Background:Bile acid diarrhoea (BAD) is an increasingly recognized cause of chronic diarrhoea. The 75-selenium homocholic acid taurine (SeHCAT) test remains the gold standard for diagnosis. The primary pharmacological treatment involves bile acid-binding agents, most commonly colestyramine. This study aimed to review the management of BAD at our centre and to identify factors associated with response to colestyramine. Materials and methods:This single-centre retrospective study included all patients with an abnormal SeHCAT test (retention <15%) from 1 January 2020 to 31 December 2023 associated with chronic diarrhoea. Patients receiving empiric bile acid chelators without prior SeHCAT testing and those under 18 years of age were excluded. The primary endpoint was treatment success with colestyramine, defined as complete or partial clinical response without treatment discontinuation due to intolerance. Univariable comparisons and multivariable logistic regression were performed to identify factors independently associated with treatment success. Results:Ninety-seven patients were included; 72.2% were women, with a mean age of 54.4 ± 15.1 years. Severe BAD was observed in 60.8% of cases. Overall, 77.3% of patients responded to colestyramine (43.2% complete, 34.0% partial). In multivariable analysis, baseline higher number of bowel movements per day was independently associated with a lower probability of treatment success (odds ratio 0.79, 95% confidence interval 0.68-0.92; P = 0.003). Colestyramine failure was generally due to intolerance-related discontinuation (17.5% of the cohort) followed by lack of efficacy (5.1%). No severe adverse events were documented. Conclusion:Colestyramine appears to be an effective first-line therapy for BAD in routine clinical practice. However, treatment success in this study reflects both clinical response and tolerability, as treatment failure was more frequently related to intolerance than lack of efficacy.
Background:Patients with small-bowel stricturing Crohn's disease (sbsCD) usually have a higher risk of intestinal surgical resection. We aimed to develop a machine-learning model for predicting the 1-year surgery risk in these patients. Methods:This study included 520 retrospectively enrolled patients with sbsCD (training cohort, n = 416; testing cohort, n = 104) from January 2018 to May 2021 and 126 prospectively enrolled patients in the validation cohort from July 2021 to December 2023 across four centers for inflammatory bowel disease in China. Clinical and radiological features were assessed by using logistic regression analyses to identify independent surgery risk factors. Six predictive machine-learning models for 1-year surgical risk were developed and the model performance was comprehensively evaluated by constructing receiver-operating characteristic (ROC) curves and comparing area under the curve (AUC) values. Four simplified Bayesian network (BN)-based risk matrices were constructed for clinical practice. Results:There were 158 (24.4%) Crohn's disease (CD)-related surgeries during the 1-year follow-up. Eight selected predictors of surgery included penetrating lesions, nonuse of biologics, nonuse of corticosteroids, a CD obstructive score of ≥3, endoscopic strictures, anemia, radiologic luminal narrowing, and prestenotic dilation. Among the six models evaluated, the Tree-Augmented Naïve Bayes (TAN) model demonstrated optimal performance, with a mean AUC of 0.878. A further prospective validation cohort verified the efficacy of the model, with 87.5% specificity, 76.7% sensitivity, and 84.9% accuracy for predicting 1-year surgery. Four simplified BN-based risk matrices were constructed for practical use. An online prediction tool is available at http://prebn.site/. Conclusion:We developed and validated a TAN-based BN model incorporating clinical and radiological features to accurately predict the 1-year surgical risk for clinical application in patients with sbsCD, thereby providing a promising tool for decision-making.
