The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions: insights from a single-arm, phase II trial.

Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) protein significantly improve survival in patients with advanced non-small-cell lung cancer (NSCLC), but its impact on early-stage ground-glass opacity (GGO) lesions remains unclear. This is a single-arm, phase II trial (NCT04026841) using Simon's optimal two-stage design, of which 4 doses of sintilimab (200 mg per 3 weeks) were administrated in 36 enrolled multiple primary lung cancer (MPLC) patients with persistent high-risk (Lung-RADS category 4 or had progressed within 6 months) GGOs. The primary endpoint was objective response rate (ORR). T/B/NK-cell subpopulations, TCR-seq, cytokines, exosomal RNA, and multiplexed immunohistochemistry (mIHC) were monitored and compared between responders and non-responders. Finally, two intent-to-treat (ITT) lesions (pure-GGO or GGO-predominant) showed responses (ORR: 5.6%, 2/36), and no patients had progressive disease (PD). No grade 3-5 TRAEs occurred. The total response rate considering two ITT lesions and three non-intent-to-treat (NITT) lesions (pure-solid or solid-predominant) was 13.9% (5/36). The proportion of CD8+ T cells, the ratio of CD8+/CD4+, and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time. Correspondingly, the mIHC analysis showed more CD8+ T cells infiltrated in responders. Besides, responders' cytokine concentrations of EGF and CTLA-4 increased during treatment. The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders. Collectively, PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns. Such effects were associated with specific T-cell re-distribution, EGF/CTLA-4 cytokine compensation, and regulation of metabolism pathways.

Sublobar resection reduces the risk of postoperative cognitive dysfunction compared with lobectomy.

OBJECTIVES: Sublobar resection, including wedge resection and segmentectomy, is non-inferior to lobectomy in early-stage non-small cell lung cancer treatment. We aimed to compare the risk of postoperative cognitive dysfunction (POCD) between sublobar resection and lobectomy. METHODS: We conducted a prospective cohort study. Patients with sublobar resection or lobectomy were divided into the sublobar group or the lobar group, respectively. Cognition was assessed before and after surgery with Montreal Cognitive Assessment and Minimum Mental State Examination tests. POCD is defined as Z score of Montreal Cognitive Assessment change ≤-1.96. Propensity score matching (PSM) was performed to make demographics well-balanced between the 2 groups. RESULTS: A total of 335 patients were enrolled. Both the postoperative 1-day POCD rate (sublobar 5.5% vs lobar 18.2%, P < 0.001) and the postoperative 1-month POCD rate (sublobar 7.9% vs lobar 21.8%, P < 0.001) were significantly lower in the sublobar group compared with lobar group, with demographics unbalanced between the 2 groups. In the 133 demographics-matched pairs obtained by PSM, both the postoperative 1-day POCD rate (sublobar 5.3% vs lobar 17.3%, P = 0.005) and the postoperative 1-month POCD rate (sublobar 8.3% vs lobar 18.8%, P = 0.018) remained significantly lower in the sublobar group than in the lobar group. The incidences of postoperative 1-day (P = 0.109) and postoperative 1-month (P = 0.026) Minimum Mental State Examination abnormity were also lower in the sublobar group than in the lobar group but only the latter was with statistical significance after PSM. CONCLUSIONS: Sublobar resection has an advantage over lobectomy in preventing POCD. Our findings might be a reference for selecting the most suitable type of resection for non-small-cell lung cancer patients.

Pan-mediastinal neoplasm diagnosis via nationwide federated learning: a multicentre cohort study.

BACKGROUND: Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system. METHODS: In this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human-AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance. FINDINGS: In the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969-0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738-0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497-0·554) and 0·799 (0·778-0·822), respectively. In the human-AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383-0·633) and 0·800 (0·700-0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345-0·411) and top-3 accuracy by 13·0% (0·545-0·616). INTERPRETATION: For mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.

Exploration of the Fire-Retardant Potential of Microencapsulated Ammonium Polyphosphate in Epoxy Vitrimer Containing Dynamic Disulfide Bonds.

