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Purpose Heart-lung transplantation (HLTx) is a life-saving treatment option for patients with advanced cardiopulmonary failure. However, posterior mediastinal bleeding and phrenic nerve damage are still intraoperative challenges for the traditional surgical method. This study reports an innovative non-in situ HLTx performed in our center, preventing posterior mediastinal bleeding and phrenic nerve damage effectively. Description Between September 2015 and September 2020, 12 patients without previous heart surgery underwent a traditional HLTx and were deemed a control group, and 3 patients underwent an innovative non-in situ HLTx. The operative time, cold ischemic time, intraoperative bleeding, intraoperative transfusion, and the intensive care unit and hospital lengths of stay were assessed between traditional HLTx and non-in situ HLTx. Evaluation The innovative non-in situ HLTx was successfully performed in the 3 patients. We found that the intensive care unit and hospital lengths of stay, total surgical time, cold ischemic time, intraoperative bleeding, and intraoperative transfusion were decreased in the 3 patients compared with the traditional surgical method. Conclusion Non-in situ HLTx may decrease posterior mediastinal bleeding and phrenic nerve damage effectively.

BACKGROUND: Prior cancer history is a common exclusion in thymoma trials. However, whether prior cancer impacts the survival of thymoma patients and the outcomes of clinical trials remains uncertain. The aim of this study is to identify the impact of prior cancer on outcomes in thymoma. METHODS: Patients with thymoma diagnosed between 1975 to 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Age, histologic types, and thymoma size were stratified to analyze. Propensity score matching (PSM), Kaplan-Meier methods and Cox proportional hazard models were used to analyze the prognostic effect of prior cancer on overall survival (OS). RESULTS: A total of 3,827 thymoma patients were enrolled, of whom 13.22% had a prior cancer history. The Kaplan-Meier curves showed statistically significantly different survival before (P

We performed a meta‐analysis to determine cancer risks at multiple sites and their associations with tumor mutation burden (TMB), an index for immunogenicity, in heart or lung transplant recipients. A comprehensive search of PubMed, Web of Science, EMBASE, and Medline was conducted. Random effects models were used to calculate standardized incidence ratios (SIRs) versus the general population and to determine the risks of different cancers. Weighted linear regression (WLR) was used to analyze the associations between the SIRs and TMBs. (PROSPERO CRD42020159599). Data from 21 studies including 116,438 transplant recipients (51,173 heart transplant recipients and 65,265 lung transplant recipients) with a total follow‐up of 601,330.7 person‐years were analyzed. Compared with the general population, heart transplant recipients displayed a 3.13‐fold higher cancer risk [SIR: 3.13; 95% confidence interval (CI): 2.38–4.13; p, Our study demonstrated that both heart and lung transplant recipients displayed a higher risk of certain site‐specific cancers. These findings can provide individualized guidance for clinicians for detection of cancer among heart or lung transplantation recipients. In addition, we provided evidence that increased risks of post‐transplant cancers can be attributed to immunosuppression.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no effective medication. Andrographolide (Andro), extracted from Chinese herbal Andrographis paniculata, could attenuate bleomycin (BLM)-induced pulmonary fibrosis via inhibition of inflammation and oxidative stress, however, the anti-fibrotic mechanisms have not been clarified. Myofibroblasts are the primary cell types responsible for the accumulation of extracellular matrix (ECM) in fibrotic diseases, and targeting fibroblast proliferation and differentiation is an important therapeutic strategy for the treatment of IPF. Hence, this study aimed to investigate the effects of Andro on the fibroblast proliferation and differentiation in the in vivo and in vitro models. The results showed that Andro improved pulmonary function and inhibited BLM-induced fibroblast proliferation and differentiation and ECM deposition in the lungs. In vitro, Andro inhibited proliferation and induced apoptosis of TGF-β1-stimulated NIH 3T3 fibroblasts and primary lung fibroblasts (PLFs). Andro also inhibited TGF-β1-induced myofibroblast differentiation and ECM deposition in both cells. We also found that Andro suppressed TGF-β1-induced Smad2/3 and Erk1/2 activation, suggesting that Smad2/3 and Erk1/2 inactivation mediates Andro-induced effects on TGF-β1-induced fibroblast proliferation and differentiation. These results indicated that Andro has novel and potent anti-fibrotic effects in lung fibroblasts via inhibition of the proliferation and myofibroblast differentiation of fibroblasts and subsequent ECM deposition, which are modulated by TGF-β1-mediated Smad-dependent and -independent pathways.

