Gut and Liver最新文献

Background/aims: Subcutaneous (SC) vedolizumab (VDZ) has recently become available for patients with inflammatory bowel disease (IBD) in Korea. This retrospective observational study aimed to evaluate the clinical outcomes and safety of switching from intravenous (IV) to SC VDZ.

Methods: Patients with IBD who switched from IV to SC VDZ between 2023 and 2024 were included. The primary outcome was the 24-week persistence rate of SC VDZ. Secondary outcomes included clinical factors associated with SC VDZ persistence, safety profiles, subsequent treatment courses after discontinuation of SC VDZ, and recapture success rate after reverting to IV VDZ.

Results: A total of 101 patients with IBD (72 with ulcerative colitis [UC] and 29 with Crohn's disease) were included. After 24 weeks, 72 patients (71.3%) maintained SC VDZ. Corticosteroid use at switching was the strongest predictor of 24-week SC VDZ failure in both the overall IBD cohort (p=0.018) and in patients with UC (p=0.027) in multivariable analyses. Kaplan-Meier analysis showed that patients with UC with intensified IV dosing intervals (p=0.021), failure to clinical remission (p=0.038), or concomitant corticosteroid use at switching (p<0.001) were more likely to discontinue SC VDZ. Injection-site reactions occurred in 24 patients (23.8%). A total of 34 patients (33.7%) discontinued SC VDZ; 19 resumed IV VDZ; and 13 initiated another advanced therapy. The recapture success rate after reverting to IV VDZ was 73.7%, with higher success in those who discontinued because of injection-site reactions or poor adherence.

Conclusions: SC VDZ persistence is significantly influenced by disease activity at the time of switching.

Background/aims: Although rectal neuroendocrine tumors (NETs) ≤1 cm in size are generally considered low-risk tumors that are suitable for endoscopic resection, the long-term outcomes after histologically complete resection remain unknown.

Methods: We conducted a multicenter retrospective cohort study of patients with rectal NETs who underwent complete endoscopic resection (endoscopic mucosal resection or endoscopic submucosal dissection) between January 2014 and December 2019. A total of 860 patients with ≥6 months of follow-up were included. Recurrence-free survival and its associated risk factors were analyzed using Kaplan-Meier and Cox proportional hazards models.

Results: Among 860 patients, the mean age was 47.7 years, and 57.9% of the patients were male. The overall recurrence rate was 1.4% (n=12). Univariate and multivariate analyses identified histological grade 2 (hazard ratio [HR], 19.13; 95% confidence interval [CI], 3.51 to 104.22) and mitotic count 2-20/10 high-power field (HPF) (HR, 20.88; 95% CI, 1.61 to 270.19) as independent predictors of recurrence, while >20/10 HPF (HR, 7.93; 95% CI, 0.90 to 69.87) showed a marginal association. The pathological tumor size, resection method, endoscopic ultrasonography findings, and Charlson Comorbidity Index were not associated with recurrence. The 5-year and 9-year recurrence-free survival rates were 98.4% and 84.7%, respectively. Supplementary analysis excluding patients with missing data confirmed consistent findings.

Conclusions: Although recurrence is rare after the complete resection of rectal NETs ≤1 cm in size, patients with grade 2 tumors or a mitotic count ≥2/10 HPF are at increased risk. Risk-adapted follow-up based on histological features should be considered.

Background/aims: Colorectal cancer (CRC) shows high heterogeneity. Conventional bulk transcriptome-based classification methods fail to capture the complex tumor microenvironment of CRC, limiting precision therapy advances. The Scissor algorithm integrates single-cell/bulk transcriptomic data with clinical information to identify prognosis-linked cell subpopulations, offering new insights into tumor heterogeneity resolution.

