This file contains additional methods for data in Supplementary Table S1.

This file contains 8 Supplementary Figures and 5 Supplementary Tables: Supplementary Figure S1 showed supplementary data regarding specimen processing and development of PD-SFA, which were related to Figure 1. Supplementary Figure S2 showed validation of the reported LCSC markers CD166 and CD133. Supplementary Figure S3 showed supplementary data regarding identification and characterization of novel LCSCs in vitro, which were related to Figure 4. Supplementary Figure S4 showed supplementary data regarding serial orthotopic xenograft assays to determine tumorigenic and self-renewal activity of LCSCs, which were related to Figure 4. Supplementary Figure S5 showed supplementary data regarding LCSC chemoresistance, which were related to Figure 5. Supplementary Figure S6 showed supplementary data regarding expression of stemness and LCSC-associated genes in LCSCs. Supplementary Figure S7 showed supplementary data regarding the role of NOTCH1 in LCSC self-renewal, which were related to Figure 6. Supplementary Figure S8 showed supplementary data regarding the role of NOTCH1 in LCSC platinum resistance, which were related to Figure 6. Supplementary Table S1 presented clinical information, mutational status, sphere-forming and LCSC frequencies associated with tumors. Supplementary Table S2 presented antibody information. Supplementary Table S3 presented RT-PCR primers. Supplementary Table S4 presented shRNA target sequences. Supplementary Table s5 presented primers for mutational analysis.

Current evidence has unveiled that long non-coding RNAs (lncRNAs) are pivotal regulators in the development of cancers. This study aimed to investigate the potential mechanisms of LINC01224 in esophageal squamous cell carcinoma (ESCC) cells. RT-qPCR analysis was done to test LINC01224 expression in ESCC cells. Functional assays were conducted to assess the influences of LINC01224 on ESCC cell functions. Mechanism assays were carried out to detect the regulatory mechanisms of LINC01224 at post-transcriptional and transcriptional levels. Briefly, LINC01224 expression was remarkably high in ESCC cells. LINC01224 silence restricted the proliferative, migratory, and invasive capabilities of ESCC cells. Moreover, LINC01224 could combine with miR-6884-5p by acting as a ceRNA. Further, DVL3 was proved to be targeted by miR-6884-5p. Importantly, LINC01224 could switch on Wnt/β-catenin signaling pathway by via enhancing DVL3 expression. Additionally, E2F1 could serve as a transcription factor to stimulate LINC01224 transcription. In summary, our study elucidated that E2F1-activated LINC01224 regulated miR-6884-5p/DVL3 to actuate the Wnt/β-catenin signaling pathway, which facilitates multiple phenotype of ESCC cells, including proliferation, migration, and invasion. Our findings might offer potential therapeutic targets for ESCC treatment.

PURPOSE:To evaluate the predictive value of stair climbing test (SCT) on postoperative complications in lung cancer patients with limited pulmonary function. METHODS:A total of 727 hospitalized lung cancer patients with limited pulmonary function were retrospectively reviewed. Included in the cohort were 424 patients who underwent SCT preoperatively. Patients were grouped according to general condition, past medical history, surgical approach, pulmonary function test, and SCT results. Comparison of the postoperative cardiopulmonary complication rates was made and independent risk factors were identified. RESULTS:A total of 89 cardiopulmonary-related complications occurred in 69 cases, accounting for 16.3% of the entire cohort. The postoperative cardiopulmonary complication rates were significantly different between groups stratified by smoking index, percentage of forced expiratory volume in one second, percentage of diffusion capacity for carbon monoxide, SCT results, excision extension, and anesthetic duration (p <0.05). Multivariate analysis showed that only height achieved (p <0.001), changes in heart rate (∆HR; p <0.001), and excision extension (p = 0.006) were independent risk factors for postoperative cardiopulmonary complications. CONCLUSIONS:The SCT could be used as a preoperative screening method for lung cancer patients with limited pulmonary function. For those patients who could only climb less than 6 floors or had ∆HR >30 bpm in the test, sublobar resection should be selected to reduce the postoperative cardiopulmonary complication rate.

Background: Early-stage female lung adenocarcinoma is the most common type of lung cancer encountered in thoracic surgery departments. Tumor-node-metastasis (TNM) staging does not adequately explain a significant stratification phenomenon in the prognosis of patients with stage I lung adenocarcinoma. We aimed to investigate the contributory role of miR-940 in the prognosis prediction. Methods: We analyzed the microRNA (miRNA) expression level in tumor tissues (high-risk group vs. low-risk group) from 12 non-smoking female patients with stage I lung adenocarcinoma using miRNA array. Bioinformatic analyses of miR-940 were also carried out based on the public database. Then, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) tests of the tissue samples were further validated. And miR-940's function was analyzed and potential target genes were predicted. Results: In all, 24 miRNAs were found to be significantly different between the high-risk group and low-risk group. The expression level of miR-940 was lower in tumor tissue (P=0.011), and the survival rate in the high miR-940 group was higher [hazard ratio (HR) =0.688; P=0.011]. Gene Ontology (GO) analysis showed that the assembly functions of targets regulated by miR-940 were mainly enriched in regulation of myeloid cell differentiation, G1/S transition of mitotic cell cycle, and cellular response to environmental stimulus. miR-940 is involved in transforming growth factor-beta (TGF-beta) signaling pathway; TNF signaling pathway; and estrogen signaling pathway. The number of lung adenocarcinoma cells (A549) was significantly decreased after miR-940 was transfected. Ten epithelial-to-mesenchymal-transition (EMT)-associated genes (MMP9, ZEB1, CDH1, KRT8, KRT18 KET19, TWIST1, VIM, SNAI1, and SNAI2) were found to be significantly related to miR-940. Conclusions: The present study showed that miR-940 might be a protective factor for positive prognosis in early stage nonsmoking female lung adenocarcinoma, with transforming growth factor-beta (TGF-beta) pathway, TNF pathway, and matrix metalloprotein (MMP9) being potential targets.

