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The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy., (© 2021. The Author(s).)

Background: There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients., Methods: A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients., Results: After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy., Conclusion: Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Purpose: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor ( EGFR ) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results., Methods: From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR -activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data., Results: Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% ( P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP ( P = .316) and 5y DFS rates were 22. 6% and 23.2% ( P = .928), respectively., Conclusion: Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.

Objectives: Health-related quality of life (HRQoL) data complement conventional clinical endpoints when comparing adjuvant gefitinib with chemotherapy in patients with early-stage non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. This study aimed to assess changes in HRQoL with adjuvant gefitinib vs chemotherapy in this patient group., Materials and Methods: In the phase III ADJUVANT trial, patients with completely resected, stage II-IIIA (N1-N2), EGFR-mutant NSCLC were randomized (1:1) to receive either gefitinib for 24 months or vinorelbine plus cisplatin (VP) every 3 weeks for four cycles. HRQoL was assessed as a secondary endpoint using the Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L), Lung Cancer Symptom Scale (LCSS) questionnaires, and Trial Outcome Index (TOI) composite score. HRQoL dynamics, improvements, and time to deterioration were compared between groups., Results: At baseline, 104 of 106, and 80 of 87 patients receiving gefitinib and VP, respectively, completed two questionnaires (FACT-L and LCSS). Baseline scores were balanced between groups. Although HRQoL fluctuated and gradually improved in both groups, longitudinally higher scores were reported with gefitinib than VP (FACT-L, odds ratio 418.16, 95 % confidence interval [CI] 2.75-63509.05, p =  0.019; LCSS, 1.13, 1.04-1.22, p =  0.003; TOI, 88.39, 4.40-1775.05, p =  0.003). Time to deterioration in HRQoL was delayed with gefitinib compared with VP (FACT-L, median 69 vs 6 weeks, hazard ratio 0.62, 95 % CI 0.42-0.90, p =  0.013; LCSS, median 45 vs 6 weeks, 0.63, 0.43-0.93, p =  0.020; TOI, median 164 vs 9 weeks, 0.51, 0.33-0.77, p =  0.001)., Conclusion: Adjuvant gefitinib is associated with improved HRQoL over VP, supporting its use in patients with stage II-IIIA (N1-N2), EGFR-mutant NSCLC., (Copyright © 2020. Published by Elsevier B.V.)

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., (Copyright © 2019 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Controversy still exists in which subtype of non-small-cell lung cancer [squamous cell carcinoma (SCC) or adenocarcinoma] is more likely to have lymph node (LN) metastasis. The aim of this study is to compare the pattern of LN metastasis in two cohorts of matched patients surgically treated for SCC or adenocarcinoma., Methods: A retrospective analysis of patients undergoing lobectomy or segmentectomy with systematic lymphadenectomy without preoperative treatment for lung SCC or adenocarcinoma was conducted in this study. Data for analysis consisted of age, gender, tumor size, lobe-specific tumor location, tumor location (peripheral or central), and pathologic findings. We conducted the propensity score-matched (PSM) analysis to eliminate potential bias effects of possible confounding factors., Results: From January 2015 to December 2016 in our department, we finally included a total of 387 patients (including 63 patients with SCC and 324 patients with adenocarcinoma) for analysis. For the unmatched cohort, there was no sufficient evidence of significantly different number of positive LNs (P = 0.90) and rate of LN metastasis (P = 0.23) between SCC patients and adenocarcinoma patients. However, potential confounding factors, for example gender, tumor size, tumor location, tumor differentiation, and total number of dissected LNs, were significantly different between patients with SCC and those with adenocarcinoma. In the analysis of matched cohort after PSM analysis, those above confounding factors were comparable between the two groups. However, patients with adenocarcinoma had significantly more mean positive LNs (2.2 and 0.7; P = 0.008) and a higher rate of LN metastasis (53% and 29%; P = 0.016) than those with SCC., Conclusions: Lung adenocarcinoma had a higher risk of LN metastasis than SCC, suggesting that different therapeutic modalities may be indicated for the two different subtypes of lung cancer.

