Zhi-Qiang Wang

Effects of neutrophil elastase inhibitor in patients undergoing esophagectomy: A systematic review and meta-analysis

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.

Effects of degree of pulmonary fissure completeness on major in-hospital outcomes after video-assisted thoracoscopic lung cancer lobectomy: a retrospective-cohort study

Background To evaluate the clinical significance of degree of pulmonary fissure completeness (PFC) on major in-hospital outcomes following video-assisted thoracoscopic (VATS) lobectomy for non-small-cell lung cancer (NSCLC). Materials and methods We carried out a single-center retrospective analysis on the prospectively maintained database at our unit between August 2014 and October 2015. Patients were divided into two groups based on their fissure sum average (FSA). Patients with FSA >1 (1< FSA ≤3) were considered to have incomplete pulmonary fissures (group A), while patients with FSA of 0–1 were considered to have complete pulmonary fissures (group B). Demographic differences in perioperative characteristics and surgical outcomes between these two groups were initially assessed. Then, a multivariate logistic-regression analysis was further conducted to identify the independent predictors for major in-hospital outcomes. Results A total of 563 patients undergoing VATS lobectomy for NSCLC were enrolled. There were 190 patients in group A and 373 patients in group B. The overall morbidity and mortality rates of our cohort were 30.6% and 0.5%, respectively. Group A patients had a significantly higher overall morbidity rate than group B patients (42.1% vs 24.7%, P<0.001). Both minor morbidity (40.5% vs 22%, P<0.001) and major morbidity (11.1% vs 5.6%, P=0.021) rates in group A patients were also significantly higher than group B patients. No significant difference was observed in mortality rate between these two groups (1.1% vs 0.3%, P=0.26). The incomplete degree of PFC was significantly correlated with length of stay and chest-tube duration (log-rank P<0.001) after surgery. Finally, the incomplete degree of PFC was found to be predictive of overall morbidity (OR 2.08, P<0.001), minor morbidity (OR 2.39, P<0.001), and major morbidity (OR 2.06, P=0.031) by multivariate logistic-regression analyses. Conclusion Degree of PFC is an excellent categorical predictor for both major and minor morbidity after VATS lobectomy for NSCLC.

Presence of pleural adhesions can predict conversion to thoracotomy and postoperative surgical complications in patients undergoing video-assisted thoracoscopic lung cancer lobectomy

Background The purpose of our cohort study was to investigate the effects of pleural adhesions on perioperative outcomes in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for non-small-cell lung cancer (NSCLC). Methods We performed a single-center retrospective analysis on the prospectively-maintained dataset at our unit from February 2014 to November 2015. Patients were divided into two groups (Group A: presence of pleural adhesions; Group B: absence of pleural adhesions) according to our grading system of pleural adhesions when entering the chest cavity. Demographic differences in perioperative outcomes between these two groups were initially estimated. A multivariate logistic-regression analysis was then performed to confirm the predictive value of the presence of pleural adhesions. Results A total of 593 NSCLC patients undergoing VATS lobectomy were enrolled. The conversion and postoperative morbidity rates were 3.2% and 29.2%, respectively. There were 154 patients with pleural adhesions (Group A) and 439 patients without pleural adhesions (Group B). Group A patients had significantly higher rates of conversion to thoracotomy (9.1% vs. 1.1%; P<0.001) and surgical complications (24.0% vs. 14.4%; P=0.006) than those of Group B patients. No significant difference was found in the overall morbidity and cardiopulmonary complication rates between these two groups. The presence of pleural adhesions was also significantly associated with the prolonged length of chest tube drainage (log-rank P<0.001) and length of stay (log-rank P=0.032). Finally, the presence of pleural adhesions was identified as an independent risk factor for conversion to thoracotomy [odds ratio (OR) =5.49; P=0.003] and surgical complications (OR =1.94; P=0.033) by multivariate logistic-regression analyses. Conclusions Presence of pleural adhesions can predict conversion to thoracotomy and postoperative surgical complications in patients undergoing VATS lobectomy for NSCLC. Our study calls for an internationally accepted grading system for the presence of pleural adhesions to stratify the surgical risk.

Left thoracotomy for middle or lower thoracic esophageal carcinoma: still Sweet enough?

