Skip to main content

Advertisement

SpringerLink
Log in

Reduced plasma ghrelin levels on day 1 after esophagectomy: a new predictor of prolonged systemic inflammatory response syndrome

  • Original Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Background and purpose

Ghrelin, a stomach-derived hormone, stimulates growth hormone secretion and appetite, and inhibits excessive inflammatory response. Plasma ghrelin might affect the inflammatory response to stressful surgical interventions. The aim of this study was to investigate the relationship between serial changes in plasma ghrelin concentrations and the postoperative clinical course after esophagectomy.

Methods

The prospective cohort study subjects were 20 patients with esophageal cancer, who underwent esophagectomy with gastric tube reconstruction. Blood samples were taken six times perioperatively during the course of esophagectomy.

Results

The plasma ghrelin level decreased to 33 % (range 15–90 %) on postoperative day (POD) 1, relative to the preoperative level, then recovered to about 50 % by POD 3–10. The duration of systemic inflammatory response syndrome (SIRS) was significantly longer in patients with a marked ghrelin reduction to <33 % on POD 1, than in those with less marked reduction of ≥33 % (6.1 ± 1.3 vs. 2.1 ± 0.6 days, P = 0.019). On POD 1, the only inflammatory marker that correlated with the duration of SIRS was the % ghrelin, whereas C-reactive protein, leukocyte count, and IL-6 did not.

Conclusion

An early postoperative drop in plasma ghrelin correlated with prolonged SIRS after esophagectomy. Thus, the supplementation of low plasma ghrelin may help minimize excess inflammatory response in these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  2. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241–52.

    Article  PubMed  CAS  Google Scholar 

  3. Opal SM, Fisher CJ Jr, Dhainaut JF, Vincent JL, Brase R, Lowry SF, et al. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group. Crit Care Med. 1997;25:1115–24.

    Article  PubMed  CAS  Google Scholar 

  4. Cohen J, Carlet J. INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group. Crit Care Med. 1996;24:1431–40.

    Article  PubMed  CAS  Google Scholar 

  5. Ryugo M, Sawa Y, Takano H, Matsumiya G, Iwai S, Ono M, et al. Effect of a polymorphonuclear elastase inhibitor (sivelestat sodium) on acute lung injury after cardiopulmonary bypass: findings of a double-blind randomized study. Surg Today. 2006;36:321–6.

    Article  PubMed  CAS  Google Scholar 

  6. Akamoto S, Okano K, Sano T, Yachida S, Izuishi K, Usuki H, et al. Neutrophil elastase inhibitor (sivelestat) preserves antitumor immunity and reduces the inflammatory mediators associated with major surgery. Surg Today. 2007;37:359–65.

    Article  PubMed  CAS  Google Scholar 

  7. Shimada H, Ochiai T, Okazumi S, Matsubara H, Nabeya Y, Miyazawa Y, et al. Clinical benefits of steroid therapy on surgical stress in patients with esophageal cancer. Surgery. 2000;128:791–8.

    Article  PubMed  CAS  Google Scholar 

  8. Sato N, Koeda K, Ikeda K, Kimura Y, Aoki K, Iwaya T, et al. Randomized study of the benefits of preoperative corticosteroid administration on the postoperative morbidity and cytokine response in patients undergoing surgery for esophageal cancer. Ann Surg. 2002;236:184–90.

    Article  PubMed  Google Scholar 

  9. Guidelines for the diagnosis and treatment of esophageal cancer, edited by the Japan Esophageal Society; 2007 (in Japanese).

  10. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402:656–60.

    Article  PubMed  CAS  Google Scholar 

  11. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409:194–8.

    Article  PubMed  CAS  Google Scholar 

  12. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001;86:5992–5.

    Article  PubMed  CAS  Google Scholar 

  13. Akamizu T, Kangawa K. Translational research on the clinical applications of ghrelin. Endocr J. 2006;53:585–91.

    Article  PubMed  CAS  Google Scholar 

  14. Nagaya N, Uematsu M, Kojima M, Ikeda Y, Yoshihara F, Shimizu W, et al. Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation. 2001;104:1430–5.

    Article  PubMed  CAS  Google Scholar 

  15. Nagaya N, Itoh T, Murakami S, Oya H, Uematsu M, Miyatake K, et al. Treatment of cachexia with ghrelin in patients with COPD. Chest. 2005;128:1187–93.

    Article  PubMed  CAS  Google Scholar 

  16. Li WG, Gavrila D, Liu X, Wang L, Gunnlaugsson S, Stoll LL, et al. Ghrelin inhibits proinflammatory responses and nuclear factor-kappaB activation in human endothelial cells. Circulation. 2004;109:2221–6.

    Article  PubMed  CAS  Google Scholar 

  17. Doki Y, Takachi K, Ishikawa O, Miyashiro I, Sasaki Y, Ohigashi H, et al. Ghrelin reduction after esophageal substitution and its correlation to postoperative body weight loss in esophageal cancer patients. Surgery. 2006;139:797–805.

    Article  PubMed  Google Scholar 

  18. Saeki H, Masuda T, Okada S, Ando K, Sugiyama M, Yoshinaga K, et al. Impact of perioperative peripheral blood values on postoperative complications after esophageal surgery. Surg Today. 2010;40(7):626–31.

