6. Endoscopic ultrasound-guided fine-needle aspiration in the staging of lung cancer
Mohamad A. Eloubeidi
Lung cancer is the most common cause of cancer-related death in the United States. It is estimated by the American Cancer
Society that 171 900 cases of lung cancer were diagnosed in 2003 and 157 200 people succumbed to the disease . Up to 50% of patients with lung cancer present with malignant involvement of mediastinal lymph nodes and up to 16% have
metastasis to the left adrenal gland .
Accurate preoperative staging is important for treatment selection and as a prognostic indicator of survival . Both non-invasive and invasive staging modalities are available to assess nodal involvement and distant metastatic disease
in patients with lung cancer . Mediastinal adenopathy in patients with suspected or proven lung cancer needs to be carefully evaluated prior to surgical
resection. If non-invasive imaging modalities are trusted, nearly 20% of patients with lung cancer and mediastinal lymphadenopathy
might be erroneously precluded from potentially curative surgery . This is due mostly to abnormally enlarged lymph nodes secondary to infectious or granulomatous disease.
This chapter reviews the literature supporting a unique role of EUS in evaluating patients with lung cancer, with and without
mediastinal lymphadenopathy detected by other imaging modalities. In addition the role of EUS-FNA in detecting metastasis
to the adrenal gland is discussed. Finally, this chapter sheds some light on future directions of EUS in lung cancer.
Non-invasive imaging modalities
Chest CT is the first non-invasive step in evaluating patients with lung cancer. Any detected lymph node in the mediastinum
with a size >= 1 cm in the short axis is considered abnormal. The operating characteristics of chest CT from 20 eligible studies that included
3438 lung cancer patients have been recently reviewed . The pooled sensitivity was 57% and the pooled specificity was 82%. The positive predictive value was 56% and the negative
predictive value was 83%. This suggests that 43% of patients with 'positive disease' by CT are false positive and 17% of patients with 'negative disease' by CT have mediastinal lymph involvement.
Positron emission tomography
Positron emission tomography (PET) is increasingly being used to stage patients with lung cancer . This new technology relies on the preferential accumulation of 18F-fluoro-deoxy-D-glucose in malignant cells. In order to determine the location of the abnormality or the 'hot' spot, PET is usually interpreted in conjunction with a chest CT.
The operating characteristics of PET scans from 18 eligible studies that included 1045 lung cancer patients have been recently
reviewed . The pooled sensitivity was 84%, and the pooled specificity was 89%. The positive predictive value was 79% and the negative
predictive value was 93%. This suggests that 21% of patients with 'positive disease' by PET are false positive and 7% of patients with 'negative disease' by PET have mediastinal lymph involvement. As compared with the CT scanning summary ROC curves, the PET scan summary ROC
curve was significantly more accurate. Recent published guidelines for staging lung cancer suggest that patients with abnormally
detected mediastinal adenopathy need to be evaluated further for the confirmation of the status of these lymph nodes .
There are currently multiple invasive staging modalities for the evaluation of mediastinal adenopathy in patients with lung
cancer. These include mediastinoscopy, anterior mediastinotomy, video-assisted thoracic surgery (VATS), transthoracic needle
aspiration (TTNA), transbronchial needle aspiration (TBNA), and EUS-guided fine-needle aspiration biopsy (EUS-FNA) [6,8]. A comparison among these different modalities is difficult since each has its own advantages and disadvantages and can access
different stations of lymph nodes. For example, mediastinoscopy can access stations 2R, 4R, 7, 4L, and 2L but cannot access
posterior subcarinal lymph nodes or aorto-pulmonary lymph nodes (station 5). [Fig. 1] In contrast, EUS-FNA can access these two stations (5 and 7) with ease. In addition, EUS-FNA can easily target level 8 (lower
periesophageal), the left lobe of the liver, and, importantly, the left adrenal gland [14,15].
