Ligand recognition and G-protein coupling of trace amine receptor TAAR1.

Trace-amine-associated receptors (TAARs), a group of biogenic amine receptors, have essential roles in neurological and metabolic homeostasis1. They recognize diverse endogenous trace amines and subsequently activate a range of G-protein-subtype signalling pathways2,3. Notably, TAAR1 has emerged as a promising therapeutic target for treating psychiatric disorders4,5. However, the molecular mechanisms underlying its ability to recognize different ligands remain largely unclear. Here we present nine cryo-electron microscopy structures, with eight showing human and mouse TAAR1 in a complex with an array of ligands, including the endogenous 3-iodothyronamine, two antipsychotic agents, the psychoactive drug amphetamine and two identified catecholamine agonists, and one showing 5-HT1AR in a complex with an antipsychotic agent. These structures reveal a rigid consensus binding motif in TAAR1 that binds to endogenous trace amine stimuli and two extended binding pockets that accommodate diverse chemotypes. Combined with mutational analysis, functional assays and molecular dynamic simulations, we elucidate the structural basis of drug polypharmacology and identify the species-specific differences between human and mouse TAAR1. Our study provides insights into the mechanism of ligand recognition and G-protein selectivity by TAAR1, which may help in the discovery of ligands or therapeutic strategies for neurological and metabolic disorders.

Plasma proteometabolome in lung cancer: exploring biomarkers through bidirectional Mendelian randomization and colocalization analysis.

Unlike other cancers with widespread screening (breast, colorectal, cervical, prostate, and skin), lung nodule biopsies for positive screenings have higher morbidity with clinical complications. Development of non-invasive diagnostic biomarkers could thereby significantly enhance lung cancer management for at-risk patients. Here, we leverage Mendelian Randomization (MR) to investigate the plasma proteome and metabolome for potential biomarkers relevant to lung cancer. Utilizing bidirectional MR and co-localization analyses, we identify novel associations, highlighting inverse relationships between plasma proteins SFTPB and KDELC2 in lung adenocarcinoma (LUAD) and positive associations of TCL1A with lung squamous cell carcinoma (LUSC) and CNTN1 with small cell lung cancer (SCLC). Additionally, our work reveals significant negative correlations between metabolites such as theobromine and paraxanthine, along with paraxanthine-related ratios, in both LUAD and LUSC. Conversely, positive correlations are found in caffeine/paraxanthine and arachidonate (20:4n6)/paraxanthine ratios with these cancer types. Through single-cell sequencing data of normal lung tissue, we further explore the role of lung tissue-specific protein SFTPB in carcinogenesis. These findings offer new insights into lung cancer etiology, potentially guiding the development of diagnostic biomarkers and therapeutic approaches.

Genetic perturbation of IL-6 receptor signaling pathway and risk of multiple respiratory diseases.

Dysregulation of inflammation can lead to multiple chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Interleukin-6 (IL6) is crucial in regulating the inflammatory cascade, but the causal link between IL6 signaling downregulation and respiratory diseases risk is unclear. This study uses Mendelian randomization to examine the effects of IL6R blockade on respiratory diseases. Analyzing data from 522,681 Europeans, 26 genetic variants were obtained to mimic IL6R inhibition. Our findings show that IL6R blockade significantly reduces the risk of COPD (OR = 0.71, 95% CI = 0.60-9.84) and asthma (OR = 0.82, 95% CI = 0.74-0.90), with protective trends for bronchitis, pulmonary embolism, and lung cancer. Results were consistent across methods, with no significant heterogeneity or pleiotropy. These insights suggest IL6R downregulation as a potential therapeutic target for respiratory diseases, meriting further clinical investigation.

Trackplot: A flexible toolkit for combinatorial analysis of genomic data.

