Video-assisted mediastinoscopic lymphadenectomy (VAMLA): Mature results for staging non-small cell lung cancer with normal mediastinum.

OBJECTIVES: The aim of this study is to analyze the accuracy of video-assisted mediastinoscopic lymphadenectomy (VAMLA) and the unsuspected (u) N2/3 rates in patients with non-small cell lung cancer (NSCLC) and normal mediastinum by integrated positron emission tomography-computed tomography. METHODS: Prospective observational single-center study of 603 consecutive VAMLAs from 2010 to 2022. EXCLUSION CRITERIA: other indications (n = 32), tumors different from NSCLC (n = 91), and clinical (c) N2/3 tumors by positron emission tomography-computed tomography (n = 46). Systematic nodal dissection was the gold standard to validate negative VAMLAs. Those patients with negative VAMLA and missing reference standard test were excluded. uN2/3 rates were analyzed in the global series and in the subgroups of tumors according to their clinical nodal and tumor categories. Pathologic findings were reviewed, and staging values were calculated. RESULTS: Three hundred eighty-three patients with cN0/1 NSCLC underwent VAMLA. Staging values of VAMLA were: sensitivity, 0.98 (95% CI, 0.92-0.99); negative predictive value, 0.99 (95% CI, 0.98-1); and diagnostic accuracy, 0.99 (95% CI, 0.98-1). The uN2/3 rate for the whole series (N = 383) was 18.8%. The uN2/3 rates according to presurgical nodal and tumor categories determined by positron emission tomography computed tomography were: 3.6% (4 out of 111) in cT1N0; 16.3% (18 out of 110) in cT2N0; 10.25% (4 out of 39) in cT3N0; and 32% (7 out of 22) in cT4N0. Forty-two percent (39 out of 93) in cN1; complication rate was 7%. CONCLUSIONS: This series of NSCLC with normal mediastinum staged by VAMLA demonstrates a high accuracy of this technique and a high rate of uN2/3 disease (specially in cN1 and cT4N0). VAMLA could be considered the reference staging procedure for staging cN0/1 NSCLC.

EBUS-TBNA for mediastinal staging of centrally located T1N0M0 non-small cell lung cancer clinically staged with PET/CT.

BACKGROUND AND OBJECTIVE: To evaluate the diagnostic accuracy and clinical usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging of centrally located T1N0M0 non-small cell lung cancer (NSCLC) clinically staged with positron emission tomography/computed tomography (PET/CT). METHODS: We conducted a study that included patients with centrally located T1N0M0 NSCLC, clinically staged with PET/CT who underwent EBUS-TBNA for mediastinal staging. Patients with negative EBUS-TBNA underwent mediastinoscopy, video-assisted mediastinoscopic lymphadenectomy (VAMLA) and/or lung resection with systematic nodal dissection, that were considered the gold standard. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), overall accuracy of EBUS-TBNA for diagnosing mediastinal metastases (N2 disease) and the number needed to treat (NNT: number of patients needed to undergo EBUS-TBNA to avoid a case of pathologic N2 disease after resection) were calculated. RESULTS: One-hundred eighteen patients were included. EBUS-TBNA proved N2 disease in four patients. In the remaining 114 patients who underwent mediastinoscopy, VAMLA and/or resection there were two cases of N2 (N2 prevalence 5.1%). The sensitivity, specificity, NPV, PPV and overall accuracy for diagnosing mediastinal metastases (N2 disease) were of 66%, 100%, 98%, 100% and 98%, respectively. The NNT was 31 (95% CI: 15-119). CONCLUSION: EBUS-TBNA in patients with central clinically staged T1N0M0 NSCLC presents a good diagnostic accuracy for mediastinal staging, even in a population with low prevalence of N2 disease. Therefore, its indication should be considered in the management of even these early lung cancers.

Pathological N1/N2 in Clinical Stage I Bronchogenic Carcinoma. Analysis From a Prospective Multicentre Database.