Background: In the TNM system only the anatomic location is used to define nodal status. In this study we aim to evaluate the effectiveness of combining the location and ratio of metastatic lymph node (pN-NR) for the prognosis of non-small cell lung cancer (NSCLC). Methods: Patients with pN1/pN2 NSCLC were retrieved from the SEER database. The optimal cut point of NR was determined with the maximal selecting test. All patients were divided into 4 categories with combination of pN (pN1 or pN2) and NR (low or high). The pN-NR was investigated as a predictor of overall survival (OS) and cause-specific survival (CSS) using Cox regression models. Survival curves were plotted using the Kaplan-Meier method and the difference was compared with log-rank test. Results: A total of 12,170 patients were enrolled. The optimal cut point of NR was 0.3. Patients were divided into 4 groups: pN1-NR <0.3, pN1-NR >= 0.3, pN2-NR <0.3 and pN2-NR >= 0.3. The pN-NR was an independent prognostic factor for survival. Compared with pN1-NR <0.3, the hazard ratio of OS was 1.405 (95% CI: 1.295-1.524), 1.183 (95% CI: 1.113-1257) and 1.717 (95% CI: 1.607-1.835) times higher for pN1-NR >= 0.3, pN2-NR <0.3 and pN2-NR >= 0.3 group, respectively. The survival curves of OS separated well between the 4 pN-NR groups, with 5-year OS 47.1% for pN1-NR <0.3, 43.0% for pN2-NR <0.3, 35.0% for pN1-NR >= 0.3 and 28.5% for pN2-NR >= 0.3, and the P value between neighboring curves was statistically significantly. The same trend was observed for CSS. Subgroup analysis revealed similar results except the pneumonectomy group. Conclusions: pN-NR could be a good predictor for the prognosis of NSCLC.

目的:总结原发性纵隔脂肪肉瘤的临床特征、治疗方法及预后.方法:回顾我院2011年2月～2016年6月行手术治疗的5例原发性纵隔脂肪肉瘤患者,并结合文献检索获得的140例中国地区病例资料进行报告.结果:本院5例中男4例、女1例,平均年龄57岁.临床表现以压迫引起的呼吸困难为主.5例患者中高分化型2例、去分化型2例、黏液型1例;均行手术治疗,其中4例完成根治性切除,平均手术时间350min,平均术中出血1060ml.5例患者平均总生存期为33.2个月.3例根治性切除患者出现局部复发,平均无病生存期为27.8个月.结论:原发性纵隔脂肪肉瘤罕见,有症状发现时已体积较大,汇总文献病例:肿瘤平均最大直径17.4cm,误诊率高达67.2％.手术是首选治疗方案,但手术难度较高.根治性手术及病理亚型为高分化型的患者预后较好.

