Outcomes following minimally invasive approaches vs. open extended lobectomy for non-small cell lung cancer: a propensity-matched analysis of the National Cancer Database.

Background: Traditional thoracotomy, an invasive surgical procedure, has been the standard approach for extended lobectomy in treating non-small cell lung cancer (NSCLC). However, minimally invasive surgery (MIS) has gained traction with advancements in surgical techniques. Despite this, the outcomes of extended lobectomy via a minimally invasive approach remain largely uncharted. Using the comprehensive National Cancer Database (NCDB), our research aimed to clarify the safety, feasibility, and efficacy of minimally invasive extended lobectomy in patients diagnosed with NSCLC. Methods: Our study encompassed a selection of patients with NSCLC who underwent extended lobectomy (defined as lobectomy or bilobectomy with chest wall, diaphragm or pericardial resection) between 2010 and 2014. Through propensity score matching (PSM), we ensured a balanced comparison between patients who underwent MIS and those who opted for the traditional open extended lobectomy. Both univariate and multivariate analyses were employed to discern whether the surgical approach had any significant impact on the prognosis of patients undergoing this specific procedure. Results: Before PSM, our dataset included 3,934 patients. After 1:2 PSM, the MIS group included 683 cases, while the open group included 1,317 cases. One notable finding was the reduced average postoperative hospital stay for the MIS group at 7.15 days compared to the open group at 8.40 days (P<0.001). Furthermore, the 5-year survival rate was similar, with the MIS group at 53.1% and the open group at 51.3% (P=0.683). Conclusions: The results of our study suggest that MIS for extended lobectomy not only is safe and feasible but also is oncologically effective. However, it is imperative to note that these encouraging findings necessitate further validation through prospective studies to ascertain the full scope of benefits and potential risks associated with MIS.

Prognostic significance of limited resection in pathologic stage I lung adenocarcinoma with spread through air spaces.

Background: Tumor spread through air spaces (STAS) is now recognized as tumor invasion. However, the association between STAS and procedure-specific outcomes (limited resection and lobectomy) in patients with pathologic stage I lung adenocarcinoma (ADC) is still under investigation. Methods: To investigate whether limited resection predicts poorer survival in such patients, we retrospectively analyzed the clinicopathologic features of a large cohort of 1,566 patients with stage I ADC from 2017 to 2020 and classified them according to STAS status and surgical method. Kaplan-Meier, Cox hazard proportional regression, and propensity score matching (PSM) were adopted for prognostic evaluation. Results: STAS-positive patients had worse recurrence-free survival (RFS) (P<0.001). There was no significant difference in RFS and overall survival (OS) between limited resection and lobectomy, neither for the STAS-negative nor STAS-positive group before matching. After matching, limited resection was found to achieve comparable RFS to lobectomy in STAS-positive patients with pathologic I, IA, or IB stage tumor, (P=0.816, P=0.576, P=0.281, respectively), but worse OS in stage I and stage IB patients (P=0.029, P=0.010, respectively). Furthermore, in multivariable analysis, limited resection was not an independent prognostic factor of RFS or OS. Instead, the high-grade histological subtype was the only independent prognostic factor for RFS (P=0.001). In the subgroup analysis, adjuvant chemotherapy (ACT) did not improve the outcomes of stage IB STAS-positive patients. Conclusions: Limited resection was associated with worse survival than lobectomy in stage I STAS-positive patients, but not in stage IA STAS-positive patients.

Minimally invasive sleeve lobectomy for centrally located lung cancer: A real-world study with propensity-score matching.

