Relevance of Endobronchial Ultrasonography to Thoracic Surgeons

Relevance of Endobronchial Ultrasonography to Thoracic Surgeons

STATE OF THE ART Relevance of Endobronchial Ultrasonography to Thoracic Surgeons Rafael S. Andrade, MD The relevance of endobronchial ultrasonography...

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STATE OF THE ART

Relevance of Endobronchial Ultrasonography to Thoracic Surgeons Rafael S. Andrade, MD The relevance of endobronchial ultrasonography (EBUS) to thoracic surgeons is 2-fold: first, EBUS is an accurate and versatile diagnostic tool; second, EBUS is of importance to our specialty. The diagnostic performance of endobronchial ultrasonography (EBUS) is similar to that of mediastinoscopy, except for a lower negative predictive value for EBUS. Consequently, EBUS does not replace mediastinoscopy, but instead EBUS and mediastinoscopy are complementary. A thoracic surgeon proficient in EBUS has the ability to decide which tool or combination of tools to use to optimize patient care. The relevance of EBUS can be described in evolutionary terms: proficiency in EBUS exemplifies a new trait that can enhance our adaptability to the current environment. An indirect measure of the acquisition of this new skill by our specialty can be gleaned from an overview of original EBUS publications: nearly one-half are authored or coauthored by thoracic surgeons. EBUS is an excellent diagnostic tool available to thoracic surgeons to optimize patient care and an example of a skill that may enhance our survival as a surgical specialty. Semin Thoracic Surg 22:150-154 © 2010 Elsevier Inc. All rights reserved. INTRODUCTION To understand the importance of endobronchial ultrasonography (EBUS) to thoracic surgeons, one must address 2 issues: (1) the specific facts about EBUS as a clinical tool, and (2) the relevance of EBUS to thoracic surgeons.

Division of General Thoracic and Foregut Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.

with thoracic malignancies can be evaluated accurately with EBUS-TBNA alone, reserving surgical biopsy (eg, mediastinoscopy, thoracoscopy) for cases with a negative EBUS examination and a high pretest probability of malignancy (ie, suspicious lymph node with negative cytology by EBUS-TBNA). On the basis of several EBUS reports, the thoroughness of mediastinal lymph node (MLN) station sampling in patients with non-small cell lung cancer (NSCLC) has been justifiably questioned: the authors of some studies report the sampling, on average, of only 1.5 MLN stations.1,4 However, incomplete mediastinal staging with EBUS is not a flaw of the procedure itself because recent publications by thoracic surgeons demonstrate that patients with lung cancer can be appropriately staged by sampling 2.5 or more MLN stations.5,8 Several researchers also indicate that more sophisticated diagnostic analyses can be performed on tissue obtained via EBUS-TBNA, such as immunohistochemical analysis of cell-cycle proteins,9 quantitative polymerase chain reaction,10 and epidermal growth factor receptor (EGFR) mutational analysis.2,9-12 In addition, therapeutic implications of EBUS are gradually surfacing, for example EBUS-guided fiducial marker placement and brachytherapy.13,14 In concise terms, EBUS is a very useful tool and is here to stay.

Address reprint requests to Rafael S. Andrade, MD, Division of General Thoracic and Foregut Surgery, Department of Surgery, University of Minnesota, MMC 207, 420 Delaware Street, SE, Minneapolis, MN 55455. Email: [email protected]

Technical Pearls We have previously described our technique in detail15; in the present review we put emphasis on some important technical pearls of EBUS-TBNA.

