Rationale: Current guidelines for non–small cell lung cancer (NSCLC) mediastinal staging recommend starting invasive staging with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). However, the indication to confirm a negative result of EBUS-TBNA by means of video-assisted mediastinoscopy (VAM) before resection differs in every guideline. Objectives: Our aim was to evaluate the current evidence regarding the added value of confirmatory VAM after a negative EBUS-TBNA result for mediastinal staging in patients with NSCLC. Methods: Systematic searches of studies on EBUS-TBNA for NSCLC mediastinal staging with or without confirmatory VAM but with surgical confirmation of negative results were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement in PubMed, SCOPUS, the Cochrane Library, and guidelines from 2005 through November 2021. In the meta-analysis, the sensitivity of confirmatory VAM after a negative EBUS-TBNA result, as well as the sensitivity and negative predictive value of the combination EBUS-TBNA plus confirmatory VAM, alongside the number of confirmatory VAMs required to detect additional N2/3 disease (number needed to treat [NNT]), in patients with a previous negative EBUS-TBNA result were estimated. Results: A total of 5,412 articles were found, of which 29 studies were included. Random effects meta-analysis showed a sensitivity of 66.9% (95% confidence interval [CI], 55.8–77.1%) for confirmatory VAM, and 96.7% (95% CI, 95.1–98%) for the combination EBUS-TBNA plus confirmatory VAM. Negative predictive value in studies with confirmatory VAM increased of 79.2% (95% CI, 71.4–86.1%) for EBUS-TBNA alone to 91.8% (95% CI, 87.1–95.5%) for EBUS-TBNA plus confirmatory VAM. The NNT of confirmatory VAM in patients with a previous negative EBUS-TBNA result was 23.8 (95% CI, 19.3–31.2). Conclusions: Confirmatory VAM after negative EBUS-TBNA reduces the rate of unforeseen N2/3 disease, but with a high NNT, and it should be recommended only for certain cases yet to be defined.

Endobronchial ultrasonography (EBUS) has been applied as a routine procedure for the diagnostic of hiliar and mediastinal nodes. The authors assessed the relationship between the echographic appearance of mediastinal nodes, based on endobronchial ultrasound images, and the likelihood of malignancy.

Intrathoracic lymph node enlargement is a common finding in patients with extrathoracic malignancies. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a technique that is commonly used for lung cancer diagnosis and staging but that has not been widely investigated for the diagnosis of enlarged mediastinal and lobar lymph nodes in patients with extrathoracic malignancies. We conducted a retrospective study of 117 patients with extrathoracic malignancies who underwent EBUS-TBNA for diagnosis of intrathoracic lymph node enlargement from October 2005 to December 2009 and compared the EBUS-TBNA findings with the final diagnoses. EBUS-TBNA diagnosed mediastinal metastases in 51 of the 117 (43.6 %) cases and gave an alternate diagnosis or ruled out the presence of malignancy in 35 (56.4 %). Fourteen of these 35 patients underwent further surgical investigation, while the remaining 21 had clinical and radiological follow-up for 18 months. No false negatives were found in the surgery group. In the follow-up group, 13 patients had stable or regressive lymphadenopathy, and eight developed clinicoradiological progression and were assumed to have been false negatives by EBUS-TBNA. The sensitivity and negative predictive value of EBUS-TBNA were 86.4 and 75 %, respectively. Immunohistochemical staining (IHC) was performed in 80.4 % of the samples obtained by EBUS-TBNA. In samples obtained from ten patients with metastatic breast cancer, estrogen receptor expression was successfully assessed in eight patients and progesterone receptor and human epidermal growth factor receptor 2 in four. EBUS-TBNA is an accurate procedure for the diagnosis of thoracic lymph node metastases in patients with extrathoracic malignancies and should be an initial diagnostic tool in these patients. Furthermore, EBUS-TBNA can obtain high-quality specimens from metastatic lymph nodes for use in molecular analyses.

Background: Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers, and is the leading cause of tumor-related death. Lung adenocarcinoma (LUAD) is the most prevalent subtype of NSCLC. Although significant progress of LUAD treatment has been made under multimodal strategies, the prognosis of advanced LUAD is still poor due to recurrence and metastasis. There is still a lack of reliable markers to evaluate the LUAD prognosis. This study aims to explore novel biomarkers and construct a prognostic model to predict the prognosis of LUAD patients. Methods: The Genomic Data Commons-The Cancer Genome Atlas-Lung Adenocarcinoma (GDC-TCGA-LUAD) dataset was downloaded from the University of California, Santa Cruz (UCSC) Xena browser. The GSE72094 and GSE13213 datasets and corresponding clinical information were downloaded from the Gene Expression Omnibus (GEO) database. By analyzing these datasets using DESeq2 R package and Limma R package, differentially expressed genes (DEGs) were found. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to analyze possible enrichment pathways. A protein-protein interaction (PPI) network was constructed to explore possible relationship among DEGs by using the STRING database. A survival analysis was performed to identify reliable prognostic genes using the Kaplan-Meier method. A multi-omics analysis was performed using the Gene Set Cancer Analysis (GSCA). The Tumor Immune Estimation Score (TIMER) database was used to analyze the association between prognostic genes and immune infiltration. A Spearman correlation analysis was conducted to examine the correlation between prognostic genes and drug sensitivity. A multivariate Cox regression was used to identify independent prognostic factors. Next, a nomogram was constructed using the rms R package. Finally, the expressions of aspartyl-tRNA synthetase 2 (DARS2) and phosphoribosyl aminoimidazole carboxylase (PAICS) were detected using immunohistochemistry (IHC). Results: We screened out 30 DEGs prior to functional enrichment and PPI network analysis revealing potential enrichment pathways and interactions of these DEGs. Then survival analysis revealed the CENPL, DARS2, and PAICS expression was negatively correlated with LUAD prognosis. Additionally, multi-omics analysis showed CENPL, DARS2, and PAICS expressions were significantly higher in LUAD tissues than normal tissues. CENPL, DARS2, and PAICS were all up-regulated in late stage and M1 stage. Correlation analysis indicated CENPL, DARS2, and PAICS may not be associated with activation or suppression of immune cells. Drug sensitivity analysis revealed many potentially effective drugs and small molecule compounds. Moreover, we successfully constructed a robust and stable nomogram by combining the DARS2 and PAICS expression with other clinicopathological variables. Finally, IHC results showed DARS2 and PAICS were significantly up-regulated in LUAD. Conclusions: The CENPL, DARS2, and PAICS expression was negatively correlated with LUAD prognosis. A prognostic model, which integrated DARS2, PAICS, and other clinicopathological variables, was able to effectively predict LUAD patients prognosis.