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Journal of Cancer Research and Therapeutics, Vol. 7, No. 2, April-June, 2011, pp. 148-151 Original Article Endobronchial ultrasound in hilar and conventional TBNA-negative/inconclusive mediastinal lymphadenopathy Prashant N Chhajed1, Rahel Odermatt1, Christophe von Garnier1, Parag Chaudhari2, Joerg D Leuppi1, Daiana Stolz1, Michael Tamm1 1 Pulmonary Medicine, University Hospital Basel, Swaziland Code Number: cr11035 PMID: 21768701 Abstract Objective: Assess the diagnostic yield of real-time bronchoscopic ultrasound transbronchial needle aspiration (EBUS TBNA) in conventional TBNA-negative mediastinal lymphadenopathy and hilar lymphadenopathy. Materials and Methods: Sixty-two patients having either conventional TBNA-negative mediastinal lymphadenopathy or hilar lymphadenopathy underwent real-time EBUS TBNA. Results: EBUS TBNA was performed on 72 lymph nodes (mediastinal = 48; and hilar = 24). 31 of the 72 (43%) lymph node samples were positive for malignancy (29) or benign diagnosis (2), and 17 of the 72 (24%) lymph nodes were true negative at EBUS TBNA confirmed at surgery. Out of 48 mediastinal lymph nodes EBUS TBNA was diagnostic for malignancy in 19 (40%) and negative in 14 of which 12 (86%) were surgically confirmed true negative and 2 (14%) false negative. In 10 of the 24 (42%) hilar lymph nodes, EBUS TBNA was diagnostic for malignancy while 5 were true negative and 1 false negative. All false-negative lymph nodes were PET positive. Adequacy of EBUS TBNA based on positive aspiration and surgically confirmed true negative was 67% and in patients suspected for malignancy was 77%. Conclusions: EBUS TBNA has a good diagnostic yield in hilar lymphadenopathy and in conventional TBNA-negative mediastinal lymphadenopathy.Keywords: EBUS, mediastinal lymphadenopathy, TBNA Introduction Conventional transbronchial needle aspiration (TBNA) is performed routinely for the diagnosis of mediastinal lymphadenopathy during diagnostic bronchoscopy. [1] Flexible bronchoscopy is most often the first diagnostic procedure performed to obtain a pathological diagnosis in patients with suspected lung cancer. TBNA of mediastinal lymph nodes as a staging procedure can also be performed during the same session of routine bronchoscopy-guided by enlarged lymph nodes on CT scanning. A positive TBNA may preclude the need for additional surgical staging of the mediastinum. Compared with mediastinoscopy, TBNA is generally more convenient, less risky, and less expensive. The yield of TBNA has been reported to vary widely. The factors associated with this wide variation include learning curve of bronchoscopist, specimen preparation and the prevalence of bulky lymphadenopathy. [2],[3] Various complimentary tools have been reported to enhance the yield of TBNA, which include endobronchial ultrasound, CT fluoroscopy, and electromagnetic navigation bronchoscopy. [4],[5],[6],[7],[8] Endobronchial ultrasound (EBUS) TBNA can be performed real-time under direct visualization of the needle with simultaneous ultrasound and optical imaging. [9] EBUS TBNA has been shown to have a high diagnostic yield. [6],[10] However, EBUS TBNA needs dedicated equipment, is only available in selected centers and has a high initial setup costs. Although EBUS TBNA clearly has an excellent diagnostic yield, it does not yet seem pragmatic that every bronchoscopy suite in the near future will have access to this specialized technique. Furthermore, conventional TBNA is being increasingly performed. [11],[12] Whether EBUS TBNA should be performed in all patients with enlarged lymph nodes is under discussion. A randomized trial has shown that conventional TBNA can be as good as EBUS TBNA in subcarinal region. [13] This raises a question if EBUS should be recommended as a first step procedure or only in case of negative conventional TBNA-negative mediastinal lymph nodes. Hilar localization of lymph nodes is markedly facilitated by EBUS as it allows clear identification of the vascular structures. The aim of our study was to assess the diagnostic yield of EBUS TBNA in hilar lymphadenopathy and conventional TBNA-negative mediastinal lymphadenopathy. Materials and Methods Sixty-two patients (49 males; mean age, 66 years) over 2 years having either hilar lymphadenopathy or conventional TBNA-negative/inconclusive mediastinal lymphadenopathy underwent real-time CP-EBUS TBNA. Bronchoscopy was performed under local anesthesia and sedation with