Objective. Considering the demerits of a high-definition 2-dimensional (HD-2D) system, with its lack of stereopsis, and a conventional 3-dimensional (C-3D) system, which results in a dimmed image, we have recently developed a glasses-free 3-dimensional (GF-3D) display system for reconstruction surgeries such as video-assisted thoracic surgery (VATS) for tracheal reconstruction. Methods. Thoracic surgeons were invited to complete thoracoscopic continuous suture of a transected porcine trachea using the HD-2D, C-3D, and GF-3D systems on separate mornings in randomized order. The duration, numbers of stitches, and distance between every 2 stitches were recorded for every procedure. The surgeons’ spontaneous eye blink rate was recorded for 5 minutes before the procedure and the last 5 minutes of the procedure. Results. Fifteen volunteers successfully completed the tracheal reconstruction procedures in this study. Both C-3D (0.403 ± 0.064 stitch/min, P < .001) and GF-3D (0.427 ± 0.079 stitch/min, P < .001) showed significant advantages in speed compared with HD-2D (0.289 ± 0.065 stitch/min). Both C-3D (2.536 ± 2.223 mm, P < .001) and GF-3D (2.603 ± 2.159 mm, P < .001) showed significant advantages in accuracy compared with HD-2D (3.473 ± 3.403 mm). Both HD-2D (1.240 ± 0.642, P < .001) and GF-3D (1.307 ± 0.894, P < .001) showed significant advantages in eye fatigue compared with C-3D (3.333 ± 1.44). Conclusions. All 3 available display systems are efficient for complex VATS. With the help of stereopsis, surgeons can achieve faster operation using C-3D and GF-3D systems in a thoracoscopic simulated setting. GF-3D may be a more effective display system for VATS reconstruction in terms of speed, accuracy, and eye fatigue during operations.

The aerodynamic optimization method was presented to design a propeller airfoil for a stratosphere airship at low Reynolds numbers. The delta class and shape transformation were adopted to describe the airfoil geometry as the design variables. The flow field was calculated by an open-source code XFOIL to obtain the aerodynamic characteristics as the design targets. The separated particle swarm optimization was employed as the optimization algorithm. The optimization case started with a typical low Reynolds number airfoil E387 and obtained a thicker and more cambered airfoil using the proposed method. The flow fields of the optimized and initial airfoils were analysed by CFD. Results suggested that the lift-to-drag ratio of the optimized airfoil changed from 35.7 to 45.9 with an increasing rate by 28.5% at design cruise condition. The overall aerodynamic performance of the optimized airfoil has been significantly improved at both design and off-design conditions within a wide range of attack angle. The optimization platform presented here is an efficient and effective method for the low-Reynolds-number airfoil designs.

BACKGROUND: It has been reported that tubeless video-assisted thoracoscopic surgery (tubeless-VATS) is feasible and safe for thoracic diseases. Herein, we compared the early outcomes of mediastinal lesion resection between the tubeless and traditional VATS. METHODS: Clinical data of all patients who underwent thoracoscopic mediastinal tumor resection were retrospectively collected. The study involved two groups: tubeless and traditional VATS group. Propensity score matching (PSM) was applied to eliminate the population bias. Intraoperative and postoperative variables were compared among matched cohorts. RESULTS: In total, 43 patients in the tubeless group and 231 patients in the traditional VATS group were included. After 1:1 PSM, baseline characteristics were comparable. Anesthesia time (177.63 vs. 202.53 min; P=0.004) was shorter in tubeless group, while operation time (90.95 vs. 101.47 min; P=0.109) was similar. Overall, the total postoperative morbidity rate was similar in the two groups (15% vs. 12.5%; P=0.556). Specially, 4/43 patients in tubeless VATS group need to be re-put chest tubes postoperatively. A significant lower similar level of visual analogue scale score was observed in tubeless VATS group (1.73±0.48 vs. 3.41±0.87, P

Currently, lung transplantation is the standard of care for patients with end-stage lung disease, with interstitial lung disease (ILD) being the most common reason in the recent years In the other hand, in cases where stage II and III lung cancer have been identified following lung transplantation, long-term survival outcomes are poor when compared to lung cancer patients that have not received a lung transplant because the use of immunosuppressant and the problem of rejection and infection and the treatment of recurrence and so on. However, there is no statistical difference observed in stage I (pT1N0M0) patients. In this paper we report about a patient with ILD receiving left lung transplantation in the early time. A lesion of the right lung which was considered the normal ILD tissue and without enough attention. Post-transplant it showed progress and finally the whole right lung (native lung) was occupied by the tumor. Some ground glass changes could also be found in the transplanted lung several months later. A secondary lung transplant was performed for this patient, and there has been no postoperative recurrence thus far. For lung transplant patients with high-risk factors, effective surveillance methods are required for the early detection of lung cancer.

Background The purpose of this study was to uncover preoperative risk factors for extubation failure or re-intubation for patients undergoing lung transplant (LTx). Methods We performed a retrospective case-control study of LTx from our center between January 2017 and March 2019. Demographic and preoperative characteristics were collected for all included patients. Univariable analysis and multivariable logistic regression were used to analyze risk factors of postoperative unsuccessful extubation following LTx. Results Among 107 patients undergoing first LTx investigated, 74 (69.16%) patients who were successfully liberated from mechanical ventilation (MV), and 33 (30.84%) patients who were unsuccessful extubation, which 18 (16.82%) patients suffered from reintubation. associated preoperative factors for unsuccessful extubation following LTx included preoperative extracorporeal membrane oxygenation (ECMO) support [OR =4.631, 95% confidence interval (CI): 1.403-15.286, P=0.012], the preoperative ability of independent expectoration (OR =4.517, 95% CI: 1.498-13.625, P=0.007), the age older than 65-year-old (OR =4.039, 95% CI: 1.154-14.139, P=0.029), and receiving the double lung and heart-LTx (OR =3.390, 95% CI: 0.873-13.162, P=0.078; and OR =16.579, 95% CI: 2.586-106.287, P=0.012, respectively). Further, we investigated the preoperative predicted factors for reintubation. Only the preoperative ECMO remained a significant predictor of re-intubation (OR =4.69, 95% CI: 1.56-15.286, P=0.012). Conclusions Preoperative independent sputum clearance, preoperative ECMO, older than 65-year-old, and double lung or heart-LTx were four independent risk factors for unsuccessful extubation. Moreover, preoperative ECMO was the only independent risk factor for reintubation.