Here, we introduce Trackplot, a Python package for generating publication-quality visualization by a programmable and interactive web-based approach. Compared to the existing versions of programs generating sashimi plots, Trackplot offers a versatile platform for visually interpreting genomic data from a wide variety of sources, including gene annotation with functional domain mapping, isoform expression, isoform structures identified by scRNA-seq and long-read sequencing, as well as chromatin accessibility and architecture without any preprocessing, and also offers a broad degree of flexibility for formats of output files that satisfy the requirements of major journals. The Trackplot package is an open-source software which is freely available on Bioconda (https://anaconda.org/bioconda/trackplot), Docker (https://hub.docker.com/r/ygidtu/trackplot), PyPI (https://pypi.org/project/trackplot/) and GitHub (https://github.com/ygidtu/trackplot), and a built-in web server for local deployment is also provided.

Differential expression profiles and functional prediction of circular RNAs in lung cancer patients with chronic obstructive pulmonary disease: a pilot study.

Chronic obstructive pulmonary disease (COPD), characterized by clinical sub-phenotypes such as emphysema (E) and chronic bronchitis (CB), is associated with a greater risk of lung cancer (LC). This study aimed to assess the expression patterns of circRNA and their potential functional involvement in LC patients with COPD. A circRNA microarray was used to characterize differentially expressed circRNAs (DEcircRNAs) profiles. A total of 176, 240, 163, and 243 DEcircRNAs were identified in comparisons between CB vs. LC patients (Con), E vs. Con, E vs. CB, and CBE vs. Con, respectively. DEcircRNAs in all comparison groups were primarily associated with immune-related GO terms and were also enriched in immune and inflammatory pathways. In total, 49 DEcircRNAs were significantly correlated with the infiltration of multiple immune cells. Among them, hsa-MROH9_0001 and hsa-RP11-35J10_0013 were positively and negatively correlated with plasma cells and T-cell CD4 memory resting cells, respectively; these two DEcircRNA-sponged miRNAs have good diagnostic performance. WGCNA identified six key circRNAs associated with CB progression. The expression patterns of hsa-MROH9_0001 and circRNA_21729 in E and CB groups were confirmed by RT-qPCR. In conclusion, we reported circRNA profiles and the findings demonstrated that hsa-MROH9_0001 and circRNA_21729 may be potential therapeutic targets for LC with COPD.

Perioperative outcomes of uniportal versus three-port video-assisted thoracoscopic surgery in lung cancer patients aged ≥ 75 years old: a cohort study.

BACKGROUND: Increasing attention has been raised on the surgical option for lung cancer patients aged ≥75 years, however, few studies have focused on whether uniportal video-assisted thoracoscopic surgery (VATS) is safe and feasible for these patients. This study aimed to evaluate short-term results of uniportal versus three-port VATS for the treatment of lung cancer patients aged ≥75 years. METHODS: We retrospectively evaluated 582 lung cancer patients (≥75 years) who underwent uniportal or three-port VATS from August 2007 to August 2021 based on the Western China Lung Cancer Database. The baseline and perioperative outcomes between uniportal and three-port VATS were compared in the whole cohort (WC) and the patients undergoing lobectomy (lobectomy cohort, LC) respectively. Propensity score matching (PSM) was used to minimize confounding bias between the uniportal and three-port cohorts in WC and LC. RESULTS: Intraoperative blood loss was significantly less in the uniportal than three-port LC (50 mL vs. 83 mL, P = 0.007) before PSM and relatively less in the uniportal than three-port LC (50 mL vs. 83 mL, P = 0.05) after PSM. Significantly more lymph nodes harvested (13 vs. 9, P = 0.007) were found in the uniportal than three-port LC after PSM. In addition, in WC and LC, there were no significant differences between uniportal and three-port cohorts in terms of operation time, the rate of conversion to thoracotomy during surgery, nodal treatments (dissection or sampling or not), the overall number of lymph node stations dissected, postoperative complications, volume and duration of postoperative thoracic drainage, hospital stay after operation and hospitalization expenses before and after PSM (P > 0.05). CONCLUSIONS: There were no significant differences in short-term outcomes between uniportal and three-port VATS for lung cancer patients (≥75 years), except relatively less intraoperative blood loss (P < 0.05 before PSM and P = 0.05 after PSM) and significantly more lymph nodes harvested (P < 0.05 after PSM) were found in uniportal LC. It is reasonable to indicate that uniportal VATS is a safe, feasible and effective operation procedure for lung cancer patients aged ≥75 years.

