Gastroenterology Report最新文献

Background: Irritable bowel syndrome (IBS) is a condition with undetermined pathophysiology. Dysregulation of the gut-brain axis has been implicated in its development. This study aimed to investigate the association between gut microbial dysbiosis and brain N-methyl-D-aspartate receptor (NMDAR) hyperfunction in a mouse model of post-infectious IBS (PI-IBS) with visceral hypersensitivity.

Methods: Four-week-old mice were divided into four groups: control mice, PI-IBS mice, PI-IBS mice co-housing with normal mice, and PI-IBS mice administrated with a cocktail of antibiotics. The PI-IBS mouse model was established by using Trichinella spiralis infection. Visceral sensitivity was measured by using the abdominal withdrawal reflex in response to colorectal distension. c-FOS and NMDAR expression in the insula, hippocampus, and hypothalamus were evaluated by using immunostaining and Western blot, respectively. Additionally, NMDAR-mediated evoked excitatory postsynaptic currents (eEPSCs) in these brain regions were recorded by using patch clamp techniques.

Results: Visceral hypersensitivity was observed in PI-IBS mice compared with control mice. Increased c-FOS expressions were observed in the insula and hippocampus of PI-IBS mice. Although no changes in the NMDAR subtypes expression were observed, enhanced NMDAR-mediated eEPSCs were detected in the insula and hippocampus of PI-IBS mice compared with control mice. Co-housing and antibiotics treatment effectively reduced NMDAR-mediated eEPSCs and alleviated visceral hypersensitivity.

Conclusion: Gut microbiota dysbiosis may serve as an initiating factor for NMDAR hyperfunction in PI-IBS with visceral hypersensitivity.

Background: Gastric cancer predominantly occurs in middle-aged and elderly individuals, whereas cases arising in individuals before the age of 45 years are defined as early-onset gastric cancer (EOGC). The biological and clinical characteristics of EOGC remain insufficiently understood. This study aimed to investigate the sex-specific clinicopathological and molecular features of EOGC.

Methods: We retrospectively analysed a large cohort of 4,903 gastric cancer patients, including 410 EOGC patients, to compare survival outcomes and clinicopathological features between EOGC patients and late-onset gastric cancer (LOGC) patients and between male and female EOGC patients. Additionally, transcriptome and genome sequencing data from a public Korean EOGC cohort were analysed to identify sex-specific molecular alterations, which were further validated in a Chinese EOGC cohort by using immunohistochemistry.

Results: Overall survival was significantly shorter in the LOGC group than in the EOGC group. In contrast, EOGC patients were characterized by a greater proportion of females, later T and N stages, more tumours located in the middle third of the stomach, a higher prevalence of diffuse and signet ring cell types, poorer differentiation, smaller tumour size, and lower HER2- and Ki67-positive rates. Among patients with EOGC, females accounted for the majority but had worse outcomes; these female EOGC patients were diagnosed earlier, presented with high proportions of lymph node metastasis and advanced stage, and a higher incidence of differentiated diffuse-type tumours than male EOGC patients. Molecular analyses further revealed female-specific HOXB8 expression upregulation, increased CDH1 mutation numbers, and distinct immune infiltration patterns, which were validated in a Chinese cohort.

Conclusion: EOGC displays pronounced sex-specific clinicopathological and molecular features. These findings highlight the need for sex-based considerations in understanding EOGC biology and tailoring clinical management strategies.

Background: There is no consensus on the adjuvant treatment regimen for patients with colorectal cancer liver metastasis (CRLM) who have achieved successful conversion after surgery. This study aimed to compare the efficacy and safety of chemotherapy alone (CA) versus chemotherapy plus targeted therapy (CT) as adjuvant therapy for CRLM patients.

Methods: Initially unresectable CRLM patients who were converted to hepatectomy with no evidence of disease between June 2013 and June 2020 were retrospectively analysed. The baseline characteristics were balanced between the CA and CT cohorts by using 1:2 propensity score matching (PSM). After PSM, disease-free survival (DFS) and overall survival (OS) were evaluated. A comprehensive subgroup analysis compared the efficacy between the cohorts, with DFS and OS assessed by using a stratified log-rank test and summarized by using Kaplan-Meier and Cox proportional hazards methods.

Results: After PSM, 66 CA and 132 CT patients were included. DFS and OS were similar between the CA and CT cohorts (median DFS: 8.5 vs 10.8 months; median OS: 51.7 vs 56.5 months; both P > 0.050). In the CT cohort, subgroup analysis indicated a favorable trend of DFS for patients with KRAS/NRAS/BRAF mutations and receiving up to four cycles of conversion therapy (P_interaction, 0.005 and 0.013, respectively). In the KRAS/NRAS/BRAF-mutated cohort, CT significantly improved median DFS compared with CA (11.3 vs 7.4 months; hazard ratio, 0.42; 95% confidence interval, 0.26-0.69; P < 0.001).

