Neutrophil elastase inhibitor improves postoperative clinical courses after thoracic esophagectomy

Suda, Koichi; Kitagawa, Yuukou; Ozawa, Soji; Miyasho, Taku; Okamoto, Minoru; Saikawa, Yoshirou; Ueda, Mitsuharu; Yamada, Shingo; Tasaka, Sadatomo; Funakoshi, Yosuke; Hashimoto, Satoru; Yokota, Hiroshi; Maruyama, Ikuro; Ishizaka, Akitoshi; Kitajima, Masaki

doi:10.1111/j.1442-2050.2007.00699.x

Cited by 50 publications

(60 citation statements)

References 41 publications

(101 reference statements)

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“…These elevated levels correlate with the severity of the lung injury (103,104). Moreover, small clinical trials provided evidence for the protective effect of elastase inhibition (105)(106)(107)(108). Furthermore, administration of elastase induces lung damage in murine models of ALI (109-111) whereas elastase inhibition attenuated the development of ALI (112)(113)(114)(115)(116) (Table 1).…”

Section: Neutrophil-derived Serine Proteasesmentioning

confidence: 99%

Contribution of Neutrophils to Acute Lung Injury

Grommes

Soehnlein

2010

Mol Med

1,092

897

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Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

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Section: Neutrophil-derived Serine Proteasesmentioning

confidence: 99%

Contribution of Neutrophils to Acute Lung Injury

Grommes

Soehnlein

2010

Mol Med

1,092

897

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“…Sato et al reported that steroid use significantly reduces the incidence of postoperative pneumonia (23). Furthermore, the efficacy of NEI, a selective inhibitor of neutrophil elastase, used for preventing postoperative pneumonia in esophagectomies has been evaluated (25,26). Suda et al concluded that the duration of postoperative SIRS after esophagectomy, the duration of mechanical ventilation, and the length of ICU stay were significantly shortened in NEI-treated patients (25).…”

Section: Variablesmentioning

confidence: 99%

“…Furthermore, the efficacy of NEI, a selective inhibitor of neutrophil elastase, used for preventing postoperative pneumonia in esophagectomies has been evaluated (25,26). Suda et al concluded that the duration of postoperative SIRS after esophagectomy, the duration of mechanical ventilation, and the length of ICU stay were significantly shortened in NEI-treated patients (25). In their study, Ono et al reported that the preventive administration of NEI reduced the rate of postoperative SIRS in patients with severe conditions on mechanical ventilation after esophagectomy (26).…”

Section: Variablesmentioning

confidence: 99%

Risk factors for postoperative respiratory complications following esophageal cancer resection

et al. 2012

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Abstract. The development of surgical and postoperative management techniques has improved the treatment outcomes of esophageal cancer resection. However, respiratory morbidity is still the most frequent complication after esophagectomy. The objective of the present study was to identify risk factors for respiratory complications following resection for esophageal cancer. This study included 96 patients with esophageal cancer who had undergone esophagectomy with lymph node dissection. The patients were divided into 2 groups according to the presence (20 patients, 17 had pneumonia and 3 had acute respiratory distress syndrome) or absence (76 patients) of postoperative respiratory complications (PRC). The two groups were compared with respect to their preoperative clinical variables, such as age, body mass index, smoking history, serum albumin, serum C-reactive protein (CRP), number of lymphocytes, %VC, FEV1.0% and FEV1.0. Furthermore, multiple logistic regression analyses were used to estimate relative risk factors for respiratory complications. Results of the univariate analysis showed that smoking history (+/-, patients with PRC, 19/1 and without PRC, 53/23), serum CRP (≥1.0 mg/ dl/<1.0 mg/dl, patients with PRC, 6/14 and without PRC, 6/70) and FEV1.0% (≥60%/<60%, patients with PRC, 16/4 and without PRC, 73/3) were significantly different between the two groups. Multiple logistic regression analysis showed that FEV1.0% was the strongest predictor of PRC. FEV1.0%, serum CRP and smoking history are reliable predictors of the risk of respiratory complications following esophageal cancer resection. For patients with these factors, perioperative management for the prevention of postoperative respiratory complications should be considered.

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“…Several animal and clinical studies have revealed its ability to restore various types of tissue injuries as well as aspiration pneumonia (6), hepatoenteric ischemia (7), ALI (8) and lung injury associated with SIRS in humans (9). Recently, it has been reported that post-operative sivelestat administration after transthoracic esophagectomy improved the pathophysiological condition of SIRS and the post-operative clinical course even in patients without complications, as well as the deterioration of the PaO 2 (arterial oxygen tension)/FIO 2 (inspired oxygen fractional concentration) ratio in the post-operative period following esophagectomy (10,11). however, its prophylactic effect on transthoracic esophagectomy is still unknown.…”

Section: Introductionmentioning

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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Neutrophil elastase inhibitor improves postoperative clinical courses after thoracic esophagectomy

Cited by 50 publications

References 41 publications

Contribution of Neutrophils to Acute Lung Injury

Contribution of Neutrophils to Acute Lung Injury

Risk factors for postoperative respiratory complications following esophageal cancer resection

Effects of sivelestat on bronchial inflammatory responses after esophagectomy

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