OBJECTIVES: To determine the incidence of occult N1/N2 nodal metastases and associated risk factors in patients with non-small cell lung cancer no larger than 3cm and deemed cN0 by CT and PET-CT in a prospective, multicentre national database. METHODS: Patients with a NSCLC no larger than 3cm, deemed cN0 by PET-CT and CT scan, who had undergone at least a lobectomy, were selected from a national multicentre database of 3533 patients who had undergone anatomic lung resection between 2016 and 2018. Clinical and pathological variables of patients with pN0 and patients with pN1/N2 were compared to identify factors associated with the presence of lymph node metastases. Chi2 and the Mann-Whitney U test were used for categorical and numerical variables, respectively. All variables with p<0.2 in the univariate analysis were included in the multivariate logistic regression analysis. RESULTS: The study included 1205 patients from the cohort. The incidence of occult pN1/N2 disease was 10.70% (95%CI, 9.01-12.58). The multivariable analysis revealed that the degree of differentiation, size, location (central or peripheral) and SUV of the tumour in PET, surgeon experience and number of lymph nodes resected were associated with occult N1/N2 metastases. CONCLUSIONS: The incidence of occult N1/N2 in patients with bronchogenic carcinoma with cN0 tumours no larger than 3cm is no negligible. Data about the degree of differentiation, tumour size in CT scan, maximal uptake of the tumour in PET-CT, location (central or peripheral), number of lymph nodes resected and surgeon seniority is relevant in order to detect patients at risk.

Results in mediastinal lymph node staging of surgical lung cancer: Data from the prospective cohort of the Spanish Video-Assisted Thoracic Surgery Group.

OBJECTIVES: The objective of this study was to assess the diagnostic performance of combined computerised tomography (CT) and positron emission tomography (PET) in mediastinal staging of surgical lung cancer based on data obtained from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS). METHODS: A total of 2782 patients underwent surgery for primary lung carcinoma. We analysed diagnostic success in mediastinal lymph node staging (cN2) using CT and PET. Bivariate and multivariate analyses were performed of the factors involved in this success. The risk of unexpected pN2 disease was analysed for cases in which an invasive testing is recommended: cN1, the tumour centrally located or the tumour diameter >3 cm. RESULTS: The overall success of CT together with PET was 82.9% with a positive predictive value of 0.21 and negative predictive value of 0.93. If the tumour was larger than 3 cm and for each unit increase in mediastinal SUVmax, the probability of success was lower with OR 0.59 (0.44-0.79) and 0.71 (0.66-0.75), respectively. In the video-assisted thoracic surgery (VATS) approach, the probability of success was higher with OR 2.04 (1.52-2.73). The risk of unexpected pN2 increased with the risk factors cN1, the tumour centrally located or the tumour diameter >3 cm: from 4.5% (0 factors) to 18.8% (3 factors) but did not differ significantly as a function of whether invasive testing was performed. CONCLUSIONS: CT and PET together have a high negative predictive value. The overall success of the staging is lower in the case of tumours >3 cm and high mediastinal SUVmax, and it is higher when VATS is performed. The risk of unexpected pN2 is higher if the disease is cN1, the tumour centrally located or the tumour diameter >3 cm but does not vary significantly as a function of whether patients have undergone invasive testing.

External validation of the European Society of Thoracic Surgeons morbidity and mortality risk models.

OBJECTIVES: There is a wide variety of predictive models of postoperative risk, although some of them are specific to thoracic surgery, none of them is widely used. The European Society for Thoracic Surgery has recently updated its models of cardiopulmonary morbidity (Eurolung 1) and 30-day mortality (Eurolung 2) after anatomic lung resection. The aim of our work is to carry out the external validation of both models in a multicentre national database. METHODS: External validation of Eurolung 1 and Eurolung 2 was evaluated through calibration (calibration plot, Brier score and Hosmer-Lemeshow test) and discrimination [area under receiver operating characteristic curves (AUC ROC)], on a national multicentre database of 2858 patients undergoing anatomic lung resection between 2016 and 2018. RESULTS: For Eurolung 1, calibration plot showed suboptimal overlapping (slope = 0.921) and a Hosmer-Lemeshow test and Brier score of P = 0.353 and 0.104, respectively. In terms of discrimination, AUC ROC for Eurolung 1 was 0.653 (95% confidence interval, 0.623-0.684). In contrast, Eurolung 2 showed a good calibration (slope = 1.038) and a Hosmer-Lemeshow test and Brier score of P = 0.234 and 0.020, respectively. AUC ROC for Eurolung 2 was 0.760 (95% confidence interval, 0.701-0.819). CONCLUSIONS: Thirty-day mortality score (Eurolung 2) seems to be transportable to other anatomic lung-resected patients. On the other hand, postoperative cardiopulmonary morbidity score (Eurolung 1) seems not to have sufficient generalizability for new patients.