Introduction: Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized., Methods: Overall, 222 stage N1-N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted., Results: There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 [27.4%]), extracranial metastases were most frequent in the VP group (32 of 87 [36.8%]). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib., Conclusions: Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1-N2 EGFR-mutant NSCLC but longer duration should be explored., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC., Methods: We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m 2 on days 1 and 8) plus intravenous cisplatin (75 mg/m 2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079., Findings: Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8-44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9-32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6-22·3]; hazard ratio [HR] 0·60, 95% CI 0·42-0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related., Interpretation: Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature., Funding: Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: To retrospectively investigate the clinical characteristics, surgical treatments of the patients with lung ground-glass opacities (GGO)., Methods: All the patients, who underwent surgical resection of GGO in our department from Jan. 2013 to Dec. 2016 were retrospectively reviewed. The clinicpathological features were analyzed., Results: A total of 663 patients were included in this study. The rate of malignancy was 92.6% (614/663). The diameter of GGO in benign group [(0.8±0.2) cm] was significant smaller than that in malignant group [ (1.5±0.8) cm]( P <0.001). The rate of irregular margin in malignant group was far higher than that in benign group (93.8% vs. 20.4%, P <0.001), but other CT signs such as vacuole sign, plural retraction, speculation and lobulation did not show significant difference between the two groups. A total of 652 (98.3%) cases were resected by video-assisted thoracoscopic surgery (VATS), and only 11 (1.7%) cases were resected by thoracotomy. A total of 336 (50.7%) patients underwent lobectomy, 226 (34.1%) underwent segmentectomy and 101 (15.2%) undewent wedge resection. The rate of surgery-related complications was 9.0% (60/663), and one (0.2%) patient died., Conclusions: With careful selection of GGO by experienced surgeons, the rate of malignancy is very high. Surgical resection may be recommended for highly suspected malignant cases. Sublobar resection or lobcotomy by VATS can achieve good treatment effect.

Lung cancer is the leading contributor to morbidity and mortality from cancer worldwide, with its 5-year overall survival being only about 15.6%. Due to the lack of specific early screening methods for lung cancer, about 75% patients are diagnosed late. Therefore, it remains the big challenge for the early diagnosis of lung cancer. We need to pay more attention to the screening of lung cancer, and more precise assessment and management to the pulmonary nodules screened out. Further study on liquid biopsy, optimization of new fiberoptic bronchoscopy and the sampling methods to harvest small volume of lung tissue, could be helpful to improve the early diagnosis of lung cancer., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Currently, there is no reliable biomarker to clinically predict the prognosis of lung adenocarcinoma (ADC). The receptor-tyrosine-kinase like orphan receptor 1 (ROR1) is reported to be overexpressed and associated with poor prognosis in several tumors. This study aimed to examine the expression of ROR1 and evaluate its prognostic significance in human lung ADC patients. In this present study, Western blot analysis and immunohistochemistry were performed to characterize expression of ROR1 protein in lung ADC patients. The results revealed that ROR1 protein expression was significantly higher in lung ADC tissues than that in their adjacent non-tumor tissues. Patients at advanced stages and those with positive lymph node metastasis expressed higher level of ROR1 (P < 0.001). Moreover, Chi-square test showed that ROR1 expression was correlated to gender (P = 0.028), the 7 th edition of the American Joint Committee on Cancer tumor-node-metastasis (AJCC TNM) staging system and lymph node metastasis (P < 0.001). Kaplan-Meier survival analysis indicated an association of high ROR1 expression with worse overall survival (OS) in lung ADC patients (P < 0.001). Multivariate COX regression analysis further confirmed that ROR1 is an independent prognostic predictor (P < 0.001, HR = 4.114, 95% CI: 2.513-6.375) for OS. Therefore, ROR1 expression significantly correlates with malignant attributes of lung ADC and it may serve as a novel prognostic marker in lung ADC patients.