BACKGROUND Esophagectomy via left thoracotomy (the Sweet procedure) has long been the conventional route for resection of esophageal carcinoma, especially in China. However, this procedure is being increasingly critiqued, mainly regarding the lymphadenectomy. The objective of this study was to compare the Sweet procedure with the right upper mediastinal lymph node resection (MS) and Ivor-Lewis (IL) procedure in the treatment of middle or lower thoracic esophageal squamous cell carcinoma (OSCC-MLT) in terms of lymphadenectomy, postoperative complications, and long-term survival. METHODS A total of 336 OSCC-MLT patients underwent radical intent surgery (188 with MS and 148 with IL procedure) between January 2007 and September 2013 in our hospital. After propensity score matching, 129 patients from each procedure were included. The efficacy of lymph node dissection at each station was estimated by the index of estimated benefit from lymph node dissection (IEBLD). RESULTS IEBLD is relatively high in stations 2L, 2R, 8, 16 and 17. The metastasis rates and ratios were similar between the MS and IL procedures at each station. The MS procedure significantly outperformed the IL procedure with a shorter operating time (212 vs. 317 min), shorter in-hospital stay (10.7 vs. 15.3 days), and fewer postoperative complications (30.2% vs. 43.4%). However, the 5-year survival rates were not significantly different between the two procedures (46.9% vs. 44.0%). CONCLUSIONS The MS procedure of esophagectomy is not inferior to the IL procedure in efficiency, moreover the MS procedure is safer.

Notch Signaling Pathway Is Inhibited in the Development of Barrett’s Esophagus: An In Vivo and In Vitro Study

Objective To explore the role of Notch signaling in the development of Barretts esophagus. Methods Patients with esophagectomy and gastric interposition were recruited as a human model of gastroesophageal reflux disease. The expressions of Notch signaling genes in normal esophagus from surgical specimen and columnar metaplasia in the esophageal remnant after esophagectomy were evaluated by real time quantitative Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry (IHC). For in vitro experiments, Het-1A cells were treated with hydrochloric acid, deoxycholic acid, mixture of hydrochloric acid and deoxycholic acid, or Notch1-siRNA, and expressions of Notch1, Hes1, MUC2, and K13 were evaluated via RT-qPCR and western blot. Results Samples were obtained from 36 patients with columnar metaplasia in the esophageal remnant. Both IHC and RT-qPCR indicated that Notch1 and Hes1 expressions were significantly higher in normal esophagus than that in metaplasia. Hydrochloric acid and deoxycholic acid suppressed Notch1, Hes1, and K13 expressions, in concert with increasing MUC2 expressions. Notch inhibition by Notch1-siRNA contributed to the downregulation of Notch1, Hes1, and K13 expressions, whereas MUC2 expression was enhanced. Conclusions Both hydrochloric acid and deoxycholic acid could suppress Notch signaling pathway in esophageal epithelial cells, and inhibited Notch signaling has important functions in the development of Barretts esophagus.

High expression of Ki-67 is an independent favorable prognostic factor for esophageal small cell carcinoma

Background The prognostic value of Ki-67 expression in small cell carcinoma of the esophagus (SCCE) has not been explored in any previous studies. Therefore, we conducted this retrospective study to investigate the prognostic role of Ki-67 in SCCE for the first time. Results A total of 44 patients were included for analysis. The baseline clinicopathological data of these SCCE patients shared similar characteristics with previous studies. Ten patients were at stage I, 17 at stage II, and the remaining 17 were at stage III. Postoperatively, 23 patients received adjuvant therapy. Twenty-eight patients were found to have a high expression of Ki-67 (> 50%). After a median follow-up time of 54.8 months, the median survival time of those patients was 22.1 months. Early TNM stage, application of adjuvant therapy, and high expression of Ki-67 (Hazard Ratio = 0.314, 95% CI: 0.127–0.774; P = 0.012) were found to be favorable prognostic factors of patients with SCCE. In subgroup analysis, adjuvant therapy could only bring significant survival benefit for patients with high expression of Ki-67 (P = 0.008). Materials and Methods Patients undergoing esophagectomy with lymphadenectomy for SCCE from January 2009 to January 2015 in our department were retrospectively analyzed. Data for analysis included demographic data, pathologic findings, tumor stage, adjuvant therapy, and survival time as well as Ki-67 index. Conclusions This study suggested that high expression of Ki-67 may not only serve as a favorable prognostic factor of SCCE but also an indication of providing adjuvant therapy for SCCE patients with surgical resection.BACKGROUND The prognostic value of Ki-67 expression in small cell carcinoma of the esophagus (SCCE) has not been explored in any previous studies. Therefore, we conducted this retrospective study to investigate the prognostic role of Ki-67 in SCCE for the first time. RESULTS A total of 44 patients were included for analysis. The baseline clinicopathological data of these SCCE patients shared similar characteristics with previous studies. Ten patients were at stage I, 17 at stage II, and the remaining 17 were at stage III. Postoperatively, 23 patients received adjuvant therapy. Twenty-eight patients were found to have a high expression of Ki-67 (> 50%). After a median follow-up time of 54.8 months, the median survival time of those patients was 22.1 months. Early TNM stage, application of adjuvant therapy, and high expression of Ki-67 (Hazard Ratio = 0.314, 95% CI: 0.127-0.774; P = 0.012) were found to be favorable prognostic factors of patients with SCCE. In subgroup analysis, adjuvant therapy could only bring significant survival benefit for patients with high expression of Ki-67 (P = 0.008). MATERIALS AND METHODS Patients undergoing esophagectomy with lymphadenectomy for SCCE from January 2009 to January 2015 in our department were retrospectively analyzed. Data for analysis included demographic data, pathologic findings, tumor stage, adjuvant therapy, and survival time as well as Ki-67 index. CONCLUSIONS This study suggested that high expression of Ki-67 may not only serve as a favorable prognostic factor of SCCE but also an indication of providing adjuvant therapy for SCCE patients with surgical resection.

