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Many deep learning methods have been developed for pulmonary lesion detection in chest computed tomography (CT) images. However, these methods generally target one particular lesion type, that is, pulmonary nodules. In this work, we intend to develop and evaluate a novel deep learning method for a more challenging task, detecting various benign and malignant mediastinal lesions with wide variations in sizes, shapes, intensities, and locations in chest CT images.Our method for mediastinal lesion detection contains two main stages: (a) size-adaptive lesion candidate detection followed by (b) false-positive (FP) reduction and benign-malignant classification. For candidate detection, an anchor-free and one-stage detector, namely 3D-CenterNet is designed to locate suspicious regions (i.e., candidates with various sizes) within the mediastinum. Then, a 3D-SEResNet-based classifier is used to differentiate FPs, benign lesions, and malignant lesions from the candidates.We evaluate the proposed method by conducting five-fold cross-validation on a relatively large-scale dataset, which consists of data collected on 1136 patients from a grade A tertiary hospital. The method can achieve sensitivity scores of 84.3% ± 1.9%, 90.2% ± 1.4%, 93.2% ± 0.8%, and 93.9% ± 1.1%, respectively, in finding all benign and malignant lesions at 1/8, 1/4, ½, and 1 FPs per scan, and the accuracy of benign-malignant classification can reach up to 78.7% ± 2.5%.The proposed method can effectively detect mediastinal lesions with various sizes, shapes, and locations in chest CT images. It can be integrated into most existing pulmonary lesion detection systems to promote their clinical applications. The method can also be readily extended to other similar 3D lesion detection tasks.

Early stage non-small cell lung cancer (NSCLC) patients who undergo complete resection continue to demonstrate high risk of recurrence and death. The advent of the neoadjuvant regimen has brought new hope for these patients. The present study aims to further demonstrate the efficacy of neoadjuvant chemoimmunotherapy.A real-world observational study was conducted concerning patients who received neoadjuvant pembrolizumab or nivolumab combined with chemotherapy between January 2018 and December 2020 in Shanghai Pulmonary Hospital. The primary endpoint was major pathologic response (MPR), and the secondary endpoints were objective response rate (ORR), pathologic complete response (pCR), disease-free survival (DFS) and toxicity.A total of 76 patients were analyzed and divided into the pembrolizumab (n = 42) and nivolumab groups (n = 34) with a median follow-up time of 12.2 months. Most patients (92%) had stage III disease, with 41 (54%) and 29 (38%) patients initially diagnosed clinical stage IIIA and IIIB, respectively. Fifty (66%), 21 (28%) and 5 (6%) patients received two, three and four cycles of neoadjuvant treatment, separately, achieving an ORR of 75%. None of them needed a reduced initial dose or delay due to intolerable adverse events. Forty-nine (64%) and 28 (37%) patients achieved MPR and pCR, respectively. RNA sequencing showed that MPR associated with increased infiltration of cytotoxic immune cells with tertiary lymphoid structures (TLSs). Histological evaluation highlighted the localization of B cells within TLSs. Forty-two (69%) patients with clinically N2 disease at baseline were downstaged to pathological N0 (39 patients) or N1 (3 patients). One-year-PFS rate of stage III patients was 91%. No difference in baseline characteristics and treatment outcomes was observed between 2 groups.The feasibility of neoadjuvant chemoimmunotherapy for resectable NSCLC was further validated, with a high MPR rate and manageable adverse events.

BACKGROUND: We aimed to characterize the outcomes of sleeve resection after neoadjuvant chemoimmunotherapy for the treatment of non-small cell lung cancer (NSCLC), including perioperative and oncologic outcomes, and to identify any impact of operative approach on resultant findings. METHODS: We identified patients with NSCLC who underwent sleeve resection after ≥2 cycles of neoadjuvant chemoimmunotherapy between May 2019 and April 2021 and retrospectively reviewed clinical records. Perioperative data were collected and compared between video-assisted thoracoscopic surgery (VATS) (n=8) and thoracotomy (n=15) groups. Immunohistochemistry (IHC) scores were compared between tumors with and without major pathological response (MPR). RESULTS: Twenty-three patients met inclusion criteria, with clinical stages as follows: IB, 2 (8.7%); IIIA, 14 (60.9%); and IIIB, 7 (30.4%). Treatment-related adverse events (TRAE) were recorded in 17 patients (73.9%), including anemia and neutropenia, with no patients exhibiting serious TRAE. Radiological evaluation revealed 5 (21.7%) patients with complete response (CR), 14 (60.9%) with partial response (PR), and 4 (17.4%) with stable disease (SD). Complete resection was accomplished for all patients. One VATS procedure was converted to thoracotomy due to extensive pleural adhesions. There were no significant differences in intraoperative blood loss (87.5±51.8 vs. 193.9±145.3 mL), operative time (198.8±79.7 vs. 225.5±55.0 min), number of lymph node examined (16.9±6.6 vs. 18.2±6.5), and hospital stay (5.5±2.8 vs. 9.2±11.2 days) between the VATS and thoracotomy groups (all P>0.05). Postoperative complications occurred in 3 patients, and 1 patient died of bronchopleural fistula (BPF) in the thoracotomy group. Complete pathological response (CPR) and MPR were achieved in seven (30.4%) and 13 (56.5%) patients, respectively. Both preoperative histopathology (P=0.024) and radiological response (P=0.002) were significantly associated with MPR. In postoperative specimens with MPR, the IHC scores of cluster of differentiation (CD)4, CD8, and CD20 were modestly higher, while programmed cell death receptor 1 (PD-1), lymphocyte-activation gene 3 (LAG3) and T cell immunoglobulin and ITIM domain (TIGIT) were lower compared with non-MPR specimens, albeit insignificantly. CONCLUSIONS: Sleeve resection after neoadjuvant chemoimmunotherapy was feasible in patients with locally advanced NSCLC. Perioperative outcomes were comparable between the VATS and thoracotomy groups.

