Background: Immunonutrition (IN) significantly reduces the incidence of postoperative infectious complications and the length of hospitalization in patients undergoing major elective surgery for gastrointestinal malignances. However, the clinical benefit of IN in patients who have undergone esophagectomy for esophageal cancer is unclear. Moreover, the effect of enteral IN in patients during preoperative adjuvant chemoradiotherapy and in patients treated with concurrent chemoradiotherapy for advanced esophageal cancer is unknown. Summary: This review analyzes the evidence supporting the enteral administration of IN in patients who have undergone esophagectomy and/or chemoradiotherapy for esophageal cancer. Twelve trials that evaluated IN exclusively in patients who underwent esophagectomy were published between January 1980 and August 2017. Two trials concerning IN during chemoradiotherapy for esophageal cancer were identified in the same period. However, the evidence is insufficient to recommend enteral IN in patients who have undergone esophagectomy and/or chemoradiotherapy for esophageal cancer. Key Message: Further evidence from well-designed randomized controlled trials is required to verify the clinical benefits of enteral IN in patients undergoing esophagectomy and/or chemoradiotherapy for esophageal cancer. Practical Implications: Resolvins, which are generated from EPA, are novel anti-inflammatory lipid mediators and may play a key role in the resolution of acute inflammation when IN is supplemented with EPA in patients undergoing severely stressful operations.

Keywords:
Chemoradiotherapy, Esophageal cancer, Immunonutrition, Surgery
1.
Bozzetti F: Screening the nutritional status in oncology: a preliminary report on 1,000 outpatients. Support Care Cancer 2009;17:279-284.
2.
Daly JM, Fry WA, Little AG, et al: Esophageal cancer: results of an American College of Surgeons Patient Care Evaluation Study. J Am Coll Surg 2000;190:562-572; discussion 572-573.
3.
Van der Schaaf MK, Tilanus HW, van Lanschot JJ, et al: The influence of preoperative weight loss on the postoperative course after esophageal cancer resection. J Thorac Cardiovasc Surg 2014;147:490-495.
4.
Correia MI, Caiaffa WT, da Silva AL, et al: Risk factors for malnutrition in patients undergoing gastroenterological and hernia surgery: an analysis of 374 patients. Nutr Hosp 2001;16:59-64.
5.
Marin FA, Lamônica-Garcia VC, Henry MA, et al: Grade of esophageal cancer and nutritional status impact on postsurgery outcomes. Arq Gastroenterol 2010;47:348-353.
6.
Braga M, Ljungqvist O, Soeters P, et al: ESPEN Guidelines on Parenteral Nutrition: surgery. Clin Nutr 2009;28:378-386.
7.
Johansen N, Kondrup J, Plum LM, et al: Effect of nutritional support on clinical outcome in patients at nutritional risk. Clin Nutr 2004;23:539-550.
8.
Jie B, Jiang ZM, Nolan MT, et al: Impact of nutritional support on clinical outcome in patients at nutritional risk: a multicenter, prospective cohort study in Baltimore and Beijing teaching hospitals. Nutrition 2010;26:1088-1093.
9.
Wang JY, Hong X, Chen GH, et al: Clinical application of the fast track surgery model based on preoperative nutritional risk screening in patients with esophageal cancer. Asia Pac J Clin Nutr 2015;24:206-211.
10.
Braga M, Wischmeyer PE, Drover J, et al: Clinical evidence for pharmaconutrition in major elective surgery. JPEN J Parenter Enteral Nutr 2013;37(5 suppl):66S-72S.
11.
Cerantola Y, Hübner M, Grass F, et al: Immunonutrition in gastrointestinal surgery. Br J Surg 2011;98:37-48.
12.
Marimuthu K, Varadhan KK, Liungqvist O, et al: A meta-analysis of the effect of combinations of immune modulating nutrients on outcome in patients undergoing major open gastrointestinal surgery. Ann Surg 2012;255:1060-1068.
13.
Zhang Y, Gu Y, Guo T, et al: Perioperative immunonutrition for gastrointestinal cancer: a systematic review of randomized controlled trials. Surg Oncol 2012;21:e87-e95.
14.
Weimann A, Braga M, Harsanyi L, et al: ESPEN Guidelines on Enteral Nutrition: surgery including Organ Transplantation. Clin Nutr 2006;25:224-244.
15.
Wong CS, Aly EH: The effects of enteral immunonutrition in upper gastrointestinal surgery: a systematic review and meta-analysis. Int J Surg 2016:29:137-150.
16.
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;99:346-355.
17.
Hallay J, Kovács G, Kiss S, et al: Changes in the nutritional state and immune-serological parameters of esophagectomized patients fed jejunaly with glutamine-poor and glutamine-rich nutriments. Hepatogastroenterology 2002;49:1555-1559.
18.
Sakurai Y, Masui T, Yoshida I, et al: Randomized clinical trial of the effects of preoperative use of immune-enhancing enteral formula on metabolic and immunological status in patients undergoing esophagectomy. World J Surg 2007;31:2150-2157.
19.
Takeuchi H, Ikeuchi S, Kawaguchi Y, et al: Clinical significance of perioperative immunonutrition for patients with esophageal cancer. World J Surg 2007;31:2160-2167.
20.
Aiko S, Yoshizumi Y, Ishizuka T, et al: Enteral immune-enhanced diets with arginine are safe and beneficial for patients early after esophageal cancer surgery. Dis Esophagus 2008;21:619-627.
