title: Effects of neutrophil elastase inhibitor in patients undergoing esophagectomy: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To evaluate the benefit and safety of sivelestat (a neutrophil elastase inhibitor) administration in patients undergoing esophagectomy.
  
  
  METHODS
  Online databases including PubMed, EMBASE, the Cochrane Library, Web of Knowledge, and Chinese databases (Wanfang database, VIP and CNKI) were searched systematically up to November 2013. Randomized controlled trials and high-quality comparative studies were considered eligible for inclusion. Three reviewers evaluated the methodological quality of the included studies, and Stata 12.0 software was used to analyze the extracted data. The risk ratio (RR) was used to express the effect size of dichotomous outcomes, and mean difference (MD) or standardized mean difference was used to express the effect size of continuous outcomes.
  
  
  RESULTS
  Thirteen studies were included in this systematic review and nine studies were included in the meta-analysis. The duration of mechanical ventilation was significantly decreased in the sivelestat group on postoperative day 5 [I (2) = 76.3%, SMD = -1.41, 95%CI: -2.63-(-0.19)]. Sivelestat greatly lowered the incidence of acute lung injury in patients after surgery (I (2) = 0%, RR = 0.27, 95%CI: 0.08-0.93). However, it did not decrease the incidence of pneumonia, intensive care unit stay or postoperative hospital stay, and did not increase the incidence of complications such as anastomotic leakage, recurrent nerve palsy, wound infection, sepsis and catheter-related fever.
  
  
  CONCLUSIONS
  A neutrophil elastase inhibitor is beneficial in patients undergoing esophagectomy. More high quality, large sample, multi-center and randomized controlled trials are needed to validate this effect.
authors.affiliation: Zhi-Qiang Wang, Long-Qi Chen, Yong Yuan, Wen-Ping Wang, Zhong-Xi Niu, Yu-Shang Yang, Jie Cai, Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Wang
authors.affiliation: Zhi-Qiang Wang, Long-Qi Chen, Yong Yuan, Wen-Ping Wang, Zhong-Xi Niu, Yu-Shang Yang, Jie Cai, Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Long-Qi
authors.initials: LQ
authors.lastname: Chen
authors.affiliation: Zhi-Qiang Wang, Long-Qi Chen, Yong Yuan, Wen-Ping Wang, Zhong-Xi Niu, Yu-Shang Yang, Jie Cai, Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Zhi-Qiang Wang, Long-Qi Chen, Yong Yuan, Wen-Ping Wang, Zhong-Xi Niu, Yu-Shang Yang, Jie Cai, Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Wang
authors.affiliation: Zhi-Qiang Wang, Long-Qi Chen, Yong Yuan, Wen-Ping Wang, Zhong-Xi Niu, Yu-Shang Yang, Jie Cai, Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Zhong-Xi
authors.initials: ZX
authors.lastname: Niu
authors.affiliation: Zhi-Qiang Wang, Long-Qi Chen, Yong Yuan, Wen-Ping Wang, Zhong-Xi Niu, Yu-Shang Yang, Jie Cai, Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Yu-Shang
authors.initials: YS
authors.lastname: Yang
authors.affiliation: Zhi-Qiang Wang, Long-Qi Chen, Yong Yuan, Wen-Ping Wang, Zhong-Xi Niu, Yu-Shang Yang, Jie Cai, Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000517:prevention & control; D000368:Aged; D016629:Esophagectomy / Q000009:adverse effects; D005260:Female; D005998:Glycine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012121:Respiration, Artificial; D012307:Risk Factors; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine
keywords: Esophageal cancer; Esophagectomy; Meta-analysis; Neutrophil elastase inhibitor; Systematic review
references.citation: Dis Esophagus. 2010 May;23(4):329-39
references.pmid: 19788440
references.citation: Shock. 2010 Jan;33(1):14-8
references.pmid: 19487982
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Br J Surg. 2011 Jul;98(7):975-82
references.pmid: 21557207
references.citation: Int J Mol Med. 2011 Aug;28(2):187-92
references.pmid: 21567070
references.citation: World J Surg. 2011 Jul;35(7):1573-9
references.pmid: 21479682
references.citation: Hepatogastroenterology. 2011 Sep-Oct;58(110-111):1583-7
references.pmid: 22086688
references.citation: Surg Today. 2012 Jul;42(7):659-65
references.pmid: 22200755
references.citation: Mol Med Rep. 2013 Apr;7(4):1091-5
references.pmid: 23404144
references.citation: Surg Today. 2013 Apr;43(4):361-6
references.pmid: 23412514
references.citation: Thorac Surg Clin. 2013 Nov;23(4):535-50
references.pmid: 24199703
references.citation: Lancet Respir Med. 2013 Dec;1(10):793-803
references.pmid: 24461759
references.citation: Am J Respir Crit Care Med. 2000 Jun;161(6):2013-8
references.pmid: 10852782
references.citation: Br J Anaesth. 2001 May;86(5):633-8
references.pmid: 11575337
references.citation: Ann Thorac Surg. 2002 Mar;73(3):922-6
references.pmid: 11899202
references.citation: Lancet. 2002 May 18;359(9319):1727-33
references.pmid: 12049861
references.citation: Ann Surg. 2002 Sep;236(3):376-84; discussion 384-5
references.pmid: 12192324
references.citation: Dig Surg. 2002;19(4):300-5
references.pmid: 12207074
references.citation: N Engl J Med. 2002 Nov 21;347(21):1662-9
references.pmid: 12444180
references.citation: Surg Endosc. 2002 Nov;16(11):1588-93
references.pmid: 12085146
references.citation: Br J Surg. 2003 Jan;90(1):108-13
references.pmid: 12520585
references.citation: Ann Thorac Surg. 2003 Jan;75(1):217-22; discussion 222
references.pmid: 12537219
references.citation: Ann Surg. 2003 Sep;238(3):339-47; discussion 347-8
references.pmid: 14501500
references.citation: N Engl J Med. 2003 Dec 4;349(23):2241-52
references.pmid: 14657432
references.citation: Pulm Pharmacol Ther. 2004;17(5):271-9
references.pmid: 15477122
references.citation: Surgery. 1985 Nov;98(5):892-9
references.pmid: 2414855
references.citation: Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):293-301
references.pmid: 7842182
references.citation: Ann Surg. 1997 Aug;226(2):162-8
references.pmid: 9296509
references.citation: Crit Care Med. 1997 Dec;25(12):1994-2000
references.pmid: 9403749
references.citation: Ann Thorac Surg. 2005 Aug;80(2):611-7
references.pmid: 16039215
references.citation: Masui. 2005 Aug;54(8):884-8
references.pmid: 16104542
references.citation: Surg Today. 2007;37(5):359-65
references.pmid: 17468814
references.citation: World J Surg. 2007 Oct;31(10):1996-2001
references.pmid: 17674097
references.citation: Dis Esophagus. 2007;20(6):478-86
references.pmid: 17958722
references.citation: Dis Esophagus. 2008;21(1):30-6
references.pmid: 18197936
references.citation: Bull World Health Organ. 2008 May;86(5):390-398C
references.pmid: 18545742
references.citation: Dis Esophagus. 2010 Sep;23(7):565-71
references.pmid: 20353442