Transbronchial and transoesophageal (ultrasound-guided) needle aspirations for the analysis of mediastinal lesions

Equipment

All needle systems for transbronchial aspiration consist of: a retractable, sharp, bevelled, flexible needle; a flexible catheter; a proximal control device to manipulate the needle, the stylet, or both; and a proximal port through which suction can be applied. To obtain cytology specimens, 20–22-gauge needles are usually used, while 19-gauge needles are needed to obtain a “core” of tissue for histology 16, 24. Histology specimens are commonly obtained using a 19-gauge histology needle. Several systems are available commercially as a dual-needle system involving 21- and 19-gauge bevelled, retractable needles 7.

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 performed safely and successfully for unexpected endobronchial lesions encountered during routine flexible bronchoscopy 25. To prevent needle damage to the working channel of the fibrebronchoscope, the fiberbronchoscope 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 working channel. The catheter can then be retracted, keeping the tip of the needle distal to the end of the fibrebronchoscope. The scope 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 (fig. 1⇓) 26.

The following techniques may be used to insert the needle through the airway wall. 1) The “jabbing method”, whereby 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”, whereby the distal end of the catheter (the metal hub) can be placed directly in contact with the target, with the needle in the retracted position, and held firmly while the needle is pushed out of the catheter for its spontaneous penetration through the tracheobronchial wall. 3) The “piggyback method”, whereby, 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”, named because, while the physician is applying the jabbing or piggyback technique, the patient is asked to give a hard cough to encourage the spontaneous penetration of the needle. All of these techniques can be used alone or in combination to achieve penetration of the needle through the tracheobronchial wall 7, 26.

With the needle inserted, suction is applied at the proximal port using a syringe. Aspiration of blood indicates inadvertent penetration of a blood vessel. In this case, 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 moved up and down 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 suction is released. The tip of the scope is straightened and the needle assembly is pulled out of the scope in a single, smooth motion 26.

Proper handling of the 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 out to the slide (smear technique) 5 before smearing it using another slide.

The technique of obtaining a histology specimen via TBNA requires use of the 19-gauge 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 fibrebronchoscope, the 19-gauge needle is advanced beyond the metal hub and locked in place. The automatically advanced 21-gauge 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 up and down, 4–5 times, to obtain a core of tissue 7, 26.

At least two satisfactory core specimens are obtained at each location and multiple passes may be required to increase the diagnostic yield. Rapid on-site evaluation of the specimen by the cytopathologist for sample adequacy has been shown to increase diagnostic yield 7.

Results

The diagnostic yield of TBNA in the assessment of hilar–mediastinal lymph nodes involvement in lung cancer varies greatly in the published literature, from 15%, reported by Shure and Fedullo 27, to >85%, obtained by Schenk et al. 17. Recently, a meta-analysis regarding TBNA for the mediastinal staging for nonsmall cell lung cancer demonstrated that TBNA is highly specific for the identification of mediastinal metastases, whereas the sensitivity depends heavily on the study population under investigation 28. In studies that included patients with a prevalence of mediastinal metastases of 34%, sensitivity was only 39%, whereas in a population with a prevalence of 81% it was 78%.There are several reasons that explain the wide variety of diagnostic yield of TBNA (table 1⇓).

A higher sensitivity is obtained in patients with established lymph node enlargement on CT. In the study by Shure and Fedullo 27, the sensitivity increased from 15 to 38% if only subjects with evidence of lymphadenopathy at CT were considered. Utz et al. 29 reported a positive subcarinal TBNA in 36% out of 88 patients with lung cancer, but this value rose to 43% in the 67 cases with radiographic evidence of mediastinal adenopathy, while it 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. 13, can further improve the sensitivity of the technique. Schenk et al. 16 studied the sensitivity of 22- and 19-gauge needles at identical endotracheal locations in 64 patients, 55 with proven malignant mediastinal adenopathy. The sensitivity of the 19-gauge needle (85.5%) was statistically higher than that of the 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 mediastinal nodal stages in patients, while the 22-gauge needle was diagnostic in only 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 in 360 patients, Harrow et al. 25 found that needle size influenced the frequency of positive TBNA recovery. Aspirates were positive with a histology needle in 57%, and positive with a cytology needle in 41%.

