摘要信息：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.

摘要信息：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.

摘要信息：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.

摘要信息：Aim: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. Conclusion: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.

摘要信息：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.

摘要信息：Purpose:The goal of this retrospective study was to evaluate the effects of perioperative administration of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, on the clinical course after radical surgery for esophageal cancer. Methods:The effects of sivelestat on postoperative systemic inflammatory reactions and respiratory function were examined in 53 patients who underwent radical surgery for esophageal cancer between April 2004 and March 2005 with (n = 26, sivelestat group) and without (n = 27, control group) the administration of sivelestat. Results:The average age in the sivelestat group was higher than that in the control group, but there were no other differences in the background factors between the two groups. The postoperative oxygenation (PaO(2)/FiO(2) ratio) did not differ between the groups, but the decrease in oxygen saturation (SpO(2)) was significantly inhibited in the sivelestat group compared with the control group (p < 0.01). A significant inhibition of the increase in the CRP level also occurred in the sivelestat group (p < 0.01). The patients in the sivelestat group were also hospitalized for shorter periods compared to those in the control group. Conclusion:The early administration of sivelestat to patients receiving radical surgery for esophageal cancer can inhibit postoperative systemic inflammatory reactions and it might also have a beneficial effect on the prognosis.

摘要信息：Background:This study was undertaken to assess the value of administering perioperative sivelestat sodium hydrate (SSH), a selective neutrophil elastase inhibitor, after video-assisted thoracoscopic oesophagectomy for cancer. Method:Thirty-one consecutive patients with thoracic oesophageal cancer selected to undergo video-assisted thoracoscopic oesophagectomy with lymph node dissection between March 2007 and March 2009 were assigned randomly to a treatment group that received SSH intravenously for 7 days from the beginning of surgery (16 patients) and a control group that received saline (15). The primary endpoint was pulmonary function based on the arterial partial pressure of oxygen/fraction of inspired oxygen ratio (P/F ratio) during the first 9 days after surgery. Secondary endpoints included platelet count, serum C-reactive protein (CRP) concentration, plasma neutrophil elastase-α(1)-antitrypsin complex level, duration of mechanical ventilation and systemic inflammatory response syndrome (SIRS), and length of intensive care unit (ICU) and hospital stay. Results:The mean P/F ratio of patients who received SSH was significantly higher than that of the control group on postoperative days 1-5 and 7. Duration of mechanical ventilation and SIRS, and length of ICU stay were significantly shorter in the treatment group. Serum CRP concentration on postoperative day 9 was significantly lower (P = 0·048), platelet counts on days 2, 3 and 5 were higher (P = 0·012, P = 0·049 and P = 0·006 respectively), and the incidence of postoperative acute lung injury was significantly lower following SSH treatment (P = 0·023). Conclusion:Perioperative sivelestat may maintain postoperative pulmonary function following video-assisted oesophagectomy.

摘要信息：Thoracic trauma in China was scarcely reported. This study aimed to summarize the clinical profiles and to analyze the management approaches of patients with traumatic thoracic injury.Data for consecutive patients with thoracic trauma from January 2003 to January 2018 were retrospectively collected and analyzed. Patients' profiles and clinical outcomes were compared between those patients treated with a dedicated thoracic trauma team and those without.The study included 4168 patients with mean age of 49.0 years, of whom 82.1% were male. Traffic accident accounted for 42.7% of the injuries. Most of the patients (66.8%) had rib fractures. Associated injuries were present in 48.3% of the patients; of them 86.0% were extremity fractures. Majority of the patients were managed without surgical procedures other than tube thoracostomy (33.2%). ICU service was needed in 12.0% of the patients. Patients treated with thoracic trauma team were older (53.59 ± 16.8 year vs 45.1 ± 18.0 year, P < .001), less male (78.3% vs 85.2%, P < .001), with higher injury severity scores (17.5 ± 10.1 vs 13.7 ± 8.2, P < .001), required more ventilator support (48.3% vs 25.3%, P < .001) and underwent more tube thoracostomy and other surgeries (43.8% vs 24.2%, and 34.4% vs 14.1%, respectively, all P < .001), yet with a shorter hospital stay (11.7 ± 9.0 days vs 12.7 ± 8.8 days, P < .001), and numerically lower ICU usage and mortality when compared to those without.Thoracic trauma in China usually affects mid-age males. Traffic accident is the top one etiology. The most common type of thoracic injuries is rib fracture. Associated injuries occur frequently. Nonoperative treatment and tube thoracostomy are effective for majority of the patients. A multidisciplinary approach with a dedicated thoracic trauma team could improve the treatment for these patients.