Background:Celecoxib is widely used in the prevention and treatment of colorectal cancer (CRC). Although its mechanism of action involves both cyclooxygenase-2 (COX-2)-dependent and COX-2-independent pathways, the non-COX-2 targets of celecoxib remain poorly understood. Preliminary experiments revealed that celecoxib can inhibit the expression of the propionyl-CoA carboxylase alpha chain (PCCA); hence, this study aimed to investigate the role and underlying mechanisms of PCCA as a non-COX-2 target of celecoxib. Methods:Wound-healing, transwell, and Cell Counting Kit-8 assays were conducted to evaluate the effects of celecoxib on migration, invasion, and proliferation in PCCA-overexpressing CRC cell lines. Western blotting was performed to assess the expression of epithelial-mesenchymal transition (EMT) markers. In vivo tumor growth and angiogenesis were examined by using mouse models. Quantitative polymerase chain reaction was used to analyse the transcriptional levels of placental growth factor (PLGF). Results:Celecoxib inhibited PCCA expression in CRC and suppressed PCCA-mediated migration, invasion, and proliferation in COX-2-deficient CRC cell lines (HCT116 and DLD1). These effects were associated with the reversal of PCCA-induced downregulation of E-cadherin and upregulation of N-cadherin and vimentin. In addition, celecoxib inhibited PCCA-driven tumor growth and angiogenesis in HCT116 cells, which correlated with altered PLGF expression. Conclusion:Celecoxib suppresses PCCA-induced EMT and angiogenesis via a COX-2-independent mechanism. These findings suggest that celecoxib may offer additional therapeutic benefits for patients with CRC with elevated PCCA expression and reveal a novel potential antitumor mechanism of celecoxib.
Background:Per-oral endoscopic myotomy (POEM) has become the mainstream treatment for achalasia. Previous studies have found that some patients with achalasia might experience partial recovery of esophageal peristalsis after POEM. However, the clinical significance of this recovery and the associated factors remain to be further elucidated. Methods:This was a multicenter retrospective cohort study conducted by four academic hospitals in China. Patients diagnosed with achalasia who underwent POEM between 2020 and 2025 were included. Demographics, Eckardt score, gastroesophageal reflux disease questionnaire (GERDQ) score, presence of esophagitis, high-resolution manometry parameters, and myotomy length were collected. Normal, weak, and fragmented contractions were defined as partial recovery of esophageal peristalsis. Results:Partial recovery of esophageal peristalsis was observed in 32.8% (95 of 290) of patients with achalasia. A significantly higher preoperative proportion of pan-esophageal pressurization was found in the recovery group compared with the non-recovery group [median (interquartile range), 80.0% (30.0%, 100.0%) vs 30.0% (0.0%, 90.0%), P < 0.001] and this proportion positively correlated with the degree of peristalsis recovery (r = 0.247, P < 0.001). Patients with peristalsis recovery had significantly lower GERDQ scores and reduced incidence of dysphagia symptoms. Multivariate analysis further confirmed that the preoperative proportion of pan-esophageal pressurization was an independent predictor of peristalsis recovery (odds ratio = 1.02, P = 0.007). Conclusions:A higher preoperative proportion of pan-esophageal pressurization was independently associated with postoperative recovery of esophageal peristalsis in patients with achalasia. Peristalsis recovery was related to superior symptom relief. Preoperative assessment of pan-esophageal pressurization might help guide individualized postoperative follow-up and patient counseling.
The combination of trastuzumab and chemotherapy, with or without pembrolizumab, is the current first-line standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer and gastroesophageal junction cancer. However, upon disease progression, subsequent therapies often yield limited clinical benefit. The mechanisms of drug resistance to trastuzumab remain unresolved. Current studies on its resistance mechanisms have largely focused on alterations in the HER2 pathway, including HER2 heterogeneity, reduced or absent HER2 expression, variations in HER2 dimerization, and mutations in downstream components, among others. Crucially, as a monoclonal antibody, the antitumor activity of trastuzumab is partially mediated by the immune system, yet the immunology-related mechanisms of resistance are frequently overlooked. In this review, we systematically analyse the outcomes of both successful and failed clinical trials of anti-HER2 agents to propose that immune escape within the tumor microenvironment is a key driver of trastuzumab resistance in HER2-positive gastric cancer.
Background:Endoscopic full-thickness resection (EFTR) is an effective technique for endoscopic resection of gastric submucosal tumors (G-SMTs); however, the closure of the post-operative perforation wound presents a significant challenge. We invented a dual action tissue closure device (DAT), and aimed to evaluate its feasibility and safety in closing perforation wounds following EFTR of G-SMTs. Methods:This is a retrospective study that included the data of patients who underwent EFTR for G-SMTs at Nanfang Hospital (Guangzhou, China) between 1 January 2021 and 1 April 2024. All these wounds were closed using the DAT and through-the-scope clip. The collected data included tumor size and location, total procedure time, closure success rate, closure time, complications, and follow-up outcomes. The closure efficacy of the DAT was evaluated accordingly. Results:Twenty-nine patients (median age, 57 years old, 37.9% women) completed EFTR of G-SMTs, which included 2 cases utilizing cap-assisted full-thickness resection and 27 cases using EFTR. The tumors had a median long diameter of 20 (15-30) mm and short diameter of 15 (10-25) mm. All wounds were successfully closed without complications. The median total operation time was 55 minutes (interquartile range: 33.5-70.0 minutes), and the median wound closure time was 19 minutes (range: 12.0-27.0 minutes). The median number of DAT used was 1 (interquartile range: 1-3), with a median operation time of 3 minutes (1.6-6.5) for per DAT. Seven patients underwent endoscopic follow-up, with 88.2% of the DATs falling off naturally. Conclusions:DAT can effectively and safely close perforation wounds following EFTR of G-SMTs.