Epoxy vitrimers appear as a promising alternative to common epoxy thermoset composites. Nevertheless, the possibilities of applying these materials are limited due to their high flammability which may cause high fire risks. To date, the flame-retardant epoxy vitrimer systems reported in the literature almost all rely on intrinsic flame retardancy to achieve high fire safety; however, the complex and expensive synthesis process hinders their large-scale application. In this work, disulfide-based epoxy vitrimer (EPV) was fabricated with 4, 4'-dithiodianiline as the curing agent, and microencapsulated ammonium polyphosphate (MFAPP) was employed as a potential additive flame retardant to improve their fire retardancy. As a comparative study, common epoxy (EP) composites were also prepared using 4,4'-diaminodiphenylmethane as the curing agent. The results showed that the introduction of dynamic disulfide bonds led to a reduction in the initial thermal decomposition temperature of EPV by around 70 °C compared to EP. Moreover, the addition of 7.5 wt.% of MFAPP endowed EP with excellent fire performance: the LOI value was as high as 29.9% and the V-0 rating was achieved in the UL-94 test (3.2 mm). However, under the same loading, although EPV/MFAPP7.5% showed obvious anti-dripping performance, it did not reach any rating in the UL-94 test. The flame-retardant mechanisms in the condensed phase were evaluated using SEM-EDS, XPS, and Raman spectroscopy. The results showed that the residue of EPV/MFAPP7.5% presented numerous holes during burning, which failed to form a continuous and dense char layer as a physical barrier resulting in relatively poor flame retardancy compared to EP/MFAPP7.5%.

Novel poly(arylene ether ketone)/poly(ethylene glycol)-grafted poly(arylene ether ketone) composite microporous polymer electrolyte for electrical double-layer capacitors with efficient ionic transport.

Polymer electrolytes have attracted considerable research interest due to their advantages of shape control, excellent safety, and flexibility. However, the limited use of traditional polymer electrolytes in electric double-layer capacitors due to their unsatisfactory ionic conductivities and poor mechanical properties makes them difficult to operate for long periods of time in large-scale energy storage. Therefore, we fabricated a high-performance microporous electrolyte based on poly(arylene ether ketone) (PAEK)/poly(ethylene glycol)-grafted poly(arylene ether ketone) (PAEK-g-PEG) using a certain amount of carboxylated chitosan with a high electrolyte uptake rate of 322 wt% and a high ionic conductivity of 2 × 10-2 S cm-1 at room temperature. A symmetric solid-state supercapacitor that uses activated carbon as electrodes and a composite microporous polymer film as the electrolyte shows a high specific capacitance of 134.38 F g-1 at a current density of 0.2 A g-1, while liquid electrolytes demonstrate a specific capacitance of 126.92 F g-1. Energy density of the solid-state supercapacitor was 15.82% higher than that of the liquid supercapacitor at a current density of 5 A g-1. In addition, the solid-state supercapacitor exhibited excellent cycling stability of over 5000 charge/discharge cycles at a current density of 1 A g-1. Furthermore, solid-state supercapacitors display lower self-discharge behavior with an open-circuit potential drop of only 36% within 70 000 s, which is significantly better than that of conventional supercapacitors (52% @ 70 000 s), at a charging current density of 1 mA cm-2. The satisfactory results indicated that the PAEK/PAEK-g-PEG composite microporous polymer film demonstrates high potential as an electrolyte material in practical applications of solid-state and portable energy storage devices.

Endosonography with lymph node sampling for restaging the mediastinum in lung cancer: A systematic review and pooled data analysis.

BACKGROUND: Mediastinal restaging after induction treatment is still a difficult and controversial issue. We aimed to investigate the diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle aspiration and endoscopic ultrasound-guided fine-needle aspiration for restaging the mediastinum after induction treatment in patients with lung cancer. METHODS: Embase and PubMed databases were searched from conception to March 2019. Data from relevant studies were analyzed to assess sensitivity and specificity of endobronchial ultrasound-guided transbronchial needle aspiration and endoscopic ultrasound-guided fine-needle aspiration, and to fit the hierarchical summary receiver operating characteristic curves. RESULTS: A total of 10 studies consisting of 558 patients fulfilled the inclusion criteria. All patients were restaged by endobronchial ultrasound-guided transbronchial needle aspiration, endoscopic ultrasound-guided fine-needle aspiration, or both. Negative results were confirmed by subsequent surgical approaches. There were no complications reported during any endosonography approaches reviewed. The pooled sensitivities of endobronchial ultrasound-guided transbronchial needle aspiration and endoscopic ultrasound-guided fine-needle aspiration were 65% (95% confidence interval [CI], 52-76) and 73% (95% CI, 52-87), respectively, and specificities were 99% (95% CI, 78-100) and 99% (95% CI, 90-100), respectively. The area under the hierarchical summary receiver operating characteristic curves were 0.85 (95% CI, 0.81-0.88) for endobronchial ultrasound-guided transbronchial needle aspiration and 0.99 (95% CI, 0.98-1) for endoscopic ultrasound-guided fine-needle aspiration. Moreover, for patients who received chemotherapy alone, the pooled sensitivity of endosonography with lymph node sampling for restaging was 66% (95% CI, 56-75), and specificity was 100% (95% CI, 34-100); for patients who received chemoradiotherapy, the results seemed similar with a sensitivity of 77% (95% CI, 47-92) and specificity of 99% (95% CI, 48-100). CONCLUSIONS: Endosonography with lymph node sampling is an accurate and safe technique for mediastinal restaging of lung cancer.

