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Background: The aim of this retrospective study was to assess the influence of the sequence of pulmonary vessel ligation during video-assisted thoracoscopic lobectomy on long-term survival in patients with non-small cell lung cancer (NSCLC). Methods: This retrospective study included 60 patients treated surgically with lobectomy and standard lymphadenectomy between 2012 and 2013. Patients had primary ligation of the pulmonary vein or veins (PV group, 33 patients) or of the pulmonary artery or arteries (PA group, 27 patients). Patients were excluded if they had undergone pulmonary wedge resection before lobectomy. Subgroup and sensitivity analyses were also used to investigate the effect of clinical characteristics of interest on survival. Results: Median follow-up was 54.5 months. Baseline characteristics of the two groups were statistically comparable regarding gender, histology, type of resection, T stage, and overall stage (all P>0.05). Overall, 5-year survival reached 66.67% in the PV group and 44.44% in the PA group (P=0.084). There were no differences between two groups regarding overall survival (OS) (P=0.063, HR: 2.093; 95% CI: 0.960–4.564), disease-free survival (DFS) (P=0.180, HR: 1.539; 95% CI: 0.820–2.889), or cancer-specific deaths (P=0.227, 14/33 vs. 17/27). Subgroup analyses showed no significant difference of OS (P=0.374, HR: 1.541; 95% CI: 0.594–3.997) or DFS (P Log-rank =0.746) for isolated adenocarcinoma, but significant differences in OS (P Log-Rank =0.036; HR: 3.992; 95% CI: 0.987–16.139) and DFS (P=0.044, HR: 3.011; 95% CI: 1.031–8.795) between the two groups of patients in whom squamous cell carcinomas. Sensitivity analysis showed that the differences were not statistically significant between the two groups regarding OS (P=0.140, HR: 1.944; 95% CI: 0.804–4.700) and DFS (P=0.190, HR: 1.605; 95% CI: 0.791–3.255) for patients with a tumour diameter of greater than 3 cm. Conclusions: In summary, the sequence of pulmonary vessel ligation during video-assisted thoracoscopic lobectomy for NSCLC has no different effects on long-term survival, but for patients with squamous cell carcinoma, venous ligation should be preferred first since it may bring survival advantage after surgery.

Background Epidermal growth factor receptor (EGFR) mutation represents a good response to EGFR-tyrosine kinase inhibitor and an advantageous prognostic factor in advanced-stage non-small cell lung cancer (NSCLC). However, the predictive value of EGFR mutation for prognosis in NSCLC patients after complete surgery, which more reflective of natural process, remains controversial. We sought to examine the predictive value of EGFR mutation in NSCLC. Several studies with small sample sizes have been reported but small studies bring bias especially in a postoperative setting. Therefore, we sought to pool all current evidence to show the true effects. Methods Electronic databases were used to search the relevant articles. Disease-free survival (DFS), which will be less effected by subsequent treatments after recurrence, was the primary endpoint. The DFS between EGFR mutated and wild-type patients were compared focus on stage I patients who are rarely received adjuvant therapy. Besides, the DFS of patients with 19 exon deletion (19del) and 21 exon L858R mutation (L858R) were compared. A random effects model was used. Results A total of 19 relevant studies which involved 4,872 cases were enrolled and 2,086 patients were EGFR-mutated. The majority of studies used PCR-based methods to detect EGFR mutations. Through meta-analysis, we observed the DFS of EGFR-mutated patients were similar to wild type patients in overall population (HR 0.93, 95% CI: 0.74 to 1.17). Similar results were observed in stage I subgroup (HR 0.82, 95% CI: 0.50 to 1.33). DFS of 19 del patients were potentially inferior to L858R patients but the difference was not significant (HR 1.38, 95% CI: 0.76 to 2.52). Conclusions There was no significant difference in postoperative DFS between EGFR-mutant patients and wild-type with resected NSCLC. In addition, there is still insufficient evidence to support different postoperative treatment strategies (especially for stage I) for both mutated and wild-type patients. However, 19 del may be a negative factor, which may require more strict management. Thus, we strongly encourage reporting specific prognostic impacts of different mutation types.

Career situation of first and presenting author Student for a master or a PhD. Introduction Neutrophilic asthma is Corticosteroid-resistant and increases the burden of global health care. Multiple studies have indicated that there are a large amount of neutrophil extracellular traps (NETs) in the airways of neutrophil asthmatics.1 Although NETs are able to entrap and kill pathogens, extensive accumulation of NETs which aggravate the condition of asthmatics and promote the progression of the disease.2 However to our knowledge, the mechanisms by which NETs influence the progression of asthma have not been clearly elucidated and neutrophilic asthma requires novel effective therapeutic strategies. Objectives We sought to explore the underlying mechanisms of NETs aggravate the severity of asthma, and to investigate a new strategy of effective treatment against corticosteroid-insensitive neutrophilic asthma. Methods Mouse models of neutrophil-dominated asthma and phorbolester(PMA) aggravated neutrophil asthma were used in this study to clarify the role of NETs in the pathogenesis of neutrophil asthma. Neutrophil release NETs was detected in bronchoalveolar lavage fluid (BALF)of neutrophil-dominated asthma. Finally a small molecule Necrostatin-1(Nec-1) which has been shown to inhibit neutrophil release NETs was tested for its therapeutic effects against neutrophilic airway inflammation. Results NETs could induce human epithelium human bronchial epithelial cell deth and detachment in vitro study. NETs significantly increased in neutrophil asthma model and PMA aggravated neutrophil asthma. In vivo studies, Nec-1 could relieve airway hyperresponse, also reduced total protein, myeloperoxidase activity and inflammatory cytokines. Histological examination of the lungs also showed that Nec-1 markedly reduced the inflammation. We further explored that Nec-1 could induce human neutrohils and mice BALF neutrohils apoptosis. BALF and lung tissue immunofluorescence showed neutrophils increased expression of cleaved-casepase.3 Conclusions NETs could damage airway epithelium and trigger inflammatory responses. Nec-1 inhibit neutrophil release NETs ameliorates neutrophil airway inflammation. May be the inherent mechanism of Nec-1 inhibit neutrophil release NETs is related to it specificitly promotes neutrophil apoptosis. References Porto BN, et al. Neutrophil Extracellular Traps in Pulmonary Diseases: Too Much of a Good Thing? Frontiers Immunolugy 2016;7:311. Toussaint M, et al. Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation. Nature Medicine, 2017;23(6):681–691. Pham, DL, et al. Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma. Clin Exp Allergy, 2017;47(1):57–70. Acknowledgements Thanks to the colleagues in the team of Dr Erwei Sun. Disclosure of Interest None declared.