To the Editor: The differentiation of multiple primary lung adenocarcinomas (MPLAs) from metastases is important to allow for proper clinical management and prognostic prediction. The current revised diagnostic criteria for MPLAs proposed by the American College of Chest Physicians (ACCP) have been commonly applied since 2003.[1] However, it remains technically challenging to determine whether 2 or more lung adenocarcinomas from the same patient are homologous. Various approaches and algorithms including gene mutation analysis addressing this problem have been described.[2,3] Here, we present a cohort of 45 patients with synchronous multifocal lung adenocarcinomas. All of the 45 patients were diagnosed through surgical resection from October 2012 to December 2017. Patients with multiple lung adenocarcinomas in the same lobe were excluded from the study because of their limited impact on treatment strategy. Of the 45 patients, 39 had double lung adenocarcinomas, 5 had triple lung adenocarcinomas, and 1 had 4 lung adenocarcinomas. All patients underwent bronchoscopy before surgery. Cranial computed tomography (CT)/magnetic resonance imaging (MRI), abdominal ultrasonography/CT, and nuclide bone scanning were adopted to rule out extrapulmonary metastasis before positron emission tomography (PET)-CT was widely adopted. PET-CT was performed in 36 patients, and mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed in 14 patients preoperatively to exclude suspicious N2 cases. Pulmonary function test (PFT) and general condition assessment were routinely performed before surgery. The detailed clinical and pathological characteristics of the patients are shown in Supplementary Table 1, https://links.lww.com/CM9/A6. All 97 lung adenocarcinomas from the 45 patients were surgically removed. Different surgical procedures are illustrated in Supplementary Table 2, https://links.lww.com/CM9/A6. Thirty-seven patients underwent completely unilateral or bilateral video assisted thoracic surgery (VATS), while 8 patients received or were converted to open thoracotomy. Of the 14 patients with bilateral disease, 6 received synchronous bilateral procedures and 8 received operations within a 6- to 12-week interval. The patients generally recovered well. Two patients (4.4%) suffered postoperative complications, one developed sustained pulmonary air leakage but recovered after the application of prolonged intermittent negative pressure suction, and the other developed postoperative atrial fibrillation but recovered after being given antiarrhythmic treatment. There were no perioperative deaths. Comprehensive histologic assessment was used to determine whether the adenocarcinomas were metastatic carcinomas or synchronous MPLAs. According to the updated diagnostic criteria proposed by ACCP[1] and the international multidisciplinary classification,[4] lung adenocarcinoma was classified as invasive adenocarcinoma and preinvasive lesion including atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA). For invasive adenocarcinoma, the relative percentage of each histologic subtype was semiquantitatively evaluated in 10% increments, including lepidic, acinar, papillary, micropapillary, and solid components; variants of invasive adenocarcinomas were also included and evaluated. Two cases were diagnosed as multiple AIS/MIA and were considered synchronous MPLAs. The largest or main lesions of the other 43 patients were all identified as invasive adenocarcinoma. Among these 43 patients, 18 were identified as having only 1 invasive lung adenocarcinoma, while the other 25 proved to have multiple invasive lung adenocarcinomas. The tumor pairs from 8 of the 25 patients had similar histologic subtypes and were considered possible intrapulmonary metastases. The remaining 35 patients with at least 1 invasive lung adenocarcinoma had different histologic subtypes or different cytological features and were considered synchronous MPLAs [Figure 1].Figure 1: Diagnostic flow chart of the 45 patients with synchronous multifocal lung adenocarcinomas. MPLA: multiple primary lung adenocarcinoma; MIA: minimally invasive adenocarcinoma.The mutational status of EGFR in exon 18 to 21 was obtained using kits from San Valley Diagnostics (Beijing, China) based on amplification refractory mutation system real-time polymerase chain reaction technology. Next-generation gene sequencing (NGS) was applied to patients with similar EGFR mutation types for further differentiation from intrapulmonary metastases. Semiconductor sequencing based on the Ion Personal Genome Machine (PGM™) System (Thermo Fisher Scientific, USA) was performed using the Ion AmpliSeq Cancer Hotspot Panel v2 (Thermo Fisher Scientific) to sequence more than 2800 loci from 50 oncogenes and tumor suppressor genes in the tumor DNA.[5] Among the 37 synchronous MPLA patients, the EGFR mutation status of 64 tumors of 35 patients was available. EGFR mutation was found in 29 tumors (28 invasive lung adenocarcinoma, 1 MIA) of 19 patients, including 15 tumors with Exon 19 deletion mutation, 9 tumors with Exon 21 L858R mutation, 3 tumors with Exon 20 insertion mutation, 1 tumor with Exon 21 L861Q mutation and 1 tumor with Exon 20 S768I mutation. The concordant frequency rate of the EGFR mutation distribution was 31.6% (6/19). For the 8 possible intrapulmonary metastasis patients, EGFR mutation status was available for all 16 tumors. Eight tumors from 5 patients were EGFR mutation-positive, 2 patients had both tumors presenting Exon 19 deletion mutation, and 1 patient had both tumors presenting Exon 21 L858R mutation. The remaining 2 patients each had 1 tumor with an Exon 19 deletion mutation showing a discordant EGFR mutation status and the tumors were identified as synchronous MPLAs. To further differentiate synchronous MPLAs from intrapulmonary metastases, NGS was applied to the 12 tumors of the 6 patients with similar histologic subtypes and concordant EGFR mutation status. One patient (Patient 4) was detected as having discordant gene mutation status and was identified as having synchronous MPLAs [Figure 1, Table 1].Table 1: NGS results for the 6 patients with similar histologic subtypes and concordant EGFR mutation statusAccording to the 8th edition of TNM staging for NSCLC, the tumor pairs from 40 synchronous MPLA patients were staged separately. If the pT stage of the largest tumor or main lesion was defined as the highest pT stage, 27 cases would be classified as pT1, and 11 and 2 cases would be classified as pT2 and pT3, respectively. Similarly, 29 of the 40 synchronous MPLA patients were confirmed as pN0, while 11 patients were confirmed as having at least 1 pN1 lesion. The 5 patients with intrapulmonary metastases were all staged as pT4N1M0 because of their location in different lobes of the same side and being identified with positive hilar, interlobular or intrapulmonary lymph nodes. No positive N2 lymph node was identified in the entire cohort. Postoperative adjuvant chemotherapy was applied to 2 of 4 synchronous MPLA patients with one pT2aN0M0, IB stage lung adenocarcinoma; to all 11 synchronous MPLA patients with at least 1 pN1 lesion; and to the 5 patients with intrapulmonary metastases. A combination chemotherapy regimen with pemetrexed and platinum was regularly adopted. All patients received regular follow-up at the clinic. The median follow-up time was 45 months (10–83 months). Chest CT was performed every 3 months for the first year, every 6 months for the second year, and annually thereafter. Serum tumor markers, cranial CT/MRI, abdominal ultrasonography/CT, and nuclide bone scans were performed annually or whenever necessary as positive symptoms arose. SPSS 19.0 (IBM SPSS Statistics for Windows, IBM Corp., Armonk, NY, USA) was used for the statistical analysis. The Kaplan–Meier estimator was used to draw survival curves. Univariate analysis was performed to compare the progression-free survival (PFS) and overall survival (OS) between groups according to age, sex, smoking history, tumor distribution, the largest tumor's dimension on high-resolution CT, the preoperative percentage of forced expiratory volume in the first second (FEV1%, defined as actual FEV1/predicted FEV1 × 100%), Charlson comorbidity index, Eastern Cooperative Oncology Group (ECOG) performance status, the use of a minimally invasive approach and different operational options, highest pT stage, pN stage, the number of invasive adenocarcinomas and the use of postoperative adjuvant chemotherapy using the log-rank test. Based on the univariate analysis results, candidate variables (P < 0.15) were selected for inclusion into the Cox proportional hazards model for multivariable analysis and to identify the independent risk factors. The odds ratio and 95% confidence interval were identified for multivariate predictors, and significance was defined as P < 0.05. Kaplan–Meier survival curves of the PFS and overall survival OS time of the 40 synchronous MPLA patients and 5 patients with intrapulmonary metastases are shown in Figure 2. The postoperative median PFS time of the 40 synchronous MPLA patients was 51 months. The 3-year and 5-year progression-free survival rates were 72.8% and 42.4%, respectively, which were significantly better than those of the 5 patients who were diagnosed as having intrapulmonary metastases (P = 0.001). The postoperative median OS time of the 40 synchronous MPLA patients was 64 months. The 3-year and 5-year overall survival rates were 86.7% and 52.7%, respectively, which were significantly better than those of the intrapulmonary metastasis patients (P < 0.001).Figure 2: Kaplan–Meier PFS and OS curves of the 45 patients diagnosed as synchronous MPLAs and intrapulmonary metastases. PFS: Progression-free survival, OS: Overall survival; MPLA: Multiple primary lung adenocarcinoma.For further identify the risk factors of PFS and OS for the synchronous MPLA patients, univariate analysis was first adopted to exclude potentially meaningless variables (Supplementary Table 3, https://links.lww.com/CM9/A6). Candidate variables (P < 0.150) that were selected for the multivariable analysis of PFS risk factors included larger maximal tumor dimension (P < 0.001), ECOG performance status (P = 0.033), the use of a minimally invasive approach (P < 0.001), operational option (P = 0.132), highest pT stage (P < 0.001), pN stage (P < 0.001), the number of invasive adenocarcinomas (P = 0.048) and the use of postoperative chemotherapy (P < 0.001). Candidate variables (P < 0.15) selected for multivariable analysis of OS risk factors included larger maximal tumor dimension (P = 0.006), ECOG performance status (P = 0.029), the use of a minimally invasive approach (P = 0.001), highest pT stage (P = 0.004), pN stage (P = 0.003), the number of invasive adenocarcinomas (P = 0.144) and the use of postoperative chemotherapy (P = 0.001). The results of the multivariate analysis are shown in Table 2. For progression-free survival rate, ECOG performance status (P = 0.002), highest pT stage (P = 0.003) and pN stage (P = 0.016) were identified as independent risk factors. Larger maximal tumor dimension (P = 0.848), the use of a minimally invasive approach (P = 0.137), operational option (P = 0.348), the number of invasive adenocarcinomas (P = 0.254) and the use of postoperative chemotherapy (P = 0.252) were not independent predictors. For overall survival rate, ECOG performance status (P = 0.011), the use of a minimally invasive approach (P = 0.038) and highest pT stage (P = 0.040) were identified as independent risk factors, while larger maximal tumor dimension (P = 0.941), pN stage (P = 0.261), the number of invasive adenocarcinomas (P = 0.669) and the use of postoperative chemotherapy (P = 0.147) had no effect on overall survival rate in our cohort. As far as we know, the diagnosis, staging, and treatment of multiple primary lung cancer has always been a subject of intense interest in thoracic surgery.Table 2: Multivariate analysis result of the independent risk factors of PFS and OS for the 40 patients with synchronous MPLAsComprehensive histologic assessment has proven an ideal method for the identification of synchronous MPLAs.[6] However, a proportion of patients with 2 or more lung adenocarcinomas of similar pathological subtypes do exist. In our cohort, this rate was as high as 8/45, and 3 of the 8 patients were finally confirmed to have synchronous MPLAs on this occasion. The EGFR mutation status of 80 tumors in 43 patients was available (80/97, 82.5%) in our cohort. EGFR mutations were identified in 37 tumors of 24 patients (37/80, 46.3%). Two of the 8 patients with similar pathological subtypes were identified as having discordant EGFR mutation status and were diagnosed as having synchronous MPLAs. In theory, the simultaneous identification of multiple tumor drive genes should provide better identification.[7] A diagnostic lineage test based on genomic rearrangements from mate-pair sequencing had previously been applied for distinguishing independent primary from metastatic lung cancers.[8] We chose to apply NGS due to the awareness of genetic heterogeneity in non-small-cell lung cancers. In our cohort, 1 of the 6 patients with a similar comprehensive histologic assessment result and EGFR mutation type was identified as having different gene mutation types by NGS, and the patient was diagnosed as having synchronous MPLAs. Timely surgical treatment might be helpful for the prognosis of synchronous MPLA patients, especially for those with multiple GGO-like tumors.[9] Although there were high numbers of pT2 and pN1 lung adenocarcinoma patients in our cohort, the 3-year PFS and OS rates still reached 72.8% and 86.7%, values that were significantly higher than those for the intrapulmonary metastasis patients. Our study proved that ECOG performance status can affect both the postoperative PFS and OS of synchronous MPLA patients, which again emphasizes the importance of preoperative evaluation and patient selection due to the complexity of the surgical procedures involved and the particulars of the perioperative management. The highest pT stage was undoubtedly a direct influential factor for the prognosis of the synchronous MPLA patients. Interestingly, pN stage was only an independent risk factor for PFS rate and did not affect OS. A possible explanation for this is that pN stage is strongly related to tumor progression, but the progress in chemotherapy and target therapy effectively prolongs the interval time from tumor progression to death. The use of a minimally invasive approach did not affect the PFS but had a positive impact on OS, indicating that VATS would bring overall benefit to the synchronous MPLA patients and should be applied to suitable cases. Some limitations exist, mainly due to the retrospective nature of this study. In addition, the limited number of cases enrolled and the specific characteristics of the synchronous MPLAs could have led to selection bias. Future well-designed, multicenter studies with larger sample sizes are needed to validate these results and clarify the related issues. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Conflicts of interest None.

