CHAPTER 4

Transbronchial needle aspiration and endobronchial ultrasound

F.J.F. Herth Correspondence: F.J.F. Herth, Dept of Pneumology and Critical Care Medicine, Thoraxklinik at the University of Heidelberg, Amalienstrae 5, D-69126 Heidelberg, Germany. E-mail: Felix.Herth@thoraxklinikheidelberg.de

Imaging techniques (computed tomography (CT) scan and nuclear magnetic resonance (NMR)) and surgical biopsy methods (mediastinoscopy, mediastinotomy, video-assisted thoracic surgery and thoracotomy) are the most widely used means for the diagnosis of mediastinal lesions, either with the aim of identifying the aetiology of pathological processes or to stage lung cancer [14]. For staging of nonsmall cell lung lung cancer (NSCLC), the TNM classication has been developed, in which T stands for local tumour extension, N for lymph node metastasis, and M for distant metastasis [5, 6]. The lymph node maps by MOUNTAIN and DRESLER [7], and subsequent revisions, are often used for the description of the N factor of the TNM classication. Although imaging techniques provide a high sensitivity (CT scan and NMR are able to identify small lymph nodes ,1 cm in diameter), the specificity of such methods is not satisfactory (lymph nodes of increased size are not always neoplastic) [1, 3, 8]. In contrast, surgical biopsy methods, which provide a good sensitivity (87%) and an excellent specificity (100%), involve some risk of morbidity (1%) and mortality (0.2%), and, as they require general anaesthesia and the use of an operating theatre, incur high costs [912]. In this context, since the mid-1980s, the technique has been developed of obtaining cytological or histological samples from hilar-mediastinal lesions with flexible transbronchial needles (transbronchial needle aspiration (TBNA)) introduced through the tracheal or bronchial wall during a bronchoscopy [13]. The latest development is the endobronchial ultrasound-guided (EBUS)-TBNA scope. At the tip of the scope, an ultrasound transducer is added, which allows a real-time controlled TBNA. TBNA and EBUS-TBNA will be discussed in the present chapter.

TBNA
Merely a curiosity at inception, today flexible bronchoscopy has emerged as an essential diagnostic and therapeutic modality for a variety of lung diseases [14, 15]. The addition of TBNA had not only improved its diagnostic yield, it had further extended its role in the evaluation of mediastinal pathology, and the diagnosis and staging of bronchogenic carcinoma [8, 1618]. The first description of sampling mediastinal lymph nodes through the tracheal carina using a rigid bronchoscope was by SCHIEPPATI [19, 20], an Argentinian physician who presented the technique at the Argentine Meeting of Bronchoesophagology in 1949. In 1978, WANG et al. [21] demonstrated that with this technique it was also possible to sample paratracheal nodes. In 1979, OHO et al. [13]
Eur Respir Mon, 2010, 48, 4558. Printed in UK - all rights reserved. Copyright ERS 2010; European Respiratory Monograph. Print ISSN: 1025-448x; online ISSN: 2075-6674. DOI: 10.1183/1025448x.00990409

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introduced a flexible needle that could be utilised through a bronchoscope and, in 1983, WANG and co-workers [22, 23] pointed out the diagnostic possibility of the method in staging of lung cancer and developed new types of needles. Subsequent publications highlighted its utility in the diagnosis of endobronchial and peripheral lesions and the ability of TBNA to provide a diagnosis even in the absence of endobronchial disease, in a nonsurgical fashion, confirmed its usefulness to bronchoscopists [2432].

Equipment
All needle systems for transbronchial aspiration consist of: 1) a retractable sharp bevelled flexible needle; 2) a flexible catheter; and 3) a proximal control device to manipulate the needle, the stylet, or both, and a proximal port through which suction can be applied. The 20- to 22-gauge needles are usually used to obtain cytology specimens while the 19-gauge needles are needed to obtain a core of tissue for histology (figs 1 and 2) [25, 33]. Histology specimens are commonly obtained using a 19-gauge histology needle. On the market, some systems are available as a dual needle system involving 21- and 19gauge bevelled, retractable needles [17].