Career situation of first and presenting author Young investigator. Introduction Evidences revealed that chemotherapies could trigger DNA release, then induce inflammation of intestinal tissues which damp the effect of anti-cancer treatment.1 2 DNA released induces the translocation of TLR9 to endolysosomes and subsequent nuclear factor-κB (NF-κB) activation, which leads to interleukin-1β (IL-1β) secretion and inflammation.3 Targeting TLR9-dependent DNA sensing pathway may be a valuable therapy for chemotherapy induced intestinal mucositis. Objectives This study aims to investigate whether hydroxychloroquine (HCQ), suppresses 5-FU-induced intestinal mucositis through inhibiting TLR9-dependent DNA sensing pathway. Methods The effect of HCQ on 5-FU-induced intestinal mucositis were examined in vivo and in vitro. We established 5-FU-induced intestinal mucositis model and assessed body weight, diarrhea score and histopathologic changes following HCQ treatment in vivo, then TLR9 and NF-κB expression of small intestine and IL-1β secretion of serum were analyzed. Bone marrow-derived macrophages (BMDMs) were cultured, transfected with calf-thymus DNA(CT-DNA) and treated with HCQ for 6 hour in vitro. TLR9 and NF-κB expression and IL-1β secretion in BMDMs were then investigated. Results HCQ treatment markedly attenuated body weight loss, severity of diarrhea, intestine shortening, and destruction of small intestinal in histopathology of 5-FU- treated mice in vivo. Also HCQ treatment inhibited TLR9 and NF-κB expression in small intestine of 5-FU- treated mice and pro-inflammatory IL-1β secretion in serum of 5-FU- treated mice. Meanwhile administration of HCQ reduced the number of macrophages in small intestine of 5-FU-treated mice. Then BMDMs were cultured, transfected with CT-DNA and treated with HCQ in vitro. We found HCQ efficiently inhibited TLR9 expression, translocation of NF-κB to nucleus, and IL-1β secretion in supernatant of CT-DNA stimulated BMDMs. Conclusions These results provides a new insight into the mechanism of chemotherapy induced intestinal mucositis and indicate HCQ may be used as a strategy against intestinal mucositis during 5-FU chemotherapy. References Woo S-R, Fuertes MB, Corrales L, et al. STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors. Immunity 2014;41:830–42. Hu B, Jin C, Li H-B, et al. The DNA Sensing Aim2 Inflammasome Controls Radiation Induced Cell death and Tissue Injury. Science (New York, NY). 2016;354:765–8. Miura K, Kodama Y, Inokuchi S, et al. Toll-Like Receptor 9 Promotes Steatohepatitis by Induction of Interleukin-1β in Mice. Gastroenterology. 2010;139:323–34.e7. Acknowledgements The authors confirm that there are no conflicts of interest. Disclosure of Interest None declared.

Extramedullary plasmacytoma (EMP) is an uncommon monoclonal plasma cell malignancy that arises outside of the bone marrow. Rarely, EMPs can occur in the trachea, resulting in severe respiratory distress. Due to a small number of cases, the optimal management of tracheal EMP remains a topic of debate. Here, we report a rare case of solitary tracheal EMP causing symptoms of cough, sputum, paroxysmal nocturnal dyspnea, and progressive exertional dyspnea in a 65-year-old male patient. Computerized tomography and fibro bronchoscopy indicated a pedicled nodular mass on the anterior tracheal wall obstructing over 95% of the lumen. The patient was soon successfully managed with partial tracheal resection and reconstruction surgery under non-intubated anesthesia and was diagnosed as EMP by histopathology of the resected mass. Additional laboratory tests excluded the diagnosis of multiple myeloma (MM). There are no signs of recurrence after 6 months of follow-up. Although traditional intubated anesthesia with single-lung mechanical ventilation has been widely applied to radical surgery for tracheal tumors, it is associated with a higher incidence of intubation-related complications and thus prolongs the surgical procedure and postoperative recovery. In this article, we reported the application of tracheal resection and reconstruction under non-intubated anesthesia for the treatment of tracheal EMP, which was proved to be feasible and safe. Non-intubated anesthesia for tracheal resection and reconstruction is likely to be an alternative minimally invasive option for patients with tracheal EMP involving central airways.

Common lung diseases are first diagnosed using chest X-rays. Here, we show that a fully automated deep-learning pipeline for the standardization of chest X-ray images, for the visualization of lesions and for disease diagnosis can identify viral pneumonia caused by coronavirus disease 2019 (COVID-19) and assess its severity, and can also discriminate between viral pneumonia caused by COVID-19 and other types of pneumonia. The deep-learning system was developed using a heterogeneous multicentre dataset of 145,202 images, and tested retrospectively and prospectively with thousands of additional images across four patient cohorts and multiple countries. The system generalized across settings, discriminating between viral pneumonia, other types of pneumonia and the absence of disease with areas under the receiver operating characteristic curve (AUCs) of 0.94-0.98; between severe and non-severe COVID-19 with an AUC of 0.87; and between COVID-19 pneumonia and other viral or non-viral pneumonia with AUCs of 0.87-0.97. In an independent set of 440 chest X-rays, the system performed comparably to senior radiologists and improved the performance of junior radiologists. Automated deep-learning systems for the assessment of pneumonia could facilitate early intervention and provide support for clinical decision-making.

Background Risk of adverse outcomes in COVID-19 patients by stratifying by the time from symptom onset to confirmed diagnosis status is still uncertain. Methods We included 1,590 hospitalized COVID-19 patients confirmed by real-time RT-PCR assay or high-throughput sequencing of pharyngeal and nasal swab specimens from 575 hospitals across China between 11 December 2019 and 31 January 2020. Times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit and from first medical visit to confirmed diagnosis were described and turned into binary variables by the maximally selected rank statistics method. Then, survival analysis, including a log-rank test, Cox regression, and conditional inference tree (CTREE) was conducted, regarding whether patients progressed to a severe disease level during the observational period (assessed as severe pneumonia according to the Chinese Expert Consensus on Clinical Practice for Emergency Severe Pneumonia, admission to an intensive care unit, administration of invasive ventilation, or death) as the prognosis outcome, the dependent variable. Independent factors included whether the time from symptom onset to confirmed diagnosis was longer than 5 days (the exposure) and other demographic and clinical factors as multivariate adjustments. The clinical characteristics of the patients with different times from symptom onset to confirmed diagnosis were also compared. Results The medians of the times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit, and from first medical visit to confirmed diagnosis were 6, 3, and 2 days. After adjusting for age, sex, smoking status, and comorbidity status, age [hazard ratio (HR): 1.03; 95% CI: 1.01-1.04], comorbidity (HR: 1.84; 95% CI: 1.23-2.73), and a duration from symptom onset to confirmed diagnosis of >5 days (HR: 1.69; 95% CI: 1.10-2.60) were independent predictors of COVID-19 prognosis, which echoed the CTREE models, with significant nodes such as time from symptom onset to confirmed diagnosis, age, and comorbidities. Males, older patients with symptoms such as dry cough/productive cough/shortness of breath, and prior COPD were observed more often in the patients who procrastinated before initiating the first medical consultation. Conclusions A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.

4028 Background: Despite multidisciplinary therapies, prognosis of pts with resectable esophageal squamous cell carcinoma (ESCC) remains poor. Combining PD-1 blockade to neoadjuvant chemotherapy might be a feasible and effective strategy. Camrelizumab (an anti-PD-1 antibody) was approved for advanced or metastatic ESCC in the second-line setting and showed improved anti-tumor activity and survival benefit when combined with chemotherapy in multiple advanced tumors. Methods: In this NIC-ESCC2019 phase 2 study, histologically or cytologically confirmed ESCC pts (stage II-IVA) were enrolled to receive two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m² in total on day 1 and day 8) and cisplatin (75 mg/m² in total on days 1-3) of each 21-day cycle, followed by esophagectomy. The primary endpoint was complete pathologic response (CPR) rate in the primary tumor. Besides, we also explored the relationship between the tumor genomic profile or primary-tumor microenvironment and the pathological response. Results: Between Jan 17, 2020 and Dec 8, 2020, 56 pts were enrolled. 51 pts underwent surgical resection, and all had complete tumor resection. CPR was achieved in 18 (35.3%; 95% CI, 21.7%-48.9%) pts; 12 (23.5%) pts had major pathologic response (MPR), and 21 (41.2%) had incomplete pathological response (IPR). Of note, 16 (31.4%) pts achieved CPR in both primary tumor and lymph nodes. The objective response rate was 66.7% (95% CI, 40.0-70.4). No in-hospital mortality occurred. The most common treatment-related adverse events (TRAEs) were decreased WBC (20 [36%] of 56 pts), vomiting (19 [34%]), and alopecia (18 [32%]). Grade 3 TRAEs only occurred in 6 (11%) pts, and there were no grade 4 or 5 TRAEs. The most common immune-related AEs included grade 1-2 rash maculo-papular (7 [13%]) and reactive cutaneous capillary endothelial proliferation (5 [9%]). Presence of mutations in CREBBP and KMT2D at treatment-naïve time-point was correlated with non-response group (IPR and stable disease) (CREBBP, p = 0.046; KMT2D, p = 0.047). Among the immune populations, CD8+, CD8+PD-1+ and CD8+PD-L1+ T cells increased significantly after two doses of NIC, especially in the CPR+MPR group (CD8+, p = 0.013; CD8+PD-1+, p < 0.001; CD8+PD-L1+, p = 0.068). Conclusions: The addition of camrelizumab to neoadjuvant chemotherapy in ESCC demonstrated promising efficacy with acceptable toxicity, supporting the further investigation in a randomized phase 3 clinical trial. Clinical trial information: NCT04225364. [Table: see text]