Objective To identify risk factors that affect the verification of malignancy in patients with solitary pulmonary nodule (SPN) and verify different prediction models for malignant probability of SPN. Methods We retrospectively analyzed the clinical data of 117 SPN patients with definite postoperative pathological diagnosis who underwent surgical procedure in China-Japan Friendship Hospital from March to September 2017. There were 59 males and 58 females aged 59.10±11.31 years ranging from 24 to 83 years. Imaging features of the nodule including maximum diameter, location, spiculation, lobulation, calcification and serum level of CEA and Cyfra21-1 were assessed as potential risk factors. Univariate analysis was used to establish statistical correlation between risk factors and postoperative pathological diagnosis. Receiver operating characteristic (ROC) curve was drawn by different predictive models for the malignant probability of SPN to get areas under the curves (AUC), sensitivity, specificity, positive predictive values, negative predictive values for each model. The predictive effectiveness of each model was statistically assessed subsequently. Results Among 117 patients, 93 (79.5％) were malignant and 24 (20.5％) were benign. Statistical differencewas found between the benign and malignant group in age, maximum diameter, serum level of CEA and Cyfra21-1, spiculation, lobulation and calcification of the nodules. The AUC value was 0.813±0.051 (Mayo model), 0.697±0.066 (VA model) and 0.854±0.045 (Peking University People's Hospital model), respectively. Conclusion Age, maximum diameter of the nodule, serum level of CEA and Cyfra21-1, spiculation, lobulation and calcification are potential independent risk factors associated with the malignant probability of SPN. Peking University People's Hospital model is of high accuracy and clinical value for patients with SPN. Adding serum index into the prediction model as a new risk factor and adjusting the weight of age in the model may improve the accuracy of prediction for SPN.