Methods: We integrated bulk RNA-seq data, single-cell RNA-seq data, and clinical information from The Cancer Genome Atlas and Gene Expression Omnibus databases. The Scissor algorithm was employed to screen fibroblast subpopulations strongly associated with prognosis. Multidimensional analyses, including signature gene identification, functional enrichment analysis, Gene Set Variation Analysis (GSVA)-based subtyping, survival analysis, immune landscape assessment, cell-cell communication, mutational profiling, and drug sensitivity prediction, were conducted.

Results: We identified Scissor+ fibroblast subpopulations significantly correlated with prognosis, whose signature genes were associated with pro-metastatic pathways such as extracellular matrix remodeling and transforming growth factor-beta signaling. GSVA scoring stratified samples into Scissor_high and Scissor_low subtypes, with the former being associated with worse survival outcomes, immunosuppressive microenvironment features (including Treg and M2 macrophage enrichment), and stronger immune evasion tendencies. Cell communication analysis revealed that the Scissor_high subtype strongly interacted with many cell types, with remarkable enrichment in the ANNEXIN, SPP1, and NIF signaling pathways. Drug sensitivity predictions suggested that patients with this cell subtype may respond better to specific anticancer agents (e.g., AZD3759, Erlotinib, Gefitinib).

Conclusions: This study was the first to identify Scissor+ fibroblast subpopulations markedly associated with poor prognosis in CRC, revealing their ability to activate pro-metastatic pathways and immune-activated but functionally exhausted characteristics. Moreover, their predictive value in CRC therapy was revealed. The study provided new perspectives for CRC prognosis evaluation and personalized immune-targeted combination therapies.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Worldwide, population-based systematic screening programs for the disease, which is essential to address this burden, rely primarily on fecal immunochemical testing (FIT). However, this test has multiple limitations, including an inability to detect right-sided CRCs and low individual adherence to follow-up colonoscopy among those with positive FIT results. Thus, primary colonoscopy screening is currently being explored as a more reliable strategy. Although randomized controlled trials published to date have not conclusively demonstrated beneficial effects of colonoscopy screening on mortality, limited evidence has suggested that improved participation rates in such programs may increase their effectiveness. That said, the evaluation of cost-effectiveness is another critical consideration when assessing these programs. To date, 11 simulation studies have compared the cost-effectiveness of colonoscopy-based screening with alternative strategies, of which six found that the colonoscopy-based screening strategy to be more cost-effective. Notably, among seven studies that assessed strategies based on repeat colonoscopies at regular intervals, five demonstrated favorable cost-effectiveness. However, among the 11 simulation studies, only five modeled the adenoma-carcinoma sequence, and only three accounted for interval cancers, limiting their clinical applicability. Moreover, repeated colonoscopy screening may increase the total number of procedures, potentially straining healthcare resources. Thus, in addition to evaluating mortality reduction, careful consideration of cost-effectiveness is essential in assessing the feasibility of implementing colonoscopy screening programs in public health practice.

Background/aims: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder influenced by stress, microbial dysbiosis, and immune activation. Microbiota-directed therapies, including fecal microbiota transplantation and probiotics, show promise, but their sex-specific effects remain unclear. We compared the therapeutic effects of lyophilized fecal microbiota (LFM) with Bifidobacterium longum BBH016 in male and female Wistar rats subjected to repeated water avoidance stress.

Methods: Fecal pellet output (FPO), colonic mast cell infiltration, and fecal short-chain fatty acids were measured. Gut microbial composition and function were analyzed by 16S rRNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway prediction.

Results: Both interventions significantly reduced FPO and mast cell infiltration in males but had less pronounced effects in females. Microbiota analyses revealed sex-dependent responses, with distinct microbial trajectories in each treatment group. Using linear discriminant analysis effect size, we identified seven key taxa with treatment- or sex-specific enrichment. Alistipes onderdonkii and Bacteroides uniformis consistently increased in both LFM- and B. longum-treated groups, regardless of sex. Bacteroides finegoldii and Barnesiella intestinihominis were specifically enriched in the LFM group. In males, Blautia faecis and Fusicatenibacter saccharivorans were enriched following the interventions, whereas Parabacteroides goldsteinii appeared exclusively in stressed males. Functional predictions revealed the enrichment of estrogen signaling and bile acid pathways in males and the attenuation of proinflammatory pathways in females following LFM. Correlations between microbial taxa and host outcomes were predominantly observed in male rats.

