World Journal of Gastroenterology最新文献

Background: Obesity is a global epidemic frequently associated with gastroesophageal reflux disease (GERD). Metabolic and bariatric surgery (MBS) is the most effective treatment for weight reduction in patients with obesity, with the most commonly performed procedures being sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one-anastomosis gastric bypass (OAGB). Many recent studies focused on determining the best procedure for patients with obesity and GERD; however, results from these studies vary, and the optimal procedure remains uncertain.

Aim: To compare the effects of MBSs - SG, RYGB, and OAGB - and their combinations with antireflux procedures on weight loss and GERD outcomes.

Methods: A systematic search was performed to identify randomized controlled trials evaluating MBS in patients with obesity and GERD. A network meta-analysis was conducted to estimate the relative effectiveness of different procedures on body mass index reduction, percent excess weight loss, GERD remission, GERD onset, postoperative proton pump inhibitor use, esophagitis, and complication rates.

Results: Sixteen randomized controlled trials including SG, RYGB, OAGB and their combined procedures (i.e., SGantiflux and OAGBantiflux), were analyzed. OAGBantiflux showed the highest body mass index reduction, and OAGB and RYGB had similar efficacies. In terms of percent excess weight loss, OAGB and RYGB ranked higher than other MBSs, whereas SGantiflux was the least effective. RYGB had the highest probability of GERD remission, followed by SG, SGantiflux, OAGB, and OAGBantiflux. SGantiflux showed the highest probability of the postoperative GERD onset, while SG was most likely to require postoperative proton pump inhibitor use and cause esophagitis. SGantiflux also demonstrated the highest complication rate, whereas OAGBantiflux was associated with the lowest, with OAGB, RYGB, and SG yielding intermediate rates in a descending order.

Conclusion: RYGB and OAGB were more effective than SG in patients with obesity and GERD, and addition of antireflux procedures to MBS did not improve GERD outcome.

Background: Sarcopenia has been indicated to be related to the postoperative outcome of patients with various digestive tract diseases. However, no studies have investigated the association between sarcopenia and esophageal stenosis after endoscopic submucosal dissection (ESD).

Aim: To explore the correlation between sarcopenia and post-ESD esophageal stenosis, and subsequently develop a risk prediction model.

Methods: Retrospective data from 499 patients who underwent esophageal ESD were collected. After stratification via the L3 skeletal muscle indices (L3-SMIs) into sarcopenia and non-sarcopenia groups, post-ESD stenosis rates were compared. Propensity score matching (PSM) was used for sensitivity analysis. The original cohort was randomly split at a ratio of 7:3 into training (n = 350) and validation (n = 149) groups to construct and validate a risk prediction model for post-ESD stenosis.

Results: Sarcopenia was significantly associated with post-ESD esophageal stenosis (48.23% vs 22.35%, P < 0.001). Furthermore, multivariate analysis confirmed its independence as a predictor of this postoperative complication [odds ratio (OR): 3.86; 95% confidence interval: 1.76-8.45; P < 0.001]. This conclusion was consistent across the subgroup analyses and PSM analyses. The risk prediction model incorporating sarcopenia had area under the curve values of 0.848 (training set) and 0.794 (validation set). Calibration curves and Hosmer-Lemeshow tests indicated good calibration of the model. Moreover, decision curve analysis confirmed a positive net clinical benefit for the model.

Conclusion: Sarcopenia is an independent risk predictor of post-ESD esophageal stenosis. Our model integrating muscle mass assessment aids in early high-risk identification and intervention.

Gastric ulcer (GU) remains a significant global health concern, often leading to severe complications such as bleeding and perforation. While Helicobacter pylori infection and nonsteroidal anti-inflammatory drug use are well-recognized etiological factors, systemic inflammation plays a pivotal but underexplored role in GU pathogenesis. Shen et al provide compelling evidence linking complete blood count-derived inflammatory biomarkers with GU prevalence, identifying the systemic inflammatory response index as the most discriminative marker. Their cross-sectional analysis underscores the potential of routine hematological parameters as cost-effective, accessible tools for early identification of high-risk individuals. Importantly, this study adds to the growing body of literature suggesting that simple indices - neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and systemic inflammatory response index - may serve not only as diagnostic aids but also as windows into disease mechanisms involving immune dysregulation and oxidative stress. Future prospective and mechanistic studies are warranted to determine whether these markers can predict ulcer recurrence, guide therapeutic interventions, or integrate into precision gastroenterology. By leveraging widely available blood tests, we may move closer to a paradigm where inexpensive inflammatory indices refine GU risk stratification and management strategies.

Background: The clinical outcomes of endoscopic rubber band ligation (ERBL), injection sclerotherapy (IS), and endoscopic polidocanol sclerobanding (ESB) have not yet been well studied.

Aim: To evaluate the efficacy and safety of ERBL, IS, and ESB for treating grade I-III internal hemorrhoids.