Background Andrographolide (Andro), a diterpenoid extracted from Andrographis paniculata, has been shown to attenuate pulmonary fibrosis in rodents; however, the potential mechanisms remain largely unclear. This study investigated whether and how Andro alleviates bleomycin (BLM)-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and epithelial-mesenchymal transition (EMT) in the lung epithelial cells. Methods The in vivo effects of Andro were evaluated in a rat model of BLM-induced pulmonary fibrosis. The roles of Andro in BLM-induced NLRP3 inflammasome activation, EMT and AKT/mTOR signaling were investigated using human alveolar epithelial A549 cells. Results We found that Andro significantly alleviated pulmonary edema and histopathological changes, decreased weight loss, and reduced collagen deposition. Andro downregulated the levels of NLRP3, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in the lungs of BLM-treated rats, suggesting the inhibitory effect of Andro on NLRP3 inflammasome activation in vivo. Additionally, the symptoms of BLM-mediated EMT phenotype in the lung were also attenuated after Andro administration. In vitro, Andro also markedly inhibited BLM-induced NLRP3 inflammasome activation and EMT in A549 cells. Moreover, Andro inhibited BLM-induced phosphorylation of AKT and mTOR in A549 cells, suggesting that AKT/mTOR inactivation mediates Andro-induced effects on BLM-induced NLRP3 inflammasome activation and EMT. Conclusions These data indicate that Andro can reduce BLM-induced pulmonary fibrosis through suppressing NLRP3 inflammasome activation and EMT in lung epithelial cells via AKT/mTOR signaling pathway.

Weizhe Huang,1 Xin Xu,2– 5 Mengyang Liu,2– 5 Weixue Cui,2– 5 Guilin Peng2– 5 1Department of Thoracic Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, Guangdong, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, Guangzhou 510120, Guangdong, People’s Republic of China; 4National Clinical Research Center for Respiratory Disease, Guangzhou 510120, Guangdong, People’s Republic of China; 5Guangzhou Institute of Respiratory Health, Guangzhou 510120, Guangdong, People’s Republic of ChinaCorrespondence: Guilin Peng Tel +86-20-83062114Email pvlpl4@163.comBackground: Lung cancer is the most commonly diagnosed cancer and the major cause of cancer-related deaths worldwide. The increasing studies have demonstrated that circular RNA (circRNA) was involved in the progression of various cancers, including non-small-cell lung cancer (NSCLC). This study was designed to assess the expression, roles and functional mechanisms of circ_0000735 in NSCLC.Materials and Methods: The expression levels of circ_0000735, miR-940 and bone morphogenetic protein binding endothelial cell precursor-derived regulator (BMPER) were estimated by the real-time quantitative polymerase chain reaction (RT-qPCR). The biological behaviors of NSCLC cells such as proliferation, migration and invasion were analyzed by cell counting kit-8 (CCK-8), colony-forming assays and transwell assay, respectively. Furthermore, extracellular acid ratio and lactate production were tested to assess glycolysis levels of NSCLC cells. The interaction relationship among circ_0000735, BMPER and miR-940 was analyzed by bioinformatics database and dual-luciferase reporter assay. The protein expression level of BMPER was assessed by Western blot assay. Tumorigenesis assay was established to clarify the functional roles of circ_0000735 in vivo.Results: Circ_0000735 was upregulated and significantly correlated with overall survival in patients with NSCLC. In addition, the loss-of-functional experiments revealed that knockdown of circ_0000735 repressed proliferation, migration, invasion and glycolysis of NSCLC cells and tumor growth in vivo, which was overturned by overexpression of BMPER. Similarly, overexpression of circ_0000735 enhanced proliferation, migration, invasion, and glycolysis of NSCLC cells. In addition, we also confirmed that overexpression of miR-940 impeded proliferation, migration, invasion, and glycolysis of NSCLC cells. Furthermore, overexpression of BMPER abolished si-circ_0000735 induced effects on NSCLC cells.Conclusion: Circ_0000735 regulated proliferation, migration, invasion, and glycolysis in NSCLC cells by targeting miR-940/BMPER axis.Keywords: circRNA, circ_0000735, miR-940, BMPER, NSCLC

