Introduction Mucinous adenocarcinoma (MA) and signet ring cell carcinoma (SRCC) are less common histological subtypes of colorectal cancer (CRC) and may carry distinct prognostic implications. However, data comparing incidence and outcomes across histologic subtypes in early-onset CRC (EOCRC) remain limited. Patients and Methods Using the SEER database, we identified patients aged 20–49 years diagnosed with CRC. Incidence analyzes were performed across subtypes. For survival analysis, 1:1 propensity score matching (PSM) was performed between AC and SRCC cohorts based on demographic and tumor-related characteristics. A Kaplan-Meier (KM) analysis was then performed for the overall survival (OS) and case-specific survival (CSS). Among patients with SRCC, multivariable logistic regression was performed to identify factors associated with mortality, reported as odds ratios (ORs) with 95% confidence intervals (CIs). A p-value < 0.05 was considered statistically significant. Results A total of 69,914 patients with EOCRC were identified: AC (90.5%), MA (7.8%), and SRCC (1.7%). Compared to AC, SRCC patients had significantly worse clinical outcomes after PSM, including lower OS (35.1% vs. 73.5%, p < 0.001), shorter median survival (19 vs. 37.5 months, p < 0.001), and a higher 5-year mortality (81.6% vs. 66.5%, p < 0.001). No significant difference was observed in CSS between matched cohorts (p = 0.96). Among SRCC patients, positive pretreatment CEA (OR = 1.83), regional stage (OR = 3.13), distant stage (OR = 18.55), and distant metastases at diagnosis (OR = 7.10) were independently associated with mortality. Conclusion In EOCRC, SRCC histology is associated with markedly worse overall survival compared with AC, with positive CEA, stage at diagnosis, and distant metastasis at diagnosis independently predicting mortality.

Abstract Topic Esophageal Cancer: Barrett‘s Esophagus: High-Grade Dysplasia and Early Invasive Cancer Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying and are linked to increased gastroesophageal reflux, a recognized risk factor for Barrett’s esophagus (BE) progression to esophageal cancer (EC). Extended use of GLP-1 RAs facilitates weight loss, mitigating reflux, possibly offering a protective effect against EC. This large retrospective study aimed to assess the association between GLP-1 use with the development of dysplastic Barrett’s esophagus (BE) and EC in patients with non-dysplastic BE (NDBE). Methods We used ICD and CPT codes within the TriNetX (a large multicenter claims based) database to identify NDBE patients. The cohort was then categorized as GLP-1 users vs. non-users based on ATC code A10BJ. A 1:1 propensity matched analysis was performed with balancing of confounders (Table 1). Primary outcomes included incidence of dysplastic BE and EC. Time to event analyses were performed. Results A total of 4,534 patients were identified in the GLP-1 cohort and 55,621 in the non-GLP-1 cohort. After 1:1 matching, 4,530 patients were included in each cohort. Mean follow-up was 3.57 years in GLP-1 cohort and 3.30 years in non-GLP-1 cohort. Incidence of dysplastic BE/EC in the GLP 1 cohort was 1.24% (N=56) compared to 0.54% (N=24) in non-GLP 1 cohort. GLP-1 users demonstrated significantly higher risk of developing dysplastic BE/EC compared to non-users (RR: 2.30; 95% CI: 1.47–3.70, P = 0.0004. The cumulative incidence of dysplastic BE/EC was higher among GLP-1 cohort at 3 and 5 years—0.90 %, and 1.11%, respectively—compared to 0.47%, and 0.49 % in the non-GLP-1 group. Conclusion Our findings indicate that GLP-1 therapy was associated with an increased risk of progression to dysplastic BE/EC in patients with non-dysplastic BE. Further prospective studies are warranted to validate these results.

BACKGROUND AND AIMS:Extraintestinal manifestations (EIMs) occur in one-fifth of patients with inflammatory bowel diseases (IBDs) (Crohn's disease[CD]; ulcerative colitis [UC]). As advanced therapies (ATs) for IBD become more targeted, effectiveness for luminal disease may not be extrapolatable to EIMs. We conducted a systematic review to evaluate the efficacy of ATs on EIMs in IBD. METHODS:We conducted searches in PubMed/Embase (inception March 2025) for studies of any of the 5 FDA approved AT classes (tumor necrosis factor [TNF] antagonists, Janus kinase [JAK] inhibitors, anti-integrins, anti-interleukins [anti-ILs], and S1P receptor modulators) for musculoskeletal (arthritis, arthralgias), dermatologic (erythema nodosum, pyoderma gangrenosum), or ocular EIMs in patients with IBD. The primary outcome was clinical improvement. The pooled improvement rates by EIM type and AT class were calculated using a random effects model to account for anticipated heterogeneity. RESULTS:A total of 49 studies were included in the final analysis (6 randomized clinical trials [RCTs], 1 pooled analysis of clinical trials, and 42 observational studies). For musculoskeletal EIMs, TNF antagonists achieved response in 61% of patients, with higher response rates for peripheral (73%) than axial (57%) arthritis. JAK inhibitors were similarly effective (65%) while vedolizumab had significantly lower efficacy (42% improvement), particularly for axial arthritis (12%). For dermatologic EIMs, systemically directed ATs had high efficacy (TNF antagonists 89%, anti-IL 91%). There was a paucity of data on ocular EIMs. CONCLUSION:Systemically directed ATs (TNF-antagonists, JAK inhibitors, anti-ILs) demonstrated strong efficacy for musculoskeletal or cutaneous EIMs; vedolizumab achieved clinical response in lower rates, particularly for axial arthritis.

Background: Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are frequently experienced by patients and may lead to severe symptoms and fatigue. However, the reporting patterns of these outcomes in IBD randomized controlled trials (RCTs) are not clear. Methods: We searched placebo-controlled phase 3 RCTs of advanced therapies in IBD and assessed the frequency and means of reporting EIM and fatigue data in these studies. Results: Thirty-three phase 3 RCTs for Crohn's disease (CD) (n = 16) or ulcerative colitis (UC) (n = 16) were identified between 2002 and 2023. While all trials (16/16) in CD collected some EIM data, we could only ascertain 6/16 (38%) collected EIM data in UC trials. Fewer than one-third (9/32, 28%) reported EIM prevalence at baseline; fewer reported the improvement with active treatment (9%). Fatigue was measured in 20/32 trials (63%). Conclusions: EIM and fatigue data are inconsistently collected in RCTs of IBD. Standardizing collection methods across RCTs would provide greater insight on these agents and their efficacy in treating these manifestations of disease.