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BACKGROUND: Airway management in tracheobronchial surgeries, especially carinal resection and reconstruction, remains one of the greatest challenges to thoracic surgeons. This study investigated the safety and effectiveness of venovenous extracorporeal membrane oxygenation (VV-ECMO) for respiratory support during tracheobronchial surgeries. METHODS: The data of patients who underwent VV-ECMO-assisted tracheobronchial surgeries at the Shanghai Chest Hospital from August 2006 to August 2021 were retrospectively reviewed. The clinicopathological, perioperative, and follow-up outcomes were analyzed. RESULTS: A total of 7 patients (4 males and 3 females) with a median age of 56 years (range, 11–70 years) were included in the study. The following tracheobronchial surgeries were conducted: carinal resection and reconstruction with complete pulmonary parenchyma preservation (n=4), left main bronchus and hemi-carinal sleeve resection (n=1), right upper sleeve lobectomy and hemi-carinal resection (n=1), and tracheal resection and reconstruction (n=1). The mean time on VV-ECMO was 167.7±65.8 min, and the mean operative time was 192.4±55.0 min. The average estimated blood loss was 271.4±125.4 mL. No perioperative death or reimplantation of VV-ECMO occurred. Postoperative complications were observed in 2 patients, including 1 case of respiratory failure due to preoperative severe chronic obstructive pulmonary disease (COPD) and 1 case of chylothorax. The median hospital stay was 11 days (range, 7–46 days). The median follow-up time was 30 months (range, 21–33 months). All the patients remained alive, and no postoperative readmission occurred during the follow-up period. CONCLUSIONS: VV-ECMO is a safe and feasible ventilation mode when intraoperative oxygen saturation cannot be well maintained during tracheobronchial surgery.

BACKGROUND: This study assessed the incidence and risk factors (RFs) of postoperative atrial fibrillation (POAF) and its impact on clinical outcomes in patients undergoing pneumonectomy for lung cancer. METHODS: Between 2013 and 2018, this monocentric retrospective study enrolled 324 consecutive pneumonectomy patients for primary lung cancer from our institution and 350 lobectomy and 349 segmentectomy cases matched by age, sex and body mass index (BMI). RF for POAF and postoperative death in pneumonectomy patients were assessed by logistic regression, and long-term outcomes after a median follow-up of 30 (range, 2–61) months by Cox proportional hazard model. Electrophysiology study (EPS) files of 30 AF patients with lung resection history were reviewed. RESULTS: POAF developed more often after pneumonectomy than lobectomy and segmentectomy (23.2% vs. 6.6% vs. 1.4%, respectively; P60 years and left atrial diameter (LAd) ≥35 mm as independent predictors. POAF, infection and hemorrhage were independent RFs for perioperative death after pneumonectomy; however, POAF was not RF for long-term death. Pulmonary vein (PV) trigger was identified in 60% (18/30) of AF patients with lung resection history, with stump PVs being more active than non-stump PVs (38.2% vs. 10.5%, P60 years and LAd ≥35 mm, was mostly solitary and possibly secondary to stump and non-stump PV triggers. POAF, along with infection and hemorrhage, was a RF for perioperative death.

