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Effects of a preoperative immune-modulating diet in patients with esophageal cancer: a prospective parallel group randomized study

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Abstract

Purpose

The aim of this pilot study was to investigate the effects of a preoperative immune-modulating diet (IMD) before thoracoscopic esophagectomy for patients with esophageal cancer.

Methods

Thirty patients who were diagnosed with resectable esophageal cancer were assigned to two groups: the IMD (n = 15) and the standard liquid diet (SLD; n = 15) groups. We evaluated postoperative parameters, such as the incidence of complications and the postoperative levels of cytokines as the primary endpoints. The secondary endpoint was the length of hospital stay.

Results

The peak levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α appeared on postoperative day (POD) 1 and POD 2 in the IMD and SLD group, respectively. The peak level of C-reactive protein (CRP) appeared on POD 3 in both groups (IMD 9.9 mg/dL, SLD 15.2 mg/dL).

Overall, TNF-α levels in the IMD group were lower than those in the SLD group (P = 0.033). Furthermore, IL-6 (P = 0.182) and CRP (P = 0.191) levels, and the incidence of postoperative pneumonia (7.1 vs. 26.7%; P = 0.330) tended to be lower in the IMD group than in the SLD group.

Conclusions

Preoperative IMD suppressed the elevation of the TNF-α levels after thoracoscopic esophagectomy in patients with esophageal cancer, although no different tendency was detected in terms of IL-6, CRP or postoperative complications.

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References

  1. Morita M, Nakanoko T, Fujinaka Y, Kubo N, Yamashita N, Yoshinaga K, Saeki H, Emi Y, Kakeji Y, Shirabe K, Maehara Y (2011) In-hospital mortality after a surgical resection for esophageal cancer: analyses of the associated factors and historical changes. Ann Surg Oncol 18:1757–1765

    Article  PubMed  Google Scholar 

  2. Takeuchi H, Miyata H, Gotoh M, Kitagawa Y, Baba H, Kimura W, Tomita N, Nakagoe T, Shimada M, Sugihara K, Mori M (2014) A risk model for esophagectomy using data of 5354 patients included in a Japanese nationwide web-based database. Ann Surg 260:259–266

    Article  PubMed  Google Scholar 

  3. Findlay JM, Gillies RS, Millo J, Sgromo B, Marshall RE, Maynard ND (2014) Enhanced recovery for esophagectomy: a systematic review and evidence-based guidelines. Ann Surg 259:413–431

    Article  PubMed  Google Scholar 

  4. Weimann A, Braga M, Harsanyi L, Laviano A, Ljungqvist O, Soeters P, DGEM (German Society for Nutritional Medicine), Jauch KW, Kemen M, Hiesmayr JM, Horbach T, Kuse ER, Vestweber KH, ESPEN (European Society for Parenteral and Enteral Nutrition) (2006) ESPEN guidelines on enteral nutrition: surgery including organ transplantation. Clin Nutr 25:224–244

    Article  CAS  PubMed  Google Scholar 

  5. ASPEN (2002) Board of Directors and the Clinical Guidelines Task Force Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enteral Nutr 26 (1 Suppl):1SA-138SA

  6. Takayanagi T, Sasaki H, Kawashima A, Mizuochi Y, Hirate H, Sugiura T, Azami T, Asai K, Sobue K (2011) A new enteral diet, MHN-02, which contains abundant antioxidants and whey peptide, protects against carbon tetrachloride-induced hepatitis. JPEN J Parenter Enteral Nutr 35:516–522

    Article  CAS  PubMed  Google Scholar 

  7. Nakamura K, Ogawa S, Dairiki K, Fukatsu K, Sasaki H, Kaneko T, Yamaji T (2011) A new immune-modulating diet enriched with whey-hydrolyzed peptide, fermented milk, and isomaltulose attenuates gut ischemia-reperfusion injury in mice. Clin Nutr 30:513–516

    Article  CAS  PubMed  Google Scholar 

  8. Kume H, Okazaki K, Yamaji T, Sasaki H (2012) A newly designed enteral formula containing whey peptides and fermented milk product protects mice against concanavalin A-induced hepatitis by suppressing overproduction of inflammatory cytokines. Clin Nutr 31:283–289

    Article  CAS  PubMed  Google Scholar 

  9. Kaido T, Mori A, Ogura Y, Hata K, Yoshizawa A, Iida T, Yagi S, Uemoto S (2010) Impact of enteral nutrition using a new immune-modulating diet after liver transplantation. Hepato-Gastroenterology 57:1522–1525