Radicality of lymphadenectomy in lung cancer resections by thoracotomy and video-assisted thoracoscopic approach: A prospective, multicentre and propensity-score adjusted study.

OBJECTIVE: To analyse differences in intraoperative nodal assessment in patients undergoing lung cancer resection by thoracotomy and video-assisted thoracoscopy (VATS) in the Spanish Video-Assisted Thoracic Surgery Group (GEVATS). METHODS: Prospective multicentre cohort study of anatomic pulmonary resections (n = 3533) performed from December 2016 to March 2018. Main surgical, clinical and oncological variables related with lymphadenectomy were compared according to surgical approach. Corresponding tests for homogeneity were performed. Multiple logistic regression analyses were used to determine the odds ratio (OR) and 95% confidence interval (95%CI). Covariate adjustment using the propensity score (PS) was performed to reduce confounding effects. RESULTS: After exclusions, 2532 patients were analysed. Systematic nodal dissection (SND) was performed in 65%, with a median of resected/sampled lymph nodes (LN) of 7 (IQR 4-12) and pathologic (p) N2 and uncertain (u) pNu rates of 9.4% and 28.9%, respectively. At multivariate analysis, the following were associated with thoracotomy (OR; 95%CI): SND (1.4; 1.08-1.96; p = 0.014), staging mediastinoscopy (2.6; 1.59-4.25; p < 0.001), tumor > 3 cm (2.1; 1.66-2.78; p < 0.001), central tumor (2.5; 1.90-3.24; p < 0.001); pN1 (1.8; 1.25-2.67; p < 0.002), pN2 (1.8; 1.18-2.76; p = 0.006), lower FEV1 (0.9; 0.98-0.99; p < 0.001), squamous cell carcinoma (1.5; 1.16-1.98; p = 0.002) and inexperienced surgeons in VATS (compared with > 100 VATS experience) (37.6; 13.55-104.6; p < 0.001). After PS adjustment, SND maintained the OR, but in the limit of signification (1.4; 1-1.98; p = 0.05). Nodal upstaging was significantly higher in the thoracotomy group. Complication rates of SND and no SND were similar. CONCLUSIONS: Thoracotomy was associated with a more thorough lymphadenectomy in GEVATS. Therefore, intraoperative lymph node evaluation performed at VATS should be improved to have better prognostic information and more solid grounds to indicate adjuvant therapy.

Geometrical Measurement of Central Tumor Location in cT1N0M0 NSCLC Predicts N1 but Not N2 Upstaging.

BACKGROUND: In patients with non-small cell lung cancer (NSCLC) and normal mediastinum, the central tumor location predicts occult nodal disease (both N1 and N2). We evaluated a novel definition of central location based on a geometrical measurement of the tumor location within the lung that could predict N2, N1, or both. METHODS: This retrospective study included patients with confirmed NSCLC, radiologically and metabolically staged T1 N0 M0, who underwent invasive mediastinal staging and/or lung resection. The central tumor location was measured considering 2 ratios. The inner margin ratio (IMR) and outer margin ratio (OMR) were both calculated as the distance from the inner margin of the lung to both margins of the tumor (inner [IMR], outer [OMR]) divided by the lung width. Optimal cutoffs for IMR and OMR were calculated. Tumors with values lower than the cutoffs were considered central. Prevalences of N1 and N2 upstaging were estimated and bivariate logistic regression analysis was performed to predict the odds of N1 and N2 upstaging using IMR and OMR cutoffs. RESULTS: A total of 209 patients were included. The prevalence of N1 and N2 upstaging was 11% and 5.3%, respectively. Cutoffs of 0.5 for IMR and 0.64 for OMR were estimated. Both ratios predicted N1 upstaging (adjusted odds ratio [95% confidence interval]: 4.2 [1.5-12]; P < .007; area under the curve, 0.65) but did not predict N2 upstaging. CONCLUSIONS: Central tumor location can be assessed by means of IMR and OMR and predicts N1 upstaging in patients with radiologically and metabolically T1 N0 M0 tumors. This is important for the selection of patients for therapies that require N0 tumors.

