Gastroenterology Report最新文献

Background: Pancreatic angiosarcoma is a rare and highly aggressive tumor originating from lymphatic or vascular endothelial cells, with poor prognosis and few effective treatments. In this study, we aimed to characterize the tumor ecosystem of metastatic pancreatic angiosarcoma, along with its potential treatment strategies.

Methods: Single-cell RNA-sequencing and bioinformatics analysis were performed on samples obtained from one patient, including at total of 16,841 cells from pancreatic angiosarcoma liver metastasis and adjacent normal liver tissue.

Results: Pancreatic angiosarcoma cells exhibited marked upregulation of nuclear factor kappa-B (NF-κB), hypoxia-inducible factor 1 (HIF-1), and myelocytomatosis oncogene (MYC) proto-oncogene signaling pathways, while presenting limited upregulation of actionable therapeutic targets except for cyclin-dependent kinase 4 (CDK4) and epidermal growth factor receptor. Several immune checkpoint genes, including cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), programmed cell death protein 1 (PDCD1), and cluster of differentiation 86 (CD86), were upregulated in tumor-infiltrating T cells, natural killer (NK) cells, and myeloid cells. Furthermore, intercellular interaction profiling demonstrated enhanced activity of the programmed death-ligand 1 (PD-L1) and CD86 signaling pathways within the tumor microenvironment. The gene-set scores of T/NK-cell exhaustion, regulatory T cell, and macrophage angiogenesis were significantly higher in tumor tissues compared with adjacent normal tissues. However, the phagocytosis scores of macrophages within the tumor-infiltrating region were significantly lower than those in the adjacent normal tissues.

Conclusions: Our findings outlined an immunosuppressive and angiogenic tumor ecosystem in pancreatic angiosarcoma liver metastasis, suggesting that pancreatic angiosarcoma may be insensitive to most targeted therapies. Conversely, immunotherapies targeting LAG3, PD-L1, and CD86 (e.g. isatuximab, Opdualag, and abatacept) and anti-angiogenic agents may be therapeutically effective and worthy of subsequent exploration.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been proposed to replace the term of non-alcoholic fatty liver disease (NAFLD). To investigate the effect of MASLD on liver fibrosis and validate the clinical utility of MASLD criteria, differences in disease severity and clinical outcomes between MASLD and NAFLD were compared in a biopsy-proven pediatric cohort. The retrospective clinical data of 427 children with biopsy-proven steatotic liver between 2010 and 2021 were consecutively collected and categorized into three distinct subgroups of MASLD-only, NAFLD-only, and MASLD-NAFLD according to the diagnostic guidelines. Patients with MASLD-only and MASLD-NAFLD had more features of metabolic disorders, with higher level of triglycerides but lower level of high-density lipoprotein cholesterol than NAFLD-only. The proportion of significant fibrosis was highest in MASLD-only patients (68.0%), followed by those with MASLD-NAFLD and NAFLD-only (43.3% and 19.4%, respectively; P < 0.001). More steatohepatitis was presented in MASLD-NAFLD group than the other two groups (66.1% vs 30.8% vs 22.6%, P < 0.001). Multivariate regression revealed that children with MASLD-only had 5.8-fold greater risk of significant fibrosis than those with NAFLD-only (P = 0.001). After a median follow-up of 83 months, 14 of 427 patients developed clinical outcomes. Kaplan-Meier curves indicated no difference in the cumulative incidence of clinical events between the groups (log-rank, P = 0.073). Children in MASLD group tended to have concomitant with severe liver fibrosis and related metabolic diseases compared to those with NAFLD-only in pediatric cohort. Thus, the redefinition of MASLD may improve the detection of children with severe disease that need early intervention.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a promising therapeutic approach for treating advanced gastric cancer with peritoneal metastases. Herein, we conducted this meta-analysis to evaluate the feasibility, efficacy, and safety of PIPAC in this patient population. The literature between January 2011 and February 2024 was comprehensively searched on the following databases: PubMed, Embase, Web of Science, and the Cochrane Library. The search, guided by the Population-Intervention-Comparison-Outcome (PICO) framework, focused on studies reporting on the feasibility, efficacy, and safety of PIPAC. Data were pooled by using log transformation (PLN) or Freeman-Tukey double arcsine transformation. Of the 451 initially identified studies, 18 were included in the meta-analysis, comprising 671 patients who underwent 1,357 PIPAC procedures. Our data analysis indicated that 32.6% of the patients (95% confidence interval [CI], 23.5%-42.3%) completed three or more PIPAC procedures. Conversely, 2.3% of patients (95% CI, 0.6%-5%) either did not have access to or could not undergo PIPAC. The average rate of histological response across the included studies was 66.3% (95% CI, 59.1%-73.1%). Pooled results showed that 13.1% of patients (95% CI, 7.0%-20.7%) had reduced ascites after PIPAC, and 7.8% (95% CI, 4.8%-11.4%) became resectable. Adverse events were reported in 17.1% of patients (95% CI, 5.3%-33.4%), with 3.6% (95% CI, 1.4%-6.6%) experiencing severe adverse events (grade 3-5, Common Terminology Criteria for Adverse Events [CTCAE]). The pooled mortality related to PIPAC was 0.1% (95% CI, 0%-0.5%). The pooled proportions for 6-month, 1-year, and 2-year overall survival rates were 82.4% (95% CI, 69.2%-92.8%), 54.0% (95% CI, 45.7%-62.3%), and 20.0% (95% CI, 11.3%-30.3%), respectively. The average median overall survival was 11.7 months (95% CI, 9.3-14.0 months). Our study suggests that most patients can benefit from PIPAC treatment, such as improved quality of life and significantly longer median overall survival. Patients who received first-line chemotherapy prior to PIPAC and concomitant systemic chemotherapy during PIPAC treatment, and who underwent the PIPAC procedure on more than three occasions, exhibited a more favorable survival prognosis.

