty-four clinical variables were screened, and Spearman correlation analysis revealed correlation coefficients exceeding 0.6 between some variables. To address multicollinearity, LASSO regression was employed to identify key predictive factors in the training set. A predictive model was constructed using multivariate logistic regression, and a nomogram was developed.

Results: All ERAT procedures were technically successful, and a clinical success rate of 92.4% was achieved. The median follow-up period was 37 months, and the overall recurrence rate was 16.1%; most recurrences (13%) were observed in the first year. Based on LASSO regression analysis, the final predictors identified were: age >60 years (odds ratio (OR) = 2.981, 95% confidence interval (CI): 1.368-6.497, p = 0.006), recurrence appendicitis (OR = 4.048, 95% CI: 1.931-8.587, p < 0.001), Alvarado score >6 (OR = 5.649, 95% CI: 2.586-12.339, p < 0.001), fecalith (OR = 2.680, 95% CI: 1.146-6.267, p = 0.023), inexperienced operator (OR = 2.286, 95% CI: 1.141-4.580, p = 0.020), procedure time >40 min (OR = 2.472, 95% CI: 1.240-4.927, p = 0.010), appendix lumen distortion (OR = 7.634, 95% CI: 1.414-41.219, p = 0.018), and stent placement (OR = 5.970, 95% CI: 0.121-0.793, p = 0.015). Based on these eight predictive factors, a nomogram model was constructed to predict recurrence risk within 1 year after ERAT.

Conclusion: ERAT is a safe and effective treatment for acute appendicitis. The risk of recurrence is highest within the first year. Eight independent risk factors for recurrence within 1 year after ERAT were identified, and a recurrence risk prediction model based on these predictive factors can assist in future clinical decision-making for ERAT.

Background: No established predictive biomarker beyond tissue HER2 status currently exists for trastuzumab deruxtecan (T-DXd) treatment response in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). Serum HER2 extracellular domain (HER2 ECD) has shown potential in breast cancer; however, its clinical significance in gastric cancer remains unclear.

Objectives: To evaluate the efficacy and safety of T-DXd in HER2-positive AGC and investigate the predictive role of serum HER2 ECD for T-DXd response.

Design: Retrospective single-institution study.

Methods: Data of HER2-positive AGC patients treated with T-DXd were analyzed. According to their baseline serum HER2 ECD levels, the patients were classified into high (⩾12.1 ng/mL) and low (<12.1 ng/mL) HER2 ECD groups. Tumor responses, HER2 ECD dynamics, HER2 re-biopsy status, progression-free survival (PFS), and overall survival (OS) were evaluated.

Results: Altogether, 67 patients were enrolled. The HER2 ECD data were available only for 38 patients, with 23 and 15 patients in the high and low HER2 ECD groups, respectively. The objective response rate (ORR) was significantly higher in the high HER2 ECD group (65.2%, 15/23 vs 26.7%, 4/15; p = 0.045). Among the patients with immunohistochemistry (IHC) 2+/in situ hybridization (ISH+) tumors, responses were observed exclusively in the high HER2 ECD group (57.1%, 4/7 vs 0%, 0/8). Additionally, the HER2 ECD level changes post-treatment initiation also reflected tumor response, with no responses observed in the high HER2 ECD group. HER2 positivity in re-biopsy was associated with higher ORR (50.0%, 3/6 vs 25.0%, 1/4). Contrarily, the baseline HER2 ECD levels were not associated with PFS or OS.

Conclusion: Baseline serum HER2 ECD may be a potential non-invasive predictor of T-DXd response in HER2-positive AGC, particularly in IHC 2+/ISH+ cases. Dynamic HER2 ECD level changes during therapy may also reflect treatment response.

The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) study group was initially established to ascertain the precise incidence of inflammatory bowel disease (IBD) within a specific region of Norway, thereby contributing to a global initiative aimed at elucidating the increasing prevalence of these conditions. The study was designed to foster close collaboration among national and international experts, including gastroenterologists, specialists, and private practitioners within the study area. Patients were enrolled prospectively over a 4-year period, from January 1, 1990, to December 31, 1993, based on established international diagnostic criteria and a follow-up protocol encompassing 1, 5, 10, 20, and 30-year intervals. The consortium operated through a bidirectional communication network connecting primary and secondary specialized hospitals, encompassing general hospitals and research laboratories. In 2017, the IBSEN III study was launched to facilitate a comparison of clinical and epidemiological outcomes with those of the original IBSEN study, involving an expanded catchment area and more extensive clinical and molecular assessments of the cohort. This narrative review reflects the consortium's activities through 2024 and provides comprehensive details regarding the research areas and outcomes of national and international collaborations for both IBSEN study.

