Robotic-assisted Versus Video-assisted Thoracoscopic Lobectomy: Short-term Results of a Randomized Clinical Trial (RVlob Trial).

OBJECTIVE: To determine whether RAL affects perioperative outcomes and long-term efficacy in NSCLC patients, compared with traditional VAL. SUMMARY OF BACKGROUND DATA: RAL is a promising treatment for NSCLC. However, its efficacy has not been fully evaluated. METHODS: A single-center, open-labeled prospective randomized clinical trial was launched in May 2017 to compare the efficacy of RAL and VAL. By May 2020, 320 patients were enrolled. The perioperative results of RAL and VAL were compared. RESULTS: The 320 enrolled patients were randomly assigned to the RAL group (n = 157) and the VAL group (n = 163). Perioperative outcomes were comparable between the 2 groups, including the length of hospital stay (P = 0.76) and the rate of postoperative complications (P = 0.45). No perioperative mortality occurred in either group. The total amount of chest tube drainage {830 mL [interquartile range (IQR), 550-1130 mL] vs 685 mL [IQR, 367.5-1160 mL], P = 0.007} and hospitalization costs [$12821 (IQR, $12145-$13924) vs $8009 (IQR, $7014-$9003), P < 0.001] were significantly higher in the RAL group. RAL group had a significantly higher number of LNs harvested [11 (IQR, 8-15) vs 10 (IQR, 8-13), P = 0.02], higher number of N1 LNs [6 (IQR, 4-8) vs 5 (IQR, 3-7), P = 0.005], and more LN stations examined [6 (IQR, 5-7) vs 5 (IQR, 4-6), P < 0.001]. CONCLUSIONS: Both RAL and VAL are safe and feasible for the treatment of NSCLC. RAL achieved similar perioperative outcomes, together with higher LN yield. Further follow-up investigations are required to evaluate the long-term efficacy of RAL. (ClinicalTrials.gov identifier: NCT03134534).

Translational value of IDH1 and DNA methylation biomarkers in diagnosing lung cancers: a novel diagnostic panel of stage and histology-specificity.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide, and the timely and serial assessment of low-dose computed tomography (LDCT) in high-risk populations remains a challenge. Furthermore, testing a single biomarker for the diagnosis of lung cancers is of relatively low effectiveness. Thus, a stronger diagnostic combination of blood biomarkers is needed to improve the diagnosis of non-small cell lung cancer (NSCLC). METHODS: The blood levels of individual biomarkers [IDH1, DNA methylation of short stature homeobox 2 gene (SHOX2), and prostaglandin E receptor 4 gene (PTGER4)] were measured and statistically analyzed in samples from healthy controls and patients with lung cancer. In total, 221 candidates were enrolled and randomly assigned into two groups for the training and validation of a diagnostic panel. Additionally, a subgroup analysis was performed in the whole cohort. RESULTS: A newly combined 3-marker diagnostic model for lung cancers was established and validated with area under the receiver operating characteristic (ROC) curve (AUC) values ranging from 0.835 to 0.905 in independent groups showing significantly stronger diagnostic value compared with a single tested biomarker. The sensitivity of the diagnostic model was as high as 86.1% and 80.0% in the training and validation sets, respectively. Although no apparent differences were found between the 3-marker and 2-marker models, the high clinical T-stage and histological type specificity of IDH1 and two other methylated DNA biomarkers were demonstrated in the subgroup analysis. CONCLUSIONS: The combination of single biomarkers with high stage-specificity and histological type specificity (SHOX2 and PTGER4 DNA methylation and IDH1) showed better diagnostic performance in the detection of lung cancers compared with single marker assessment. A greater clinical utility of the panel may be developed by adding demographic/epidemiologic characteristics.

Early Outcomes of Robot-Assisted Versus Thoracoscopic-Assisted Ivor Lewis Esophagectomy for Esophageal Cancer: A Propensity Score-Matched Study.

