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Clinical and Immunological Impact of Early Postoperative Enteral Immunonutrition After Total Gastrectomy in Gastric Cancer Patients: A Prospective Randomized Study

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Enteral immunodiet has been gaining increasing attention, but experimental data of its clinical effects in patients with gastric cancer are inconsistent, contradictory, and poorly investigated. The aim of this study was to assess the impact of early postoperative enteral immunonutrition on clinical and immunological outcomes in a homogeneous group of gastric cancer patients submitted to total gastrectomy.

Methods

A total of 109 patients with gastric cancer were randomized to receive early postoperative enteral immunonutrition (formula supplemented with arginine, omega-3 fatty acids and ribonucleic acid [RNA]), or an isocaloric–isonitrogenous control. The postoperative outcome was evaluated based on clinical variables, including postoperative infectious complications, anastomotic leak rate, and length of hospitalization. In addition, state of cellular immunity was evaluated and compared between the 2 groups.

Results

The incidence of postoperative infectious complications in the immunodiet group (7.4 %) was significantly (p < .05) lower than that of the control group (20 %), as well as the anastomotic leak rate (3.7 % in immunodiet group vs 7.3 % in standard nutrition group, p < .05). Mortality rate did not show any significant differences; patients of the immunodiet group were found to have a significantly reduced length of hospitalization (12.7 ± 2.3 days) when compared with standard diet group (15.9 ± 3.4 days, p = .029). The data on cellular immunity showed that the postoperative CD4+ T-cell counts decreased in both groups, but the reduction in the IED group was significantly higher (p = .032) compared with the SND group.

Conclusions

Early postoperative enteral immunonutrition significantly improves clinical and immunological outcomes in patients undergoing gastrectomy for gastric cancer.

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References

  1. Okamoto Y, Okano K, Izuishi K, Usuki H, Wakabayashi H, Suzuki Y. 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;33:1815–21.

    Article  PubMed  Google Scholar 

  2. Chang HR, Bistrian B. The role of cytokines in the catabolic consequences of infection and injury. JPEN J Parenter Enteral Nutr. 1998;22:156–66.

    Article  PubMed  CAS  Google Scholar 

  3. Bistrian BR, Blackburn GL, Hallowell E, Heddle R. Protein status of general surgical patients. JAMA. 1974;230:858–60.

    Article  PubMed  CAS  Google Scholar 

  4. Nixon DW, Heymsfield SB, Cohen AE, Kutner MH, Ansley J, Lawson DH, et al. Protein-calorie undernutrition in hospitalized cancer patients. Am J Med. 1980;68:683–90.

    Article  PubMed  CAS  Google Scholar 

  5. Meakins JL. Host defense mechanisms in surgical patients: effect of surgery and trauma. Acta Chir Scand Suppl. 1989;550:43–53.

    PubMed  CAS  Google Scholar 

  6. Decker D, Schoendorf M, Bidlingmaier F, Himer A, von Ruecker AA. Surgical stress induces a shift in the type-1/type-2 T-helper cell balance, suggesting down-regulation of cell-mediated and up-regulation of antibody-mediated immunity commensurate to the trauma. Surgery. 1996;119:316–25.

    Article  PubMed  CAS  Google Scholar 

  7. Klek S, Sierzega M, Szybinski P, Szczepanek K, Scislo L, Walewska E, et al. The immunomodulating enteral nutrition in malnourished surgical patients―a prospective, randomized, double-blind clinical trial. Clin Nutr. 2011;30:282–8.

    Article  PubMed  Google Scholar 

  8. Fujitani K, Tsujinaka T, Fujita J, Miyashiro I, Imamura H, Kimura Y, et al. Prospective randomized trial of preoperative enteral immunonutrition followed by elective total gastrectomy for gastric cancer. Br J Surg. 2012;99:621–9.

    Article  PubMed  CAS  Google Scholar 

  9. Bonenkamp JJ, Songun I, Hermans J, Sasako M, Welvaart K, Plukker JT, et al. Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet. 1995;345:745–8.