Background and objective Non-small cell lung cancer with left atrial tumor thrombus accounts for a small proportion of local advanced lung cancer. Whether surgery could bring benefits, as well as surgical options are still controversial, and have always been hot spots in surgical research. We report a single center experience of surgical treatment to non-small cell lung cancer with left atrial tumor thrombus, aim to figure out more reasonable treatment strategy. Methods From August 2006 to July 2017, a total of 11 cases of non-small cell lung cancer with left atrial tumor thrombus underwent surgery in Thoracic Surgery Department of China-Japan Friendship Hospital. Clinical data, treatment options, pathological types and prognosis of these patients were collected to perform a retrospective study. Results Of the 11 patients (mean age of 57.9),7 were men and 4 were women. Six of them received neoadjuvant radiotherapy and/or chemotherapy. All patients underwent smooth operation, including 3 cases with cardiopulmonary bypass, 1 case of posterolateral approach under extracorporeal membrane oxygenation, 6 cases of conventional posterolateral approach and 1 case of video-assisted minithoracotomy. Nine patients were evaluated as R0 resection while 2 cases were evaluated as R1 resection. The Surgeries cost an average of 292 min (210 min-380 min), with an average of 436 mL (100 mL-1,600 mL) blood loss. One patient (9.1％) died within 90 days after surgery, and another 4 cases (36.4％) suffered postoperative complications such as arrhythmia, cerebral infarction or hypoxemia.Six cases of squamous cell carcinoma, 4 cases of adenocarcinoma and 1 case of sarcomatoid carcinoma were identified by pathology. Seven cases were staged as pT4N0M0 while 4 cases were staged as pT4N1M0. Nine patients underwent adjuvant chemotherapy, and two patients underwent radiotherapy during follow-up. The overall follow-up time was 2 to 53 months, the 3-year disease-free survival rate was 30.7％, the median disease-free survival time was 31 months, the 3-year overall survival rate was 49.1％ and the median overall survival time was 33 months. Conclusion For selected patients of non-small cell lungcancer complicated with left atrial tumor thrombus, choose a reasonable surgical approach to resect both the tumor and the thrombus, strengthen the perioperative management and apply neoadjuvant/adjuvant radiotherapy and/or chemotherapy,might obtain satisfying prognosis.