EBUS FACTS Diagnostic Performance During the past decade, EBUS has emerged as a safe, accurate, and versatile tool. Relevant data on the performance of EBUS-guided transbronchial needle aspiration biopsy (EBUS-TBNA) as a diagnostic test, and comparison with the diagnostic performance of mediastinoscopy, are summarized in Table 1.1-6 The Achilles’ heel of EBUS-TBNA has been the variability in negative predictive value (NPV), which has been reported as low as 14%.7 However, the NPV of studies that include surgical confirmation of negative EBUS-TBNA (a true calculation of NPV) ranges between 80% and 98.9%. In our experience,5 the most patients (85%)

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1043-0679/$-see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2010.08.006

RELEVANCE OF ENDOBRONCHIAL ULTRASONOGRAPHY TO THORACIC SURGEONS Table 1. Diagnostic Performance of EBUS and Mediastinoscopy in Patients With Thoracic Malignancies Sensitivity Specificity PPV NPV Accuracy

EBUS 88.1-99.1 97.4-100 98.1-100 14-98.9 91.7-98.7

Mediastinoscopy 86-93 100 100 80-99 93-96

Values are expressed in percentages. EBUS, endobronchial ultrasonography; NPV, negative predictive value; PPV, positive predictive value.

Anesthesia We perform EBUS under general endotracheal anesthesia with an 8.5- to 9-mm endotracheal tube (ETT) to easily accommodate the EBUS bronchoscope (Olympus Exera; Olympus Imaging American, Inc, Center Valley, PA). We deliberately position the tip of the ETT in the proximal trachea (cuff in subglottic space) to allow better apposition of the EBUS bronchoscope tip to the tracheal wall (important to see and sample stations 2 and 4). Intravenous anesthesia is preferable to gaseous anesthesia because the biopsy channel of the EBUS bronchoscope allows for gas leakage. The advantages of general anesthesia from our perspective include patient comfort, easy accessibility to normal-sized paratracheal lymph nodes (suppression of cough reflex and intermittent apnea reduce movement artifact), and the option to perform additional procedures in the same setting.

Figure 2. A needle aspiration biopsy can be obtained without piercing the water-filled balloon. (Color version of figure is available online at http:// www.semthorcardiovascsurg.com.)

Mediastinal Evaluation A systematic MLN evaluation is imperative in patients with NSCLC. We start with the contralateral paratracheal MLN stations to rule out N3 disease, after that we proceed with subcarinal and ipsilateral paratracheal MLN stations; we routinely sample 3 MLN stations (4 R, 4 L, and 7). The short axis of every target MLN should be measured with ultrasound (US) and compared with the patient’s computed tomography scan to further ensure accurate staging. A fluid-filled balloon can be placed on the US probe of the EBUS bronchoscope and may be useful to enhance US imaging of normal-sized MLNs

Figure 1. Ultrasonographic view of the left paratracheal region (4 L) without (A) and with (B) the waterfilled balloon: (B) is clearer and actually permits one to determine that there are no MLNs of appropriate size to sample. PA, pulmonary artery. Seminars in Thoracic and Cardiovascular Surgery ● Volume 22, Number 2

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Figure 3. Maximum flexion of EBUS bronchoscope without TBNA needle in place (A) and with TBNA needle in place (B). Sampling of 10 R (C, arrow) can be challenging with the TBNA needle in place, because the less acute angle of the scope may prohibit proper imaging. (Color version of figure is available online at http://www.semthorcardiovascsurg.com.)

in the paratracheal positions (Fig. 1); however, other than for stations 2 and 4, the balloon is generally superfluous. It is unnecessary to deflate the balloon before performing TBNA because TBNA infrequently pierces the balloon (Fig. 2) and proper visualization of the target is more important than preservation of balloon integrity. ●

EBUS-TBNA Technique Tips ● EBUS image loss with the TBNA needle in place: on occasion MLNs or masses just above the bifurcation of the upper lobes can be seen without the needle in place but are no longer visible after loading the TBNA needle. Figure 3 provides a graphic explanation of this phenomenon: the tip of the EBUS bronchoscope can bend almost at a 90° angle (Fig. 3A) when the TBNA needle has not been loaded and may be able to provide a good image of a 10 R MLN (Fig. 3C); however, after loading the TBNA needle, the maximum deflection angle is less acute (Fig. 3B), and the area of interest may no longer be visible. There is no practical solution to this particular problem. ● MLN sampling: We prefer to leave the stylet inside the TBNA needle as we pierce the airway wall and position the needle in the target to minimize contamination of the sample with epithelial cells; we then perform 10 to 15 needle passes without suction and apply the suction syringe only for the last 2 or 3 needle passes. Every lymph node or mass is sampled 1 to 3 times if cytology is positive for malignancy and 3 times if cytology is benign or nondiagnostic; sampling more than 3 times, because of a nondiagnostic specimen, almost never yields a reliable pathologic diagnosis. ● TBNA needle replacement: We use the same 152

