Enteral Immunonutrition for Malignant Gastrointestinal Tumor during Perioperative Period: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

CAO Wei ,  ZHANG Changle

Department of Gastrointestinal Surgery, The First Hospital Affiliated to Anhui Medical University, Hefei 230022, China;

Corresponding author：

ZHANG Changle, Email: aydzcl2004@163.com

Keywords：

Malignant gastrointestinal tumor; Enteral immunonutrition (EIN); Postoperative infection; Length of postoperative hospital stay; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.20130172

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To systematically review the effects of enteral immunonutrition (EIN) on postoperative infection and the length of hospital stay in patients with gastrointestinal cancer after surgery, in order to provide high quality evidence for the rational perioperation nutrition plan for patients with malignant gastrointestinal tumor.
Methods 　Randomized controlled trials (RCTs) published in English about application of EIN vs. general treatment for gastrointestinal surgery published from Jan. 1st, 1997 to Oct. 31st 2012 were retrieved in the following databases: PubMed, Ovid, and EMbase. References of the included studies were also retrieved. According to the inclusion and exclusion criteria, two reviewers independently screened studies, extracted data, and evaluated the methodological quality. Then, meta-analysis was conducted using RevMan 5.2 software.
Results 　19 RCTs involving 2 298 patients were included. The results of meta-analysis showed that: there was no significant difference between the postoperative EIN group and the control group in reducing the risk of postoperative infection (OR=0.91, 95%CI 0.56 to 1.47, P=0.70); But postoperative and perioperative EIN had reduced the risk of postoperative infection with a significant difference (OR=0.57, 95%CI 0.39 to 0.82, P=0.002; OR=0.52, 95%CI 0.35 to 0.76, P=0.000 9). Additionally, the results of sensitivity analysis revealed that: no matter when EIN was used (during preoperative, postoperative, or perioperative periods), it reduced the length of postoperative hospital stay with significant differences, compared to the standard nutrition group (OR= −2.39, 95%CI −3.28 to −1.49, P lt;0.000 01; OR= −2.42, 95%CI −4.07 to −0.78, P=0.004; OR= −2.76, 95%CI −3.46 to −2.06, P lt;0.000 01).
Conclusion 　Current evidence shows that perioperative EIN can decrease postoperative infection and reduce the length of hospital stay of patients with malignant gastrointestinal tumor. Due to the limited quantity and quality of the included studies, high quality RCTs are needed to verify the above conclusion.

Citation： CAO Wei,ZHANG Changle. Enteral Immunonutrition for Malignant Gastrointestinal Tumor during Perioperative Period: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2013, 13(8): 992-1000. doi: 10.7507/1672-2531.20130172 Copy