Background: The safety, feasibility, and prognosis of sleeve lobectomy by minimally invasive surgery (MIS) remain to be validated. The purpose of this study was to investigate outcomes in real-world patients receiving minimally invasive sleeve lobectomy in a balanced large cohort. Methods: Between January 2013 and December 2018, 578 consecutive patients undergoing sleeve resection at a high-volume center were retrospectively analyzed. Surgical and oncologic outcomes were compared between MIS and thoracotomy patients after propensity-score matching (PSM). Results: MIS sleeve lobectomy was increasingly used as a time-trend in real-world. Before PSM, the MIS group had smaller tumor size, more T2-stage cases, and more right upper lobe sleeve lobectomies compared to the Open group. After 1:4 PSM by patient demographics and tumoral characteristics, 100 cases of MIS and 338 cases of Open sleeve lobectomy were further analyzed. Although median operation time was longer in the MIS group than in the Open group (170.5 minutes vs.149.5 minutes, P < 0.001), patients in MIS group had significantly less estimated intraoperative blood loss (100 ml vs. 200 ml, P = 0.003), shorter drainage duration (5 days vs. 6 days, P = 0.027) and less amount of drainage (1280 ml vs. 1640 ml, P < 0.001) after surgery. Complete resection rate, combined angioplasty, number of dissected lymph nodes, post-operative length of stay, postoperative morbidity and mortality rate, and application of adjuvant therapy were similar between the two matched groups. Conversion to open thoracotomy was necessary in 13.6% patients, but with similar perioperative outcomes compared to Open cases except for longer operation time. More lower lobe sleeve lobectomies were accomplished via robot-assisted thoracoscopic surgery than via video-assisted thoracoscopic surgery (40.0% vs. 12.0%, P = 0.017) in MIS patients. Five-year overall survivals (MIS vs. Open: 72.7% vs. 64.4%, P = 0.156) and five-year progression-free survivals (MIS vs. Open: 49.2% vs. 50.5%, P = 0.605) were similar between the two matched groups. Conclusions: MIS sleeve lobectomy is associated with similar or even better perioperative results and oncologic outcomes to open thoracotomy. Conversion to thoracotomy does not compromise perioperative outcomes. Robot surgery may be preferable for more complex sleeve resections.

Molecular, clinicopathological characteristics and surgical results of resectable SMARCA4-deficient thoracic tumors.

PURPOSE: SMARCA4-deficient thoracic tumors are rapid aggressive malignancies, often diagnosed at an advanced and inoperable stage. The value of pulmonary resection for resectable SMARCA4-deficient thoracic tumors is largely unknown. METHODS: In this observational study, we included 45 patients who received surgery for stage I-III SMARCA4-deficient tumors. We compared the molecular, clinicopathological characteristics and survival between SMARCA4-dNSCLC and SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) patients. RESULTS: Thirty-four SMARCA4-dNSCLC and 11 SMARCA4-dUT patients were included in this study. Molecular profiles were available in 33 out of 45 patients. The most common mutated gene was TP53 (21, 64%), and followed by STK11 (9, 27%), KRAS (5, 15%), FGFR1 (4, 12%) and ROS1 (4, 12%). There were 3 patients that harbored ALK mutation including 1 EML4-ALK rearrangement. There were 2 patients that harbored EGFR rare site missense mutation. SMARCA4-dUT patients had significance worse TTP (HR = 4.35 95% CI 1.77-10.71, p = 0.001) and OS (HR = 4.27, 95% CI 1.12-16.35, p = 0.022) compared to SMARCA4-dNSCLC patients. SMARCA4-dUT histologic type, stage II/III, R1/2 resection and lymphovascular invasion were independent poor prognostic predictors for both TTP and OS. There were 8 patients who received immunotherapy, the objective response rate was 50%. The SMARCA4-dNSCLC patient with ALK rearrangement was treated with crizotinib as second-line therapy, and achieved stable disease for 9.7 months. CONCLUSION: Patients with SMARCA4-deficient tumors have a high probability of early recurrence after surgery, except for stage I patients. Immunotherapy seems to be a valuable strategy to treat recurrence.

Surgical Outcomes of Video-Assisted versus Open Pneumonectomy for Lung Cancer: A Real-World Study.

BACKGROUND: The safety, feasibility and potential benefits of Video-assisted thoracoscopic surgery (VATS) pneumonectomy remain to be investigated. METHODS: Patients receiving VATS or Open pneumonectomy during the study period were included to compare surgical outcomes. Propensity-score matched (PSM) analysis was performed to eliminate potential biases. RESULTS: From 2013 to 2020, 583 consecutive patients receiving either VATS (105, 18%) or Open (478, 82%) pneumonectomy were included. Conversion from VATS to open was found in 20 patients (19.0%). The conversion patients had similar rates of major complications and perioperative mortality compared with the Open group. After PSM, 203 patients were included. No significant differences were observed in major complications and perioperative mortality between the two groups. For patients with stage pT2 tumors, the major complication rate in the VATS group was significantly lower than in the Open group (7.6% vs. 20.6%, p = 0.042). Compared with left pneumonectomy, the incidence of bronchopleural fistula (BPF) was significantly higher in right pneumonectomy for both VATS (0 vs. 16.7%, p = 0.005) and Open (0.7% vs. 6.5%, p = 0.002) approaches. CONCLUSIONS: Perioperative results of VATS pneumonectomy are non-inferior to those of the Open approach. Conversion to open surgery does not compromise perioperative outcomes. Patients with lower pT stage tumors who need pneumonectomy may benefit from VATS.

