Published ahead of print on January 21, 2005, doi:10.1164/rccm.200411-1560OC
© 2005 American Thoracic Society doi: 10.1164/rccm.200411-1560OC
Transbronchial versus Transesophageal Ultrasound-guided Aspiration of Enlarged Mediastinal Lymph NodesDepartment of Internal Medicine, Pneumology and Critical Care Medicine, Thoraxklinik at the University of Heidelberg, Heidelberg, Germany; and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts Correspondence and requests for reprints should be addressed to Armin Ernst, M.D., Director, Interventional Pulmonology BIDMC/ Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215. E-mail: aernst{at}bidmc.harvard.edu
Rationale: Transesophageal and transbronchial, ultrasound-guided, fine-needle aspiration of enlarged mediastinal lymph nodes have become popular, but have never been compared directly. Objectives: To compare the relative diagnostic yield and ability of the transesophageal and transbronchial approaches to reach abnormal mediastinal lymph nodes. Methods: A total of 160 patients with enlarged lymph nodes in one of eight mediastinal lymph node stations underwent transbronchial and transesophageal biopsies in a crossover design. Each of the eight stations was allocated 20 patients. Two needle punctures were done with each approach. Measurements: Percentage of successful biopsies, percentage of patients diagnosed, and biopsy time were measured from when the lymph node was identified with ultrasound. Main Results: Among the 106 men and 54 women (mean age 53.2 years), transbronchial aspiration was successful in 85%, and transesophageal aspiration was successful in 78% (p = 0.2). For each station, the number of positive samples for the transbronchial/transesophageal approaches was: 2R: 19/13; 2L: 16/19; 3: 17/15; 4R: 19/12; 4L: 17/20; 7: 19/20; 10R: 18/9; and 10L: 17/18. Combining both approaches produced successful biopsies in 97% and diagnoses in 94% of patients. Mean biopsy times were 3.2 minutes for the transbronchial approach and 4.1 minutes for the transesophageal approach. The transbronchial approach was superior in nodes 2R, 4R, and 10R. No complications were encountered. Conclusions: In experienced hands, enlarged mediastinal lymph nodes may be aspirated with either the transbronchial or transesophageal approach. These nonsurgical approaches have similar diagnostic yields, although the transbronchial approach is superior for right-sided lymph nodes. Combining both approaches provides results similar those of mediastinoscopy.
Key Words: endobronchial ultrasound • endoesophageal ultrasound • lung cancer • mediastinal lymphadenopathy • transbronchial needle aspiration Enlarged mediastinal lymph nodes and mediastinal masses are a common diagnostic problem for chest physicians. In patients with lung cancer, evaluating mediastinal nodes is crucial for proper staging (1, 2) and for assessing the extent of the disease. Mediastinoscopy is a surgical procedure commonly performed in this circumstance and is considered to be the reference standard for establishing a diagnosis. It requires use of an operating room and general anesthesia, and the sensitivity of the procedure has been reported to be as low as 81% (3). Alternative, minimally invasive biopsy methods for mediastinal lymph nodes have been developed. They include endoesophageal and endobronchial, ultrasound-guided fine-needle aspiration. Both procedures have the advantage of being performed under conscious sedation and have been reported to give excellent yields: 88–96% for the endoesophageal approach (4–9) and 80–86% for the endobronchial approach (10–12). In addition, endoscopic needle aspiration may allow access to stations not easily reached by mediastinoscopy, such as hilar nodes and posterior carinal nodes. Endoesophageal and endobronchial ultrasound-guided transbronchial needle aspiration have developed in parallel, but the techniques have never been compared directly in their yields or in their ability to reach specific lymph node stations. This trial was designed to answer these questions.
The study was approved by the Institutional Review Board of the Thoraxklinik Heidelberg. Between January 2002 and January 2004, patients with enlarged mediastinal lymph nodes (> 1 cm) as assessed by contrast-enhanced computed tomography who underwent endoscopy were eligible for the trial. The location of the lymph nodes was described according to the classification of the American Thoracic Society (13). The eight mediastinal lymph node station groups included were: 2R, 2L, 3, 4R, 4L, 7, 10R, and 10L. Because endoesophageal ultrasound allows for biopsies of lymph nodes close to the esophagus and transbronchial needle aspiration follows the airways, slightly different strengths should be expected. To keep the comparison fair, we did not include hilar nodes in positions 5, 6, or 11 (which are accessible only by bronchoscopy) and stations 8 and 9 nodes (which are accessible only by esophagoscopy) (5, 7, 10). After informed consent was obtained, patients were prospectively assigned to one of the eight lymph node station groups depending on their image findings. Patients were accrued until all groups were filled. Patients underwent ultrasound-guided transbronchial and transesophageal needle biopsies in a crossover design. A successful puncture was defined as either obtaining a specific diagnosis or by detecting lymphocytes in the aspirate. The presence of lymphocytes themselves was not considered diagnostic. Patients with nondiagnostic aspirates underwent either mediastinoscopy or another surgical procedure to obtain a definitive diagnosis. The endoscopic procedures were performed in the same setting with the patients under conscious sedation with intravenous midazolam or propofol and fentanyl as needed. Different operators performed endoesophageal ultrasound-guided and endobronchial ultrasound-guided procedures to decrease any potential bias.