    Article  PubMed  CAS  Google Scholar 

  10. Cuschieri A, Fayers P, Fielding J, Craven J, Bancewicz J, Joypaul V, et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. Lancet. 1996;347:995–9.

    Article  PubMed  CAS  Google Scholar 

  11. Maruyama T, Mimura K, Izawa S, Shiba S, Watanabe M, Kawaguchi Y, et al. Immunonutritional diet modulates natural killer cell activation and Th17 cell distribution in patients with gastric and esophageal cancer. Nutrition. 2011;27:146–52.

    Article  PubMed  CAS  Google Scholar 

  12. Druyan ME, Compher C, Boullata JI, Braunschweig CL, George DE, Simpser E, et al. Clinical Guidelines For the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients: applying the GRADE system to development of A.S.P.E.N. clinical guidelines. JPEN J Parenter Enteral Nutr. 2012;36:77–80.

    Article  PubMed  Google Scholar 

  13. Weimann A, Braga M, Harsanyi L, Laviano A, Ljungqvist O, Soeters P, et al. ESPEN guidelines on enteral nutrition: surgery including organ transplantation. Clin Nutr. 2006;25:224–44.

    Article  PubMed  CAS  Google Scholar 

  14. Senkal M, Zumtobel V, Bauer KH, Marpe B, Wolfram G, Frei A, 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;134:1309–16.

    Article  PubMed  CAS  Google Scholar 

  15. Gianotti L, Braga M, Frei A, Greiner R, Di Carlo V. Health care resources consumed to treat postoperative infections: cost saving by perioperative immunonutrition. Shock. 2000;14:325–30.

    Article  PubMed  CAS  Google Scholar 

  16. Klek S, Kulig J, Sierzega M, Szybinski P, Szczepanek K, Kubisz A, et al. The impact of immunostimulating nutrition on infectious complications after upper gastrointestinal surgery: a prospective, randomized, clinical trial. Ann Surg. 2008;248:212–20.

    Article  PubMed  Google Scholar 

  17. Senkal M, Kemen M, Homann HH, Eickhoff U, Baier J, Zumtobel V. Modulation of postoperative immune response by enteral nutrition with a diet enriched with arginine, RNA, and omega-3 fatty acids in patients with upper gastrointestinal cancer. Eur J Surg. 1995;161:115–22.

    PubMed  CAS  Google Scholar 

  18. Heys SD, Walker LG, Smith I, Eremin O. 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: 467–77.

    Article  PubMed  CAS  Google Scholar 

  19. Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA. 2001;286:944–53.

    Article  PubMed  CAS  Google Scholar 

  20. Montejo JC, Zarazaga A, Lòpez-Martìnez J, Urrùtia G, Roquè M, Blesa AL, et al. Immunonutrition in the intensive care unit. A systematic review and consensus statement. Clin Nutr. 2003;22:221–33.

    Article  PubMed  Google Scholar 

  21. Zheng Y, Li F, Qi B, Luo B, Sun H, Liu S, 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):253–7.

    PubMed  Google Scholar 

  22. Farreras N, Artigas V, Cardona C, Rius X, Trias M, Gonzàlez JA. Effect of early postoperative enteral immunonutrition on wound healing in patients undergoing surgery for gastric cancer. Clin Nutr. 2005;24:55–65.

    Article  PubMed  Google Scholar 

  23. Daly JM, Lieberman MD, Goldfine J, Shou J, Weintraub F, Rosato EF, et al. Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome. Surgery. 1992;112:56–67.

    PubMed  CAS  Google Scholar 

  24. Atkinson S, Sieffert E, Bihari D. A prospective, randomized, double-blind, controlled clinical trial of enteral immunonutrition in the critically ill. Crit Care Med. 1998;26:1164–72.

    Article  PubMed  CAS  Google Scholar 

  25. Braga M, Gianotti L, Radaelli G, Vignali A, Mari G, Gentilini O, et al. Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double-blind phase 3 trial. Arch Surg. 1999;134:428–33.