Procedure
Selection of the proper site for needle insertion to increase diagnostic yield may be facilitated by reviewing the CT scan of the chest. TBNA can be safely and successfully performed for unexpected endobronchial lesions encountered during routine flexible bronchoscopy [34, 35]. To prevent damage to the working channel of the flexible bronchoscope (FB) by the needle, the FB should be kept as straight as possible, with its distal tip in the neutral position during catheter insertion. The bevelled end of the needle must be secured within the metal hub during its passage through the working channel. The needle is advanced and locked in place only after the metal hub is visible beyond the tip of the FB. The catheter can then be retracted, keeping the tip of the needle distal to end of the FB. The FB is then advanced to the target area, and the tip of the needle is anchored in the intercartilaginous space in an attempt to penetrate the airway wall as perpendicularly as possible. Using the working channel to splint the distal end of the catheter further facilitates sampling [36].

Fig. 1. Classical transbronchial needle aspiration needle: the smaller 21-gauge needle (upper) and the larger 19gauge needle with a stylet (lower).

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Fibrescope

Bronchial tree Needle

Tumour or lymph nodes

Fig. 2. Schematic diagram of a transbronchial needle aspiration.

The following techniques may be used to insert the needle through the airway wall. 1) The jabbing method: the needle is thrust through the intercartilaginous space with a quick, firm jab to the catheter, while the scope is fixed at the nose or mouth. 2) The hub against the wall method: with the needle in the retracted position, the distal end of the catheter (the metal hub) can be placed directly in contact with the target and held firmly while the needle is pushed out of the catheter for its spontaneous penetration through the tracheobronchial wall. 3) The piggyback method: once the needle is advanced and locked in position, the catheter is fixed against the proximal end of the insertion port, using the index finger in a single port scope or the little finger in a dual port scope, to prevent recoil when resistance is met; the bronchoscope and catheter are then pushed forward as a single unit, until the entire needle penetrates the tracheobronchial wall. 4) The cough method: while applying the jabbing or piggyback technique, the patient is asked to give a hard cough for the spontaneous penetration of the needle. All of these techniques can be used either alone or in combination for successful penetration of the needle through the tracheobronchial wall [17, 36]. With the needle inserted, suction is applied at the proximal port using a syringe. Aspiration of blood indicates inadvertent penetration of a blood vessel, suction is released, the needle is retracted, and a new site is selected for aspiration. When there is no blood in the aspirate, the catheter is agitated to and fro, with continuous suction, in an attempt to shear off cells from the mass or lymph node. The needle is withdrawn from the target site after releasing suction. The tip of the FB is straightened and the needle assembly is pulled out of the FB in a single, smooth motion [36].
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Proper handling of the obtained specimen is a crucial and underappreciated aspect of the procedure. The specimen for cytology is prepared by using air from a 60-mL syringe to blow the specimen onto the slide (the smear technique) [15], before smearing it using another slide. The technique of obtaining a histology specimen via TBNA requires the use of the 19gauge needle assembly and is a variation on the technique used to obtain cytology specimens. Once the metal hub is visible beyond the tip of the FB, the 19-gauge needle is advanced beyond the metal hub and locked in place. The automatically advanced 21gauge needle is used to puncture the airway wall and anchored at the target site using any of the techniques previously described. The 21-gauge needle acts as a trocar for the 19-gauge needle and prevents its plugging by bronchial wall tissue. Using a syringe, suction is applied at the proximal port to ascertain the safety of the location. This is followed by the insertion of the 19-gauge needle to its fullest extent. Under continuous suction, the 19-gauge needle is moved to and fro, partially, four or five times, to obtain a core of tissue [17, 36].