Methods: This retrospective cohort study was performed on 201 patients, who were grouped according to their endoscopic treatment (ERBL, IS, and ESB groups). Postoperative follow-ups were initially carried out at 1, 3, and 6 months, and then every 6 months, with the longest follow-up extending to 24 months. The study analyzed clinical efficacy, short-term and overall recurrence rates, and postoperative adverse events. Additionally, subgroup analysis was conducted based on the internal hemorrhoid grade (I or II-III).

Results: The patient distribution across the ERBL, IS, and ESB groups was 70, 66, and 65, respectively. Both the ERBL and ESB groups demonstrated lower overall recurrence rates compared with the IS group (post-hoc analysis, P' = 0.024 and P' = 0.015, respectively). Subgroup analysis revealed that sclerotherapy resulted in a higher total recurrence rate than that achieved by sclerobanding (45.95% vs 19.57%, P' = 0.03), specifically for grade II-III internal hemorrhoids. No significant difference was found in grade I hemorrhoids. The ERBL group exhibited a higher incidence of postoperative pain, a worse median visual analog scale score, and a longer median duration of pain compared with those reported by the other groups (P < 0.001). This trend was consistent for grade II-III hemorrhoids. No significant differences were found among the three groups regarding clinical efficacy or recurrence rates within 6 months post-surgery, even when examined by subgroup.

Conclusion: The three treatments evaluated (ERBL, IS, and ESB) provide durable clinical outcomes for grade I hemorrhoids, with no significant differences in postoperative adverse events. For grade II-III hemorrhoids, ESB possesses the dual advantages of lower recurrence rates and reduced postoperative pain compared with IS and ERBL.

Background: Chemoresistance significantly limits the therapeutic efficacy of neoadjuvant chemotherapy (NACT) in advanced gastric cancer (AGC). There is an urgent need to identify robust biomarkers predictive of NACT response and to elucidate the molecular mechanisms that drive resistance. In this study, we systematically assess whether intercellular adhesion molecule 2 (ICAM2) predicts NACT response in patients with AGC and delineate its mechanistic role in chemoresistance.

Aim: To investigate the predictive significance and mechanistic role of ICAM2 in mediating 5-fluorouracil (5-FU) resistance in gastric cancer (GC).

Methods: Real-time PCR, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry were conducted to assess alterations in ICAM2 expression between 5-FU-sensitive and -resistant GC cells as well as in AGC patient samples. Cytotoxicity assays, colony formation, flow cytometry, analyses of apoptosis-related proteins, and xenograft experiments were employed to elucidate the role of ICAM2 in mediating chemoresistance. The mechanism underlying ICAM2-mediated chemoresistance was further explored through RNA sequencing (RNA-seq), nuclear-cytosolic fractionation, co-immunoprecipitation, luciferase reporter, and chromatin immunoprecipitation assays.

Results: Low ICAM2 expression correlated significantly with poor NACT response, advanced tumor stage, worse differentiation, and reduced overall survival and disease-free survival in AGC patients. Pre-NACT serum ICAM2 demonstrated high predictive accuracy (area under the curve = 0.876) in discriminating chemotherapy responders from non-responders. Mechanistically, ICAM2 knockdown conferred 5-FU resistance through two intertwined processes: Inhibition of caspase-dependent apoptosis and promotion of immunosuppressive M2 macrophage polarization within the tumor microenvironment. At the molecular level, loss of ICAM2 activated the TGF-β/Smad pathway, leading to transcription factor SP1-mediated pleiotrophin (PTN) upregulation. Elevated PTN further enhanced GC cell survival and may contribute to M2 macrophage polarization, thereby amplifying chemoresistance. Importantly, targeted inhibition of TGF-β signaling reversed ICAM2-associated chemoresistance in both cell culture and xenograft models.

Conclusion: Our study highlights the clinical impact of ICAM2 downregulation predicting poor outcome and NACT response in AGC patients, and reveals a novel ICAM2/TGF-β/Smad/SP1/PTN signaling mediating 5-FU resistance in GC.

Background: The Danggui-Baishao herb pair is the foundation of a traditional Chinese medicine formula known as Shaoyao decoction, which is widely used in the treatment of colitis.

Aim: To uncover the mechanisms underlying the anti-colitis effects of the Danggui-Baishao herb pair.

Methods: The chemical composition of the herb pair was characterized by high performance liquid chromatography-quadrupole/time of flight mass spectrometry analysis. A mouse model of colitis was induced by administering 2.5% dextran sulfate sodium. The therapeutic effects of the herb pair were evaluated based on body weight changes, colon length, histopathological, intestinal inflammation, and barrier function. To investigate the underlying mechanisms, RNA sequencing, metabolomics, 16S rRNA sequencing, metagenomics, and the β-catenin inhibitor ICG-001 were utilized. Furthermore, molecular docking and dextran sulfate sodium-treated HCT 116 cells were conducted to explore the protective mechanisms of benzoylpaeoniflorin.

