BACKGROUND: Ultra-low anterior resection (ULAR) preserves sphincter function for low rectal cancer but often causes bowel, sexual, sleep, and psychological dysfunction, impairing recovery and survival. Persistent inflammation and immunometabolic dysregulation contribute significantly. We evaluated whether perioperative inflammatory modulation plus biomarker-guided immunometabolic support improved recovery and outcomes after ULAR.
METHODS: In this prospective nonrandomized cohort, 198 patients with stage I-III rectal adenocarcinoma (April 2021-April 2023) received ERAS care or a biomarker-guided multicomponent targeted intervention combining perioperative inflammatory modulation and immunometabolic support. The intervention began 14 days preoperatively and continued 6 months, combining short-chain fatty acids, probiotics, and ω-3 fatty acids guided by C-reactive protein, interleukin-6, and tumor necrosis factor-α with individualized optimization (T-cell profiling, skeletal muscle preservation, tailored nutrition). Primary endpoints were depressive symptoms (BDI-II), sleep quality (PSQI), sexual function (IIEF-5/FSFI), and anorectal function (LARS) over 24 months. Secondary endpoints included inflammatory markers, skeletal muscle index (SMI), and survival.
RESULTS: The intervention improved BDI-II (- 4.5), PSQI (- 3.3), IIEF-5 (+ 4.9), FSFI (+ 5.4), and LARS (- 6.8; all p < 0.01), with 69.2% achieving composite response versus 35.4% of controls. Day-7 CRP, IL-6, and TNF-α were lower; T-cell recovery enhanced; and SMI decline attenuated (- 1.2% vs. - 3.8%; p < 0.001). Recovery accelerated, hospitalization shortened, and complications decreased. At 25.3 months, 2-year DFS (91.0% vs. 77.1%; HR 0.44; p = 0.015) and OS (94.6% vs. 82.3%; HR 0.39; p = 0.018) were higher.
CONCLUSION: A biomarker-guided perioperative program integrating inflammatory modulation and immunometabolic support was associated with improved multidomain recovery and survival after ULAR. Confirmation in randomized multicenter trials is warranted.