LncAS2Cancer: a comprehensive database for alternative splicing of lncRNAs across human cancers.

Accumulating studies demonstrated that the roles of lncRNAs for tumorigenesis were isoform-dependent and their aberrant splicing patterns in cancers contributed to function specificity. However, there is no existing database focusing on cancer-related alternative splicing of lncRNAs. Here, we developed a comprehensive database called LncAS2Cancer, which collected 5335 bulk RNA sequencing and 1826 single-cell RNA sequencing samples, covering over 30 cancer types. By applying six state-of-the-art splicing algorithms, 50 859 alternative splicing events for 8 splicing types were identified and deposited in the database. In addition, the database contained the following information: (i) splicing patterns of lncRNAs under seven different conditions, such as gene interference, which facilitated to infer potential regulators; (ii) annotation information derived from eight sources and manual curation, to understand the functional impact of affected sequences; (iii) survival analysis to explore potential biomarkers; as well as (iv) a suite of tools to browse, search, visualize and download interesting information. LncAS2Cancer could not only confirm the known cancer-associated lncRNA isoforms but also indicate novel ones. Using the data deposited in LncAS2Cancer, we compared gene model and transcript overlap between lncRNAs and protein-coding genes and discusses how these factors, along with sequencing depth, affected the interpretation of splicing signals. Based on recurrent signals and potential confounders, we proposed a reliable score to prioritize splicing events for further elucidation. Together, with the broad collection of lncRNA splicing patterns and annotation, LncAS2Cancer will provide important new insights into the diverse functional roles of lncRNA isoforms in human cancers. LncAS2Cancer is freely available at https://lncrna2as.cd120.com/.

A Competing Risk Model Nomogram to Predict the Long-Term Prognosis of Lung Carcinoid.

BACKGROUND: The prediction of long-term, cancer-specific survival of lung carcinoid remains controversial. We aimed to build a prognostic model by using competing-risk analysis to predict the long-term, cancer-specific survival of lung carcinoid patients. METHODS: Patients were retrospectively enrolled from the SEER database, and clinicopathological data were collected. Univariable and multivariable competing-risk analyses were conducted to identify prognostic factors. A competing-risk model and a nomogram were developed by using independent prognostic factors. The model was assessed by using concordance index and calibration curves. RESULTS: A total of 2496 patients were enrolled, of which 267 (10.7%) died of diagnosed carcinoma; 316 (12.7%) died because of other reasons. The 5-year, 10-year, and 15-year cancer-specific survival of carcinoid patients were 91.35%, 86.60%, and 84.39%, respectively. Multivariable analysis demonstrated that increasing age, male, larger tumor size, higher N stage, M1, atypical carcinoid, and undergoing no surgery were independent risk factors. A competing-risk model based on the risk factors and a corresponding nomogram were developed. Concordance index of the developed model for 5-year, 10-year, and 15-year were 0.891, 0.856, 0.836 respectively in the training cohort and 0.876, 0.841, 0.819 respectively in the validation cohort after bootstrap adjustment. The calibration curves of 5-year, 10-year, and 15-year showed good agreement. CONCLUSIONS: Increasing age, male, larger tumor size, higher N stage, M1, atypical carcinoid, and undergoing no surgery were independent risk factors. A competing risk model of excellent performance in predicting long-term survival was developed, and a nomogram was established.

