Gustave Roussy Immune Score based on a three-category risk assessment scale serves as a novel and effective prognostic indicator for surgically resectable early-stage non-small-cell lung cancer: A propensity score matching retrospective cohort study.

BACKGROUNDS: The Gustave Roussy Immune score (GRIm-Score) emerges as a novel prognostic scoring system for patient selection in phase I trials testing targeted immunotherapy for advanced-stage cancer. We tried to assess potential prognostic roles of preoperative GRIm-Score in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for stage I-II non-small-cell lung cancer (NSCLC) by propensity score-matching (PSM) analysis. METHODS: This PSM-based analysis was performed on our single-center prospectively-maintained database between January 2014 and October 2015. A Kaplan-Meier survival analysis using the log-rank test was used to distinguish differences in both overall survival (OS) and disease-free survival (DFS) between the patients stratified by preoperative GRIm-Score. Multivariable Cox-proportional hazards regression analysis and PSM analysis were both carried out to determine the final independent prognostic parameters. RESULTS: There were 405 patients with surgically resectable stage I-II NSCLC included. Both OS and DFS were significantly shortened along with each number increase in the GRIm-Score group, showing a step-wise fashion. Such strong correlations between preoperative GRIm-Score estimated by a modified 3-category risk scale and survival outcomes still remained validated after PSM analysis. In addition, this GRIm-Score held the superior discriminatory power for predicting both OS and DFS to the other peripheral blood biomarkers. Multivariable analyses on the entire cohort and the PSM cohort demonstrated that GRIm-Score based on a 3-category risk assessment scale could be independently predictive of both OS and DFS. CONCLUSIONS: The GRIm-Score tool can also serve as an effective and noninvasive marker to optimize prognostic prediction for surgically resectable stage I-II NSCLC.

Fat-free mass index is superior to body mass index as a novel risk factor for prolonged air leak complicating video-assisted thoracoscopic surgery lobectomy for non-small-cell lung cancer.

BACKGROUND: To evaluate whether fat-free mass index (FFMI) could be predictive of prolonged air leak (PAL) complicating video-assisted thoracoscopic (VATS) lobectomy for non-small-cell lung cancer (NSCLC). METHODS: A retrospective study was conducted on the prospectively-maintained database in our institution between January 2015 and July 2017. The gender-specific median values of FFMI for males and females were applied as their respective cutoffs to stratify patients into low-FFMI group and high-FFMI group in initial univariable analyses. An effective multivariable logistic-regression analysis was then performed to demonstrate the predictive value of dichotomized FFMI. RESULTS: There were 1,091 surgical patients with NSCLC included (616 males and 475 females), with a PAL incidence of 14.6%. The median FFMI values among males and females were 17.3 and 14.6 kg/m2, respectively. PAL cases in both male (16.9±1.5 vs. 17.4±1.5 kg/m2; P=0.002) and female (14.0±0.9 vs. 14.6±1.1 kg/m2; P<0.001) groups had a significantly lower mean FFMI than that of non-PAL cases. The incidence of PAL was significantly increased in male patients with FFMI <17.3 kg/m2 (23.7% vs. 14.3%; P=0.003) and female patients with FFMI <14.6 kg/m2 (12.7% vs. 5.0%; P=0.003). Lower dichotomized FFMI was also significantly associated with prolonged time to air leak cessation and length of stay (LOS). Finally, multivariable logistic-regression analysis indicated that lower dichotomized FFMI [odds ratio (OR) =1.98; 95% confidence interval (CI): 1.33-2.96; P=0.001] could independently predict the occurrence of PAL. CONCLUSIONS: FFMI acts as an excellent categorical risk factor for PAL complicating VATS lobectomy and shows a much superior significance than body mass index (BMI) in terms of the prediction of PAL.

Albumin-to-alkaline phosphatase ratio as a novel prognostic indicator for patients undergoing minimally invasive lung cancer surgery: Propensity score matching analysis using a prospective database.