For non-small cell lung cancer (NSCLC) patients receiving neoadjuvant therapy, the major pathologic response (MPR) is defined as the percentage of residual viable tumor cells (%RVT) in the tumor bed of no more than 10%. It has been proposed as a predictor of survival in neoadjuvant therapy-treated cohorts. Nonetheless, the significance of %RVT in the pathological assessment of lung adenocarcinoma cohorts remains undetermined.Overall, 152 lung adenocarcinoma patients were included in this retrospective study, among whom 67 received neoadjuvant targeted therapy and 85 received neoadjuvant chemotherapy. Clinicopathological characteristics, neoadjuvant treatment response, and survival status were investigated. The routinely adopted standard for MPR (%RVT ≤10%) failed to differentiate prognosis in the lung adenocarcinoma population. For the neoadjuvant chemotherapy cohort, the optimal %RVT cutoff value of RFS was 60%. However, this cutoff value was clinically insignificant in the neoadjuvant targeted therapy cohort. Hence, for these patients, we built a nomogram model including high-grade patterns and ypN stage to predict disease recurrence, demonstrating a high efficacy (a bootstrap-corrected C-index of 0.731).%RVT served as a strong indicator of the prognosis of lung adenocarcinoma in patients receiving neoadjuvant chemotherapy but not neoadjuvant targeted therapy. Residual high-grade pathological patterns might substitute MPR in prognostic evaluation of lung adenocarcinoma post-targeted therapy.

The International Association for the Study of Lung Cancer (IASLC) recently proposed a new grading system for lung adenocarcinoma (LUAD). We aimed to validate the prognostic performance of the grading system and explore its role in guiding the strategy of lymph node (LN) dissection. We retrospectively reviewed 1029 patients with clinical stage I LUAD who underwent surgery between 2011 and 2013. The association between mediastinal nodal metastasis and grading system was evaluated. To investigate the value of the grading system in guiding LN dissection strategies, 3 pathologists evaluated the feasibility of identifying the grading system using frozen section (FS). The differences in prognosis between all neighboring grades were highly significant based on the grading system ( P0.001). Notably, almost no grade 1 LUAD (1.4%) had pN2 disease, whereas higher rates were found in grade 2 LUAD (9.6%) and grade 3 LUAD (18.3%) ( P0.001). Multivariate logistic regression analysis revealed that higher tumor grade was an independent predictor of mediastinal nodal metastasis ( P =0.002). Moreover, limited mediastinal LN dissection had equivalent prognosis in grade 1 LUAD, but significantly worse prognosis in grade 2 and grade 3 LUAD than systematic mediastinal LN dissection. The overall accuracy of using intraoperative FS to identify the IASLC grading system was 85.4% (κ=0.765) with substantial agreement. The IASLC grading system could accurately stratify prognosis and predict mediastinal nodal metastasis in patients with clinical stage I LUAD. FS was feasible for identifying the IASLC grading system.

BACKGROUND: Although orthotopic single lung transplantation in rats has long been established, this model is still highly challenging. Therefore, we made several modifications in anesthesia, lung extraction, vascular clamp, and transplantation procedures for this model. METHODS: Fifty cases of rat left lung transplantation were performed using traditional procedures and modified surgical techniques, respectively. Two hundred Sprague Dawley male rats, half as donors and half as recipients, were randomized equally to the two groups. The modifications included orotracheal intubation via a video laryngoscope, retrograde perfusion following anterograde perfusion, a Rummel tourniquet for the occlusion of pulmonary vessels, flushing the vessels and cuffs before anastomosis with heparin, and a simple pleural drainage. The surgical time, warm and cold ischemia time, vascular complications, and survival rate on postoperative day seven were compared between the two groups. RESULTS: The modified surgical techniques significantly reduced the surgical duration (35.7 vs. 46.3 min, P

Objectives The aim of this study is to evaluate the time course and caseload required to achieve proficiency by plotting the learning curve of uniportal thoracoscopic segmentectomy. Methods We retrospectively analyzed the first 238 and 159 cases of uniportal thoracoscopic segmentectomy performed by two surgeons (A and B). The learning curves were assessed using cumulative sum analysis. Perioperative outcomes were evaluated as the learning curve developed. Two subtypes of this surgical approach, simple and complex segmentectomy, were separately analyzed. Results Based on the learning curve, the inflection points occurred at 64 and 90 cases for surgeon A, 71 and 100 cases for surgeon B. Significantly longer operative time (p = .013), length of stay (p = .002), and drainage duration (p = .039) were observed between phase I and phase II compared to phase III for surgeon A. Operative times (p = .001) were significantly reduced for surgeon B. Furthermore, 26-28 and 52-56 cases were necessary to master the simple and complex segmentectomy, respectively. Conclusions A total 64-71 cases were required to master uniportal thoracoscopic segmentectomy and 90-100 cases were necessary to achieve proficiency.