21.
Fukuda T, Seto K, Yamada K, et al: Can immune-enhancing nutrients reduce postoperative complications in patients undergoing esophageal surgery? Dis Esophagus 2008;21:708-711.
22.
Ryan AM, Reynolds JV, Healy L, et al: Enteral nutrition enriched with eicosapentaenoic acid (EPA) preserves lean body mass following esophageal cancer surgery: results of a double-blinded randomized controlled trial. Ann Surg 2009;249:355-363.
23.
Aiko S, Kumano I, Yamanaka N, et al: Effects of an immune-enhanced diet containing antioxidants in esophageal cancer surgery following neoadjuvant therapy. Dis Esophagus 2012;25:137-145.
24.
Nagano T, Fujita H, Tanaka T, et al: A randomized controlled trial comparing antioxidant-enriched enteral nutrition with immune-enhancing enteral nutrition after esophagectomy for cancer: a pilot study. Surg Today 2013;43:1240-1249.
25.
Kubota K, Kuroda J, Yoshida M, et al: Preoperative oral supplementation support in patients with esophageal cancer. J Nutr Health Aging 2014;18:437-440.
26.
Matsuda Y, Habu D, Lee S, et al: Enteral diet enriched with ω-3 fatty acid improves oxygenation after thoracic esophagectomy for cancer: a randomized controlled trial. World J Surg 2017;41:1584-1594.
27.
Kitagawa H, Namikawa T, Yatabe T, Munekage M, Yamasaki F, Kobayashi M, Hanazaki K: Effects of a preoperative immune-modulating diet in patients with esophageal cancer: a prospective parallel group randomized study. Langenbecks Arch Surg 2017;402:531-538.
28.
Healy LA, Ryan A, Doyle SL, et al: Does prolonged enteral feeding with supplemental omega-3 fatty acids impact on recovery post-esophagectomy: results of a randomized double-blind trial. Ann Surg 2017;266:720-728.
29.
Zhou M, Martindale RG: Arginine in the critical care setting. J Nutr 2007;137(6 suppl 2):1687S-1692S.
30.
Mudge L, Isenring E, Jamieson GG: Immunonutrition in patients undergoing esophageal cancer resection. Dis Esophagus 2011;24:160-165.
31.
Bertolini G, Lapichino G, Radrizzani D, et al: Early enteral immunonutrition in patients with severe sepsis: results of an interim analysis of a randomized multicenter clinical trial. Intensive Care Med 2003;29:834-840.
32.
Dent DL, Heyland DK, Levy H, et al: Immunonutrition may increase mortality in critically ill patients with pneumonia: results of a randomized trial. Crit Care Med 2003;30:A17.
33.
McClave SA, Martindale RG, Vanek VW, et al: Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2009;33:277-316.
34.
Yoshida S, Matsui M, Shirouzu Y, et al: Effects of glutamine supplements and radiochemotherapy on systemic immune and gut barrier function in patients with advanced esophageal cancer. Ann Surg 1988;227:485-491.
35.
Sunpaweravong S, Puttawibul P, Ruangsin S, et al: Randomized study of antiinflammatory and immune-modulatory effects of enteral immunonutrition during concurrent chemoradiotherapy for esophageal cancer. Nutr Cancer 2014;66:1-5.
36.
Kubota H, Matsumoto H, Higashida M, et al: Eicosapentaenoic acid modifies cytokine activity and inhibits cell proliferation in an oesophageal cancer cell line. Anticancer Res 2013;33:4319-4324.
37.
Mizoguchi K, Ishiguro H, Kimura M, et al: Induction of apoptosis by eicosapentaenoic acid in esophageal squamous cell carcinoma. Anticancer Res 2014;34:7145-7150.
38.
Chen H, Ward MH, Graubard BI, et al: Dietary patterns and adenocarcinoma of the esophagus and distal stomach. Am J Clin Nutr 2002;75:137-144.
39.
Wilson KT, Fu S, Ramanujam KS, et al: Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas. Cancer Res 1998;58:2929-2934.
40.
Mehta SP, Boddy AP, Cook J, et al: Effect of n-3 polyunsaturated fatty acids on Barrett's epithelium in the human lower esophagus. Am J Clin Nutr 2008;87:949-956.
41.
Osland E, Hossain MB, Khan S, et al: Effect of timing of pharmaconutrition (immunonutrition) administration on outcomes of elective surgery for gastrointestinal malignancies: a systematic review and meta-analysis. JPEN J Parenter Enteral Nutr 2014;38:53-69.
42.
Fujitani K, Tsujinaka T, Fujita J, et al: Prospective randomized trial of preoperative enteral immunonutrition followed by elective total gastrectomy for gastric cancer. Br J Surg 2012;99:621-629.
43.
Serhan CN, Clish CB, Brannon J, et al: Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med 2000;192:1197-1204.
44.
Moro K, Nagahashi M, Ramanathan R, et al: Resolvins and omega three polyunsaturated fatty acids: clinical implications in inflammatory diseases and cancer. World J Clin Cases 2016;4:155-164.
45.
Uno H, Furukawa K, Suzuki D, et al: Immunonutrition suppresses acute inflammatory responses through modulation of resolvin E1 in patients undergoing major hepatobiliary resection. Surgery 2016;160:228-236.
© 2017 S. Karger AG, Basel
2017
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.