BACKGROUND: Both robot-assisted Ivor Lewis esophagectomy (RAILE) and conventional thoracoscopic-assisted Ivor Lewis esophagectomy (TAILE) are minimally invasive surgical techniques for the treatment of middle and distal esophageal cancer. However, no research studies comparing early outcomes between RAILE and TAILE have been reported. METHODS: A retrospective analysis was made of 184 patients, 76 in the RAILE group and 108 in the TAILE group, who underwent minimally invasive Ivor Lewis esophagectomy between December 2014 and June 2018. Propensity score-matched analysis was performed between the two groups based on demographics, comorbidities, American Society of Anesthesiologists score, tumor location, tumor size, and pathological stage. Perioperative outcomes were compared. RESULTS: Two conversions to thoracotomy occurred in the RAILE group. There was no 30-day in either group. Sixty-six matched pairs were identified for each group. Within the propensity score-matched cohorts, the operative time in the RAILE group was significantly longer than that in the TAILE group (302.0 ± 62.9 vs. 274.7 ± 38.0 min, P = 0.004). There was no significant difference in the blood loss [200.0 ml (interquartile range [IQR], 100.0-262.5 ml) vs. 200.0 ml (150.0-245.0 ml), P = 0.100], rates of overall complications (28.8 vs. 24.2%, P = 0.554), length of stay [9.0 days (IQR 8.0-12.3 days) vs. 9.0 days (IQR 8.0-11.3 days), P = 0.517], the number of total dissected lymph nodes (19.2 ± 9.2 vs. 19.3 ± 9.5, P = 0.955), and detailed categories of lymph nodes. CONCLUSIONS: RAILE demonstrated comparable early outcomes compared with TAILE and should be considered as an alternative minimally invasive option for treating esophageal cancer.

Robotic sleeve resection for pulmonary disease.

BACKGROUND: Few studies have described robotic sleeve resection with pulmonary resection. Here, we report the successful implementation of a completely portal robotic sleeve resection with or without pulmonary resection using a modified suture mode. METHODS: In total, 339 patients underwent curative robotic pulmonary surgery at Ruijin Hospital between May 2015 and September 2017. Three of these patients underwent robotic sleeve resection (right upper lobe, one; left upper lobe, one; and lingular segmental bronchus, one). Five port incisions were utilized, and a simple continuous running suture combined with two interrupted sutures of the membranous and cartilaginous junction portion was preferred for the anastomosis. RESULTS: The postoperative course was uneventful for two patients with squamous cell carcinoma. The lingular segmental bronchus patient without pulmonary resection (a salivary gland tumor) underwent short-term atelectasis. The median operation time was 155 (range 132-230) minutes. The median anastomosis time was 25 (range 23-32) minutes. The median length of postoperative hospital stay was 7 (range 6-10) days. There was no mortality or conversion to thoracotomy for any of the patients. All patients were followed for 3-6 months, and there is no tumour recurrence. CONCLUSIONS: Our limited experience suggested that robotic sleeve resection for pulmonary disease with or without pulmonary resection may be safe and effective. The anastomosis time can be shortened with more robotic surgery experiences and the modified suture mode.

Clusterin modulates transdifferentiation of non-small-cell lung cancer.

BACKGROUND: Secreted clusterin (sCLU), a 75-80 kDa disulfide-linked heterodimeric protein, plays crucial roles in various pathophysiological processes, including lipid transport, tissue remodeling, cell apoptosis and reproduction. Our previous studies demonstrated that sCLU could influence cell apoptosis, proliferation, and invasion of non-small cell lung cancer (NSCLC) cells. METHODS: In this study, clusterin's function in regulating transdifferentiation of NSCLC cells was investigated. In addition, we examined the correlation between clusterin and clinicopathological features of lung cancer. RESULTS: We found that clusterin was increased in lung adenocarcinoma tissues and decreased in lung squamous cell carcinoma tissues through immunohistochemical technique. In cultured lung adenocarcinoma cell lines, clusterin addition could increase SP-C protein expression in 2.75-fold, and decrease p63 protein expression in 0.65-fold (1.54 to 1). And also clusterin addition could increase SP-C mRNA expression in 4.05-fold, decreased p63 mRNA expression in 0.51-fold. CONCLUSIONS: Our study demonstrated that clusterin could promote EMT and influence transdifferentiation from lung squamous cell carcinoma to lung adenocarcinoma. However, we found that clusterin expression have no correlation with malignance associate clinicopathological data. Our study may help to further elucidate the development and progression of NSCLC, also it may contribute to the research of therapies targeting sCLU.