Conclusion: CT, as adjuvant therapy, effectively reduced intrahepatic and extrahepatic recurrence in initially unresectable CRLM patients. The patients with KRAS/NRAS/BRAF mutations or undergoing up to four cycles of conversion therapy benefited more from CT than from CA.

Background: Many meta-analyses and systematic reviews have explored the impact of omega-3 supplementation on clinical outcomes in individuals with gastrointestinal (GI) cancers. Thus, this study aimed to capture the effects of omega-3 supplementation on GI cancers and associated complications.

Methods: This umbrella study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive advanced search was executed across Scopus, PubMed, and Web of Science until 25 January 2025. Data were pooled by using random-effects models based on heterogeneity. The entire statistical analysis was performed via RStudio and R. The statistical analysis results are presented as the mean difference (MD), standard mean difference (SMD), and relative risk (RR) in conjunction with their 95% confidence intervals (CIs).

Results: Eight meta-analysis papers were included in our umbrella review. Omega-3 fatty acid supplementation improved the serum concentrations of tumor necrosis factor alpha (TNF-α) (SMD: -0.34; 95% CI: -0.56, -0.11), interleukin-6 (IL-6) (SMD: -0.30; 95% CI: -0.49, -0.12; MD: -4.96; 95% CI: -6.62, -3.30), and C-reactive protein (CRP) (MD: -5.46; 95% CI: -10.06, -0.87). Omega-3 supplementation improved the CD4⁺/CD8⁺ ratio (SMD: 0.48; 95% CI: 0.26, 0.71) and reduced the length of hospitalization (MD: -2.45 d; 95% CI: -3.11, -1.80). Omega-3 supplementation was associated with a 24% significant reduction in the risk of overall complications (RR: 0.76; 95% CI: 0.67, 0.86).

Conclusion: Omega-3 supplementation may reduce the risk of overall complications and length of hospitalization in individuals suffering from GI cancers. Additionally, supplementation with omega-3 may alleviate the levels of pro-inflammatory cytokines such as TNF-α and IL-6, and acute-phase proteins such as CRP.

Background: Although selecting the appropriate patients for vedolizumab (VDZ) treatment was challenging, this multicenter, retrospective study evaluated the real-world effectiveness of VDZ and identified the patients who would benefit from VDZ therapy.

Methods: A total of 264 patients from three tertiary care centers specializing in inflammatory bowel disease were treated with VDZ. The outcomes assessed included steroid-free remission, clinical remission, objective response, and remission at Weeks 26 and 52. Least Absolute Shrinkage and Selection Operator regression and multivariate analyses were performed to identify independent predictors, and a nomogram was developed to predict steroid-free remission at Week 26.

Results: The rates of steroid-free remission and clinical remission were 46.6% and 47.0% at Week 26, and both were 38.6% at Week 52. Objective response and remission were achieved in 41.5% and 14.8% of patients at Week 26, compared with 20.7% and 11.4% at Week 52. Bio-naïve patients without active intestinal fistula, and with low inflammation burden (Crohn's Disease Activity Index ≤ 220 and C-reactive protein ≤ 10 mg/L) showed the highest rates of steroid-free remission and objective remission at both time points (all P < 0.05), along with a superior therapeutic continuation (P < 0.001). The nomogram, incorporating these factors, effectively predicted steroid-free remission at Week 26 (area under the curve = 0.830) and Week 52 (area under the curve = 0.702). VDZ was well tolerated with an adverse reaction rate of 4.2% and no serious adverse events.

Conclusions: VDZ was effective and safe in treating Crohn's disease. Patients who were bio-naïve, without active intestinal fistulas, and who had milder baseline disease activity were more likely to benefit from VDZ therapy.

Background: The survival benefits of pulmonary metastasectomy (PM) in colorectal cancer (CRC) patients with pulmonary metastasis remain controversial. This study aimed to assess the survival effect of PM on CRC patients with pulmonary metastasis.

Methods: Data from CRC patients with pulmonary metastasis were collected from the Surveillance, Epidemiology, and End Results database between 2010 and 2020. A 1:1 propensity score matching (PSM) analysis was employed to minimize heterogeneity between the groups. Kaplan-Meier analysis was performed to evaluate the overall survival (OS) of CRC patients with pulmonary metastasis who underwent PM.

Results: A total of 1,399 CRC patients with pulmonary metastasis were included; 140 patients and 1,259 patients underwent PM and did not, respectively. After PSM, there were 140 patients in each group. Patients who underwent PM demonstrated a longer median OS than those who did not, in both the overall cohort and the PSM cohort. In the PSM cohort, the median OS was 51 months (95% confidence interval [CI], 45-64 months) for CRC patients with pulmonary metastasis who underwent PM and 36 months (95% CI, 31-42 months) for those who did not undergo PM. Additionally, Cox proportional hazard models indicated that PM was a significant protective factor for OS in CRC patients with pulmonary metastasis (hazard ratio: 0.57; 95% CI, 0.41-0.80, P < 0.01).

Conclusion: PM prolongs the survival of CRC patients with pulmonary metastasis.