Background Phrenic nerve injury (PNI) during lung cancer surgery, without apparent nerve section or damage, is still not well-studied. The aim of our study is to find an easy and objective way to evaluate a significant diaphragm elevation (SDE) suggestive of inadvertent PNI and its incidence and impact on lung cancer patients undergone video-assisted thoracoscopic surgery (VATS) lobectomy. Methods Extent of diaphragm elevation was first examined on chest X-ray in a cohort of patients with invasive thymoma in whom phrenic nerve was intentionally transected. The result was then used as the criterion to diagnose a SDE suggestive of PNI in another cohort of VATS lobectomy patients. Fluoroscopy test was used to validate the results. Spirometry test was repeated to evaluate pulmonary function loss after surgery. Results Diaphragm elevation was 24.24%±6.2% in 22 invasive thymoma-patients, with 30% elevation adopted as the criterion to diagnose SDE suggestive of PNI. In 753 VATS lobectomy patients, 56 (7.4%) were diagnosed of SDE. On Fluoroscopy test, diaphragm movement was significantly less in patients with diaphragm elevation >30% than those without (5.0 vs. 11.0 mm, P=0.003), together with a significantly smaller diaphragm movement ratio on the operation (OP) side than on the contralateral side (17% vs. 42%, P=0.018). Although no difference in postoperative complications was found, reduction in FEV1, FVC, and DLCO was significantly greater in patients with a SDE than those without (P=0.009). Conclusions Patients with more than 30% diaphragm elevation after VATS lobectomy is highly likely to have PNI and should undergo fluoroscopic validation. Inadvertent PNI during VATS lobectomy is an underestimated phenomenon and is associated with significantly greater loss of pulmonary function.

Background Locally-advanced lung squamous cell carcinoma represents a special subset that is challenging to resect completely with surgery alone. Immunotherapy has achieved great success in treating late-stage lung cancer. However, whether neoadjuvant immunotherapy can facilitate resection of initially locally-advanced and surgically-difficult locally-advanced lung squamous cell carcinoma remains to be investigated. Methods We retrospectively collected clinical records of locally-advanced lung squamous cell carcinoma patients who received neoadjuvant immunotherapy followed by surgery between 2018 and 2020 at a large academic thoracic cancer center. Results A total of 23 patients (22 males, 1 female) with locally-advanced locally-advanced lung squamous cell carcinoma were included, initially clinically staged at IIIA (16, 69.6%), IIIB (n=4, 17.4%), IIB (n=2, 8.7%) and IIIC (n=1, 4.3%). The median interval between final treatment to surgery was 36 days (range, 25-93 days), without treatment-related delay in surgery. The neoadjuvant treatment resulted in a high rate of radical resection (n=20, 87.0%). The final histopathological examination demonstrated 6 (26.1%) cases with pathological complete response and 8 (34.8%) with pathological major response. Comparing with the computed tomography scan-based response, we observed a very low consistency (weighted kappa =0.122, P=0.315) between the computed tomography scan-based and final pathological evaluation. The median follow-up time was 510 days (range, 217-920 days). At the end of the follow-up, 1 patient died. Conclusions Our findings showed the clinical promise of neoadjuvant immunotherapy plus surgery for locally-advanced lung squamous cell carcinoma. Computed tomography scan displays a poor role in assessing the resectability after neoadjuvant immunotherapy.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has been increasingly used in the treatment of lung cancers. But it is still unclear whether mediastinal lymph node dissection (LND) under VATS is safe and feasible. The aim of this study is to figure out whether LND by VATS is safe and feasible. METHODS: Consecutive patients with primary resectable lung cancers referred for lobectomy and LND or sampling by VATS between January 2012 and December 2016 were retrospectively reviewed. Clinicopathological characteristics and perioperative results were collected for statistical analysis. RESULTS: Seven-hundred and seventy-three VATS lobectomy patients were included in this study, 494 received LND and 279 received lymph node sampling (LNS). There were more male patients, higher pathological T and N stage in the LND group than in the LNS group. Multivariate analysis suggested that clinical N stage higher than cN0 category and LND were independent risk factors for finding pN2 diseases in all lung cancers, while higher than cN0 category, solid or micropapillary component, and LND were independently related to finding pN2 stage in adenocarcinomas. Propensity-score matching rendered 279 pairs of patients with no significant difference in age, gender, co-morbidity, tumor location, or T stage. Although the LND group had longer operation time (128 vs. 114 minutes, P