1.	Bozzetti F, Gianotti L, Braga M, et al. Postoperative complications in gastrointestinal cancer patients: the joint role of the nutritional status and the nutritional support. Clin Nutr, 2007, 26(6): 698-709.
2.	Gianotti L, Braga M, Nespoli L, et al. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology, 2002, 122(7): 1763-1770.
3.	Weimann A, Braga M, Harsanyi L, et al. ESPEN Guidelines on Enteral Nutrition:surgery including organ transplantation. Clin Nutr, 2006, 25(2): 224-244.
4.	Heys SD, Walker LG, Smith I, et al. Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials. Ann Surg, 1999, 229(4): 467-477.
5.	Heyland DK, Novak F, Drover JW, et al. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA, 2001, 286(8): 944-953.
6.	Montejo JC, Zarazaga A, L´ opez-Mart´ınez J, et al. Spanish Society of Intensive Care Medicine and Coronary Units. Immunonutrition in the intensive care unit. A systematic review and consensus statement. Clin Nutr, 2003, 22(3): 221-233.
7.	Gianotti L, Braga M, Vignali A, et al. Effect of route of delivery and formulation of postoperative nutritional support in patients undergoing major operations for malignant neoplasms. Arch Surg, 1997, 132(11): 1222-1229; discussion 1229-1230.
8.	Senkal M, Zumtobel V, Bauer KH, et al. Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: a prospective randomized study. Arch Surg, 1999, 134(12): 1309-1316.
9.	Braga M, Gianotti L, Radaelli G, et al. Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double-blind phase 3 trial. Arch Surg, 1999, 134(4): 428-433.
10.	Di Carlo V, Gianotti L, Balzano G, et al. Complications of pancreatic surgery and the role of perioperative nutrition. Dig Surg, 1999, 16(4): 320-326.
11.	Gianotti L, Braga M, Frei A, et al. Health care resources consumed to treat postoperative infections: cost saving by perioperative immunonutrition. Shock, 2000, 14(3): 325-330.
12.	Braga M, Gianotti L, Vignali A, et al. Preoperative oral arginine and n-3 fatty acid supplementation improves the immunometabolic host response and outcome after colorectal resection for cancer. Surgery, 2002, 132(5): 805-814.
13.	Braga M, Gianotti L, Nespoli L, et al. Nutritional approach in malnourished surgical patients: a prospective randomized study. Arch Surg, 2002, 137(2): 174-180.
14.	Farreras N, Artigas V, Cardona D, et al. Effect of early postoperative enteral immunonutrition on wound healing in patients undergoing surgery for gastric cancer. Clin Nutr, 2005, 24(1): 55-65.
15.	Xu J, Zhong Y, Jing D, et al. Preoperative enteral immunonutrition improves postoperative outcome in patients with gastrointestinal cancer. World J Surg, 2006, 30(7): 1284-1289.
16.	Finco C, Magnanini P, Sarzo G, et al. Prospective randomized study on perioperative enteral immunonutrition in laparoscopic colorectal surgery. Surg Endosc, 2007, 21(7): 1175-1179.
17.	Giger U, Büchler M, Farhadi J, et al. Preoperative immunonutrition suppresses perioperative inflammatory response in patients with major abdominal surgery-a randomized controlled pilot study. Ann Surg Oncol, 2007, 14(10): 2798-2806.
