Endoscopic submucosal dissection (ESD) has emerged as an organ-preserving strategy for superficial colorectal neoplasia, offering high rates of en bloc and curative resections. However, the ileocecal valve (ICV) remains one of the most technically challenging sites because of its complex anatomy, thin wall, and potential ileal extension. Evidence from Western countries is limited, with few studies and small sample sizes. This national multicenter study aimed to evaluate the efficacy, safety, and long-term outcomes of ESD for ICV neoplasia in expert Italian centers. 

A retrospective multicenter study involving 14 high-volume Italian units of the Endoscopic Resection Italian Network (ERIN) was performed. Patients with superficial neoplastic lesions involving the ICV treated with ESD or hybrid ESD (h-ESD) between January 2018 and July 2025 were retrospectively enrolled in this study. The primary outcomes were en bloc, R0, and curative resection rates. Secondary outcomes included intra-procedural and delayed adverse events (AEs), the need for surgery, local recurrence rate, recurrence-free survival (RFS), and surgery-free survival (SFS).

A total of 142 patients were included (median age, 67 years). Lesions had a median size of 34 mm, and nearly half (49%) extended into the terminal ileum. Most lesions were LST-G (56%), and ESD was performed in 88% of cases, with h-ESD in 12% of cases. En bloc resection was achieved in 93% of patients, and R0 resection was achieved in 89% of patients. Curative resection according to the ESGE guidelines was achieved in 87% of patients.  Intraprocedural AEs occurred in 22% of patients, all of whom were successfully managed endoscopically. Delayed AEs occurred in 5% of patients, with only two cases requiring surgery. Most lesions were benign, with adenocarcinoma in 12%(n=17) of cases. At 10 months follow-up, local recurrence occurred in 7% of patients, and only 5% of patients required surgery. In the Firth logistic regression, h-ESD was significantly associated with an increased risk of non-R0 resection (OR 7.59; p = 0.001) and non-curative resection (OR 12.40, p < 0.001). Moreover, T-ESD was a protective factor for R0 resection (OR 0.22; p = 0.038). Lesion morphology, size, circumferential involvement, and ileal extension were not associated with adverse outcomes. The estimated probability of RFS at 6 months was 97.3%, 88.9% at 12 months, then stabilized at 14 months.

In expert hands, ESD for ICV neoplasia demonstrates high efficacy and safety, yielding excellent curative resections.  Despite the anatomical complexity inherent to the ileocecal region, these findings endorse ESD as a viable organ-preserving alternative to surgery for these superficial neoplastic lesions,mostly benign,of the ICV. This affirms the long-term durability and safety of endoscopic management of ICV lesions.