A multicenter randomized controlled trial on the effects of preoperative immunonutrition in minimally invasive colorectal cancer surgery: clinical and translational outcomes

Background: Malnutrition and systemic inflammation worsen outcomes in colorectal cancer surgery. Immunonutrition (IN), enriched with arginine, omega-3 fatty acids, and nucleotides, may improve immune response and recovery, but evidence in homogeneous colorectal cohorts remains limited. Methods: A multicenter, ERAS-compliant randomized controlled trial compared 10-day preoperative IN (Impact® Oral) versus isocaloric–isonitrogenous standard supplementation (Resource®) in patients undergoing minimally invasive colorectal resection for cancer. Primary outcomes were postoperative and infectious complications; secondary analyses included cytokine profiling (IL-1β, IL-6, IL-8, IL-10, IL-15, IL-18, TNF-α) and CT-based body composition (L3 SMI, TAT, VAT, SAT). Results: Among 125 randomized patients, IN significantly reduced overall complications (24.1% vs 44.4%, p = 0.037) and infectious complications (12.1% vs 27.8%, p = 0.037), with a trend toward shorter hospital stay and faster intestinal recovery (first flatus 1.73 ± 0.72 vs 2.23 ± 0.95 days, p = 0.035). Cytokine levels were higher in colorectal cancer than in healthy controls, confirming a pro-inflammatory baseline, though intergroup differences after IN were not significant. Sarcopenia correlated with increased morbidity, while adipose-tissue indices showed no significant variation between groups. Conclusions: Preoperative immunonutrition significantly improves postoperative outcomes even in ERAS-standardized, minimally invasive colorectal cancer surgery. The integration of body composition and inflammatory biomarkers provides a translational setting for tailored perioperative nutrition.