Integrin ß4-Targeted Cancer Immunotherapies Inhibit Tumor Growth and Decrease Metastasis.

Integrin ß4 (ITGB4) has been shown to play an important role in the regulation of cancer stem cells (CSC). Immune targeting of ITGB4 represents a novel approach to target this cell population, with potential clinical benefit. We developed two immunologic strategies to target ITGB4: ITGB4 protein-pulsed dendritic cells (ITGB4-DC) for vaccination and adoptive transfer of anti-CD3/anti-ITGB4 bispecific antibody (ITGB4 BiAb)-armed tumor-draining lymph node T cells. Two immunocompetent mouse models were utilized to assess the efficacy of these immunotherapies in targeting both CSCs and bulk tumor populations: 4T1 mammary tumors and SCC7 head and neck squamous carcinoma cell line. Immunologic targeting of ITGB4 utilizing either ITGB4-DC or ITGB4 BiAb-T cells significantly inhibited local tumor growth and metastases in both the 4T1 and SCC7 tumor models. Furthermore, the efficacy of both of these ITGB4-targeted immunotherapies was significantly enhanced by the addition of anti-PD-L1. Both ITGB4-targeted immunotherapies induced endogenous T-cell cytotoxicity directed at CSCs as well as non-CSCs, which expressed ITGB4, and immune plasma-mediated killing of CSCs. As a result, ITGB4-targeted immunotherapy reduced not only the number of ITGB4high CSCs in residual 4T1 and SCC7 tumors but also their tumor-initiating capacity in secondary mouse implants. In addition, treated mice demonstrated no apparent toxicity. The specificity of these treatments was demonstrated by the lack of effects observed using ITGB4 knockout 4T1 or ITGB4-negative CT26 colon carcinoma cells. Because ITGB4 is expressed by CSCs across a variety of tumor types, these results support immunologic targeting of ITGB4 as a promising therapeutic strategy.Significance: This study identifies a novel mechanism of resistance to anti-PD-1/PD-L1 immunotherapy mediated by HPV E5, which can be exploited using the HPV E5 inhibitor rimantadine to improve outcomes for head and neck cancer patients.

Development and clinical applications of glasses-free three-dimensional (3D) display technology for thoracoscopic surgery.

The conventional two-dimensional (2D) and glasses-assisted three-dimensional (3D) display systems can no longer meet the clinical requirements with the development of minimally invasive video-assisted thoracoscopic surgery (VATS). The glasses-free 3D display technology adopts both lenticular lens technology and face-tracking and -positioning systems and offers high brightness, large viewing area, and strong anti-interference capability, which significantly improve the operator's experience. When applied in VATS, it has many advantages including good display depth, convenience for performing complex and fine operations, and short learning curve. This novel display technology will greatly promote the development of minimally invasive surgery.

Thoracoscopic surgery for tracheal and carinal resection and reconstruction under spontaneous ventilation.

OBJECTIVES: To describe and assess the techniques of spontaneous-ventilation video-assisted thoracoscopic surgery (SV-VATS) for tracheal/carinal resections and compare the outcomes with the conventional thoracoscopic intubated method. METHODS: From May 2015 to November 2016, some 18 consecutive patients with malignant or benign diseases invading distal trachea and carina who met the criteria for SV were treated by SV-VATS resection. To evaluate the feasibility of this novel technique, they were compared with a control group consisting of 14 consecutive patients with the same diseases who underwent VATS resection using intubated general anesthesia from October 2014 to April 2015. Data were collected with a median follow-up of 10.2 months 75 (range: 1-27). RESULTS: The SV-VATS group consisted of 4 carinal resections and 14 tracheal resections. In the control group, 2 patients underwent carinal resection and 12 underwent tracheal resection. Median operative time was shorter in the SV-VATS group compared with the intubated group (162.5 minutes vs 260 minutes), as was the median time for tracheal end-to-end anastomosis (22.5 minutes vs 45 minutes) and carinal reconstruction (40 minutes vs 86 minutes). The lowest oxygen saturation during the procedure was 94.2% ± 4.9% in SV-VATS group and 93.9% ± 4.5% in the control group. The peak carbon dioxide level at the end of expiration was greater in the SV-VATS group (47.7 ± 4.2 mm Hg vs 39.1 ± 5.7 mm Hg). No conversion to tracheal intubation was needed in the SV-VATS group. Postoperative complications occurred in 6 patients in the SV-VATS group and 9 in the control group. Patients who underwent SV-VATS had a trend toward shorter postoperative hospital stays (11.5 ± 4.3 days vs 13.2 ± 6.3 days). One recurrence (SV-VATS group) and 2 deaths (one in each group) were observed during follow-up. CONCLUSIONS: SV-VATS is a feasible procedure in tracheal and carinal resection and reconstruction in highly selected patients. It can be a valid alternative to conventional intubated VATS for airway surgery.