This study evaluated the clinicopathologic characteristics and prognostic impact of atypical epidermal growth factor receptor (EGFR) mutations in patients with completely resected lung adenocarcinoma (LUAD) and investigate whether adjuvant chemotherapy could benefit the survival outcomes for these subjects.We retrospectively reviewed resected LUAD samples from 8437 patients and identified 5358 EGFR-mutated (EGFRm) cases. Of these, 4847 had classical mutations, while 511 had atypical mutations. For further survival analysis, propensity score matching, Kaplan-Meier curve, and Cox regression analyses were conducted.Of the 511 patients with atypical EGFRm LUAD, 131 patients had compound mutations. The frequency of exon 20 insertion (20-ins), G719X, L861Q, S768I, and de novo T790M were 30.3%, 32.7%, 21.9%, 9.2%, and 11.4%, respectively. These patients included a higher proportion of males than those with classical EGFRm LUAD. Between the 483 matched pairs of the classical and atypical EGFRm patients, no significant difference emerged in disease-free survival (DFS) (p = 0.476). Patients with the L861Q mutation had the poorest DFS among those with atypical EGFRm LUAD (p = 0.005). Cox regression analyses revealed that the L861Q mutation was an independent prognostic factor for DFS in 487 patients with solely atypical EGFRm LUAD. In addition, adjuvant chemotherapy did not improve the DFS for those patients, whether in stage IB (p = 0.638) or II-III (p = 0.505) of the disease.The L861Q mutation is an independent prognostic factor for DFS in patients with atypical EGFRm LUAD after complete resection who would not benefit from adjuvant chemotherapy regardless of disease stage.

The presence of micropapillary (MIP) in early-stage lung adenocarcinoma is associated with a poorer prognosis, especially in patients undergoing sublobectomy. However, data on the sensitivity of frozen section (FS) evaluation of MIP is still limited. We included the concept of a filigree pattern on FS to assess its effect on the diagnostic sensitivity and specificity of MIP, and to verify its prognostic value in stage T1 lung adenocarcinoma.A panel of five pathologists evaluated 125 patients with T1 lung adenocarcinoma from January to February 2014 as a study cohort, and 151 patients from January to February 2020 as a validation cohort. The diagnostic accuracy of the filigree and classical micropapillary (cMIP) pattern on FS was investigated.The diagnostic sensitivity of the MIP pattern on FS increased from 43.2% to 65.3% and 56.8% to 81.1% in the study cohort and validation cohort, respectively, and both with good specificity. Filigree not only increased the sensitivity of identifying MIP when there was an absence of cMIP, but also increased the sensitivity when the presence of a minor amount of cMIP. The almost perfect agreement among five pathologists was reached on cMIP and substantial agreement was reached on the filigree in the two cohorts. Moreover, the cMIP and filigree were both correlated with poorer recurrence-free survival (pThe identification of a filigree may improve the diagnostic sensitivity of the MIP pattern on FS. FS was feasible for the detection of filigree and cMIP patterns in stage T1 lung adenocarcinomas.

To evaluate perioperative risk factors for AF in patients undergoing uniportal VATS pneumonectomy versus open thoracotomy, and to investigate mediastinal lymph nodes dissection (MLND) on the occurrence of AF.Patients were divided into 2 groups based on the surgical approach: uniportal VATS and open pneumonectomy. Analysis was done using chi-square test. Multiple variables were tested using univariate analysis. A p value ≤ 0.05 was considered statistically significant.Three-hundred and forty-one patients underwent pneumonectomy between 2014 and 2018 in Shanghai Pulmonary Hospital. Fifty-eight patients underwent uniportal VATS, and 283 underwent thoracotomies. AF was the most common event observed. The overall occurrence of peri-operative AF was 33/341 (9.67%). In the uniportal, converted, and open group the incidence of AF was: 3/52 (5.76%), 1/6 (16.6%), and 29/283 (10.42%), respectively. Overall, there was no specific surgical technique correlated with increased incidence of AF (p = 0.432). By univariate analysis; large tumor size 4.5 cm (p 0.010), operative time (OT) 125 min (p 0.002), and greater volume of blood loss (p 0.001) increased the risk of AF. Additionally, patients who experienced higher post-operative pain (p 0.002) were more vulnerable to developing AF. Mortality occurred in one AF patient (1/33, 3%). Number of lymph nodes harvested was not related to AF incidence (p = 0.520).Although AF incidence was lower in uniportal group, it was not statistically significant. Large tumor size, long operative time, and increased blood loss were associated with increased risk of perioperative AF. These results need to be confirmed by larger studies.