摘要信息：Background:This study reports a 10-year retrospective analysis of multiple trauma complicated by pulmonary contusion. The purpose of this study is to ascertain the risk factors for mortality due to trauma in patients with pulmonary contusion, the impact of various treatment options for prognosis, and the risk factors for concurrent Acute Respiratory Distress Syndrome (ARDS). Methods:We retrospectively analyzed 252 trauma patients with lung contusion admitted to the General Hospital of Guangzhou Command from January 2000 to June 2011 by using the statistical processing system SPSS 17.0 for Windows. Results:We included 252 patients in our study, including 214 males and 38 females. The average age was 37.1 ± 14.9 years. There were 110 cases admitted to the ICU, of which 26 cases with ARDS. Nine of the 252 patients died. We compared those who survived with those who died by gender and age, the difference was not statistically significant (P = 0.199, P = 0.200). Separate univariate analysis of those who died and those who survived found that shock on admission (P = 0.000), coagulation disorders (P = 0.000), gastrointestinal bleeding (P = 0.02), the need for emergency surgery on admission (P = 0.000), pre-hospital intubation (P = 0.000), blood transfusion within 24 hours (P = 0.006), the use of mechanical ventilation (P = 0.000), and concurrent ARDS (P = 0.000) are poor prognosis risk factors. Further logistic analysis, including the admission GCS score (OR = 0.708, 95% CI 0.516-0.971, P = 0.032), ISS score (OR 1.135, 95% CI 1.006-1.280, P = 0.039), and concurrent ARDS (OR = 15.814, 95% CI 1.819-137.480, P = 0.012), identified the GCS score, ISS score and concurrent ARDS as independent risk factors of poor prognosis. Shock (OR = 9.121, 95% CI 0.857-97.060, P = 0.067) was also related to poor prognosis. Patients with injury factors such as road accident, falling injury, blunt injury and crush injury, et al.(P = 0.039), infection (P = 0.005), shock (P = 0.004), coagulation disorders (P = 0.006), emergency surgery (P = 0.01), pre-hospital intubation (P = 0.000), chest tube insertion (P = 0.004), blood transfusion (P = 0.000), usage of hormones (P = 0.002), phlegm (P = 0.000), ventilation (P = 0.000) were at a significantly increased risk for ARDS complications. Conclusions:Those patients with multiple trauma and pulmonary contusion admitted to the hospital with shock, coagulopathy, a need for emergency surgery, pre-hospital intubation, and a need for mechanical ventilation could have a significantly increased risk of mortality and ARDS incidence. A risk for poor prognosis was associated with gastrointestinal bleeding. A high ISS score, high APACHE2, and low GCS score were independent risk factors for poor prognosis. If patients developed an infection or were given drainage, hormones, and phlegm treatment, they were at higher risk of ARDS. Pre-hospital intubation and drainage were independent risk factors for ARDS. In patients with ARDS, the ICU stay, total length of stay, and hospital costs might increase significantly. A GCS score < 5.5, APACHE 2 score > 16.5, and ISS score > 20.5 could be considered indicators of poor prognosis for patients with multiple trauma and lung contusion.

摘要信息：Background:There are conflicting views on the of sivelestat sodium (sivelestat-Na) on acute lung injury. Methods:The efficacy of sivelestat-Na on aspiration-related acute lung injury was analyzed by reviewing case reports published before or after the appearance of the drug on the clinical practice in Japan. Data were analyzed from the 23 sivelestat-treated cases and 5 non-sivelestat cases. Results:Sivelestat-Na was administered by 0.2 mg x kg(-1) x hr(-1) for 10 +/- 4 (mean +/- SD) days. PaO2/ ratio increased significantly from 124 +/- 59 mmHg of baseline to 253 +/- 79 mmHg on the third and to 361 +/- 84 mmHg on the termination of the therapy. Significantly better response was observed if the drug was administered within 24 hours after aspiration for patients with background of neurological disease, in which the increases in the P/F ratio were greater and the duration of the drug administration was shorter compared with other patients. In comparison with the non-sivelestat cases, sivelestat-Na therapy appears to be associated with shorter ventilator days or higher P/F increase, although sivelestat-Na costs higher. Conclusions:These results suggest the possibility of conducting prospective clinical trials to assess the efficacy of early sivelestat-Na therapy for aspiration-related acute lung injury.