8545 Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) have been proven its significant efficacy on advanced non-small cell lung cancer (NSCLC). However, it remains unknown and is of great interest whether the PD-1 antibody affects early-stage lung cancer. Here, we reported the preliminary efficacy and safety outcomes of sintilimab on these early-stage GGO lesions in patients (pts) with multiple primary lung cancer in the CCTC-1901 study, the first trial evaluating PD-1 antibody in preinvasive or low invasive lung cancer worldwide. Methods: This single-center, phase II, Simon's two-stage design trial included pts who had a pathological diagnosis of resected lung cancer and at least one unresectable GGO lesion suspicious malignant which evaluated by a multidisciplinary team's consensus. The enrolled pts received 4 cycles of intravenous sintilimab 200 mg every 3 weeks. The primary endpoint is the objective response rate (ORR) of unresectable GGO lesions. For persistent GGO lesions that did not respond to treatment, either observation or second operation was taken. Also, immune biomarkers (T/B/NK subpopulation etc.) were monitored during treatment to validate the immune activity. Results: A total of 36 pts were included, with median age 59.5 (53.5-69), 66.7% females, 80.6% never smokers. All resected lesions were adenocarcinomas, of which 52.8% were EGFR mutated. 49 unresected GGOs (pure 11[22.4%], mixed 38[77.6%]) were defined as target lesions from 36 enrolled pts, with a mean size of 13.20±5.06 mm. The ORR (RECIST v1.1) was 5.6% (2/36, 1 PR and 1 CR); none of the pts had PD. Additionally, 3 non-target lesions (unresected solid lesions) from 3 included pts showed PR after the treatment of sintilimab, and the rest lesions (target or non-target) of 31 pts performed SD. Grade 1-2 fatigue (13, 36%), rash (13, 36%) and arthralgia (8, 22%) were the most common treatment-related adverse events (TrAEs), and no grade 3-5 TrAEs occurred. The proportion of CD8+ T-cell and the ratio of CD8+/CD4+ in 5 patients who showed PR of unresected lesions were significantly higher compared to those with SD lesions at baseline (CD8+ 36.6% vs 24.6%, p < 0.01; CD8+/CD4+ 1.09±0.18 vs 0.64±0.22, p < 0.01). Conclusions: This study is the first to confirm that PD-1 antibody sintilimab has immune-related antitumor activity on GGO-featured lung cancer and could be well tolerated among pts with early-stage lung cancer. Clinical trial information: NCT04026841.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are treatments commonly used for lung cancer. The toxicity profile including toxicity incidence, severity, and spectrum (involving various specific adverse events) of each EGFR-TKI are of particular clinical interest and importance. Data from phase II and III randomized controlled trials comparing treatments among EGFR-TKIs (osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib) and chemotherapy for lung cancer were synthesized with Bayesian network meta-analysis. The primary outcome was systemic all-grade and grade ≥3 adverse events. The secondary outcome was specific all-grade adverse events including those of the skin, gastrointestinal tract, lung, etc. 40 trials randomizing 13,352 patients were included. Generally greater toxicity for dacomitinib and afatinib, and safety for icotinib were suggested. Furthermore, we found individual EGFR-TKIs had different toxicity spectrums. These findings provide a compelling safety reference for the individualized use of EGFR-TKIs for patients with lung cancer.

BACKGROUND: Primary pulmonary mucoepidermoid carcinoma (PMEC) is a rare malignant tumor, and the clinical manifestations lack specificity. The study evaluates the prognostic factors and constructs a practicable nomogram to estimate the individualized survival status for PMEC patients. METHODS: Surveillance, Epidemiology, and End Results (SEER) database was used to selected eligible patients between 1975 and 2016. The baseline characteristics including age, sex, race, marital status, tumor stage, differentiated degree, tumor laterality, primary tumor site, tumor size, lymph node metastases status, distant metastases status, surgery, chemotherapy, and radiation. We identified independent variables to build 3-, 5-, 10-year overall survival (OS) and cancer-specific survival (CSS) nomograms by univariate and multivariate analyses. RESULTS: A total of 438 PMEC patients met our selection criteria. In multivariate analysis, age, tumor stage, differentiated grade, tumor size, lymph node metastases status, distant metastases status, surgery and radiation were involved in the nomogram. The C-index (0.887 (95% CI: 0.863–0.911), calibrate plots and ROC curves (AUC =0.941, 0.951, 0.935 for 3-, 5-, 10-year OS, respectively) indicated the satisfied accuracy and practicability of our nomograms. Compared to TNM system, our model also showed a superior prediction (IDI =0.167, 0.171, 0.172, P

Subglottic stenosis is an uncommon structural abnormality that can pose as a difficulty for patients undergoing surgery, and treatment is complex due to the special anatomical location. Pulmonary nodule resection in patients with subglottic stenosis is challenging and has not yet been reported. Here we present a case of pulmonary nodule resection in a patient with subglottic stenosis using uniportal thoracoscopy under spontaneous ventilation anesthesia (SVA). Compared with traditional double lumen endotracheal intubation, we believe this modified technique can significantly reduce airway trauma, and accelerate patient recovery.

Epidermal growth factor receptor ( EGFR) gene copy number has been proposed as a candidate biomarker for predicting treatment response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced non-small-cell lung cancer (NSCLC). MEDLINE, PubMed, Cochrane, and Google Scholar databases were searched until October 21, 2015 using the following search terms: lung neoplasms/lung cancer/non-small cell lung cancer/NSCLC, EGFR, gene amplification, copy number, erlotinib, gefitinib, tyrosine-kinase inhibitor/TKI, predictor. 17 studies were included in the analysis with a total of 2047 patients. The overall analysis found that increased EGFR gene copy number was associated with higher overall response rate (ORR), overall survival (OS) and progression-free survival (PFS; p values ≤0.008) compared with patients without a high EGFR gene copy number. Subgroup analysis found that in a population of patients who were primarily Caucasian, a higher EGFR gene copy number was also associated with increased ORR, OS, and PFS (p values ≤0.018). The results were similar in a population of Asian patients, except that a higher EGFR gene copy number was not associated with improved OS (p=0.248). Sensitivity analysis indicated that no one study overly influenced the results and that the findings are robust. The result of the analysis found that EGFR gene copy number was associated with increased OS and PFS, supporting the idea that EGFR gene copy number is a biomarker for response to EGFR-TKI therapy in patients with advanced NSCLC.

Background and objective National Comprehensive Cancer Network (NCCN) guidelines recommend video-assisted thoracoscopic surgery (VATS) anatomical lobectomy as the first choice for the treatment of resectable lung cancer. However, sublobar resection offers significantly better functional preservation compared with lobectomy for stage I lung cancer. At present, the inferiority of sublobar resection to lobectomy is still uncertain. Herein, we compared the prognoses of these two types of surgical treatment for stage I lung adenocarcinoma. Methods Retrospective research was conducted on 258 patients with stage I lung adenocarcinomas who underwent VATS lobectomy and sublobar resection at the First Affiliated Hospital of Guangzhou Medical University between January 2009 and December 2011. VATS lobectomy was performed on 222 patients, and VATS sublobe resection was performed on 36 patients. Propensity score matching analyses were conducted on the two groups. Results A total of 70 patients were matched in the two groups. No significant difference was observed between the lobectomy and sublobar resection groups after matching (P=0.137). The disease-free survival (DFS) of the two groups were 49.3 and 42.7 months, and their overall survival (OS) were 50.3 and 49.0 months (P=0.122). Further, stratified analysis showed no significant differences in DFS and OS between the two groups with stage Ia lung adenocarcinoma. Nevertheless, the DFS and OS of the two groups significantly differed in matched patients with stage Ib lung adenocarcinomas. Conclusion Sublobar resection could achieve a similar prognosis to VATS lobectomy for stage Ia lung adenocarcinoma. Lobectomy should still be the first choice for the treatment of stage Ib lung adenocarcinoma.