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has been widely used in the lung resections. Reports regarding three-dimension (3D) single-port VATS are very limited. The purpose of this study is to evaluate the perioperative outcomes of 3D single-port VATS in a single medical center. METHODS: Totally 523 clinical stage I lung cancer patients underwent surgical resection through VATS operation between September 2016 and October 2017 in our single institution were retrospectively collected and 374 were enrolled. The comparison between 3D single-port VATS and conventional VATS (c-VATS), single-port VATS was conducted focusing on intraoperative and postoperative outcomes. Continuous and categorical variables were analyzed through SPSS software. RESULTS: The 3D singe-port VATS demonstrated no significant difference neither on the intraoperative outcomes including the operative time and the intraoperative blood loss nor the postoperative outcomes including the length of drainage duration and postoperative complications when against c-VATS and single-port VATS. Besides, 3D singe-port VATS elucidated comparable ability of lymph node dissection with c-VATS in subgroup analysis (P=0.192), both of which were better than single-port VATS group (P

Background There is a paucity of biomarkers that can predict the degree of pathological response [e.g., pathological complete response (pCR) or major response (pMR)] to immunotherapy. Neoadjuvant immunotherapy provides an ideal setting for exploring responsive biomarkers because the pathological responses can be directly and accurately evaluated. Methods We retrospectively collected the clinicopathological characteristics and treatment outcomes of non-small cell lung cancer (NSCLC) patients who received neoadjuvant immunotherapy or chemo-immunotherapy followed by surgery between 2018 and 2020 at a large academic thoracic cancer center. Clinicopathological factors associated with pathological response were analyzed. Results A total of 39 patients (35 males and 4 females) were included. The most common histological subtype was lung squamous cell carcinoma (LUSC) (n=28, 71.8%), followed by lung adenocarcinoma (LUAD) (n=11, 28.2%). After neoadjuvant treatment, computed tomography (CT) scan-based evaluation showed poor agreement with the postoperatively pathological examination (weighted kappa =0.0225; P=0.795), suggesting the poor performance of CT scans in evaluating the response to immunotherapy. Importantly, we found that the smoking signature displayed a better performance than programmed death-ligand 1 (PD-L1) expression in predicting the pathological response (area under the curve: 0.690 vs. 0.456; P=0.0259), which might have resulted from increased tumor mutational burden (TMB) and/or microsatellite instability (MSI) relating to smoking exposure. Conclusions These findings suggest that CT scan-based evaluation is not able to accurately reflect the pathological response to immunotherapy and that smoking signature is a superior marker to PD-L1 expression in predicting the benefit of immunotherapy in NSCLC patients.

Background Intrinsic or acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is common, thus strategies for the management of EGFR-TKIs resistance are urgently required. Ferroptosis is a recently discovered form of cell death that has been implicated in tumorigenesis and resistance treatment. Accumulating evidence suggests that ferroptosis can be therapeutically exploited for the treatment of solid tumors; however, whether ferroptosis can be targeted to treat EGFR mutant lung cancer and/or overcome the resistance to EGFR-TKIs is still unknown. Methods The effect of ferroptosis inducers on a panel of EGFR mutant lung cancer cell lines, including those with EGFR-TKI intrinsic and acquired (generated by long-term exposure to the third-generation EGFR-TKI osimertinib), was determined using cytotoxicity assays. Further, drug candidates to enhance the effect of ferroptosis inducers were screened through implementing WGCNA (weighted gene co-expression network analysis) and CMAP (connectivity map) analysis. Flow cytometry-based apoptosis and lipid hydroperoxides measurement were used to evaluate the cell fates after treatment. Results Compared with EGFR-TKI-sensitive cells, those with intrinsic or acquired resistance to EGFR-TKI display high sensitivity to ferroptosis inducers. In addition, Vorinostat, a clinically used inhibitor targeting histone deacetylase, can robustly enhance the efficacy of ferroptosis inducers, leading to a dramatic increase of hydroperoxides in EGFR mutant lung cancer cells with intrinsic or acquired resistance to EGFR-TKI. Mechanistically, Vorinostat promotes ferroptosis via xCT downregulation. Conclusions Ferroptosis-inducing therapy shows promise in EGFR-activating mutant lung cancer cells that display intrinsic or acquired resistance to EGFR-TKI. Histone deacetylase inhibitor (HDACi) Vorinostat can further promote ferroptosis by inhibiting xCT expression.