The Endobronchial Procedure
The Endoesophageal Procedure The echoendoscope (Hitachi EUB 6500 ultrasound console with a Pentax FU36 endosonoscope, Tokyo, Japan, and Olympus UC 30P; Olympus Optical) was introduced up to the level of the celiac axis and gradually withdrawn upward for detailed mediastinal imaging (4, 5). The size, location, and morphology of the lesions were recorded with endoesophageal ultrasound imaging, and fine-needle aspiration was performed with a 22-gauge Vilmann-Hancke needle (GIP MedizinTechnik, Grassau, Germany) on suspicious lesions. If more than one lymph node was detected, the most suspicious (hypoechoic or inhomogeneous and large) and easily accessible nodes were aspirated. Aspiration was performed by introducing the needle through the biopsy channel of the echoendoscope. Because ultrasound waves are emitted parallel to the long axis of the endoscope, the entire needle could be visualized approaching a target in the sector-shaped sound field (Figure 2).
Pulsed-wave Doppler ultrasonography was performed whenever vascular structures were potentially in the pathway of the needle or adjacent to it to correct the target line if necessary. The needle was advanced through the wall of the esophagus and guided into the target lesion. The 170-mm central stylet was removed, and suction was applied with a special 10-ml syringe attached to the hub of the needle as the needle was moved back and forth within the mass. The suction was released slowly, and the needle assembly removed from the biopsy channel. Two needle passes were made to obtain adequate tissue.
Biopsy Time
Handling of Aspirates
Statistical Methods Alpha was set at 0.05, and the SPSS 11.5 (SPSS Inc., Chicago, IL) statistical software package was used for all analyses.
Of the 160 patients enrolled and who underwent both techniques, 54 were women and 106 were men, with a mean (SD) age of 53.2 years (11.8 years) and a range of 33 to 76 years. The main indications for biopsy were for diagnosis of enlarged lymph nodes with unknown origin and cancer staging, especially exclusion of N3 nodes. The mean (SD) punctured lymph node size was 1.7 cm (± 0.36; range). In 142 patients (89%), the lymph nodes were aspirated successfully (resulting in either a specific diagnosis or the presence of lymphocytes in the aspirate) through the transbronchial approach (Table 1). With endoesophageal ultrasound guidance, 126 (78%) nodes were aspirated successfully. Table 1 also shows the differences between lymphocyte-positive specimens and specific diagnosis obtained. The result for stations 2R, 4R, and 10R were better for the transbronchial approach than for the transesophageal approach, which is explained by the fact that the esophagus commonly is located more to the left of the trachea.
Combining the results of both approaches, a successful puncture of the included enlarged lymph nodes was achieved in 97% of patients and resulted in a specific diagnosis in 94%. All nondiagnostic biopsies in nine patients were followed by a surgical procedure, but a more specific diagnosis could not be obtained in five of the nine (Table 2).
Mean examination time was 3.2 minutes for the endobronchial technique (SD ± 2, median, 3.2 minutes; range, 2–10 minutes; interquartile range, 25–75; percentile, 2–3.9) and 4.1 minutes for the transesophageal technique (SD ± 2.35; median, 3.5 minutes; range, 2–11 minutes; interquartile range, 25–75; percentile, 2.9–5). The time difference was highly significant (p < 0.001). There were no complications in either approach.
Chest physicians often need to assess enlarged mediastinal lymph nodes (1, 2). Lymph nodes may be enlarged for a variety of inflammatory, infectious, or malignant reasons, and it is important to ascertain a diagnosis or in case of malignancy to determine the stage of disease (20). Mediastinoscopy has long been the mainstay of mediastinal lymph node sampling and does have disadvantages. It is a surgical procedure requiring general anesthesia and the use of an operating room. It is difficult to perform the procedure a second time in a given patient. Additionally, the reach of the procedure is limited, and lymph nodes in the posterior carina, hilar stations, and station 8 are generally inaccessible. Last, although it is the reference standard, mediastinoscopy's specificity and sensitivity are not optimal (3, 21, 22). Interest in nonsurgical staging has been increasing since endoscopic needle aspiration of mediastinal lymph nodes has been possible (17, 18). The introduction of endoesophageal ultrasound-guided and endobronchial ultrasound-guided needle aspiration and the resulting increase in yield has further enhanced this diagnostic instrument. Endoscopic imaging supported by ultrasound use has several advantages over mediastinoscopy: there is no need for surgery or general anesthesia, it can be done repetitively in the same person, and, depending on which endoscopic modality is used, lymph node stations not surgically accessible are within reach (4–12). In the case of bronchoscopy, an airway assessment and use of additional modalities, such as autofluorescence bronchoscopy, is also possible. Our trial confirms the excellent yield of ultrasound-guided needle aspirations for both modalities and shows a slight advantage of endobronchial ultrasound-guided transbronchial needle aspiration in right-sided stations. For the whole group, the difference was not significant and the endoscopic approaches were comparing well with each other. One of the most interesting findings of the study is that the combined yield of both approaches for the included lymph node stations was at least as good as surgical mediastinoscopy. Taking into account the ability of the combined endoscopic approach to also reach hilar nodes and station 8 nodes in a complementary fashion, these approaches are potentially a more powerful tool than surgical staging. A downside of these approaches is obviously the need to be able to perform both endoscopic techniques to avoid the logistical problems of arranging for two subspecialists to converge onto one procedure. However, the endoesophageal approach can easily be learned after mastering the endobronchial approach, and it may make sense to incorporate both techniques into the armamentarium of an advanced chest endoscopist.
Conclusions
Conflict of Interest Statement: F.J.F.H. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; W.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; R.E. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; H.D.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; A.E. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. Received in original form November 22, 2004; accepted in final form January 12, 2005
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