The utilization of neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy has increased significantly for resectable non-small cell lung cancer (NSCLC). It is still unclear whether such a treatment paradigm affects perioperative outcomes compared with other neoadjuvant treatment. We aimed to evaluate the perioperative outcomes of pulmonary resection after neoadjuvant ICI plus chemotherapy and to compare them with neoadjuvant epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) and neoadjuvant chemotherapy alone for resectable NSCLC.A retrospective cohort including 194 stage IB-IIIB NSCLC underwent surgical resection after neoadjuvant treatment between 2018 and 2020 were reviewed. Perioperative complications were evaluated using the Common Terminology Criteria for Adverse Events, and were compared using one-way analysis of variance for continuous variables and Pearson chi-square test.There were 42, 54, and 98 patients in the neoadjuvant ICI plus chemotherapy, EGFR-TKI, and chemotherapy alone groups, respectively. The tumor size before neoadjuvant treatment was well balanced among the three groups (P=0.122). A shorter median surgical time was observed in the EGFR-TKI group than ICI plus chemotherapy group and chemotherapy group alone (120Surgical resection for NSCLC following neoadjuvant ICI plus chemotherapy was safe and feasible, the perioperative outcomes were similar with neoadjuvant EGFR-TKI and chemotherapy alone without unexpected perioperative complications. Additional prospective studies are necessary to validate our findings.

BACKGROUND: Percutaneous transthoracic lung biopsy is customarily conducted under computed tomography (CT) guidance, which primarily depends on the conductors’ experience and inevitably contributes to long procedural duration and radiation exposure. Novel technique facilitating lung biopsy is currently demanded. METHODS: Based on the reconstructed anatomical information of CT scans, a three-dimensionally printed navigational template was customized to guide fine-needle aspiration (FNA). The needle insertion site and angle could be indicated by the template after proper placement according to the reference landmarks. From June 2020 to August 2020, patients with peripheral indeterminate lung lesions ≥30 mm in diameter were enrolled in a pilot trial. Cases were considered successful when the virtual line indicated by the template in the first CT scan was pointing at the target, and the rate of success was recorded. The insertion deviation, procedural duration, radiation exposure, biopsy-related complications, and diagnostic yield were documented as well. RESULTS: A total of 20 patients consented to participate, and 2 withdrew. The remaining 18 participants consisting of 11 men and 7 women with a median age of 63 [inter-quartile range (IQR), 50–68] years and a median body mass index (BMI) of 23.5 (IQR, 20.8–25.8) kg/m(2) received template-guided FNA. The median nodule size of the patients was 41.2 (IQR, 36.2–51.9) mm and 17 lesions were successfully targeted (success rate, 94.4%). One lesion was not reached through the designed trajectory due to an unpredictable alteration of the lesion’s location resulting from pleural effusion. The median deviation between the actual position of the needle tip and the designed route was 9.4 (IQR, 6.8–11.7) mm. The median procedural duration was 10.7 (IQR, 9.7–11.8) min, and the median radiation exposure was 220.9 (IQR, 198.6–249.5) mGy×cm. No major biopsy-related complication was encountered. Definitive diagnosis of malignancy was reached in 13 of the 17 (76.5%) participants. CONCLUSIONS: The feasibility and safety of navigational template-guided FNA were preliminarily validated in lung biopsy cohort. Nonetheless, patients with pleural effusion were not recommended to undergo FNA guided by such technique. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (identifier: NCT03325907).

Evidence of neoadjuvant chemoimmunotherapy for locally advanced non-small cell lung cancer remains investigational and requires prospective validation. This phase II trial (https://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR1900023758) aimed to investigate the safety and effectiveness of neoadjuvant PD-1 inhibitor sintilimab in addition to chemotherapy in the management of resectable stage IIIA non-small cell lung cancer.Eligible patients received two to four 21-day cycles of neoadjuvant therapy: sintilimab (200 mg) and carboplatin (area under the curve 5) on day 1, gemcitabine (1000 mg/mFifty patients were enrolled, and 23 (46%) achieved partial response after neoadjuvant chemoimmunotherapy. Four (8%) patients experienced grade 3 to 5 adverse events. Thirty patients received surgery, none of whom experienced treatment-related surgery delays, and 13 (43.3%) of 30 patients achieved major pathological response (viable tumor ≤10%). With a median follow-up of 13.6 months, 85.3% of patients were disease-free at 1 year (N = 50).Neoadjuvant sintilimab with platinum-containing dual-agent chemotherapy was feasible and safe for patients with resectable stage IIIA non-small cell lung cancer.

Background The long noncoding RNA cancer susceptibility 9 (CASC9) has been recognized as an important modulator of cell growth and metastasis in many cancers. However, its detailed roles in lung cancer remain unclear. In this study, we aimed to investigate its functions and molecular mechanism in lung cancer progression. Methods Expression of CASC9 was determined in lung cancer tissues and cell lines by real-time PCR. CCK-8, colony formation, wound healing and transwell assays were done to evaluate the cell proliferation, migration and invasion capacities in vitro. Real-time PCR, Western blot and RNA immunoprecipitation (RIP) assays were performed to dissect the mechanisms. Results CASC9 was overexpressed in lung cancer specimens and cell lines. Knockdown of CASC9 inhibited cell proliferation, migration, invasion and EMT in lung cancer cells. While overexpression of CASC9 in normal lung epithelial cells did the opposite. CASC9 interacted with HIF-1α and enhanced its protein stability. They formed a positive feedback loop by reciprocally inducing each other expression and regulated cell proliferation and metastasis. Conclusion Our findings demonstrated a novel regulatory signaling pathway, namely the CASC9/HIF-1α axis, which was involved in lung cancer progression. These findings can provide valuable insights on the potential therapy application for lung cancer.

