Objective To explore the clinical significance of estrogen receptor α( ERα) , estrogen receptor β( ERβ) in non-small cell lung cancer( NSCLC) .Methods EnVision method was used to detect the expressions of ERα, ERβ, vascular endothelial growth factor( VEGF) , and microvessel density( MVD) in 54 NSCLC patients, 10 patients with lung benign lesions, and 10 normal controls. The interrelation between ERα, ERβ, VEGF, and MVD was analyzed. Results No obvious expressions of ERα and ERβwere observed in the normal lung tissues and lung benign lesions. The positive expression rates of ERα, ERβ, and VEGF in NSCLC were 20. 4% ( 11/54) , 64. 8% ( 35/54) , and 64. 8% ( 35/54) , respectively. There were no significant differences between ERαin regard to clinical parameters of NSCLC. But the expression of ERβwas dependent on pathological classification and differentiation of NSCLC. The expression of ERβ was significantly higher in adenocarcinoma than in squamous cell carcinoma( P lt; 0. 05) . The expression rate of ERβin well differentiated group was significantly higher than that in low, moderately differentiated group( P lt;0. 05) . There were significant differences between VEGF in regard to lymph node metastasis and TNM stage. The expression of ERαinterrelated with VEGF and MVD with r value of 0. 4 and 0. 685 respectively ( P lt;0. 05) . There was little correlation between ERβ and VEGF, MVD( P gt; 0. 05) . Conclusion Theexpression of ERβ correlates with pathological classification and differentiation of NSCLC, suggesting its significance in evaluating the pathological classification and malignant degree of NSCLC. The expression of ERαcorrelates with VEGF and MVD, suggesting that ERαpossibly promote micro-angiogenesis of NSCLC by VEGF pathway.
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.
ObjectiveTo evaluate the efficacy of thoracoscopic complex segmentectomy for stageⅠnon-small cell lung cancer (NSCLC).MethodsWe retrospectively reviewed the perioperative clinical data of patients with stageⅠNSCLC who underwent thoracoscopic complex segmentectomy (n=58) or simple segmentectomy (n=33) between January 2017 and March 2020 in our hospital. There were 36 males and 55 females with a median age of 57 years (range: 50-66 years). The clinical data of the two groups were compared.ResultsThere were no significant differences between the two groups in characteristics including age, sex, weight, comorbidities, preoperative pulmonary function, dominant composition of tumor, tumor histology and size, overall complications, estimated blood loss, prolonged air leakage, length of hospital stay, length of drainage, surgical margin distance or number of dissected lymph nodes. Only the operation time and number of staples for making intersegmental plane were significantly different between the two groups (P<0.05). There was no perioperative death in both groups.ConclusionThoracoscopic complex segmentectomy is a feasible and safe technique for stageⅠNSCLC.
Objective To investigate the clinical significance of serum cystatin C ( Cys C) in patients with non-small cell lung cancer ( NSCLC) .Methods The serumlevel of cystatin C was determined by enzyme linked immunosorbent assay ( ELISA) in patients with NSCLC, patients with benign lung diseases, and normal controls. Results The serum level of Cys C in the NSCLC patients was much higher than those in the patients with benign lung diseases and the normal control subjects [ ( 1.47 ±0.78) mg/L vs. ( 1.04 ±0.51) mg/L and ( 1.06 ±0.36) mg/L, Plt;0.01] . The level of Cys C in the NSCLC patients was significantly related to clinical stage [ TNM stage -Ⅱ vs. Ⅲ-Ⅳ: ( 1.38 ±0.88) mg/L vs. ( 1.57 ± 0.79) mg/L] , lymph node metastasis [ metastatic vs. non-metastatic: ( 1.83 ±0.97) mg/L vs. ( 1.06 ± 0.39) mg/L] , and differentiation degree [ medium-high differentiation vs. low differentiation: ( 1.63 ± 0.73) mg/L vs. ( 1.26 ±0.48) mg/L] ( all Plt;0.05) . However no correlation of Cys C with gender, age, and histological type was revealed ( Pgt;0.05) . Conclusion Cys C may contribute to the occurrence and development of NSCLC.
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.
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.
Objective To evaluate the value of 18 F-fluorodeoxyglucose ( 18 F-FDG) metabolism imaging in evaluating the response of patients with non-small cell lung cancer ( NSCLC) in stable diseaseafter chemotherapy. Methods 28 patients with NSCLC in stable disease after chemotherapy admitted between September 2010 to September 2012 were retrospectively investigated. The reduction ratio of targetto-nontarget ratio ( T/N) before and after chemotherapy was calculated. The patients were followed up 3 to 12 months to measure progression-free survival ( PFS) . The correlation between the reduction ratio of T/N and PFS was analyzed. The patients were divided into a reduction group and a non-reduction group according to the difference of the reduction ratio of T/N and was compared the difference of the PFS.Results The reduction ratio of T/N had positive correlation with PFS( Pearson r = 0. 668, P lt; 0. 01) . The PFS of the reduction group was longer than that in the non-reduction group ( 8. 0 ±2. 5 months vs. 5. 3 ±1. 2 months,P lt;0. 05) . Conclusions The reduction ratio of T/N is positively correlated with PFS in NSCLC patients in stable disease after chemotherapy. It is possible to evaluate the efficacy of the treatment according to the reduction ratio of T/N.