The metastasis suppressor NDRG1 modulates the phosphorylation and nuclear translocation of ß-catenin through mechanisms involving FRAT1 and PAK4.

N-myc downstream-regulated gene 1 (NDRG1) is a potent metastasis suppressor that has been demonstrated to inhibit the transforming growth factor ß (TGF-ß)-induced epithelial-to-mesenchymal transition (EMT) by maintaining the cell-membrane localization of E-cadherin and ß-catenin in prostate and colon cancer cells. However, the precise molecular mechanism remains unclear. In this investigation, we demonstrate that NDRG1 inhibits the phosphorylation of ß-catenin at Ser33/37 and Thr41 and increases the levels of non-phosphorylated ß-catenin at the plasma membrane in DU145 prostate cancer cells and HT29 colon cancer cells. The mechanism of inhibiting ß-catenin phosphorylation involves the NDRG1-mediated upregulation of the GSK3ß-binding protein FRAT1, which prevents the association of GSK3ß with the Axin1-APC-CK1 destruction complex and the subsequent phosphorylation of ß-catenin. Additionally, NDRG1 is shown to modulate the WNT-ß-catenin pathway by inhibiting the nuclear translocation of ß-catenin. This is mediated through an NDRG1-dependent reduction in the nuclear localization of p21-activated kinase 4 (PAK4), which is known to act as a transporter for ß-catenin nuclear translocation. The current study is the first to elucidate a unique molecular mechanism involved in the NDRG1-dependent regulation of ß-catenin phosphorylation and distribution.

miR-320a suppresses colorectal cancer progression by targeting Rac1.

MicroRNAs (miRNAs) have emerged as critical epigenetic regulators involved in cancer progression. miR-320a has been identified to be a novel tumour suppressive miRNA in colorectal cancer (CRC). However, the detailed molecular mechanisms are not fully understood. Here, we reported that miR-320a inversely associated with CRC aggressiveness in both cell lines and clinical specimens. Functional studies demonstrated that miR-320a significantly decreased the capability of cell migration/invasion and induced G0/G1 growth arrest in vitro and in vivo. Furthermore, Rac1 was identified as one of the direct downstream targets of miR-320a and miR-320a specifically binds to the conserved 8-mer at position 1140-1147 of Rac1 3'-untranslated region to regulate Rac1 protein expression. Over-expression of miR-320a in SW620 cells inhibited Rac1 expression, whereas reduction of miR-320a by anti-miR-320a in SW480 cells enhanced Rac1 expression. Re-expression of Rac1 in the SW620/miR-320a cells restored the cell migration/invasion inhibited by miR-320a, whereas knockdown of Rac1 in the SW480/anti-miR-320a cells repressed these cellular functions elevated by anti-miR-320a. Conclusively, our results demonstrate that miR-320a functions as a tumour-suppressive miRNA through targeting Rac1 in CRC.

Robot-assisted minimally invasive bronchial resection with primary anastomosis for schwannoma arising from left main bronchus: a case report.

Background: Tracheobronchial schwannomas are extremely rare, which account for lower than 0.2% in all pulmonary tumors. In large part because of the rarity and insufficient reported clinical details, tracheobronchial schwannoma lacks guidelines or expert consensus for diagnosis and treatment, and the delay in diagnosis can range from months to years. The main treatment option is surgery. Endoscopic intervention can also be selected. An increasing number of thoracic surgery cases were performed on the robotic platforms in recent years. With their assistance, surgeons can accomplish the high technique required surgical procedures with ease. Case Description: In this case, a 48-year-old female had a history of shortness of breath for more than 1 year. The chest computed tomography (CT) and bronchoscopy examination revealed a new growth of nodule in the left main bronchus. The nodule was considered a schwannoma by transbronchial biopsy, which was removed by robot-assisted bronchial resection with primary anastomosis. The application of Da Vinci Si robotic surgical system benefited the process of this surgery. Pathology and immunohistochemistry results confirmed the diagnosis of schwannomas. The patient tolerated the treatment without any complications. No sign of recurrence was discovered at present, 6 months after the intervention. Conclusions: We reported the first sleeve resection for bronchial schwannoma using Da Vinci robotic surgical system. The clinical details of tracheobronchial schwannoma should be revealed more specifically to achieve more systematic diagnosis and treatment.

