Effects of a protease inhibitor on reduction of surgical stress in esophagectomy

Ono, Satoshi; Aosasa, Suefumi; Mochizuki, Hidetaka

doi:10.1016/s0002-9610(98)00300-6

Cited by 46 publications

(39 citation statements)

References 25 publications

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“…hypercytokinemia elicits excessive stress that may trigger post-operative pulmonary complications (17). Transthoracic esophagectomy induced considerably higher post-operative serum IL-6 levels than distal gastrectomy for gastric cancer (18), and could induce an excessive inflammatory response leading to SIRS and pulmonary complications (19).…”

Section: Discussionmentioning

confidence: 99%

Effects of sivelestat on bronchial inflammatory responses after esophagectomy

Yamaguchi

Sugasawa²,

Takeuchi³

et al. 2011

Int J Mol Med

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Abstract. Post-operative pulmonary complications such as systemic inflammatory response syndrome (SIRS), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are strongly associated with morbidity and mortality after esophagectomy. Post-operative administration of sivelestat sodium hydrate (sivelestat), a selective inhibitor of neutrophil elastase (NE), has been shown to improve the post-operative clinical course after esophagectomy. This study aimed to evaluate the effect of prophylactic administration of sivelestat on bronchial inflammatory responses. We randomized 24 patients into two groups. One group received 0.2 mg/kg/h sivelestat from the induction of anesthesia to post-operative day 1 (sivelestat group) and the other group received the same amount of physiological saline (control group). Bronchial alveolar epithelial lining fluid (ELF) samples were obtained from both groups at the induction of anesthesia and at the end of surgery. The serum and ELF levels of interleukin (IL)-6 and IL-8 were measured by enzyme-linked immunosorbent assay, and NE activity was spectrophotometrically determined using the same samples. Although IL-6 levels in the ELF significantly increased at the end of surgery compared with the pre-operative levels in both groups, the IL-8 levels and NE activity did not significantly increase at the end of the surgery compared to the corresponding pre-operative values in the sivelestat group. Moreover, IL-8 levels and NE activity in the ELF were significantly reduced at the end of surgery in the sivelestat group compared with corresponding values in the control group. The durations of ALI and ARDS were apparently shorter in the sivelestat group and the duration of SIRS was significantly shorter in the sivelestat group compared to the control group. We demonstrated that prophylactic use of sivelestat mitigated bronchial inflammation by suppressing NE activity and IL-8 levels in the ELF and shortened the duration of SIRS after transthoracic esophagectomy.

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Section: Discussionmentioning

confidence: 99%

Effects of sivelestat on bronchial inflammatory responses after esophagectomy

Yamaguchi

Sugasawa²,

Takeuchi³

et al. 2011

Int J Mol Med

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“…Diminished interleukin-6 (IL-6) and C-reactive protein (CRP) responses to laparoscopic versus open cholecystectomy have already been reported [13,15]. This suggested that serum levels of IL-6 and CRP could be sensitive to the magnitude of trauma and injury associated with abdominal wall wounds and therefore are reported to reflect the severity of surgical stress [3,13,15,18,19]. Both interleukin-1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor-type I (sTNF-R55) have been reported to be induced as host responses after the operative stress and bacterial insults [9-11, 14, 21, 24].…”

Section: Discussionmentioning

confidence: 99%

The analysis of the usefulness of laparoscopic microwave coagulation therapy for hepatocellular carcinoma in patients with poor hepatic reserve by serial measurements of IL-6, cytokine antagonists, and C-reactive protein

et al. 2003

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“…Previous studies have demonstrated that UTI, a trypsin inhibitor in a human urine preparation, suppresses the activity of trypsin as well as the activity of PMN elastase, cathepsin G, and hyaluronidase, all of which participate in the catabolism of the intracellular and extracellular matrix components, such as fibronectin [5]. More recently, it has been speculated that protease inhibition can suppress the in vitro production of proinflammatory cytokines [6, 7]. …”

Section: Discussionmentioning

confidence: 99%

“…It inhibits polymorphonuclear neutrophil (PMN) elastase as well as other proteases [5]. In addition, it inhibits the production of inflammatory cytokines in vitro [6, 7]. In Japan, UTI has been clinically applied to treat acute pancreatitis and shock [8].…”

Section: Introductionmentioning

confidence: 99%

Influence of a Human Protease Inhibitor on Surgical Stress Induced Immunosuppression

Sato

Endo²,

Kimura³

et al. 2002

Dig Surg

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Background/Aim: Postoperative tissue injury and immunosuppression can occur after major surgery. In this study, we explore the potential benefits of administering a protease inhibitor to treat immunosuppression caused by surgical stress. Methods: Sixteen patients with esophageal cancer were preoperatively allocated at random into two equal groups. A urinary trypsin inhibitor, ulinastatin (UTI), was intravenously administered to the treatment (UTI) group at a dose of 150,000 U every 12 h from the start of surgery until postoperative day 5, whereas the control group received a placebo. One unit of UTI was defined as the amount of UTI necessary to inhibit the activity of 2 µg of bovine pancreatic trypsin by 50%. We measured the plasma levels of polymorphonuclear neutrophil elastase, interleukin 8, circulating T lymphocyte subsets, and mitogenic activity and in vitro production of tumor necrosis factor alpha in lipopolysaccharide-stimulated whole blood. Results: The postoperative serum value of polymorphonuclear neutrophil elastase was significantly lower in the UTI group, but the interleukin 8 concentrations did not significantly vary between the two groups. On the other hand, the severity of the postoperative immunosuppression was reduced in the UTI group, and immune functions, such as the numbers of T lymphocytes, the mitogenic activity of lymphocytes, and the level of tumor necrosis factor alpha production in whole blood, recovered significantly earlier in the UTI group. Conclusion: These data suggest that a protease-modulating therapy may be a new strategy for the treatment of surgical stress induced immune dysfunction.

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Effects of a protease inhibitor on reduction of surgical stress in esophagectomy

Cited by 46 publications

References 25 publications

Effects of sivelestat on bronchial inflammatory responses after esophagectomy

Effects of sivelestat on bronchial inflammatory responses after esophagectomy

The analysis of the usefulness of laparoscopic microwave coagulation therapy for hepatocellular carcinoma in patients with poor hepatic reserve by serial measurements of IL-6, cytokine antagonists, and C-reactive protein

Influence of a Human Protease Inhibitor on Surgical Stress Induced Immunosuppression

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