Objective: To identify changes in patterns of primary bronchogenic carcinoma., Methods: We reviewed clinical data of patients with primary bronchogenic carcinoma, who were identified as permanent residents of Sichuan province and were treated in West China Hospital of Sichuan University in 2000 and 2010. The distributions of gender, age, urban/rural residency, smoking history, occupational exposure and histological types of tumor were compared between the 2000 group and 2010 group., Results: A total of 2 167 patients (616 in 2000 and 1551 in 2010) met the inclusion criteria. Compared with the 2000 group, the 2010 group had a lower proportion of male patients (male/female sex ratio dropped from 2.78:1 to 2.13:1, P = 0.013), more patients from medium and small sized cities (patients from large city decreased from 42.1% to 32.0%, P < 0.001, and patients from medium and small sized cities decreased from 39.9% to 31.7%, P < 0.001), more patients from rural areas (patients from townships increased from 5.5% to 8.1%, P = 0.041, and patients from villages increased from 12.5% to 28.2%, P < 0.001). No significant difference in age was found in the two cohorts of patients. The proportion of squamous cell carcinoma dropped from 44.8% in 2000 to 28.7% in 2010 (P < 0.001). The proportion of adenocarcinoma increased from 43.0% in 2000 to 53. 1% in 2010 (P < 0.001). The proportion of small cell lung cancer increased from 3.7% in 2000 to 11.9% in 2010 (P < 0.001). The proportion of squamous cell carcinoma in male patients was higher than that of female patients (60.7% vs. 36.6% in 2000; 75.8% vs. 42.9% in 2010). The proportion of adenocarcinoma was higher in female patients than that of male patients (60.7% vs. 36.6% in 2000; 75.8% vs. 42.9% in 2010). The proportion of squamous cell carcinoma was higher in elderly patients (> or = 60) than that of young patients (< 45) (50.5% vs. 33.8% in 2000; 30.2% vs. 15.6% in 2010). The proportion of adenocarcinoma in young patients was higher than of elderly patients (54.9% vs. 36.9% in 2000; 57.1% vs. 51.8% in 2010). Squamous cell carcinoma was predominate in smoking patients (55.6% in 2000; 40.9% in 2010). Adenocarcinoma was predominate in no-smoking patients (58.4% in 2010; 75.7% in 2010) and the patients exposed to risk occupations (46.2% in 2000; 60.2% in 2010)., Conclusion: Over the past decade, the percentages of female patients, adenocarcinoma and small cell lung cancer increased significantly in the patients with lung cancer. Male gender, old age (> or = 60) and smoking are risk factors of squamous cell carcinoma. Female gender, young age (< 45) and occupational exposure are risk factors of adenocarcinoma.

Objective: To modify and improve the procedures of video-assisted thoracoscopic surgery (VATS) bronchial sleeve lobectomy for lung cancers., Methods: From December 2010 to July 2012, 11 patients with nonsmall cell lung cancers underwent VATS bronchial sleeve lobectomy in our department, which included 7 cases of right upper lobectomy, 3 cases of left upper lobectomy and 1 case of left lower lobectomy. We modified the surgical procedures in relation to the distribution of VATS ports, the techniques of dissecting hilar structures and the method of bronchial reconstruction. The position of incisions for the left side differed from the right side. The lobe was resected with the technique of "hollow out" and the bronchus was reconstructed using a running prolene stitch., Results: Blood loss of these 11 patients ranged from 50-400 (median 200) mL. The operations were completed within 200-320 (median 235) minutes and the duration needed for bronchial reconstruction ranged from 35 to 60 (median 50) minutes. A total of 8-28 (median 15) lymph nodes were dissected. There was no conversion to thoracotomy or blood transfusion. Chest drainage tubes were removed within 2-12 (median 3) days after surgery. The patency of bronchial anastomosis was confirmed by bronchoscopy. Postoperative complications occurred in three patients, which included one case of bronchial pleural fistula (BPF) and two cases of pneumonia. The patient suffered from BPF died 49 days after surgery from intrabronchial bleeding. The postoperative hospital stay of those patients ranged from 8 to 49 (median 8) days. The reconstructed bronchus continued to work well during the three month follow-up visits., Conclusion: VATS bronchial sleeve lobectomy is feasible and safe. The modifications of the surgical procedures may promote the use of this complex operation.

Objective: To determine the duration of the resection of pulmonary lobe (RPL) and the effect of video-assisted thoracoscopic surgery (VATS) procedure on the duration of RPL., Methods: The records of 126 patients who had VATS lobectomy from October 2009 to October 2010 with a single-direction thoracoscopic procedure in one hospital were reviewed., Results: The patients included 65 (52%) men and 61 (48%) women with a mean age of 56 years (range, 15 years to 82 years). Four cases were excluded because of intraoperative complication. The average length of operation of RPL in the 122 patients without intraoperative complications was 38.98 min +/- 13.243 min (range, 17 min to 100 min), and the average length of the entire operation was 153.36 min +/- 39.64 min (range, 70 min to 245 min). Regardless which lobes, the average length of a single RPL remained the same (P > 0.05). The RPL of bilobectomies took longer than a single lobectomy (P < 0.05). However, no significant differences in the length of the entire operations were found between bilobectomy and single lobectomy (P > 0.05)., Conclusion: The length of RPL reflects the difficulties of the core step of thoracoscopic lobectomy. Single-direction thoracoscopic lobectomy is an easy procedure to manipulate.