To determine the optimal number of lymph nodes (LNs) examined and the role of adjuvant chemotherapy in stage I lung cancer.The National Cancer Database was queried for surgically treated patients with pathologic stage I lung cancer between 2006 and 2014 (N = 65,438). The optimal LN numbers were determined in the multivariate Cox model and were further validated in the cohort with clinical stage I disease (N = 117,112) in terms of nodal upstaging and prognostic stratification. The role of adjuvant chemotherapy in patients with suboptimal staging (number of LNs examined was less than than the optimum) was evaluated in each T stage.The number of LNs examined correlated with tumor size (p0.001). There were increasing survival benefits with each additional LN examined-up to eight, nine, 10, and 11 nodes for patients with T1a, T1b, T1c, and T2a, respectively. Validation from the cohort with clinically staged disease showed that the threshold of eight to 11 LNs was an independent predictor of nodal upstaging (OR = 1.706, 95% confidence interval [CI] 1.608-1.779) and survival outcome (hazard ratio = 0.890, 95% CI: 0.865-0.916). After propensity matching, adjuvant chemotherapy was associated with improved survival in patients with stage T2a disease having suboptimal staging (hazard ratio = 0.841, 95% CI: 0.714-0.990), but not in patients with stage T1a to T1c disease.LN evaluation was important for accurate staging and adequate treatment, and examinations of an increasing number of nodes for progressively higher T components (i.e., eight, nine, 10, and 11 nodes for T1a, T1b, T1c, and T2a tumors, respectively) seemed crucial to predict upstaging and survival outcomes. Adjuvant chemotherapy might be beneficial to patients with stage T2a disease who have suboptimal nodal staging.

The behavior of the pathological subtypes of tracheal glomus tumor (benign, uncertain malignant potential UMP, malignant) is vague. In a 51-year-old gentleman, suffering from cough for 4 months, computed tomography scan showed a mass at lower third of the trachea and the bronchoscope revealed exophytic mass at the tracheal lumen. Segmental tracheal resection was done using special modified endotracheal tube for the distal lung ventilation. The tracheal glomus tumor was also diagnosed based on the immunohistochemical staining. The tumor was 2 cm in diameter, deeply located, mitotic phase was difficult to identify, and a diagnosis of UMP subtype was made. There was no recurrence after 2 years follow-up. This is the first reported case of UMP subtype in lower trachea and we studied the treatment options with the clinic-pathological behavior of this tumor and its sequel by regular follow-up.

BACKGROUND: The aim of this study was to investigate the feasibility and safety of simultaneous bilateral thoracoscopic lobectomy and compare perioperative and late outcomes between simultaneous and staged bilateral thoracoscopic lobectomy. METHODS: Between January 2013 and December 2017, the medical records of patients who underwent bilateral thoracoscopic lobectomy for synchronous bilateral multiple primary lung cancer (SPLC) were reviewed retrospectively. Univariate analysis was used to examine the factors associated with morbidity. Survival was estimated with the Kaplan-Meier method. RESULTS: In the simultaneous resection group (n=41) and the staged groups (n=66), 11 and 16 patients underwent postoperative complication, respectively, whereas no significant differences existed between two groups (P=0.850). Univariate analysis showed that preoperative comorbidities (P=0.009), FEV(1) 3 cm. CONCLUSIONS: Bilateral thoracoscopic lobectomy could be a feasible option for SPLC based on appropriate patient selection and careful perioperative management. Meanwhile, simultaneous resection has significantly advantaged in reducing the cost, preventing tumor progression compare to staged resection.

Uniportal (U-VATS) pneumonectomy in lung cancer patients remains disputed in terms of oncological outcomes, and has not been compared to open approaches previously. We evaluated U-VATS versus open pneumonectomy at a high-volume centre.Patients undergoing pneumonectomy for lung cancer between 2014 and 2018 were retrospectively reviewed and divided into two groups based on surgical approach. Propensity-score matching was performed (1:1), and intention-to-treat analysis applied. Overall survival, operative time, intraoperative blood loss, hospital-stay and readmission, pain, time to adjuvant therapy, morbidity and mortality were tested. Statistical analysis was performed using SAS version 9.4 (SAS Institute Inc. NC) RESULTS: 341 patients underwent pneumonectomy; 23 patients with small-cell lung cancer were excluded, thus 318 patients were submitted to surgery by either U-VATS (n = 54) or open (n = 264). After matching, 52 patients were selected from each group. Five patients (9.2%) in the uniportal group required conversion. There was no significant difference in intraoperative outcomes, complication rates, readmission rates or mortality. The U-VATS group experienced significantly shorter hospital stay (mean ± SD; 6.7 ± 2.7 vs 9.1 ± 2.3 days, p 0.001) and reported less pain postoperatively (p 0.0001). Adjuvant chemotherapy was initiated sooner after U-VATS (38.1 ± 8.4 vs 50.8 ± 11.5 days, p 0.0001). Overall survival appeared to be superior in U-VATS when pathology stage was aligned (p = 0.001).Uniportal VATS is a safe and effective alternative approach to open surgery for pneumonectomy in lung cancer. Complications and oncologic outcomes were comparatively similar. U-VATS showed lower postoperative pain, shorter hospital stay and superior overall survival. The study is a preliminary analysis.