Longitudinal study of esophageal mucosal damage after esophagectomy and gastric interposition: relationship between reflux-related mucosal injury and Notch signaling

Background Esophagectomy with gastric interposition could serve as a good human reflux model to study the molecular pathogenesis of esophageal mucosal damage induced by gastroesophageal reflux. This study was to investigate the role of Notch signaling in reflux injury of esophageal mucosa. Methods Patients undergoing Ivor-Lewis esophagectomy for early stage esophageal squamous cell carcinoma were included. Follow-ups were scheduled at 6, 18, 36 and 48 months postoperatively, including reflux symptom assessment, endoscopic and histological evaluation of esophageal mucosal damage. The expressions of Notch1 and its downstream target gene Hes1 were evaluated by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC). Results Forty-four out of 48 patients completed four follow-ups. Injuries of esophageal remnant confirmed by endoscopical and histological examinations were both more often with a longer postoperative period (P<0.05). The mRNA expression levels of Notch1 and Hes1 were decreased in a time-dependent manner after operation (P<0.001). Notch1 and Hes1 mRNA levels were significantly higher in normal squamous mucosa than in esophagitis, and higher in esophagitis than in metaplasia (P<0.05). Immunohistochemical study also demonstrated a similar protein expression pattern. Samples with endoscopic evidence of mucosal damage exhibited lower expression of Notch1 mRNA levels as compared to biopsies without visualized damage (P=0.035). Conclusions This is the first longitudinal study on Notch signaling in human esophagectomy model, our preliminary findings suggest decreased Notch signaling might be involved in the development of mucosa damage caused by gastroesophageal reflux.

The safety profile of preoperative administration of heparin for thromboprophylaxis in Chinese patients intended for thoracoscopic major thoracic surgery: a pilot randomized controlled study

BACKGROUND Patients undergoing major thoracic surgery especially for cancers are at a high risk of perioperative thromboembolism. Current guidelines recommended either heparin sodium (unfractionated heparin) or low-molecular-weight heparin (LMWH) for those patients at high risk of deep vein thrombosis (DVT). However, the rational timing of starting heparin has not yet been well established, because DVT can be caused by not only surgery but also comorbidities as well as prolonged hospital stay, and thoracic surgeons always concerned about heparin-related increased risk of intra- or post-operative bleeding. Therefore, this study aimed to establish the safety profile of preoperative administration of heparin for thromboprophylaxis in Chinese patients intended for thoracoscopic major thoracic surgery. METHODS From June to August 2016, patients intended for thoracoscopic lobectomy, esophagectomy, and thymectomy were randomly assigned into two groups: the case group (starting heparin sodium 5,000 U, bid preoperatively upon the admission into our department) and the control group (starting heparin sodium 5,000 U, bid postoperatively from postoperative day 1). The baseline data including demographic data and preoperative conditions were collected. The end points included operation time, intraoperative bleeding volume, postoperative chest tube drainage volume and duration as well as lab coagulation function data. RESULTS A total of 58 qualified patients were randomized into case group (29 patients) and control group (29 patients), and after excluding 6 conversion patients, the case group and control group each had 26 patients for analysis. The baseline data of the two groups were comparable. Operation time (P=0.368), intraoperative bleeding volume (P=0.231), postoperative drainage days (P=0.466), and mean drainage volume per day (P=0.108) were not significantly increased in case group compared with those of control group. Moreover, there were no significant differences of perioperative coagulation function between these two groups. CONCLUSIONS Preoperative administration of heparin for thromboprophylaxis in Chinese patients intended for thoracoscopic major thoracic surgery was safe and feasible. TRIAL REGISTRATION NCT02940444 (https://register.clinicaltrials.gov/).