Outcome and Safety of Radical Resection in Non-Small Cell Lung Cancer Patients via Glasses-Free 3-Dimensional Video-Assisted Thoracoscope Versus 2-Dimensional Video-Assisted Thoracoscope.

OBJECTIVES: The investigation was aimed to evaluate the safety and efficacy of glasses-free 3-dimensional (3D) video-assisted thoracoscopic surgery (VATS) versus 2D VATS for radical resection of non-small cell lung cancer (NSCLC). METHODS: We reviewed the clinical data of patients with pathologically proven NSCLC who underwent glasses-free 3D (the 3D group) and 2D VATS radical lobectomy (the 2D group) with systematic lymph node dissection. The outcomes of this study included operative characteristics and safety of 2D and 3D VATS, and duration of lymphadenectomy of right stations 2 and 4. RESULTS: A total of 190 patients were eligible for the study. The 2D group consisted of 108 patients while the 3D group included 82 patients. The 2 groups were comparable in demographic and baseline variables ( P > .05). The median number of resected lymph nodes was 19 in both groups ( P = .583). The median length of hospital stay was comparable between the 2 groups (2D, 7 days vs 3D, 8 days; P = .167). No operative mortality was reported in either group. Complications developed in 21 (19.4%) patients in the 2D group and 14 (17.1%) in the 3D group ( P = .710). A subgroup analysis of patients who underwent right station 2 and 4 lymphadenectomy showed that the mean time for right station 2 and 4 lymph node dissection was significantly shorter in the 3D group than in the 2D group (3D, 430.9 ± 237.2 vs 2D, 648.6 ± 364.1 seconds; P < .001). CONCLUSIONS: Glasses-free 3D VATS and 2D VATS are comparable in operative characteristics and safety profile for radical resection of NSCLC. Glasses-free 3D visualization facilitates more rapid right-sided mediastinal lymphadenectomy.

Spontaneous ventilation thoracoscopic thymectomy without muscle relaxant for myasthenia gravis: Comparison with "standard" thoracoscopic thymectomy.

OBJECTIVES: Myasthenia gravis (MG) benefits from thymectomy. However, its unpredictable response to muscle relaxants and volatile anesthetic agents may result in muscle weakness and subsequently in postoperative myasthenic crisis. The aim of this study was to determine the surgical outcomes after spontaneous ventilation compared with conventional intubated video-assisted thoracoscopic thymectomy (spontaneous-ventilation video-assisted thoracic thymectomy [SV-VATT] vs intubated video-assisted thoracic thymectomy) in patients with MG. METHODS: Data from all minimally invasive thymectomy procedures performed at our institute between January 2009 and June 2016 were collected. Patient characteristics, perioperative results, and treatment outcomes between SV-VATT (group 1) and the intubated video-assisted thoracic thymectomy (group 2) groups were compared. Furthermore, a propensity score-matching analysis was generated to control for selection bias due to nonrandom group assignment in a 1:1 manner. RESULTS: Thirty-six patients were included in group 1 and 68 in group 2. Matching of patients according to propensity score resulted in a cohort that consisted of 27 patients in both groups. Patients had similar clinical characteristics in both groups. Operating time (P = .07) and lowest pulse oxygen saturation (P = .09) between the procedures were comparable after matching, but peak CO2 level at the end of expiration was significantly greater in group 1 both before and after matching (P < .01). Moreover, the incidence of postoperative myasthenic crisis and postoperative prolonged tracheal intubation was lower in group 1. The postoperative pain visual analog scale score (P < .01) and the length of hospital stay (P = .03) were shorter in group 1. CONCLUSIONS: SV-VATT is a feasible procedure in patients with MG. It might be beneficial by reducing postoperative myasthenic crisis and postoperative prolonged tracheal intubation. Further prospective research is needed.