Objective: To evaluate the safety and technical feasibility of single-direction video-assisted thoracoscopic lobectomy for patients with pulmonary diseases., Methods: From May 2006 to Sep 2012, 1040 patients with pulmonary diseases were treated by single-direction video-assisted thoracoscopic lobectomy. These included 565 men (54.3%) and 475 women (45.7%), with a mean age of (56.3 +/- 13.2) years. The patients suffered from lung cancer (800), benign disease (205), pulmonary metastases (34), and lymphoma (1). Their perioperative data were collected and reviewed., Results: Of the 1040 patients, 7 died (0.67%); 18 (1.73%) were converted to open surgery; 134 had postoperative complications (12.88%). The patients underwent an average of (169 +/- 64) min operations, lost an average of (93 +/- 113) mL (range, 5-935 mL) blood, had an average of (3.3 +/- 1.9) cm (range, 1.2-12 cm) diameters of mass removed and an average (15.8 +/- 7.7) (range, 5-52) lymph nodes dissected. The patients had an average of (3.8 +/- 2.6) days (range, 1-16 days) drainage during an average of (7.0 +/- 2.8) days (range, 4-19 days) postoperative hospital stay., Conclusion: Single-direction thoracoscopic lobectomy is a safe and feasible surgical procedure in the treatment of pulmonary diseases.

Objective: To determine the effect of video-assisted thoracoscopic lobectomy on the pulmonary rehabilitation of patients with lung cancers., Methods: Between September 2010 and December 2011, 138 patients. with lung cancers were treated with lobectomy: 68 using video-assisted thoracoscopic surgery (VATS) and 70 using thoracotomy. The preoperative and postoperative (7 d and 30 d) pulmonary functions and Cardio-pulmonary Exercise Capacities as well as postoperative (7 d and 30 d) DE Morton Index of the two groups of patients were assessed. The two groups of patients had similar in clinical characteristics., Results: (1) Patients in the VATS group had greater FEV1 (1.64 +/- 0.21) L and PEF [(310.58 +/- 30.13) L/min] on the 7 d after operations than those with thoracotomy [FEV1 (1.34 +/- 0.11) L and PEF (270.18 +/- 25.67) L/min], P < 0.05. (2) Patients in the VATS group had lower fatigue index (0.27 +/- 0.08) and dyspnea index (0.28 +/- 0.17) on the 7 d after operations than those with thoracotomy (0.44 +/- 0.10 fatigue index and 0.39 +/- 0.09 dyspnea index), P < 0.05. (3) Patients in the VATS group had longer 6-min walking distance on the 7 d [(490.57 +/- 118.33) m] and 30 d [(524.32 +/- 140.87) m] after operations than those with thoracotomy [(395.07 +/- 100.19) m at 7 d and (471.10 +/- 118.57) m at 30 d], P < 0.05. (4) Patients in the VATS group had higher DE Morton index (74.58 +/- 16.23) on the 7 d after operations than those with thoracotomy (55.87 +/- 14.79), P < 0.05., Conclusion: VATS lobectomy for curative lung cancer resection appears to provide a superior functional health recovery compared with thoracotomy.

Video-assisted thoracoscopic surgery (VATS) lobectomy is a less invasive procedure when compared with the traditional thoracotomy. With the development of operative techniques, VATS lobectomy has become a definite procedure for stage I and some stage II a lung cancer. However, it is still controversial due to operative difficulty whether it is feasible to perform thoracoscopic surgery in anatomic pulmonary segmentectomy, bronchial sleeve lobectomy, bronchial and arterial sleeve lobectomy, large tumor (> 5 cm), pneumonectomy and resection of Pancoast tumor. Some difficulties in performing thoracoscopic lobectomy such as: pleural cavity adhesions or atresia, local invasion, interlobar fissure dysplasia, bleeding, as well as "troublesome hilum", were once thought to be indication for conversion to thoracotomy. We proposed a new concept of thoracoscopic lung resection: "single-direction thoracoscopic lobectomy", which has been proved to be simple, safe, and effective and has been widely accepted in our country. In practice, we are still proceeding with further exploration, technical optimization and expanding its application in more complicated lung surgery. For instance, we have developed strategies of "fast recovery" and "mini-invasive diagnosis and synchronous treatment of lung cancer" and a series of stylized techniques such as thoracoscopic adhesiolysis, bloodless technique, suction-compressing angiorrhaphy technique, presumptive control of the main pulmonary artery, hollow-out method in thoracoscopic lobectomy. With accumulative experience utilizing these innovative techniques, we believe that thoracoscopic lobectomy would become the mainstream for surgical management of pulmonary diseases.