BACKGROUND Early endotracheal extubation in operating room (E-OR) after lung transplantation is rarely reported worldwide. Herein, we aim to explore the feasibility and safety of E-OR after lung transplantation and demonstrate its potential benefits. METHODS This study is a single-center retrospective database analysis of 18 patients. All lung transplantation patients with E-OR attempted between June 2018 and September 2019 were included retrospectively. Perioperative variables, including ischemia time, total blood loss, blood lactic acid, the partial pressure of oxygen, partial pressure of oxygen/fraction of inspiration oxygen ratio, time of semi-open pulmonary artery occlusion clamp, extubation rate, and complications after E-OR, were analyzed. Data were compared using non-parametric tests and expressed as the median or number (percentage). RESULTS Clinical data of 18 patients with E-OR attempted were collected. Overall, 15/18 (83.33%) patients successfully underwent E-OR without reintubation. Reintubation occurred in 3/18 (16.67%) patients; one patient presented with decreased blood oxygen saturation and unconsciousness, while two patients developed hypoxemia and respiratory failure after E-OR. Extracorporeal membrane oxygenation (ECMO) was not used postoperatively. No grade 3 primary graft dysfunction was observed and all eighteen patients were alive 1 year after the transplant. No postoperative hemodialysis and tracheotomy occurred. The median length of stay in the intensive care unit (ICU) for E-OR patients was 120 hours, the median length of postoperative hospital stay was 19 days, and the median hospitalization cost was 35,577 USD. CONCLUSIONS Early endotracheal extubation in operating room was feasible and did not delay postoperative recovery in these 18 lung transplantation recipients.

Background: Thymoma is an uncommon intrathoracic malignant tumor and has a long natural history. It is uncertain whether the survival of thymoma patient is affected by prior cancer history. Finding out the impact of a prior cancer history on thymoma survival has important implications for both decision making and research.Method: The Surveillance, Epidemiology, and End Results (SEER) database was queried for thymoma patients diagnosed between 1975 and 2015. Kaplan-Meier methods and Cox proportional hazards model were used to analyze overall survival across a variety of stages, age, and treatment methods with a prior cancer history or not.Results: A total of 3604 patients with thymoma were identified including 507 (14.1%) with a prior cancer history. The 10-year survival rate of patients with a prior cancer history (53.8%) was worse than those without a prior cancer history (40.32%, 95%CI 35.24-45.33, P < 0.0001). However,adjusted analyses showed that the impact of a prior cancer history was heterogenous across age and treatment methods. In subset analyses, prior cancer history was associated with worse survival among patients who were treated with chemoradiotherapy (HR: 2.80, 95% CI: 1.51-5.20, P = 0.001) and age ≤ 65 years (HR: 1.33, 95%CI: 1.02-1.73, P = 0.036).Conclusions: Prior cancer history provides an inferior overall survival for patients with thymoma. But it does not worsen the survival in some subgroups and these thymoma patients should not be excluded from clinical trials.

Background The correlation between the number of examined lymph nodes (ELNs) and lung cancer-specific survival (LCSS) of stage IA non-small cell lung cancer (NSCLC) patients, who underwent sublobar resection in which lymph node (LN) sampling was relatively restricted as compared with standard lobectomy remains unclear. Methods Patients from the Surveillance, Epidemiology, and End Results database with stage IA NSCLC who underwent sublobar resection were categorized based on ELN count (1-6 vs. ≥7; the cut point 7 was identified by Cox model). Results Collectively, 3,219 patients with a median follow-up time of 37 months were included in this study (G1: 1-6 ELN, n=2,410; G2: ≥7 ELN, n=809). The 5-year LCSS rate of the G1 and G2 cohorts were 75% and 83%, respectively. Cox analysis suggested that the LCSS of G1 cohort patients was lower as compared with the G2 cohort [hazard ratio (HR) =1.530; 95% confidence interval (CI): 1.240-1.988, P

Background: Reduction of solid organ transplant (SOT) became notable while limited data are available regarding its resumption during the novel coronavirus disease 2019 (COVID-19) pandemic. Methods: Based on the SOT and COVID-19 diagnosis data collected from open-access official organizations, we studied the trend changes of SOT in the U.S.A. since the COVID-19 outbreak, and made the validation using the U.K. dataset. Trend curves were divided into virus-free, restrictive, and/or recovery phases. Kruskal-Wallis H test was performed to assess the differences among those phases with significance set at adjusted P < 0.05 (two-sided). Findings: In a 30-week (January 5 to August 1, 2020) observing period for the U.S.A. dataset, there was an obvious association between the trends of SOT and COVID-19 diagnosis (both overall and death cases) in the 10-week restrictive phase; significant reduction of overall SOTs per day were found in the restrictive phase (median 78.0, IQR 64.6-91.4) compared with the virus-free phase (median 115.0, IQR 97.5-132.5; P < 0.001); The most affected organ transplants were kidney (35.5% reduction) and lung (35.4% reduction), and the most affected U.S. region was Northeast (62.2% reduction). Resumption occurred with no significant difference found between the comparison of recovery (median 118.5, IQR 99.3-137.8) versus virus-free phases (P = 1.000) in overall SOTs per day, as well as those stratified by donor type (deceased and living), organ, and region. The SOT reduction and resumption were validated by the U.K. dataset. Interpretation: Using the U.S.A. and U.K. datasets, our study thoroughly presented the reduction and resumption patterns of SOT during the COVID-19 pandemic. It is essential that transplant units, based on the gained experience, make adequate preparations for any further possible COVID-19 attack. Funding Statement: This study received no external funding. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Exemptions of ethics approval, institutional review board, and informed consent were granted as data used in this study were publicly available.