Background: Gastric outlet obstruction (GOO) caused by malignancy significantly impairs patient quality of life. Surgical gastrojejunostomy (SGJ), endoscopic stenting (ES), and endoscopic ultrasound-guided gastroenterostomy (EUS-GE) are the three main palliative treatments. However, the optimal approach remains unclear because of variations in study results and limited studies comparing treatment types.

Objectives: To evaluate and compare the effectiveness and safety of EUS-GE, ES, and SGJ in the management of GOO.

Design: Network meta-analysis.

Data sources and methods: The PubMed, Cochrane Library, and Web of Science databases were systematically searched for full-length articles of randomized controlled trials and cohort studies in English comparing SGJ, ES, and EUS-GE in adult patients with malignant GOO. Studies with unbalanced baseline characteristics or technical variations within a single modality were excluded. The primary outcome was the reintervention rate for recurrent GOO. Secondary outcomes included clinical success and adverse event rates.

Results: Fifty-four studies involving 6110 patients were analyzed (SGJ, n = 1974, ES, n = 3226, EUS-GE, n = 910). Compared with ES, both SGJ (odds ratio (OR): 0.32, 95% confidence interval (CI): 0.22-0.46) and EUS-GE (OR: 0.29, 95% CI: 0.17-0.51) significantly reduced the risk of reintervention. EUS-GE achieved a higher clinical success rate than ES (OR: 2.46, 95% CI: 1.50-4.04) and also lower adverse event rate than both SGJ (OR: 0.33, 95% CI: 0.19-0.56) and ES (OR: 0.61, 95% CI: 0.37-0.99). Heterogeneity was moderate across outcomes, with no major inconsistency or publication biases detected.

Conclusion: Of the three treatments for GOO, EUS-GE demonstrated the most favorable profile in terms of efficacy, safety, and durability. SGJ remains a viable alternative, particularly in centers lacking expertise in advanced endoscopy. These findings may inform future clinical guidelines and support the broader adoption of EUS-GE in appropriate settings.

Background: Proton pump inhibitors (PPIs) are the standard treatment for erosive esophagitis (EE), yet 20%-40% of patients show inadequate response. Vonoprazan, a potassium-competitive acid blocker (P-CAB), provides faster and more sustained acid suppression than PPIs.

Objectives: To evaluate the efficacy and safety of vonoprazan compared with lansoprazole in the treatment and maintenance of EE, and to explore dose-response and duration effects using meta-regression analysis.

Design: Systematic review and meta-analysis of randomized controlled trials (RCTs).

Data sources and methods: Electronic databases (PubMed, Embase, Cochrane CENTRAL, ClinicalKey, ProQuest, ScienceDirect, Web of Science, and ClinicalTrials.gov) were searched through March 31, 2025. Eligible RCTs compared vonoprazan with lansoprazole for EE treatment. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Meta-regression assessed dose- and duration-dependent effects.

Results: Seven RCTs involving 3754 participants (mean age 54.6 ± 3.2 years; 68.5% male) were included. Vonoprazan significantly improved healing rates versus lansoprazole (OR = 1.855; 95% CI: 1.386-2.482; p < 0.001; I ² = 8.38%) and recurrence-free rates (OR = 2.920; 95% CI: 1.636-5.211; p < 0.001; I ² = 70.99%). Serum gastrin levels were higher with vonoprazan (OR = 2.707; 95% CI: 1.430-5.123; p = 0.002). Meta-regression showed that longer treatment duration (β = 0.0163 per day; p < 0.0001) and higher dosage (β = 0.0293 per mg; p < 0.0001) were associated with improved healing. Adverse event rates did not differ significantly between groups (OR = 1.104; 95% CI: 0.922-1.321; p = 0.331; I ² = 12.99%).