Background:Intestinal autotransplantation (IATx) facilitates radical resection for advanced intra-abdominal cancers involving major vessels, which were previously deemed unresectable. This study systematically reviewed and meta-analyzed its perioperative safety and mid-term survival outcomes. Methods:A search of databases was conducted up to December 2025, adhering to PRISMA guidelines. Studies reporting outcomes of IATx were included in the review. A total of 12 studies involving 160 patients were reviewed, with meta-analysis performed on six studies comprising 122 patients, using random-effects models. Primary outcomes included the 3-year overall survival (OS) rate, 90-day mortality, major complications (Clavien-Dindo ≥ III), and R0 resection rates. Secondary outcomes involved cold ischemia time, operative time, and length of hospital stay. Study quality was assessed by using the MINORS criteria. Results:The pooled 3-year OS rate was 57.9% (95% CI, 34.1%-75.7%; 4 studies; I 2 = 36.8%, P = 0.040). Analysis of perioperative outcomes from six studies (122 patients) revealed a pooled 90-day mortality of 6.6% (95% CI, 3.1%-13.5%; I 2 = 0%), a major complication rate (Clavien-Dindo ≥ III) of 27.9% (95% CI, 12.9%-50.3%; I 2 = 71.8%), and an R0 resection rate of 92.3% (95% CI, 84.3%-96.4%; I 2 = 0%). The pooled mean cold ischemia time was 124 minutes (95% CI, 75-173 minutes; 5 studies; I 2 = 98.9%), the operative time was 10.4 h (95% CI, 9.1-11.7 h; 6 studies; I 2 = 90.4%), and the postoperative length of stay averaged 22 days (95% CI, 19-25 days; 5 studies; I 2 = 35%). Conclusions:IATx for unresectable complex intra-abdominal tumors demonstrates high R0 resection rates, low mortality, and encouraging 3-year OS outcomes. Given the procedural complexity, IATx should be performed exclusively at expert centers. Further long-term follow-up studies are necessary to validate these findings.
Postoperative recurrence remains a major challenge in Crohn's disease (CD), with ileocolonoscopy still considered the reference standard for detecting recurrence and guiding postoperative management. However, repeated endoscopic assessment is invasive, costly, and poorly tolerated, highlighting the need for reliable non-invasive monitoring strategies. Intestinal ultrasound (IUS) has emerged as a promising complementary tool for postoperative surveillance, allowing real-time evaluation of transmural and extramural inflammation. Recent studies and meta-analyses have demonstrated good diagnostic performance of IUS for detecting postoperative recurrence, with pooled sensitivities and specificities reaching 94% and 84%, respectively, while higher bowel wall thickness thresholds (≥5.5 mm) are strongly associated with severe postoperative recurrence. Current evidence supports the integration of IUS with fecal calprotectin, clinical assessment, and endoscopy within a multimodal and risk-adapted follow-up strategy. In particular, IUS may help identify patients requiring closer surveillance, earlier ileocolonoscopy, therapeutic escalation, or additional cross-sectional imaging. Emerging data also suggest that the timing of postoperative IUS assessment is clinically relevant, as very early examinations may be confounded by postoperative inflammatory and remodeling changes. Nevertheless, important limitations remain. No IUS score has yet been specifically validated for postoperative CD anatomy, standardized postoperative-specific thresholds are lacking, and interpretation may be influenced by surgical configuration and operator expertise. This review summarizes the current evidence regarding the role of IUS in postoperative CD, discussing its diagnostic performance, integration with biomarkers and endoscopy, current limitations, and potential role in personalized postoperative monitoring strategies.