miRNA-199a-5p/SLC2A1 axis regulates glucose metabolism in non-small cell lung cancer.

Lung cancer is acknowledged as a common cancer with high morbidity and mortality. MicroRNAs (miRNAs), kind of non-coding single-stranded RNA molecules, can be used in cancer clinical treatments. In this research, miR-199a-5p was seen lowly expressed in NSCLC sera samples. miR-199a-5p suppressed the cell proliferation, migration and arrested cell cycle in NSCLC cell lines. The results showed that SLC2A1 (glucose transporter 1, GLUT1) was a direct target of miR-199a-5p. Downregulation of SLC2A1 could not only inhibit cell proliferation, migration and cell cycle, but also promote cell apoptosis. The data suggests that miR-199a-5p can inhibit glucose metabolism in NSCLC by targeting SLC2A1.This study proves that miR-199a-5p / SLC2A1 can play an essential role in the development of NSCLC by targeting SLC2A1. It puts forward a new approach for clinical treatments of NSCLC.

Occult pleural dissemination detected intraoperatively in patients with thymic tumors: a retrospective analysis.

BACKGROUND: Thymic tumors usually present with adjacent organ invasion or pleural dissemination, but very few studies have reported on occult pleural dissemination detected intraoperatively. This study aimed to investigate the risk factors that can predict pleural dissemination preoperatively. METHODS: Consecutive patients with thymic tumors who underwent surgery from January 2010 to January 2017 were reviewed. Only patients without pleural dissemination detected preoperatively were included in this study. Demographic, clinical, pathological, and survival data were collected for statistical analysis. Further analyses were performed to find the risk factors of occult pleural dissemination. RESULTS: A total of 352 patients with thymic tumors were included in this study. Seven patients had pleural dissemination detected intraoperatively. All pleural dissemination cases were in clinical Masaoka-Koga stage III, and most underwent the video-assisted thoracoscopic surgery (VATS) approach (or VATS exploration). Univariate analysis showed that positive squamous cell carcinoma (SCC) antigen was the only predictor of pleural dissemination (p = 0.009). Tiny nodules close to the diaphragm were detected in the computed tomography scans of 1 case after reviewing the imaging data. Tumor recurrence occurred in 5 patients during follow-up. The disease-free survival rates were better in patients with a solitary nodule than those with multiple nodules (p = 0.019). No significant difference was detected in terms of disease-free survival rates between SCC antigen positive and SCC antigen negative patients. CONCLUSIONS: Positive SCC antigen was the only detected risk factor for predicting pleural dissemination in thymic tumors preoperatively in this study. The VATS approach (including VATS exploration) is suggested for patients with clinical Masaoka-Koga stage III and SCC antigen positive thymic tumors, according to our experience.

Surgical choice for patients with stage I non-small-cell lung cancer ≤2 cm: an analysis from surveillance, epidemiology, and end results database.