Margin quality analysis for wedge resection of lung cancer and construction of a predictive model.

Background: Insufficient pulmonary wedge resection margin is associated with malignant positive margins and high local recurrence risk for lung cancer. This study aimed to identify the risk factors of insufficient or guideline discordant resection margin distance and establish a predictive model to preoperatively estimate the risk of discordant margin for individual patient. Methods: Guideline discordant resection margin was defined as ratio of resection margin distance to tumor size less than one. Patients who had pulmonary malignancies and underwent wedge resection between April 2014 and February 2023 were enrolled and stratified by quality of resection margin. Multivariable logistic regression analysis was employed to identify risk factors of guideline discordant margin and a predictive model was developed. Data from March 2023 to January 2024 were collected for internal validation. Results: A total of 530 patients were included. The incidence of guideline discordant wedge resection margin was 37.2%. Longer tumor's max distance to pleura and larger tumor size were variables associated with increased risk and included in the final model. Preoperative localization and right-side surgery were protective variables in the predictive model. A nomogram was built based on the predictive model. The model showed satisfying predictive performance with a concordance index of 0.720 for the predictive model, and 0.761 for internal validation. The goodness-if-fit tests were non-significant for both model development and internal validation data set. Conclusions: The preoperative predictive model and nomogram show good predictive performance to estimate the risk of guideline discordant wedge resection margin. Individualized surgical plans or preoperative nodule localization can be made for high-risk patients.

Development and external validation of a novel model for predicting new clinically important atrial fibrillation after thoracoscopic anatomical lung cancer surgery: a multicenter retrospective cohort study.

BACKGROUND: New clinically important postoperative atrial fibrillation (POAF) is the most common arrhythmia after thoracoscopic anatomical lung cancer surgery and is associated with increased morbidity and mortality. The full spectrum of predictors remains unclear, and effective assessment tools are lacking. This study aimed to develop and externally validate a novel model for predicting new clinically important POAF. METHODS: This retrospective study included 14 074 consecutive patients who received thoracoscopic anatomical lung cancer surgery from January 2016 to December 2018 in Shanghai Chest Hospital. Based on the split date of 1 January 2018, we selected 8717 participants for the training cohort and 5357 participants for the testing cohort. For external validation, we pooled 2941 consecutive patients who received this surgical treatment from July 2016 to July 2021 in Shanghai Ruijin Hospital. Independent predictors were used to develop a model and internally validated using a bootstrap-resampling approach. The area under the receiver operating characteristic curves (AUROCs) and Brier score were performed to assess the model discrimination and calibration. The decision curve analysis (DCA) was used to evaluate clinical validity and net benefit. New clinically important POAF was defined as a new-onset of POAF that causes symptoms or requires treatment. RESULTS: Multivariate analysis suggested that age, hypertension, preoperative treatment, clinical tumor stage, intraoperative arrhythmia and transfusion, and operative time were independent predictors of new clinically important POAF. These seven candidate predictors were used to develop a nomogram, which showed a concordance statistic (C-statistic) value of 0.740 and good calibration (Brier score; 0.025). Internal validation revealed similarly good discrimination (C-statistic, 0.736; 95% CI: 0.705-0.768) and calibration. The decision curve analysis showed positive net benefits with the threshold risk range of 0-100%. C-statistic value and Brier score were 0.717 and 0.028 in the testing cohort, and 0.768 and 0.012 in the external validation cohort, respectively. CONCLUSIONS: This study identified seven predictors of new clinically important POAF, among which preoperative treatment, intraoperative arrhythmia, and operative time were rarely reported. The established and externally validated model has good performance and clinical usefulness, which may promote the application of prevention and treatment in high-risk patients, and reduce the development and related adverse outcomes of this event.