Conclusion: Vonoprazan provides superior healing and maintenance efficacy compared with lansoprazole without increasing adverse events. Its benefits are dose- and duration-dependent, supporting vonoprazan as a first-line option for EE, particularly in severe or PPI-refractory cases.

Trial registration: This study was registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY; INPLASY202590075; DOI: 10.37766/inplasy2025.9.0075).

Background: Small intestinal-predominant Crohn's disease (CD) exhibits distinct therapeutic patterns and is characterized by increased biological use and intestinal resection rates. However, systematic evaluations of the objective response of ustekinumab (UST), particularly related to disease location, are limited.

Objectives: To compare the therapeutic efficacy of UST between small intestinal CD (SICD) and non-small intestinal CD (NSICD).

Design: A prospective observational cohort study.

Methods: Demographic and clinical characteristics were collected at baseline and 52-week follow-up, assessments including endoscopy, imaging, ultrasonography (US), histopathology, fecal calprotectin (FCP), C-reactive protein (CRP), and hemoglobin results. Patients with isolated ileal involvement (Montreal classification L1) were classified as having SICD, while NSICD was defined by L2 and L3. Primary outcome was objective remission, defined by meeting one of the following: (1) endoscopic remission (ER): Simple endoscopic score for CD (SES-CD) ⩽ 2. (2) US remission: normal bowel wall thickness and absence of Doppler signals or detectable complications, or (3) radiological remission: complete resolution of inflammatory features. Secondary outcomes included (1) mucosal healing (MH): absence of ulcerations. (2) transmural healing (TH): complete healing of all intestinal wall layers, and (3) biochemical remission: FCP/CRP normalization, (4) objective response: a clear improvement from baseline, and (5) endoscopic response: SES-CD ⩽ 4.

Results: This study included 331 patients with CD (SICD 36.9%, NSICD 63.1%). Of these, 309 completed a 52-week follow-up. Objective remission, MH, and TH were achieved by 32.7%, 25.6%, and 13.6% of patients, respectively. Biochemical remission occurred in 41.5% (FCP) and 35.2% (CRP). Objective and endoscopic responses were observed in 70.2% and 42.1% of patients, respectively. Objective remission was achieved in 54/116 patients (46.6%) in the SICD group and 47/193 (24.4%) in the NSICD group. Regression analyses and propensity score matching showed significantly higher rates of objective remission, MH, and endoscopic response in the SICD group.

Conclusion: Disease location influenced UST treatment outcomes, with SICD showing higher rates of objective remission, MH, and endoscopic response than NSICD.

Background: Intraepithelial eosinophils have been described in patients with esophageal motor disorders. Conversely, motor disorders and even achalasia have been reported in patients with eosinophilic esophagitis (EoE).

Objectives: This prospective study aimed to further investigate the association between eosinophilia and achalasia.

Design: This is a prospective study.

Methods: A series of 30 consecutive treatment-naïve achalasia patients (mean age: 45.5 years, 53% female) undergoing laparoscopic myotomy were prospectively enrolled. Preoperative demographic and clinical data, radiological findings, and high-resolution manometry (HRM) features were collected. Patients underwent upper endoscopy with biopsy sampling before surgery, and two samples of distal esophageal muscle were obtained during myotomy. Histopathologic findings were analyzed, and clinical characteristics were compared based on the presence and absence of eosinophils on biopsy samples.

Results: Intraepithelial eosinophils were found in seven patients (23%; mean 8 eos/high-power field, 95% CI 0-15), but only one patient demonstrated >15 eos/high-power field, and one had eosinophilic infiltration of the esophageal muscle. Patients with intraepithelial eosinophilia had a narrower esophageal diameter on barium radiography (2.4 vs 3.6 cm without eosinophilia, p < 0.05). There were no additional differences in histopathology or preoperative and postoperative data between patients with and without intraepithelial eosinophilia.

Conclusion: Our study confirmed that intraepithelial and intramuscular eosinophils are present in some patients with achalasia, but seldom meet the criteria for EoE. Only a narrower esophagus was found in patients with intraepithelial eosinophils as compared to those without, possibly reflecting an earlier stage of the disease.