// Lihua Peng 1, 2, * , Leo J Lee 2, 3, * , Heng Xiong 2 , Hong Su 2 , Junhua Rao 2 , Dakai Xiao 4, 5, 6 , Jianxing He 4, 5, 7 , Kui Wu 2, 8 , Dongbing Liu 2 1 BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China 2 BGI-Shenzhen, Shenzhen 518083, China 3 Department of Electrical and Computer Engineering, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3G4, Canada 4 Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China 5 Guangzhou Institute of Respiratory Disease & State Key Laboratory of Respiratory Disease, Guangzhou 510120, China 6 Research Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China 7 National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China 8 Department of Biology, University of Copenhagen, Copenhagen N DK-2200, Denmark * These authors have contributed equally to this work Correspondence to: Dongbing Liu, email: liudongbing@genomics.cn Keywords: lung adenocarcinoma, RNA editing, hyper-editing, primary, metastatic Received: May 27, 2016 Accepted: November 21, 2016 Published: December 21, 2016 ABSTRACT RNA editing results in post-transcriptional modification and could potentially contribute to carcinogenesis. However, RNA editing in advanced lung adenocarcinomas has not yet been studied. Based on whole genome and transcriptome sequencing data, we identified 1,071,296 RNA editing events from matched normal, primary and metastatic samples contributed by 24 lung adenocarcinoma patients, with 91.3% A-to-G editing on average, and found significantly more RNA editing sites in tumors than in normal samples. To investigate cancer relevant editing events, we detected 67,851 hyper-editing sites in primary and 50,480 hyper-editing sites in metastatic samples. 46 genes with hyper-editing in coding regions were found to result in amino acid alterations, while hundreds of hyper-editing events in non-coding regions could modulate splicing or gene expression, including genes related to tumor stage or clinic prognosis. Comparing RNA editome of primary and metastatic samples, we also discovered hyper-edited genes that may promote metastasis development. These findings showed a landscape of RNA editing in matched normal, primary and metastatic tissues of lung adenocarcinomas for the first time and provided new insights to understand the molecular characterization of this disease.

Background: The aims of this study were to analyze the association of LMO4 with non-small-cell lung cancer (NSCLC) survival rate, and to determine its functional role and signaling pathway in lung cancer. Methods: Immunohistochemistry (IHC) was used to detect the expression of LMO4 in NSCLC cell lines and tumor tissues. Migration and invasion ability was detected respectively by wound healing test and transwell test. Immunofluorescence and western blot were detected of AKT/PI3K pathway related genes MAPK, PI3K, AKT. Results: LMO4 has high expression level of NSCLC cell lines and tumor tissues, and correlated with a lower survival rate. LMO4 can regulate the migration and invasion of NSCLC cells through the AKT/PI3K pathway. Conclusions: LMO4 could serve as a promising biomarker and therapeutic target for NSCLC.

Background: We aimed to summarize the diagnostic accuracy of white light bronchoscopy (WLB) and advanced techniques for airway pre-cancerous lesions and early cancer, such as autofluorescence bronchoscopy (AFB), AFB combined with WLB (AFB + WLB) and narrow-band imaging (NBI) bronchoscopy. Methods: We searched for eligible studies in seven electronic databases from their date of inception to Mar 20, 2015. In eligible studies, detected lesions should be confirmed by histopathology. We extracted and calculated the 2×2 data based on the pathological criteria of lung tumor, including high-grade lesions from moderate dysplasia (MOD) to invasive carcinoma (INV). Random-effect model was used to pool sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the receiver-operating characteristic curve (AUC). Results: In 53 eligible studies (39 WLB, 39 AFB, 17 AFB + WLB, 6 NBI), diagnostic performance for high-grade lesions was analyzed based on twelve studies (10 WLB, 7 AFB, 7 AFB + WLB, 1 NBI), involving with totally 2,880 patients and 8,830 biopsy specimens. The sensitivity, specificity, DOR and AUC of WLB were 51% (95% CI, 34–68%), 86% (95% CI, 73–84%), 6 (95% CI, 3-13) and 77% (95% CI, 73–81%). Those of AFB and AFB + WLB were 93% (95% CI, 77–98%) and 86% (95% CI, 75–97%), 52% (95% CI, 37–67%) and 71% (95% CI, 56–87%), 15 (95% CI, 4–57) and 16 (95% CI, 6–41), and 76% (95% CI, 72–79%) and 82% (95% CI, 78–85%), respectively. NBI presented 100% sensitivity and 43% specificity. Conclusions: With higher sensitivity, advanced bronchoscopy could be valuable to avoid missed diagnosis. Combining strategy of AFB and WLB may contribute preferable diagnosis rather than their alone use for high-grade lesions. Studies of NBI warrants further investigation for precancerous lesions.

Purpose According to the lung cancer staging project, T1a (≤ 2 cm) non–small-cell lung cancer (NSCLC) should be additionally classified into ≤ 1 cm and > 1 to 2 cm groups. This study aimed to investigate the surgical procedure for NSCLC ≤ 1 cm and > 1 to 2 cm. Methods We identified 15,760 patients with T1aN0M0 NSCLC after surgery from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and lung cancer–specific survival (LCSS) were compared among patients after lobectomy, segmentectomy, or wedge resection. The proportional hazards model was applied to evaluate multiple prognostic factors. Results OS and LCSS favored lobectomy compared with segmentectomy or wedge resection in patients with NSCLC ≤ 1 cm and > 1 to 2 cm. Multivariable analysis showed that segmentectomy and wedge resection were independently associated with poorer OS and LCSS than lobectomy for NSCLC ≤ 1 cm and > 1 to 2 cm. With sublobar resection, lower OS and LCSS emerged for NSCLC > 1 to 2 cm after wedge resection, whereas similar survivals were observed for NSCLC ≤ 1 cm. Multivariable analyses showed that wedge resection is an independent risk factor of survival for NSCLC > 1 to 2 cm but not for NSCLC ≤ 1 cm. Conclusion Lobectomy showed better survival than sublobar resection for patients with NSCLC ≤ 1 cm and > 1 to 2 cm. For patients in whom lobectomy is unsuitable, segmentectomy should be recommended for NSCLC > 1 to 2 cm, whereas surgeons could rely on surgical skills and the patient profile to decide between segmentectomy and wedge resection for NSCLC ≤ 1 cm.

Objective Store operated calcium channels (SOCCs) and Receptor-operated calcium channels (ROCCs) are important pathways participating in regulation of intracellular Ca2 + concentration in various cell types. The purpose of our study is to determine whether genetic variations in key components of SOCCs and ROCCs are associated with lung cancer risk. Methods We identified 236 tagSNPs in 9 key genes related to SOCCs and ROCCs (TRPC1, TRPC3, TRPC4, TRPC6, TRPC7, ORAI1, ORAI2, STIM1, and STIM2) and evaluated their association with lung cancer risk in a two-stage case-control study with a total of 2433 lung cancer cases and 2433 cancer-free controls using Illumina high throughput genotyping platform. Results We found consistently significant associations of TRPC4 rs9547991 and rs978156, and TRPC7 rs11748198 with increased risk of lung cancer among the three kinds of sources of populations (additive model in combined population: adjusted OR = 1.33, 95% CI = 1.11–1.59 for rs9547991; adjusted OR = 1.21, 95% CI = 1.08–1.35 for rs978156; and adjusted OR = 1.28, 95% CI = 1.10–1.47 for rs11748198). When combining the effects of TRPC7 rs11748198, and TRPC4 rs9547991 and rs978156, subjects carrying “≥ 1” variant alleles had a 1.29-fold increased risk of lung cancer (95% CI = 1.15–1.46), compared with those carrying “0” variant allele. Lung cancer risk significantly increased with the increasing number of variant alleles of the three SNPs in a dose-dependent manner (P for trend = 7.2 × 10− 7). Conclusion These findings suggested that TRPC4 rs9547991 and rs978156, and TRPC7 rs11748198 were candidate susceptibility markers for lung cancer in Chinese population. Our study provides the epidemiological evidence supporting a connection between TRPC members and lung cancer risks., Highlights • TRPC4 and TRPC7 associated with lung cancer risk in 4866 case-control • Adverse effects of TRPCs variants estimated based on the pathway study • Subjects carrying “≥ 1” variant alleles had a 1.29-fold risk, compared with “0”. • Lung cancer risk increased with variant allele's number in a dose-response.