Results
The diagnostic sensitivity of TBNA in the assessment of hilar-mediastinal lymph node involvement in lung cancer varies greatly in the literature reports, from 15%, reported by SHURE and FEDULLO in 1984 [37], to a value .85%, obtained by SHENK et al. [26]. There are several reasons that can explain this range of results (table 1). Higher values of sensitivity are obtained in patients with established lymph node enlargement on CT. In fact, in the study of SHURE and FEDULLO [37], the sensitivity increased from 15% to 38% if only subjects with CT scan evidence of lymphoadenopathy were considered. UTZ et al. [38] reported a positive subcarinal TBNA in 36% of 88 patients with lung cancer, but this value rose to 43% in the 67 cases with radiographic evidence of mediastinal adenopathy, while was only 10% in the 21 patients without imaging evidence of subcarinal lymph node enlargement. It seems that the kind of needle employed can influence the results and that the use of histology needles, introduced by WANG et al. [22], can further improve the sensitivity of the technique. SHENK et al. [25] studied the sensitivity of 22- and 19-gauge needles, both utilised at the identical endotracheal location in 64 patients, 55 with proven malignant mediastinal adenopathy. The sensitivity of the 19-gauge needle (85.5%) was statistically higher than that obtained by 22-gauge needle (52.7%) (p,0.0001). In 20 patients, only the 19-gauge needle was diagnostic, while the 22-gauge needle was exclusively diagnostic in two patients. Overall, the 19-gauge needle correctly identified 47 patients, while the 22-gauge needle was diagnostic only in 29 patients. The sensitivity of the combined cytology and histology samples was higher (89.1%) than either individual sampling. In a prospective multi-institutional study conducted on 360 patients, HARROW et al. [34] found that needle size influenced the frequency of positive TBNA recovery. Aspirates
Table 1. Factors influencing the diagnostic yield of transbronchial needle aspiration Presence of lymph node enlargement on computed tomography scan Type of needle employed Site of the tumour and lymph node location Lymph node size Number of aspirates performed Rapid on-site cytopathological examination Ability and experience of the operators Nature of the lesion (malignancy, type of malignancy)

