United European Gastroenterology Journal最新文献

Background: Gastric cancer remains a major cause of cancer-related mortality in intermediate-risk countries. Although endoscopic screening is widely implemented in high-risk regions, its effectiveness and economic viability in intermediate-risk settings remain uncertain. This systematic review and meta-analysis evaluated the effectiveness and cost-effectiveness of endoscopic screening in these countries.

Methods: A systematic review and meta-analysis was conducted to assess the effectiveness and cost-effectiveness of upper gastrointestinal endoscopic screening by esophagogastroduodenoscopy (EGD) for gastric cancer. Searches were performed in Medline, Scopus, Embase, and Web of Science up to 30 September 2024. Pooled estimates were calculated for the detection of precancerous conditions, gastric cancer (overall and early-stage), and gastric cancer-specific mortality. Subgroup analyses were performed by screening strategy and geographic setting.

Results: Thirty-two studies met inclusion criteria-24 on screening effectiveness and eight on cost-effectiveness. Among 404,159 individuals screened, the pooled detection rate for precancerous conditions was 25.5%, for gastric neoplastic lesions 3.3%, and for early-stage cancer among neoplastic cases 91.6%. Gastric cancer-specific mortality was 26.1%, and 5-year survival reached 75.7%. Subgroup analyses of studies using direct EGD versus pre-selection indicated higher detection of precancerous conditions (32.5% vs. 17.0%, p < 0.001) and early-stage cancer (95.8% vs. 87.3%, p < 0.001). Comparing Chinese versus other settings, similar detection rates were found for precancerous conditions (25.3% vs. 26.0%) and early-stage detection (91.5% vs. 100%). Economic analyses suggest that endoscopic screening is cost-effective in intermediate-risk settings, particularly when combined with colorectal screening, with incremental cost-effectiveness ratios within accepted willingness-to-pay thresholds.

Conclusions: Endoscopic screening by EGD shows strong potential for early detection of gastric cancer in intermediate-risk countries. However, formal comparative analyses with unscreened populations are lacking, and most survival and mortality data originate from Chinese studies, limiting generalizability. Nevertheless, economic evaluations suggest implementing endoscopic screening-especially when integrated with colorectal screening or guided by risk stratification-could be a feasible and effective strategy.

Trial registration: PROSPERO-CRD42024502174.

Background and study aims: Endoscopic resection (ER) is curative for early-stage oesophageal adenocarcinoma (OAC) without high-risk features. Piecemeal endoscopic mucosal resection (pEMR) prevents assessment of lateral margins, complicating risk estimation for neoplastic recurrence. We investigated the risk factors for residual and recurrent OAC post-pEMR.

Methods: We performed a longitudinal study of two independent patient cohorts: the test cohort who underwent piecemeal or en-bloc ER (n = 140) and the validation cohort who underwent pEMR only (n = 89). Inclusion criteria were: OAC stage T1a or low-risk T1b, no lympho-vascular invasion, and R0 resection. The primary outcome was residual OAC at first post-ER endoscopy, and secondary outcomes were residual neoplasia (high-grade dysplasia and/or OAC), recurrence of neoplasia at any post-ER endoscopy, and remission of neoplasia, dysplasia and metaplasia at most recent endoscopy.

Results: In the test cohort, the incidence of neoplastic recurrence was higher in patients treated with pEMR (n = 54, 49%) versus en-bloc ER (n = 7, 23%) (p = 0.021). The percentage of pEMR specimens with OAC was an independent risk factor for residual OAC at the first post-pEMR endoscopy (OR for a 10% increase = 1.24, CI = 1.03-1.51, p = 0.025). A 50% cut-off of pEMR specimens with OAC was optimal to predict residual OAC (specificity = 0.68, sensitivity = 0.63). Rates of residual (p = 0.039) and recurrent (p = 0.0052) OAC were higher when > 50% of pEMR specimens were involved by OAC. In the validation cohort, recurrent OAC was also more frequent when cancer burden was > 50% (p = 0.013).

Conclusions: High cancer burden on pEMR specimens correlates with the risk of residual OAC. Post-pEMR site check before endoscopic ablation is recommended if more than 50% of pEMR specimens show OAC.

Background: Emerging RAS inhibitors show promise in treating KRAS-mutated malignancies, but resistance mechanisms limit their clinical efficacy. Given recent clinical findings associating KRAS mutations with reduced response to neoadjuvant therapy in rectal cancer (RC), we aimed to investigate their impact on treatment outcomes and explore potential therapeutic strategies.

Methods: We conducted a retrospective analysis of 390 rectal cancer patients to evaluate the association of KRAS mutations with disease-free survival (DFS) and response to therapy. We assessed the efficacy of KRAS inhibitors in rectal cancer cell lines, patient-derived organoids (PDOs), and patient-derived cell lines (PDCLs), and explored adaptive resistance mechanisms through transcriptomic profiling and unbiased drug screening experiments.