Three-dimensional reconstruction computed tomography in thoracoscopic segmentectomy: a randomized controlled trial.

OBJECTIVES: Thoracoscopic segmentectomy is the recommended treatment option for small peripheral pulmonary nodules. To assess the ability of preoperative three-dimensional (3D) reconstruction computed tomography (CT) to shorten the operative time and improve perioperative outcomes in thoracoscopic segmentectomy compared with standard chest CT, we conducted this randomized controlled trial. METHODS: The DRIVATS study was a multicentre, randomized controlled trial conducted in 3 hospitals between July 2019 and November 2023. Patients with small peripheral pulmonary nodules not reaching segment borders were randomized in a 1:1 ratio to receive either 3D reconstruction CT or standard chest CT before thoracoscopic segmentectomy. The primary end-point was operative time. The secondary end-points included incidence of postoperative complications, intraoperative blood loss and operative accident event. RESULTS: A total of 191 patients were enrolled in this study: 95 in the 3D reconstruction CT group and 96 in the standard chest CT group. All patients underwent thoracoscopic segmentectomy except for 1 patient in the standard chest CT group who received a wedge resection. There is no significant difference in operative time between the 3D reconstruction CT group (median, 100 min [interquartile range (IQR), 85-120]) and the standard chest CT group (median, 100 min [IQR, 81-140]) (P = 0.82). Only 1 intraoperative complication occurred in the standard chest CT group. No significant difference was observed in the incidence of postoperative complications between the 2 groups (P = 0.52). Other perioperative outcomes were also similar. CONCLUSIONS: In patients with small peripheral pulmonary nodules not reaching segment borders, the use of 3D reconstruction CT in thoracoscopic segmentectomy was feasible, but it did not result in significant differences in operative time or perioperative outcomes compared to standard chest CT.

Lymph node metastasis in early invasive lung adenocarcinoma: Prediction model establishment and validation based on genomic profiling and clinicopathologic characteristics.

BACKGROUND: The presence of lymph node (LN) metastasis directly affects the treatment strategy for lung adenocarcinoma (LUAD). Next-generation sequencing (NGS) has been widely used in patients with advanced LUAD to identify targeted genes, while early detection of pathologic LN metastasis using NGS has not been assessed. METHODS: Clinicopathologic features and molecular characteristics of 224 patients from Ruijin Hospital were analyzed to detect factors associated with LN metastases. Another 140 patients from Huashan Hospital were set as a test cohort. RESULTS: Twenty-four out of 224 patients were found to have lymph node metastases (10.7%). Pathologic LN-positive tumors showed higher mutant allele tumor heterogeneity (p < 0.05), higher tumor mutation burden (p < 0.001), as well as more frequent KEAP1 (p = 0.001), STK11 (p = 0.004), KRAS (p = 0.007), CTNNB1 (p = 0.017), TP53, and ARID2 mutations (both p = 0.02); whereas low frequency of EGFR mutation (p = 0.005). A predictive nomogram involving male sex, solid tumor morphology, higher T stage, EGFR wild-type, and TP53, STK11, CDKN2A, KEAP1, ARID2, KRAS, SDHA, SPEN, CTNNB1, DICER1 mutations showed outstanding efficiency in both the training cohort (AUC = 0.819) and the test cohort (AUC = 0.780). CONCLUSION: This study suggests that the integration of genomic profiling and clinical features identifies early-invasive LUAD patients at higher risk of LN metastasis. Improved identification of LN metastasis is beneficial for the optimization of the patient's therapy decisions.

A risk score combining co-expression modules related to myeloid cells and alternative splicing associates with response to PD-1/PD-L1 blockade in non-small cell lung cancer.