Background: To assess the feasibility and safety of tubeless video-assisted thoracoscopic surgery (VATS) under non-intubated, intravenous anesthesia with spontaneous ventilation and no placement of a chest tube postoperatively compared with VATS under intubated anesthesia with single-lung mechanical ventilation. Methods: A total of 91 patients undergoing tubeless VATS (60 sympathectomies, 22 bullae resections, and 9 mediastinal tumor resections) between December 2012 and December 2015 were included. Additionally, 82 patients were treated by VATS by the same team while under intubated general anesthesia (52 sympathectomies, 19 bullae resections, and 11 mediastinal tumor resections). Comprehensive early outcome data, including intraoperative and postoperative variables, were compared between the subgroups. Results: In total, 89 patients in the tubeless group underwent an effective operation and exhibited good postoperative recovery, while 2 (one sympathectomy and one bullae resection) had their operation aborted for some reason. The tubeless group showed advantages in the postoperative fasting time, the mean duration of the postoperative hospital stay, and postoperative pain scores, while no significant difference was found in intraoperative blood loss, the operation time or postoperative complications between the tubeless group and the intubated group. Furthermore, 83% (49/59) of sympathectomies, 81% (17/21) of bullae resections, and 56% (5/9) of mediastinal tumor resections were achieved via day surgery. Conclusions: In this study, our experience has shown that tubeless VATS is a safe and feasible surgery with certain advantages in selected patients with thoracic disease and that we can achieve day surgery in these cases.

MicroRNAs are a class of small endogenous non-coding RNAs that play crucial roles in the initiation and progression of human cancers. miR-186 was found decreased in various human malignancies and function as a tumor suppressor. However, the regulating mechanism of miR-186 in growth and metastasis of human non-small cell lung cancer (NSCLC) is still poorly understood. We investigated the role of miR-186 in the growth and metastasis of human NSCLC. In the present study, we found that miR-186 was significantly decreased in lung cancer tissues and cells. Furthermore, overexpression of miR-186 suppressed lung cancer cell proliferation, migration and invasion, and induced cell apoptosis. Moreover, we found that confirmed mitogen-activated protein kinase kinase kinase 2 (MAP3K2) protein was increased in lung cancer tissues and confirmed that MAP3K2 is a target gene of miR-186. In addition, knockdown of MAP3K2 by RNA interference inhibited lung cancer cell proliferation, migration and invasion, and promoted cell apoptosis in vitro. Furthermore, we observed tthat the overexpression of MAP3K2 partially reversed the inhibitory effect of miR-186 on the proliferation and metastasis of A549 and HCC827 cell lines. Taken together, our data indicated that miR-186 regulates lung cancer growth and metastasis through suppressing MAP3K2 expression, at least partly. Therefore, miR-186-MAP3K2 may represent a new and useful potential clinical treatment and diagnosis target for NSCLC.

Background: To investigate the estimated value of spiral computed tomography (CT) post-processing techniques in preoperative stage T3, central-type non-small cell lung cancer (NSCLC) with double sleeve lobectomy under complete video-assisted thoracoscopic surgery (c-VATS). Methods: Preoperative clinical date and CT reconstructed data of 10 patients who underwent double sleeve lobectomy with upper lobe stage T3, central-type NSCLC were retrospectively analysed and compared to surgical pathological results and cross-sectional CT data. The diagnostic criterions of tumour invasion of pulmonary artery and bronchus were divided into five grades, which included estimation of upper lobe pulmonary arteries and bronchi (40 branches, respectively). Results: The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of cross-sectional CT images of pulmonary artery tumour invasion were 78.57%, 58.33%, 81.48%, 53.85%, and 72.50%, respectively, while the respective values for CT reconstructed images were 93.55%, 87.50%, 96.67%, 70.00%, and 90.00%, showing statistical significance (χ 2 =4.021, P=0.045). Similarly, the evaluate, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of cross-sectional CT images of bronchial tumour invasion were 82.76%, 45.45%, 80.00%, 50.00%, and 72.50%, respectively, while the respective values for CT reconstructed images were 97.06%, 66.67%, 94.29%, 80.00%, 92.50%; these results were also statistically significant (χ 2 =5.541, P=0.019). Conclusions: The sensitivity, specificity, and diagnostic accuracy of the spiral CT post-processing techniques were better than cross-sectional CT images in estimating the extent of tumour invasion in the pulmonary arteries and bronchi of central-type NSCLC. CT post-processing techniques are essential tools in preoperative examination and operative method selection of central-type lung cancer with double sleeve lobectomy under c-VATS.

Background Although video-assisted thoracoscopic surgery (VATS) has been widely applied to both peripheral and central lung cancer treatment in many centers, there is great hesitation to adopt it for carinal or tracheal surgical procedures. The aims of this study were to explore the feasibility of VATS in the treatment of benign and malignant diseases involving the carina and trachea and to highlight relevant techniques. Methods Patients undergoing VATS carinal or tracheal procedures between May 2012 and July 2015 from three centers in China were included in this study. Their clinical characteristics, operative details, and postoperative course were analyzed. Results Twelve patients underwent five different types of VATS airway reconstructions with or without lobectomy: including right bronchial resection with partial carinal reconstruction (3 patients), tracheal resection and reconstruction (4 patients), tracheal or right bronchial resection with carinal reconstruction (3 patients), left bronchial resection with carinal reconstruction (1 patient), and right pneumonectomy with carinal reconstruction (1 patient). Complete resection was achieved in all patients. The mean operative time was 224 ± 78 minutes, and the median time of the first anastomosis was 41 minutes (range, 15 to 60 minutes), regardless of whether the reconstruction was a tracheal or carinal. The median estimated blood loss was 100 mL (range 10 to 1000 mL). The mean postoperative hospital stay was 12.5 ± 2.5 days. There was no perioperative mortality or major morbidity. Median duration of follow-up was 12 months (range 5 to 43 months). Conclusions VATS resection and reconstruction of the carina or trachea are feasible, and these procedures can be safely performed using the techniques described. We believe, with the accumulation of VATS experience, these procedures could be adopted as routine approaches in tracheal surgery.

Objectives At present, few data exist regarding the comparisons of perioperative outcomes and recurrence of spontaneous ventilation (SV) video-assisted thoracic surgery (VATS) bullectomy using total intravenous anaesthesia (TIVA) with local anaesthesia (LA) or thoracic epidural anaesthesia (TEA). We evaluated the feasibility and safety of TIVA with LA in the management of primary spontaneous pneumothorax (PSP). Methods We conducted a single-institution retrospective analysis of patients undergoing VATS bullectomy between July 2011 and May 2015; 240 patients were included for analysis. Preoperative, intraoperative and postoperative variables of patients undergoing VATS bullectomy using TIVA-TEA (n = 140) were compared with those using TIVA-LA (n = 100). Results Baseline demographics were similar between groups. No patients in either group required conversion to thoracotomy. Three patients (TIVA-TEA: 2; TIVA-LA: 1) required conversion to intubated general anaesthesia. Both groups had comparable surgical duration, estimated blood loss, peak EtCO2 and lowest intraoperative SpO2 level. Postoperatively, thoracic drainage volume, duration of chest tube drainage and hospitalization cost did not differ between groups. The incidence of postoperative complications between groups was not significant (2% for TIVA-TEA vs 2% for TIVA-LA, P = 1.00). Pneumothorax recurrence rate was 3% in TIVA-TEA cases (n = 4) and 2% in TIVA-LA cases (n = 2). Conclusions SV-VATS bullectomy using TIVA with LA or TEA is technically feasible and safe. Both groups have comparable short-term outcomes and recurrence rates; TIVA-LA seems a valid alternative to TIVA-TEA for the surgical management of PSP under SV.