needle when the clinical and US evaluation suggest low risk for a malignancy, and we sample low risk MLN first (ie, N3). We never use the same needle for another MLN station if our suspicion for malignancy is high or after obtaining cytologic confirmation of malignancy. Subcarinal MLN: sampling of level 7 MLN requires special attention to avoid the risk of a false-positive result. The central airways in patients with squamous cell cancer may have widespread dysplasia or even carcinoma insitu that may lead to a false-positive result (Fig. 4).5 To avoid this problem, we always sample level 7 MLN via endoesophageal ultrasound (EUS) in patients with squamous cell cancer.

Figure 4. Example of a patient with a squamous cell cancer of the left lung and a false-positive station 7 EBUS-TBNA despite taking the sample through the right main stem bronchus. Patients with centrally located squamous cell lung cancers should have station 7 sampled via endesophageal ultrasound or mediastinoscopy.

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RELEVANCE OF ENDOBRONCHIAL ULTRASONOGRAPHY TO THORACIC SURGEONS ●

Rapid on-site evaluation (ROSE) of cytologic specimen: Our EBUS program relies heavily on a close collaboration between thoracic surgeons and cytopathologists. The cytopathologists at the University of Minnesota have extensive experience with TBNA as evidenced by a correlation of ROSE and final cytology of 95%5; we make intraoperative decisions on the basis of the ROSE result.

THE RELEVANCE OF EBUS TO THORACIC SURGEONS The population of thoracic surgeons has decreased during the past decade because of poor adaptation to our changing environment. The number of thoracic surgery residency candidates decreased by 51% between 1996 and 2008, and in 2004 we recorded the first actual reduction in the total population of thoracic surgeons.16-18 How does our decreasing population link with EBUS and why is EBUS relevant to thoracic surgeons? Because our decrease in population was the result of inadequate adaptability, we might have learned a lesson in natural selection: we now recognize the need to acquire relevant new skills to enhance the chances of survival of our specialty.19 EBUS is an excellent example of such a trait. An indirect measure of our EBUS aptitudes can be gleaned from the peer-reviewed medical literature

1. Herth FJF, Eberhardt R, Krasnik M, et al: Endobronchial ultrasound-guided transbronchial needle aspiration of lymph nodes in the radiologically and positron emission tomography-normal mediastinum in patients with lung cancer. Chest 133:887-891, 2008 2. Yasufuku K, Nakajima T, Motoori K, et al: Comparison of endobronchial ultrasound, positron emission tomography, and CT for lymph node staging of lung cancer. Chest 130: 710-718, 2006 3. Hwangbo B, Kim SK, Lee HS, et al: Application of endobronchial ultrasound-guided transbronchial needle aspiration following integrated PET/CT in mediastinal staging of potentially operable non-small cell lung cancer. Chest 135:1280-1287, 2009 4. Szlubowski A, Kuzdzal J, Kotodziej M, et al: Endobronchial ultrasound-guided needle aspiration in the non-small cell lung cancer staging. Eur J Cardiothorac Surg 35:332-336, 2009 5. Andrade RS, Groth SS, Rueth NM, et al: Evaluation of mediastinal lymph nodes with endobronchial ultrasound: The thoracic surgeon’s perspective. J Thorac Cardiovasc Surg 139: 578-583, 2010

