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The impact of prophylactic administration of a neutrophil elastase inhibitor on the postoperative course in older patients undergoing esophagectomy for esophageal cancer: a propensity score-matched analysis

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Abstract

Background

Sivelestat, a selective inhibitor of neutrophil elastase, has been reported to reduce acute lung injury associated with systemic inflammatory response syndrome (SIRS). However, no study has addressed the effect of prophylactic sivelestat administration on the postoperative course following an esophagectomy in older patients.

Methods

In this retrospective study of patients aged >70 years, we performed a propensity score-matched analysis to compare short and long-term outcomes between patients who received early postoperative sivelestat administration (n = 42) and those who did not receive sivelestat (controls; n = 42) after a transthoracic esophagectomy for esophageal cancer (EC).

Results

Patient backgrounds were well balanced between the two groups. The sivelestat group showed significantly shorter SIRS durations compared to the control group (2 vs 5 days, p = 0.001). In addition, postoperative hospital stays were shorter in the sivelestat group than in the control group (26 vs 31 days, p = 0.013). Other factors did not differ between the two groups, including the reoperation rate, ICU stay, duration of mechanical ventilation, and duration of O2 supply. Postoperatively, the sivelestat group showed significantly lower heart rates than the control group (repeated-measures ANOVA, p = 0.0389) while respiratory rates, the SpO2 levels, and body temperatures did not significantly differ between the two groups. Finally, long-term survival appeared to be not different between the two groups.

Conclusions

Sivelestat effectively stabilized postoperative vital signs and shortened SIRS durations. Thus, prophylactic sivelestat led to shorter hospital stays among older patients with EC who underwent an esophagectomy.

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Abbreviations

CT:

Computed tomography

EC:

Esophageal cancer

FDG-PET:

18F-fluorodeoxyglucose-positron emission tomography

LN:

Lymph node

SIRS:

Systemic inflammatory response syndrome

References

  1. Ando N, Ozawa S, Kitagawa Y, et al. Improvement in the results of surgical treatment of advanced squamous esophageal carcinoma during 15 consecutive years. Ann Surg. 2000;232(2):225–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Atkins BZ, Shah AS, Hutcheson KA, et al. Reducing hospital morbidity and mortality following esophagectomy. Ann Thorac Surg. 2004;78(4):1170–6.

    Article  PubMed  Google Scholar 

  3. Sato N, Koeda K, Ikeda K, 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(2):184–90.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Razavi HM, le Wang F, Weicker S, et al. Pulmonary neutrophil infiltration in murine sepsis: role of inducible nitric oxide synthase. Am J Respir Crit Care Med. 2004;170(3):227–33.

    Article  PubMed  Google Scholar 

  5. Nishiyama J, Matsuda M, Ando S, et al. The effects of the early administration of sivelestat sodium, a selective neutrophil elastase inhibitor, on the postoperative course after radical surgery for esophageal cancer. Surg Today. 2012;42(7):659–65.

    Article  CAS  PubMed  Google Scholar 

  6. Tanaka H, Sugimoto H, Yoshioka T, et al. Role of granulocyte elastase in tissue injury in patients with septic shock complicated by multiple-organ failure. Ann Surg. 1991;213(1):81–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Petty TL. Protease mechanisms in the pathogenesis of acute lung injury. Ann N Y Acad Sci. 1991;624:267–77.

    Article  CAS  PubMed  Google Scholar 

  8. Yang HX, Ling L, Zhang X, et al. Outcome of elderly patients with oesophageal squamous cell carcinoma after surgery. Br J Surg. 2010;97(6):862–7.

    Article  PubMed  Google Scholar 

  9. Guo L, Yamaguchi Y, Ikei S, et al. Neutrophil elastase inhibitor (ONO-5046) prevents lung hemorrhage induced by lipopolysaccharide in rat model of cerulein pancreatitis. Dig Dis Sci. 1995;40(10):2177–83.

    Article  CAS  PubMed  Google Scholar 

  10. Matsuzaki K, Hiramatsu Y, Homma S, et al. Sivelestat reduces inflammatory mediators and preserves neutrophil deformability during simulated extracorporeal circulation. Ann Thorac Surg. 2005;80(2):611–7.

    Article  PubMed  Google Scholar 

  11. Tamakuma S, Ogawa M, Aikawa N, et al. Relationship between neutrophil elastase and acute lung injury in humans. Pulm Pharmacol Ther. 2004;17(5):271–9.

    Article  CAS  PubMed  Google Scholar 

  12. Nagai Y, Watanabe M, Baba Y, et al. Preventive effect of sivelestat on postoperative respiratory disorders after thoracic esophagectomy. Surg Today. 2013;43(4):361–6.

    Article  PubMed  Google Scholar 

  13. Mimatsu K, Oida T, Kawasaki A, et al. Influence of neutrophil elastase inhibitor on the postoperative course in patients with esophageal cancer after transthoracic esophagectomy. Hepatogastroenterology. 2011;58(110–111):1583–7.