Summary Background Fewer than half of the patients with completely resected non-small-cell lung cancer (NSCLC) are cured. Since the introduction of adjuvant chemotherapy in 2004, no substantial progress has been made in adjuvant treatment. We aimed to assess the efficacy of the MAGE-A3 cancer immunotherapeutic in surgically resected NSCLC. Methods In this randomised, double-blind, placebo-controlled trial, we recruited patients aged at least 18 years with completely resected stage IB, II, and IIIA MAGE-A3-positive NSCLC who did or did not receive adjuvant chemotherapy from 443 centres in 34 countries (Europe, the Americas, and Asia Pacific). Patients were randomly assigned (2:1) to receive 13 intramuscular injections of recMAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic) or placebo during 27 months. Randomisation and treatment allocation at the investigator site was done centrally via internet with stratification for chemotherapy versus no chemotherapy. Participants, investigators, and those assessing outcomes were masked to group assignment. A minimisation algorithm accounted for the number of chemotherapy cycles received, disease stage, lymph node sampling procedure, performance status score, and lifetime smoking status. The primary endpoint was broken up into three co-primary objectives: disease-free survival in the overall population, the no-chemotherapy population, and patients with a potentially predictive gene signature. The final analyses included the total treated population (all patients who had received at least one treatment dose). This trial is registered with ClinicalTrials.gov, number NCT00480025. Findings Between Oct 18, 2007, and July 17, 2012, we screened 13 849 patients for MAGE-A3 expression; 12 820 had a valid sample and of these, 4210 (33%) had a MAGE-A3-positive tumour. 2312 of these patients met all eligibility criteria and were randomly assigned to treatment: 1515 received MAGE-A3 and 757 received placebo and 40 were randomly assigned but never started treatment. 784 patients in the MAGE-A3 group also received chemotherapy, as did 392 in the placebo group. Median follow-up was 38·1 months (IQR 27·9–48·4) in the MAGE-A3 group and 39·5 months (27·9–50·4) in the placebo group. In the overall population, median disease-free survival was 60·5 months (95% CI 57·2–not reached) for the MAGE-A3 immunotherapeutic group and 57·9 months (55·7–not reached) for the placebo group (hazard ratio [HR] 1·02, 95% CI 0·89–1·18; p=0·74). Of the patients who did not receive chemotherapy, median disease-free survival was 58·0 months (95% CI 56·6–not reached) in those in the MAGE-A3 group and 56·9 months (44·4–not reached) in the placebo group (HR 0·97, 95% CI 0·80–1·18; p=0·76). Because of the absence of treatment effect, we could not identify a gene signature predictive of clinical benefit to MAGE-A3 immunotherapeutic. The frequency of grade 3 or worse adverse events was similar between treatment groups (246 [16%] of 1515 patients in the MAGE-A3 group and 122 [16%] of 757 in the placebo group). The most frequently reported grade 3 or higher adverse events were infections and infestations (37 [2%] in the MAGE-A3 group and 19 [3%] in the placebo group), vascular disorders (30 [2%] vs 17 [3%]), and neoplasm (benign, malignant, and unspecified (29 [2%] vs 16 [2%]). Interpretation Adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Based on our results, further development of the MAGE-A3 immunotherapeutic for use in NSCLC has been stopped. Funding GlaxoSmithKline Biologicals SA.

// Jun Huang 1, 3, * , Xing-Xing Fan 2, * , Jiaxi He 1, * , Hui Pan 1 , Run-Ze Li 2 , Liyan Huang 1 , Zebo Jiang 2 , Xiao-Jun Yao 2 , Liang Liu 2 , Elaine Lai-Han Leung 2 , Jian-Xing He 1,3 1 State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The 1st Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 2 State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau (SAR), China 3 Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Jian-Xing He, email: hejx@vip.163.com Elaine Lai-Han Leung, email: lhleung@must.edu.mo Keywords: lung adenocarcinoma, SCD1, EGFR, biomarker, lipid metabolism Received: November 12, 2015 Accepted: April 23, 2016 Published: May 19, 2016 ABSTRACT The discovery of Warburg effect opens a new era in anti-cancer therapy. Aerobic glycolysis is regarded as a hallmark of cancer cells and increasing literatures indicates that metabolic changes are critical for the maintenance and progression of cancer cells. Besides aerobic glycolysis, increased fatty acid synthesis is also required for the rapid growth of cancer cells, and is considered as one of the most typical metabolic symbols of cancer either. Thus, targeting fatty acid metabolism may provide a potential avenue for the diagnosis and therapeutic treatment of cancer. In this study, we have identified Sterol-CoA desaturase-1 (SCD1) which is the rate-limiting enzyme of unsaturated fatty acid synthesis, universally and highly expressed in lung adenocarcinoma and was required for the cell proliferation, migration and invasion. Both in vitro and in vivo studies demonstrated that high expression of SCD1 remarkably enhanced the ability of tumor formation and invasion, while knockdown of SCD1 significantly repressed tumorigenesis and induced cell apoptosis. Clinical association study suggested that high expression of SCD1 is more frequently observed in late stage patients and presents poor prognosis. Taken together, our results suggested that SCD1 is a potentially novel biomarker of lung adenocarcinoma, and targeting SCD1 may represent a new anti-cancer strategy.

OBJECTIVES Through a retrospective study, we assessed the feasibility and safety of simultaneous bilateral thoracoscopic wedge resection of blebs or bullae for the treatment of primary spontaneous pneumothorax (PSP) under thoracic epidural anaesthesia with spontaneous ventilation. METHODS This retrospective analysis involved a cohort of 37 consecutive patients undergoing simultaneous bilateral thoracoscopic bullectomy under spontaneous ventilation thoracic epidural anaesthesia (n = 15) or intubated general anaesthesia (n = 22) between July 2011 and September 2015. The perioperative data, short-term outcomes and recurrence rates of the two groups were compared. RESULTS The two groups had comparable preoperative demographic profiles. There were no conversions to thoracotomy or intubated single-lung ventilation. The peak end-tidal carbon dioxide in the non-intubated group was significantly higher than that in the intubated group (mean: 48 vs 34 mmHg, P < 0.001). Both groups had comparable surgical duration, blood loss and lowest intraoperative pulse oxygen saturation level. Postoperatively, the two groups had comparable chest tube duration, volume of fluid administration, length of hospital stay and complication rates. No mortality occurred. The total anaesthesia cost in non-intubated group was significantly lower (mean: CNY 4584 vs 5649, P = 0.016). The mean follow-up was 23.6 ± 12.9 months in the non-intubated group and 21.1 ± 13.4 months in the intubated group. Two recurrent pneumothoraxes in 2 patients were observed after surgical procedures for PSP. One recurrence developed in the non-intubated group (7%) and one in the intubated group (5%). CONCLUSIONS Simultaneous bilateral non-intubated thoracoscopic bullectomy is not only well tolerated and technically feasible but also a safe alternative for selected patients with simultaneous bilateral PSP or with high risk of contralateral recurrence.