Objective: To compare acute inflammatory responses and immunosuppression to lobectomy in lung cancer patients with video-assisted thoracoscopic surgery (VATS) and posterolateral thoracotomy (PLT)., Methods: A total of 103 patients who underwent either a VATS (n = 51) or a PLT (n = 52) lobectomy for early non-small cell lung cancers (NSCLC, stage I ) were recruited for this study. Blood samples of the participants were taken preoperatively and at 24 h and 72 h post-operatively for analyses of C-reactive protein (CRP), interleukin (IL)-6, IL-2 receptors (IL-2R), and serum amyloid A (SAA). Blood samples taken pre-operatively and at 2 d and 7 d post operations were also analyzed for total lymphocytes, NK cells, CD4+ T, and CD8+ T., Results: Patients in the VATS group lost significantly less blood than those in the PLT group (P = 0.001). Patients in the PLT group had significantly higher serum SAA than those in the VATS group (P = 0. 006). Significant reduction of CD8+ T was found in the patients with PLT after operations (P < 0.01). Patients in the PLT group had significantly lower at CD8+ T 7 d post operations than those in the VATS group (P = 0.015)., Conclusion: VATS pulmonary lobectomy is associated with reduced acute inflammatory responses and immunosuppression compared with the PLT approach.

Objective: To investigate the expressions of adenomatous polyposis coli (APC) protein and c-Myc protein in non-small cell lung cancer (NSCLC) and their lymph node metastases., Methods: APC and c-Myc proteins were detected in 270 cases of primary NSCLC, 55 cases of lymph node metastatic tissues and 46 cases of adjacent normal lung tissues by EliVision and EnVision methods of immunohistochemical staining., Results: Higher rates of the expressions of both APC and c-Myc proteins in NSCLC primary foci were found compared with those in lymph node metastases (P < 0.05). Furthermore, the expressions of APC and c-Myc proteins varied with histological types, TNM stagings and metastasis of the NSCLC (P < 0.05). The Spearman correlation analysis showed that the expressions of APC and c-Myc proteins were positively correlated (r(s) = 0.376, P = 0.000). The Kaplan-Meier survival analysis revealed that the survival rate was lower in patients with positive expressions of APC and c-Myc proteins than in patients with negative expressions (P < 0.05). Histological type, pathologic grading, metastasis and c-Myc were identified as independent risk factors with related to the prognosis of NSCLC patients in the multivariate Cox regression model (P < 0.05)., Conclusion: APC and c-Myc may play an important role in the progression of NSCLC.

Objective: To analyze the learning curve of single-direction complete video-assisted thoracoscopic surgery (cVATS) for lung cancer., Methods: From May 2006 to April 2009, 125 cases of cVATS for lung cancer were performed by two dedicated surgeons. Clinical data were collected prospectively and analyzed retrospectively. The patients operated by different surgeon were divided into 2 groups (group A, n = 24; group B, n = 101), and group B was further divided sequentially into 4 subgroups (B1, B2, B3 and B4) by the number of patients. The patients in group A and B were operated by the surgeons with 2-year and 5-year experience of VATS respectively. The operating time, blood loss, number of resected lymph nodes (NLN), rate of thoracotomy conversion (RTC) and postoperative complications (POC) were compared., Results: Compared with group B, the operating time of group A was significantly prolonged [(237 ± 85) min vs. (187 ± 43) min, P = 0.013], but there were no significant differences in blood loss, NLN, RTC and POC. Comparing group A with B1, the same results were got. From group B1 to B4, the operating time was gradually reduced and blood loss decreased, but the difference was not statistically significant. And in group B, there was a significant reduction of blood loss for the last 51 cases compared to the first 50 cases [(122 ± 141) ml vs. (87 ± 81) ml, P = 0.009]., Conclusions: At the early stage of cVATS resection of lung cancer, the duration of operation was longer, which it was more significant for the surgeons with short carrier of thoracoscopic experience. But the morbidity of operation related complications did not increase. The indicator of proficiency in this operation is achievement of 50 cases of complete thoracoscopic resection of lung cancer.

Objective: To study the expression and clinical significance of AKT2, phosphorylated AKT2 (p-AKT2) in non-small cell lung cancer (NSCLC)., Methods: The tumor tissues were obtained from 137 cases of NSCLC, the expressions of AKT2 and p-AKT2 in the tissues were measured by immunohistochemistry. The statistic analysis was carried on to study the correlation of AKT2, p-AKT2 expression to the type of lung cancer, TNM stage, pathological grading. Survival analysis was also studied., Results: The positive rates of AKT2 in lung adenocarcinoma and squamous carcinoma were 60.5% and 54.1% respectively (P > 0.05). While the positive rates of p-AKT2 in lung adenocarcinoma and squamous carcinoma were 68.4% and 47.5% (P < 0.05). The expressions of AKT2 and p-AKT2 were not correlated with age, gender, TNM stage and cell differentiation degree. Further more, survival analysis revealed that 5-year survival rate and median survival time for the patients with positive expression of p-AKT2 were significantly poorer than those with negative expression (20% vs 56%, (28.464 +/- 2.235) months vs (39.214 +/- 3.075) months, P < 0.053, while there were no significant differences with regard to AKT2 expression., Conclusion: The positive expression of p-AKT2 in lung adenocarcinoma was higher than that in lung squamous carcinomas. p-AKT2 may be a prognostic factor for non-small cell lung cancer.

