Preoperative Immunonutrition Modulates Inflammatory Cytokine Expression in Colorectal Cancer: Findings from a Pilot Randomized Clinical Trial

Surgery is the cornerstone treatment for colorectal cancer, and preoperative nutritional support is commonly used to reduce perioperative complications. Immunonutrition, in particular, is suggested to enhance outcomes, but its direct effects on tumor-associated inflammation are not well established. In this pilot randomized trial, 26 patients undergoing colonoscopy at diagnosis provided baseline blood and tumor samples (sample A). Patients were assigned to either standard oral nutritional supplements (3× Nutricia Nutridrink Protein daily; group 1) or immune-enriched supplements (2× Nestle Impact Oral daily; group 2) for two weeks before surgery. Tumor tissue was subsequently collected at resection (sample B). We assessed perioperative changes in inflammatory mediators, including TNF-α, CXCL8, SDF1a, CXCL6, CXCL2, MPO, and CXCL1, as well as leukocyte infiltration.

TNF-α levels differed between groups after supplementation (immune: 31.63 ± 13.28 vs control: 21.54 ± 6.84; p = 0.049) and decreased in the control group from baseline (35.68 ± 24.41 to 21.54 ± 6.84; p = 0.038). CXCL8 expression also declined in the control group (2975.93 ± 1484.04 to 1584.85 ± 1659.84; p = 0.041). CXCL1 increased in the immune group but decreased in controls (2698.27 [1538.14–5124.70] vs 953.75 [457.85–1534.60]; p = 0.032). Both groups exhibited reduced superficial neutrophil infiltration, statistically significant only in the immune group. Surgical outcomes, including complications, length of stay, and readmission rates, were similar across groups. Short-term preoperative immunonutrition appears to alter tumor inflammatory signaling and immune cell infiltration in colorectal cancer, highlighting potential immunomodulatory effects independent of immediate surgical outcomes.