Skip to main content
Top
Published in: Esophagus 3/2017

01-07-2017 | Original Article

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

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

Published in: Esophagus | Issue 3/2017

Login to get access

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.
Literature
1.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
2.
go back to reference Atkins BZ, Shah AS, Hutcheson KA, et al. Reducing hospital morbidity and mortality following esophagectomy. Ann Thorac Surg. 2004;78(4):1170–6.CrossRefPubMed Atkins BZ, Shah AS, Hutcheson KA, et al. Reducing hospital morbidity and mortality following esophagectomy. Ann Thorac Surg. 2004;78(4):1170–6.CrossRefPubMed
3.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
6.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
7.
go back to reference Petty TL. Protease mechanisms in the pathogenesis of acute lung injury. Ann N Y Acad Sci. 1991;624:267–77.CrossRefPubMed Petty TL. Protease mechanisms in the pathogenesis of acute lung injury. Ann N Y Acad Sci. 1991;624:267–77.CrossRefPubMed
8.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
9.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
10.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
11.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
12.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
13.
go back to reference 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.PubMed 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.PubMed
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
18.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
19.
go back to reference 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.PubMed 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.PubMed
20.
go back to reference Sobin LGM, Wittekind C. TNM classification of malignant tumours. 7th ed. New York: Wiley; 2009. Sobin LGM, Wittekind C. TNM classification of malignant tumours. 7th ed. New York: Wiley; 2009.
21.
go back to reference Rosenbaum PR, Rubin D. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat. 1985;39:33–8. Rosenbaum PR, Rubin D. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat. 1985;39:33–8.
22.
go back to reference 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.CrossRef 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.CrossRef
23.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
24.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
25.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
26.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
27.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
28.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
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
Authors
Tomoki Makino
Makoto Yamasaki
Koji Tanaka
Noriko Wada
Yasuhiro Miyazaki
Tsuyoshi Takahashi
Yukinori Kurokawa
Kiyokazu Nakajima
Shuji Takiguchi
Masaki Mori
Yuichiro Doki
Publication date
01-07-2017
Publisher
Springer Japan
Published in
Esophagus / Issue 3/2017
Print ISSN: 1612-9059
Electronic ISSN: 1612-9067
DOI
https://doi.org/10.1007/s10388-017-0571-y

Other articles of this Issue 3/2017

Esophagus 3/2017 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.