Background: Comprehensive analysis of transcriptomic profiles of non-small cell lung cancer (NSCLC) may provide novel evidence for biomarkers associated with response to PD-1/PD-L1 immune checkpoint blockade (ICB). Methods: We utilized weighted gene co-expression network analysis (WGCNA) to analyze transcriptomic data from two NSCLC datasets from Gene Expression Omnibus (GSE135222 and GSE126044) that involved patients received ICB treatment. We evaluated the correlation of co-expression modules with ICB responsiveness and functionally annotated ICB-related modules using pathway enrichment analysis, single-cell RNA sequencing, flow cytometry and alternative splicing analysis. We built a risk score using Lasso-COX regression based on hub genes from ICB-related modules. We investigated the alteration of tumor microenvironment between high- and low- risk groups and the association of the risk score with previously established predictive biomarkers. Results: Our results identified a black with positive correlation and a blue module with negative correlation to ICB responsiveness. The black module was enriched in pathway of T cell activation and antigen processing and presentation, and the genes assigned to it were consistently expressed on myeloid cells. We observed decreased alternative splicing events in samples with high signature scores of the blue module. The Lasso-COX analysis screened out three genes (EVI2B, DHX9, HNRNPM) and constructed a risk score from the hub genes of the two modules. We validated the predictive value of the risk score for poor response to ICB therapy in an in-house NSCLC cohort and a pan-cancer cohort from the KM-plotter database. The low-risk group had more immune-infiltrated microenvironment, with higher frequencies of precursor exhausted CD8+ T cells, tissue-resident CD8+ T cells, plasmacytoid dendritic cells and type 1 conventional dendritic cells, and a lower frequency of terminal exhausted CD8+ T cells, which may explain its superior response to ICB therapy. The significant correlation of the risk score to gene signature of tertiary lymphoid structure also implicated the possible mechanism of this predictive biomarker. Conclusions: Our study identified two co-expression modules related to ICB responsiveness in NSCLC and developed a risk score accordingly, which could potentially serve as a predictive biomarker for ICB response.

Health-Related Quality of Life Following Robotic-Assisted or Video-Assisted Lobectomy in Patients With Non-Small Cell Lung Cancer: Results From the RVlob Randomized Clinical Trial.

BACKGROUND: Robot-assisted lobectomy (RAL) is increasingly used as an alternative to video-assisted lobectomy (VAL) for resectable non-small cell lung cancer (NSCLC). However, there is little evidence of any difference in postoperative health-related quality of life (HRQoL) between these two approaches. RESEARCH QUESTION: Is RAL superior to VAL in improving quality of life in patients with resectable NSCLC? STUDY DESIGN AND METHODS: We performed a single-center, open-label randomized clinical trial from May 2017 to May 2020 with 320 enrolled patients undergoing RAL or VAL for resectable NSCLC (RVlob trial; NCT03134534). Postoperative pain was evaluated by visual analog score or numeric rating score on postoperative day 1 and at weeks 4, 24, and 48. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire in Lung Cancer (QLQ-LC13), and the European Quality of Life 5 Dimensions (EQ-5D) questionnaire were also administered at weeks 4, 24, and 48 after surgery. RESULTS: One hundred and fifty-seven patients underwent RAL and 163 underwent VAL. The mean pain score of patients after RAL was significantly lower at week 4 (2.097 ± 0.111 vs 2.431 ± 0.108; P = .032). QLQ-C30 and QLQ-LC13 summary scores (P > .05) were similar for both RAL and VAL during the first 48 weeks of follow-up. HRQoL scores assessed with the EQ-5D questionnaire were also comparable between the two groups (P > .05) during the whole study period. INTERPRETATION: Both RAL and VAL showed satisfactory and comparable HRQoL and postoperative pain up to 48 weeks after surgery, despite some minor statistical differences at week 4. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03134534; URL: www. CLINICALTRIALS: gov.

Intraoperative Identification of the Intersegmental Plane: From the Beginning to the Future.