A further element that can influence the sensitivity of TBNA is the site of the lymph node. For mediastinal and hilar lymph node mapping, the Mountain Dressler classification is used (fig. 2⇓). In a study carried out by Patelli et al. 8 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 higher sensitivity of TBNA reported for cancer located in the right lung in comparison to left lung neoplasms, had already been reported by Wang et al. 24, in a study carried out on 39 patients. The overall sensitivity of TBNA was 76%, broken down as 92% for right lung and 56% for left lung tumours. Likewise, Harrow et al. 25 found a higher sensitivity in the right-sided tumours than those originating from the left lung, and that righ 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. 25 underline the fact that lymph node size can influence the results of TBNA, showing that tumour-positive aspirates increased linearly from lymph nodes of <1 cm to lymph nodes of 2–2.5 cm. None of the TBNAs performed on lymph nodes of <5 mm were positive, but 15 (15%) out of 103 samples from nodes of 5–9 mm were diagnostic for malignancy. For lymph nodes >2.5 cm, the diagnostic yield did not increase further.

Another factor that may modify the sensitivity of the technique is the number of aspirates performed at each lymph node station. Chin et al. 31, studied the effect of each successive TBNA specimen in 79 patients with (suspected) lung cancer. They reported a tumour-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. The authors recommended the performance of at least four TBNAs for a single node station in order to obtain adequate material, but seven passes will maximise yield 31. In the same study, the role of rapid on-site cytopathologic examination (ROSE) was examined in relation to the diagnostic yield of TBNA. The results demonstrate that the presence of ROSE was associated with a yield of 71%, which was higher than the value obtained if ROSE was absent (25%). That ROSE improved the results of TBNA had already been demonstrated by Davenport 32, who found a significant increase in the percentage of specimens containing malignant cells in 73 aspirates performed using ROSE in comparison with 134 routinely processed TBNAs (56 versus 31%). In the same way, Diette et al. 33, in a study including 204 bronchoscopies where not only TBNA but also the results of bronchial and transbronchial biopsies and brushing were evaluated, obtained a better yield when ROSE was used (81 versus 50% without ROSE).

Perhaps the most important factor that can influence the results of TBNA is the ability and the experience of the operators. Haponik and Sture 22 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. 34 reported that the diagnostic yield of an expert bronchoscopist was 77%, while the yield of a pulmonologist without specific experience on TBNA was 23.5%. This value rose to 78% after a training of 24 months. The role of experience in performing TBNA is also supported by the analysis of the results of more recent studies, which consistently report sensitivities of TBNA >70% 8, 25.

In addition to lung cancer staging, TBNA can be used for diagnostic purposes, in lung cancer and other pathological conditions of the hilar–mediastinal area. In the study by Harrow et al. 25, TBNA was exclusively diagnostic of carcinoma in 65 (18%) out of 360 patients. In a study conducted to determine the diagnostic yield of TBNA in 166 patients with mediastinal lesions, Sharafkhaneh et al. 35 obtained a diagnosis in 104 patients (61%) and in 69% of patients with malignancies. In this study, the TBNA yield was higher for malignant lesions when compared with benign disease; 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 were obtained for sarcoidosis (63%) 35. Cetinkaya et al. 36, studying 60 patients with mediastinal lymphadenopathy, were able to make a diagnosis in 45 (75%). TBNA was the only diagnostic tool in 30 (50%), including patients with carcinoma, tuberculosis, lymphoma and carcinoma.

The possibility of diagnosing sarcoidosis with TBNA was already known before the introduction of flexible needles. Using a rigid needle through a rigid bronchoscope, Pauli et al. 20 obtained a diagnosis in 66.3% out of 258 patients with suspected sarcoidosis. In a series of 59 patients with undiagnosed mediastinal lymph adenopathy, Kelly and Wang 37 reported a diagnosis of sarcoidosis with a 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% 38. In a study on 51 patients with suspected sarcoidosis, Morales et al. 39 reported 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 (53–90%) than in stage II (42–50%) 40. Bilaceroglu 41 studied 74 patients, all suspected of having sarcoidosis, and found that TBNA had sensitivities of 61 and 42% in stage I and II disease, respectively. Trisolini et al. 42, in a study conducted on 55 patients with hilar–mediastinal adenopathy (32 of whom were proven to have stage I sarcoidosis), obtained a positive TBNA in 23 (72%) and reported that in the patients who underwent TBNA and transbronchial lung biopsy, the yield of TBNA (73%) exceeded that of lung biopsy (40%).

A number of hilar–mediastinal pathological processes besides sarcoidosis have been identified using TBNA. The following diseases have been assessed by TBNA: tuberculous adenitis 43; lymphoma 35, 36; post-transplantation lymphoproliferative disorder 44; thymoma 45; and carcinoid 46 metastases from nonlung cancer diseases 4. The specificity of the technique is very high (96–100%) 40, 46, although false-positive results have been reported 47, 48. To reduce this risk, TBNA of hilar–mediastinal 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 43.