    CAS  PubMed  Google Scholar 

  14. Makino H, Kunisaki C, Kosaka T, et al. Perioperative use of a neutrophil elastase inhibitor in video-assisted thoracoscopic oesophagectomy for cancer. Br J Surg. 2011;98(7):975–82.

    Article  CAS  PubMed  Google Scholar 

  15. Iwahashi M, Nakamori M, Nakamura M, et al. Optimal period for the prophylactic administration of neutrophil elastase inhibitor for patients with esophageal cancer undergoing esophagectomy. World J Surg. 2011;35(7):1573–9.

    Article  PubMed  Google Scholar 

  16. Kawahara Y, Ninomiya I, Fujimura T, et al. Prospective randomized controlled study on the effects of perioperative administration of a neutrophil elastase inhibitor to patients undergoing video-assisted thoracoscopic surgery for thoracic esophageal cancer. Dis Esophagus. 2010;23(4):329–39.

    Article  CAS  PubMed  Google Scholar 

  17. Suda K, Kitagawa Y, Ozawa S, et al. Neutrophil elastase inhibitor improves postoperative clinical courses after thoracic esophagectomy. Dis Esophagus. 2007;20(6):478–86.

    Article  CAS  PubMed  Google Scholar 

  18. Ono S, Tsujimoto H, Hiraki S, et al. Effects of neutrophil elastase inhibitor on progression of acute lung injury following esophagectomy. World J Surg. 2007;31(10):1996–2001.

    Article  PubMed  Google Scholar 

  19. Yamaguchi K, Sugasawa Y, Takeuchi K, et al. Effects of sivelestat on bronchial inflammatory responses after esophagectomy. Int J Mol Med. 2011;28(2):187–92.

    CAS  PubMed  Google Scholar 

  20. Sobin LGM, Wittekind C. TNM classification of malignant tumours. 7th ed. New York: Wiley; 2009.

    Google Scholar 

  21. Rosenbaum PR, Rubin D. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat. 1985;39:33–8.

    Google Scholar 

  22. Jr DAR. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–81.

    Article  Google Scholar 

  23. Makino T, Yamasaki M, Miyata H, et al. Solitary lymph node recurrence of esophageal squamous cell carcinoma: surgical failure or systemic disease? Ann Surg Oncol. 2016;23(6):2087–93.

    Article  PubMed  Google Scholar 

  24. Makino T, Yamasaki M, Miyazaki Y, et al. Short and long-term outcomes of larynx-preserving surgery for cervical esophageal cancer: analysis of 100 consecutive cases. Ann Surg Oncol. 2016;23(5):858–65.

    Article  PubMed  Google Scholar 

  25. Yamashita K, Makino T, Miyata H, et al. Postoperative infectious complications are associated with adverse oncologic outcomes in esophageal cancer patients undergoing preoperative chemotherapy. Ann Surg Oncol. 2016;23(6):2106–14.

    Article  PubMed  Google Scholar 

  26. Qiu D, Kaneko S. Comparison of esophageal cancer mortality in five countries: France, Italy, Japan, UK and USA from the WHO mortality database (1960–2000). Jpn J Clin Oncol. 2005;35(9):564–7.

    Article  PubMed  Google Scholar 

  27. Shimada H, Shiratori T, Okazumi S, et al. Surgical outcome of elderly patients 75 years of age and older with thoracic esophageal carcinoma. World J Surg. 2007;31(4):773–9.

    Article  PubMed  Google Scholar 

  28. Tsukada K, Miyazaki T, Katoh H, et al. Effect of perioperative steroid therapy on the postoperative course of patients with oesophageal cancer. Dig Liver Dis. 2006;38(4):240–4.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

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

    Tomoki Makino, Makoto Yamasaki, Koji Tanaka, Noriko Wada, Yasuhiro Miyazaki, Tsuyoshi Takahashi, Yukinori Kurokawa, Kiyokazu Nakajima, Shuji Takiguchi, Masaki Mori & Yuichiro Doki

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  1. Tomoki Makino
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  2. Makoto Yamasaki
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  3. Koji Tanaka
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  4. Noriko Wada
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  5. Yasuhiro Miyazaki
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  6. Tsuyoshi Takahashi
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  7. Yukinori Kurokawa
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  8. Kiyokazu Nakajima
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  9. Shuji Takiguchi
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  10. Masaki Mori
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  11. Yuichiro Doki
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Corresponding author

Correspondence to Tomoki Makino.

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Ethical Statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study.

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There are no conflicts of interest.

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Makino, T., Yamasaki, M., Tanaka, K. et al. The impact of prophylactic administration of a neutrophil elastase inhibitor on the postoperative course in older patients undergoing esophagectomy for esophageal cancer: a propensity score-matched analysis. Esophagus 14, 241–248 (2017). https://doi.org/10.1007/s10388-017-0571-y

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  • DOI: https://doi.org/10.1007/s10388-017-0571-y

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