Objective: To screen the serum proteins related to human lung adenocarcinoma using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) technology., Methods: The blood samples were collected from 10 patients of lung adenocarcinoma before and one week after the surgery, while 10 healthy subjects were used as control. The differential protein expression between the two groups and the change of those proteins after surgery were studied by ClinProt magnetic bead enrichment and MALDI-TOF-MS., Results: Six protein peaks were identified, 2 of them were highly expressed protein biomarkers with relative molecular weights of 2661, 2991, and increased after the surgery, 4 of them were lowly expressed protein biomarkers with relative molecular weights of 4091, 4210, 4644, 5336, which continuously decreased after the surgery., Conclusion: ClinProt magnetic bead enrichment and MALDI-TOF-MS is a quick, easy and sensitive method of proteomics. The differential expressed proteins may be the latent tumor marker of lung adenocarcinoma. The alteration of those proteins after surgery might be helpful to assess the therapeutic effect and prognosis.

Due to the advanced diagnostic technique and better understanding for multiple primary lung cancers (MPLC), the increasing incidence of MPLC has been reported. Very often, MPLC are misdiagnosed as metastasis because of lacking efficient molecular biomarkers for prediction and diagnosis. Studies on the molecular mechanism for tumorgenesis and progression of MPLC may therefore facilitate the discovery of biomarkers for disease diagnosis and prognosis, so that an individual and rational treatment can be achieved. We tried to further our understanding and improve the diagnostic skill for MPLC by reviewing the current status and the latest advancement of molecular markers related to MPLC.

Objective: To study the expression of CD133, CD34 and CD44 in lung cancer, and distribution of cell subpopulations that generated by combination of different markers., Methods: By collecting 10 normal lung tissues and 40 lung cancer fresh samples that were diagnosed pathologically, preparing single cell suspension, and labelling cells with CD133, CD34, CD44, CD117, CD43, CD45 and LIN(CD2, CD3, CD31, CD64) monoclone antibodies, we analyzed the distribution of the above-mentioned antibodies in lung cancer cells on FCM. By double-parameters plots, we analyzed the naive cell subpopulations that were generated through combination of positive and negative antigen expression., Results: In lung cancer parenchymal-cells (LIN- CD45-) expressed CD133, CD34 and CD44 dim positive and, expressed CD117 and CD43 negative. The mann-Whitney rank test results shows that there was no significant difference for the expression of CD133, CD34, CD44 between lung cancer and normal lung tissue, and CD44+, CD133- CD34-, CD133+ CD44+, CD133+ CD44-, CD133+ CD34+, CD133- CD34+ and CD133- CD44+ expressed differently (P < 0.05) between lung adenocarcinoma and lung squamous cell carcinoma. The cluster analysis results suggest that they are classified to 4 subsets., Conclusion: CD133, CD34, CD44 could be the marker of lung cancer naive cells, which could contribute to study lung cancer cell development.

Objective: To study the co-expression and prognostic significance of hnRNP B1 and CD44 in non-small cell lung cancers (NSCLC)., Methods: The co-expressions of CD44 and hnRNP B1 in the tissues from 88 cases of NSCLC were measured by immunohistochemistry. The relationship between the expressions and the prognosis of NSCLC was analysed., Results: The NSCLC had a high expression of hnRNP B1 (68.18%) and CD44 (52.27%). The cells had the longest average life [(59.607 +/- 4.092) months] in the conditions of high expressed hnRNP B1 and low expressed CD44, and shortest average life [(21.357 +/- 3.545) months] in the conditions of low expressed hnRNP B1 and high expressed CD44., Conclusion: Combined detection of hnRNP B1 and CD44 can help forecast the prognosis of NSCLC.