Abstract Cancer stem–like cells (CSC) are thought to drive tumor initiation, metastasis, relapse, and therapeutic resistance, but their specific pathogenic characters in many cancers, including non–small cell lung cancer (NSCLC), have yet to be well defined. Here, we develop findings that the growth factor HGF promotes CSC sphere formation in NSCLC cell populations. In patient-derived sphere-forming assays (PD-SFA) with HGF, CD49f and CD104 were defined as novel markers of lung CSC (LCSC). In particular, we isolated a subpopulation of CD166+CD49fhiCD104−Lin− LCSC present in all human specimens of NSCLC examined, regardless of their histologic subtypes or genetic driver mutations. This specific cell population was tumorigenic and capable of self-renewal, giving rise to tumor spheres in vitro and orthotopic lung tumors in immune-compromised mice. Mechanistic investigations established that NOTCH1 was preferentially expressed in this cell subpopulation and required for self-renewal via the transcription factor HES1. Through a distinct HES1-independent pathway, NOTCH1 also protected LCSCs from cisplatin-induced cell death. Notably, treatment with a γ-secretase inhibitor that blunts NOTCH1 function ablated self-renewing LCSC activity and restored platinum sensitivity in vitro and in vivo. Overall, our results define the pathogenic characters of a cancer stem–like subpopulation in lung cancer, the targeting of which may relieve platinum resistance in this disease. Cancer Res; 77(11); 3082–91. ©2017 AACR.

We report a case of pulmonary squamous cell carcinoma complicated with a tumor thrombus in the left atrium. The left atrial tumor thrombus, together with the left lower lobe, was removed via complete video-assisted thoracoscopic surgery (VATS), with cardiopulmonary bypass standby. The patient recovered well from surgery, received four cycles of postoperative chemotherapy, and is now under follow-up at the outpatient clinic. Although the optimal treatment is still controversial, simultaneous VATS and atriotomy under the premise of preoperative evaluation of the thrombus, including size and extent, might prevent systemic embolization and sudden death, alleviate the wound, promote postoperative rehabilitation, and improve prognosis in selected patients.

肺癌是我国发生率及死亡率最高的恶性肿瘤,而非小细胞肺癌(SCLC)占其中的80%.早期SCLC仍以手术治疗为主.精准的淋巴结分期直接影响到患者的T M分期、后续治疗方案及预后.近来,多个研究发现,胸腔镜手术(VATS)的淋巴结升级率(odal upstaging)低于传统开胸手术.这使人们开始怀疑VATS手术的淋巴结评估能否完全替代传统手术.产生这一现象的原因也值得胸外科医生进一步探讨.

BACKGROUNDThe diagnosis, staging, and therapeutic strategy for synchronous multiple primary non-small cell lung cancer (SMP-NSCLC) remain unclear. Distinguishing SMP-NSCLC from intrapulmonary metastasis is difficult but of great importance for selecting the surgical procedure and prognoses.METHODSFifty-two patients diagnosed with SMP-NSCLC according to the modified Martini-Melamed criteria in the thoracic surgery department of the China-Japan Friendship Hospital from November 2004 to December 2015 were enrolled in this retrospective study. A total of 106 tumors were subjected to pathological examination. Close follow-up and survival analysis were performed.RESULTSThe perioperative morbidity rate was 5.8%, with no cases of perioperative death. The overall 5-year survival rate was 40.6%, the cancer-specific 5-year survival rate was 54.5%, and the median survival time was 52 months. Older age (P=0.553), sex (P=0.600), smoking history (P=0.496), tumor distribution (P=0.461), video-assisted thoracoscopic surgery (VATS) (P=0.398), and adjuvant chemotherapy (P=0.078) did not affect survival. Preoperative percentage of forced expiratory volume in the first second (P=0.022), Charlson comorbidity index (P=0.034), surgical procedure (P=0.040), and highest pT stage (P=0.022) were independent risk factors in the multivariate analysis. Different pathological subtypes were identified in 13 of 18 cases of multiple adenocarcinomas. Different gene mutation types and correlations between tumors were identified through NGS in those with the same pathological subtype.CONCLUSIONSPostoperative survival rates in SMP-NSCLC were satisfactory. Non-radical resection might improve the prognosis for patients with a tolerable general condition and pulmonary function. Higher pT stage might result in poorer survival rates. Larger sample size and future study are still needed to identify the prognostic factors. Comprehensive histologic assessment and next generation sequencing (NGS) could be effective methods for screening SMP-NSCLC.