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were positive with a histology needle in 57%, while with a cytology needle in 41% of patients. A further element that can influence the sensitivity of TBNA is the site where the lymph node is located. In a study carried out by PATELLI et al. [18] on 194 procedures, the overall sensitivity of the technique in assessing lymph node metastases was 71%, but TBNAs performed in the left paratracheal station, with a sensitivity of 52%, have been significantly less sensitive than those performed in the right paratracheal (sensitivity 84%) or in the subcarinal stations (sensitivity 79%). The better sensitivity of TBNA performed for cancer located in the right lung in comparison to left lung neoplasms had already been reported by WANG et al. [33] in 1983. In this study carried out on 39 patients, the overall sensitivity of TBNA was 76%, with value of 92% for right lung and 56% for left lung tumours. Likewise, HARROW et al. [34] found a better sensitivity in the right-sided tumours than those originating from the left lung, and that right paratracheal and subcarinal lymph nodes aspirates were more likely to provide a positive cytology than left paratracheal TBNA. In the same study, HARROW et al. [34] underline that the lymph node size can influence the results of TBNA, showing that positive aspirates increased with a linear relationship from lymph nodes ,1 cm to lymph nodes of 22.5 cm in size. None of the TBNAs performed on lymph nodes ,5 mm was positive, but 15 of 103 samples (15%) from nodes between 5 and 9 mm in size were diagnostic for malignancy. For lymph nodes .2.5 cm, the sensitivity did not increase further. Another factor that may modify the sensitivity of the technique is the number of aspirates performed in each lymph node station. In a study performed on 79 patients to evaluate the sequential effect of each successive specimen on diagnostic yield, CHIN et al. [39] found a positive aspiration in the initial specimen in 42% of patients and this value rose incrementally with successive aspirates up to 57% at the seventh sample. The increase in yield was small after the fourth needle pass and no diagnosis of cancer was obtained after the seventh aspirate. CHIN et al. [39] recommend that at least four TBNAs in a single node station should be attempted to obtain adequate material, but seven passes will maximise yield in the staging of mediastinal disease in patients with lung cancer. In the same article [39], the role of rapid on-site cytopathological examination (ROSE) in amelioration of the diagnostic yield of TBNA is also reported. In fact, the presence of ROSE was associated with a yield of 71%, which was higher than the value obtained if ROSE was absent (25%). The role of ROSE in improving the results of TBNA was already demonstrated by DAVENPORT [40] that found a significant increase in the percentage of specimens containing malignant cells in 73 aspirates performed using ROSE in comparison with 134 routinely processed TBNA (56% versus 31%). In the same way, in a study including 204 bronchoscopies where not only TBNA, but also the results of bronchial and transbronchial biopsies and brushing were evaluated, DIETTE et al. [41] obtained a better yield when ROSE was used (81% versus 50% without ROSE). Maybe the most important factor that can influence the results of TBNA is the ability and the experience of the operators. HAPONIK and STURE [31] demonstrated that the diagnostic yield on TBNA performed by 14 bronchoscopists increased from 21.4% to 47.6% during a 3-yr period of training and of educational intervention. DE CASTRO et al. [42] showed that the diagnostic sensitivity of an expert bronchoscopist was 77%, while the sensitivity of a pulmonologist without specific experience on TBNA was 23.5%. This value rose to 78% after a training of 24 months. The relevant role of experience in performing TBNA is also supported by the analysis of the results of the more recent studies published in the last few years, where the sensitivity of TBNA is greater with experienced users (constantly reported .70%) than that obtained in the early experiences [18, 25, 34]. These results have been reached thanks to the numerous technical papers published by mentors of TBNA that have
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standardised the method, providing the bronchoscopists with the elements to correctly perform the technique. In addition to lung cancer staging, TBNA can be used also for diagnostic purposes both, in lung cancer and in other pathological conditions of the hilar-mediastinal area. In a study conducted to determine the diagnostic yield of TBNA in 166 patients with mediastinal lesions, SHARAFKHANEH et al. [43] obtained a diagnosis in 104 patients (61%) and in 69% of patients with malignancies. In this study [43], the TBNA yield was higher for malignant lesions when compared with benign disease and, among malignancy, it was higher for small cell carcinoma (87%). The lowest yield among malignancy was for lymphoma (50%), while the best results among benign conditions was obtained for sarcoidosis (63%) [43]. CETINKAYA et al. [44], studying 60 patients with mediastinal lymphadenopathy, were able to make a diagnosis in 45 (75%), where TBNA was the only diagnostic tool in 30 (50%), including patients with carcinoma, tuberculosis, lymphoma and carcinoma. The possibility to diagnose sarcoidosis with TBNA was already known before the invention of flexible needles. In 1987, in a series of 59 patients with undiagnosed mediastinal adenopathy, WANG et al. [21] reported a diagnosis of sarcoidosis with flexible needle in 17 patients. With the use of the histology needle, the sensitivity of TBNA for the diagnosis of sarcoidosis may increase up to 90% [45]. In 1994, in a study of 51 patients with suspected sarcoidosis carried out with the use of TBNA and transbronchial lung biopsy, MORALES et al. [46] showed that the addition of TBNA to the lung biopsy increased the diagnostic yield from 60% to 83% for stage I and from 76% to 86% for stage II sarcoidosis. TBNA seems to provide a better yield in stage I sarcoidosis (5390%) than in stage II (4250%) [47]. In 74 patients suspected of having sarcoidosis, BILACEROGLU [48] found a TBNA sensitivity of 61% and 42%, respectively, in stage I and stage II disease. In a study conducted on 55 patients with hilar-mediastinal adenopathy, 32 of whom were proven to have stage I sarcoidosis, TRISOLINI et al. [49] obtained a positive TBNA in 23 (72%) and found that in the patients who underwent TBNA and transbronchial lung biopsy, the yield of TBNA (73%) exceeded that of lung biopsy (40%). Besides sarcoidosis, a number of different hilar-mediastinal pathological processes have been identified using TBNA, including the diagnosis of tuberculus adenitis [50], lymphoma [43, 44] and post-transplantation lymphoproliferative disorder [51], thymoma [52], carcinoid [53] and other metastatic adenopathies (14 have been reported). The specificity of the technique is very high (96100%) [47, 53], although some cases of false-positive results have been reported [54, 55]. To reduce this risk, TBNA of hilarmediastinal lymph nodes should be performed following some precautions, such as always sampling the lymph nodes before the bronchial lesion (in order to avoid the possible contamination of the main bronchi or trachea with cellular material from the more distal airways) and avoiding puncturing an area where the mucosa is involved by the pathological process [50].