OBJECTIVES: To evaluate prognostic significance of albumin-to-alkaline phosphatase ratio (AAPR) for patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for non-small-cell lung cancer (NSCLC) by a propensity score-matching (PSM) analysis. METHODS: This PSM study was conducted on the prospectively-maintained database in our institution between December 2013 and March 2015. Overall survival analyses and further subgroup analyses were both performed to distinguish the differences in postoperative survival between patients stratified by an optimal cutoff of AAPR. Multivariable Cox proportional hazards regression models were established to determine the independent prognostic factors. RESULTS: There were 390 patients with operable NSCLCs included. An AAPR of 0.57 was identified as the optimal cutoff regarding to postoperative survival. Both overall survival (OS) and disease-free survival (DFS) in patients with AAPR≤0.57 were significantly shortened compared to those in patient with AAPR>0.57 (Log-rank P < 0.001). Patients with AAPR≤0.57 had significantly lower rates of OS and DFS than those of patients with AAPR>0.57 (P < 0.001). These differences still remained significant after subgroup analyses and PSM analyses. Multivariate analyses on the entire cohort and the PSM cohort commonly indicated that low preoperative AAPR could be an independent prognostic factor for unfavorable OS and DFS of resected NSCLCs. CONCLUSIONS: AAPR can serve as a novel risk stratification tool to refine prognostic prediction for surgical NSCLC. It may help surgeons to screen high-surgical-risk patients and further formulate individualized treatment schemes.

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.

Body surface area: a novel predictor for conversion to thoracotomy in patients undergoing video-assisted thoracoscopic lung cancer lobectomy.

BACKGROUND: The purpose of our study was to explore the value of body surface area (BSA) for predicting conversion to thoracotomy in patients undergoing video-assisted thoracoscopic (VATS) lobectomy for non-small cell lung cancer (NSCLC). METHODS: We performed a monocentric retrospective analysis based on a prospectively-maintained dataset of consecutive patients between March 2014 and August 2015 at our unit. The median value of BSA was used as the cut-off. Patients with BSA > median value were classified as the "large" group, while those with BSA ≤ median value were classified as the "non-large" group. The conversion rate and post-VATS morbidity between these two groups were evaluated. Finally, a multivariate logistic-regression analysis was performed to identify the predictors for conversion to thoracotomy. RESULTS: A total of 475 patients with a median BSA of 1.73 m2 were enrolled. There were 16 patients converted to thoracotomy (ratio =3.4%). The overall morbidity rate was 28.4%. The "large" group (BSA >1.73 m2) included 236 patients, while the "non-large" group (BSA ≤1.72 m2) included the remaining 239 patients. The conversion (5.5% vs. 1.3%; P=0.010) in the "large" patients was significantly higher than that in the "non-large" patients. No difference was found in the overall morbidity rate between these two groups (32.2% vs. 24.7%; P=0.069). The multivariate logistic-regression analysis demonstrated that BSA >1.73 m2 could be a strongly independent predictor for conversion to thoracotomy [odds ratio (OR): 7.17; P=0.028]. CONCLUSIONS: BSA is an excellent categorical predictor for conversion to thoracotomy in NSCLC patients undergoing VATS lobectomy. It may be considered when informing patients about intraoperative risks and selecting cases in the early learning curve of VATS techniques.

Efficacy of the fissureless technique on decreasing the incidence of prolonged air leak after pulmonary lobectomy: A systematic review and meta-analysis.

OBJECTIVE: The objective of our study was to evaluate the efficacy and safety of fissureless technique in pulmonary lobectomy by applying a meta-analysis of the current evidence. METHODS: We searched the PubMed, EMBASE and the Web of Science databases to recognize the eligible articles. The relative risk (RR) and weighted mean difference (WMD) with the corresponding 95% confidence interval (CI) served as the summarized estimates for dichotomous variables and continuous variables, respectively. Sensitivity analysis and publication bias tests were also performed to perceive potential bias risks. RESULTS: There were 6 studies with 843 surgical patients included into this meta-analysis. Finally, the meta-analysis demonstrated that fissureless technique could significantly reduce the incidence of prolonged air leak (PAL)[RR = 0.40; 95%CI=(0.24, 0.68); P = 0.001], the length of hospital stay [WMD = -0.52; 95%CI=(-0.87, -0.18); P = 0.003] and the duration of chest tube [WMD = -0.44; 95%CI=(-0.74, -0.14); P = 0.004]. Fissureless technique had also showed the benefit on decreasing the complication rate after lobectomy but without a statistical significance [RR = 0.77; 95%CI=(0.55, 1.07); P = 0.119]. In addition, no difference was observed in the operation time between the fissureless lobectomy and conventional lobectomy [WMD = 5.32; 95%CI=(-3.18, 13.83); P = 0.220]. CONCLUSIONS: Fissureless lobectomy is a superior alternative to conventional lobectomy in terms of preventing the PAL and shortening the length of hospital stay and chest tube duration. More multi-institution randomized controlled trials are required to confirm the validity of our findings in the future.

Clinicopathological and prognostic significance of chemokine receptor CXCR4 in patients with bone and soft tissue sarcoma: a meta-analysis.