Background: We aimed to investigate associations between three perinatal early-life factors and the risk of irritable bowel syndrome (IBS) in middle-aged and elderly people by using data from UK Biobank.

Methods: This is a population-based cohort study. Participants who had available data on early-life factors-namely maternal smoking around birth, being breastfed as a baby, and being one of a multiple birth and without IBS at the time of recruitment in UK Biobank-were included.

Results: Among a total of 334,586 subjects, 93,908 (28.07%) were exposed to maternal smoking around birth, 243,778 (72.86%) were breastfed as a baby, and 7,551 (2.26%) were part of a multiple birth. During a median follow-up of 13.58 years, 7,254 participants developed IBS, at a median age of 63 years. The hazard ratios of IBS were 1.22 [95% confidence interval (CI), 1.16-1.28, P < 0.001], 0.92 (95% CI, 0.87-0.97, P = 0.002), and 1.22 (95% CI, 1.06-1.40, P = 0.006) for maternal smoking, breastfeeding, and multiple birth, respectively. The joint effect of any two of these three factors was related to added influence instead of interaction between them. The effect of maternal smoking on IBS was modified by age, while the modifiers of the effect of being breastfed as a baby on IBS were the age and sex of the offspring.

Conclusions: Participants exposed to maternal smoking around birth and being one of a multiple birth had a higher risk of IBS in middle-aged and elderly stages, while being breastfed as a baby had a protective effect against IBS. Future efforts should be made to validate the results.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, particularly among individuals with chronic liver diseases. Early detection through surveillance significantly improves survival rates and current guidelines recommend semiannual ultrasound, with or without alpha-fetoprotein (AFP) testing, for high-risk populations. However, limitations in ultrasound sensitivity, physician adherence, and patient compliance affect the effectiveness of these surveillance efforts. This review explores both current and emerging strategies for HCC surveillance. Individualized surveillance approaches, utilizing risk stratification tools such as the aMAP and PAGE-B scores, enable tailored monitoring based on individual risk profiles, potentially reducing unnecessary screening in low-risk groups. Advanced imaging techniques, including contrast-enhanced ultrasound and abbreviated magnetic resonance imaging, demonstrate improved sensitivity over traditional ultrasound, particularly for early-stage HCC detection. Additionally, combining clinical characteristics with novel HCC biomarkers-such as the Gender, Age, AFP-L3, AFP, and Des-gamma-carboxy prothrombin (GALAD) score; HCC early detection screening score version 2 (HES V2.0) score; Gender, Age, AFP, and Des-gamma-carboxy prothrombin (GAAD) score; and AFP, Sex, Age, and Protein induced by vitamin K absence-II (ASAP) score-has shown higher sensitivity for early detection, with GALAD and HES V2.0 performing particularly well in phase 3 biomarker studies. Emerging molecular diagnostics, including liquid biopsy and genetic markers, also show promise in refining future HCC surveillance protocols. Despite these advancements, a limited number of at-risk patients currently undergo surveillance. Therefore, solutions must focus on enhancing awareness, adherence, and accessibility to surveillance tools. This review discusses various strategies for optimizing HCC surveillance, emphasizing a multifaceted approach that integrates risk-assessment tools, advanced imaging, and novel biomarkers to improve early detection and reduce mortality.