Conclusions: These findings highlight sex-specific microbial and host responses to microbiota-targeted therapies in a stress-induced IBS model, emphasizing sex as a biological variable in designing personalized microbiome-based treatments.

Background/aims: Postpolypectomy bleeding (PPB) is a major complication of pedunculated colonic polyps. Various prophylactic interventions, including clips, endoloops, and epinephrine injections, have been proposed to prevent PPB; however, their comparative effectiveness remains unclear. This study aimed to evaluate the efficacy of these interventions through a network meta-analysis.

Methods: We searched the MEDLINE, EMBASE, and Cochrane CENTRAL databases for randomized controlled trials that compared the effectiveness of clips, endoloops, and epinephrine injection in the prevention of PPB in pedunculated polyps with a head diameter ≥10 mm. Primary outcomes included immediate and delayed PPB. Data synthesis was performed with the netmeta package in R, which integrates direct and indirect evidence and yields odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Of 601 identified studies, 11 trials involving 2,096 patients were included. In the network meta-analysis, endoloops (OR, 0.23; 95% CI, 0.08 to 0.63), clips (OR, 0.25; 95% CI, 0.14 to 0.48), and epinephrine injection (OR, 0.33; 95% CI, 0.11 to 0.96) were significantly more effective than no treatment in the prevention of immediate bleeding. Combinations of endoloops or clips with epinephrine injection also demonstrated satisfactory efficacy. For delayed bleeding, no significant differences were observed among the interventions or between each intervention and no treatment, which may be due to the small number of events across studies. According to surface under the cumulative ranking curve rankings, endoloops plus epinephrine injection was the most effective method for preventing immediate PPB, followed by endoloops and clips alone.

Conclusions: This network meta-analysis supports the use of endoloops with epinephrine as the most effective strategy for preventing immediate bleeding after resection of pedunculated colonic polyps, while current measures remain insufficient for delayed bleeding.

Background/aims: Severe alcoholic hepatitis (SAH) is a life-threatening form of alcoholic liver disease resulting in high short-term mortality. Mesenchymal stem cells (MSCs) have potent immunomodulatory effects and have been evaluated in various clinical trials for the treatment of chronic liver diseases. However, clinical evidence in patients with alcoholic hepatitis remains scarce, and the underlying mechanisms of MSCs in this population are not yet fully understood.

Methods: An integrative meta-analysis identified conserved transcriptomic signatures of alcoholic hepatitis. These signatures were validated in an ethanol-induced murine model. A mouse model of SAH was induced via subacute ethanol exposure (5 g/kg) combined with thioacetamide injection. MSCs were administered at two concentrations (5×10⁵ or 1×10⁶ cells), depending on the treatment group.

Results: In the animal model, MSCs treatment visibly alleviated liver injury induced by thioacetamide and ethanol. Significant reductions in tumor necrosis factor-α (p<0.05) and α-smooth muscle actin (p<0.01) levels were observed, accompanied by notable changes in inducible nitric oxide synthase, interleukin-1β, and transforming growth factor-β1 levels. From the meta-analysis, seven upregulated and 17 downregulated genes were identified. Subsequent quantitative polymerase chain reaction and Western blot analyses consistently validated four upregulated genes that demonstrated overlapping expression patterns across both the meta-analysis and in vivo experiments.

Conclusions: MSCs therapy significantly attenuates liver injury, inflammation, and fibrosis in SAH model mice. The observed messenger RNA-protein expression mismatches highlight the complexity of molecular regulation in acute hepatitis and underscore the importance of multilevel analysis in evaluating stem cell therapy. These results provide valuable insights into the mechanisms of MSC-mediated liver repair and suggest key targets for MSC therapy and response assessment in SAH.