Abstract： Objective To evaluate the safety, feasibility, and clinical outcome of complete video-assisted thoracoscopic surgery （VATS） lobectomy for patients with early-stage non-small cell lung cancer （NSCLC）. Methods We retrospectively analyzed the clinical data of 160 consecutive patients（the VATS group, 83 males and 77 females with average age at 60.8 years）with early-stage NSCLC who underwent complete VATS lobectomy between January 2005 andDecember 2008 in Zhongshan Hospital of Fudan University，and compared them with 357 patients（the thoracotomy group, 222 males and 135 females with average age at 59.5 years）who underwent open thoracotomy in the same period. Results The conversion rate of the VATS group was 5.0%（8/160）. The operation time of the VATS group was significantly shorter than that of the thoracotomy group（113.0 min vs.125.0 min, P=0.039）. Length of postoperative hospital stay was not statistically different between the two groups（10.3±4.3 d vs.9.1±4.6 d，P=0.425）. The postoperative morbidity of the VATS lobectomy group and the thoracotomy group was 9.4%（15/160）and 10.1% （36/357） respectively，and the postoperative mortality of the two groups was 0.6%（1/160）and 2.0%（7/357）respectively. There was no statistical difference in the mean group of lymph node dissection （2.4±1.5 groups vs.2.4±1.7 groups，P=0.743） and the mean number of lymph node dissection （9.8±6.3 vs.10.1±6.4，P=0.626） between the two groups. The overall 5-year survival rate of the VATS group was significantly higher than that of the thoracotomy group （81.5% vs.67.8%, P=0.001）. Subgroup analysis showed that the 5-year survival rate of pⅠa stage, pⅠb stage, and pⅢa stage was 86.0%, 84.5%, and 58.8% respectively in the VATS group, and 92.9%, 76.4%, and 25.3% respectively in the thoracotomy group. Conclusion Complete VATS lobectomy is technically safe and feasible for patients with early-stage NSCLC. The lymph node dissection extension of complete VATS lobectomy is similar to that of open thoracotomy, and long-term outcome of complete VATS lobectomy is superior to that of open thoracotomy. Randomized controlled trials of large sample size are further needed to demonstrate superiority.
ObjectiveTo reveal the potential mechanism of cisplatin resistance in non-small cell lung cancer A549 cells by comparing the expression profiles of wild-type A549 cells and cisplatin-resistant A549 cells (A549/DPP) through whole transcriptome sequencing analysis.MethodsThe cisplatin resistant A549 (A549/DDP) cell line was first established. Then, the whole-transcriptome analysis was conducted both on A549 and A549/DDP cells. Next, the differentially expressed RNAs of lncRNA-seq, circRNA-seq, and miRNA-seq data were identified, respectively, followed by functional enrichment analysis. Finally, a comprehensive analysis based on the whole transcriptome data was performed and the construction of the ceRNA network was carried out.ResultsA total of 4 517 lncRNA, 123 circRNA, and 145 miRNA were differentially expressed in A549/DDP cells compared with the A549 cell line. These different RNAs were significantly enriched in cancer-related pathways. The ceRNA network contained 12 miRNAs, 4 circRNAs, 23 lncRNAs, and 9 mRNA nodes, of which hsa-miR-125a-5p and hsa-miR-125b-5p were important miRNAs based on the topological analysis.ConclusionTumor necrosis factor signaling pathway and p53 signaling pathway are involved in A549/DPP resistance. Hsa-miR-125a-5p and hsa-miR-125b-5p may be potential targets for reversing cisplatin resistance.
ObjectiveTo systematically review the clinical efficacy and safety of afatinib in the treatment of advanced non-small cell lung cancer (NSCLC).MethodsWe electronically searched databases including The Cochrane Library, PubMed, EMbase, CNKI, WanFang Data and VIP to collect randomized controlled trials (RCTs) about the afatinib for advanced non-small cell lung cancer from inception to October 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. ResultsEight RCTs were included. The results of meta-analysis showed that afatinib could significantly prolonged progression-free survival (PFS) for lung adenocarcinoma patients (HR=0.43, 95%CI 0.32 to 0.57, P<0.000 01), but there was no significant difference between the two groups in terms of overall survival (OS) in patients with lung adenocarcinoma (HR=1.03, 95%CI 0.85 to 1.23, P=0.79). In addition, afatinib significantly increased the patient’s adverse reactions including diarrhea, skin rashes, nausea and vomiting.ConclusionAfatinib can improve PFS in patients with lung adenocarcinoma, but it does not prolong OS. Due to the limited quantity and quality of included studies, the above conclusions are still needed to be verified by more high quality studies.