Increasing evidence suggests that non-operative management (NOM) with antibiotics could serve as a safe alternative to surgery for the treatment of uncomplicated acute appendicitis (AA). However, accurately differentiating between uncomplicated and complicated AA remains challenging. Our aim was to develop and validate machine-learning-based diagnostic models to differentiate uncomplicated from complicated AA. This was a multicenter cohort trial conducted from January 2021 and December 2022 across five tertiary hospitals. Three distinct diagnostic models were created, namely, the clinical-parameter-based model, the CT-radiomics-based model, and the clinical-radiomics-fused model. These models were developed using a comprehensive set of eight machine-learning algorithms, which included logistic regression (LR), support vector machine (SVM), random forest (RF), decision tree (DT), gradient boosting (GB), K-nearest neighbors (KNN), Gaussian Naïve Bayes (GNB), and multi-layer perceptron (MLP). The performance and accuracy of these diverse models were compared. All models exhibited excellent diagnostic performance in the training cohort, achieving a maximal AUC of 1.00. For the clinical-parameter model, the GB classifier yielded the optimal AUC of 0.77 (95% confidence interval [CI]: 0.64-0.90) in the testing cohort, while the LR classifier yielded the optimal AUC of 0.76 (95% CI: 0.66-0.86) in the validation cohort. For the CT-radiomics-based model, GB classifier achieved the best AUC of 0.74 (95% CI: 0.60-0.88) in the testing cohort, and SVM yielded an optimal AUC of 0.63 (95% CI: 0.51-0.75) in the validation cohort. For the clinical-radiomics-fused model, RF classifier yielded an optimal AUC of 0.84 (95% CI: 0.74-0.95) in the testing cohort and 0.76 (95% CI: 0.67-0.86) in the validation cohort. An open-access, user-friendly online tool was developed for clinical application. This multicenter study suggests that the clinical-radiomics-fused model, constructed using RF algorithm, effectively differentiated between complicated and uncomplicated AA.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the leading cause of chronic liver disease worldwide, with fibrosis recognized as the main prognostic factor and therapeutic target. While early-stage fibrosis is reversible, advanced fibrosis poses a significant clinical challenge due to limited treatment options, highlighting the need for innovative management strategies. Recent studies have shown that alternative pre-mRNA splicing, a critical mechanism regulating gene expression and protein diversity, plays a fundamental role in the pathogenesis of MAFLD and associated fibrosis. Understanding the complex relationship between alternative splicing and fibrosis progression in MAFLD could pave the way for novel therapeutic approaches and improve clinical outcomes. In this review, we describe the intricate mechanisms of alternative splicing in fibrosis associated with MAFLD. Specifically, we explored the pivotal of splicing factors, and RNA-binding proteins, highlighting their critical interactions with metabolic and epigenetic regulators. Furthermore, we provide an overview of the latest advancements in splicing-based therapeutic strategies and biomarker development. Particular emphasis is placed on the potential application of antisense oligonucleotides for rectifying splicing anomalies, thereby laying the foundation for precision medicine approaches in the treatment of MAFLD-associated fibrosis.