Objective: To evaluate the efficacy and practicability between bronchial sleeve resection or reconstruction of the pulmonary artery by video-assisted thoracic small incision and routine posterolateral incision for lung cancer., Methods: The clinic data was analyzed retrospectively, including 139 cases in our hospital underwent sleeve lobectomy and bronchoplasty by video-assisted thoracic small incision surgery for lung cancer from January 1995 to July 2007 and 99 cases in the HUAXI Hospital of SICHUAN University underwent routine posterolateral incision from April 2000 to December 2005. All patients whose bronchus and/or pulmonary artery were involved underwent the operation and experienced the bronchial sleeve resection or reconstruction of the pulmonary artery., Results: All patients were done operation successfully with no perioperative mortality and no occurrence of anastomosis stenosis as well as fistula. The median survival period of video-assisted thoracic small incision patients and the posterolateral incision patients were 63.17 months and 42.00 months, respectively (P > 0.05). There was no sign of reperfusion injury in the reconstruction of the pulmonary artery patients. The small incisions' length was from 8 to 13 cm and the mean length was 10 cm. The routine posterolateral incisions' mean length was 30 cm. Compared to the patients underwent the routine posterolateral incision, patients underwent the operation of video assisted thoracic small incision had less operation time, less chest tube time, less hospitalization time and less postoperative shoulder joint dysfunction., Conclusions: The bronchial sleeve resection and reconstruction of the pulmonary artery by video-assisted thoracic small incision surgery for lung cancer can finish the same work as the traditional thoracic lateral incision with less trauma and recovery time.

Objective: To study the molecular mechanisms of nm23-H1 for regulating PKC signal pathway before and after transfection with nm23-H1 gene., Methods: Using Western-blot, Boyden-chamber, MTT and laser scanning confocal microscopy (LSCM) techniques to detect the distribution of PKC in cytosol and plasma membrane, changes of invasion and proliferation activity, PKC translocation status and changes of intracellular Ca(2+) concentration among different human pulmonary carcinoma cells with transfected or untransfected nm23-H1 gene, and changes of the three cell lines after treatment with Calphostin C, a PKC inhibitor., Results: (1) The expression of PKCalpha, PKCbeta II on L9981 and L9981-pLXSN cell membrane, which was in activated status, was remarkably higher than those in L9981-nm23-H1 cell line (P < 0.001). The expression of PKCalpha, PKCbeta II in cytosol in L9981 and L9981-pLXSN cell lines, which was in inactivated status, was lower than those in L9981-nm23-H1 cell line (P < 0.001). It means that the PKC signal pathway was activated in L9981 and L9981-pLXSN cell lines. (2) PKCalpha and PKCbeta II mainly located in nuclei and perinuclear area in L9981 and L9981-pLXSN cells, which were in active status, and the Ca(2+) concentration in these cells was obviously higher than that in L9981-nm23-H1 cell line (P < 0.01). In L9981-nm23-H1 cell line, which was transfected with nm23-H1 gene, PKCalpha and PKCbeta II mainly located in soluble cytosolic section, in an inactive status. (3) The invasion and proliferation ability of L9981 and L9981-pLXSN lung cancer cells was higher than that of L9981-nm23-H1 cell line (P < 0.001). There was no statistically significant difference between L9981 and L9981-pLXSN cell lines (P > 0.05). (4) After treated with PKC inhibitor Calphstin C, the expression of PKC and PKCbeta II in membrane in L9981 and L9981-pLXSN cell lines was down-regulated (P < 0.001), PKCalpha and PKCbeta II were mainly located in cytosolic area, mainly in an inactive status, and the Ca(2+) concentration was found to be decreased in all the three cell lines. The invasion and proliferation ability of the three lung cancer cell lines were obviously decreasing (P < 0.001). However, the invasion and proliferation ability of L9981-nm23-H1 lung cancer cell line was still lower than that of L9981 and L9981-pLXSN lung cancer cell lines (P < 0.001). There was also no significant difference between L9981 and L9981-pLXSN cell lines (P > 0.05)., Conclusion: The results of this study suggest that nm23-H1 gene might inhibit the invasion and metastasis of lung cancer cells by down-regulating PKC signaling pathway. The Ca(2+) in cells might be involved in this process.