Complications

The numerous papers on TBNA confirm the safety of the procedure. No cases of mortality related to TBNA have been described. The rare complications reported are pneumothorax 24, pneumomediastinum 25, 15, haemomediastinum 49, bacteraemia 50 and pericarditis 51. None of these complications determined major clinical consequences. The cases of haemomediastinum 49, 51, one caused by histology needle 49, showed spontaneous resolution of the mediastinal haematoma after 1 week. One of the major complications of TBNA is the possible severe damage to the working channel of the scope 18. This is more frequent with nonretractable needles (that should no longer be available) 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.

Use of TBNA in clinical practice

Despite the impact of TBNA on patient management, surveys demonstrate that only 10–30% of pulmonologists regularly use TBNA 22, 52. The main reasons for the limited use of TBNA are lack of needle monitoring 53, difficulties in performing the procedure and a belief, despite the evidence in the literature, that TBNA is not useful 52. Training in TBNA is urgently advocated as it will optimise the care of patients with lung cancer 54.

EBUS mini-probe: radial scanning

Real-time EBUS-TBNA: linear scanning

Equipment and procedure

For the analysis of mediastinal lesions, tissue sampling is essential. Linear and not radial ultrasound equipment is needed. Curved linear array ultrasound transducers (fig. 8⇓) are available from various companies and typically scan with a frequency of 7.5 MHz (range 5–10 MHz). EUS-FNA is usually performed under local anaesthesia and conscious sedation using midazolam. It is important to perform EUS-FNA in a standardised fashion in order to visualise all mediastinal regions that can be detected from the oesophagus 66. The echo-endoscope is initially introduced up to the level of the coeliac axis and gradually withdrawn upwards for a detailed mediastinal imaging. Since the ultrasound waves are emitted parallel to the long axis of the endoscope, the entire needle can be visualised approaching a target in the sector-shaped sound field. Pulse and colour Doppler ultrasonography imaging can be performed in cases of suspected vascular structures (fig. 9⇓). For the aspirations, 22-gauge needles are standard, although smaller (25-gauge) and larger needles (19-gauge) can be used as well. Aspirations occur under real-time ultrasound control, by advancing the needle through the oesophageal wall into the target lesion (fig. 10⇓). After removal of the stylet, the needle is moved back and forth within target lesions. Most investigators use suction, although its added benefit in terms of diagnostic yield is still the subject of debate 69. In the absence of on-site cytology, at least four needle passes are required for optimal yield 70. EUS-FNA is contraindicated in patients with a Zenker's diverticulum, or bleeding tendency.

Indications and results

The diagnosis and mediastinal staging of lung cancer is by far the most common indication for EUS-FNA in pulmonary medicine. For mediastinal staging, most studies have been performed in selected patients with enlarged or PET positive nodes. Sensitivity (range 72–100%), specificity (range 88–100%), negative predictive value (range 39–100%) and accuracy (77–100%) have been reported (table 3⇓). In the three studies performed in patients without enlarged nodes, sensitivities between 35 and 61% and accuracies between 76 and 89% regarding mediastinal staging are reported 81, 82, 87. The decreased accuracy in small nodes may be due to sampling error, technical difficulty in sampling small nodes or the fact that nodes with a normal sonographic appearance are just not biopsied 88. EUS- FNA has been suggested as a restaging method after induction chemoradiotherapy, for which accuracies of 83% and 86% were reported 89, 90.

EUS-FNA provides a minimally invasive alternative for surgical staging as it can prevent ∼70% of scheduled mediastinoscopies 76, 85, 86. Thanks to its complementary diagnostic reach, the addition of EUS to mediastinoscopy improves staging 83 and, therefore, reduces the number of futile thoracotomies 91.

EUS-FNA has a yield of 82 % 92–94 in assessing granulomas in patients with suspected sarcoidosis. Patients with sarcoidosis often present with multiple, clustered, well-demarcated nodes 92 that are frequently well vascularised 93. EUS-FNA provides an alternative to bronchoscopy and peripheral lung biopsies (including a risk of haemoptysis and pneumothorax) should be performed where available prior to a mediastinoscopy. EUS-FNA can also be used for the mediastinal staging for extrathoracic tumours, for instance for suspected mediastinal metastases of mammarian or renal carcinoma 95. Bronchogenic and paraoesophageal cysts can be visualised well by EUS 96. EUS-FNA of mediastinal nodes is considered safe, as no serious complications have been reported. FNA of acystic mediastinal lesions, however, should be avoided, owing to the risk of mediastinitis 96, 97.