Gastroenterology Report最新文献

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.

Background: Gastric cancer (GC) is the fifth-leading cause of cancer-related mortality, with a 5-year survival rate less than 20%. It develops from preneoplastic lesions to adenocarcinoma, but these early genetic alterations remain poorly understood. Therefore, we aimed to identify early genetic drivers underlying the development of preneoplastic lesions and the initiation of gastric carcinogenesis.

Methods: We characterized preneoplastic and early gastric adenocarcinoma using 48 samples from 16 Guatemalan patients, a country with a high incidence of GC. We sequenced a panel of 127 genes to identify early genetic drivers and possible actionable targets.

Results: We identified extensive genetic heterogeneity, including single nucleotide and copy number variations. After comparing our data with other studies, we identified TP53 and APC as the most mutated genes in preneoplastic lesions and early GC. Our mean tumor mutational burden was higher in diffuse (0.017 mutations/Mb) and intestinal adenocarcinomas (0.015) than in chronic gastritis (0.005), and analysis of the mutational signatures revealed several processes acting at different stages of the disease. Signatures S15 (DNA mismatch repair deficiency) and S03 (homologous recombination deficiency) were more frequent in early adenocarcinoma than in chronic gastritis, intestinal metaplasia, necrosis, tubular adenoma, and atrophy. Notably, 10 of 16 patients (62.5%) had at least one actionable mutation in their preneoplastic lesions or gastric adenocarcinomas.

Conclusions: We show that at the preneoplastic and earliest stages, GC is genetically heterogeneous and presents key cancer-driving mutations that may participate in neoplastic transformation and progression, with 62.5% of lesions having the potential for treatment. This study expands the limited research on early GC and highlights key opportunities for precision medicine in populations with high GC incidence.

Alcohol-related liver disease (ALD) is a prevalent global health issue, contributing to significant mortality and encompassing a spectrum of liver damage from steatosis to decompensated cirrhosis and hepatocellular carcinoma. This review summarizes the current state of ALD, emphasizing both early and advanced stages, including alcohol-related hepatitis (AH). The epidemiology, diagnostic tools, natural history, and key progression factors of ALD are discussed, highlighting the role of diagnostic tools and pathways in early and advanced stages of ALD. The review also addresses the importance and particularities of the treatment of alcohol use disorder in patients with ALD, covering both psychological and pharmaceutical interventions. Finally, treatments for ALD-related fibrosis and AH are discussed, presenting both the currently available and future treatment options. The conclusions of this review underscore the need for comprehensive strategies to improve diagnosis, prognostic stratification, and treatment strategies at all stages of ALD.

Background: Transglutaminase 2 (TG2)-mediated enzymatic modification of gliadin peptides plays a major role in the pathogenesis of celiac disease (CD). Different inhibitory mechanisms have been reported to reduce TG2 activity but comparative data on the cellular level are lacking. Furthermore, recent evidence suggested that endogenous redox proteins such as endoplasmic reticulum resident protein 57 (ERp57, inhibits TG2) and thioredoxin-1 (TRX, activates TG2) may regulate TG2 activity. In this study, we aimed to compare the effects and applicability of different inhibitors on the activity of recombinant and cellular TG2. Furthermore, we investigated the role of ERp57 and TRX in the context of CD by using siRNA-mediated knockdown in Caco-2 cells.

Methods: The effect of TG2 inhibitors on recombinant and extracellular TG2 activity was investigated by using photometric and fluorometric quantitation of the cross-linking of biotinylated gliadin peptide P56-88 or 5-(biotinamido)-pentylamine. After siRNA knockdown, the protein levels of ERp57, TRX, and TG2 as well as TG2 activity were investigated by using Western blotting and fluorometry in Caco-2 cells.

Results: The active-site-directed inhibitors ERW1041, KCC009, and cysteamine as well as the allosteric inhibitor LDN27219 revealed the most prominent reduction in recombinant and cellular (35%-50%) TG2 activity. In contrast, PX12, S-Nitroso-N-acetyl-DL-penicillamine, zinc chloride, and ascorbic acid either did not affect TG2 activity or had only moderate effects at high doses close to cytotoxic concentrations. SiRNA knockdown of TG2 resulted in a prominent reduction (63%) in TG2 activity, whereas knockdown of ERp57 did not; knockdown of TRX only slightly (27%) reduced TG2 activity.

Conclusion: Active-site-directed inhibitors, LDN27219 and knockdown of TG2 expression significantly reduced extracellular TG2 activity and represent potential alternative treatment targets in the context of CD.

Background: Here, we aimed to identify the impact of the histamine (HA)-histamine receptor H2 (HRH2) signaling pathway on stimulating the secretion of hepatocyte growth factor (HGF) by cancer-associated fibroblasts (CAFs), as well as elucidating the mechanisms through which HGF promotes the progression of cholangiocarcinoma. In addition, our study has identified novel targets and investigated the potential use of Cimetidine and Capmatinib in cholangiocarcinoma.

Methods: Single-cell RNA sequencing revealed a noteworthy correlation between the expression of HRH2 and HGF in CAFs. HA was able to promote the transcription of HGF through the upregulation of the transcription factor hypoxia inducible factor 1 subunit alpha (HIF-1α), which was revealed by using in vitro/vivo experiments. That HGF promotes the progression of cholangiocarcinoma was identified by using orthotopic models and in vitro experiments.

Results: HRH2 and HGF were primarily expressed in CAFs within the tumor microenvironment of cholangiocarcinoma. HA sourced from mast cells could bind to the HRH2 receptor on CAFs, consequently upregulating HIF-1α and subsequently enhancing the transcription and secretion levels of HGF. HGF upregulates the phosphorylation of FOS-like 1 (FOSL1) within cholangiocarcinoma cells, promoting the expression of matrix metallopeptidase 10 (MMP10), and consequently enhancing the invasive and migratory abilities of cholangiocarcinoma cells.

Conclusions: The HA-HRH2 signaling pathway mediates the proliferation and secretion of HGF in CAFs. HIF-1α and FOSL1 played crucial roles in driving the proliferation, invasion, and migration of cholangiocarcinoma cells within the tumor microenvironment, orchestrated by CAFs. Furthermore, this study has provided theoretical support for the application of the HA receptor HRH2 inhibitor, Cimetidine, and the HGF receptor cellular mesenchymal-epithelial transition factor (c-MET) inhibitor, Capmatinib, in biliary tract tumors.