Left-side secondary carina resection and reconstruction is a rare, complex procedure, performed just in a few specialized centers in a restricted group of patients. Few studies describe this technique and report its short and long-term results. We reviewed our experience to evaluate the perioperative and short-term outcomes of a very demanding surgery. We retrospectively collected the information of all the patients who underwent secondary carina resection and reconstruction for low-grade malignant bronchial tumors at our center. Between January 2012 and September 2018, 23 patients received surgery for low-grade malignant bronchial tumors. In all patients, a secondary carina resection and reconstruction with total lung parenchymal preservation was performed. The mean age was 44.5 ± 12.2 years. Pathologies included adenoid cystic carcinoma in ten patients, carcinoid in 7 (6 typical and 1 atypical), mucoepidermoid carcinoma in 4, myoepithelioma in 1 and inflammatory myofibroblastic tumor in 1. The median length of the resected bronchus was 25 mm (range 15-50 mm). Three patients (13%) had, at least, one postoperative complication with no deaths. Two patients had lymph node metastases and eight had positive margins. Nine patients received adjuvant therapy. Follow-up ranged from 13 to 96 months, all patients are currently alive and free of recurrence. Resection and reconstruction of the left secondary carina with preservation of the lung parenchyma can be performed safely in anatomically and oncologically appropriate patients, providing good short-term results when combined with adjuvant therapies.

Objectives A rare and complex procedure, total lung sparing left secondary carinal resection and reconstruction is only performed in a few specialized centers in a restricted group of patients. We reviewed our experience to evaluate its safety. Methods Patients who underwent left secondary carinal resection and reconstruction with complete lung parenchymal preservation for low-grade bronchial malignancies at the Shanghai Chest Hospital and the Padua University Hospital were retrospectively reviewed. Clinicopathologic factors and perioperative outcomes were analyzed. Results Thirty patients underwent the procedure between July 2012 and July 2019 (mean age, 42.9 years). No operative mortality occurred and postoperative complications developed in 4 patients (13.3%), including pneumonia (n = 3 [10.0%]), subcutaneous emphysema (n = 2 [6.7%]), and prolonged air leak (n = 2 [6.7%]). Pathologies included adenoid cystic carcinoma (n = 11), mucoepidermoid carcinoma (n = 6), carcinoid tumors (n = 9 [8 typical and 1 atypical subtypes]), inflammatory myofibroblastic tumor (n = 3), and myoepithelioma (n = 1). The margins were positive in 8 patients (26.7%), whereas 2 patients (6.7%) had positive lymph nodes. Adjuvant therapies were performed postoperatively, including chemoradiotherapy for positive lymph nodes and radiotherapy for positive margins. Conclusions Total lung sparing left secondary carinal resection and reconstruction can be performed safely in well-selected and oncologically appropriate patients with low-grade bronchial malignancies.

Sarcomeres are the force-generating and load-bearing devices of muscles. A precise molecular understanding of how the entire sarcomere is built is required to understand its role in health, disease and ageing. Here, we determine thein situmolecular architecture of vertebrate skeletal sarcomeres through electron cryo-tomography of cryo-focused ion beam-milled native myofibrils. The reconstructions reveal the three-dimensional organisation and interaction of actin and myosin filaments in the A-band, I-band and Z-disc and demonstrate how α -actinin cross-links antiparallel actin filaments to form a mesh-like structure in the Z-disc at an unprecedented level of molecular detail. A prominent feature is a so-far undescribed doublet of α-actinin cross-links with ∼ 6 nm spacing. Sub-volume averaging shows the interaction between myosin, tropomyosin and actin in molecular detail at ∼ 10 Å resolution and reveals two coexisting conformations of actin-bound heads. The flexible orientation of the lever arm and the essential and regulatory light chains allow the two heads of the “double-headed” myosin not only to interact with the same actin filament but also to split between two actin filaments. Our results provide new insights into the conformational plasticity and fundamental organisation of vertebrate skeletal muscle and serve as a strong foundation for futurein situinvestigations of muscle diseases.

