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      Mediastinal staging for non-small cell lung cancer

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          Abstract

          The staging of mediastinal lymph nodes for lung cancer is crucial for planning treatments or reinterventions. In potentially curable patients the aim of mediastinal staging is to exclude the presence of malignancy in mediastinal lymph nodes with a high level of accuracy while also considering clinical factors and the balance of the benefits and risks of tissue sampling techniques. Mediastinal staging is based on computed tomography (CT) and positron emission tomography (PET) and can be sufficient when no mediastinal abnormalities are present and the probability of unforeseen N2 disease is low. In the case of bulky lymph nodes with a high probability of malignancy in PET-CT, tissue confirmation is not normally required. If mediastinal sampling is needed it can be achieved by endosonographic techniques, including endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) or a combination of the two. Positive results do not need further confirmation. In the case of negative results, surgical techniques still play a role in the selected cases discussed by multidisciplinary lung cancer committees. New mediastinal surgical techniques including video-assisted cervical mediastinoscopy (VACM), video-assisted mediastinoscopic lymphadenectomy (VAMLA), and transcervical extended mediastinal lymphadenectomy (TEMLA) have been shown to be useful in selected patients. Final pathological staging is based on lymph node removal during surgery and can be achieved by taking one of two approaches: lymph node sampling or systematic lymph node sampling. The accuracy of PET-CT and mediastinal endosonography is lower for mediastinal restaging than it is for surgical techniques; their false positive and false negative (FN) rate is high and so, they require histological confirmation. Here we explain and revise the results from the most recent studies and current international guidelines.

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          Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer.

          Accurate preoperative staging and restaging of mediastinal lymph nodes in patients with potentially resectable non-small-cell lung cancer (NSCLC) is of paramount importance. In 2007, the European Society of Thoracic Surgeons (ESTS) published an algorithm on preoperative mediastinal staging integrating imaging, endoscopic and surgical techniques. In 2009, the International Association for the Study of Lung Cancer (IASLC) introduced a new lymph node map. Some changes in this map have an important impact on mediastinal staging. Moreover, more evidence of the different mediastinal staging technique has become available. Therefore, a revision of the ESTS guidelines was needed. In case of computed tomography (CT)-enlarged or positron emission tomography (PET)-positive mediastinal lymph nodes, tissue confirmation is indicated. Endosonography [endobronchial ultrasonography (EBUS)/esophageal ultrasonography (EUS)] with fine-needle aspiration (FNA) is the first choice (when available), since it is minimally invasive and has a high sensitivity to rule in mediastinal nodal disease. If negative, surgical staging with nodal dissection or biopsy is indicated. Video-assisted mediastinoscopy is preferred to mediastinoscopy. The combined use of endoscopic staging and surgical staging results in the highest accuracy. When there are no enlarged lymph nodes on CT and when there is no uptake in lymph nodes on PET or PET-CT, direct surgical resection with systematic nodal dissection is indicated for tumours ≤ 3 cm located in the outer third of the lung. In central tumours or N1 nodes, preoperative mediastinal staging is indicated. The choice between endoscopic staging with EBUS/EUS and FNA or video-assisted mediastinoscopy depends on local expertise to adhere to minimal requirements for staging. For tumours >3 cm, preoperative mediastinal staging is advised, mainly in adenocarcinoma with high standardized uptake value. For restaging, invasive techniques providing histological information are advisable. Both endoscopic techniques and surgical procedures are available, but their negative predictive value is lower compared with the results obtained in baseline staging. An integrated strategy using endoscopic staging techniques to prove mediastinal nodal disease and mediastinoscopy to assess nodal response after induction therapy needs further study.
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            A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediastinal lymph node staging of lung cancer.