on EBUS. A search for “EBUS” in PubMed retrieved a list of 211 English language articles since the first report of EBUS-TBNA in 200120; inclusion of all clinical series and exclusion of review articles, case reports, articles written by pathologists, and pediatric papers resulted in 107 papers. Of these 107 papers, thoracic surgeons wrote 21 (19.6%), thoracic surgeons collaborated with pulmonologists in 28 (26.2%), and pulmonologists exclusively authored 58 (54.2%). Proficiency in EBUS is just one example of a new and useful trait; we will have to continue acquiring skills in a large variety of disciplines (eg, basic and science innovations, education, administration, financial sustainability, advocacy, etc) to attract high-quality resident candidates and reverse our negative population growth. THE BOTTOM LINE ON EBUS AND THORACIC SURGEONS The ultimate value of EBUS in thoracic surgery is as a complimentary tool that adds to our armamentarium. It does not represent the end of an era but rather may mark the beginning of a new generation of thoracic surgeons. Hence, the discussion of EBUS versus mediastinoscopy is shortsighted and irrelevant. A thoracic surgeon proficient in EBUS has the ability to decide which tool or combination of tools to use to optimize patient care.

6. Groth SS, Andrade RS: Endobronchial and endoscopic ultrasound-guided fine-needle aspiration: A must for thoracic surgeons. Ann Thorac Surg 89:S2079-S2083, 2010 7. Herth FJF, Eberhardt R, Vilmann P, et al: Realtime endobronchial ultrasound guided transbronchial needle aspiration for sampling mediastinal lymph nodes. Thorax 61:795-798, 2006 8. Block MI: Endobronchial ultrasound for lung cancer staging: How many stations should be sampled? Ann Thorac Surg 89:1582-1587, 2010 9. Garcia-Olive I, Monso E, Andreo F, et al: Endobronchial ultrasound-guided transbronchial needle aspiration for identifying EGFR mutations. Eur Respir J 35:391-395, 2010 10. Nakajima T, Yasufuku K, Suzuki M, et al: Assessment of epidermal growth factor receptor mutation by endobronchial ultrasound-guided transbronchial needle aspiration. Chest 132:597-602, 2007 11. Mohamed S, Yasufuku K, Nakajima T, et al: Analysis of cell cycle-related proteins in mediastinal lymph nodes of patients with N2-NSCLC obtained by EBUS-TBNA: Relevance to chemotherapy response. Thorax 63:642-647, 2008

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12. Dango S, Cururuz B, Mayer O, et al: Detection of disseminated tumor cells in mediastinoscopic lymph node biopsies and endobronchial ultrasonography-guided transbronchial needle aspiration in patients with suspected lung cancer. Lung Cancer 68:383-388, 2010 13. Harley DP, Krimsky WS, Sarkar S, et al: Fiducial marker placement using endobronchial ultrasound and navigational bronchoscopy for stereotactic radiosurgery: An alternative strategy. Ann Thorac Surg 89: 368-374, 2010 14. Harms W, Krempien R, Grehn C, et al: Electromagnetically navigated brachytherapy as a new treatment option for peripheral pulmonary tumors. Stahlenther Onkol 182:108111, 2006 15. Groth SS, Andrade RS: Endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal lymph node staging in non-small cell lung cancer. Semin Thorac Cardiovasc Surg 20:274-278, 2008 16. Mathisen DJ: Is it an opportune time to be interested in cardiothoracic surgery? A American Association for Thoracic Surgery web site. Available at: http://www.aats.org/TSR/Cardiothoracic-Surgeon/

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RELEVANCE OF ENDOBRONCHIAL ULTRASONOGRAPHY TO THORACIC SURGEONS Interested-in-cardiothoracic-surgery.html. Accessed June 2010 17. Prasad SM, Massad MG, Chedrawy EG, et al: Weathering the storm: How can thoracic surgery training programs meet the new challenges in the era of less-invasive technologies?

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J Thorac Cardiovasc Surg 137:1317-1326, 2009 18. Wilcox BR: The match and changing times: CTSNet 2007. Available at: www.ctsnet.org/ sections/newsandviews/specialreports/article5.html. Accessed June 2010

19. Encyclopedia britannica web site. http://www. britannica.com. Accessed June 2010 20. Herth F, Becker HD, Manegold C, et al: Endobronchial ultrasound (EBUS)—assessment of a new diagnostic tool in bronchoscopy for staging of lung cancer. Onkologie 24:151-154, 2001

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