Complications
The numerous papers on TBNA performed during the last few years confirm the safety of the procedure. No cases of mortality related to TBNA have been described. The rare complications reported are as follows: pneumothorax [33], pneumomediastinum [34, 24], haemomediastinum [56], bacteraemia [57] and pericarditis [58, 59]. None of these complications determined clinical major consequences. The cases of haemomediastinum [56, 58] showed spontaneous resolution of mediastinal haematoma after 1 week. One of the major complications of TBNA is the possible severe damage to the
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working channel of the bronchoscope [27]. This is more frequent with a nonretractable needle (which, in any case, should no longer be available in the market) and can be avoided if the operator takes care in introducing and extracting the needle from the bronchoscope with the tip completely retracted in the sheath.

EBUS-TBNA
The EBUS-TBNA scope is an ultrasound puncture bronchoscope with a 7.5-MHz convex transducer placed at the tip of a exible bronchoscope. This EBUS-TBNA is a linear curved array transducer that scans parallel to the insertion direction of the bronchoscope (fig. 3). Images can be obtained by directly contacting the probe with the bronchial wall. The ultrasound image is processed in an ultrasound scanner and is visualised along with the conventional bronchoscopy image. The outer diameter of the insertion tube of the EBUS-TBNA is 6.2 mm, and that of the tip is 6.9 mm. The angle of view is 90u, and the direction of view is 35u forward oblique. The inner diameter of the instrument channel is 2.0 mm. A dedicated 22-gauge needle is used to perform EBUS-TBNA. The needle is also equipped with an internal sheath that is withdrawn after passing the bronchial wall, avoiding contamination during TBNA. This internal sheath is also used to clear out the tip of the needle after passing the bronchial wall. The use of this sheath has signicantly increased the yield of EBUS-TBNA. The exit of the needle is at 20u with respect to the outer covering of the insertion tube. The needle can be visualised through the optics and on the ultrasound image (fig. 4) [60]. Because the endobronchial images obtained by the EBUS-TBNA scope is not as clear as the conventional exible videoscope image, most of the users prefer to examine the tracheobronchial tree using the conventional scopes. All procedures can be performed under local anaesthesia and conscious sedation (midazolam) [61]. Nasal insertion may be difficult owing to the probe on the tip of the scope. After identifying the lesion of interest with EBUS-TBNA, the surrounding structures are visualised with the use of the Doppler mode to confirm blood vessels (fig. 5). The dedicated TBNA needle is inserted through the working channel of the bronchoscope, and the lesion is punctured under direct EBUS guidance (EBUS-TBNA).

Fig. 3. The tip of the ultrasonic puncture bronchoscope and the 22-gauge transbronchial needle aspiration (TBNA) needle is inserted through the working channel to perform direct real-time endobronchial ultrasound-guided TBNA.

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Fig. 4. Representative case of endobronchial ultrasound-guided (EBUS)-transbronchial needle aspiration. An EBUS scan demonstrates station 4R lymph node. The 22-gauge needle is seen in the lymph node.

Indications for EBUS-TBNA are assessment of mediastinal and hilar lymph nodes, diagnosis of lung tumours, and diagnosis of mediastinal tumours. All of the mediastinal lymph nodes except for the subaortic and para-oesophageal lymph nodes (levels 5, 6, 8 and 9) are assessable by EBUS-TBNA. The hilar nodes [1012] are also approachable [60].