Understanding the cancer risks in different transplant recipients helps early detection, evaluation, and treatment of post-transplant malignancies. Therefore, we performed a meta-analysis to determine the cancer risks at multiple sites for solid organ transplant recipients and their associations with tumor mutation burden (TMB), which reflects the immunogenicity. A comprehensive search of PubMed, Web of Science, EMBASE, Medline, and Cochrane Library was conducted. Random effects models were used to calculate the standardized incidence ratios (SIRs) versus the general population and determine the risks of different cancers. Linear regression (LR) was used to analyze the association between the SIRs and TMBs. Finally, seventy-two articles met our criteria, involving 2,105,122 solid organ transplant recipients. Compared with the general population, solid organ transplant recipients displayed a 2.68-fold cancer risk (SIR 2.68; 2.48–2.89; P

Background: To show our experiences of using the axillary artery with a side graft as a cannulation technique for the inflow of veno-arterial extracorporeal membrane oxygenation (ECMO) in lung transplantation (LTx). This method can avoid complications associated with central and femoral vessel cannulation techniques, and be convenient for the use of intraoperative ECMO into the early postoperative period. Methods: Between November 2016 and July 2017, we established intraoperative V/A-ECMO in 32 patients. Among these patients, 5 patients were performed on via axillary artery-percutaneous femoral vein cannulation (15.6%), 2 patients were performed on with veno-venous ECMO (V/V-ECMO) as a bridge to transplantation with hemodynamic instability during transplantation, and additional axillary artery cannulations were performed to establish veno-veno-arterial (V/V/A) ECMO. Mean age was 45.2±10.1 years (range, 26–71 y). Results: In 7 patients undergoing ECMO support during operation, the ECMO was removed in 4 patients immediately after the procedure, 3 patients with “prolonged ECMO” were transferred to the ICU. There were no ECMO-related complications and no patients died. Conclusions: Our protocol for V/A-ECMO cannulation that uses the axillary artery for arterial cannulation provides a safe and improved means for delivering V/A-ECMO support during LTx. Also, it is helpful for prolonging the intraoperative ECMO in the early postoperative period.

Purpose The 2015 European Society of Cardiology/European Respiratory Society Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension state that lung biopsy is still the gold standard for confirming pulmonary capillary hemangiomatosis; however, the surgical lung biopsy is no longer recommended in most cases for its inherent risks. Nonintubated and uniportal video-assisted thoracoscopic surgery are the new developments in video-assisted thoracoscopic surgery technology. We combined these 2 technologies to create a novel approach for pulmonary capillary hemangiomatosis lung biopsy. Description A incision is made in chest wall. Sponge forceps are used to pull the lung out of the pleural space, and to resect target lung tissue. The incised margin is sutured with 3-0 Prolene (Ethicon, Somerville, NJ), and a negative pressure suction tube is used to fully expand the lung. Evaluation Three patients were definitively diagnosed with pulmonary capillary hemangiomatosis by this technology. One patient developed a postoperative fever, with no other complications. Conclusions The tubeless and uniportal video-assisted thoracoscopic surgery lung biopsy is a safe, effective, and feasible technology for definitively diagnosing patients with pulmonary capillary hemangiomatosis.

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.

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.

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.

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.

To minimize surgical invasion and morbidity, video-assisted thoracic surgery (VATS) techniques, were developed and proven feasible and safe. Furthermore, long-term results proved comparable to thoracotomy, for resection of lung cancer [1], esophageal cancer [2], and thymic tumors [3], but with less morbidity. However, compared with thoracotomy, there is a steep learning curve with VATS because of poorer optics of the hilar structures and dissection planes that result from the two dimensional (2D) view.

Trachea and carina resection and reconstruction is a difficult surgical technique. In the past, such procedures were completed via large incisions (Pearson FG, Thompson DW, Weissberg D, Simpson WJ, Kergin FG, Ann Thorac Surg 18:16–29, 1974) and, consequently, patients’ time to make a full recovery was much longer. In addition, the high potential for postoperative complications have led to many thoracic surgeons avoiding performing these procedures. With the advances of surgical techniques and equipment (Jiao W, Zhu D, Cheng Z, Zhao Y, Ann Thorac Surg 99:e15–7, 2015), including advances in the management of anesthesia, the implementation of tracheal and carina resection/reconstruction is now feasible under complete video-assisted thoracoscopic surgery (c-VATS). For surgeons with extensive VATS experience, the uniportal technique is also a feasible and safe choice that further reduces surgical injury and may accelerate postoperative recovery. Here we introduce two cases: one tracheal and one carinal resection/reconstruction performed under the uniportal VATS technique.