hydrocodone and midazolam or propofol. Conventional TBNA was performed using a 22-gauge cytology needle (Bard, Billerica, MA, USA). When coupled with a diagnostic bronchoscopy, TBNA was performed first followed by other diagnostic procedures to avoid needle contamination. [14] Patients in whom conventional TBNA was negative or inconclusive for the diagnosis of mediastinal lymphadenopathy were subjected to CP-EBUS TBNA. Patients with hilar lymphadenopathy directly underwent CP-EBUS TBNA. The CP-EBUS TBNA (Olympus, Tokyo, Japan) has an integrated convex transducer with a frequency of 7.5 MHz at the tip of the flexible bronchoscope. [5] This linear curved array transducer scans parallel to the insertion direction of the bronchoscope. This system also has a Doppler mode, which can be used to identify blood vessels. The outer diameter of the insertion tube is 6.7 mm and that of the tip is 6.9 mm. The angle of view is 90 degrees and the direction of view is 30 degrees forward oblique. A dedicated 22-guage needle was used to perform transbronchial needle aspiration. The needle is visualized through the optics and on the ultrasound image. Details of the procedure have been published earlier. [6] TBNA aspirates were flushed with normal saline in a test tube and fixed with alcohol. Cytological specimens were reported as either positive for malignancy, negative for malignancy, or an inadequate specimen when lymphocytes were not found in the specimen. [15] Results Seventy-two lymph nodes were subjected to EBUS TBNA in 62 patients. The final diagnoses in these patients are presented in [Table - 1]. The 14 patients with benign lesions as final diagnosis were based on clinical follow-up in 10 patients, 2 patients with suspected lung cancer were confirmed benign on surgical documentation, pulmonary embolism, and sarcoidosis. Lymph nodes sampled were paratracheal 31 (right 26, left 5), subcarinal 17, and hilar 24 (right 19, left 5). Three to four aspirates were made per site. Overall, 31 of the 72 (43%) lymph node samples were positive for malignancy (29) or positive benign diagnosis (2), and 17 of the 72 (24%) lymph nodes were true negative at EBUS TBNA confirmed at surgery. EBUS TBNA was performed in 48 mediastinal lymph nodes. EBUS TBNA was diagnostic for malignancy in 19 of the 48 (40%) lymph nodes. EBUS TBNA was negative in 14 lymph nodes and out of these 12 (86%) lymph nodes were surgically confirmed to be true negative and 2 (14%) were false negative. EBUS TBNA was performed on 24 hilar lymph nodes. EBUS TBNA was diagnostic of malignancy in 10 of the 24 (42%) lymph nodes. EBUS TBNA was true negative in 5 lymph nodes and false negative in one lymph node. Therefore, the adequacy was 63%. The false-negative lymph node was PET positive. Among the remaining 8 patients, 5 patients were followed-up clinically for benign disease and malignancy was a strong suspicion in 3 patients. Surgical confirmation of the TBNA-negative lymph node was not obtained in these 3 patients as 1 patient had lymphoma, the second had lung metastasis of colon cancer and the third was not fit for surgical intervention. Malignant lymphadenopathy was clinically suspected in 50 patients and EBUS TBNA was performed at 60 sites in these patients [Figure - 1]. Malignancy was diagnosed in 29 of these 60 (48%) lymph nodes and 17 of the 60 (28%) lymph nodes were true negative confirmed at surgery. EBUS TBNA sampling was inadequate at a right paratracheal lymph node. Surgical confirmation was not done in this patient as he was diagnosed to have M1 disease. Surgical confirmation was not obtained for 10 lymph node sites. Three patients were not fit for surgery, 2 patients were diagnosed with M1 disease, 1 patient each was diagnosed to have chronic lymphoid leukemia, lung metastasis of colon cancer, small cell lung cancer, and lymphoma. In another patient with oropharyngeal cancer, the subcarinal lymph node was both TBNA and PET negative, and hence it was decided to operate only on a singular brain metastasis. [15] Malignancy was not a strong clinical suspicion in 12 patients (paratracheal 5, hilar 5, subcarinal 2). Nine of these 12 patients had a negative EBUS TBNA. All these patients were followed-up and did not develop malignancy. One patient had sarcoidosis and pus was aspirated in another HIV-positive patient with lymphadenopathy. In one patient who was suspected to have hilar lymphadenopathy, the final diagnosis was pulmonary embolism. The overall adequacy for EBUS