Objective To study the expressions of Livin, Caspase-3 and Bcl-2 in lung tissue of nonsmall cell lung cancer ( NSCLC) , and their relationship with the clinicopathological features and prognosis of NSCLC. Methods The expressions of Livin, Caspase-3 and Bcl-2 proteins were evaluated by immunohistochemical method in 87 NSCLC samples and 40 lung benign tissues. The relationship of their expressions with the clinicopathological features and prognosis of NSCLC were analyzed by Spearman’s Rank correlation and COX Regression. Results More NSCLC tissues showed expression of Livin than lung benign tissues( 72. 41% vs 0. 0% , P = 0. 000 ) , and the expression of Caspase-3 was significantly decreased ( 67. 82% vs 87. 5%, P lt; 0. 05 ) . The proteins of Livin, Caspase-3 and Bcl-2 were detected in the endochylema but none was detected in nucelus. There was no relationship between the expression of each of these proteins and the clinicopathological features of NSCLC such as histologic type, tumor differentiation,lymph node metastasis, TNM stage, the size of tumor, and tumor site. The expression of Livin was correlated with Caspase-3 and Bcl-2 expressions ( r1 = - 0. 260, P = 0. 015; r2 = 0. 351, P = 0. 001) . Livin, Caspase-3 and Bcl-2 were not independent prognostic factors of NSCLC. Conclusions The expression of Livin and Bcl-2 are up-regulated in NSCLC. The expression of Livin is positively correlated with that of Caspase-3 and Bcl-2, they might interact with each other in the carcinogenesis and development of NSCLC. The levels of Livin, BCl-2 and Caspase-3 proteins are not independent factors affecting the prognosis of lung cancer patients.
ObjectiveTo analyze the relationship between maximum standardized uptake value (SUVmax) of primary tumor detected by 18F-FDG positron emission tomography/computed tomography (PET/CT) and clinicopathologic factors in stageⅠnon-small cell lung cancer (NSCLC), and investigate the prognostic value of PET/CT on pathological feature. MethodsWe retrospectively analyzed clinical data of 182 patients with stageⅠNSCLC who underwent 18F-FDG PET/CT scan before lobectomy or segmentectomy in China-Japan Friendship Hospital from April 2013 to June 2014. There were 121 male and 61 female patients with their ages of 34-85 (68.1±9.8) years. Clinicopathologic factors including sex, age, smoking history, histology, TNM stage, T stage, tumor size, lymphatic vessel invasion, blood vessel invasion (BVI) and visceral pleural invasion were evaluated to identify the independent factors affecting SUVmax by univariate and multivariate regression analysis. The diagnostic efficiency and best cut-off point of SUVmax were calculated by the receiver operating characteristic curve. ResultsThe univariate analysis identified that sex (P=0.015), smoking history (P=0.001), histology (P < 0.001), TNM stage (P=0.004), T stage (P=0.001), tumor size (P < 0.001), BVI (P=0.001) were factors affecting SUVmax. Only histology (P=0.001), tumor size (P=0.006), BVI (P=0.009) were found to be significant independent factors according to multivariate regression analysis. The SUVmax of primary tumor was a predictor for BVI with the highest diagnostic accuracy at a cut-off value of 4.85, the sensitivity and specificity were 65.5% and 71.7%. ConclusionThe SUVmax is correlated with histology, tumor size and BVI in stageⅠNSCLC, higher in patients with non-adenocarcinoma, lager tumor and positive BVI. Furthermore, the probability of BVI could be predicted by SUVmax of the primary tumor.
ObjectiveTo systematically review the efficacy and safety of crizotinib in the treatment of non-small cell lung cancer (NSCLC).MethodWe electronically searched databases including the Cochrane Library (Issue 5, 2017), PubMed, Embase, China Biology Medicine Database, China National Knowledge Internet Database, VIP Database and Wangfang Data from the establishment to May 2017. The randomized controlled trials (RCTs), non-RCTs, case series and case reports on crizotinib for NSCLC were included. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, assessed the methodological quality of included studies, then make Meta-analysis and descriptive analysis.ResultA total of 15 studies were included, including 4 RCTs, 1 non-RCT, 4 case series and 6 case reports. The results indicated that the progression-free survival time of crizotinib group was 8 months, which was better than chemotherapy group (4.6 months). The results of Meta-analysis showed that the response rate in the crizotinib group was higher than that in the chemotherapy group [RR=2.35, 95%CI (1.59, 3.46), P<0.000 1]. The one year survival rate in the crizotinib group was 74.5%-78.6%. The incidences of adverse reactions including dysopsia, dysgeusia, diarrhea, vomiting, constipation, transaminase lifts, upper respiratory tract infection, edema and dizziness in the crizotinib group were higher than those in the chemotherapy group (P<0.05), while the incidences of adverse reactions including leukopenia, thrombocytopenia, alopecia and fatigue in crizotinib group were lower than those in the chemotherapy group (P<0.05). Subgroup analysis under precision treatment showed the progression-free survival time of anaplastic lymphoma kinase (ALK)-positive group was 8 months, and it was longer than ALK-negative group of 4 months.ConclusionsBased on current evidence, crizotinib is better than chemotherapy for NSCLC. Due to limited quality of the included studies, the above conclusion needs to be verifed by more high quality studies.