Background & Objective: Recently, studies showed nm23, E-cadherin, and Catenins play important roles in cellular signal transduction, which enhance complexity of their functions in tumor metastasis and can partly explain the diversity of the results from different studies. This study was to investigate correlations of expressions of nm23, E-cadherin, and beta-Catenin in non-small cell lung cancer (NSCLC) to metastasis and prognosis, and their interrelations., Methods: Expressions of nm23, E-cadherin, and beta-Catenin in 112 specimens of NSCLC and 30 specimens of benign pulmonary lesion were detected by SP immunohistochemistry., Results: The expressions of nm23, E-cadherin and beta-Catenin were significantly weaker in NSCLC tissues than in adjacent non-cancerous tissues, and benign pulmonary tissues (53.0% vs. 64.8%, and 76.9%, P < 0.01; 53.1% vs. 79.7%, and 83.5%, P < 0.01; and 47.2% vs. 80.6%, and 85.6%, P < 0.01), significantly weaker in NSCLC tissues with lymph node metastasis than in those without metastasis (48.0% vs. 65.0%, P < 0.01; 47.3% vs. 60.5%, P < 0.01; and 41.8% vs. 60.3%, P < 0.01), and significantly weaker in NSCLC tissues of stage III-IV than in those of stage I-II (44.8% vs. 67.2%, P < 0.01; 46.6% vs. 64.3%, P < 0.01; 38.1% vs. 63.1%, P < 0.01). The 5-year survival rates of patients with weak expressions of nm23, E-cadherin, and beta-Catenin were significantly lower than those of patients with strong expressions (3.6% vs. 39.3%, P < 0.01; 6.8% vs. 35.8%, P < 0.01; and 3.8% vs. 37.3%, P < 0.01)., Conclusions: Down-regulations of nm23, E-cadherin, and beta-catenin closely relate to metastasis of NSCLC. Detection of nm23, E-cadherin, and beta-Catenin might be helpful to predict prognosis of NSCLC patients.

Background & Objective: nm23-H1, a tumor metastasis suppressive gene, can reverse tumor metastasis phenotype. But the molecular mechanism of nm23-H1 in inhibiting or reversing metastasis of lung cancer is unclear. This study was to explore the molecular mechanism of nm23-H1 in reversing metastasis phenotype of lung cancer., Methods: nm23-H1 gene and pLXSN were separately transfected into human lung cancer cell line L9981. Proliferation of L9981, L9981-pLXSN, and L9981-nm23-H1 cells was detected by MTT assay, cell invasive ability was detected by modified Boyden chamber. Tumorigenesis and experimental lung metastasis were determined in vivo. mRNA and protein levels of beta-catenin, E-Cadherin, CD44S, CD44V6, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1), and vascular endothelial growth factor (VEGF) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot., Results: (1)Cell proliferation, clone formation, and invasive ability were significantly lower in L9981-nm23-H1 cells than in L9981 cells [(19.5+/-2.9)% vs. 100%, 10.3+/-0.7 vs. 21.7+/-1.3, 31.0+/-3.0 vs. 151.0+/-6.3, P<0.01]. (2) The inhibitory rate of tumorigenesis of nude mice was significantly higher in L8891-nm23-H1 group than in L9981 group (85.6% vs. 0%, P<0.001)u the lung metastatic rate was significantly lower in L9981-nm23-H1 group than in L9981 group (0% vs. 100%, P<0.001). (3)nm23-H1 up-regulated mRNA and protein levels of beta-catenin, E-Cadherin, and TIMP-1, and down-regulated levels of MMP-2, CD44V6, and VEGF (P<0.01). (4) nm23-H1 up-regulated mRNA level of CD44s, protein level of CD44s didn't change (P>0.05)., Conclusion: nm23-H1 gene can reverse malignant and metastatic phenotype of L9981 cells through regulating the expressions of lung cancer metastasis-related genes.

Objective: To evaluate the specificity, sensitivity and their clinical significance of detecting CK19 mRNA expression by nested RT-PCR for molecular diagnosis of micrometastasis in the peripheral blood and bone marrow of patients with non-small cell lung cancer., Methods: CK19 mRNA expression was detected by nested RT-PCR in peripheral blood and bone marrow samples from 59 lung cancer patients, with samples of 11 benign pulmonary lesion patients and 20 healthy adults as control., Results: The sensitivity of nested RT-PCR was 10(-6). The positive rates of micrometastasis were 33.89% (20/59) in peripheral blood and 22.03% (13/59) in bone marrow, with a highly positive correlation existing between the two groups (P < 0.05). The micrometastasis in peripheral blood and bone marrow was closely correlated with the pathological classification and cell differentiation (P < 0.05) and P-TNM stage (P < 0.01). No CK19 mRNA expression was found in the samples from patients with benign pulmonary lesion or healthy adult volunteers., Conclusion: The peripheral blood and bone marrow from patients with non-small cell lung cancer possesses micrometastasis that can not be detected by common methods. Nested RT-PCR technique shows favorable specificity and sensitivity in detecting the condition with definite clinical prospects.