RANDOMIZED CONTROLLED TRIAL The Impact of Immunostimulating Nutrition on Infectious Complications After Upper Gastrointestinal Surgery A Prospective, Randomized, Clinical Trial Stanislaw Klek, MD, PhD, Jan Kulig, PhD, Marek Sierzega, PhD, Piotr Szybinski, PhD, Kinga Szczepanek, MD, Aldona Kubisz, PhD, Tomasz Kowalczyk, MD, Tomasz Gach, MD, Radoslaw Pach, MD, and Antoni M. Szczepanik, PhD Background and Aim: Immunomodulating nutrition is supposed to reduce the number of complications and lengthen of hospital stay during the postoperative period in patients after major gastrointes- tinal surgery. The aim of the study was to assess the clinical effect of immunostimulatory enteral and parenteral nutrition in patients undergoing resection for gastrointestinal cancer in the group of well-nourished patients. Material and Methods: Between June 1, 2001, and December 31, 2005, a group of 214 well-nourished patients was initially assessed (150 men, 64 women, mean age 61.2 years) to participate in the study. Nine patients were subsequently excluded and the remaining 205 subjects were randomly assigned in a 2  2 factorial design into 4 study groups, ie, standard enteral nutrition (n = 53), immuno- modulating enteral nutrition (n = 52), standard parenteral nutrition (n = 49), and immunomodulating enteral nutrition (n = 51). The study was designed to test the hypothesis that immunonutrition and enteral nutrition would reduce the incidence of infectious compli- cations after upper gastrointestinal surgery; the secondary objective of the study was to evaluate the effect of nutritional intervention on overall morbidity and mortality rates, and hospital stay. The study was registered in the Clinical Trials Database–number NCT 00558155. Results: The overall morbidity rate was 33% and the incidence of individual complications was comparable between all groups. Infec- tious complications occurred in 26 of 102 patients given standard diets and in 22 of 103 patients receiving immunomodulatory for- mulas (odds ratio 0.81; 95% CI, 0.43–1.50). There were no signif- icant differences between infectious complications in patients using parenteral nutrition (22 of 100 patients) and parenteral formulas (26 of 105, odds ratio 1.14; 95% CI, 0.61–2.14). Neither immunos- timulating formulas nor enteral feeding significantly affected sec- ondary outcome measures, including overall morbidity and mortality rates, and hospital stay. Conclusions: Our study failed to demonstrate any clear advantage of routine postoperative immunonutrition in patients undergoing elec- tive upper gastrointestinal surgery. Both enteral and parenteral treat- ment options showed similar efficacy, tolerance, and effects on protein synthesis. Parenteral nutrition composed according to contemporary rules showed similar efficiency to enteral nutrition. However, be- cause of its cost-efficiency, enteral therapy should be considered as the treatment of choice in all patients requiring nutritional therapy. (Ann Surg 2008;248: 212–220) N utritional therapy is the unquestionable treatment option for various groups of patients; not only for the severely malnourished or seriously ill, but also for many surgical patients. 1,2 However, it has been recently demonstrated that perioperative nutritional support improves postoperative out- come but only in selected groups of patients. 3,4 The latter population includes mostly severely malnourished individu- als and those subject to major surgical procedures, such as esophagectomy, pancreatectomy, and gastrectomy. Although the need for nutritional intervention in surgical patients ex- posed to higher risk of malnutrition-related complications has been formulated into evidence-based guidelines, several is- sues remain to be determined. 1,5 One issue is the preferred route of dietary support. Numerous clinical trials have proven that enteral nutrition is at least as efficient as parenteral, but is easier and associated with fewer complications, mostly related to the central venous catheter. Therefore, the enteral route is currently recommended as the treatment of choice in patients requiring nutritional support. 1,6–8 Still, some surgical centers prefer the parenteral route during the postoperative period, or combine it with enteral nutrition if adequate energy needs cannot be provided through the gastrointestinal tract. 8 The primary goal of nutritional therapy focusing on providing the body with necessary calories and substrates to cover a patient’s needs has changed during the last decade to approaches aimed at restoring optimal metabolic and immune responses. This objective is based on the evidence that some dietary components can provide beneficial effects beyond just From the Department of Surgery, Jagiellonian University Medical College, Krakow, Poland. Reprints: Stanislaw Klek, MD, PhD, Department of Surgery, Jagiellonian University Medical College, 40 Kopernika Street, 31-501 Krakow, Poland. E-mail: klek@poczta.onet.pl. Copyright © 2008 by Lippincott Williams & Wilkins ISSN: 0003-4932/08/24802-0212 DOI: 10.1097/SLA.0b013e318180a3c1 Annals of Surgery • Volume 248, Number 2, August 2008 212