Macrophages have been suggested to contribute to constructing a cancer stem cell (CSC) niche. However, whether and how macrophages regulate the activity of CSCs through juxtacrine signaling are poorly understood. Here we report LSECtin, a transmembrane protein highly expressed on tumor-associated macrophages (TAMs), enhances stemness of breast cancer cells (BCCs). We identified BTN3A3, a B7 family member with previously unknown functions as the receptor for LSECtin on BCCs responsible for stemness-promoting effect of LSECtin. In mice bearing human tumor xenografts, either macrophage-specific ablation of LSECtin or silencing of BTN3A3 in BCCs decreased CSC frequency and tumor growth. Admixture of LSECtin-positive macrophages increased the tumorigenic activity of BCCs dependent on BTN3A3. Disruption of the LSECtin-BTN3A3 axis with BTN3A3-Fc or anti-BTN3A3 mAb has a therapeutic effect on breast cancer. These findings define a juxtacrine signaling mechanism by which TAMs promote cancer stemness. Targeting this axis in the CSC niche may provide potential therapies to breast cancer.

Background To date, few studies have evaluated the impact of lobectomy versus sublobar resection for early small cell lung cancer (SCLC). We investigated the survival rates of patients with pathological stage T1‐2N0M0 SCLC who underwent lobectomy or sublobar resection. Methods We identified 548 SCLC patients in the Surveillance, Epidemiology, and End Results database who underwent lobectomy or sublobar resection. Propensity score matching (PSM) and Cox regression analysis were used to adjust for baseline characteristics. Results The three‐year overall survival (OS) of patients treated with lobectomy (n = 376, 60%) was significantly higher than those treated with sublobar resection (n = 172, 38%). PSM and Cox multivariable analysis further confirmed this result (hazard ratio [HR] 0.543, 95% confidence interval [CI] 0.421–0.680; P

Background: The current guidelines emphasize the significant role of video-assisted thoracic surgical lung biopsy (VATS-LB) for a definite diagnosis of interstitial lung diseases (ILD), but they also encourage physicians to maintain the balance between the surgical benefits as well as risks. Both spontaneous ventilation video-assisted thoracic surgery (VATS) and uniportal VATS have emerged as remarkable progresses in VATS. We combined these two types of VATS and refined them to uniportal spontaneous ventilation VATS without urinary catheterization and chest tube drainage [uniportal and tubeless VATS (UT-VATS)] to perform LB in selected patients with ILD. Methods: From January 2014 to May 2015, 43 patients were included in the study. The surgical data was retrospectively analyzed. Results: The mean diffusion capacity for carbon monoxide (DLCO) of patients was 57.6%±13.0%, forced vital capacity (FVC) was 73.1%±17.0%. There was no 30-day mortality. No patient required a switch to intubated anesthesia. The mean age was 49.6±10.7 years. The general median operative duration was 22±5 minutes, with 25±3 minutes for multiple specimens and 15±2 minutes for single specimen, respectively. Intra-operative conversion to 2-portal VATS followed by chest tube drainage and urinary catheterization occurred in 3 (7.0%) patients due to extensive pleural adhesion, and postoperative chest tube insertion was documented in 1 (2.3%) patient due to subcutaneous emphysema. No postoperative mechanical ventilation was noted. Precise histopathological diagnosis was achieved in 38 (88.4%) patients. Conclusions: Uniportal and tubeless thoracoscopic LB using spontaneous ventilation anesthesia can be considered a feasible and safe operation method for selected patients with ILD.

We hypothesized that MAP kinase-interacting serine/threonine kinase 2 (MNK2) may contribute to non-small cell lung cancer (NSCLC) development, and serve as a new therapeutic target. Immunohistochemical staining evaluated the correlation between MNK2 expression and clinicopathological features in 367 NSCLC cancer tissues. We determined the effects of MNK2 silencing in NSCLC cell lines in vitro and in vivo. RT-PCR and western blotting was used to examine the impact of MNK2 on ERK and AKT pathways. MNK2 was overexpressed in NSCLC cell lines and tumor tissues. Patients with MNK2 overexpression had lower OS rates (P P = 0.008). MNK2 functioned as an independent prognostic factor for poor survival in patients with NSCLC (P = 0.003). MNK2 down-regulation inhibited proliferation, migration and invasion in vitro (P P

OBJECTIVES: The objectives of this study were to report the surgical techniques and clinical outcome of thoracoscopic lobectomy with partial removal of the superior vena cava for lung carcinomas. METHODS: Between January 2010 and November 2013, 1132 patients with lung cancer underwent radical surgery by thoracoscopy; 5 (0.4%) underwent thoracoscopic lobectomy with partial removal of the superior vena cava. Perioperative variables and postoperative outcomes of these cases were analysed to evaluate the technical feasibility and safety of this operation. RESULTS: For all cases, a right upper lobectomy was performed. The average time of surgery was 260 min (range, 170–380, 260 ± 90 min). The intraoperative blood loss averaged 160 ml (range, 50–300, 160 ± 90 ml). The median postoperative hospital stay was 11 days (interquartile range, 7–15 days). Postoperatively, tracheal extubation was achieved in the recovery room without further need for mechanical ventilation. In 1 case, the patient experienced postoperative superior vena cava thrombosis; he recovered after administration of anticoagulation drugs. None of the patients developed active blood leakage postoperatively. Perioperative mortality was not observed. CONCLUSION: Thoracoscopic lobectomy with partial removal of the superior vena cava can be considered a feasible and safe operation for selected patients with lung cancer.