Metformin attenuates chronic lung allograft dysfunction: evidence in rat models.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) directly causes an abysmal long-term prognosis after lung transplantation (LTx), but effective and safe drugs are not available. Metformin exhibits high therapeutic potential due to its antifibrotic and immunomodulatory effects; however, it is unclear whether metformin exerts a therapeutic effect in CLAD. We sought to investigate the effect of metformin on CLAD based on rat models. METHODS: Allogeneic LTx rats were treated with Cyclosporin A (CsA) in the first week, followed by metformin, CsA, or vehicle treatment. Syngeneic LTx rats received only vehicles. All rats were sacrificed on post-transplant week 4. Pathology of lung graft, spleen, and thymus, extent of lung fibrosis, activity of profibrotic cytokines and signaling pathway, adaptive immunity, and AMPK activity were then studied. RESULTS: Allogeneic recipients without maintenance CsA treatment manifested CLAD pathological characteristics, but these changes were not observed in rats treated with metformin. For the antifibrotic effect, metformin suppressed the fibrosis extent and profibrotic cytokine expression in lung grafts. Regarding immunomodulatory effect, metformin reduced T- and B-cell infiltration in lung grafts, spleen and thymus weights, the T- and B-cell zone areas in the spleen, and the thymic medullary area. In addition, metformin activated AMPK in lung allografts and in α-SMA+ cells and T cells in the lung grafts. CONCLUSIONS: Metformin attenuates CLAD in rat models, which could be attributed to the antifibrotic and immunomodulatory effects. AMPK activation suggests the potential molecular mechanism. Our study provides an experimental rationale for further clinical trials.

[MinerVa: A high performance bioinformatic algorithm for the detection of minimal residual disease in solid tumors].

How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 -5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.

CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma.

BACKGROUND: Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it's role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. METHODS: In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. RESULTS: As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05). CONCLUSION: In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma.

Uniportal Thoracoscopic Single-Direction Basal Subsegmentectomy (Left S10a+ci): Trans-Inferior-Pulmonary-Ligament Approach.

Thoracoscopic segmentectomy and subsegmentectomy have been widely accepted for the treatment of peripheral small lung cancers. Thoracoscopic basal subsegmentectomy, especially when performed through a uniportal procedure, is extremely technically challenging, and therefore there are seldom reports of its technical details. In this article, we present a uniportal thoracoscopic left S10a+ci subsegmentectomy following the single-direction strategy through the inferior pulmonary ligament approach.

A Comprehensive Comparison of Different Nodal Subclassification Methods in Surgically Resected Non-Small-Cell Lung Cancer Patients.

INTRODUCTION: The revision of the N descriptor in non-small-cell lung cancer has been widely discussed in the past few years. Many different subclassification methods based on number or location of lymph nodes have been proposed for better distinguishing different N patients. This study aimed to systematically collect them and provide a comprehensive comparison among different subclassification methods in a large cohort. METHOD: Pathological N1 or N2 non-small-cell lung cancer patients undergoing surgical resection between 2005 and 2016 in the Western China Lung Cancer Database were retrospectively reviewed. A literature review was conducted to collect previous subclassification methods. Kaplan-Meier and multivariable Cox analyses were used to examine the prognostic performance of subclassification methods. Decision curve analysis, Akaike's information criterion, and area under the receiver operating curve concordance were also performed to evaluate the standardized net benefit of the subclassification methods. RESULTS: A total of 1625 patients were identified in our cohort. Eight subclassification methods were collected from previous articles and further grouped into subclassification based on number categories (node number or station number), location categories (lymph node zone or chain) or combination of number and location categories. Subclassification based on combination of lymph node location and number tended to have better discrimination ability in multivariable Cox analysis. No significant superiority among the different subclassification methods was observed in the three statistical models. CONCLUSION: Subclassification based on the combination of location and number could be used to provide a more accurate prognostic stratification in surgically resected NSCLC and is worth further validation.

Clinicopathological characteristics and prognosis of resectable lung adenosquamous carcinoma: a population-based study of the SEER database.

