Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0154059 (Esophagus)
 2,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sivelestat sodium hydrate is a selective inhibitor of neutrophil elastase (NE), and is effective in acute lung injury associated with systemic inflammatory response syndrome (SIRS). The effect of Sivelestat for postoperative clinical courses after transthoracic esophagectomy was investigated. Consecutive patients with carcinoma of the thoracic esophagus who underwent transthoracic esophagectomy between 2003 and 2004 were assigned to the Sivelestat-treated group (n = 18), and those between 1998 and 2003 were assigned to the control group (n = 25). The morbidity rate, duration of postoperative SIRS, mechanical ventilation, and intensive care unit (ICU) stay, and the sum of the sequential organ failure assessment scores at all time points after the operation were compared. Serum NE activities and serum concentrations of TNF-alpha, IL-1beta, IL-6, and high mobility group box chromosomal protein 1 (HMGB1) were measured. Postoperative complications developed in three patients in the control group, and one in the Sivelestat-treated group. The durations of SIRS, mechanical ventilation, and ICU stay were significantly shorter in the Sivelestat-treated group. Even in patients without complications, the durations of mechanical ventilation, and ICU stay were also significantly shorter, and the arterial oxygen pressure/fraction of inspired oxygen ratio at postoperative day 1 was significantly higher in the Sivelestat-treated group. Serum NE activities and serum concentrations of IL-1beta, IL-6, and HMGB1 were significantly suppressed in the Sivelestat-treated group. Postoperative Sivelestat treatment after transthoracic esophagectomy improves the condition of SIRS and postoperative clinical courses, even in patients without complications.
Dis Esophagus 2007
PMID:Neutrophil elastase inhibitor improves postoperative clinical courses after thoracic esophagectomy. 1795 22

Sivelestat sodium hydrate (Ono Pharmaceutical Co., Osaka, Japan) is a selective inhibitor of neutrophil elastase (NE) and is effective in reducing acute lung injury associated with systemic inflammatory response syndrome (SIRS). We conducted a prospective randomized controlled study to investigate the efficacy of perioperative administration of sivelestat sodium hydrate to prevent postoperative acute lung injury in patients undergoing thoracoscopic esophagectomy and radical lymphadenectomy. Twenty-two patients with thoracic esophageal cancer underwent video-assisted thoracoscopic esophagectomy with extended lymph node dissection in our institution between April 2007 and November 2008. Using a double-blinded method, these patients were randomly assigned to one of two groups preoperatively. The active treatment group received sivelestat sodium hydrate intravenously for 72 hours starting at the beginning of surgery (sivelestat-treated group; n= 11), while the other group received saline (control group; n= 11). All patients were given methylprednisolone immediately before surgery. Postoperative clinical course was compared between the two groups. Two patients (one in each group) were discontinued from the study during the postoperative period because of surgery-related complications. Of the remaining 20 patients, 2 patients who developed pneumonia within a week after surgery were excluded from some laboratory analyses, so data from 18 patients (9 patients in each group) were analyzed based on the arterial oxygen pressure/fraction of inspired oxygen ratio, white blood cell count, serum C-reactive protein level, plasma cytokine levels, plasma NE level, and markers of alveolar type II epithelial cells. In the current study, the incidence of postoperative morbidity did not differ between the two groups. The median duration of SIRS in the sivelestat-treated group was significantly shorter than that in the control group: 17 (range 9-36) hours versus 49 (15-60) hours, respectively (P= 0.009). Concerning the parameters used for the diagnosis of SIRS, the median heart rates on postoperative day (POD) 2 were significantly lower in the sivelestat-treated group than in the control group (P= 0.007). The median arterial oxygen pressure/fraction of inspired oxygen ratio of the sivelestat-treated group were significantly higher than those of the control group on POD 1 and POD 7 (POD 1: 372.0 [range 284.0-475.0] vs 322.5 [243.5-380.0], respectively, P= 0.040; POD 7: 377.2 [339.5-430.0] vs 357.6 [240.0-392.8], P= 0.031). Postoperative white blood cell counts, serum C-reactive protein levels, plasma interleukin-1beta, tumor necrosis factor-alpha levels, and plasma NE levels did not differ significantly between the two groups at any point during the postoperative course, nor did serum Krebs von den Lungen 6, surfactant protein-A, or surfactant protein-D levels, which were used as markers of alveolar type II epithelial cells to evaluate the severity of lung injury. Plasma interleukin-8 levels were significantly lower in the sivelestat-treated group than in the control group on POD 3 (P= 0.040). In conclusion, perioperative administration of sivelestat sodium hydrate (starting at the beginning of surgery) mitigated postoperative hypoxia, partially suppressed postoperative hypercytokinemia, shortened the duration of SIRS, and stabilized postoperative circulatory status after thoracoscopic esophagectomy.
Dis Esophagus 2010 May
PMID: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. 1978 40

The objective of the study was to evaluate the efficacy of sivelestat, a selective neutrophil elastase inhibitor, on body fluid balance after transthoracic esophagectomy. Esophagectomy with elective lymphadenectomy may induce excessive release of neutrophil elastase, which then promotes vascular permeability and an excessive water shift from the intravascular space to the peripheral compartment. Body fluid imbalance after esophagectomy often leads to circular instability, a decrease of urine output, and a delay in the shift to a diuretic state. The study was designed as a case-control study with a historical control group. A retrospective analysis was performed to examine our hypothesis that sivelestat improves abnormal body fluid retention and prevents subsequent pulmonary complications. To reveal the direct influence of sivelestat on the postoperative course, we avoided using steroids or other diuretic agents. Eighty-eight patients who underwent thoracic esophagectomy with extended lymphadenectomy from 2000 to 2008 were divided into two groups: those treated from 2003 to 2008, who all received postoperative administration of sivelestat (n=60); and those treated from 2000 to 2002, who did not receive sivelestat and were used as the control group (n=28). Both groups received fluid management using the same protocol. The time to reach a diuretic state, time until extubation of the tracheal tube, and development of delayed respiratory dysfunction were compared between the groups using univariate and multivariate analysis. The time until a shift to a diuretic state was significantly shorter after treatment with sivelestat (p<0.0001) and with a shorter operation time (p<0.0001). The tracheal tube was extubated significantly earlier in the sivelestat group (p<0.0001) and the incidence of delayed respiratory dysfunction was also significantly lower (p=0.0028) in this group. Multivariate logistic regression analysis showed that a delay in a shift to a diuretic state was a strong independent risk factor for the time to tracheal extubation (odds ratio 2.539, p=0.0056) and occurrence of delayed respiratory dysfunction (odds ratio 1.989, p=0.0104). Sivelestat treatment was not independently associated with reduced pulmonary complications, but the diuretic state was strongly regulated by sivelestat treatment (odds ratio 0.044, p=0.0003). Thus, administration of sivelestat has a beneficial influence on recovery from body water imbalance through a more rapid return to a diuretic state after esophagectomy, which contributes to prevention of subsequent pulmonary complications.
Dis Esophagus 2010 Sep
PMID:Effect of a selective neutrophil elastase inhibitor on early recovery from body water imbalance after transthoracic esophagectomy. 2035 42