Uniportal video-assisted thoracoscopic surgery (UniVATS) has been widely adopted in China, where several ultra-high volume thoracic surgical and training centers are located. The objective of this consensus from Chinese experts was to summarize the current application and give reference for the future development of UniVATS in the treatment of lung cancer. A panel of 41 experts from 21 Chinese hospitals was invited to join this project. The Delphi method was used in this consensus consisting of two rounds of voting. The questionnaire was based on the current clinical evidence. Forty (97.6%) experts completed the 2 rounds of questionnaires. The experts' experience was relatively similar. We defined the UniVATS as monitor-dependent surgery, no use of rib-spreading and single incision less than 4 cm. Tumor with stage of T1-T3 and N0-N2 is considered amenable to UniVATS. Other consensus was reached on several points outlining the safety and feasibility, surgical skills, learning curve, short-term and long-term outcomes for lung cancer, and current application of subxiphoid and nonintubated UniVATS approach. This consensus statement represents a collective agreement among Chinese experts to suggest that UniVATS is an effective alternative to multi-portal approach, although high-level evidence is expected in the future. Some agreements can be referred in the training of young surgeons.

BACKGROUND: Toll-like receptors (TLRs) play a vital role as a first defense mechanism linking the innate with the adaptive immune system. Prior studies showed that TLR2 participated in immune responses of sarcoidosis. However, the role of TLR2 in the progression of mediastinal lymph nodes associated with sarcoidosis is still unknown. The current study aims to investigate the expression of Toll-like receptors 2 (TLR2) in mediastinal lymph nodes of patients with sarcoidosis. METHODS: Mediastinal lymph nodes biopsy specimens were collected from 10 patients with sarcoidosis and 11 normal controls. The expression of TLR2 in mediastinal lymph nodes was detected by immunohistochemistry. RESULTS: In mediastinal lymph nodes specimens, immunohistochemical examination revealed that expression of TLR2 could be detected in sarcoidosis patients, while it was scarcely detected in the mediastinal lymph nodes of control. The mean optical density of TLR2 in mediastinal lymph nodes of sarcoidosis was significantly higher than controls (124.9±24.3 vs. 92.6±35.2, P=0.026). Among patients with sarcoidosis, correlation analysis showed that the mean optical density of TLR2 in mediastinal lymph nodes positively correlated with the level of 24-hour urinary calcium (R=0.781, P=0.038). CONCLUSIONS: The expression of TLR2 was upregulated in mediastinal lymph nodes of sarcoidosis patients. The expression of TLR2 in mediastinal lymph nodes was associated with the level of 24-hour urinary calcium, suggesting that TLR2 might become another predictor of disease activity.

Metasurface can arbitrarily control the polarization states of incident light and has attracted signicant attention. However, the transmission eciency of cross-polarization conversion of transmissive type metallic metasurfaces for polarized beam-splitters reported to date are low, especially the transmission eciency of cross-polarization conversion by single-layer metallic metasurfaces has a low theoretical upper limit of 25%, whose low value severely works against the application requirements. In this work, we propose two beam-splitters based on single-layer anomalous silicon metasurfaces, which can realize high conversion eciency and broad bandwidth wavefront control. A broadband half-wave plate and the high-eciency beam splitting of quarter-wave plate with circularly polarization beam are both achieved. Moreover, with big incident angles, the metasurface still maintains high-eciency performance.

In this work, a high-efficiency and tunable dual-frequency reflective polarization converter composed of graphene metasurface with twisting double L-shaped unit is firstly realized. Numerical results demonstrate that the device can convert a linearly polarized wave to its cross-polarized wave, and meantime it can also convert to a circularly polarized wave. Subsequently, one thickness of 500 nm SiO 2 layer sandwiched by two graphene metasurfaces with similar pattern is stacked on the top of the two-layered structure, a four-frequency efficient reflective polarization converters is realized. Above all, those working frequencies can also be dynamically tuned within a large frequency range by adjusting the Fermi energy of the graphene, without reoptimizing and refabricating the nanostructures, which paves a novel way toward developing a controllable polarization converter for mid-infrared applications.

This paper presents a wideband tunable cross-polarization converter based on a graphene metasurface with a hollow-carved “H” array in the mid-infrared regions. The converter consists of three layers: the upper layer of the insulation dielectric layer is a periodic regular hollow-carved “H” array, and the bottom layer is a metal ground plane. Simulation is carried out by applying the frequency domain solver of the CST Microwave Studio software. The numerical simulation results show that the polarization converter transforms linear light into its cross-polarization light. The polarization conversion ratio is over 90% at 2.53 THz within the range of 34.39 to 36.92 THz, whereas the FWHM bandwidth is 3.87 THz within the range of 33.8 to 37.67 THz, about 11% of the central frequency. Thus, the cross-polarization converter can be dynamically tuned over a wide frequency range by altering the Fermi-energy of graphene, without reoptimizing and refabricating nanostructures. The operating frequency band of the proposed structure can also be tuned by changing the size of $w_1$ or $\Lambda$ while keeping the polarization conversion ratios high. Moreover, strong robustness is observed under the oblique incidence. Specifically, the polarization conversion ratios can be maintained at over 90% at angles of incidence of up to $50^\circ$ . Therefore, the proposed device has potential development and application in the manipulation of light polarization in the mid-infrared regions.