Objective To investigate the safety and feasibility ofthoracoscopic thymectomy in the treatment ofmy-asthenia gravis compared with trans-sternal thymectomy.Methods Retrospectively analyzed the clinical and pathologicaldata of 62 patients with myasthenia gravis admitted in the Department of thoracic surgery of China-Japan Friendship Hos-pital from January 2008 to December 2015.Results In 62 cases,38 (61.3％) underwent thoracoscopic thymectomy,24cases (38.7％) underwent transstemal thymectomy.The intraoperative bleeding in Thoracoscopic surgery group was lessthan the traditional group,the difference was statistically significant (P ＜ 0.05),and postoperative intubation time,postop-erative hospitalization time was shorter than the traditional group (P ＜ 0.05).The operative time,postoperative drainageand postoperative complications of the two groups had no significant difference (P ＞ 0.05).The total efficiency was no sig-nificantly different between the two groups of patients with MG (83.3％vs88.9％,P =0.962).Conclusion The effect ofvideo-assisted thoracoscopic surgery for myasthenia gravis is not inferior to that of the traditional Transstemal thymecto-my,and it has the advantages of less bleeding,less injury and shorter hospital stay,therefore,it is worthy of clinical appli-cation.

OBJECTIVES:The regularity of intrapulmonary lobar and segmental lymph node (LSN) metastasis in cT1N0M0 stage lung adenocarcinoma remains unclear. Thus, segmentectomy with uncertain LSN metastatic status remains a potential oncological risk. We aimed to facilitate more accurate determination of N staging and filter more suitable cases for segmentectomy. METHODS:A prospective study was performed from March 2014 to September 2016. A total of 196 patients diagnosed with cT1N0M0 stage lung adenocarcinoma were enrolled and received lobectomy together with mediastinal lymph node dissection. The intrapulmonary LSNs were dissected and classified as adjacent LSN or isolated LSN. The metastatic status of the LSNs together with the TNM staging were analysed. A comparison of the metastatic probability of isolated LSN was carried out considering the metastatic status of adjacent LSN, imaging features, smoking history, pathological subtypes, size of the lesions and serum level of tumour markers (carcinoembryonic antigen and Cyfra21-1). RESULTS:Among the 196 cases enrolled, 152 were confirmed as pN0, 36 as pN1, 6 as pN1 + N2 and 2 as skip pN2. When the LSNs had not been dissected, the false-negative rate for N staging was 9.0% (15 of 167). Patients with adjacent LSN metastasis (P < 0.001), solid nodule (P = 0.001), non-lepidic predominant invasive adenocarcinoma (P < 0.001), nodules with maximum diameter larger than 2 cm (P < 0.001) and those with elevated serum carcinoembryonic antigen level (>5 ng/ml) (P = 0.005) had a higher isolated LSN metastasis rate. No significant difference in isolated LSN metastasis rate was found between groups with or without smoking history (P = 0.90) and with different serum Cyfra21-1 levels (P = 0.14). CONCLUSIONS:Dissection of intrapulmonary LSNs reduces the false-negative rate of lymph node metastasis. Solid nodule, non-lepidic predominant invasive adenocarcinoma, lung adenocarcinoma larger than 2 cm in maximum diameter or with elevated serum carcinoembryonic antigen level (>5 ng/ml) might not be suitable for segmentectomy. The lymph node sampling area during segmentectomy should include adjacent LSNs of the target segment. When metastasis to the adjacent LSNs is confirmed by fast-frozen pathology, segmentectomy would not be suitable.

Objective To evaluate whether surgical intervention can be performed in initial onset of primary spontaneous pneumothorax (PSP) patients and whether pleural abrasion should be performed regularly in PSP treatment.Methods The clinical data of 326 PSP patients undergoing bullectomy or bullectomy combined with pleural abrasion (BLPA) between January 2008 and December 2013 were retrospectively reviewed.There were 267 males and 59 females,with a mean age of 24 years ranging from 20 to 31 years.Results The initial onset of PSP was in 229 patients,and recurrent PSP in 115 patients.Ten patients had postoperative PSP recurrence after a mean follow-up of 47 months ranging from 1 to 95 months.For the patients with initial onset of PSP,the recurrence rate was 3.1％ (7/229),and that in patients with recurrent PSP was 2.6％ (3/115,P=0.82).Compared with the bullectomy group (5.8％,7/120),recurrence rate in the BLPA group was lower (1.3％,3/224,P=0.02).There were no mortalities or significant complications in both groups.There was significant difference in body mass index (P=0.04),intraoperative adhesion (P＜0.05),operation duration (P＜0.01),number of bullae (P＜0.01),and bullae location (P＜0.01) between bullectomy and BLPA groups.Postoperative drainage (P＜0.01),air leak (P=0.01) and extubation duration (P＜0.01) were significantly lower in the bullectomy group.Total cost was significantly higher in the BLPA group (P＜0.01).Conclusion Surgical intervention could provide satisfactory outcomes for PSP patients.Compared with bullectomy,BLPA has much lower recurrence rate,but with more drainage,longer drainage duration and higher cost.