Can oesophagectomy be performed for patients with oesophageal carcinoma and concomitant liver cirrhosis? A retrospective study based on a propensity-matched cohort

OBJECTIVES For patients with oesophageal carcinoma and concomitant liver cirrhosis, the safety profile and postoperative prognosis of oesophagectomy are not clearly established due to the lack of relevant studies with large sample sizes. Our objective was to explore the surgical indications and postoperative prognosis in patients with oesophageal carcinoma and liver cirrhosis. METHODS A total of 2226 patients with oesophageal carcinoma underwent curative oesophagectomy (37 with liver cirrhosis and 2189 without) in our department from April 2008 to September 2013. Overall, 37 patients with liver cirrhosis (30 Child-Pugh Grade A and 7 Child-Pugh Grade B) and a propensity-matched cohort of 74 patients without cirrhosis were analysed. We compared the rates of postoperative complications and 5-year survival in these 2 groups. In addition, we performed an analysis of any potential risk factors for death, including patient demographic information and of operation performed. RESULTS A higher operative mortality rate was observed in patients with oesophageal carcinoma and liver cirrhosis compared to patients with oesophageal carcinoma but without cirrhosis (11 vs 1%, P = 0.042). Patients with cirrhosis included those with Child-Pugh Grade B (43%), preoperative moderate ascites (100%), a prothrombin time of ≥ 4 s (75%) and greater weight loss. Although the rates of surgical death and postoperative hydrothorax were significantly higher in patients with liver cirrhosis, the rates of other major complications and 5-year overall survival were not significantly different compared to patients without cirrhosis. CONCLUSIONS Curative oesophagectomy is a feasible, beneficial treatment option for patients with oesophageal carcinoma and liver cirrhosis, with a higher perioperative risk but reasonable longer term survival compared to patients without cirrhosis.

Oesophageal adenocarcinoma has a higher risk of lymph node metastasis than squamous cell carcinoma: a propensity score-matched study

OBJECTIVES The pattern of lymph node metastasis is a predominant element in tumour biology, which is closely related to optimal therapeutic modality. Controversy remains as to which histopathology type of oesophageal cancer-adenocarcinoma or squamous cell carcinoma (SCC)-is more likely to have lymph node metastasis. Therefore, this study aimed to apply propensity score-matched analysis to draw an objective conclusion for providing initial evidence of the potential need for different therapeutic strategies for these 2 cancer types. METHODS A retrospective analysis of patients who underwent radical oesophagectomy with lymphadenectomy, but without preoperative treatment for pathologically and immunohistochemically diagnosed oesophageal adenocarcinoma or SCC, was conducted. Data for analysis included age, gender, body mass index, pathologic findings, procedures of oesophagectomy and rate of lymph node metastasis. Propensity score-matched analysis was conducted to eliminate the bias effects of confounding factors. RESULTS A total of 1204 patients (including 118 with adenocarcinoma and 1086 with SCC) from January 2012 to June 2016 was included for analysis. In the analysis of unmatched patients, those with adenocarcinomas had significantly larger mean numbers of positive lymph nodes (3.8 and 1.5, respectively; P < 0.001) and higher rates of lymph node metastasis (71.2% and 49.0%, respectively; P < 0.001) than those with an SCC. However, other confounding factors such as surgical procedures, tumour location, pT stage and lymphovascular invasion also differed significantly between the adenocarcinoma and SCC cases. In the analysis of 96 matched patients, those confounding factors were well matched, and cases of adenocarcinoma still had a significantly larger mean number of positive lymph node (4.5 and 1.8, respectively; P = 0.003) and higher rate of lymph node metastasis (75.0% and 45.8%, respectively; P = 0.003) than did those with SCC. CONCLUSIONS Cases of oesophageal adenocarcinoma had a higher risk of lymph node metastasis than did those with SCC in this series, which indicates that different therapeutic modalities should be applied for these 2 different malignant entities.