胃肠外科领域文献阅读汇编

This multicohort, single-center, phase II trial explored the efficacy and safety of a biomarker-driven total neoadjuvant therapy (TNT) regimen in high-risk locally advanced rectal cancer (LARC) patients. The regimen included induction chemotherapy (4 cycles of mFOLFOX6) with targeted agents (bevacizumab for cohort B and cetuximab for cohort C), followed by short-course radiotherapy (25 Gy/5Fx) and consolidation chemotherapy (2 cycles of mFOLFOX6, with cetuximab in cohort C). The primary endpoint was complete response (CR; sustained clinical CR [cCR] + pathological CR [pCR]). Secondary endpoints included compliance, safety, pathological outcomes, and survival. Between April 2021 and October 2024, 90 of 96 patients completed the prescribed treatment. CR was achieved in 36 (18 in cohort B and 18 in cohort C) patients (40%). No grade IV-V toxicity was observed, although three and 41 patients experienced targeted agent-related adverse effects in cohort B and C, respectively. In the two cohorts, 43 and 38 patients underwent curative surgery with sphincter preservation in 39 (90.7%) and 34 (89.5%) patients, respectively. Postoperative complications occurred in seven (16.3%) and five (13.2%) patients, of whom one (2.6%) patient in cohort C received reoperation. This intensified TNT regimen with targeted agents for high-risk LARC patients achieved a satisfactory CR rate with acceptable toxicities and complications.

Endoscopic and radiological staging of early rectal cancer (ERC) remains suboptimal, contributing to inaccurate treatment allocation and the risk of under- and overtreatment. This study aimed to evaluate the feasibility and safety of the Pocket-detection method with Real-time Intraprocedural Muscle-retracting sign Evaluation (PRIME) resection algorithm for ERC. We retrospectively analyzed a prospective registry of rectal lesions managed according to the PRIME algorithm between August 2023 and October 2025. The muscle-retracting sign (MRS) status guided adaptive dissection plane selection: endoscopic submucosal dissection (ESD) if MRS negative; endoscopic intermuscular dissection (EID) or full-thickness resection (knife-assisted [kFTR] or device-assisted [FTRD]) for MRS-positive lesions. Primary outcomes were technical success and the rate of R0 endoscopic resection. The secondary outcomes were the technical success of deep-margin optical diagnosis and adverse events. 47 lesions were included. MRS prevalence was 34.0% (16/47). Technical success of endoscopic resection was 97.9% (46/47; 95%CI 88.7%-99.9%). ESD was performed in 31 lesions, EID in nine, kFTR in five, and FTRD in one. R0 resection was achieved in 89.1% (41/46; 95%CI 76.4%-96.4%) and R0 vertical margin in 95.7% (44/46; 95%CI 85.2%-99.5%). Technical success of deep-margin optical diagnosis was 100% (47/47; 95%CI 92.5%-100%). Nonsevere (AGREE classification grade I-IIIa) adverse events occurred in 10.6% of patients (5/47; 95%CI 3.5%-23.1%). The MRS-guided adaptive endoscopic resection algorithm (PRIME) was feasible and safe for ERC achieving high R0 rates. These findings support its validation in larger studies with longer follow-up.

Designing nanozymes with enhanced catalytic performance remains a fundamental challenge in functional nanomaterials; concurrently, achieving synergistic multifunctionality constitutes an unmet need in nanozyme engineering. This study introduces an ultrasmall heterostructure nanozyme via interface electronic modulation. The heterostructure nanozyme is constructed through the facile growth of ultrasmall Cu4SnS4 crystals on SnS nanosheets, named as SCS. A spherical aberration-corrected transmission electron microscope is used to unveil the atomic arrangement characteristics of SCS heterostructures for the first time. The spontaneous transfer of electrons from SnS to Cu4SnS4 is revealed by density functional theory (DFT) calculations, demonstrating that the interface creates an ideal environment for accelerated mass and electron transfer. The enhanced peroxidase-like activity (129-fold) and photothermal efficiency are mediated through heterostructure-induced electron enrichment. The SCS nanozyme enables triple-modal lateral flow immunoassay signals (colorimetric, enhanced colorimetric, and photothermal) for carcinoembryonic antigen detection, achieving a 15-min rapid assay with an ultralow limit of 0.209 ng mL-1. It also facilitates visual tumor-normal tissue differentiation based on its superior catalytic performance. This work provides a paradigm for activity-oriented nanozyme design via interfacial electronic modulation.

Gastrointestinal stromal tumor (GIST) is the most common gastrointestinal mesenchymal tumor, driven by tyrosine-protein kinase (KIT) and platelet-derived growth factor receptor A (PDGFRA) mutations. Specific variants, such as KIT exon 11 deletions, carry prognostic and therapeutic implications, whereas wild-type variants derive limited benefit from tyrosine kinase inhibitors. Given the limited reproducibility of established clinicopathologic risk models, deep learning (DL) applied to whole-slide images (WSI) emerged as a promising tool for molecular classification and prognostic assessment. We analyzed 8398 GIST cases from 21 centers in seven countries, including 7,238 with molecular data and 2,638 with clinical follow-up. DL models were trained on WSIs to predict mutations, treatment sensitivity, and recurrence-free survival (RFS). DL predicted mutational status in GIST from WSIs, with area under the curve of 0.87 for KIT and 0.96 for PDGFRA, and high performance was observed for subtypes, including KIT exon 11 del-inss 557 to 558 (0.67) and PDGFRA exon 18 D842V (0.93). For therapeutic categories, performance reached 0.84 for avapritinib sensitivity and 0.81 for imatinib sensitivity. DL models predicted RFS, with hazard ratios of 8.44 in the overall cohort and 4.74 in patients receiving adjuvant therapy. Prognostic performance was comparable with pathology-based scores, with highest discrimination in the overall cohort and in patients without adjuvant therapy. DL applied to WSIs enables prediction of molecular alterations, treatment sensitivity, and RFS in GIST, performing comparably with established risk scores across international cohorts, providing a baseline for future multimodal predictors. Deep learning on histology predicts KIT and PDGFRA mutations and stratifies recurrence-free survival in a large international cohort of gastrointestinal stromal tumors from multiple centers.