TBNA based on positive aspirations (malignant 29, sarcoidosis 1, pus 1) and surgically confirmed true negative (17) was 67% (48 out of 72). In patients suspected to have malignant involvement of lymph nodes, the adequacy was 77% (46 out of 60). Three lymph nodes were false negative at EBUS TBNA (PET positive) and were confirmed to harbor malignancy at surgical confirmation. Discussion EBUS TBNA has been reported to have a high diagnostic yield. When available, this technique could be the first step in the diagnosis of mediastinal lymphadenopathy. EBUS TBNA is performed using a dedicated bronchoscope, which can be used only to perform this specific procedure. [5],[6] This technique also has a learning curve due to various factors associated with the technique, such as handling of this new bronchoscope, 30 degrees angle of view, performing ultrasound in the mediastinum, and a unique method of performing TBNA under direct ultrasound guidance. [9] A recent study has shown that the learning curve of EBUS-TBNA to be greater than previously reported. [16] Furthermore, this equipment is also expensive, and hence more likely to have a place in referral centers. Conventional TBNA performed without endobronchial ultrasound guidance can be easily combined with routine diagnostic bronchoscopy and does not need to have dedicated equipment. [1] This technique is also known to have a good diagnostic yield, especially in enlarged lymph nodes and also in the subcarinal location. [17] Therefore, conventional TBNA can be performed also in community practice along with routine diagnostic bronchoscopy. In our institution conventional TBNA for diagnosis of mediastinal adenopathy has been performed for several years, which has also served to train numerous fellows. [15] It is likely that not all fellows trained in bronchoscopy and TBNA will have access to endobronchial ultrasound, at least in the near future. The findings of our study support the concept that conventional TBNA could be routinely performed for enlarged mediastinal lymph nodes as a part of routine diagnostic bronchoscopy, particularly in the setting of centers, which do not have access to EBUS TBNA. If conventional TBNA is negative then the patients can be referred for EBUS TBNA to the referral center. Such an approach may also be valuable at centers responsible for training fellows in routine diagnostic bronchoscopy. The findings of this study show that EBUS TBNA is a useful procedure in patients with hilar lymphadenopathy or mediastinal lymphadenopathy who have had a negative conventional TBNA. A final diagnosis of malignancy could be obtained in almost half the lymph node stations when malignancy was suspected. In more than 50% lymph node stations, which were EBUS TBNA negative were true negative on surgical confirmation, thus enhancing the adequacy of the technique to 67% in patients who were suspected to have malignancy. Surgical confirmation could not be obtained for 10 patients for various reasons. We took the worst case scenario and considered them as false negative. Hilar mediastinal lymph nodes can also be targeted with conventional TBNA. However, they are surrounded by large blood vessels. Hence, for sampling hilar lymph nodes, we proceeded directly with EBUS TBNA without performing conventional TBNA. We could obtain an adequacy of 63% for EBUS TBNA performed for hilar lymph nodes. These figures are also based on conservative calculations. We had complete follow-up and the decision not to perform surgical confirmation was taken at multidisciplinary meetings. EBUS facilitated localization of hilar lymph nodes amidst the vascular structures with the help of Doppler mode. In conclusion, EBUS TBNA has a good diagnostic yield in hilar lymphadenopathy and also when conventional TBNA is negative for mediastinal lymphadenopathy. The approach of first performing conventional TBNA for mediastinal lymphadenopathy and referring negative cases for EBUS TBNA has the potential for application in community practice not having access to EBUS TBNA. EBUS TBNA (or EUS-FNA or both) may gradually replace conventional TBNA for mediastinal staging of non small cell lung cancer, especially since it has been successfully implemented in community practice. [18],[19] References
Copyright 2011 - Journal of Cancer Research and Therapeutics The following images related to this document are available:Photo images[cr11035f1.jpg] [cr11035t1.jpg] |
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