OBJECTIVES Subxiphoid uniportal video-assisted thoracoscopic surgery (SUVATS) is a technically difficult and challenging operation that can help decrease pain around the incision after traditional intercostal uniportal video-assisted thoracoscopic surgery (IUVATS), and can also treat bilateral lesions through the same incision. We aimed to compare perioperative outcomes and pain scores after SUVATS and IUVATS in patients receiving synchronous treatment of bilateral lung lesions. METHODS Patients who received SUVATS and IUVATS bilateral lung resections from September 2014 to February 2018 were analysed. Ultimately a total of 381 cases were analysed after using one-to-one propensity score matching to match baseline characteristics between the 2 groups. RESULTS The 381 patients included 56 with SUVATS and 325 with IUVATS. After matching, 54 SUVATS and 54 IUVATS cases were analysed. The 2 groups had similar preoperative factors and did not differ with respect to duration of chest tube placement, length of stay in hospital and incidence of postoperative complications. SUVATS was associated with a significantly longer operative time (212.3 vs 154.6 min, P CONCLUSIONS Compared with IUVATS, despite the longer operative time and greater blood loss, SUVATS for bilateral lung lesions is a safe surgical procedure associated with significantly less postoperative pain and a similar incidence of postoperative complications in selected patients.

Subcostal access is a novel approach for anatomical lung resection. To perform surgery via this access, specially designed long instruments are required. Subcostal access provides excellent visualization of the mediastinum and anterior lung hilum. We exhibit here a subcostal middle lobectomy with systematic en-block mediastinal lymphadenectomy in an obese 52-year-old male patient with body mass index (BMI=37.7) performed via this single incision. The operation was completed efficiently within 30 minutes with negligible postoperative pain.

e14506 Background: Tumor infiltrating lymphocyte (TIL) is a kind of adoptive T cell therapy that has demonstrated clinical benefits in several types of solid tumors. GT101 is an autologous TIL therapy for the treatment of multiple solid tumors. Previous studies showed that in vitro expansion resulted in over 80% terminally differentiated effector T cells in the final TIL products, which may show good cytotoxicity but weak capability of persistence and proliferation in vivo. Herein we present phenotype and function characterization of our TIL product GT101 with a focus on its stemness attributes. Methods: We have produced more than 30 batches of GT101 TIL samples from 10 different cancer indications and analyzed their proliferation, cytokine production and phenotype at preREP and/or REP stage. Results: GT101 products keep a consistent T cell phenotype and good proliferation capacity, and are capable of secreting large amounts of cytokines after stimulation by anti-CD3/CD28 antibody, reflecting its good functionality. The residues in the final products, such as feeder cells and tumor cells, are below the detection limit. In contrast to equivalent TIL products previously reported across the world, we find that GT101 features a manufacturing process that preserves the stem cell characteristics of T cells. Analysis of all the 30 GT101 TIL samples demonstrates that the average percentage of central memory T cells (Tcm) and naïve T cells is 40-50% and 10-20% respectively in both CD8+ and CD4+ populations at the end of preREP stage. Meanwhile, CD8+TCF1+ cells are close to 50%, mainly in the form of PD-1-. In the phase of REP, the stemness of T cell is still well maintained—the average proportion of both Tcm and naïve T cells only decreases by about 5%, and that of CD8+TCF1+ cells down by about 10%. Conclusions: In general, GT101 demonstrates good stemness with a higher percentage of Tcm and TCF1+ than equivalent products previously reported across the world, suggesting better performance in persistence and proliferation in clinic.

Objectives Single-port video-assisted thoracic surgery (VATS) technique has been used for thoracic diseases. There was no report about single-port VATS in large series. Outcomes following single-port VATS were analysed to determine its efficacy and safety. Methods From June 2012 to June 2014, 1063 single-port VATSs were performed by four surgeons. Patient demographics, perioperative parameters, histopathology and outcomes were analysed. Results There were 1063 patients (524 men and 539 women). The median age was 56.1 ± 8.7 years (range, 15-86 years). Lobectomy was performed in 569 patients, segmentectomy in 162, wedge resection in 264, pleural biopsy in 7, drainage of effusion in 20, pleural tumour resection in 5, mediastinal tumour resection in 54, mediastinal tumour biopsy in 2, bilobectomy in 7, sleeve lobectomy in 3 and pneumonectomy in 2. Synchronous bilateral single-port VATS was performed in 27 cases, whereas metachronous bilateral single-port VATS was performed in 5 cases. Pathological diagnoses included primary lung cancer in 635 cases, metastatic lung cancer in 19, mediastinal tumour in 56, pleural disease in 32 and benign pulmonary conditions in 353. Fifteen intraoperative vascular injuries were identified in 15 patients. The total conversion rate was 4.6%. The average operation time was 135 ± 31 min (range, 30-230 min), and the average blood loss was 117 ± 47 ml (range, 50-2000 ml). The median intensive care unit stay was 1 day (0-4 days). The postoperative hospital stay was 6.2 ± 2.6 days on average. There was no operative death, and operative complications occurred in 59 patients (5.6%). The 1-year overall survival and 1-year disease-free survival for the primary lung cancer group were 98 and 96%, respectively. Conclusions Our findings indicate that single-port VATS for thoracic diseases is safe and feasible.