Treatment of Non-small Cell Lung Cancer by Single-direction Four-hole Complete Video-assisted Thoracoscopic Lobectomy HUANG Jia, ZHAO Xiao-jing, LIN Hao, TAN Qiang, DING Zheng-ping, LUO Qing-quan. (Shanghai Lung Tumor Clinical Medical Center, Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai 200030, P. R. China) Corresponding author：LUO Qing-quan, Email：luoqingquan@hotmail. com Abstract： Objective To explore the feasibility and safety of single-direction four-hole video-assisted thoracoscopic lobectomy in the treatment of non-small cell lung cancer (NSCLC). Methods Between January 2007 and December 2010, 428 patients with NSCLC were surgically treated by single-direction complete video-assisted thoracoscopic lobectomy in Shanghai Chest Hospital. There were 186 males and 242 females; aged 33 to 78 years. All the patients were diagnosed as primary NSCLC at early clinical stage. Among the 428 patients, 134 patients underwent right upper lobectomy, 48 patients underwent right middle lobectomy, 98 patients underwent right lower lobectomy, 4 patients underwent right middle and lower lobectomy, 72 patients underwent left upper lobectomy, and 72 patients underwent left lower lobectomy. All the 428 patients were divided into two groups according to their surgical approach：a three-hole group (300 patients) and a four-hole group (128 patients).The clinical results of the two groups were analyzed. Results A total of 412 patients underwent complete video-assisted thoracoscopic lobectomy, and 16 patients (3.7%) underwent conversion to open surgery. The average operation time was 132.1 (120-180) min, average length of incision was 3.7 (3-5) cm, and average blood loss was 150.0 (50-800) ml. There was no statistical difference in extubation time, intraoperative blood loss, and postoperative hospital stay between the two groups. But the operation time of the four-hole group is significantly shorter than that of the three-hole group （P＜0.05）. The 16 patients who underwent conversion to open surgery received intraoperative blood transfusion. Five patients died of severe pulmonary infection, pulmonary embolism, and acute cerebral infarction. Fifty two patients had squamous cancer, 340 patients had adenocarcinoma, 20 patients had adenosquamous carcinoma, 8 patients had poorly differentiated carcinoma, 6 patients had big cell lung cancer, and 2 patients had carcinoid. Postoperative persistent lung air leak occurred in 4 patients, thoracic empyema in 2 patients, pulmonary infection in 4 patients, arrhythmia in 26 patients, pulmonary embolism in 2 patients, chylothorax in 2 patients, and acute cerebral infarction in 2 patients. The overall 3-year survival rate was 83.6%（358/428）. Conclusion Single-direction four-hole complete video-assisted thoracoscopic lobectomy is feasible, safe and consistent with the operation standard in the surgical treatment for NSCLC patient. It is also helpful to reduce the operation time and facilitate lymph node dissection. Key words： Video-assisted thoracoscopic surgery； Lobectomy； Single-direction； Four-hole； Non-small cell lung cancer
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.
Abstract: Objective To evaluate the significance of expression of vascular endothelial growth factor-C （VEGF-C） and cytokeratin 19 （CK19） in patients with stage I non-small cell lung cancer （NSCLC）. Methods A total of 269 patients with NSCLC who underwent standard lobectomy and lymph node dissection by the same surgical team in our hospital from January 2004 to June 2005 were included in this study. All the clinical data and follow-up results were complete, and all the pathological specimens were well kept. No preoperative or postoperative adjuvant therapy such as radiotherapy and chemotherapy was administered to those patients. Expressions of VEGF-C in cancer tissues was detected by immunohistochemical streptavidin-peroxidase （S-P） method, and CK19 was marked to examine micrometastasis in hilar and mediastinal lymph nodes. Clinical outcomes, pathological results and follow-up data were analyzed in combination with VEGF-C and CK19 expression. Results VEGF-C expression was not statistically different between different category in sex（Hc=1.722，P=0.084）, age （Hc=0.914，P=0.360）, smoking （Hc=2.440，P=0.295）, pathology type （Hc=5.668，P=0.058）or tumor size （Hc=0.165，P=0.920） . VEGF-C expression was statistically different between different groups of pathological differentiation （Hc=29.178，P=0.000). CK19 expression was not statistically different between different category in sex（χ2=0.000，P=0.999）, age （χ2=0.005，P=0.999）, smoking （χ2=2.294，P=0.317）, pathology type （χ2=0.573，P=0.289）, tumor size（χ2=0.006，P=0.999）, and pathological differentiation （χ2=2.927，P=0.231）. Five-year survival rate was statistically different between different grade of VEGF-C expression （χ2=37.318，P=0.000), and was also statistically different between positive group and negative group of CK19 （χ2=39.987，P=0.000). There was statistical difference between different grade of VEGF-C expression and positive rate of CK19 （χ2=25.954，P=0.000). Conclusion Expression of VEGF-C and CK19 is closely related to postoperative 5-year survival of patients with stage I NSCLC. Detection of VEGF-C and CK19 is of great clinical significance as it is helpful to predict patient prognosis and choose proper postoperative adjuvant therapy.