Spanish Video-Assisted Thoracic Surgery Group: Method, Auditing, and Initial Results From a National Prospective Cohort of Patients Receiving Anatomical Lung Resections.

INTRODUCTION: Our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). METHODS: We conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for "90-day mortality" and "Grade IIIb-V complications". RESULTS: The series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). CONCLUSIONS: More than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort.

Src-Homology 2 Domain-Containing Phosphatase 2 in Resected EGFR Mutation-Positive Lung Adenocarcinoma.

INTRODUCTION: EGFR mutation-positive lung adenocarcinoma (LUAD) displays impaired phosphorylation of ERK and Src-homology 2 domain-containing phosphatase 2 (SHP2) in comparison with EGFR wild-type LUADs. We hypothesize that SHP2 expression could be predictive in patients positive with resected EGFR mutation versus patients with EGFR wild-type LUAD. METHODS: We examined resected LUAD cases from Japan and Spain. mRNA expression levels of AXL, MET, CDCP1, STAT3, YAP1, and SHP2 were analyzed by quantitative reverse transcriptase polymerase chain reaction. The activity of SHP2 inhibitors plus erlotinib were tested in EGFR-mutant cell lines and analyzed by cell viability assay, Western blot, and immunofluorescence. RESULTS: A total of 50 of 100 EGFR mutation-positive LUADs relapsed, among them, patients with higher SHP2 mRNA expression revealed shorter progression-free survival, in comparison with those having low SHP2 mRNA (hazard ratio: 1.83; 95% confidence interval: 1.05-3.23; p = 0.0329). However, SHP2 was not associated with prognosis in the remaining 167 patients with wild-type EGFR. In EGFR-mutant cell lines, the combination of SHP099 or RMC-4550 (SHP2 inhibitors) with erlotinib revealed synergism via abrogation of phosphorylated AKT (S473) and ERK1/2 (T202/Y204). Although erlotinib translocates phosphorylated SHP2 (Y542) into the nucleus, either RMC-4550 alone, or in combination with erlotinib, relocates SHP2 into the cytoplasm membrane, limiting AKT and ERK1/2 activation. CONCLUSIONS: Elevated SHP2 mRNA levels are associated with recurrence in resected EGFR mutation-positive LUADs, but not in EGFR wild-type. EGFR tyrosine kinase inhibitors can enhance SHP2 activation, hindering adjuvant therapy. SHP2 inhibitors could improve the benefit of adjuvant therapy in EGFR mutation-positive LUADs.

Nodal size ranking as a predictor of mediastinal involvement in clinical early-stage non-small cell lung cancer.

In non-small cell lung cancer (NSCLC) patients, the recommended minimum requirement for an endoscopy-based mediastinal staging procedure is sampling the largest lymph node (LN) in right and left inferior paratracheal, and subcarinal stations. We aimed to analyze the percentage of cases where the largest LN in each mediastinal station was malignant in a cohort of NSCLC patients with mediastinal metastases diagnosed in the lymphadenectomy specimen. Furthermore, we investigated the sensitivity of a preoperative staging procedure in a hypothetical scenario where only the largest LN of each station would have been sampled.Prospective data of patients with mediastinal nodal metastases diagnosed in the lymphadenectomy specimens were retrospectively analyzed. The long-axis diameter of the maximal cut surface of all LNs was measured on hematoxylin and eosin-stained sections.Seven hundred seventy five patients underwent operation and 49 (6%) with mediastinal nodal disease were included. A total of 713 LNs were resected and 119 were involved. Sixty seven nodal stations revealed malignant LNs: in these, the largest LN was malignant in 39 (58%). In a "per patient" analysis, a preoperative staging procedure that sampled only the largest LN would have attained a sensitivity of 0.67; and if the largest and the second largest were sampled, sensitivity would be 0.87.In patients with NSCLC, nodal size ranking is not reliable enough to predict malignancy. In clinical practice, regardless of the preoperative staging method, systematic thorough sampling of all visible LNs is to be recommended over selective random samplings.