Obesity is a growing global health challenge associated with major cardiometabolic complications. While bariatric surgery remains the most effective treatment for severe obesity, recent advances in incretin-based pharmacotherapy, multi-receptor agonists, and endoscopic bariatric procedures have substantially expanded therapeutic options. Beyond mechanical restriction, these interventions exert their effects through complex hormonal and neurophysiological mechanisms involving gut-brain signaling, gastric motility, and enteroendocrine adaptations. Gut-derived hormones, including ghrelin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), amylin, and leptin, play a central role in the regulation of hunger, satiation, and satiety by integrating nutrient sensing, vagal afferent signaling, and central hypothalamic pathways. Surgical procedures such as laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass induce profound and durable hormonal remodeling, whereas endoscopic sleeve gastroplasty primarily modulates gastric physiology with more modest and heterogeneous endocrine effects. Intragastric balloons induce a transient delay in gastric emptying and achieve moderate short-term weight loss, although their metabolic and weight-loss effects appear limited in durability. In parallel, GLP-1 receptor agonists and emerging multi-agonist therapies reproduce several post-bariatric hormonal adaptations and achieve clinically meaningful weight loss. In this review, we summarize current knowledge on digestive hormone physiology and provide an updated overview of the hormonal mechanisms underlying pharmacologic, endoscopic, and surgical bariatric interventions, highlighting their respective roles within a continuum of obesity treatment strategies.

Interleukin-10 (IL-10) is an essential regulator of intestinal immune homeostasis. Neutralising autoantibodies against IL-10 (anti-IL-10) have been identified in children and also adult patients with IBD. Positivity for anti-IL-10 autoantibodies was associated with carriage of HLA-DRB1*01:03 allele. To determine the prevalence of anti-IL-10 in paediatric IBD and assess the associated clinical phenotype. We conducted a cross-sectional multicentre study across paediatric IBD cohorts from four countries. Anti-IL-10 antibodies were investigated in serum and plasma from paediatric patients with IBD (mean age of IBD onset 11.2±3.8 years). IL-10-neutralisation capacity was confirmed by functional IL-10 reporter assay, competitive ELISA and cytokine release assay. Clinical data were analysed to evaluate disease phenotype and treatment outcomes, with comparison with matched controls. HLA-DRB1*01:03 analysis was performed. Anti-IL-10 positivity was identified in 26/1045 paediatric patients with IBD (2.5%) (Crohn's disease n=6, UC n=19, IBD unclassified n=1; IBD diagnosis age of 13±3 years). Anti-IL-10 autoantibodies were of the IgG class and amplified pro-inflammatory cytokine responses in vitro. Anti-IL-10-positive patients exhibited more severe disease compared with matched controls, including an increased prevalence of difficult-to-treat disease (23% vs 6%, p=0.03), higher rate of acute severe UC (26% vs 6%; p=0.038) and higher rates of colectomy (27% vs 6%, p=0.01). Eighty percent (16/20) of anti-IL-10-positive patients with available HLA data carried the HLA-DRB1*01:03 allele, compared with 1.5% in the anti-IL-10-negative group. Anti-IL-10 autoantibodies are present in a subgroup of paediatric patients with IBD and are associated with difficult-to-treat disease.

Gastrointestinal (GI) adenocarcinomas pose a significant therapeutic challenge due to highly immunosuppressive tumor microenvironments that limit effective antitumor immune responses. Dense stromal fibrosis, immune exclusion and poor responses to immune checkpoint inhibitors are hallmarks of treatment-resistant malignancies, most notably pancreatic ductal adenocarcinoma (PDAC) and subsets of gastric cancer. In this regard, IL-15 superagonists such as N-803, NIZ985, RLI, and NKTR-255 have emerged as promising immunotherapeutic candidates, as they selectively expand natural killer (NK) cells and CD8+ T-cells without the systemic toxicity and regulatory T-cell activation observed with IL-2 therapy. IL-15 superagonists have emerged as more effective therapeutic agents when used in conjunction with local inhibitors of TGF-β and IL-10, stromal remodeling, and vascular normalization. They are supported by increasingly conclusive mechanistic, preclinical and early clinical data. A combination of these interventions circumvents extracellular matrix-provoked immune barriers, reverses VEGF-induced endothelial dysfunction, and enhances the trafficking of lymphocytes into tumor cores. Moreover, several localized therapeutic delivery strategies, such as endoscopic delivery, implantable depots, biomaterial scaffolds, and nanocarriers, can improve intratumoral cytokine retention and reduce systemic inflammatory toxicity. Together, these advances define a new paradigm for cytokine-immunotherapy: IL-15 superagonists serving as key mediators of reprogramming of the tumor microenvironment. Therapeutic strategies targeting IL-15 have the potential to restore cytotoxic immunity, improve access to immune cells, and promote responsiveness to the checkpoint blockade, making them a promising yet investigational approach to converting immune-cold GI malignancies into more treatment-responsive disease states, though further clinical validation is required.