18.	Klek S, Kulig J, Sierzega M, et al. The impact of immunostimulating nutrition on infectious complications after upper gastrointestinal surgery: a prospective, randomized, clinical trial. Ann Surg, 2008, 248(2): 212-220.
19.	Okamoto Y, Okano K, Izuishi K, et al. Attenuation of the systemic inflammatory response and infectious complications after gastrectomy with preoperative oral arginine and omega-3 fatty acids supplemented immunonutrition. World J Surg, 2009 , 33(9): 1815-1821.
20.	Gunerhan Y, Koksal N, Sahin UY, et al. Effect of preoperative immunonutrition and other nutrition models on cellular immune parameters. World J Gastroenterol, 2009, 15(4): 467-472.
21.	Sodergren MH, Jethwa P, Kumar S, et al. Immunonutrition in patients undergoing major upper gastrointestinal surgery: a prospective double-blind randomised controlled study. Scand J Surg, 2010, 99(3): 153-161.
22.	Klek S, Sierzega M, Szybinski P, et al. The immunomodulating enteral nutrition in malnourished surgical patients - a prospective, randomized, double-blind clinical trial. Clin Nutr, 2011, 30(3): 282-288.
23.	Hübner M, Cerantola Y, Grass F, et al. Preoperative immunonutrition in patients at nutritional risk: results of a double-blinded randomized clinical trial. Eur J Clin Nutr, 2012, 66(7): 850-855.
24.	Fujitani K, Tsujinaka T, Fujita J, et al. Osaka Prospective randomized trial of preoperative enteral immunonutrition followed by elective total gastrectomy for gastric cancer. Br J Surg, 2012, 99(5): 621-629.
25.	Sultan J, Griffin SM, Di Franco F, et al. Randomized clinical trial of omega-3 fatty acid-supplemented enteral nutrition versus standard enteral nutrition in patients undergoing oesophagogastric cancer surgery. Br J Surg, 2012, 99(3): 346-355.
26.	Grimble RF. Immunonutrition. Current Opinion in Gastroenterology, 2005, 21(2): 216-222.
27.	郭端, 贾超, 许治华, 等. 肠内免疫营养治疗急性胰腺炎疗效的系统评价. 中国循证医学杂志, 2013, 13(3): 346-351.
28.	Raynold JV, Daly JM, Pyles T. Immunomodulatory mechanisms of arginine. Surgery, 1988, 104(2): 141-151.
29.	Palombo JD, Demichele SJ, Boyce PJ, et al. Effect of short-term enteral feeding with eicosapentaenoic and gamma-linolenic acids on alveolar macrophage eicosanoid synthesis and bactericidal function in rats. Crit Care Med, 1999, 27(9): 1908-1915.
30.	Kinsella JE, Lokesh B, Broughton S, et al. Dietary polyunsaturated fatty acids and eicosanoids: potential effects on the modulation of inflammatory and immune cells:an overview. Nutrition, 1990, 6(1): 24-62.
31.	Hall JC, Hell K, McCauley R. Glutamine. Journal of Surgery, 1996, 83(3): 305-312.
32.	Rudolph FB, Kulkarni AD, Schandle VB, et al. Involvement of dietary nucleotides in T lymphocyte function. Adv Exp Med Biol, 1984, 165(B): 175-178.
33.	Tepaske R, Velthuis H, Oudemans-van Straaten HM, et al. Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomized placebo-controlled trial. Lancet, 2001, 358(9283): 696-701.
34.	Zheng Y, Li F, Qi B, et al. Application of perioperative immunonutrition for gastrointestinal surgery: a meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr, 2007, 16(Suppl 1): 253-257.
35.	Mauskopf JA, Candrilli SD, Chevrou-Séverac H, et al. Immunonutrition for patients undergoing elective surgery for gastrointestinal cancer: impact on hospital costs. World J Surg Oncol, 2012, 6(10): 136.