Present indications of surgical exploration of the mediastinum.

Preoperative mediastinal staging is crucial in the management of patients with non-small cell lung cancer (NSCLC), especially to define prognosis and the most proper treatment. To obtain the highest certainty level before lung resection, the current American and European guidelines for preoperative mediastinal nodal staging for NSCLC recommend getting tissue confirmation of regional nodal spread in all cases except in patients with small (≤3 cm) peripheral carcinomas with no evidence of nodal involvement on computed tomography (CT) and positron emission tomography (PET). We have a wide variety of surgical methods for mediastinal staging that are well integrated in the current preoperative algorithms. Their main indication is the validation of negative results obtained by minimally invasive endoscopic techniques. However, recent studies have reported the superiority of mediastinoscopy over endosonography methods in terms of accuracy for those tumours classified as clinical (c) N0-1 by CT and PET or with intermediate risk of N2 disease (cN1 and central tumours). Apart from the exploration of the mediastinum, other surgical procedures [parasternal mediastinotomy, extended cervical mediastinoscopy (ECM) and video-assisted thoracoscopic surgery (VATS)] allow the completion of the staging process with the assessment of the primary tumour and metastasis, exploring the lung, pleural cavity, and pericardium when it is required. Transcervical lymphadenectomies represent the evolution of mediastinoscopy and they are already considered the most reliable method for mediastinal staging, mainly in the subgroup of patients in whom endosonography methods have a low sensitivity: tumours with normal mediastinum by CT and PET. In addition to their indication for staging, these procedures have also demonstrated to be feasible as preresectional lymphadenectomy in VATS lobectomy, improving the radicality of the number of lymph nodes and lymph node stations explored, mostly for left-sided tumours for which a complete mediastinal nodal dissection is not always possible by VATS approach.

Transcervical videomediastino-thoracoscopy.

Although technical advances in non-invasive and minimally invasive approaches to lung and pleural cancer diagnosis and staging have become more widely available and accurate, surgical techniques remain the gold standard in assessing the extent of loco-regional involvement. Precise surgical staging of lung or pleural tumours is pivotal in the selection of surgical candidates and for predicting survival. In some patients, both mediastinal and pleural exploration may be needed for many different reasons. Transcervical videomediastino-thoracoscopy (VMT) combines simultaneously the exploration of both the mediastinum and the pleural cavities through a single cervical incision, allowing for biopsies or sampling of the mediastinal lymph nodes, lymphadenectomy and pleuropulmonary assessment (mainly pleural effusions, tumour involvement of the visceral and parietal pleura and pulmonary nodules). Thoracic surgeons should be aware of this combined surgical approach and completely familiar with classical indications and technical details of the transcervical approach to the mediastinum and thoracoscopic exploration of the pleural cavities.

Lung cancer staging: a concise update.

Diagnosis and clinical staging of lung cancer are fundamental to planning therapy. The techniques for clinical staging, i.e anatomic and metabolic imaging, endoscopies and minimally invasive surgical procedures, should be performed sequentially and with an increasing degree of invasiveness. Intraoperative staging, assessing the magnitude of the primary tumour, the involved structures, and the loco-regional lymphatic spread by means of systematic nodal dissection, is essential in order to achieve a complete resection. In resected tumours, pathological staging, with the systematic study of the resected specimens, is the strongest prognostic indicator and is essential to make further decisions on therapy. In the present decade, the guidelines on lung cancer staging of the American College of Chest Physicians and the European Society of Thoracic Surgeons are based on the best available evidence and are widely followed. Recent advances in the classification of the adenocarcinoma of the lung, with the definition of adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma, and the publication of the eighth edition of the tumour, node and metastasis classification of lung cancer, have to be integrated into the staging process. The present review complements the latest guidelines on lung cancer staging by providing an update of all these issues.

Combination video-assisted mediastinoscopic lymphadenectomy and transcervical thoracoscopy.