Clinical results
To date, several papers have been published on this procedure. KRASNIK et al. [62] reported on 11 patients in whom 15 lesions were punctured, without complications. The lesions were located as follows: four in region 10L, four in region 10R, one in region 4L, three in region 4R, one in region 1, one in region 7, and one in region 2R. The lesions ranged from 7 mm to 80 mm. Biopsies obtained through EBUS-fine needle aspiration showed malignant cells in 13 lesions and benign cells in two. YASUFUKU et al. [63] published their first experiences in a few patients in 2004. In a second trial [64], they examined 70 patients with mediastinal (n558) and hilar lymph nodes (n512). The sensitivity, specificity and accuracy of EBUS-TBNA in distinguishing benign from malignant lymph nodes were 95.7%, 100% and 97.1%, respectively. There were no complications. In a European article by RINTOUL et al. [65], EBUS-TBNA was used in 18 patients. Cytology revealed node (N)2/N3 disease in 11 patients and provided a primary diagnosis in eight patients. Cytology results for EBUS-TBNA samples were negative in six patients, and mediastinoscopy or clinical follow-up confirmed this result in four. Sensitivity, specificity and accuracy for EBUS-TBNA were 85%, 100% and 89%, respectively. The largest trial reported the results of the method in 502 patients [66]. 572 lymph nodes were punctured, and 535 (94%) resulted in a diagnosis. Biopsies were taken from all reachable lymph node stations (2L, 2R, 3, 4R, 4L, 7, 10R, 10L, 11R and 11L).
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Fig. 5. Puncture of the lymph node in position 10R; the vessel is seen with the help of the Doppler mode.

MeanSD diameter of the nodes was 1.60.36 cm and the range was 0.83.2 cm. Sensitivity was 92%, specificity was 100%, and the positive predictive value was 93%. As in all other trials, no complications occurred. HERTH et al. [67] examined in addition the accuracy of EBUS-TBNA in sampling nodes ,1 cm in diameter. Among 100 patients 119 lymph nodes with a size from 4 mm up to 10 mm were detected and sampled. Malignancy was detected in 19 patients but missed in two others; all diagnoses were confirmed by surgical findings. The meanSD diameter of the punctured lymph nodes was 8.1 mm. The sensitivity of EBUS-TBNA for detecting malignancy was 92.3%, the specificity was 100%, and the negative predictive value was 96.3 %. Again no complications occurred. The authors [67] summarised that EBUS-TBNA can sample even small mediastinal nodes, therefore avoiding unnecessary surgical exploration in one out of five patients who have no CT evidence of mediastinal disease. Potentially operable patients with clinically nonmetastatic NSCLC may benefit from pre-surgical EBUS-TBNA biopsies and staging. In the most recent article covering this subject, HERTH et al. [68] demonstrated that despite negative CT and positron emission tomography (PET) scan results, EBUSTBNA of mediastinal lymph nodes was positive for metastatic disease in eight patients and only missed one patient. The sensitivity, specificity and negative predictive value were 89%, 100% and 99%, respectively. A study comparing EBUS-TBNA, CT and PET for lymph node staging of lung cancer showed a high yield for EBUS-TBNA [69]. Altogether, 102 potentially operable patients with proven (n596) or radiologically suspected (n56) lung cancer were included in the study. CT, PET and EBUS-TBNA were performed prior to surgery for the evaluation of mediastinal and hilar lymph node metastasis. The sensitivities of CT, PET and EBUS-TBNA for the correct diagnosis of mediastinal and hilar lymph node staging were 76.9%, 80.0% and 92.3%, respectively; the specificities were 55.3%, 70.1% and 100%, respectively; and the diagnostic accuracies were 60.8%, 72.5% and 98.0%,
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respectively. EBUS-TBNA was proven to have high sensitivity and specicity compared with either CT or PET for mediastinal staging in patients with potentially resectable lung cancer. Restaging of the mediastinum is another area of growing interest for the treatment strategy of lung cancer. In cases of advanced lymph node stage lung cancer, induction chemotherapy prior to surgical resection is an option. Mediastinoscopy is considered the gold standard for staging the mediastinum. However, re-mediastinoscopy can be technically difficult and is therefore not commonly performed. The ability to perform multiple, repeat biopsies using EBUS-TBNA allows restaging of the mediastinum after the introduction of chemotherapy. A group of 124 consecutive patients with tissue-proven IIIA-N2 disease who were treated with induction chemotherapy underwent mediastinal restaging by EBUS-TBNA. The sensitivity, specicity, positive predictive value, negative predictive value and diagnostic accuracy of EBUS-TBNA for mediastinal restaging following induction chemotherapy were 76%, 100%, 100%, 20% and 77%, respectively. EBUS-TBNA is an accurate, minimally invasive test for mediastinal restaging of patients with NSCLC. However, because of the low negative predictive value, tumour-negative ndings should be conrmed by surgical staging [70]. EBUS-TBNA can be also used for the diagnosis of intrapulmonary nodules as well as mediastinal and hilar lymph nodes. The limitation is the reach of EBUS-TBNA, which depends on the size of the bronchus. Usually the EBUS-TBNA can be inserted as far as the lobar bronchus. Lung tumours located adjacent to the airway within reach of EBUSTBNA can be diagnosed with EBUS-TBNA. TORNOUY et al. [71] have reported that their experience is this indication. In 60 patients who had previously had a nondiagnostic bronchoscopy, TORNOUY et al. [71] were able to establish the definitive diagnosis in 77% without any complication.

