Perhaps no other technology, after the introduction of the flexible bronchoscope, has generated so much interest among interventional pulmonologists as has endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). In just about 10 years it has seen numerous publications, including several debates on its place in clinical practice.1,2 However, a recent analysis of the publications on EBUS-TBNA has thrown up interesting data. Of the 883 publications identified, >60% have originated from developed countries, with the United States contributing to nearly half of them and Japan, Germany, and England being among the other major contributors. Interestingly, <5% of publications were from developing countries, including India (with 11 publications). Thus, despite its increasing popularity, EBUS-TBNA seems to be of a greater interest to clinicians and researchers in developed countries than to their counterparts in the developing world, likely because of its widespread availability or the lack of it. Although EBUS has been available in India for the last few years, its exact place in developing countries given its high cost remains unclear. Herein, we try to place EBUS-TBNA in a perspective as far as India, as well as in other emerging economies with similar socioeconomic concerns.
Although flexible bronchoscopy has become widely available in India, the first EBUS-TBNA was installed at a corporate hospital only in 2008. The first equipment installed in a government facility was at our center in 2011, at which time <10 centers had this facility. The number had gone up to approximately 30 by the end of 2013, and many more centers are lined up to add this technology in the near future. The rapidly increasing interest in EBUS-TBNA is contrary to the decline in conventional TBNA (cTBNA) that was observed between 1997 and 2005.3 What is driving more and more pulmonologists to acquire this costly gadget? Is it driven by essentiality or is it just the glamour and “me too” mentality?
To discuss the essentiality of EBUS-TBNA, we must briefly review the advantages that it has to offer over other known techniques in the diagnostic armamentarium available to the pulmonologist. No doubt, the sampling of mediastinal lymph nodes under direct vision of an ultrasound probe is an exhilarating experience for the operator and provides her/him with the confidence that pathology if any would have been picked up, similar to if not better than a fine needle aspiration from large peripheral lymph nodes under direct palpation. Moreover, one can sample small lymph nodes, <10 mm in short axis, located in challenging difficult locations (4L). Combined with esophageal ultrasound (EUS) guidance, EBUS-TBNA has been found to be extremely useful in cancer staging, superior to cTBNA, computed tomography, or positron emission tomography, and similar to, if not better than, mediastinoscopy.4–7 Thus, for lung cancer staging it is definitely advantageous to have EBUS. The million dollar question is, however, how many individuals in India actually need lung cancer staging?
Recent data have shown that almost 84% of non–small cell lung cancer patients are clearly inoperable at diagnosis and may not need mediastinal staging.8 Data collected (Pattabhiraman VR, Mehta R, Goyal R, Madan K, Narasimhan R, Chhajed P, Gupta D, wriitten communication, 2013) from 7 centers across India with variable quantum of experience have shown that <3% of the 2075 EBUS-TBNA procedures have been carried out for lung cancer staging. Therefore, clearly, the primary need for EBUS in India is diagnostic. The most common indication for TBNA in India is differential diagnosis of mediastinal adenopathy due to granulomatous lung disease, primarily tuberculosis or sarcoidosis.9,10
Several authors have investigated the role of EBUS-TBNA in isolated intrathoracic lymphadenopathy due to tuberculosis.11–14 In the largest study, EBUS-TBNA was found to have an excellent diagnostic yield (94%).13 However, in this study the most common lymph node station sampled was station 7 followed by 4R (73%). Stations 4R and 7 are in fact the stations most easily accessible by cTBNA. Several studies have shown that the yield of EBUS-TBNA is similar to that of cTBNA for station 7.15–17 Hence, in the majority of cases of tuberculous lymphadenopathy, cTBNA would be expected to provide good diagnostic yield.18 The data on EBUS-TBNA for sarcoidosis are more robust than those for tuberculosis. In a recently published meta-analysis, we found the yield of EBUS-TBNA in sarcoidosis to be about 54% to 93% in various studies, with the pooled yield being 79%.19 The yield of cTBNA in sarcoidosis was