Challenges in complex video-assisted thoracoscopic surgery and spontaneous respiration video-assisted thoracoscopic surgery procedures.

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.

Tubeless video-assisted thoracoscopic surgery (VATS) under non-intubated, intravenous anesthesia with spontaneous ventilation and no placement of chest tube postoperatively.

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.

Primary spontaneous pneumothorax: simultaneous treatment by bilateral non-intubated videothoracoscopy.

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.

The impact of non-intubated versus intubated anaesthesia on early outcomes of video-assisted thoracoscopic anatomical resection in non-small-cell lung cancer: a propensity score matching analysis.

OBJECTIVES: To comparatively assess the impact of non-intubated intravenous anaesthesia with spontaneous ventilation (NIIASV) versus intubated anaesthesia with single-lung mechanical ventilation (IASLV) on early outcomes of video-assisted thoracoscopic (VATS) anatomical resection of non-small-cell lung cancer (NSCLC). METHODS: A total of 339 patients with NSCLC undergoing VATS anatomical resection (282 lobectomies and 57 segmentectomies) between December 2011 and December 2014 were included for analysis and divided into two groups according to anaesthesia type: NIIASV (151 patients) and IASLV (188 patients). Comprehensive early outcome data including intraoperative and postoperative variables were compared between subgroups. Propensity score matching was used to control for selection bias due to non-random group assignment in a 1:1 manner, resulting in 136 pairs (20 for segmentectomy and 116 for lobectomy) with balanced baseline characteristics. RESULTS: The NIIASV procedure was completed uneventfully in all 32 patients undergoing segmentectomy and in 119 lobectomy patients undergoing lobectomy, whereas 9 lobectomy patients required conversion to IASLV. These 9 cases were excluded from the comparative analysis. Comparisons between NIIASV and IASLV results showed no intergroup differences in demographics, baseline data, operative time, intraoperative blood loss, number of resected lymph nodes and duration of chest tube dwell time. Conversely, significantly better results occurred in the NIIASV group in postoperative fasting time (P < 0.001), overall postoperative chest drainage volume (P < 0.04) and hospital stay (P < 0.02). CONCLUSIONS: In this study, VATS anatomical resection for NSCLC patients is feasible under NIIASV. Perioperative data comparisons with IASLV have shown that postoperative fasting time, overall drainage volume and hospital stay were significantly better with NIIASV, suggesting a more rapid recovery. Further investigation is warranted to assess the long-term effects and survival of this promising globally less invasive surgical strategy.

Video-assisted thoracoscopic surgery segmentectomy by non-intubated or intubated anesthesia: a comparative analysis of short-term outcome.

BACKGROUND: 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). METHODS: 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. RESULTS: Two groups had comparable surgical durations, intraoperative blood loss, postoperative chest tube drainage volume, and numbers of dissected lymph nodes (P>0.05). Patients who underwent non-intubated segmentectomy had higher peak end-tidal carbon dioxide (EtCO2) during operation (44.81 vs. 33.15 mmHg, P<0.001), 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, P<0.001), 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, P<0.001), 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. CONCLUSIONS: 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.

Non-intubated combined with video-assisted thoracoscopic in carinal reconstruction.

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.

Glasses-free three-dimensional endoscopic bronchoplasty, arterioplasty, and angioplasty of the superior vena cava for the radical treatment of right middle upper lung cancer.

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.

GABRA3 promotes lymphatic metastasis in lung adenocarcinoma by mediating upregulation of matrix metalloproteinases.

Tumor metastasis is the main reason for the poor prognosis of lung cancer patients. The GABAA receptor subunit GABRA3 is reportedly upregulated in lung cancer. Herein, we show that high GABRA3 protein expression in lung adenocarcinoma correlated positively with disease stage, lymphatic metastasis status and poor patient survival. In addition, GABRA3 induced MMP-2 and MMP-9 expression through activation of the JNK/AP-1 signaling pathway, which enhanced lymphatic metastasis by lung adenocarcinoma both in vitro and in vivo. These results indicate that GABRA3 promotes lymph node metastasis and may thus be an effective therapeutic target for anticancer treatment.

Video-Assisted Thoracic Surgery Resection and Reconstruction of Carina and Trachea for Malignant or Benign Disease in 12 Patients: Three Centers' Experience in China.

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.