The prognostic significance of CXC chemokine receptor 4 (CXCR4) in patients with bone and soft tissue sarcomas remains controversial. To investigate the impact of its expression on survival and clinicopathological features, we performed a meta-analysis. Comprehensive literature searches were conducted in PubMed, Web of Science, Embase and Cochrane Library for relevant studies. In total, 12 studies with 997 sarcoma patients were included. CXCR4 expression was found to be significantly associated with poor overall survival (HR 2.37, 95 % CI 1.86-3.01; P < 0.001). Further, when the analysis was stratified by histological subtypes (bony sarcoma including osteosarcoma and Ewing sarcoma and soft tissue sarcoma including synovial sarcoma and rhabdomyosarcoma), statistical analysis method (multivariate analysis and univariate analysis) and CXCR4 measuring method (IHC or RT-PCR), the significant correlation to poor overall survival was also observed except for that in Ewing sarcoma and RT-PCR groups. As for clinicopathological features, CXCR4 expression was significantly associated with higher rate of metastasis (OR 6.97, 95 % CI 2.28-21.31; P = 0.001) and higher tumor stage (OR 7.55, 95 % CI 1.25-45.47; P = 0.027), but not associated with gender, age and tumor site. In conclusion, CXCR4 expression may be an effective predictive factor of poor prognosis and clinicopathological features for bone and soft tissue sarcomas. Further studies are needed to validate our findings.

Clinicopathological and prognostic significance of Oct-4 expression in patients with non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Octamer-binding transcription factor 4 (Oct-4) has been identified to participate in the tumorigenicity and malignancy of non-small cell lung cancer (NSCLC). However, its definite prognostic roles in NSCLC still remain a debate. Therefore, we conducted this meta-analysis to evaluate the prognostic value of Oct-4 expression in NSCLC and its relationship to some major clinicopathological characteristics. METHODS: A comprehensive literature retrieval was performed in PubMed, EMBASE and the Web of Science to identify the full-text articles that met our eligibility criteria. Odds ratio (OR) with 95% confidence interval (CI) severed as the summarized statistics for clinicopathological assessments, and hazard ratio (HR) with 95% CI served as the summarized statistics for prognostic assessments. Q-test and I(2)-statistic were used to evaluate the level of heterogeneity. Potential publication bias was detected by both Begg's test and Egger's test. RESULTS: There were 16 retried articles with 1,363 NSCLC cases included into this meta-analysis. Oct-4 expression was found to be significantly associated with the unfavorable outcomes for differentiation degree (OR: 3.065; 95% CI: 1.568-5.957; P=0.001), TNM stage (OR: 3.695; 95% CI: 2.252-6.063; P<0.001) and lymphatic metastasis (OR: 2.372; 95% CI: 1.504-3.742; P<0.001), but not associated with the histological subtypes, gender, age and smoking status. Oct-4 expression was also significantly associated with the poor prognosis of NSCLC (HR: 3.030; 95% CI: 2.283-4.021; P<0.001). The prognostic roles of Oct-4 expression in NSCLC still remained statistically reliable in the subgroups stratified by statistical analysis, patients' origins, positively-stained sites and histological subtypes. CONCLUSIONS: Our meta-analysis indicates that Oct-4 can serve as a strong biomarker predicting the poor clinicopathological and prognostic characteristics of NSCLC. More high-quality studies based on a large sample size will be very helpful to further validate and modify our findings in the future.

A systematic review and meta-analysis-does chronic obstructive pulmonary disease predispose to bronchopleural fistula formation in patients undergoing lung cancer surgery?

BACKGROUND: we conducted this systematic meta-analysis to determine the association between chronic obstructive pulmonary disease (COPD) and risk of bronchopleural fistula (BPF) in patients undergoing lung cancer surgery. METHODS: Literature retrieval was performed in PubMed, Embase and the Web of Science to identify the full-text articles that met our eligibility criteria. Odds ratio (OR) with 95% confidence interval (CI) served as the summarized statistics. Q-test and I(2)-statistic were used to evaluate the level of heterogeneity. Sensitivity analysis was performed to further examine the stability of pooled OR. Publication bias was detected by both Begg's test and Egger's test. RESULTS: Eight retrospective observational studies were included into this meta-analysis. The overall summarized OR was 2.03 (95% CI: 1.44-2.86; P<0.001), revealing that COPD was significantly associated with the risk of BPF after lung cancer surgery. In subgroup analysis, the relationship between COPD and BPF occurrence remained statistically prominent in the subgroups stratified by statistical analysis (univariate analysis, OR: 1.91; 95% CI: 1.35-2.69; P<0.001; multivariate analysis, OR: 3.18; 95% CI: 1.95-5.19; P<0.001), operative modes (pneumonectomy, OR: 2.11; 95% CI: 1.15-3.87; P=0.016) and in non-Asian populations (OR: 2.36; 95% CI: 1.18-4.73; P=0.016). No significant impact of COPD on BPF risk was observed in Asian patients (OR: 1.48; 95% CI: 0.85-2.57; P=0.16). No significant heterogeneity or publication bias was discovered across the included studies. CONCLUSIONS: Our meta-analysis indicates that COPD can significantly predispose to BPF formation in patients undergoing lung cancer surgery. Because some limitations still exist in this meta-analysis, our findings should be further verified and modified in the future.