A 71-year-old man had experienced an irritating cough for 3 months. A diagnosis of squamous cell carcinoma in the carina was made from the bronchoscopic examination. The patient underwent a robotic-assisted resection and reconstruction of the carina. The patient’s postoperative course was uneventful. This is the first description of the feasibility of robotic-assisted carina resection and reconstruction.

Background Total lung-sparing tracheobronchial sleeve resections are a step forward in the treatment of low-grade bronchial tumors in which minimal resection margins are required to achieve complete control of the disease. Methods This study retrospectively collected data on patients who underwent total lung-sparing procedures for low-grade tracheobronchial tumors at 2 thoracic surgical centers from January 1984 to October 2019. Results The study included 98 patients, 46 –female (47%) and 52 –male (53%), with a median age of 39 years (range, 7 to 70 years). Thirty-four patients underwent operative endoscopy before surgery (32 had laser treatment, and 2 had endobronchial stenting). The surgical resections were as follows: 9 (9%), tracheal carina; 18 (18%), second carina; 31 (32%), left main bronchi; 25 (26%), right main bronchi; and 15 (15%), intermediate bronchus. The median length of the resected bronchus was 2.2 cm. The median postoperative in-hospital stay was 8 days, and no perioperative mortality was observed. Postoperative complications were recorded in 26-patients (27%). The final histologic classification was as follows: 37 typical carcinoids (38%); 10 atypical carcinoids (10%); 29 adenoid cystic carcinomas (30%); 15 mucoepidermoid carcinomas (15%); 6 inflammatory myofibroblastic tumors (6%); and 1 glomic tumor (1%). Twenty-two patients had positive resection margins and underwent adjuvant radiotherapy. Three patients with adenoid cystic carcinoma had recurrences (1 local and 2 systemic). After a median follow-up time of 54.5 months (range, 4 to 360 months), the overall actuarial 5-year survival was 97%. Conclusions Total lung-sparing tracheobronchial sleeve resection for low-grade malignant disease requires advanced surgical skills, but the hospital morbidity and mortality are very low. This technique is adequate and safe for highly selected patients with low-grade endobronchial malignant diseases, and its use should be encouraged in experienced centers.

Objectives Minimally invasive surgery provides an ideal method for pathologic diagnosis and curative intent of small pulmonary nodules (SPNs); however, the main problem with thoracoscopic resection is the difficulty in locating the nodules. The goal of this study was to determine the safety and feasibility of a new localization technique tailored for SPNs. Methods A computed tomography (CT)-guided technique, which has a tri-colored suture and claw with 4 fishhook-shaped hooks, was designed to localize SPN preoperatively. Then a multicenter, prospective study was conducted to evaluate the safety and feasibility of this device. The primary endpoints included safety (asymptomatic/symptomatic pneumothorax or parenchymal hemorrhage, and unanticipated adverse effects) and success rate (precise placement and device fracture, displacement, or dislodgement). The secondary endpoints included feasibility (duration of the localization procedure and device fracture or fault) and patient comfort (pain). Results A total of 90 SPNs were localized from 80 patients. Overall, no symptomatic complications requiring medical intervention, with the exception of asymptomatic pneumothorax (n = 7 [7.8%]) and lung hemorrhages (n = 5 [5.6%]), were observed. The device was successfully placed without dislodgment or movement in 87 of 90 lesions (96.7%). The median nodule size was 0.70 cm (range, 0.30-1.0 cm). The median duration of the procedure was 15 minutes (range, 7-36 minutes). No patient complained of notable pain during or after the procedure. Conclusions This new device for SPNs is safe, and has a high success rate, feasibility and good tolerance.