Results: Mutant KRAS was associated with a reduced DFS and RCs harboring G12C and G12V mutations had less complete pathological responses to neo-adjuvant therapies. KRAS-mutated RC cells demonstrated adaptive resistance to KRAS inhibitors, characterized by transcriptomic restoration of oncogenic pathways, including MYC and E2F, and upregulation of ERBB2/3 expression. Consistently, drug screening identified EGFR family inhibitors as potent combinatorial partners, effectively overcoming KRAS inhibitor tolerance by inducing apoptosis. In patient-derived models, the pan-RAS inhibitor RMC-6236 combined with EGFR inhibitors demonstrated significant synergistic effects and prevented long-term tumor cell outgrowth.

Conclusion: Our findings point to the negative impact of KRAS mutations, particularly G12C and G12V, on RC treatment outcomes. Adaptive resistance by upregulation of ERBB genes limits the efficacy of KRAS inhibitors. Combining these with pan-ERBB inhibitors enhances anti-tumor effects in patient-derived cellular RC models, showing its potential as an alternative to the combination with anti-EGFR antibodies.

Background and objectives: Primary sclerosing cholangitis (PSC) is a chronic liver disease with aberrant immune dysregulation and bile duct fibrosis. It is often associated with inflammatory bowel disease (IBD), especially ulcerative colitis, raising questions about distinct immune activation in these conditions. Therefore, we aimed to systematically review and compare immune activation patterns in patients with PSC and IBD (without PSC), which may provide deeper insights into PSC pathophysiology.

Methods: MEDLINE, Scopus, Cochrane Library, and Embase were searched until July 2024 for relevant studies reporting immune cell profiles, cytokine levels, and gene expression patterns in patients with PSC. Reference articles of patients with IBD were then added to compare the immune profile of patients with PSC (with or without IBD) and patients with IBD-only.

Results: Twenty-three articles studying 638 PSC and 557 non-PSC non-IBD subjects were included. PSC patients showed various degrees of immune activation in the systemic circulation, biliary fluid, and liver tissue, most notably regarding integrin β7+ gut-homing T cells, IL-2, and IL-10 compared to their respective controls. Compared with patients with IBD, patients with PSC had reduced Tregs in the systemic circulation. When comparing tissue-based immune markers, PSC-livers had increased Th17 cells, IL-1β, and TNF-α and reduced levels of B cells, IL-2, and IL-10 than the IBD-mucosa.

Conclusions: Patients with PSC and patients with IBD without PSC can be differentiated by a distinct immune activation pattern with upregulation of Th17 and downregulation of Treg functions in PSC while other immune parameters do not allow a differentiation of these conditions.

Background and aims: Elderly-onset inflammatory bowel disease (IBD) patients (age ≥ 60 at diagnosis) have unique characteristics that require special consideration. Using a real-life registry-based cohort, we compared disease phenotypes and treatment exposures between adult-onset (18 ≤ age < 60 years) and elderly-onset IBD patients.

Methods: Demographics, disease characteristics, and treatment were compared between adult- and elderly-onset IBD patients diagnosed during 2000-2022 with ≥ 12 months follow-up.

Results: Of 3307 adult IBD patients, 290 (9%) were elderly-onset. This group exhibited a higher prevalence of colon-only involvement, with higher rates of ulcerative colitis (UC, 38.3% vs. 31.4%, p = 0.02) and more colonic L2 Crohn's Disease (CD, 21% vs. 12%, p < 0.001) then adult-onset group. Elderly-onset CD also showed less ileocolonic L3 disease (14% vs. 29%, p < 0.001), less penetrating B3 phenotype (7.4% vs. 19%, p < 0.001), and less perianal involvement (10% vs. 20%, p < 0.001). Elderly-onset CD and UC patients received more 5-ASA (36% vs. 17%, p < 0.001 in CD and 75% vs. 63%, p = 0.02 in UC). In contrast, these patients were exposed to considerably less biologics and/or JAK inhibitors (37% vs. 56% for CD and 20% vs. 35% for UC, p < 0.001), with higher 15-year biologic-free survival among elderly-onset IBD. First-line biological choices also substantially differed, with adult-onset receiving more anti-TNFs and elderly-onset receiving more Vedolizumab. We did not observe higher rates of IBD-related surgeries and steroid use between the groups.

Conclusions: Elderly-onset IBD shows higher prevalences of colon-only IBD (UC and L2 CD). Treatment strategies in elderly-onset IBD favor 5-ASA and show reduced biological use, with preferences for Vedolizumab over anti-TNFs.