Diabetes Mellitus and Risk of Bronchopleural Fistula After Pulmonary Resections: A Meta-Analysis.

We conducted this meta-analysis to evaluate the association between diabetes mellitus and the risk of bronchopleural fistula in patients undergoing pulmonary resection. The PubMed and EMBASE databases were searched, and 15 retrospective observational studies were included. The pooled analysis showed that diabetes mellitus was significantly associated with the formation of bronchopleural fistula after pulmonary resection (odds ratio = 1.97; 95% confidence interval = 1.39 to 2.80; p < 0.001). This association remained statistically prominent in the subgroups classified by statistical analysis, diagnoses and operative modes and in Asian patients. Therefore, diabetes mellitus can be an independent risk factor for bronchopleural fistula after pulmonary resection.

Prognostic value of stromal decorin expression in patients with breast cancer: a meta-analysis.

BACKGROUND: Numbers of studies have investigated the biological functions of decorin (DCN) in oncogenesis, tumor progression, angiogenesis and metastasis. Although many of them aim to highlight the prognostic value of stromal DCN expression in breast cancer, some controversial results still exist and a consensus has not been reached until now. Therefore, our meta-analysis aims to determine the prognostic significance of stromal DCN expression in breast cancer patients. METHODS: PubMed, EMBASE, the Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for full-text literatures met out inclusion criteria. We applied the hazard ratio (HR) with 95% confidence interval (CI) as the appropriate summarized statistics. Q-test and I(2) statistic were employed to estimate the level of heterogeneity across the included studies. Sensitivity analysis was conducted to further identify the possible origins of heterogeneity. The publication bias was detected by Begg's test and Egger's test. RESULTS: There were three English literatures (involving 6 studies) included into our meta-analysis. On the one hand, both the summarized outcomes based on univariate analysis (HR: 0.513; 95% CI: 0.406-0.648; P<0.001) and multivariate analysis (HR: 0.544; 95% CI: 0.388-0.763; P<0.001) indicated that stromal DCN expression could promise the high cancer-specific survival (CSS) of breast cancer patients. On the other hand, both the summarized outcomes based on univariate analysis (HR: 0.504; 95% CI: 0.389-0.651; P<0.001) and multivariate analysis (HR: 0.568; 95% CI: 0.400-0.806; P=0.002) also indicated that stromal DCN expression was positively associated with high disease-free survival (DFS) of breast cancer patients. No significant heterogeneity or publication bias was observed within this meta-analysis. CONCLUSIONS: The present evidences indicate that high stromal DCN expression can significantly predict the good prognosis in patients with breast cancer. The discoveries from our meta-analysis have better be confirmed in the updated review pooling more relevant investigations in the future.

Characterization of two tartary buckwheat R2R3-MYB transcription factors and their regulation of proanthocyanidin biosynthesis.

Tartary buckwheat (Fagopyrum tataricum Gaertn.) contains high concentrations of flavonoids. The flavonoids are mainly represented by rutin, anthocyanins and proanthocyanins in tartary buckwheat. R2R3-type MYB transcription factors (TFs) play key roles in the transcriptional regulation of the flavonoid biosynthetic pathway. In this study, two TF genes, FtMYB1 and FtMYB2, were isolated from F. tataricum and characterized. The results of bioinformatic analysis indicated that the putative FtMYB1 and FtMYB2 proteins belonged to the R2R3-MYB family and displayed a high degree of similarity with TaMYB14 and AtMYB123/TT2. In vitro and in vivo evidence both showed the two proteins were located in the nucleus and exhibited transcriptional activation activities. During florescence, both FtMYB1 and FtMYB2 were more highly expressed in the flowers than any other organ. The overexpression of FtMYB1 and FtMYB2 significantly enhanced the accumulation of proanthocyanidins (PAs) and showed a strong effect on the target genes' expression in Nicotiana tabacum. The expression of dihydroflavonol-4-reductase (DFR) was upregulated to 5.6-fold higher than that of control, and the expression level was lower for flavonol synthase (FLS). To our knowledge, this is the first functional characterization of two MYB TFs from F. tataricum that control the PA pathway.