The oncogenic protein β-catenin is regulated by microRNAs (miRs) in non-small cell lung cancer (NSCLC). miR-512-5p is downregulated in NSCLC compared with healthy tissues and exhibits a tumour-suppressive effect. To study whether miR-512-5p acts on β-catenin to exert its anticancer effect in NSCLC, miR-512-5p mimic and inhibitor were transfected into NSCLC A549 and H1975 cells. miR-512-5p mimic inhibited the invasion of NSCLC cells and increased apoptosis, which suggested an inhibitory effect of miR-512-5p in NSCLC progression in vitro. By contrast, transfection with the miR-512-5p inhibitor resulted in the opposite effects. A dual-luciferase assay demonstrated that miR-512-5p complementarily bound to the 3'-untranslated region of β-catenin. miR-512-5p mimic suppressed the transcription and translation of β-catenin and reduced the expression of the downstream oncogenes cyclin D1 and matrix metalloproteinases, leading to the inhibition of Wnt/β-catenin signalling and subsequent inhibition of NSCLC tumourigenesis in vitro. In conclusion, miR-512-5p may function as a tumour suppressor in NSCLC by inhibiting the Wnt/β-catenin pathway.

Background To assess the feasibility and perioperative outcomes of single-port (SP) and multi-port (MP) approaches for video-assisted thoracoscopic surgery (VATS) lobectomy and anatomical segmentectomy. Methods Retrospective data from 458 patients who received VATS lobectomy or anatomical segmentectomy at Shanghai Chest Hospital, Korea University Guro Hospital, Affiliated Hospital of National Taiwan University, University of Hong Kong Queen Mary Hospital and Shenzhen Hospital were collected. Patients were divided into SP group and MP group according to the surgical approach. Perioperative factors such as operation time, blood loss during surgery, conversion rate, the number and stations of lymph nodes harvested, postoperative chest tube drainage time, postoperative hospitalization time, perioperative morbidity and mortality, and pain scores during the first 3 days after surgery were compared between the two groups. Results There were no differences in the number (P=0.278) and stations (P=0.564) of lymph nodes harvested, postoperative morbidity (P=0.414) or mortality(P=0.246), and pain score on the third day (P=0.630) after surgery between the two groups. The SP group had a longer operation time (P=0.042) and greater intraoperative blood loss (P

Compared to lobectomy, performing a segmentectomy needs more experience and anatomical knowledge, in particular atypical segmentectomies like S 2 resection. It is considered an uncommon but very useful procedure for the treatment of patient with early stage lung cancer in the right upper lobe. Here, we present two cases of patients with different anatomies of hilar structures in the S 2 segment of the right upper lobe. Case 1: an 82-year-old male patient came to our attention for a chest CT-scan finding of a 13 mm solid nodule in the S 2 segment of the right upper lobe. The patient was in follow up and no regression of the lesion was seen in the last CT scan. As we considered the lesion highly suspicious of early stage lung cancer, a surgical excision was proposed. So, a right S 2 segmentectomy by minimally invasive approach was carried out. Case 2: a 42-year-old female patient presented to our attention for a chest CT-scan finding of a 20 mm mixed-ground-glass opacity (GGO) in the S 2 segment of the right upper lobe. The patient was in follow up and no regression of the lesion was seen in the last CT scan. As we considered the lesion highly suspicious for a tumour, a surgical excision was proposed. A right S 2 segmentectomy by minimally invasive approach was performed. The post-operative course was uneventful in both patients. Final histopathological examination revealed an invasive mucinous adenocarcinoma of the lung, staged as pT1bN0M0 for the case 1 and an invasive papillary adenocarcinoma of the lung, staged as pT1bN0M0 for the case 2. S 2 segmentectomy is an uncommon, demanding, but very useful surgical procedure. The most difficult part lies in how to identify a recurrent A 2 and the right B 2 . A clear understanding of different anatomies is critically important to complete a successful procedure.