    CAS  PubMed  Google Scholar 

  10. Marshall K (2004) Therapeutic applications of whey protein. Altern Med Rev 9:136–156

    PubMed  Google Scholar 

  11. Arakawa Y, Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, Hanaoka J (2014) Effects of a whey peptide-based enteral formula diet on liver dysfunction following living donor liver transplantation. Surg Today 44:44–49

    Article  CAS  PubMed  Google Scholar 

  12. Fujiwara T, Naomoto Y, Motoki T, Shigemitsu K, Shirakawa Y, Yamatsuji T et al (2007) Effects of a novel palatinose based enteral formula (MHN-01) carbohydrate-adjusted fluid diet in improving the metabolism of carbohydrates and lipids in patients with esophageal cancer complicated by diabetes mellitus. J Surg Res 138:231–240

    Article  CAS  PubMed  Google Scholar 

  13. Egi M, Toda Y, Katayama H, Yokoyama M, Morita K, Arai H, Yamatsuji T, Bailey M, Naomoto Y (2010) Safer glycemic control using isomaltulose-based enteral formula: a pilot randomized crossover trial. J Crit Care 25:90–96

    Article  PubMed  Google Scholar 

  14. Kitagawa H, Namikawa T, Munekage M, Fujisawa K, Munekgae E, Kobayashi M, Hanazaki K (2016) Outcomes of thoracoscopic esophagectomy in prone position with laparoscopic gastric mobilization for esophageal cancer. Langenbeck's Arch Surg 401:699–705

    Article  Google Scholar 

  15. Kitagawa H, Akimori T, Okabayashi T, Namikawa T, Sugimoto T, Kobayashi M, Hanazaki K (2009) Total laparoscopic gastric mobilization for esophagectomy. Langenbeck's Arch Surg 394:617–621

    Article  Google Scholar 

  16. Kitagawa H, Namikawa T, Munekage M, Akimori T, Kobayashi M, Hanazaki K (2015) Visualization of the stomach's arterial networks during esophageal surgery using the HyperEye medical system. Anticancer Res 35:6201–6205

    CAS  PubMed  Google Scholar 

  17. Kitagawa H, Yatabe T, Namikawa T, Munekage M, Hanazaki K (2016) Postoperative closed-loop glycemic control using an artificial pancreas in patients after esophagectomy. Anticancer Res 36:4063–4067

    Article  PubMed  Google Scholar 

  18. Wray CJ, Mammen JM, Hasselgren PO (2002) Catabolic response to stress and potential benefits of nutrition support. Nutrition 18:971–977

    Article  PubMed  Google Scholar 

  19. Tsujimoto OS, Takahata R, Hiraki S, Yaguchi Y, Kumano I, Matsumoto Y, Yoshida K, Aiko S, Ichikura T, Yamamoto J, Hase K (2012) Systemic inflammatory response syndrome as a predictor of anastomotic leakage after esophagectomy. Surg Today 42:141–146

    Article  PubMed  Google Scholar 

  20. Sczepanik AM, Scislo L, Scully T, Walewska E, Siedlar M, Kolodziejczyk P, Lenart M, Rutkowska M, Galas A, Czupryna A, Kulig J (2011) IL-6 serum levels predict postoperative morbidity in gastric cancer patients. Gastric Cancer 14:266–273

    Article  Google Scholar 

  21. Rettig TC, Verwijmeren L, Dijkstra IM, Boerma D, van de Garde EM, Noordzij PG (2016) Postoperative interleukin-6 level and early detection of complications after elective major abdominal surgery. Ann Surg 263:1207–1212

    Article  PubMed  Google Scholar 

  22. Dimopoulou I, Armaganidis A, Douka E, Mavrou I, Augustatou C, Kopterides P, Lyberopoulos P, Tzanela M, Orfanos SE, Pelekanou E, Kostopanagiotou G, Macheras A, Giamarellos-Bourboulis EJ (2007) Tumour necrosis factor-alpha (TNF alpha) and interleukin-10 are crucial mediators in post-operative systemic inflammatory response and determine the occurrence of complications after major abdominal surgery. Cytokine 37:55–61

    Article  CAS  PubMed  Google Scholar 

  23. Mezzasoma L, Cagini L, Antognelli C, Puma F, Pacifico E, Talesa VN (2013) TNF-α regulates natriuretic peptides and aquaporins in human bronchial epithelial cells BEAS-2B. Mediat Inflamm 2013:159349