Background: One of the largest challenges in endoscopic surgical training is adapting to a two-dimensional (2D) view. The glasses-free three-dimensional (GF-3D) display system was designed to integrate the merits of both 2D and conventional 3D (C-3D) displays, allowing surgeons to perform video-assisted endoscopic surgery under a stereoscopic view without heavy and cumbersome 3D glasses. Methods: In this study, 15 junior thoracic surgeons were divided to test one routine and one complex task three times each via traditional high-definition 2D (HD-2D) and GF-3D to determine whether there was any advantage when using the GF-3D system to acquire endoscopic skills. The duration, numbers of stitches, and distance between every two stitches were recorded for every procedure. Results: Seven participants were enrolled in the HD-2D group and eight participants were enrolled in the GF-3D group. All 15 participants successfully completed porcine skin continuous suture and tracheal continuous anastomosis procedures three times each. For skin continuous suture, there was no significant difference between the two groups in terms of the learning curve for speed (P=0.683) and accuracy (P=0.556). For tracheal continuous anastomosis, there was a significant difference between the two groups in terms of the learning curve for speed (P=0.001), but no significant difference was observed between the two groups in terms of the learning curve for accuracy (P=0.211). Conclusions: In summary, both HD-2D and GF-3D display systems are efficient for routine and complex endoscopic surgery. With the help of GF-3D, surgeons can acquire new complex endoscopic skills faster than HD-2D and be free from burdensome polarized glasses. More comparative studies in a clinical setting are needed to further explore the feasibility, necessity, and economic aspects of the GF-3D display system.

Chloride intracellular channel 1 (CLIC1) is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM) database using structure-based virtual screening and molecular dynamics (MD) simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for CLIC1 inhibition.

BACKGROUND Chromosome 9 open reading frame 86 (C9orf86) is a novel subfamily of GTPases. Previous studies have implicated C9orf86 as a potential oncogene. METHODS C9orf86 expression was detected in non-small cell lung cancer (NSCLC) cell lines and human bronchial epithelial (16HBE) cell lines by RT-PCR and western blotting. Immunohistochemistry (IHC) was used to detect 180 consecutive NSCLC specimens and 16 normal lung tissues. The correlation between C9orf86 expression and clinicopathological parameters was evaluated. Kaplan-Meier survival analysis and Cox hazards ratio models were used to estimate the effect of C9orf86 expression on survival. RESULTS C9orf86 was expressed in the cytoplasm in 74 of 180 (41.11%) NSCLC specimens. In clinical pathology analysis, C9orf86 expression significantly correlated with lymph node metastasis and clinical stage significantly (P

Carinal reconstruction is a difficult technique combined with video-assisted thoracoscopic surgery (VATS). It has a high requirement on the operator's skills in operating thoracoscope and meanwhile requires the close cooperation from anesthesiologists. Tracheal intubation and ventilator-assisted ventilation are key steps to ensure the success of surgery. However, tracheal intubation itself may influence the exposure of surgical field and increase the difficulty of anastomosis. In close cooperation of anesthesiologists, we did not perform tracheal intubation; rather, we carried out non-intubated complete VATS carinal reconstruction in a patient with adenoid cystic carcinoma (ACC) of the lower trachea. The awake complete VATS carinal reconstruction was successfully performed. The anastomosis lasted about 36 hours, and the whole surgical procedure lasted 230 min. The intraoperative blood loss was about 80 mL. The patient recovered well 100 min after surgery. A semi-solid diet began 6 hours following the surgery. This non-intubated anesthesia method makes the surgery easier, especially during the anastomosis of stumps. It is feasible and safe to apply this anesthesia technique in carinal reconstruction.

The role of video-assisted thoracoscopic surgery (VATS) radical resection in the treatment of lung cancer has widely recognized. Studies have demonstrated that the thoracoscopic radical treatment of lung cancer can achieve similar long-term survival as that of conventional open surgeries; meanwhile, it can be applied for bronchial sleeve resection that is more challenging for most thoracic surgeons. Bronchial sleeve pneumonectomy can avoid total pneumonectomy when removing tumors, and therefore it can lower the surgery-associated mortality and improve the long-term survival by maximizing the preservation of lung function. Thus, it has become a standard procedure for central-type lung cancer. We have completed a glasses-free three-dimensional (3D) complete thoracoscopic surgery in a patient with central-type lung cancer in his right lung. During the surgery, we found the tumor had invaded the right pulmonary trunk, right main bronchus, and lateral wall of superior vena cava.

The application of gene therapy in cancer treatment is limited by non-specific targeting. In the present study, we constructed a recombinant plasmid, containing a carcinoembryonic antigen (CEA) promoter and double suicide genes thymidine kinase (TK) and cytosine deaminase (CD), henceforth referred to as pCEA-TK/CD. Our results showed that the CEA promoter can specifically drive target gene expression in CEA-positive lung cancer cells. In the presence of prodrugs 5-flucytosine and ganciclovir, pCEA-TK/CD transfection decreased inhibitory concentration 50 and increased apoptosis and cyclomorphosis. Our result suggests that gene therapy using pCEA-TK/CD may be a promising new approach for treating lung cancer.