Lung cancer is often diagnosed by molecular markers for prediction and treatment. To date, the golden standard for detection of anaplastic lymphoma kinase (ALK) rearrangements is fluorescence in situ hybridization (FISH). We performed a pooled-data analysis on the diagnostic operating characteristics of immunohistochemistry (IHC) assay on non-small cell lung cancer (NSCLC). We searched Embase, Pubmed, and Springer databases. The results of IHC were evaluated using a modified H-score. We used a 2-level bivariate meta-analysis following a random effect model to summarize sensitivity and specificity and fit hierarchical summary receiver-operating characteristic curves. We also performed sensitivity analysis using different antibodies to investigate potential heterogeneity. Twelve studies consisting of a total of 3754 NSCLC specimens were analyzed. When we defined 1+/2+/3+, 2+/3+, and 3+ as ALK positive, we found the sensitivities to be 99% (95% confidence interval [CI], 97%-100%), 86% (95% CI, 73%-93%), and 56% (95% CI, 36%-74%) and the specificities to be 98% (95% CI, 95%-99%), 99% (95% CI, 99%-100%), and 100% (95% CI, 100%-100%), respectively. We demonstrated that when defining 3+ as positive and 0 as negative the sensitivity was 99% and specificity was 100%. In our sensitivity analysis, we found the sensitivity of D5F3 and 5A4 antibodies to be much higher than that of ALK1. We concluded that IHC scores 0 and 3+ were nearly 100% concordant with FISH-negative and FISH-positive status, respectively. However, IHC scores 1+ and 2+ might require further confirmatory testing by FISH assay. IHC assay using D5F3 and 5A4 antibodies reliably detected NSCLC with ALK rearrangement and may be useful as a screening method to identify these tumors.

Background It is unclear whether three-dimensional (3D) video-assisted thoracic surgery (VATS) pulmonary resections are comparable to two-dimensional (2D) VATS pulmonary resections in patients with potentially operable benign pulmonary diseases. Methods We analyzed the clinical data of patients who underwent 2D and 3D VATS pulmonary resections for benign diseases in our hospital from November 2013 to August 2014. Perioperative factors (estimated blood loss and operative time) and postoperative factors (postoperative hospital length of stay, postoperative complications, and duration of chest tube drainage) were evaluated. Results VATS was performed in 278 patients during the 10-month study period. The 2D VATS system was used in 142 patients (51.08%), and the 3D VATS system was used in 136 (48.92%). Operative time was significantly different between the two groups ( p = 0.007). However, no significant differences were found in estimated blood loss ( p = 0.75), chest drainage tube placement time ( p = 0.852), rate of postoperative complications ( p = 0.566), or postoperative hospital length of stay ( p = 0.951). Conclusions The use of 3D VATS appears to facilitate precise execution of surgical techniques in specific operative tasks and, as a result, reduces lung resection performance time in patients with benign pulmonary diseases.

Although non-small cell lung cancer (NSCLC) with malignant pleural effusion (M1a) is generally contraindicated for surgery, several reports have demonstrated favorable prognosis. This study aimed to describe the results of surgical intervention in this disease. In this retrospective study, we evaluated NSCLC patients with ipsilateral malignant pleural effusion selected from Surveillance Epidemiology and End-Results database (SEER). Primary tumor resection was compared to no tumor resection in the overall survival (OS) and lung cancer-specific survival (LCSS). Multivariate analyses and propensity score matching were applied to compare the two groups. The study included 2,217 eligible patients. Primary tumor resection group was significantly associated with better OS and LCSS compared to no tumor resection group (the median survival time (MST), 20 vs 7 months; OS, p

Thoracoscopic bronchoplasty combined with pulmonary arterial angioplasty can be particularly challenging. In the past, it was often done by using a conventional incision or hybrid video-assisted small incision. In recent years, anecdotal articles have described the application of thoracoscopic bronchoplasty/pulmonary arterial angioplasty. This chapter will describe the details associated with thoracoscopic bronchoplasty/pulmonary arterial angioplasty.

Lung cancer invading pulmonary trunk is a locally advanced condition, which may indicate poor prognosis. Surgical resection of the lesion can significantly improve survival for some patients. Lobectomy/Pneumonectomy with pulmonary arterioplasty via thoracotomy were generally accepted and used in the past. As the rapid development of minimally invasive techniques and devices, pulmonary arterioplasty is feasible via video-assisted thoracic surgery (VATS). However, few studies have reported the VATS surgical techniques. In this study, we reported the techniques of pulmonary arterioplasty via VATS.

Lung cancer invading the superior vena cava (SVC) is a locally advanced condition, for which poor prognosis is expected with conservative treatment alone. Surgical resection of the lesion can rapidly relieve the symptoms and significantly improve survival for some patients. Replacement, repair and partial resection of SVC via thoracotomy were generally accepted and used in the past. As the rapid development of minimally invasive techniques and devices, partial resection and repair of SVC are feasible via video-assisted thoracic surgery (VATS). However, few studies have reported the VATS surgical techniques. In this study, we reported the crucial techniques of partial resection of SVC via VATS.

The aim of this study was to reveal the short-term outcomes of video-assisted thoracoscopic surgery (VATS) segmentectomy without tracheal intubation compared with intubated general anesthesia with one-lung ventilation (OLV).We performed a retrospective review of our institutional database of consecutive 140 patients undergoing VATS anatomical segmentectomy from July 2011 to June 2015. Among them, 48 patients were treated without tracheal intubation using a combination of thoracic epidural anesthesia (TEA), intrathoracic vagal blockade, and sedation (non-intubated group). The other 92 patients were treated with intubated general anesthesia (intubated group). Safety and feasibility was evaluated by comparing the perioperative profiles and short-term outcomes of these two groups.Two groups had comparable surgical durations, intraoperative blood loss, postoperative chest tube drainage volume, and numbers of dissected lymph nodes (P0.05). Patients who underwent non-intubated segmentectomy had higher peak end-tidal carbon dioxide (EtCO2) during operation (44.81 vs. 33.15 mmHg, P0.001), less white blood cell changes before and after surgery (△WBC) (6.08×10(9) vs. 7.75×10(9), P=0.004), earlier resumption of oral intake (6.76 vs. 17.58 hours, P0.001), shorter duration of postoperative chest tube drainage (2.25 vs. 3.16 days, P=0.047), less cost of anesthesia (¥5,757.19 vs. ¥7,401.85, P0.001), and a trend toward shorter postoperative hospital stay (6.04 vs. 7.83 days, P=0.057). One patient (2.1%) in the non-intubated group required conversion to intubated OLV since a significant mediastinal movement. In the intubated group, there was one patient (1.1%) required conversion to thoracotomy due to uncontrolled bleeding. The incidence difference of postoperative complications between groups was not significant (P=0.248). There was no in-hospital death in either group.Compared with intubated general anesthesia, non-intubated thoracoscopic segmentectomy is a safe, technically feasible and economical alternative with comparable short-term outcomes. Patients underwent non-intubated thoracoscopic segmentectomy could gain a prompt recovery.

Previous tracheal surgeries were performed under tracheal and cross-field intubation. However, the intubation would lead to bleeding if the tumors were large or hemorrhagic. Moreover, the tracheal intubation might interfere the surgical vision and anastomosis during the reconstruction process. Therefore, we performed a tracheal tumor resection and reconstruction via nonintubated spontaneous anesthesia. We describe the feasibility and safety of tracheal surgeries via such anesthesia.

We present an innovative method using uniportal video-assisted thoracoscopic surgery under spontaneous ventilation anaesthesia (SVA) to perform tracheal surgery in a 46-year-old man with distal tracheal squamous cell carcinoma. SVA offered better exposure of the surgical field and facilitated anastomosis following a single incision. Such simplification of the ventilation strategy and uniportal incision accelerated the postoperative recovery and reduced the side effects of conventional anaesthesia.

Background Population-based cohort studies have indicated that systemic sclerosis (SSc) may be associated with an increased risk of lung cancer. However, there are few studies that comprehensively investigate their correlation and the causal effect remains unknown. Methods A systematic search of PubMed, Web of Science, Cochrane Library and Embase from the inception dates to December 1, 2019 was carried out. Meta-analysis was performed to calculate odds ratio (OR) and corresponding 95% confidence interval (CI) using random-effects models. Subgroup analyses were performed regarding gender. Two-sample Mendelian randomization (MR) was carried out with summary data from published genome-wide association studies of SSc (Neale Lab, 3871 individuals; UK Biobank, 463,315 individuals) and lung cancer (International Lung Cancer Consortium, 27,209 individuals; UK Biobank, 508,977 individuals). Study-specific estimates were summarized using inverse variance-weighted, weighted median, and MR-Egger method. Results Through meta-analysis of 10 population-based cohort studies involving 12,218 patients, we observed a significantly increased risk of lung cancer among patients with SSc (OR 2.80, 95% CI 1.55–5.03). In accordance with subgroup analysis, male patients (OR 4.11, 95% CI 1.92–8.79) had a 1.5-fold higher lung cancer risk compared with female patients (OR 2.73, 95% CI 1.41–5.27). However, using a score of 11 SSc-related single nucleotide polymorphisms (p Conclusions This study indicated an increased risk of lung cancer among patients with SSc by meta-analysis, whereas the MR study did not support a causality between the two diseases. Further studies are warranted to investigate the factors underlying the attribution of SSc to lung cancer risk.