    Article  Google Scholar 

  24. Mizock BA (2001) Alterations in fuel metabolism in critical illness: hyperglycaemia. Best Pract Res Clin Endocrinol Metab 15:533–551

    Article  CAS  PubMed  Google Scholar 

  25. Shimada H, Okazumi S, Maysubara H, Nabeya Y, Shiratori T, Hayashi H, Shuto K, Akutsu Y, Ochiai T (2007) Is the surgical stress associated with worse survival in patients with esophageal cancer?—Analysis of colon substitution for 37 patients with remnant stomach. Hepato-Gastroenterology 54:791–795

    PubMed  Google Scholar 

  26. Goh SL, De Silva RP, Dhital K, Gett RM (2015) Is low serum albumin associated with postoperative complications in patients undergoing oesophagectomy for oesophageal malignancies? Interact Cardiovasc Thorac Surg 20:107–113

    Article  PubMed  Google Scholar 

  27. Beale RJ, Bryg DJ, Bihari DJ (1999) Immunonutrition in the critically ill: a systematic review of clinical outcome. Crit Care Med 27:2799–2805

    Article  CAS  PubMed  Google Scholar 

  28. Heys SD, Walker LG, Smith I, Eremin O (1999) Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials. Ann Surg 229:467–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Braga M, Gianotti L, Radaelli G, Vignali A, Mari G, Gentilini O, Di Carlo V (1999) Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double-blind phase 3 trial. Arch Surg 134:428–433

    Article  CAS  PubMed  Google Scholar 

  30. Gianotti L, Braga M, Nespoli L, Radaelli G, Beneduce A, Di Carlo V (2002) A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology 122:1763–1770

    Article  CAS  PubMed  Google Scholar 

  31. Takeuch H, Ikeuchi S, Kawaguchi Y, Kitagawa Y, Isobe Y, Kubochi K, Kitajima M, Matsumoto S (2007) Clinical significance of perioperative immunonutrition for patients with esophageal cancer. World J Surg 31:2160–2167

    Article  Google Scholar 

  32. Sakurai Y, Masui T, Yoshida I, Tonomura S, Shoji M, Nakamura Y, Isogaki J, Uyama I, Komori Y, Ochiai M (2007) Randomized clinical trial of the effects of perioperative use of immune-enhancing enteral formula on metabolic and immunological status in patients undergoing esophagectomy. World J Surg 31:2150–2157

    Article  PubMed  Google Scholar 

  33. Rice TW, Wheeler AP, Thompson BT, deBoisblanc BP, Steingrub J, Rock P, NIH NHLBI Acute Respiratory Distress Syndrome Network of Investigators (2011) Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA 306:1574–1581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sultan J, Griffin SM, Di Franco F, Kirby JA, Shenton BK, Seal CJ, Davis P, Viswanath YK, Preston SR, Hayes N (2012) Randomized clinical trial of omega-3 fatty acid-supplemented enteral nutrition versus standard enteral nutrition in patients undergoing oesophagogastric cancer surgery. Br J Surg 99:346–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fujitani K, Tsujinaka T, Fujita J, Miyashiro I, Imamura H, Kimura Y, Kobayashi K, Kurokawa Y, Shimokawa T, Furukawa H, Osaka Gastrointestinal Cancer Chemotherapy Study Group (2012) Prospective randomized trial of preoperative enteral immunonutrition followed by elective total gastrectomy for gastric cancer. Br J Surg 99:621–629

    Article  CAS  PubMed  Google Scholar 

  36. Lobo DN, Williams RN, Welch NT, Aloysius MM, Nunes QM, Padmanabhan J, Crowe JR, Iftikhar SY, Parsons SL, Neal KR, Allison SP, Rowlands BJ (2006) 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 25:716–726

    Article  PubMed  Google Scholar 

  37. Klek S, Kulig J, Sierzega M, Szybinski P, Szczepanek K, Kubisz A, Kowalczyk T, Gach T, Pach R, Szczepanik AM (2008) The impact of immunostimulating nutrition on infectious complications after upper gastrointestinal surgery: a prospective, randomized, clinical trial. Ann Surg 248:212–220

    Article  PubMed  Google Scholar 

  38. Klek S, Kulig J, Sierzega M, Szczepanek K, Szybiński P, Scislo L, Walewska E, Kubisz A, Szczepanik AM (2008) Standard and immunomodulating enteral nutrition in patients after extended gastro-intestinal surgery: a prospective, randomized, controlled clinical trial. Clin Nutr 27:504–512