Presently, the clinical effect of radical video-assisted thoracic surgery (VATS) is equal to that of traditional open chest surgery and has received worldwide recognition of its advantages: less trauma and faster recovery. In the attempt to further the advancement of minimally invasive surgery the operative techniques of uniportal VATS and non-intubated anesthesia have been developed. These techniques have been widely applied in hospitals around the world, however there are few reports on the combined use of these techniques: non-intubated uniportal VATS.We report a case of peripheral lung cancer in the right-upper-lobe for which a non-intubated uniportal VATS resection was performed. This method was chosen as a result of the small size of the lesion and the placement in the right upper lobe.The postoperative course of this patient was good. Pathological results indicated infiltrating adenocarcinoma of the right upper lobe; there was no metastasis in hilar or mediastinal lymph nodes. Pathology results of the stump of the bronchus and vessels were also negative.Uniportal VATS with non-intubated anesthesia was a feasible and safe option for this patient, and may be an alternative minimally invasive option for patients with peripheral lung cancer.

Platform and Gene-list for the Multiplex Genotyping of Circulating Tumor DNA. (DOC 45 kb)

We report a case of video-assisted thoracoscopic surgery (VATS) tracheal resection and carinal reconstruction in a patient with tracheal tumor. The patient presented with adenoid cystic carcinoma (ACC) of the distal trachea, extending along the right main bronchus with carinal invasion. The reconstruction procedure was assisted with cross-field ventilation. Postoperative clinical course of this case was good. The forced expiratory volume in the first second (FEV1) improved from 0.461 L (17% pred.) to 2.31 L (87% pred.) 1 month after the operation. VATS tracheal resection and carinal reconstruction is a feasible option for patients with tracheal tumor with carina involvement.

Supplemental Digital Content is available in the text, The expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) has been observed in various epithelial-originated malignancies. However, whether the expression of PD-L1 on tumor cells or the expression of PD-1 on tumor-infiltrating lymphocytes (TILs) is associated with patients’ survival remains controversial. Electronic databases were searched for eligible literatures. Data of hazard ratio (HR) for overall survival (OS) with 95% confidence interval (CI) according to the expression status of PD-L1 or PD-1 evaluated by immunohistochemistry were extracted. The outcomes were synthesized based on random-effects model. Subgroup analyses were proposed. Twenty-nine studies covering 12 types of epithelial-originated malignancies involving 7319 patients (2030/3641 cases for PD-L1 positive/negative, 505/1143 cases for PD-1 positive/negative) with available data of the outcome stratified by PD-L1/PD-1 status were enrolled. Epithelial-originated cancer patients with positive expression of PD-L1 on tumor tissues were associated with significantly poorer OS when compared to those with negative expression of PD-L1 (HR 1.81, 95% CI 1.33–2.46, P

Currently, blockade of the programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling pathway has been proved one of the most promising immunotherapeutic strategies against cancer. Several antibodies have been developed to either block the PD-1 or its ligand PD-L1 are under development. So far, a series of phase I trials on PD-1/PD-L1 antibodies for non-small cell lung cancer (NSCLC) have been completed, without reports of results from phase II studies. Thus, we sought to perform a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of PD-1 or PD-L1 inhibition therapy.Electronic databases were searched for eligible literatures. Data of objective respond rate (ORR) and rate of adverse effects (AEs) with 95% confidence interval (CI) evaluated by immunohistochemistry (IHC) was extracted. The outcomes were synthesized based on random-effect model. Subgroup analyses were proposed.In overall, ORR in the whole population with PD-1 blockage treatment is 22.5% (95% CI: 17.6% to 28.2%). Additionally, the rate of Grade 3-4 AEs is 16.7% (95% CI: 6.5% to 36.8%) and drug-related death rate is 2.5% (95% CI: 1.3% to 4.6%). As for patients with PD-L1 inhibition therapy, an overall ORR is 19.5% (95% CI: 13.2% to 27.7%). A higher rate of Grade 3-4 AEs (31.7%, 95% CI: 14.2% to 56.5%) is observed with a lower drug-related death rate (1.8%, 95% CI: 0.4% to 8.3%). In exploratory analyses of anti-PD-1 agents, we observed that greater ORR was presented in the median-dose cohort (3 mg/kg) than that of both low-dose (1 mg/kg) and high-dose (10 mg/kg) cohort (low-dose vs. median-dose: OR =0.12, P=0.0002; median-dose vs. high-dose: OR =1.47, P=0.18).Anti-PD-1 and anti PD-L1 antibodies showed objective responses in approximately one fourth NSCLC patients with a tolerable adverse-effect profile. In addition, median-dose (3 mg/kg) might be a preferential dosage of anti-PD-1 agents.

The push for minimally invasive techniques had led to the development of many surgical tools and the innovation and completion of ever more complex operations. To achieve faster postoperative recovery of patients, we have been dedicated to the development of surgical skills that have allowed us to successfully complete many procedures under video-assisted thoracoscopic surgery (VATS) that are complex even with open approach. Specifically, sleeve, trachea, and carina resections and reconstructions using either general or spontaneous respiration anesthesia (SRA) techniques. Our long term high volume thoracic experience has equipped us with a talented multidisciplinary team with the ability to confidently and safely perform many types of complicated VATS procedures.