Surgical staging of lung and pleural cancers is crucial for planning treatment and assessing prognosis. In some cases, we need to explore both the mediastinum and the pleural cavity to confirm or rule out tumor dissemination. The combination of video-assisted mediastinoscopic lymphadenectomy (VAMLA) and thoracoscopy through a single transcervical incision allows the surgeon to widen the range of the exploration and improve the staging for lung and pleural cancers.  VAMLA consists of complete removal of the mediastinal fat and lymph nodes of the subcarinal space, the right paratracheal and pretracheal areas, and the left paratracheal space. Once this mediastinal tissue is removed, the right mediastinal pleura can be identified and incised. A 30o thoracoscope is then inserted through the video-mediastinoscope into the pleural cavity to obtain samples of pleural fluid and biopsies of the parietal pleura and lung nodules, if present. In the case of left-sided thoracoscopy the access route to the left pleural cavity is anterior to the aortic arch, as for extended cervical mediastinoscopy. The combination of VAMLA and thoracoscopy is useful for exploring the mediastinum and the pleural space from a single incision and in the same surgical setting as the transcervical approach.

Role of heparin in pulmonary cell populations in an in-vitro model of acute lung injury.

BACKGROUND: In the early stages of acute respiratory distress syndrome (ARDS), pro-inflammatory mediators inhibit natural anticoagulant factors and initiate an increase in procoagulant activity. Previous studies proved the beneficial effects of heparin in pulmonary coagulopathy, which derive from its anticoagulant and anti-inflammatory activities, although it is uncertain whether heparin works. Understanding the specific effect of unfractioned heparin on cell lung populations would be of interest to increase our knowledge about heparin pathways and to treat ARDS. METHODS: In the current study, the effect of heparin was assessed in primary human alveolar macrophages (hAM), alveolar type II cells (hATII), and fibroblasts (hF) that had been injured with LPS. RESULTS: Heparin did not produce any changes in the Smad/TGFß pathway, in any of the cell types evaluated. Heparin reduced the expression of pro-inflammatory markers (TNF-α and IL-6) in hAM and deactivated the NF-kß pathway in hATII, diminishing the expression of IRAK1 and MyD88 and their effectors, IL-6, MCP-1 and IL-8. CONCLUSIONS: The current study demonstrated that heparin significantly ameliorated the cells lung injury induced by LPS through the inhibition of pro-inflammatory cytokine expression in macrophages and the NF-kß pathway in alveolar cells. Our results suggested that a local pulmonary administration of heparin through nebulization may be able to reduce inflammation in the lung; however, further studies are needed to confirm this hypothesis.

Video-Assisted Mediastinoscopic Lymphadenectomy for Staging Non-Small Cell Lung Cancer.

BACKGROUND: The aim of this study was to evaluate the results of video-assisted mediastinoscopic lymphadenectomy (VAMLA) for staging of non-small cell lung cancer (NSCLC). METHODS: This was a prospective observational study of all consecutive VAMLAs performed from January 2010 to April 2015 for staging NSCLC. For left lung cancers, extended cervical videomediastinoscopy was added to explore the subaortic and paraaortic nodes. Patients with negative VAMLA results underwent tumor resection and lymphadenectomy of the remaining nodes. Those with N2-3 disease underwent chemoradiation. The rate of unsuspected pathologic (p)N2-3 was analyzed in the global series and in the subgroups of patients according to their nodal status diagnosed by imaging and metabolic techniques. RESULTS: One hundred sixty VAMLAs were performed for staging NSCLC (138 tumors were clinical (c)N0-1 based on imaging techniques). The rate of unsuspected N2-3 disease was 18% for the whole series: 40.7% for cN1, 22.2% for cN0 and tumor size greater than or equal to 3 cm, and 6.4% for cN0 and tumor size less than 3 cm. Staging values were sensitivity, 0.96 (95% confidence interval [CI], 0.81-99.3); specificity, 1 (95% CI, 0.97-1); positive predictive value, 1 (95% CI, 0.87-1); negative predictive value, 0.99 (95% CI, 0.95-0.99); and diagnostic accuracy, 0.99 (95% CI, 0.96-0.99). The complication rate was 5.9%. CONCLUSIONS: VAMLA is a feasible and highly accurate technique. The high rate of unsuspected mediastinal node disease diagnosed by VAMLA in patients with cN1 or cN0 disease and tumor size larger than 3 cm suggests that preresection lymphadenectomies should be included in the current staging algorithms.