OBJECTIVE: Adenosquamous carcinoma is a rare subtype of non-small cell lung cancer characterized by aggressive behavior, with combination of adenocarcinoma and squamous cell carcinoma components. The clinicopathological characteristics and prognosis of resectable adenosquamous carcinoma are incompletely understood and this study aimed to depict those in a large population. METHODS: A total of 805 adenosquamous carcinoma, 7875 squamous cell carcinoma and 23 957 adenocarcinoma patients who underwent lobectomy or sublobectomy were queried from the Surveillance, Epidemiology, and End Results database (2010-17). Clinicopathological characteristics of adenosquamous carcinoma patients were compared with those of squamous cell carcinoma and adenocarcinoma patients. Prognostic factors were identified by univariable and multivariable Cox regression analyses. Propensity score matching was applied to reduce confounding effects. RESULTS: Adenosquamous carcinoma was associated with higher pleural invasion incidence and poorer differentiation compared with squamous cell carcinoma or adenocarcinoma (P values < 0.001). The independent risk factors of cancer-specific survival of adenosquamous carcinoma patients were increasing age, male sex, invading through visceral pleura, poor differentiation and higher stage. Stage IB adenosquamous carcinoma patients whose tumor invaded through visceral pleura had significantly worse survival than those not (P = 0.003). Adenosquamous carcinoma patients had worse survival compared with squamous cell carcinoma (5-year-survival: 64.55 vs. 69.09%, P = 0.003) and adenocarcinoma (5-year-survival: 64.55 vs. 76.79%, P < 0.001) patients before match. And this difference persisted after match. CONCLUSIONS: Resectable adenosquamous carcinoma patients had higher pleural invasion incidence, poorer differentiation and worse survival compared with squamous cell carcinoma and adenocarcinoma patients. Visceral pleural invasion status and differentiation grade were vital prognostic factors of adenosquamous carcinoma patients on the basis of stage.

A new basic thoracoscopic surgical skill training and assessment system using automatic scoring techniques.

PURPOSE: We report a new thoracoscopic surgical skill training and assessment system with automatic scoring techniques, the Huaxi Intelligent Thoracoscopic Skill Training and Assessment (HITSTA) system. We also evaluated the discriminative ability of this system compared to our conventional scoring method at our institution. METHODS: We retrospectively collected training data of thoracic board-certified thoracic surgeons at West China Hospital, Sichuan University from January 1, 2018 to January 1, 2019. Surgeons were assessed by HITSTA system and human examiners simultaneously. Total scores were summed from 3 tasks (grasping with delivery, pattern cutting, and suture with knot). Bland-Altman analysis was used to test agreement of scores made by HITSTA system (automatic scoring) and human examiners (manual scoring). Differentiation ability was also compared between the two scoring methods. RESULTS: Thirty-nine surgeons were recruited. Scores made by HITSTA system and human examiners were not consistent. For suture with knot, automatic scoring method could detect the score differences between different training status (trained: 26.92 ± 12.04, untrained: 19.85 ± 11.12; p = 0.026) and training duration (< 10 h: 20.67 ± 15.23, ≥ 10 h: 31.92 ± 5.56; p = 0.003). For total scores, automatic scoring approach could discriminate between different training status (trained: 71.90 ± 12.63; untrained: 61.41 ± 13.87; p = 0.016) and training duration (< 10 h: 65.23 ± 15.31; ≥ 10 h 77.23 ± 6.94; p = 0.046). CONCLUSION: HITSTA system could discriminate the different levels of thoracoscopic surgical skills better than the traditional manual scoring method. Larger prospective studies are warranted to validate the differentiation ability of HITSTA system.

Clinical Significance of Station 3A Lymph Node Dissection in Patients with Right-Side Non-Small-Cell Lung Cancer: A Retrospective Propensity-Matched Analysis.