Segmentectomy has played a crucial role in the treatment of early-stage lung cancer after the publication of JCOG0802, which indicated that patients with small-sized peripheral non-small-cell lung cancer could receive better survival from segmentectomy than lobectomy despite a higher local recurrence. The intraoperative identification of the intersegmental plane ensures complete resection of the lesion with sufficient margin so that it is deemed as the critical part of segmentectomy. Diverse methods have been developed to acquire distinguishable and lasting borderline between segments, but none of them is proved perfect. In this review, we searched and classified these techniques that emerged from the beginning when segmentectomy was used for bronchiectasis until now. Comparisons between different ways in mechanisms, facility, and safety were made to depict a comprehensive landscape for surgeons to select fit one. Furthermore, we presented our vision for the future of intersegmental plane identification.

Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials.

Lung cancer is the leading cause of cancer-related death across the world. Unlike lung adenocarcinoma, patients with lung squamous cell carcinoma (LSCC) have not benefitted from targeted therapies. Although immunotherapy has significantly improved cancer patients' outcomes, the relatively low response rate and severe adverse events hinder the clinical application of this promising treatment in LSCC. Therefore, it is of vital importance to have a better understanding of the mechanisms underlying the pathogenesis of LSCC as well as the inner connection among different signaling pathways, which will surely provide opportunities for more effective therapeutic interventions for LSCC. In this review, new insights were given about classical signaling pathways which have been proved in other cancer types but not in LSCC, including PI3K signaling pathway, VEGF/VEGFR signaling, and CDK4/6 pathway. Other signaling pathways which may have therapeutic potentials in LSCC were also discussed, including the FGFR1 pathway, EGFR pathway, and KEAP1/NRF2 pathway. Next, chromosome 3q, which harbors two key squamous differentiation markers SOX2 and TP63 is discussed as well as its related potential therapeutic targets. We also provided some progress of LSCC in epigenetic therapies and immune checkpoints blockade (ICB) therapies. Subsequently, we outlined some combination strategies of ICB therapies and other targeted therapies. Finally, prospects and challenges were given related to the exploration and application of novel therapeutic strategies for LSCC.

Management of middle lobe veins during single-portal video-assisted thoracoscopic surgery lobectomy via the fifth intercostal approach (case series): why the subcarinal triangular right base angle is helpful.

Background: The fifth intercostal space is the preferred approach during uniportal video-assisted thoracoscopic surgery (VATS) lobectomy. However, managing the right middle lobe pulmonary vein (RML PV) through this approach is technically challenging for inexperienced surgeons. To facilitate the surgical procedure, we describe our surgical strategy for managing the middle lobe vein via the fifth intercostal space and define the approach [subcarinal triangular right base angle (SCT-RBA)] utilized to manage the middle lobe vein. Case Description: Based on the characteristics of uniportal surgery, we designed a new method of managing middle lobar veins via the fifth intercostal approach, which also facilitates the dissection of the subcarinal lymph nodes. We described the short-term surgical outcomes of 7 patients who underwent single-port middle lobe resection from January 2021 to January 2022 in the Department of Thoracic Surgery, Ruijin Hospital North Campus, Shanghai Jiaotong University School of Medicine. No conversion and mortality were observed in 7 patients who underwent single-port VATS middle lobe resection. One patient had bronchial asthma and air leakage, which led to delayed drainage and hospitalization. There were no complications or delayed discharge reported among the other patients. Conclusions: Our initial results indicate that this new technique is a feasible strategy to manage the middle lobe veins and facilitate the dissection of subcarinal lymph nodes.

Three-dimensional computed tomography reconstruction in video-assisted thoracoscopic segmentectomy (DRIVATS): A prospective, multicenter randomized controlled trial.