1. Bozzetti F, Gianotti L, Braga M, et al. Postoperative complications in gastrointestinal cancer patients: the joint role of the nutritional status and the nutritional support. Clin Nutr, 2007, 26(6): 698-709.
2. Gianotti L, Braga M, Nespoli L, et al. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology, 2002, 122(7): 1763-1770.
3. Weimann A, Braga M, Harsanyi L, et al. ESPEN Guidelines on Enteral Nutrition:surgery including organ transplantation. Clin Nutr, 2006, 25(2): 224-244.
4. Heys SD, Walker LG, Smith I, et al. Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials. Ann Surg, 1999, 229(4): 467-477.
5. Heyland DK, Novak F, Drover JW, et al. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA, 2001, 286(8): 944-953.
6. Montejo JC, Zarazaga A, L´ opez-Mart´ınez J, et al. Spanish Society of Intensive Care Medicine and Coronary Units. Immunonutrition in the intensive care unit. A systematic review and consensus statement. Clin Nutr, 2003, 22(3): 221-233.
7. Gianotti L, Braga M, Vignali A, et al. Effect of route of delivery and formulation of postoperative nutritional support in patients undergoing major operations for malignant neoplasms. Arch Surg, 1997, 132(11): 1222-1229; discussion 1229-1230.
8. Senkal M, Zumtobel V, Bauer KH, et al. Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: a prospective randomized study. Arch Surg, 1999, 134(12): 1309-1316.
9. Braga M, Gianotti L, Radaelli G, et al. Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double-blind phase 3 trial. Arch Surg, 1999, 134(4): 428-433.
10. Di Carlo V, Gianotti L, Balzano G, et al. Complications of pancreatic surgery and the role of perioperative nutrition. Dig Surg, 1999, 16(4): 320-326.
11. Gianotti L, Braga M, Frei A, et al. Health care resources consumed to treat postoperative infections: cost saving by perioperative immunonutrition. Shock, 2000, 14(3): 325-330.
12. Braga M, Gianotti L, Vignali A, et al. Preoperative oral arginine and n-3 fatty acid supplementation improves the immunometabolic host response and outcome after colorectal resection for cancer. Surgery, 2002, 132(5): 805-814.
13. Braga M, Gianotti L, Nespoli L, et al. Nutritional approach in malnourished surgical patients: a prospective randomized study. Arch Surg, 2002, 137(2): 174-180.
14. Farreras N, Artigas V, Cardona D, et al. Effect of early postoperative enteral immunonutrition on wound healing in patients undergoing surgery for gastric cancer. Clin Nutr, 2005, 24(1): 55-65.
15. Xu J, Zhong Y, Jing D, et al. Preoperative enteral immunonutrition improves postoperative outcome in patients with gastrointestinal cancer. World J Surg, 2006, 30(7): 1284-1289.
16. Finco C, Magnanini P, Sarzo G, et al. Prospective randomized study on perioperative enteral immunonutrition in laparoscopic colorectal surgery. Surg Endosc, 2007, 21(7): 1175-1179.
17. Giger U, Büchler M, Farhadi J, et al. Preoperative immunonutrition suppresses perioperative inflammatory response in patients with major abdominal surgery-a randomized controlled pilot study. Ann Surg Oncol, 2007, 14(10): 2798-2806.
18. Klek S, Kulig J, Sierzega M, et al. The impact of immunostimulating nutrition on infectious complications after upper gastrointestinal surgery: a prospective, randomized, clinical trial. Ann Surg, 2008, 248(2): 212-220.
19. Okamoto Y, Okano K, Izuishi K, et al. Attenuation of the systemic inflammatory response and infectious complications after gastrectomy with preoperative oral arginine and omega-3 fatty acids supplemented immunonutrition. World J Surg, 2009 , 33(9): 1815-1821.
20. Gunerhan Y, Koksal N, Sahin UY, et al. Effect of preoperative immunonutrition and other nutrition models on cellular immune parameters. World J Gastroenterol, 2009, 15(4): 467-472.
21. Sodergren MH, Jethwa P, Kumar S, et al. Immunonutrition in patients undergoing major upper gastrointestinal surgery: a prospective double-blind randomised controlled study. Scand J Surg, 2010, 99(3): 153-161.
22. Klek S, Sierzega M, Szybinski P, et al. The immunomodulating enteral nutrition in malnourished surgical patients - a prospective, randomized, double-blind clinical trial. Clin Nutr, 2011, 30(3): 282-288.
23. Hübner M, Cerantola Y, Grass F, et al. Preoperative immunonutrition in patients at nutritional risk: results of a double-blinded randomized clinical trial. Eur J Clin Nutr, 2012, 66(7): 850-855.
24. Fujitani K, Tsujinaka T, Fujita J, et al. Osaka Prospective randomized trial of preoperative enteral immunonutrition followed by elective total gastrectomy for gastric cancer. Br J Surg, 2012, 99(5): 621-629.
25. Sultan J, Griffin SM, Di Franco F, et al. Randomized clinical trial of omega-3 fatty acid-supplemented enteral nutrition versus standard enteral nutrition in patients undergoing oesophagogastric cancer surgery. Br J Surg, 2012, 99(3): 346-355.
26. Grimble RF. Immunonutrition. Current Opinion in Gastroenterology, 2005, 21(2): 216-222.
27. 郭端, 贾超, 许治华, 等. 肠内免疫营养治疗急性胰腺炎疗效的系统评价. 中国循证医学杂志, 2013, 13(3): 346-351.
28. Raynold JV, Daly JM, Pyles T. Immunomodulatory mechanisms of arginine. Surgery, 1988, 104(2): 141-151.
29. Palombo JD, Demichele SJ, Boyce PJ, et al. Effect of short-term enteral feeding with eicosapentaenoic and gamma-linolenic acids on alveolar macrophage eicosanoid synthesis and bactericidal function in rats. Crit Care Med, 1999, 27(9): 1908-1915.
30. Kinsella JE, Lokesh B, Broughton S, et al. Dietary polyunsaturated fatty acids and eicosanoids: potential effects on the modulation of inflammatory and immune cells:an overview. Nutrition, 1990, 6(1): 24-62.
31. Hall JC, Hell K, McCauley R. Glutamine. Journal of Surgery, 1996, 83(3): 305-312.
32. Rudolph FB, Kulkarni AD, Schandle VB, et al. Involvement of dietary nucleotides in T lymphocyte function. Adv Exp Med Biol, 1984, 165(B): 175-178.
33. Tepaske R, Velthuis H, Oudemans-van Straaten HM, et al. Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomized placebo-controlled trial. Lancet, 2001, 358(9283): 696-701.
34. Zheng Y, Li F, Qi B, et al. Application of perioperative immunonutrition for gastrointestinal surgery: a meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr, 2007, 16(Suppl 1): 253-257.
35. Mauskopf JA, Candrilli SD, Chevrou-Séverac H, et al. Immunonutrition for patients undergoing elective surgery for gastrointestinal cancer: impact on hospital costs. World J Surg Oncol, 2012, 6(10): 136.

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