Context.-The mutation analysis of epidermal growth factor receptor (EGFR) has become a common test to guide therapeutic decision making for lung cancer. Molecular testing with circulating tumor DNA in plasma allows diagnosis of mutations when tumor tissue is not available as well as monitoring treatment response with repeat biopsies.Objectives.-To develop a timely and cost-effective assay that can accurately detect EGFR mutations in circulating tumor DNA and to evaluate the analytic and clinical performance of the assay.Design.-Analytic assessment was conducted with a set of reference materials carrying classic EGFR mutations. A recently developed Poisson distribution-based approach was employed to understand the assay sensitivity. Clinical evaluation was performed with 224 pairs of plasma and matched tissues from patients with stage I to IV disease. EGFR mutation rates of 390 consecutive plasma samples processed in the central service laboratory were compared with previously reported prevalence in an Asian population.Results.-Our results suggested that limit of detection for the EGFR quantitative polymerase chain reaction assay was 10 mutation copies, and the lowest detectable copy numbers could be extended to a single-digit level. The clinical sensitivity was 53.3% for all stages combined and 81.4% for late stages, with a high specificity of 100%. Clinical observations showed an overall positive finding rate of 32.5% and 41.4% for stage IV disease, which is consistent with previously reported EGFR mutation prevalence in an Asian population.Conclusions.-Our results supported the clinical utility of the ultrasensitive, quantitative polymerase chain reaction assay for EGFR mutation analysis with circulating tumor DNA.

Objective To investigate the regularity of intrapulnonary lobar and segmental lymph nodes metastasis in patients with cT1N0M0 stage lung adenocarcinoma.To provide a basis for more accurate determination of N stage and indication for pulmonary segmental resection.Methods A prospective study was performed from March 2014 to December 2015.103 cases of cT1 N0M0 stage lung adenocarcinoma received lobectomy and mediastinal lymph node dissection in the thoracic surgery department of China-Japan Friendship Hospital.Intrapulmonary lobar and segmental lymph nodes were dissected and sorted carefully then sent to the pathological department with the corresponding lung specimen and other lymph nodes.Statistical analysis was carried out considering size of the lesion,imaging features,serum CEA levels,pathological subtypes and so on.Results In total 103 cases,pN0 was confirmed in 82 cases,pN1 in 15 cases,pN1 + N2 in 5 cases,and skipping-pN2 in 1 case.14 cases(93.3％) in pN1 group were detected with station 12-14 lymph node metastasis,while only 5 cases (33.3％) were detected with station 12-14 LSNs metastasis.4 cases(66.7％) in pN2 group were detected with station 12-14 lymph node metastasis,while only 1 case(16.7％) with station 13 and station 7 lymph node metastasis.If LSNs were not detected,the false negative rate of N staging could be as high as 6.1％ (5/82),The rate of missed diagnosis of lymph node metastasis might be 30％ (6/20) to N1 stations alone.41.2％ (7/17)cases with metastasis to the adjacent LSNs had been proved with metastasis to the isolated LSNs.The metastasis rate of the isolated LSNs was significantly lower(P =0.049) in pure GGNs compared with those part-solid/solid nodules.Invasive adenocarcinoma had higher metastasis rate of isolated LSNs,compared with preinvasive lesions or minimally invasive adenocarcinomas,with no statistical difference between groups (P =0.055).No significant difference in isolated LSNs metastasis rate was found between groups with different serum CEA levels(P =0.251) or tumor size(P =0.197).Conclusion Dissection of intrapulmonary lobar and segmental lymph nodes might facilitate a more accurate N stage,reduce the false negative rate of lymph node metastasis,and provide basis for more accurate assessment of prognosis and postoperative adjuvant treatment.The sampling area of lymph nodes during segmental resection should include the adjacent LSNs of the target segment.The isolated LSNs metastasis rate of cT1N0M0 stage lung adenocarcinoma with pureGGN as imaging feature is relative low,which might be suitable for segmentectomy when meeting other criteria.

Background: The platelet-to-lymphocyte ratio (PLR) is a useful predictive factor in several cancers. However, the prognostic value of PLR in patients with non-small-cell lung cancer (NSCLC) is still indistinct. Therefore, it was necessary for us to perform a meta-analysis to assess the prognostic value of PLR in patients with NSCLC.Methods: A systematic literature search was performed by using PubMed, EMBASE, and Web of Science databases for relevant studies until May 2015. Published studies investigating the association between PLR and overall survival (OS) and disease-free survival (DFS) were selected. Data from each eligible study were extracted. A meta-analysis was performed to analyze the prognostic value of PLR by using the hazard ratio (HR) and 95% confidence intervals (95% CI).Results: A total of seven studies involving 1,554 patients were included in our meta-analysis. Our pooled results demonstrated that high PLR was associated with poor OS (HR: 1.60, 95% CI: 1.34-1.90, I-2=22.3%, P-heterogeneity = 0.259) and DFS (HR: 1.38, 95% CI: 1.11-1.73, I-2= 0%, P-heterogeneity = 0.482). Subgroup analysis between PLR and OS was performed in a further investigation. When the patients were segregated according to ethnicity, sample size, cutoff value, stage, and treatment modality, high PLR was also significantly correlated with OS. There was no significant heterogeneity among included studies.Conclusion: High PLR is associated with poor prognosis in patients with NSCLC. PLR may be a significant predictive biomarker in patients with NSCLC.