点击显示 收起
Department of Internal Medicine, Pneumology and Critical Care Medicine, Thoraxklinik at the University of Heidelberg, Heidelberg, Germany
Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
ABSTRACT
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: 88eC96% for the endoesophageal approach (4eC9) and 80eC86% for the endobronchial approach (10eC12). 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.
METHODS
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
Endobronchial ultrasound was performed as previously described (14, 15). A flexible ultrasound probe with a 20-MHz transducer (UM-2R/3R with driving unit MH-240 and processor EU-M 20 and 30; Olympus, Tokyo, Japan) was introduced through a bronchoscope with 2.8-mm working channel (Olympus p 20 and Olympus p 40D). The exact location of the target lymph nodes and their relation to the tracheobronchial tree were noted (Figure 1). The probe was then removed from the working channel and transbronchial needle aspiration was performed as previously described (16, 17). We used 22-gauge needles (MW 522; Bard, Billerica, MA) for obtaining aspirates. The "jabbing" method was used for all punctures. Two needle punctures were performed in each abnormal node.
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
Biopsy time was measured from when the lymph node station was identified with ultrasound until the aspiration needle was removed with the sample. Examination times were compared for the two approaches.
Handling of Aspirates
The aspirate was placed onto at least four glass slides and were air dried, stained, and classified. Papanicolaou staining (18, 19) and light microscopy were performed by a cytopathologist who was blinded to the details of the patients. No rapid onsite cytology was performed.
Statistical Methods
Descriptive statistics and percentages are presented as appropriate. Wilcoxon test for paired two-tailed data were used for comparing the size and the procedure time. The chi-quadrate test for nonparametric distribution were used to calculate the statistical value comparing the techniques.
Alpha was set at 0.05, and the SPSS 11.5 (SPSS Inc., Chicago, IL) statistical software package was used for all analyses.
RESULTS
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, 2eC10 minutes; interquartile range, 25eC75; percentile, 2eC3.9) and 4.1 minutes for the transesophageal technique (SD ± 2.35; median, 3.5 minutes; range, 2eC11 minutes; interquartile range, 25eC75; percentile, 2.9eC5). The time difference was highly significant (p < 0.001).
There were no complications in either approach.
DISCUSSION
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 (4eC12). 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
Our trial confirms the excellent yield of ultrasound-guided needle aspirations for both approaches. The endobronchial approach has a slight advantage in obtaining biopsies from right-sided stations. In our patients, the differences between approaches were neither clinically nor statistically significant. Combining both endoscopic approaches is potentially as or more effective as surgical staging of enlarged nodes.
REFERENCES
Sihoe AD, Yim AP. Lung cancer staging. J Surg Res 2004;117:92eC106.
Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med 2004;350:379eC392.
Toloza EM, Harpole L, Detterbeck F, McCrory DC. Invasive staging of non-small cell lung cancer: a review of the current evidence. Chest 2003;123:157eC166.
Fritscher-Ravens A, Sriram PV, Bobrowski C, Pforte A, Topalidis T, Krause C, Jaeckle S, Thonke F, Soehendra N. Mediastinal lymphadenopathy in patients with or without previous malignancy: EUS-FNA based differential cytodiagnosis in 153 patients. Am J Gastroenterol 2000;95:2278eC2284.
Vilmann P. Endoscopic ultrasonography guided fine needle aspiration biopsy of lymph nodes. Gastrointest Endosc 1996;43:24eC29.
Wiersema MJ, Vilmann P, Giovannini M, Chang KJ, Wiersema LM. Endosonography guided fine needle aspiration biopsy: diagnostic accuracy and complication assessment. Gastroenterology 1997;112:1087eC1095.
Pedersen BH, Vilmann P, Milman N, Folke K, Hancke S. Endoscopic ultrasonography with guided fine needle aspiration biopsy of a mediastinal mass lesion. Acta Radiol 1995;36:326eC328.
Silvestri GA, Hoffman BJ, Bhutani MS, Hawes RH, Coppage L, Sanders-Cliette A, Reed CE. Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer. Ann Thorac Surg 1996;61:1441eC1446.
Gress FG, Savides TJ, Sandler A, Kesler K, Conces D, Cummings O, Mathur P, Ikenberry S, Bilderback S, Hawes R. Endoscopic ultrasonography, fine-needle aspiration biopsy guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-small-cell lung cancer: a comparison study. Ann Intern Med 1997;15:604eC612.
Herth F, Becker HD, Ernst A. Conventional vs endobronchial ultrasound-guided transbronchial needle aspiration: a randomized trial. Chest 2004;125:322eC325.
Herth FJ, Becker HD, Ernst A. Ultrasound-guided transbronchial needle aspiration: an experience in 242 patients. Chest 2003;123:604eC607.
Okamoto H, Watanabe K, Nagatomo A, Kunikane H, Aono H, Yamagata T, Kase M. Endobronchial ultrasonography for mediastinal and hilar lymph node metastases of lung cancer. Chest 2002;121:1498eC1506.
Mountain CF, Dressler CM. Regional lymph node classification for lung cancer staging. Chest 1997;111:1718eC1723.
Herth F, Becker HD. Endobronchial ultrasound of the airways and the mediastinum. Monaldi Arch Chest Dis 2000;55:36eC45.
Falcone F, Fois F, Grosso D. Endobronchial ultrasound. Respiration (Herrlisheim) 2003;70:179eC194.
Gasparini S, Zuccatosta L, DeNictolis M. Transbronchial needle aspiration of mediastinal lesions. Monaldi Arch Chest Dis 2000;55:29eC32.
Mehta AC, Kavuru MS, Meeker DP, Gephardt GN, Nunez C. Transbronchial needle aspiration for histology specimens. Chest 1989;96:1268eC1272.
Mehta AC, Meeker DP. Transbronchial needle aspiration for histology specimens. In: Wang KP, Mehta AC, editors. Flexible bronchoscopy. Cambridge, UK: Blackwell Science; 1995. pp. 199eC205.
Wagner ED, Ramzy I, Greenburg SO, Gonzalez JM. Transbronchial fine needle aspiration: reliability and limitations. Am J Clin Pathol 1989;92:36eC41.
Coughlin M, Deslauriers J, Beaulieu M, Fournier B, Piraux M, Rouleau J, Tardif A. Role of mediastinoscopy in pretreatment staging of patients with primary lung cancer. Ann Thorac Surg 1985;40:556eC560.
Luke WP, Pearson FG, Todd TR, Patterson GA, Cooper JD. Prospective evaluation of mediastinoscopy for assessment of carcinoma of the lung. J Thorac Cardiovasc Surg 1986;91:53eC56.
Hoffmann H. Invasive staging of lung cancer by mediastinoscopy and video-assisted thoracoscopy. Lung Cancer 2001;34:3eC5.