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OBJECTIVE: The aim of this study was to elucidate the impact of pleural lavage cytology positivity on early recurrence in patients operated on non-small cell lung cancer (NSCLC). METHODS: This is a multicentre prospective cohort study of 684 patients undergoing an anatomical lung resection for NSCLC between October 2015 and October 2017 at 12 national centres. A pleural lavage was performed before and after lung resection. The association between the different predictors of early recurrence and PLC positivity was performed using univariate and multivariate logistic regression models. A propensity score analysis was performed by inverse probability weighting (IPSW) using average treatment effect (ATE) estimation to analyse the impact of PLC positivity on early recurrence. RESULTS: Overall PLC positivity was observed in 15 patients (2.2%). After two years, 193 patients (28.2%) relapsed, 182 (27.2%) with a negative PLC and 11 (73.3%) with a positive PLC (p<0.001). Factors associated to early recurrence were adenocarcinoma histology (OR=1.59, 95%CI 1.06-2.38, p=0.025), visceral pleural invasion (OR=1.59, 95%CI 1.04-2.4, p=0.03), lymph node involvement (OR=1.84, 95%CI 1.14-2.96, p=0.013), advanced pathological stage (OR=2.12, 95%CI 1.27-3.54, p=0.004) and PLC positivity (OR=4.14, 95%CI 1.25-16.36, p=0.028). After IPSW, PLC positivity was associated with an increased risk of early recurrence (OR=3.46, 95%CI 2.25-5.36, p<0.001). CONCLUSIONS: Positive pleural lavage cytology was found to be the strongest predictor of early recurrence.

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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.

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BACKGROUND: The aim of this study is to analyze the survival of patients with non-small cell lung cancer (NSCLC) without clinical suspicion of mediastinal lymph node involvement who underwent complete resection and whose tumors were finally proven to be pathologic N2 (pN2). METHODS: This is a retrospective study of a prospective database from January 2004 to December 2010. A total of 621 patients with NSCLC were staged and operated according to the European Society of Thoracic Surgeons guidelines. After exclusions (previous induction treatment, carcinoid tumors, small cell carcinomas), 540 patients were analyzed; 406 (75%) required surgical exploration of the mediastinum and 134 (25%) underwent surgery directly. Survival analysis was performed by the Kaplan-Meier method and the log-rank test was used for comparisons. RESULTS: Thirty (5.5%) patients had unsuspected pN2 and complete resection was achieved in 27 (90%). Three- and 5-year survival rates were 87% and 81%, respectively, for patients with a true negative result of the protocol (pN0-1), and 79% and 40%, respectively, for those with a false negative result (unsuspected pN2) (p < 0.0001). CONCLUSIONS: The rate of unsuspected pN2 in patients whose tumors were staged according to the European Society of Thoracic Surgeons guidelines was low. The survival of this group of patients was better than expected. Therefore, resection of properly staged unsuspected pN2 NSCLC is reasonable and should not be avoided if complete resection can be achieved.

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OBJECTIVE: The objective of this study is to evaluate the accuracy of extended cervical mediastinoscopy (ECM) in the staging of bronchogenic carcinoma (BC) of the left lung based on our updated experience. METHODS: From 1998 to 2003, 89 patients underwent routine ECM for staging of BC of the left lung. In 2004, routine positron emission tomography (PET) was included in our staging protocol and ECM was reserved for those with positive mediastinal or hilar PET images, large lymph nodes on computed tomography (CT) scan or central tumours. Following this protocol, from 2004 to 2010, we performed 132 selective ECM. ECM was considered positive when metastatic nodes or tumour involvement directly in the subaortic or para-aortic regions was confirmed pathologically. Patients with negative ECM underwent subsequent thoracotomy for tumour resection and systematic nodal dissection (SND). RESULTS: Two hundred and twenty-one ECMs were performed from 1998 to 2010 (89 routine and 132 selective). In the routine ECM protocol, four cases were positive and thoracotomy was contraindicated. The remaining 85 patients were operated and five had nodal disease in subaortic (LN5) or para-aortic (LN6) stations. In the selective ECM protocol (n = 188), 132 patients underwent ECM and in 19 it was positive; the remaining 113 patients underwent thoracotomy and SND found involved LN5 or LN6 in six patients; the other 56 patients underwent direct thoracotomy and four had positive LN5 or LN6. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ECM were 0.67, 1, 1, 0.94 and 0.95, respectively. The staging values of routine/selective ECM protocols were 0.44/0.65, 1/1, 1/1, 0.94/0.94 and 0.94/0.95, respectively. CONCLUSIONS: Selective ECM protocol according to CT and PET findings has high negative predictive value and accuracy. Therefore, its selective use is recommended because it saves around 30% ECM without decreasing staging values of the current protocol.