Objective: Anatomical segmentectomy has been proven to be a viable surgical treatment for small-size peripheral lung nodules. Three-dimensional (3D) reconstruction computed tomography (CT) has been proposed as an effective approach to overcome the challenges of encountering pulmonary anatomical variations when performing segmentectomy. Therefore, to further investigate the usefulness of preoperative 3D reconstruction CT in segmentectomy, we will conduct this prospective, multicenter randomized controlled DRIVATS study to compare the use of 3D reconstruction CT with standard chest CT in video-assisted segmentectomy (ClinicalTrials.gov ID: NCT04004494). Methods: This study began in July 2019 and a total of 190 patients will be accrued from three clinical centers within 4 years. The main inclusion criteria are patients with a single peripheral nodule 0.8-2 cm with at least one of the following requirements: (i) histology of adenocarcinoma in situ; (ii) nodule has ≥50% ground-glass appearance on CT; (iii) radiologic surveillance confirms a long doubling time (≥400 days). Surgical procedures include segmental resection of the lesion and mediastinal lymph node sampling (subsegmental resection or combined subsegmental resection will not be included in this study). The primary endpoint is operative time. The secondary endpoints include incidence of change of surgical plan, intraoperative blood loss, conversion rate, operative accident event, incidence of postoperative complications, postoperative hospital stay, length of hospitalization, duration of chest tube placement, postoperative 30-day mortality, dissection of lymph nodes, overall survival, disease-free survival, preoperative lung function, and postoperative lung function. Discussion: This multicenter DRIVATS study aims to verify the usefulness of preoperative 3D reconstruction CT compared with standard chest CT in segmentectomy. If successfully completed, this multicenter prospective study will provide a higher level of evidence for the use of 3D reconstruction CT in segmentectomy.

Long-term and short-term outcomes of robot- versus video-assisted anatomic lung resection in lung cancer: a systematic review and meta-analysis.

OBJECTIVES: Minimally invasive thoracic surgery has evolved with the introduction of robotic platforms. This study aimed to compare the long-term and short-term outcomes of the robot-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) for anatomic lung resection. METHODS: We searched published studies that investigated RATS and VATS in anatomic lung resection. Long-term outcomes (disease-free survival and overall survival) and short-term outcomes (30-day mortality, postoperative complications, conversion rate to open surgery and lymph node upstaging) were extracted. The features were compared and tested as hazard ratios (HRs) and odds ratios (ORs) at a 95% confidence interval (CI). RESULTS: Twenty-five studies with 50 404 patients (7135 for RATS and 43 269 for VATS) were included. The RATS group had a longer disease-free survival than the VATS group (HR: 0.76; 95% CI: 0.59-0.97; P = 0.03), and the overall survival showed a similar trend but was not statistically significant (HR: 0.77; 95% CI: 0.57-1.05; P = 0.10). The RATS group showed a significantly lower 30-day mortality (OR: 0.55; 95% CI: 0.38-0.81; P = 0.002). No significant difference was found in postoperative complications (OR: 1.01; 95% CI: 0.87-1.16; P = 0.94), the conversion rate to open surgery (OR: 0.92; 95% CI: 0.56-1.52; P = 0.75) and lymph node upstaging (OR: 0.89; 95% CI: 0.52-1.54; P = 0.68). CONCLUSIONS: RATS has comparable short-term outcomes and potential long-term survival benefits for anatomic lung resection compared with VATS.

A nomogram for preoperative prediction of prolonged air leak after pulmonary malignancy resection.

BACKGROUND: Prolonged air leak (PAL) is one of the most common postoperative complications after lung surgery. This study aimed to identify risk factors of PAL after lung resection and develop a preoperative predictive model to estimate its risk for individual patients. METHODS: Patients with pulmonary malignancies or metastasis who underwent pulmonary resection between January 2014 and January 2018 were included. PAL was defined as an air leak more than 5 days after surgery, risk factors were analyzed. Forward stepwise multivariable logistic regression analysis was performed to identify independent risk factors, and a derived nomogram was built. Data from February 2018 to September 2018 were collected for internal validation. RESULTS: A total of 1,511 patients who met study criteria were enrolled in this study. The overall incidence of PAL was 9.07% (137/1,511). Age, percent forced expiratory volume in 1 second, surgical type, surgical approach and smoking history were included in the final model. A nomogram was developed according to the multivariable logistic regression results. The C-index of the predictive model was 0.70, and the internal validation value was 0.77. The goodness-of-fit test was non-significant for model development and internal validation. CONCLUSIONS: The predictive model and derived nomogram achieved satisfied preoperative prediction of PAL. Using this nomogram, the risk for an individual patient can be estimated, and preventive measures can be applied to high-risk patients.