Objective To investigate the indication of carina reconstruction surgery for locally advanced non-small cell lung cancer through analyzing the clinicopathological characteristics and prognosis of these patients.Methods Fifteen patients were involved in this retrospective analysis. One patient underwent carina resection and reconstruction, 6 patients underwent right pneumonectomy plus carina resection and reconstruction, 3 patients underwent right upper lobe and carina resection plus carina reconstruction, and 5 patients underwent left pneumonectomy plus carina resection and carina reconstruction. Kaplan-Meier method was used to calculate the survival rate, and Logrank test was used to compare the survival difference between groups. Results The mean duration time for operation was 410 min(261.3±81.6min). The number of resected mediastinal lymph nodes was 10.8±3.7. No perioperative death occurred. Two patients complicated with pneumonitis after surgery, both of them recovered through machine supported respiratory combined with antibiotics administering; 1 patient complicated with chylothorax and recovered through noninvasive procedure; 1 patient underwent thoracotomy exploration due to the persistant air leak and cured by suturing the air leaking lung tissue.The median survival time for whole group was 39 months, 3-year and 5-year survival rate were 52.5%，22.5%, respectively. The median survival time for the patients underwent right pneumonectomy was 12 months, compared 40 months with that of other patients. Conclusion Carina reconstruction is necessary for some patients with locally advanced nonsmall cell lung cancer with main bronchus or carina invasion, despite the sophisticated operation procedure and high morbidity rate. While the right pneumonectomy plus carinal reconstruction should be avoided due to the poor prognosis.
Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.
ObjectiveTo evaluate the methodological quality of systematic reviews and meta-analysis (SRs/MAs) in fields of integrated Chinese-western therapy for non-small cell lung cancer (NSCLC). MethodsSRs/MAs in fields of integrated Chinese-western therapy for NSCLC were searched inPubMed, EMbase, CBM, CNKI, VIP and WanFang Data from inception to July 10th, 2016. We also handsearched relevant journals such as Chin J Evid-based Med and reference of included studies, and tried to find the grey literature for additional studies. Two researchers independently screened literature and extracted data. Then methodological quality of included SRs/MAs were evaluated by AMSTAR scale. ResultsA total of 53 SRs/MAs were included, the highest and lowest scores of methodological quality were 9 and 1, respectively. The average score was 5.98±1.50. Results on the qualities of methodology or evaluation showed that 46 SRs/MAs (88.68%) was rated as moderate and 6 (11.32%) as low． The main problems were found in such areas as preliminary design scheme, literature searching, a list of included and excluded studies, etc.. ConclusionThe methodology of SRs/MAs in fields of integrated Chinese-western therapy for NSCLC have quality problems at different levels, further improvement should be expected.
Objective To evaluate the clinical effectiveness and safety of radiotherapy (RT) combined with hyperthermia (HT) for locally-advanced non-small cell lung cancer (NSCLC). Methods The randomized controlled trials (RCTs) on RT plus HT vs. RT alone for locally-advanced NSCLC were searched in PubMed, The Cochrane Library, EMbase, VIP, CNKI, CBM and other electronic databases from inception to November 2011. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and assessed quality of the included studies independently. Then meta-analyses were performed using RevMan 5.0.2. Results A total of 9 RCTs involving 527 cases were included. The results of meta-analyses showed that compared with the RT alone group, the RT plus HT group could increase the total effective rate (OR=2.08, 95%CI 1.44 to 3.02, P=0.000 1) and the progression-free survival rate (OR=4.85, 95%CI 1.88 to 12.48, P=0.001). However, there were no significant differences between the two groups in the overall survival rate (OR=1.13, 95%CI 0.64 to 1.98, P=0.68), symptoms improve rate (OR=3.37, 95%CI 1.68 to 6.78, P=0.000 6), and other acute adverse reactions. Conclusion Current results of systematic review show that radiotherapy combined with hyperthermia can obviously increase the total effective rate and improve the progression-free survival rate for locally-advanced NSCLC, and doesn’t increase the incidence of adverse reaction. Therefore, radiotherapy combined with hyperthermia is a fairly reasonable and effective treatment method for locally-advanced NSCLC.