Intersphincteric complex a potential metastasis niche in ultralow rectal cancer and prognostic significance of its complete excision following intersphincteric resection – a prospective cohort study

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Abstract
Background: The precise anatomical plane and the pathological significance of circumferential resection margin integrity for ultralow rectal cancer remain inadequately defined. This article investigates the spatial architecture of the intersphincteric complex (ISC) and its clinical implications in intersphincteric space dissection for ultra-low rectal cancer. Materials and methods: Formalin-fixed hemipelvis specimens ( n = 37) from the laboratory of applied surgical anatomy were analyzed by macroscopic dissection and multiplexed immunofluorescence to characterize anatomical features of the ISC. Additionally, patients diagnosed with ultra-low rectal cancer ( n = 221) between 2019 and 2024 were enrolled prospectively. Primary endpoints for the patient group included disease free survival, local recurrence free survival and overall survival. Secondary endpoints involved the assessment of anorectal function using prospective questionnaires. Results: Anatomy and histologic research introduced the concept of the intersphincteric complex. Proportion of patients with tumor metastasis in the intersphincteric complex was 61/197 (30.96%), indicating that the intersphincteric complex represented a potential site for metastasis in ultra-low rectal cancer. Complete intersphincteric complex excision was associated with favorable disease-free survival (HR, 0.382 [95% CI, 0.187–0.781]; P = 0.008) and local recurrence-free survival (HR, 0.251 [95% CI, 0.085–0.741]; P = 0.012) in patients and no significant differences was found among three subgroups concerning Wexner scores and LARS scores. Conclusion: A systematic anatomical analysis of the intersphincteric complex clearly elucidated key structures facilitating for ultralow rectal cancer. The intersphincteric complex is frequently a site for tumor metastasis and complete intersphincteric complex excision conferring favorable prognosis in patients with ultralow rectal cancer.

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