Results: The herb pair improved body weight, colon length, intestinal inflammation, and barrier function. Additionally, the herb pair upregulated the expression of intestinal stem cells marker leucine-rich repeat-containing G-protein coupled receptor 5 and proliferation-related proteins. RNA sequencing analysis showed that the herb pair activated the Wnt/β-catenin signaling pathway. Metabolomic analysis revealed changes in bile acids composition. Through 16S rRNA and metagenomic sequencing, it was observed that the herb pair modulated the gut microbiota, with an enrichment of probiotics and a depletion of pathogenic bacteria. Following intraperitoneal injection of antagonist ICG-001, the therapeutic efficacy was diminished. Molecular docking showed that benzoylpaeoniflorin can bind to β-catenin. Furthermore, benzoylpaeoniflorin can activated the Wnt/β-catenin signaling pathway and the therapeutic efficacy was also diminished by the ICG-001 in vitro.

Conclusion: The herb pair effectively reduces colonic inflammation and maintains the integrity of the intestinal barrier. Moreover, the anti-colitis efficacy of the herb pair is closely associated with activation of the Wnt/β-catenin pathway.

Cancer-related incomplete intestinal obstruction (CRIO) presents a significant challenge in patients with advanced malignancies, affecting quality of life and complicating treatment regimens. This editorial explores the multifaceted approaches to managing CRIO, emphasizing recent advancements in diagnostic techniques, pharmacological treatments, minimally invasive procedures, and surgical interventions. The pathophysiology of CRIO is complex, involving tumor invasion, fibrosis, and peritoneal dissemination, which result in partial bowel obstruction and impaired motility. Traditional management has focused on supportive care and palliative measures; however, new interventions, such as endoscopic stenting and laparoscopic surgery, have demonstrated improved outcomes with fewer complications. In addition, the integration of systemic therapies like immunotherapy and targeted agents offers promising results in reducing tumor burden and alleviating obstruction. The editorial also discusses the critical role of nutritional support and fluid management in managing CRIO symptoms and improving patient recovery. Despite these advancements, the complexity of CRIO, with its varied causes and patient-specific factors, necessitates individualized, multidisciplinary care strategies. This editorial aims to provide an updated, comprehensive framework for clinicians managing CRIO, highlighting current practices and future directions for research and therapeutic development.

Background: Fatigue is debilitating and costly for patients with Crohn's disease (CD) and the healthcare system. Thus, as there are no well-established therapies for fatigue in patients with CD, it is essential to investigate its risk factors and collaborate to prevent or reduce its burden.

Aim: To evaluate the variables associated with fatigue in outpatients with CD receiving pharmacological treatment.

Methods: It is an observational study. Data, including sociodemographic information, inflammatory bowel disease fatigue scores, visual analog scale scores, Depression Anxiety Stress Scale-21 scores, insomnia assessment results, and laboratory test results, were collected. Statistical analyses included Student's t tests, logistic and linear regressions, and receiver operating characteristic curve analysis, with a P value of < 0.05 indicating statistical significance.

Results: One hundred patients were included (77% presented with fatigue). In the linear regression analysis, symptoms of depression, anxiety, stress, and insomnia were simultaneously included as predictors of fatigue. Although the model was statistically significant (adjusted R ² = 0.128; P = 0.002), no single symptom was significantly associated. A composite score (0-4) was developed by summing the scores of the 4 symptoms, which were coded dichotomously (odds ratio = 2.60; 95% confidence interval: 1.61-4.83; P < 0.001). The composite score showed good discriminative capacity (area under the curve = 0.775). Patients with fatigue had higher total leukocyte (P = 0.034) and segmented neutrophil (P = 0.017) counts and lower lymphocyte (P = 0.019) and eosinophil (P = 0.036) counts. Effect sizes ranged from moderate to high (Cohen's d 0.39-0.61), indicating that fatigue may be associated with a leukocyte pattern consistent with relative neutrophilia and lymphopenia.

Conclusion: Fatigue is associated with psychological symptoms, a sedentary lifestyle, and alterations in leukocyte subpopulations. Assessments incorporating composite symptom scales and hematological parameters may be practical and cost-effective for patients with fatigue.

We read with great interest the article by Weng et al, wherein the authors investigated human leukocyte antigen (HLA) alleles linked to anti-drug antibody (ADA) formation in Taiwanese patients with inflammatory bowel disease. They reported that HLA-DQA1*05, a major risk allele in European cohorts, demonstrated no association with ADA development in Taiwanese patients. Instead, novel alleles emerge: HLA-C*03:04:01 correlating strongly with anti-infliximab ADAs and HLA-B*15:18:01 with anti-adalimumab ADAs. However, this finding contrasts with evidence from large cohort studies, wherein HLA-DQA1*05 consistently predicted ADA formation, particularly for infliximab. This letter aimed to contextualize these findings within the broader literature and to lay the ground for further analysis of ethnic variations and the implications for personalized medicine in inflammatory bowel disease. This divergence may suggest how genetic architecture shapes immunogenicity risk across ethnicities.