    Article  PubMed  CAS  Google Scholar 

  26. Galban C, Montejo JC, Mesejo A, Marco P, Celaya S, Sánchez-Segura JM, et al. An immune-enhancing enteral diet reduces mortality and episodes of bacteremia in septic ICU patients. Crit Care Med. 2000;28:643–8.

    Article  PubMed  CAS  Google Scholar 

  27. Gianotti L, Braga M, Fortis C, Soldini L, Vignali A, Colombo S, et al. A prospective, randomized clinical trial on perioperative feeding with arginine-, omega-3 fatty acid, and RNA-enriched enteral diet. Effect on host response and nutritional status. JPEN J Parenter Enteral Nutr. 1999;23:314–20.

    Article  PubMed  CAS  Google Scholar 

  28. Giger U, Büchler M, Farhadi J, Berger D, Hüsler J, Schneider H, et al. Preoperative immunonutrition suppresses perioperative inflammatory response in patients with major abdominal surgery―a randomized controlled pilot study. Ann Surg Oncol. 2007;4:2798–806.

    Article  Google Scholar 

  29. Beale RJ, Bryg DJ, Bihari DJ. Immunonutrition in the critically ill: a systematic review of clinical outcome. Crit Care Med. 1999;27:2799–805.

    Article  PubMed  CAS  Google Scholar 

  30. Sultan J, Griffin SM, Di Franco F, Kirby JA, Shenton BK, Seal CJ, 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;99:346–55.

    Article  PubMed  CAS  Google Scholar 

  31. Gianotti L, Braga M, Nespoli L, Radaelli G, Beneduce A, Di Carlo V. A randomised controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology. 2002;122:1763–70.

    Article  PubMed  CAS  Google Scholar 

  32. Senkal M, Mumme A, Eickhoff U, Geier B, Späth G, Wulfert D, et al. Early postoperative enteral immunonutrition: clinical outcome and cost-comparison analysis in surgical patients. Crit Care Med. 1997;25:1489–96.

    Article  PubMed  CAS  Google Scholar 

  33. Braga M, Gianotti L, Nespoli L, Radaelli G, Di Carlo V. Nutritional approach in malnourished surgical patients: a prospective randomized study. Arch Surg. 2002;137:174–80.

    Article  PubMed  Google Scholar 

  34. Braga M, Gianotti L, Vignali A, Carlo VD. Preoperative oral arginine and n-3 fatty acid supplementation improves the immunometabolic host response and outcome after colorectal resection for cancer. Surgery. 2002;132:805–14.

    Article  PubMed  Google Scholar 

  35. Gunerhan Y, Koksal N, Sahin UY, Uzun MA, Ek□ioglu-Demiralp E. Effect of preoperative immunonutrition and other nutrition models on cellular immune parameters. World J Gastroenterol. 2009;15:467–72.

    Article  PubMed  Google Scholar 

  36. Lobo DN, Williams RN, Welch NT, Aloysius MM, Nunes QM, Padmanabhan J, et al. Early postoperative jejunostomy feeding with an immune modulating diet in patients undergoing resectional surgery for upper gastrointestinal cancer: a prospective, randomized, controlled, double-blind study. Clin Nutr. 2006;25:716–26.

    Article  PubMed  Google Scholar 

  37. Heslin MJ, Latkany L, Leung D, Brooks AD, Hochwald SN, Pisters PW, et al. A prospective, randomised trial of early enteral feeding after resection of upper gastrointestinal malignancy. Ann Surg. 1997;226:567–80.

    Article  PubMed  CAS  Google Scholar 

  38. Kondrup J, Allison SP, Elia M, Vellas B, Plauth M, Educational and Clinical Practice Committee, European Society of Parenteral and Enteral Nutrition (ESPEN). ESPEN guidelines for nutrition screening 2002. Clin Nutr. 2003;22:415–21.

    Article  PubMed  CAS  Google Scholar 

  39. Japan Gastric Cancer Association. Japanese classification of gastric carcinoma. 13th ed. Tokyo: Japan Gastric Cancer Association; 1999.

    Google Scholar 

  40. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. ACCP/SCCM Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:1644–55.