    Article  PubMed  Google Scholar 

  19. Akamizu T, Shinomiya T, Irako T, Fukunaga M, Nakai Y, Nakai Y, et al. Separate measurement of plasma levels of acylated and desacyl ghrelin in healthy subjects using a new direct ELISA assay. J Clin Endocrinol Metab. 2005;90:6–9.

    Article  PubMed  CAS  Google Scholar 

  20. Nagaya N, Moriya J, Yasumura Y, Uematsu M, Ono F, Shimizu W, et al. Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation. 2004;110:3674–9.

    Article  PubMed  CAS  Google Scholar 

  21. Nagaya N, Miyatake K, Uematsu M, Oya H, Shimizu W, Hosoda H, et al. Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. J Clin Endocrinol Metab. 2001;86:5854–9.

    Article  PubMed  CAS  Google Scholar 

  22. Deboer MD, Zhu X, Levasseur PR, Inui A, Hu Z, Han G, et al. Ghrelin treatment of chronic kidney disease: improvements in lean body mass and cytokine profile. Endocrinology. 2008;149:827–35.

    Article  PubMed  CAS  Google Scholar 

  23. Adachi S, Takiguchi S, Okada K, Yamamoto K, Yamasaki M, Miyata H, et al. Effects of ghrelin administration after total gastrectomy: a prospective, randomized, placebo-controlled phase II study. Gastroenterology. 2010;138:1312–20.

    Article  PubMed  CAS  Google Scholar 

  24. Yamamoto K, Takiguchi S, Miyata H, Adachi S, Hiura Y, Yamasaki M, et al. Randomized phase II study of clinical effects of ghrelin after esophagectomy with gastric tube reconstruction. Surgery. 2010;148:31–8.

    Article  PubMed  Google Scholar 

  25. Wu R, Dong W, Zhou M, Zhang F, Marini CP, Ravikumar TS, et al. Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats. Am J Respir Crit Care Med. 2007;176:805–13.

    Article  PubMed  CAS  Google Scholar 

  26. ElBarbary M, Khabar KS. Soluble tumor necrosis factor receptor p55 predicts cytokinemia and systemic inflammatory response after cardiopulmonary bypass. Crit Care Med. 2002;30:1712–6.

    Article  CAS  Google Scholar 

  27. Samimi-Fard S, Dominguez-Rodriguez A, Abreu-Gonzalez P, Enjuanes-Grau C, Blanco-Palacios G, Hernandez-Baldomero IF, et al. Role of myeloperoxidase as predictor of systemic inflammatory response syndrome in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention. Am J Cardiol. 2009;104:634–7.

    Article  PubMed  CAS  Google Scholar 

  28. Seidelin JB, Nielsen OH, Strøm J. Soluble L-selectin levels predict survival in sepsis. Intensive Care Med. 2002;28:1613–8.

    Article  PubMed  Google Scholar 

  29. Maruna P, Gürlich R, Rosická M. Ghrelin as an acute-phase reactant during postoperative stress response. Horm Metab Res. 2008;40:404–9.

    Article  PubMed  CAS  Google Scholar 

  30. Wu R, Zhou M, Dong W, Ji Y, Miksa M, Marini CP, et al. Ghrelin hyporesponsiveness contributes to age-related hyperinflammation in septic shock. Ann Surg. 2009;250:126–33.

    Article  PubMed  Google Scholar 

  31. Shah KG, Wu R, Jacob A, Blau SA, Ji Y, Dong W, et al. Human ghrelin ameliorates organ injury and improves survival after radiation injury combined with severe sepsis. Mol Med. 2009;15:407–14.

    Article  PubMed  CAS  Google Scholar 

  32. Schwenke DO, Tokudome T, Kishimoto I, Horio T, Shirai M, Cragg PA, et al. Early ghrelin treatment after myocardial infarction prevents an increase in cardiac sympathetic tone and reduces mortality. Endocrinology. 2008;149:5172–6.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Tomoyuki Sugimoto from the Department of Biomedical Statistics, Osaka University, for his help with statistical analyses. We also thank the doctors and nursing staff of the ICU at Osaka University Hospital for their expert care of the patients who participated in this clinical study.

Conflict of interest

We declare no potential conflicts of interest.

Author information

Authors and Affiliations

  1. Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, 2-2, E2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Kazuyoshi Yamamoto, Shuji Takiguchi, Hiroshi Miyata, Yasuhiro Miyazaki, Yuichiro Hiura, Makoto Yamasaki, Kiyokazu Nakajima, Yoshiyuki Fujiwara, Masaki Mori & Yuichiro Doki

  2. Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka, Japan

    Kenji Kangawa

Authors
  1. Kazuyoshi Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuji Takiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroshi Miyata
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasuhiro Miyazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuichiro Hiura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Makoto Yamasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kiyokazu Nakajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yoshiyuki Fujiwara
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masaki Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kenji Kangawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yuichiro Doki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shuji Takiguchi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamamoto, K., Takiguchi, S., Miyata, H. et al. Reduced plasma ghrelin levels on day 1 after esophagectomy: a new predictor of prolonged systemic inflammatory response syndrome. Surg Today 43, 48–54 (2013). https://doi.org/10.1007/s00595-012-0342-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-012-0342-2

Keywords

Search

Navigation