    Article  PubMed  Google Scholar 

  39. Kaya SO, Akcam TI, Ceylan KC, Samancılar O, Ozturk O, Usluer O (2016) Is preoperative protein-rich nutrition effective on postoperative outcome in non-small cell lung cancer surgery? A prospective randomized study. J Cardiothorac Surg 11:14

    Article  PubMed  PubMed Central  Google Scholar 

  40. Takesue T, Takeuchi H, Ogura M, Fukuda K, Nakamura R, Takahashi T, Wada N, Kawakubo H, Kitagawa Y (2015) A prospective randomized trial of enteral nutrition after thoracoscopic esophagectomy for esophageal cancer. Ann Surg Oncol 22:802–809

    Article  Google Scholar 

  41. Ata A, Lee J, Bestle SL, Desemone J, Stain SC (2010) Postoperative hyperglycemia and surgical site infection in general surgery patients. Arch Surg 145:858–864

    Article  PubMed  Google Scholar 

  42. NICE-SUGAR Study Investigators (2009) Intensive versus conventional glucose control in critically ill patients. N Engl J Med 360:1283–1297

    Article  Google Scholar 

  43. Casaer MP, Wilmer A, Hermans G, Wouters PJ, Mesotten D, Van den Berghe G (2013) Role of disease and macronutrient dose in the randomized controlled EPaNIC trial: a post hoc analysis. Am J Respir Crit Care Med 187:247–255

    Article  PubMed  Google Scholar 

  44. Singer P, Anbar R, Cohen J, Shapiro H, Shalita-Chesner M, Lev S, Grozovski E, Theilla M, Frishman S, Madar Z (2011) The tight calorie control study (TICACOS): a prospective, randomized, controlled pilot study of nutritional support in critically ill patients. Intensive Care Med 37:601–609

    Article  PubMed  Google Scholar 

  45. Heidegger CP, Berger MM, Graf S, Zingg W, Darmon P, Costanza MC, Thibault R, Pichard C (2013) Optimization of energy provision with supplemental parenteral nutrition in critically ill patients: a randomized controlled clinical trial. Lancet 381:385–393

    Article  PubMed  Google Scholar 

  46. Hanazaki K, Kitagawa H, Yatabe T, Munekage M, Dabanaka K, Takezaki Y, Tsukamoto Y, Asano T, Kinoshita Y, Namikawa T (2014) Perioperative intensive insulin therapy using an artificial endocrine pancreas with closed-loop glycemic control system: the effect of no hypoglycemia. Am J Surg 207:935–941

    Article  PubMed  Google Scholar 

  47. Egi M, Bellomo R, Stachowski E, French CJ, Hart G (2006) Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology 105:244–252

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Authors’ contributions

H. K and T. N contributed to the study conception and design. H. K, T. Y, and M. M contributed to the acquisition of the data. H. K and F. Y did the analysis and interpretation of the data. H. K contributed to the drafting of the manuscript. The critical revision of the manuscript was done by T. N, M. K, and K. H.

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Authors and Affiliations

  1. Department of Surgery, Kochi Medical School, Kohasu-Okocho, Nankoku, Kochi, 783-8505, Japan

    Hiroyuki Kitagawa, Tsutomu Namikawa, Masaya Munekage & Kazuhiro Hanazaki

  2. Department of Anesthesiology, Kochi Medical School, Kohasu-Okocho, Nankoku, Kochi, 783-8505, Japan

    Tomoaki Yatabe

  3. Department of Clinical Laboratory, Kochi Medical School, Kohasu-Okocho, Nankoku, Kochi, 783-8505, Japan

    Fumiyasu Yamasaki

  4. Department of Human Health and Medical Sciences, Kochi Medical School, Kohasu-Okocho, Nankoku, Kochi, 783-8505, Japan

    Michiya Kobayashi

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  1. Hiroyuki Kitagawa
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Correspondence to Tsutomu Namikawa.

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Conflict of interest

The authors declare that they have no conflict of interest.

Preoperative MHN-02 and MEIBARANCE® were offered by Meiji Dairies Co., Tokyo, Japan.

Ethical board approval

The study protocol was approved by the Institutional Review Board of Kochi Medical School, registered to UMIN 000014321, and was performed in accordance with the ethics standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Kitagawa, H., Namikawa, T., Yatabe, T. et al. Effects of a preoperative immune-modulating diet in patients with esophageal cancer: a prospective parallel group randomized study. Langenbecks Arch Surg 402, 531–538 (2017). https://doi.org/10.1007/s00423-016-1538-5

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  • DOI: https://doi.org/10.1007/s00423-016-1538-5

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