    Article  PubMed  CAS  Google Scholar 

  41. Xu J, Zhong Y, Jing D, Wu Z. Preoperative enteral immunonutrition improves postoperative outcome in patients with gastrointestinal cancer. World J Surg. 2006;30:1284–9.

    Article  PubMed  Google Scholar 

  42. Christou NV, Meakins JL, Gordon J, Yee J, Hassan-Zahraee M, Nohr CW, et al. The delayed hypersensitivity response and host resistance in surgical patients. 20 years later. Ann Surg. 1995;222:534–46.

    PubMed  CAS  Google Scholar 

  43. Lundy J, Lovett EJIII, Wolinsky SM, Conran P. Immune impairment and metastatic tumor growth: the need for an immunorestorative drug as an adjunct to surgery. Cancer. 1979;43:945–51.

    Article  PubMed  CAS  Google Scholar 

  44. Kudsk KA, Tolley EA, DeWitt RC, Janu PG, Blackwell AP, Yeary S, et al. Preoperative albumin and surgical site identify surgical risk for major postoperative complications. JPEN J Parenter Enteral Nutr. 2003;27:1–9.

    Article  PubMed  Google Scholar 

  45. Moore FA, Feliciano DV, Andrassy RJ, McArdle AH, Booth FV, Morgenstein-Wagner TB, et al. Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis. Ann Surg. 1992;216:172–83.

    Article  PubMed  CAS  Google Scholar 

  46. Helminen H, Raitanen M, Kellosalo J. Immunonutrition in elective gastrointestinal surgery patients. Scand J Surg. 2007;96:46–50.

    PubMed  CAS  Google Scholar 

  47. Sacks GS, Genton L, Kudsk KA. Controversy of immunonutrition for surgical critical-illness patients. Curr Opin Crit Care. 2003;9:300–5.

    Article  PubMed  Google Scholar 

  48. Daly JM, Weintraub FN, Shou J, Rosato EF, Lucia M. Enteral nutrition during multimodality therapy in upper gastrointestinal cancer patients. Ann Surg. 1995;221:327–38.

    Article  PubMed  CAS  Google Scholar 

  49. Schilling J, Vranjes N, Fierz W, Joller H, Gyurech D, Ludwig E, et al. Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids, and nucleotide-enriched enteral feeding: a randomized prospective comparison with standard enteral and low calorie/low fat i.v. solutions. Nutrition. 1996;12:423–9.

    Article  PubMed  CAS  Google Scholar 

  50. Kudsk KA. Immunonutrition in surgery and critical care. Annu Rev Nutr. 2006;26:463–79.

    Article  PubMed  CAS  Google Scholar 

  51. Cerantola Y, Hübner M, Grass F, Dermartines N, Schäfer M. Immunonutrition in gastrointestinal surgery. Br J Surg. 2011;98:37–48.

    Article  PubMed  CAS  Google Scholar 

  52. Braga M, Gianotti L, Vignali A, Carlo VD. Immunonutrition in gastric cancer surgical patients. Nutrition. 1998;14:831–5.

    Article  PubMed  CAS  Google Scholar 

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All authors have no conflict of interest or financial ties to disclose.

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Authors and Affiliations

  1. 8th General and Gastrointestinal Surgery—Department of Internal Medicine, Surgical, Neurological Metabolic Disease and Geriatric Medicine, Second University of Naples, Naples, Italy

    Luigi Marano MD, Raffaele Porfidia MD, Modestino Pezzella MD, Michele Grassia MD, Marianna Petrillo MD, Giuseppe Esposito MD, Bartolomeo Braccio MD, PierLuigi Gallo MD, Virginia Boccardi MD, Angelo Cosenza MD, Giuseppe Izzo MD & Natale Di Martino MD

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  1. Luigi Marano MD
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Marano, L., Porfidia, R., Pezzella, M. et al. Clinical and Immunological Impact of Early Postoperative Enteral Immunonutrition After Total Gastrectomy in Gastric Cancer Patients: A Prospective Randomized Study. Ann Surg Oncol 20, 3912–3918 (2013). https://doi.org/10.1245/s10434-013-3088-1

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