Complications
Complications related to EBUS-TBNA are similar to those of conventional TBNA, including bleeding from major vessels, pneumomediastinum, mediastinitis, pneumothorax, bronchospam and laryngospasm. All authors of the published literature have not encountered complications related to EBUS-TBNA and to date no major complications have been reported in the literature. Although EBUS has enabled the bronchoscopist to see beyond the airway, one must be aware of the possible complications related to the procedure [72, 73].

Conclusion
Mediastinal lesion sampling can be performed with different methods. Mediastinal NSCLC staging will discriminate between N2 or N3 lymph nodes. Imaging techniques can poorly assess N1 lymph nodes (either hilar or segmental). However, this seems not to be a major drawback, because N1 assessment will easily be resected. Only poor pulmonary function N1 lymph nodes must be carefully assessed in advance, because segmentectomy may then be the only option to resect the primary tumour, thus extending life expectancy. Endoscopic techniques, TBNA, endoscopic ultrasound-guided fine needle aspiration or EBUS-TBNA should be the preferred methods to establish the definitive N-staging. Depending on the local situation, ultrasound guidance should be used because of the increased yield compared with the blind TBNA technique.
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Summary
A tissue diagnosis of mediastinal nodes is frequently needed for accurate lung cancer staging as well as the assessment of mediastinal masses. Transbronchial needle aspiration (TBNA) is a safe procedure that is performed during routine bronchoscopy. Provided mediastinal metastases are confirmed, TBNA has a high impact on patient management. Unfortunately, TBNA remains underused in current daily practice, mainly due to the lack of real-time needle visualisation. The introduction of echo-endoscopes has overcome this problem. Endobronchial ultrasound-guided (EBUS)-TBNA allows real-time controlled tissue sampling of paratracheal, subcarinal and hilar lymph nodes. Mediastinal lymph nodes located adjacent to the oesophagus can be assessed by transoesophageal ultrasoundguided fine needle aspiration (EUS-FNA). Owing to the complementary reach of EBUS-TBNA and EUS-FNA in assessing different regions of the mediastinum, recent studies suggest that complete and accurate mediastinal staging can be achieved by the combination of both procedures. It is expected that implementation of minimally invasive endoscopic methods of EBUS-TBNA and EUS-FNA will reduce the need for surgical staging of lung cancer significantly. Keywords: Endobronchial ultrasound, endoscopy, lung cancer, mediastinal lymph nodes, transbronchial needle aspiration.

Statement of interest None declared.

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