Carme Obiols

Repeat mediastinoscopy in all its indications: experience with 96 patients and 101 procedures

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.

Survival of Patients With Unsuspected pN2 Non-Small Cell Lung Cancer After an Accurate Preoperative Mediastinal Staging

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.

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.

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. Lung cancer staging is a multidisciplinary activity that involves specialists in imaging, endoscopists, surgeons and pathologists at clinical and pathological staging http://ow.ly/z3M030jzmhN

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

BackgroundIn 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.MethodsIn 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.ResultsHeparin 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.ConclusionsThe 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.

Utility of the transcervical approach in bilateral synchronous lung cancer

Bilateral pulmonary nodules represent a challenge in distinguishing between synchronous bronchogenic carcinomas and metastatic disease. In the case of potentially curable synchronous lung cancer, it is recommended to treat each lesion with curative intent if there is no evidence of mediastinal involvement or extrathoracic disease. In this situation, surgical staging of the mediastinum is recommended. This case shows the utility of a transcervical approach to perform precise mediastinal staging and lymphadenectomy, and to access the pleural cavity to resect a pulmonary nodule. Moreover, video-assisted mediastinoscopic lymphadenectomy combined with video-assisted lobectomy could be a good option for a radical lymphadenectomy.

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.

Pros: should a patient with stage IA non-small cell lung cancer undergo invasive mediastinal staging?

Mediastinal lymph node involvement is an important prognostic factor in patients with non-small cell lung cancer (NSCLC). The American and European guidelines for preoperative mediastinal lymph node staging agree in which situations a pre-surgical exploration of the mediastinum is required in order to avoid futile pulmonary resections (1,2). Invasive mediastinal staging with cyto-histological confirmation is indicated when computed tomography (CT) shows enlarged mediastinal or hilar lymph nodes, when positron emission tomography (PET) shows an increase uptake in the mediastinum or hilum, when the tumour is centrally located and when the tumour size is more than 3 cm, especially in adenocarcinoma with high 18F-Fluorodeoxyglucose (FDG) uptake.

Rebuttal from Dr. Obiols and Dr. Call

First of all, we would like to congratulate Dr. Decaluwe and Dr. Dooms for their rigorous revision on this topic. As they have commented in their manuscript, following the recommendations of the European Society of Thoracic Surgeons (ESTS) guidelines for preoperative mediastinal nodal staging, high negative predictive values (91–95%) and low rates of unsuspected pathologic (p) N2 disease (5.1–5.5%) are achieved (1,2). The majority of patients with unsuspected pN2 have single station involvement and better survival compared with the global cohort of pN2 (2).