Advertisement

Annals of Surgical Oncology

, Volume 20, Issue 12, pp 3912–3918 | Cite as

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

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

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.

Keywords

Gastric Cancer Gastric Cancer Patient Enteral Nutrition Total Gastrectomy Anastomotic Leak Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Disclosure

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

References

  1. 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.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 3.
    Bistrian BR, Blackburn GL, Hallowell E, Heddle R. Protein status of general surgical patients. JAMA. 1974;230:858–60.PubMedCrossRefGoogle Scholar
  4. 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.PubMedCrossRefGoogle Scholar
  5. 5.
    Meakins JL. Host defense mechanisms in surgical patients: effect of surgery and trauma. Acta Chir Scand Suppl. 1989;550:43–53.PubMedGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.PubMedCrossRefGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 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.CrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 39.
    Japan Gastric Cancer Association. Japanese classification of gastric carcinoma. 13th ed. Tokyo: Japan Gastric Cancer Association; 1999.Google Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 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.PubMedCrossRefGoogle Scholar
  42. 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.PubMedGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 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.PubMedCrossRefGoogle Scholar
  46. 46.
    Helminen H, Raitanen M, Kellosalo J. Immunonutrition in elective gastrointestinal surgery patients. Scand J Surg. 2007;96:46–50.PubMedGoogle Scholar
  47. 47.
    Sacks GS, Genton L, Kudsk KA. Controversy of immunonutrition for surgical critical-illness patients. Curr Opin Crit Care. 2003;9:300–5.PubMedCrossRefGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 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.PubMedCrossRefGoogle Scholar
  50. 50.
    Kudsk KA. Immunonutrition in surgery and critical care. Annu Rev Nutr. 2006;26:463–79.PubMedCrossRefGoogle Scholar
  51. 51.
    Cerantola Y, Hübner M, Grass F, Dermartines N, Schäfer M. Immunonutrition in gastrointestinal surgery. Br J Surg. 2011;98:37–48.PubMedCrossRefGoogle Scholar
  52. 52.
    Braga M, Gianotti L, Vignali A, Carlo VD. Immunonutrition in gastric cancer surgical patients. Nutrition. 1998;14:831–5.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2013

Authors and Affiliations

  • Luigi Marano
    • 1
  • Raffaele Porfidia
    • 1
  • Modestino Pezzella
    • 1
  • Michele Grassia
    • 1
  • Marianna Petrillo
    • 1
  • Giuseppe Esposito
    • 1
  • Bartolomeo Braccio
    • 1
  • PierLuigi Gallo
    • 1
  • Virginia Boccardi
    • 1
  • Angelo Cosenza
    • 1
  • Giuseppe Izzo
    • 1
  • Natale Di Martino
    • 1
  1. 1.8th General and Gastrointestinal Surgery—Department of Internal Medicine, Surgical, Neurological Metabolic Disease and Geriatric MedicineSecond University of NaplesNaplesItaly

Personalised recommendations