PURPOSE: To investigate the prognostic impact of station 3A lymph node (LN) dissection in patients with right-side non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We retrospectively reviewed data of 1906 patients with primary right-side NSCLC who underwent lobectomy between January 2005 and December 2017 (570 patients underwent station 3A LN dissection and 1336 patients did not). Propensity score matching was conducted to minimize the effects of potential confounding factors. Disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: The metastasis rate of station 3A LN was 15.3% (87/570), which was second only to station 4 (17.3%). Only stations 10 and 11 LN metastases were found to be independent risk factors for station 3A LN metastasis (odds ratio = 19.43, 95% CI 1.21-311.12; P = 0.036 and odds ratio = 53.28, 95% CI 2.02-1404.90; P = 0.016, respectively). After propensity score matching, patients with dissection of station 3A LNs showed higher DFS (5-year DFS, 52.4% vs. 37.1%; P = 0.001) and OS (5-year OS, 58.8% vs. 48.7%; P = 0.007) than those without dissection. Subgroup analysis indicated that station 3A LN dissection was associated with significantly higher DFS and OS in patients with stage II and III disease. In multivariate survival analysis, dissection of 3A LNs retained its independent favorable effect on both DFS (hazard ratio = 0.76, 95% CI 0.64-0.90; P = 0.001) and OS (hazard ratio = 0.73, 95% CI 0.60-0.88; P = 0.001). CONCLUSION: Station 3A LN involvement was not rare and station 3A LN dissection was associated with a more favorable prognosis in patients with right-side NSCLC.

Uniportal Single-Direction Thoracoscopic Right S9 Segmentectomy: Trans-Inferior-Pulmonary-Ligament Approach.

BACKGROUND: We previously described a three-port single-direction thoracoscopic segmentectomy for the right S9, which is the most challenging anatomic segmentectomy. However, uniportal thoracoscopic surgery has been widely accepted for the therapy of early stage non-small cell lung cancer in the past decade. METHODS: In this multimedia article, we describe a uniportal thoracoscopic right S9 segmentectomy through an inferior pulmonary ligament approach following a single-direction strategy and using the stem-branch method for segmental structure tracking. RESULTS: The operation went successfully and the patient recovered smoothly. CONCLUSIONS: By taking advantage of the stem-branch method, trans-inferior-pulmonary-ligament approach, and single-direction strategy, the uniportal thoracoscopic S9 segmentectomy can be performed successfully through optimization of some technical details.

Primary Mediastinal Nonseminomas: A Population-Based Surveillance, Epidemiology, and End Results Analysis.

BACKGROUND: This study aimed to determine the disease characteristics and prognosis of patients with primary mediastinal nonseminomas (PMNS) in a Surveillance, Epidemiology, and End Results (SEER) analysis. MATERIALS AND METHODS: Demographic, treatment, and survival outcome data of cases with PMNS from 1975 to 2016 were retrieved. Cases with unknown variables mentioned in the analysis were excluded. Relative statistical methods were applied to analyze clinical characteristics and prognosis. RESULTS: A total of 587 PMNS patients met the selection criteria, 526 of whom were men. The mean age of patients was 28 (1-85) y. A total of 511 PMNS patients had validated subtypes, including 172 mixed germ cell tumors, 117 yolk sac tumors, 111 malignant teratomas, 70 choriocarcinomas, and 41 embryonal carcinomas. Patients with yolk sac tumors had the highest 3-y cancer-specific survival (CSS) rate (66.9%), while those with choriocarcinoma and embryonal carcinoma showed the worst prognosis. Surgery + chemotherapy (46.2%) was the most common and effective treatment for each subtype of PMNS. Multivariate Cox proportional hazards analysis identified embryonal carcinoma, malignant teratoma, choriocarcinoma, tumor size >15 cm, nodal metastasis, and distant stage as risk factors. In contrast, surgery-based care and younger age were protective factors. Propensity score matching analysis revealed significant improvement in the 5-y CSS rate from 35.8% to 60.3% with surgery (P < 0.001). However, radiotherapy (P = 0.436) and chemotherapy (P = 0.978) showed no survival benefits. CONCLUSIONS: 10 percent of the PMNS patients were female. Choriocarcinomas and embryonal carcinomas had the worst prognosis. Surgery was demonstrated to be the only way to prolong survival time. Chemotherapy and radiotherapy had minimal effects on prognosis.