BACKGROUND: No consensus was reached on the surgical procedure for patients with stage I non-small-cell lung cancer (NSCLC) ≤ 2 cm. The aim of this study is to investigate the appropriate surgical procedure for stage I NSCLC ≤2 cm. METHODS: Patients with stage I NSCLC ≤2 cm received wedge resection, segmentectomy, lobectomy between January 2004 and December 2015 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Data were stratified by age, gender, race, side, location, grade, histology, extent of lymphadenectomy. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared among patients received wedge resection, segmentectomy, lobectomy. Univariate analysis and multivariable Cox regression were performed to identify the prognostic factors of OS and LCSS. RESULTS: A total of 16,511 patients with stage I NSCLC ≤2 cm were included in this study, of whom 2945 patients were classified as stage I NSCLC ≤1 cm. Lobectomy had better OS and LCSS when compared with wedge resection in patients with NSCLC ≤2 cm. Only OS favored lobectomy compared with segmentectomy in stage I NSCLC>1 to 2 cm. Multivariable analysis showed that segmentectomy had similar OS and LCSS compared with lobectomy in patients with stage I NSCLC ≤2 cm. Lymph node dissection (LND) was associated with better OS in patients with NSCLC ≤2 cm and better LCSS in patients with stage I NSCLC>1 to 2 cm. CONCLUSIONS: Segmentectomy showed comparable survival compared with lobectomy in patients with stage I NSCLC ≤2 cm. LND can provide more accurate pathological stage, may affect survival, and should be recommended for above patients.

Feasibility of Surgical Resection After Induction Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Therapy for N2 Lung Adenocarcinomas.

BACKGROUND: Prognosis of patients with stage IIIA-N2 lung adenocarcinoma is still not optimistic. The aim of this study was to evaluate safety, feasibility, and outcomes of surgery after induction epidermal growth factor receptor-tyrosine kinase inhibitor therapy in a clinical trial setting. METHODS: Fourteen patients with IIIA-N2 lung adenocarcinoma and epidermal growth factor receptor mutation received erlotinib induction followed by surgery in a phase II clinical trial. Perioperative outcomes and survival results were compared with a control group of 15 patients receiving neoadjuvant chemotherapy during the same time period. RESULTS: Thirteen patients showed partial response to induction, whereas 16 patients remained stable. Serum carcinoembryonic antigen level in the erlotinib group was significantly higher than in the chemotherapy group before treatment but was reduced to similar levels after induction. Operation time, blood loss, resection extents, complete resection rates, postoperative drainage, complication rates, and length of hospital stay were all comparable between the 2 groups. Thoracoscopic resection was accomplished in 78.6% of patients in the erlotinib group and 80.0% of patients in the chemotherapy group (P = .924) but was higher in patients who responded to induction than those who did not (92.3% vs 68.8%, P = .119). A resection extent greater than lobectomy and incomplete resections were only seen in stable disease after induction. No significant difference was detected in 1-year and 3-year overall or disease-free survivals between the 2 groups. CONCLUSIONS: Pulmonary resection is safe and feasible after induction treatment with erlotinib for stage IIIA-N2 lung adenocarcinomas. Better surgical and oncologic outcomes may be expected in patients who respond to effective induction therapies.

Significant diaphragm elevation suggestive of phrenic nerve injury after thoracoscopic lobectomy for lung cancer: an underestimated problem.

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.

Upregulated lncRNA CASC9 Contributes to Progression of Non-Small Cell Lung Cancer Through Inhibition of miR-335-3p and Activation S100A14 Expression.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is a deadly cancer type worldwide and the main sub-type of lung cancer. Cancer susceptibility candidate-9 (CASC9) was reported to be a key player in cancer progression. However, its function and underlying mechanism in NSCLC remain unclear. MATERIALS AND METHODS: Expression level of CASC9 in NSCLC tissues and cells was measured with RT-qPCR. Biological roles of CASC9 in NSCLC were analyzed with a series of in vitro experiments. Potential mechanisms of CASC9 in NSCLC were analyzed by predicting and validating the possible targets of CASC9 in NSCLC. RESULTS: In this study, we found CASC9 expression was upregulated in NSCLC tissues and cell lines. High CASC9 expression was identified as a predictor for poorer overall survival of NSCLC patients. Furthermore, functional assays showed CASC9 knockdown suppressed NSCLC cell proliferation, migration, and invasion, while CASC9 overexpression caused opposite effects. We also found microRNA-335-3p (miR-335-3p) could act as a target of CASC9 in NSCLC and the inhibition effect of CASC9 knockdown on NSCLC progression required the activity of miR-335-3p. In addition, we identified S100 calcium-binding protein A14 (S100A14) acts as a target of miR-335-3p. DISCUSSION: Taken together, our study suggested CASC9 could promote NSCLC progression via miR-335-3p/S100A14 axis. The CASC9/miR-335-3p/S100A14 regulatory triplets identified in this work might provide new therapeutic strategies for NSCLC treatment.