found to be 6% to 90% in different studies, with a pooled efficacy of 62%.20 The yield is clearly less when compared with EBUS-TBNA; however, if cTBNA is combined with transbronchial lung biopsy (TBLB), the yield increases to 83%.20 More definite evidence regarding the position of EBUS-TBNA in sarcoidosis has come in the form of 2 recently published large randomized trials. The Granuloma trial (304 patients) found the yield of endoscopic ultrasound procedures (EUS or EBUS) to be about 74%, which was significantly higher than that of conventional bronchoscopy procedures (48%).21 However, it still meant that one in 4 patients would remain potentially undiagnosed with the use of EBUS-TBNA alone. Recently, we have reported the results of a randomized trial of EBUS-TBNA versus cTBNA combined with endobronchial (EBB) and TBLB in the diagnosis of sarcoidosis. Although EBUS-TBNA alone was superior to cTBNA (74.5% vs. 48.4%, P=0.004), the most remarkable finding was that the diagnostic yields of EBUS-TBNA versus cTBNA, in combination with EBB and TBLB, were similar (92.7% vs. 85.5%; P=0.34).22 The results of this study bring out 2 important points: (a) EBUS-TBNA has to be combined with conventional bronchoscopy procedures such as EBB and TBLB to optimize the diagnostic yield; and (b) cTBNA with EBB and TBLB is as good, if not better, in the diagnostic workup of sarcoidosis. The lymph node imaging characteristics are an obvious advantage of EBUS. Recently, we have shown that the finding of a heterogeneous echotexture or coagulation necrosis in the lymph nodes on EBUS along with a positive Tuberculin Skin Testing strongly favors the diagnosis of tuberculosis over sarcoidosis.23
What is the role of EBUS-TBNA in the developing world? The superiority of sampling mediastinal nodes by EBUS-TBNA over cTBNA for the diagnosis of malignant and nonmalignant conditions is a fact. There is no denying that, faced with a situation in which mediastinal lymphadenopathy is the only or the easiest site for obtaining tissue, EBUS is perhaps the safest way with maximum yield. However, one should not forget the high initial cost of the equipment and the higher recurring costs of EBUS-TBNA compared with cTBNA.24 The startup cost ranges between $150,000 and $200,000, the EBUS-TBNA needle (with balloon) costs approximately $200, and the professional and technical charges vary between $115 and $820 depending on the centers. If general anesthesia and rapid on-site cytologic evaluation are also used, the cost would increase further. In contrast, a video bronchoscope costs between $15,000 and $25,000, the cTBNA needle approximately $60, and the other charges between $75 and $125. Not factored into this are the maintenance and repair costs,25 as well as traveling and other costs incurred by the patient for EBUS, as it is not available at all centers. The learning curve is steeper for EBUS compared with cTBNA.26 About 50 EBUS-TBNA procedures are required to acquire an initial working knowledge of this technique, and another 50 (100, total) to attain enough proficiency to perform lymph node mapping and staging of lung cancer. Moreover, to maintain competence, one has to carry out at least 50 procedures per year.27–30 This obviously will not be possible in the majority of centers across the country.
What are our views on EBUS-TBNA as a modality in the developing world? EBUS-TBNA is clearly superior to cTBNA for sampling lymph nodes that are <10 mm in their short axis, located at station 4L, and for staging and restaging of the mediastinum in the context of a malignancy.31–34 However, in clinical practice, in the developing world, the indication for EBUS-TBNA is primarily diagnostic. The majority of lymph nodes encountered are >10 mm in size and generally involve the subcarinal areas, with the most common differential being either sarcoidosis or tuberculosis. In this situation, conventional bronchoscopy and cTBNA for tuberculosis, and combined with TBLB for sarcoidosis, would provide diagnosis for a large group of patients.18 In general, we envisage a strategy in which cTBNA is performed by the majority of pulmonary physicians across the country and is the initial procedure for lymph nodes >10 mm in stations 4R and 7. If cTBNA is inconclusive then it should be followed by EBUS-TBNA. In those with a suspected diagnosis of sarcoidosis, TBNA (either EBUS or conventional) should be routinely accompanied by EBB and TBLB. Patients who require sampling of nodes <10 mm in size or lymph node stations 4R and 7 or lung cancer staging or a failed cTBNA should be referred for EBUS-TBNA.
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