Background: Almonertinib (HS-10296) is an oral, potent, high selective third generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) for sensitizing mutations and EGFR T790M mutation. The preliminary clinical data of almonertinib reported in WCLC showed favorable efficacy and safety in target populations. Here, we presented the latest efficacy data, including the subgroup analysis of central nervous system (CNS) response. Methods: Patients aged at least 18 years with centrally confirmed EGFR T790M mutation, locally advanced or metastatic non-small cell lung cancer (NSCLC) progressing on prior EGFR-TKI treatment, received almonertinib 110 mg orally once daily until disease progression. Patients with asymptomatic, stable brain metastases not requiring steroids were enrolled. The primary endpoint was objective response rate (ORR) by independent central review (ICR) using RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), depth of response (DepOR), overall survival (OS) and safety. Response endpoints were assessed in full analysis set (NCT02981108). Results: From May 2018 to October 2018, 244 patients entered study in 36 sites in mainland China (189 patients) and Taiwan (55 patients). Of 88 patients with CNS metastases on baseline brain scans, 23 had at least one intracranial measurable target lesion. At cutoff date (Aug 1, 2019), the median duration of follow-up for progression-free survival was 11.8 months. 168 of 244 patients achieved confirmed partial responses. The ORR was 68.9% (95% CI: 62.6, 74.6). The DCR was 93.4% (95% CI: 89.6, 96.2). The mPFS (48.0% maturity) and mDOR were 12.3 (95% CI: 9.6, 13.8) and 12.4 (95% CI: 11.3, NA) months, respectively. The confirmed CNS ORR and DCR were 60.9% (95% CI: 38.5, 80.3) and 91.3% (95% CI: 72.0, 98.9), respectively. The CNS mPFS (47.8% maturity) was 10.8 (95% CI: 5.5, 12.6) months. The safety profile was consistent with the previous report. The most common grade 3 and 4 adverse reactions were increased blood creatine phosphokinase (17 [7.0%]) and pulmonary embolism (6 [2.5%]). There was no interstitial lung disease reported. Conclusions: Almonertinib demonstrated progression-free survival benefit in EGFR T790M positive NSCLC patients who had progressed after previous EGFR-TKI treatment, especially showed clinically meaningful efficacy against CNS metastases, and the safety profile was consistent with that reported previously. A randomized, controlled, double-blinded, phase III study is ongoing comparing almonertinib with gefinitib in first-line treatment of advanced NSCLC patients. Citation Format: Shun Lu, Qiming Wang, Guojun Zhang, Xiaorong Dong, Cheng-Ta Yang, Yong Song, Gee-Chen Chang, You Lu, Hongming Pan, Chao-Hua Chiu, Zhehai Wang, Jifeng Feng, Jianying Zhou, Xingxiang Xu, Renhua Guo, Jianhua Chen, Haihua Yang, Yuan Chen, Zhuang Yu, Her-Shyong Shiah, Chin-Chou Wang, Nong Yang, Jian Fang, Ping Wang, Kai Wang, Yanping Hu, Jianxing He, Ziping Wang, Jianhua Shi, Shaoshui Chen, Qiong Wu, Changan Sun, Chuan Li, Hongying Wei, Ying Cheng, Wu-Chou Su, Te-Chun Hsia, Jiuwei Cui, Yuping Sun, James Chih-Hsin Yang. A multicenter, open-label, single-arm, phase II study: The third generation EGFR tyrosine kinase inhibitor almonertinib for pretreated EGFR T790M-positive locally advanced or metastatic non-small cell lung cancer (APOLLO) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT190.

BACKGROUND: The generation of subclonal (low-frequency) mutations is driven by tumor mutations and the relationship between the heterogeneity of tumor mutation abundance and non-small cell lung cancer (NSCLC) remains unknown. We investigate the role of allele frequency heterogeneity (AFH) defined by circulating tumor DNA (ctDNA) profiling in predicting prognosis in advanced NSCLC patients. METHODS: Publicly available data set of POPLAR (N=211) and OAK (N=642) trials were used for analyzing. A low ratio of allele frequency (AF) of a mutation to the maximum-somatic-allele-frequency (MSAF) was used to define the presence of AFH. The prognostic value of AF/MSAF ratio that was below a defined cutoff point in overall survival (OS) was evaluated using Cox-proportional hazards regression; and the structural break point was determined by LOESS regression and Chow test. The derived AFH was also explored in an independent cohort (N=259) of advanced NSCLC receiving first-line EGFR-TKIs from the First Affiliated Hospital of Guangzhou Medical University. RESULTS: In the POPLAR and OAK cohort, low AF/MSAF ratio was found to be significantly associated with unfavorable OS in univariate and multivariate analysis. The structural break point analysis demonstrated that AF/MSAF

To develop multifunctional delivery systems of targeted properties for biomedical applications, hybrid fiber-nanoparticle matrices capable of controlled and monitored nanoparticles (NPs) delivery properties were prepared. Firstly, electropinning technique was applied to produce carbon nanotubes (CNTs) incorporated biodegradable poly(ϵ-caprolactone)/gelatin (PG) polymer fibers (PGC fibers). Subsequently, the photoluminescent mesoporous silica nanoparticles (PLMSNs) were electrostatically attached on the surface of PGC fibers to form a localized delivery platform. The PGC-PLMSNs fibers can emit red light under excitation at ~395 nm, 465 nm, and ~533 nm. Additionally, under NIR (808 nm) irradiation, PGC-PLMSNs fibers revealed good photothermal effect. PLMSNs loading efficiency onto the PGC fibers and PLMSNs release kinetics were assessed by TG method. More importantly, the 808 nm NIR irradiation enabled remarkably promoted PLMSNs release rate, validating the typical NIR-triggered release properties. Meanwhile, PLMSNs released from the composite fibers could be optically monitored by decrease in the intensity of red emission. These results suggest the possibility to develop the localized therapeutic device that may inspire other means of treatment method for cancer therapy.

Background Prolonged length of stay after surgery is considered to increase cost and hospital-acquired complications. Therefore, we aimed to identify the risk factors that were associated with an increased length of stay after mediastinal tumor resection in the setting of an enhanced recovery after surgery (ERAS)-TUBELESS protocol. Methods This prospective cohort study collected data on consecutive patients undergoing video-assisted thoracoscopic surgery (VATS) resection for mediastinal tumor between December 2015 and November 2018 at a single center in China. All patients followed the ERAS-TUBELESS protocol. A length of stay after VATS tumor resection (LOS) greater than 3 days was considered an increased LOS. Univariable and multivariable logistic regression models were used to identify potential factors associated with increased LOS. Factors were divided into patient-related risk factors and procedure-related risk factors. Results A total of 204 patients were included, of which 85 (41.67%) patients had a LOS of more than 3 days. The median LOS for the entire cohort was 3 days. All the patient-related risk factors had no significantly associated with a prolonged LOS. Procedure-related risk factors that were significantly associated with a prolonged LOS were surgeon, operation time, intraoperative blood loss, drainage tube, analgesic drugs, and complications. Anesthesia with spontaneous ventilation was correlated with early discharge (LOS ≤1 day). Conclusions In the setting of an ERAS-TUBELESS protocol, the main drivers of LOS were procedure-related factors. Anesthesia with spontaneous ventilation was associated with early discharge (LOS ≤1 day) and thus promoted thoracic day surgery.