The Effect of Perioperative Nutrient Status on Post-Radical Cystoprostatectomy Complications

Abstract

Introduction Radical Cystoprostatectomy (RC) is a major surgery for the treatment of muscle-invasive urinary bladder cancer with high postoperative complication rates. Evidence suggests surgeries such as RC induce arginine deficiency, leading to immunosuppression and morbidity. The supplementation of specialized immunonutrition (SIM), containing L-arginine, omega-3 fatty acids, RNA nucleotides, and vitamin A, has shown to improve postoperative outcomes in other surgical cohorts. The purpose of this project is to investigate the effects of perioperative SIM to meet nutrient demands and improve outcomes following RC. Methods Men undergoing RC at the University of Kansas Hospital (KUH) were randomized to receive either SIM (Impact Advanced Recovery®) or the oral nutrition supplement (ONS, Boost Plus®) drink. The study participants were blind to the intervention and consumed the supplements 5 days before and after surgery. Plasma arginine, citrulline, and ornithine concentrations were measured at days -6, 0, 2, 14, and 30. Early (0-30 days) and late (31-90 days) complications were graded based on the Clavien-Dindo scheme. Fisher’s exact tests, T-tests, and linear mixed effect models were used to detect differences in outcomes. Results The SIM and ONS groups experienced 71% and 73% early complication rates (P = 1), and 14% and 43% late complication rates (P = 0.21), respectively. The SIM group had a non-significantly lower rate of antibiotic use in the late period (14%) compared to the ONS group (50%, P = 0.10). Plasma arginine significantly decreased from baseline to POD2 (P = 0.0003) in the ONS group, with no significant change in the SIM group. There was no significant difference in plasma arginine and citrulline concentrations between the two groups over time (P 0.05). There was a significant difference between in plasma ornithine concentrations between the two groups over time (P = 0.04). At the time of surgery, the SIM group had significantly higher plasma ornithine compared to ONS (P = 0.001). Conclusion The perioperative supplementation of SIM in RC patients induces a shift in metabolism of amino acids related to immune function and wound healing. Though SIM supplementation was unable to fully replete arginine status by surgery, the supplementation prevented a further depletion in plasma arginine following surgery. The trend toward lower infection rates in the SIM group suggests preserved immune function. A greater amount of arginine may be necessary to fully replete this population and optimize immune function following surgery. Additionally, the SIM supplementation produced an increase in plasma ornithine concentration at the time of surgery, which may enhance wound healing. More research is needed to confirm the benefits of SIM in the RC cohort.