Long-term outcomes of ureteral replacement and epithelial regeneration with tapered demucosalized ileum

BACKGROUND: Ileal substitution is the mainstream treatment for long-segment ureteral defects (LSUDs) but is complicated by the ileum's wide lumen and mucus secretion. This study investigated the long-term efficacy of a modified technique using tapered demucosalized ileum (TDI) in a canine model, with a specific focus on the type and origin of the regenerated epithelium. METHODS: Twenty-five beagle dogs with modeled LSUDs underwent TDI substitution. In the TDI replacement group (TDIR, n = 15), long-term outcomes were assessed at 3, 6, and 12 months using intravenous urography, intraluminal pressure measurement, and histological (H&E, Masson) and protein (Smad2, α-SMA, Collagen III) analysis. In the TDI stoma group (TDIS, n = 10), the impact of mucosal stripping depth was tested: a control group (stripped to mucosa) and an experimental group (stripped to submucosa). Neoureter biopsies at 1, 3, and 6 months were analyzed via histology, transmission electron microscopy, and immunohistochemistry for epithelial (MUC2, UPK2) and stem cell (CD44, LGR5) markers. RESULTS: The TDIR group showed patent neoureters without significant inflammation or fibrosis. The intraluminal pressure was intermediate between that of the native ureter and the ileum. Notably, the ileal mucosa regenerated by 3 months after conventional stripping. Protein analysis revealed reduced Smad2 and α-SMA in neoureters, with no change in Collagen III. In the TDIS group, epithelial regeneration was driven by stripping depth: the control group regenerated ileal mucosa, while the experimental group regenerated a uroepithelial layer. The regenerated epithelia in both groups were positive for UPK2 and LGR5, but negative for CD44. CONCLUSION: TDI replacement is a safe and feasible long-term solution for LSUDs. Crucially, stripping to the submucosal layer promotes the regeneration of uroepithelium, which is better adapted to the urinary environment and may lead to improved clinical outcomes.