OBJECTIVES: The surgical outcome of neurogenic tumours arising at the thoracic apex remains largely undefined. In this retrospective study, we compared the efficacy and safety of thoracoscopic surgery and thoracotomy for neurogenic tumours at the thoracic apex in 63 patients who received surgical treatment between 1992 and 2012 at our medical centre. METHODS: Forty-four (69.8%) patients received thoracotomy (Group A) and 19 (30.2%) patients underwent video-assisted thoracoscopic surgery (Group B). Operative time, estimated blood loss (EBL), postoperative length of hospital stay and nervous system complications were recorded. RESULTS: The two groups of patients were comparable in demographic and baseline characteristics except that Group A patients had a significantly larger tumour size (mean, 4.9 ± 1.0 cm) than Group B patients (mean, 4.1 ± 1.2 cm; P = 0.01). The mean operative time was markedly greater for Group A (120.2 ± 41.2 min) than Group B (93.2 ± 34.5 min; P = 0.009). Group A had significantly greater EBL (245.23 ± 197.78 ml) than Group B (117.4 ± 138.2 ml; P < 0.001). Total tumour resection was achieved in all patients and all neurogenic tumours were benign. The mean length of postoperative hospital stay was markedly longer in Group A (7.0 ± 2.1 days) than Group B (4.8 ± 2.0; P < 0.001). Postoperatively, brachial plexus injury was found in 1 patient (2.3%) in Group A and 4 patients (21.1%) in Group B (P = 0.026). CONCLUSIONS: Though thoracoscopic surgery is associated with diminished blood loss, reduced operative time and shortened hospital stay, it has a markedly increased incidence of brachial plexus injury.

Objective Malignant peripheral neurogenic tumor is always found in large peripheral nerve of the extremities, however, benign peripheral neurogenic tumors of chest is an uncommon disorder, furthermore, malignant transition is even rare. So far, few cases have been reported. We studied 45 neurogenic thoracic tumors patients with malignant transition. Methods We retrospectively reviewed clinical data of 45 malignant neurogenic thoracic tumors from 1992 to 2012, including 11 (24.44%) cases of borderline tumors (group X), 13 cases of (28.88%) low-grade malignant tumor (group L), and 21 cases (46.66%) of malignant tumors (group M). Specifically, we reviewed the clinical characteristics, surgical approach, postoperative outcome, complications and prognosis of these patients. Results All tumors are located in the thoracic cavity, and arising from sympathetic or spinal nerve or their branches from the lung or posterior mediastinum. The patients from groups X and L had more complete resection than group M. Unfortunately, one patient was dead intra operatively in Group M. Group M had more recurrence than groups X and L. Our results indicates that, the survival rate may be correlated with tumor size, malignant degree (P = 0.018), tumor recurrence and incomplete resection (P Conclusion The most effective treatment method for these tumors is early identification and resection by minimally invasive surgery during benign stage. In addition, regarding low-grade malignant tumor, non-radical surgery could also be responsible for the low survival rate.

Many studies have described the use of intrapleural fibrinolytics for the treatment of complex pleural processes and traumatic hemothorax, but data are scarce regarding their use for hemothorax after lung surgery.To evaluate the utility of intrapleural fibrinolytic therapy with urokinase for residual coagulated hemothorax (blood clot accumulation in the pleural cavity) after lung surgery.From July 2009 to November 2013, 46 patients (33 males; mean age, 56.9 ± 10.7 years) were treated with intrapleural urokinase (250,000 IU per dose) for residual hemothorax after lung surgery. Complete response was defined as clinical improvement with complete drainage of the retained collection shown by chest X-ray, and partial response as substantial resolution with minimal residual opacity (25 % of the thorax). Follow-up was at least 30 days.The procedure was successful in 42 patients (91.3 %), with complete response observed in 35/46 patients (76.1 %) and partial response in 7/46 (15.2 %). These 42 patients did not require re-intervention for fluid accumulation in the pleural cavity. Treatment failed in 4 patients (8.7 %): one developed bronchopleural fistula that later resolved spontaneously and three (6.5 %) required thoracoscopic drainage for pleural cavity fluid accumulation and lung collapse. No patient required thoracotomy for total decortication. Intrapleural urokinase administration was not associated with serious adverse events, including bleeding complications or allergic reactions.Intrapleural fibrinolytic agents should be considered a useful therapeutic option for the treatment of postoperative residual hemothorax. This method appears to be safe and effective in90 % of patients with postoperative hemothorax.

Fanconi Anemia (FA) is a rare genetic disease characterized by chromosome instability mostly resulting from an improper regulation of FANCD2 monoubiquitination. The E2 ubiquitin conjugating enzyme UBE2T along with a multi-protein E3 ubiquitin-ligase complex containing a catalytic subunit FANCL mediates monoubiquitination of FANCD2. However, the upstream events involved in regulating FANCD2 monoubiquitination remain unclear. Here we report that HHR6, human homologs of the yeast ubiquitin-conjugating enzyme Rad6, regulates FANCD2 monoubiquitination in a manner distinct from that of UBE2T. Indeed, although downregulation of HHR6 compromised FANCD2 monoubiquitination and overexpression of HHR6 enhanced FANCD2 monoubiquitination, HHR6 did not directly interact with FANCL. Cells deficient in HHR6, UBE2T or FANCL did, however, all exhibit similar sensitivities to the DNA crosslinking agent mitomycin C (MMC). As an HHR6-induced increase in oncogenic potential could be partially suppressed by co-expression of non-monoubiquitinated FANCD2, a tight regulation of appropriate levels of monoubiquitinated FANCD2 appears to play an important role in tumor suppression. Thus, these results provide further insights into the regulation of FANCD2 monoubiquitination as well as indicate a common link between the FA-BRCA and HHR6 pathways in the maintenance of genome integrity.