            The study objective was to compare endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with mediastinoscopy for mediastinal lymph node staging of potentially resectable non-small cell lung cancer. Patients with confirmed or suspected non-small cell lung cancer who required mediastinoscopy to determine suitability for lung cancer resection were entered into the trial. All patients underwent EBUS-TBNA followed by mediastinoscopy under general anesthesia. If both were negative for N2 or N3 disease, the patient underwent pulmonary resection and mediastinal lymphadenectomy. Between July 2006 and August 2010, 190 patients were registered in the study, 159 enrolled, and 153 were eligible for analysis. EBUS-TBNA and mediastinoscopy sampled an average of 3 and 4 lymph node stations per patient, respectively. The mean short axis of the lymph node biopsied by EBUS-TBNA was 6.9 ± 2.9 mm. The prevalence of N2/N3 disease was 35% (53/153). There was excellent agreement between EBUS-TBNA and mediastinoscopy for mediastinal staging in 136 patients (91%; Kappa, 0.8; 95% confidence interval, 0.7-0.9). Specificity and positive predictive value for both techniques were 100%. The sensitivity, negative predictive value, and diagnostic accuracy for mediastinal lymph node staging for EBUS-TBNA and mediastinoscopy were 81%, 91%, 93%, and 79%, 90%, 93%, respectively. No significant differences were found between EBUS-TBNA and mediastinoscopy in determining the true pathologic N stage (McNemar's test, P = .78). There were no complications from EBUS-TBNA. Minor complications from mediastinoscopy were observed in 4 patients (2.6%). EBUS-TBNA and mediastinoscopy achieve similar results for the mediastinal staging of lung cancer. As performed in this study, EBUS-TBNA can replace mediastinoscopy in patients with potentially resectable non-small cell lung cancer. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
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              Real-time endobronchial ultrasound-guided transbronchial needle aspiration in mediastinal staging of non-small cell lung cancer: how many aspirations per target lymph node station?

              The goal of this study was to determine the optimal number of aspirations per lymph node (LN) station during endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) for maximum diagnostic yield in mediastinal staging of non-small cell lung cancer (NSCLC) in the absence of rapid on-site cytopathologic examination. EBUS-TBNA was performed in potentially operable NSCLC patients with mediastinal LNs accessible by EBUS-TBNA (5 to 20 mm). Every target LN station was punctured four times. We performed EBUS-TBNA in 163 mediastinal LN stations in 102 NSCLC patients. EBUS-TBNA confirmed malignancy in 41 LN stations in 30 patients. Two malignant LN stations were missed in two patients. The sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy of EBUS-TBNA in predicting mediastinal metastasis were 93.8%, 100%, 100%, 96.9%, and 97.9%, respectively. Sample adequacy was 90.1% for one aspiration, and it reached 100% for three aspirations. The sensitivity for differentiating malignant from benign LN stations was 69.8%, 83.7%, 95.3%, and 95.3% for one, two, three, and four aspirations, respectively. The NPV was 86.5%, 92.2%, 97.6%, and 97.6% for one, two, three, and four aspirations, respectively. Maximum diagnostic values were achieved in three aspirations. When at least one tissue core was obtained by the first or second aspiration, the sensitivity and NPV of the first two aspirations were 91.9% and 96.0%, respectively. Optimal results can be obtained in three aspirations per LN station in EBUS-TBNA for mediastinal staging of potentially operable NSCLC. When at least one tissue core specimen is obtained by the first or second aspiration, two aspirations per LN station can be acceptable.
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                Author and article information

                Journal
                Transl Lung Cancer Res
                Transl Lung Cancer Res
                TLCR
                Translational Lung Cancer Research
                AME Publishing Company
                2218-6751
                2226-4477
                January 2021
                January 2021
                : 10
                : 1
                : 496-505
                Affiliations
                [1 ]Pulmonary Department, Hospital Álvaro Cunqueiro, Vigo Health Area, Vigo, Spain;
                [2 ]NeumoVigoI+i Research Group, Vigo Biomedical Research Institute (IBIV) , Vigo, Spain
                Author notes

                Contributions: (I) Conception and design: All authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: None; (V) Data analysis and interpretation: None; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                Correspondence to: Alberto Fernández-Villar, MD, PhD. Department of Pneumology, Research Group of Respiratory and Infectious Diseases, University Hospital Complex of Vigo, Xerencia de Xestion Integrada de Vigo, Vigo, Spain. Email: alberto.fernandez.villar@ 123456sergas.es .
                Article
                tlcr-10-01-496
                10.21037/tlcr.2020.03.08
                7867740
                33569331
                38317fd3-f1f8-4882-a0de-1aa854ea3c37
                2021 Translational Lung Cancer Research. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 10 February 2020
                : 27 February 2020
                Categories
                Review Articles on Multimodal Management of Locally Advanced N2 Non-small Cell Lung Cancer

                mediastinum,staging,non-small cell lung cancer (nsclc)

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