Naples Prognostic Score as a novel prognostic prediction tool in video-assisted thoracoscopic surgery for early-stage lung cancer: a propensity score matching study.

BACKGROUNDS: The Naples Prognostic Score (NPS) emerges as a novel prognostic scoring system in surgical oncology. We aim to assess the prognostic significance of preoperative NPS in patients undergoing completely video-assisted thoracoscopic surgery (VATS) lobectomy for early-stage non-small cell lung cancer (NSCLC) by propensity score matching (PSM) analysis. METHODS: The present study was conducted on our single-center prospectively maintained database between January 2014 and December 2015. A Kaplan-Meier survival analysis using the log-rank test was used to distinguish differences in both overall survival (OS) and disease-free survival (DFS) between the patients stratified by preoperative NPS. Finally, multivariable Cox-proportional hazards regression analysis and PSM analysis were carried out to determine the independent prognostic factors for both OS and DFS. RESULTS: There were 457 patients with operable primary stage I-II NSCLC included. Per 1-point increase in NPS was found to be significantly associated with unfavorable OS and DFS of NSCLC. Both OS and DFS were significantly shortened along with each number increase in the NPS group, showing a step-wise fashion. Such strong correlations between preoperative NPS and survival outcomes still remained validated after PSM analysis. In addition, NPS held the best discriminatory power for predicting both OS and DFS when compared to the other peripheral biomarkers. Multivariable analyses on the entire cohort and the PSM cohort demonstrated that preoperative NPS could be an independent prognostic indicator for both OS and DFS. CONCLUSIONS: The NPS scoring system can serve as a novel risk stratification tool to refine prognostic prediction after VATS lobectomy for surgically resected NSCLC.

Results of video-assisted thoracic surgery versus thoracotomy in surgical resection of pN2 non-small cell lung cancer in a Chinese high-volume Center.

PURPOSE: To investigate the short-term outcomes and long-term oncological efficacy of video-assisted thoracic surgery (VATS) for surgical treatment of pN2 non-small cell lung cancer (NSCLC) compared with open thoracotomy (OT). PATIENTS AND METHODS: We retrospectively collected data from 1034 patients who underwent pulmonary resection and systemic lymph node dissection for pathological N2 NSCLC from September 2005 to December 2017 (536 patients in VATS group and 498 patients in OT group). Propensity score matching was applied to reduce the confounding effects. Factors affecting survival were assessed by Kaplan-Meier estimates and Cox regression analysis. RESULTS: The VATS procedure was associated with shorter operative time compared with the OT procedure (147.96 ± 58.91 min vs. 165.34 ± 58.91 min, P < 0.001). No significant difference was identified between the two groups in the number of dissected mediastinal lymph nodes (MLNs) and number of dissected MLNs stations. More patients after VATS procedure received postoperative adjuvant therapy (83.4% vs. 75.5%, P = 0.002). At a median follow-up of 36 (range 4-150) months, comparing VATS procedure and OT procedure, no significant differences were noted in 5-year DFS (20.7% vs. 22.5%, P = 0.89) and 5-year OS (30.7% vs. 34.5%, P = 0.821). The VATS procedure was not found to be an independent predictor of DFS (hazard ratio, 0.986; 95% CI, 0.809 to 1.202) or OS (hazard ratio, 0.977; 95% CI 0.802 to 1.191). CONCLUSION: In this large propensity-matched comparison, the VATS procedure offered comparable short-term outcomes and long-term oncological efficacy for patients with pN2 NSCLC when compared with OT procedure.