Thoracoscopic thymectomy with partial superior vena cava resection for locally advanced thymomas.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is now increasingly used for the treatment of early stage thymic malignancies. However, VATS has not been advocated for patients with locally advanced diseases. We reviewed our initial experience in VATS thymectomy with partial superior vena cava (SVC) resection for IASLC/ITMIG stage III thymic tumors. METHODS: From August 2017 to October 2018, patients who underwent VATS thymectomy with partial SVC resection were retrospectively reviewed, and peri-operative outcomes and short-term follow-up results were analyzing. RESULTS: Four patients with partial SVC resection via VATS were identified. All of them had pathologically confirmed IASLC/ITMIG stage III thymic tumors invading the SVC. The average of operative time was 228 minutes and mean blood loss was 88 mL. The mean duration of chest tube drainage and post-operative hospital stay were 4.5 and 7.3 days respectively. No major complication was encountered after surgery. No mortality was observed. And no recurrence was detected with the longest follow-up time of 14 months. CONCLUSIONS: With careful patient selection and plenty surgical expertise, VATS thymectomy for locally invasive thymic tumors with limited the SVC invasion is challenging yet technically feasible.

Comparison of lymph node dissection and lymph node sampling for non-small cell lung cancers by video-assisted thoracoscopic surgery.

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<0.001), higher amount of postoperative drainage (920 vs. 720 mL, P<0.001), longer postoperative hospital stay (6 vs. 4 days, P<0.001) than the LNS group, no difference was observed in overall morbidity or mortality between the two groups. CONCLUSIONS: LND by VATS has acceptable perioperative results but can provide more accurate nodal staging compared with LNS. LND by VATS is safe, feasible, and should be recommended in patients with tumors in clinical N stages higher cN0 category or with more invasive histology.

Evaluation of the Properties of Asphalt Mixes Modified with Diatomite and Lignin Fiber: A Review.

Due to rapid growth of traffic density, the phenomenon of overloading on high-grade highways causes various modes of distresses to the pavement such as rutting, thermal cracking, and water damage. Modification of asphalt mixes is the most common solution to improve the performance of asphalt pavement to mitigate its damages. This paper provides a review on the influence of diatomite or lignin fiber as a modifier in asphalt mixes. In order to assess the effectiveness of selected additives on asphalt mix performance, several tests, such as wheel tracking, indirect tensile, three points bending, freeze thaw splitting, and marshall immersion, were reviewed. The review indicated that the addition of diatomite increases the high temperature rutting resistance of asphalt mixes, but some researchers observed that it has a little improvement on the low temperature performance of asphalt mixes and the optimum amount of diatomite at 12⁻14% of asphalt binder can be added into the mix. In contrast, lignin fiber has a significant effect on the low temperature cracking resistance of asphalt mixes; however, its influence on the high temperature rutting resistance of asphalt mix is limited, and the optimum amount of lignin fiber is 0.2⁻0.4% per asphalt mix composition. The review also indicated that the single additives haven't the ability to enhance the overall performance of asphalt mix. Consequently, the utilization of double additives can improve the overall performance of asphalt mixes at the same time, but it is still in an early stage in the application of highway engineering due to all previous researches concentrated on the single modification. Moreover, this review suggests that the future use of diatomite and lignin fiber compound modified asphalt mix can improve the overall mix performance.

Primary extragenital choriocarcinoma in posterior mediastinum in a male adult: a case report.

Primary extragenital choriocarcinoma is a highly malignant tumor and usually occurs in the midline of the body, such as the mediastinum, retroperitoneum, pineal gland and the middle part of the brain. In this report we present a case of primary extragenital choriocarcinoma located in the posterior mediastinum. A 40-year-old man was admitted to hospital with severe chest wall pain for 2 months. Enhanced chest computed tomography (CT) showed a mass of soft tissue measuring 5.2 cm × 4.5 cm located in the posterior mediastinum. CT-guided percutaneous fine needle aspiration (FNA) biopsy was performed and adenocarcinoma was diagnosed. After careful examination, complete tumor resection with combined resection of part left upper lobe of lung and lymph node dissection were performed. Combining hematoxylin/eosin staining and immunohistochemical a pathological diagnosis of choriocarcinoma was made.