The Tianhe Procedure is a functional sphincter-preserving surgical approach developed for patients with rectal cancer following radiotherapy. This technique involves proximal extended resection of the colon beyond the pelvic cavity, followed by anastomosis of the non-irradiated proximal colon to the distal rectum or anal canal. This strategy aims to reduce the incidence of anastomotic complications and postoperative bowel dysfunction. However, there is currently a lack of standardized practice guidelines for implementing the Tianhe Procedure in China. Therefore, the Chinese Radiation Intestinal Injury Research Group, the Colorectal Surgery Group of Surgery Branch of the Chinese Medical Association, the Anorectal Branch of Chinese Medical Doctor Association, the Colorectal Cancer Committee of the Chinese Medical Doctor Association, the Colorectal Cancer Committee of China Anti-cancer Association, and the Gastrointestinal Surgical Branch of Guangdong Medical Doctor Association have jointly convened a panel of national experts to discuss and establish this standardized surgical procedure. This standard, based on the latest evidence from literature, research advancements, and expert experience, focuses on key aspects of the Tianhe Procedure, including its precise definition, indications, critical procedural steps, postoperative complications, and functional rehabilitation strategies. It aims to promote standardized implementation and broader clinical adoption of this innovative surgical technique.
Background:Increasing randomized clinical trials evaluating novel therapies for inflammatory bowel disease necessitated the scrutiny of statistical robustness. This study aimed to quantify their fragility and identify factors associated with robustness. Methods:This cross-sectional analysis included randomized clinical trials studying biologics, small-molecule inhibitors, fecal microbiota transplantation (FMT), and stem cell therapy (SCT), and then the calculated fragility index (FI) and continuous fragility index (CFI) for binary and continuous outcomes, respectively. Factors affecting robustness were analysed through correlation analysis and multiple linear regression. Results:Among 129 trials from 53 studies, the median FI and CFI were 6 and 14.8, respectively. The FI varied significantly by the treatment type, trial phase, outcome type, and P values. The FI was positively correlated with the sample size (ρ = 0.734, P < 0.001), discontinuations (ρ = 0.479, P < 0.001), publication year (ρ = 0.253, P = 0.017), impact factor (ρ = 0.368, P < 0.001), and events percentage (ρ = 0.299, P = 0.005). The CFI was influenced by the outcome type and was strongly correlated with the sample size. After adjustment for other characteristics, biologics/small-molecule drugs displayed enhanced robustness relative to FMT/SCT (correlation coefficient B with the natural logarithm of FI: B = 0.283, P = 0.011). The primary or co-primary outcome exhibited greater robustness than did the other outcomes (FI: B = 0.288, P = 0.013; CFI: B = 0.459, P = 0.024). The sample size was positively correlated with both the FI (B = 0.001, P = 0.021) and the CFI (B = 0.001, P = 0.019), whereas discontinuation did not significantly affect the robustness. Conclusion:Randomized clinical trials of novel inflammatory bowel disease therapies exhibit varying robustness and are influenced by multiple study characteristics. Trials of biologics or small molecules, those with positive primary outcomes, and larger studies demonstrated greater robustness, supporting that robustness should be considered in future research when interpreting the efficacy.
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain and changes in bowel habits without measurable disease processes. Recent research emphasizes the gut-brain-microbiome (GBM) axis and explores how microbiota influence gastrointestinal and central nervous system functions. Here, we first discuss a brief overview of various treatment approaches for IBS, focusing on interventions such as probiotics, prebiotics, or synbiotics that target the GBM axis in adults with IBS. Relevant trials discussed the use of probiotics, prebiotics, or synbiotics. Bacillus, Lactobacillus, and Bifidobacterium featured prominently among the probiotics used. Several significant outcomes, including a reduction in symptom frequency, abdominal-pain severity, and improved stool consistency, were noted. Three prebiotic trials showed variable benefits, including a reduction in bloating and stool consistency, but showed less significant benefits compared with those with probiotics and synbiotics. Six trials on synbiotics showed a significant reduction in abdominal-pain severity, bowel-habit satisfaction, and reduced gut-related anxiety. Probiotics and synbiotics, particularly those containing Bifidobacteria or Lactobacilli strains, were effective in managing IBS symptoms. Future research is needed to assess their long-term benefits.