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OBJECTIVE: To evaluate the accuracy of repeat mediastinoscopy (reMS) in all its indications, and to analyse survival in the group of patients who underwent induction chemotherapy or chemoradiotherapy for pathologically proven stage III-N2 non-small-cell lung cancer (NSCLC). METHODS: From July 1992 to February 2009, 96 patients (87 men; median age: 61.3 years), underwent 101 reMSs (five patients required a second reMS) for the following indications: restaging after induction therapy for pathologically proven N2 disease (84 cases), inadequate first mediastinoscopy (five), metachronous second primary (six) and recurrent lung cancer (six). Patients with N2-NSCLC, who had received induction therapy and had positive reMS, underwent definitive chemotherapy or chemoradiotherapy. Patients in whom reMS was negative underwent thoracotomy for lung resection and systematic nodal dissection (SND). SND was considered the gold standard to compare the negative results of reMS. Pathologic findings were reviewed and staging values were calculated using the standard formulas. Follow-up data were completed in January 2010, and survival analysis was performed by the Kaplan-Meier method. RESULTS: In the group of reMS for restaging after induction therapy, the staging values were: sensitivity 0.74, specificity 1, positive predictive value 1, negative predictive value 0.79 and diagnostic accuracy 0.87. We also determined the diagnostic value of this technique according to the type of induction treatment. In terms of accuracy, no statistically significant differences were found. Median survival time in patients with true negative reMS was 51.5 months (95% confidence interval (CI) 0-112), and in the combined group of patients with positive and false-negative reMS, median survival time was 11 months (95% CI 7.6-14.1) (p=0.0001). In the group of miscellaneous indications, all staging values were 1. CONCLUSION: ReMS is feasible in all the indications described. After induction therapy, it is a useful procedure to select patients for lung resection with high accuracy, independently of the induction treatment used or the intensity of the first mediastinoscopy. The persistence of lymph node involvement after induction therapy has a poor prognosis. Therefore, techniques providing cytohistological evidence of nodal downstaging are advisable to avoid unnecessary thoracotomies.

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OBJECTIVE: To evaluate the technical feasibility and the sensitivity, specificity and accuracy of extended cervical mediastinoscopy (ECM) in the staging of bronchogenic carcinoma (BC) of the left lung. METHODS: From 1998 to 2003, 89 patients underwent routine ECM for staging of BC of the left lung. In 2004, positron emission tomography (PET) was included in our staging protocol and ECM was reserved for those with positive mediastinal or hilar PET images, large lymph nodes on computed tomography (CT) scan or central tumours. From 2004 to 2007 we performed selective ECM in 67 patients. ECM was considered positive when metastatic nodes or tumour involvement directly in the subaortic or para-aortic regions was confirmed pathologically. One hundred and forty-three patients with negative ECM underwent subsequent thoracotomy for tumour resection and systematic nodal dissection. Pathological findings were reviewed and staging values were calculated. RESULTS: One hundred and fifty-six patients underwent ECM (89 routine and 67 selective). In 13, ECM was positive and thoracotomy was contraindicated. The rest of the patients were operated. We performed 88 lobectomies, 34 pneumonectomies, 6 wedge resections, 13 exploratory thoracotomies and 2 parasternal mediastinotomies. Lymphadenectomy specimens showed tumour involvement of subaortic lymph nodes in 8 patients. Complication rate was 2%: two cases of mediastinitis, one ventricular fibrillation, and one superficial surgical wound infection. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of routine/selective ECM were: 0.45/0.75, 1/1, 1/1, 0.94/0.95, 0.94/0.95, respectively. CONCLUSION: ECM is a feasible staging technique that allows ruling out subaortic and para-aortic nodal disease with high negative predictive value, accuracy and sensitivity. Its indication based on the CT and PET findings seems more advisable that its routine use to stage bronchogenic carcinoma of the left lung.

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