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01-01-2013 | Original Article

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

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

Published in: Surgery Today | Issue 1/2013

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.

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

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

13.

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.CrossRef

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.PubMedCrossRef

28.

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

29.

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

Title: Reduced plasma ghrelin levels on day 1 after esophagectomy: a new predictor of prolonged systemic inflammatory response syndrome
Authors: Kazuyoshi Yamamoto
Shuji Takiguchi
Hiroshi Miyata
Yasuhiro Miyazaki
Yuichiro Hiura
Makoto Yamasaki
Kiyokazu Nakajima
Yoshiyuki Fujiwara
Masaki Mori
Kenji Kangawa
Yuichiro Doki
Publication date: 01-01-2013
Publisher: Springer Japan
Published in: Surgery Today / Issue 1/2013
Print ISSN: 0941-1291
Electronic ISSN: 1436-2813
DOI: https://doi.org/10.1007/s00595-012-0342-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Background and purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background and purpose

Methods

Results

Conclusion

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