The first three surgical options are performed under general anesthesia and have morbidity and rare mortality associated with
them. TTNA can result in pneumothorax and bleeding [6,8]. TBNA and EUS-FNA are performed on an outpatient basis and have minimal morbidity. A recent study compared EUS-FNA to TBNA
in the evaluation of patients with suspected or confirmed lung cancer . Diagnosis of malignant mediastinal lymphadenopathy was superior for EUS-FNA compared to TBNA (92% vs. 73% p= 0.01). Furthermore, cost analysis identified that EUS-FNA was the most economical approach in patient with non-small cell
lung cancer (NSCLC) and mediastinal adenopathy on CT compared to TBNA or mediastinoscopy. Many studies suggest that when performed
in patients with NSCLC and abnormal adenopathy, EUS-FNA can reduce resource utilization in these patients . In addition, despite the fact that bronchoscopy use is more widespread than endoscopic ultrasound, TBNA is underutilized
by the practicing pulmonologist .
Endoscopic ultrasound-guided fine-needle aspiration
Accuracy for diagnosing malignancy
EUS was originally introduced for the staging of gastrointestinal and pancreatic malignancies. Due to its ability to use the
esophagus as an acoustic medium to image the posterior mediastinum, it became clear that EUS can identify posterior mediastinal
adenopathy in a superior fashion to CT. Endosonographers relied initially on lymph node echofeatures to classify lymphadenopathy
as benign or malignant. While this classification is helpful, it has no superior advantage over size measurements alone (by
any technique) since it does not provide tissue confirmation, which is essential.
With the advent of curvilinear echoendoscopes it became evident that EUS-FNA is a relatively non-invasive, accurate, safe,
and cost-effective technique for the staging of patients with lung cancer [15,17,2024]. Multiple studies to date have shown the superior accuracy of EUS-FNA in staging patients with lung cancer. A summary of
the operating characteristics of EUS-FNA in patients with mediastinal adenopathy is shown in Fig. 2.
One study compared the operating characteristics of EUS-FNA, EUS, CT, and PET scans in staging patients with lung cancer . This study that included 33 patients from Germany showed that EUS-FNA is superior to CT and PET combined. The sensitivity,
specificity, and accuracy of EUS-FNA and CT plus PET were 88%, 100%, 81% and 81%, 94% and 88%, respectively.
More recently, a larger study from the United States enrolled 104 suspected lung cancer patients who underwent EUS-FNA to
sample posterior lymph nodes after EUS and PET scan . The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EUS-FNA were 92.5%,
100%, 100%, 94%, and 97%, respectively. EUS-FNA was more accurate and had a higher positive predictive value than the PET
or CT (p < 0.001) scan in confirming cancer in the posterior mediastinal lymph nodes. EUS-FNA documented metastatic cancer to the left
adrenal in all four patients with advanced disease. No deaths resulted from EUS-FNA. One patient experienced self-limited
stridor. The authors concluded that EUS-FNA is a safe, accurate, and minimally invasive technique that improves the staging
of patients with NSCLC. It is more accurate and has a higher predictive value than either the PET scan or CT scan for posterior
mediastinal lymph nodes .
More importantly, a few studies have shown that EUS-FNA can detect mediastinal disease in CT negative patients. In one study,
EUS-FNA detected mediastinal disease in 10 of 24 patients [42%]. In some instances, EUS can detect mediastinal invasion of the primary tumor .
EUS and identification of metastatic disease
In addition to identifying nodal involvement, EUS-FNA can reliably sample the left lobe of the liver and the left adrenal
gland for metastasis, resulting in a significant impact on patient management . EUS can identify the left adrenal gland in 97% of the cases [26,27]. In a recent multicenter study, EUS-FNA of the left adrenal was performed in 31 patients with thoracic or GI malignancies.
Tissue adequate for interpretation was obtained from all patients; The median number of needle passes was 4.5 (range 18). No immediate complications were encountered. EUS-guided FNA confirmed malignant left adrenal involvement in 42% (13/31) of the patients. Patients with malignant left adrenal masses were more likely to have known cancer at another site. Patients
with benign masses were more likely to have preservation of the normal sonographic appearance of the adrenal gland ('seagull' configuration, Fig. 3) compared with those with malignant masses The accuracy of EUS imaging based on size (>= 3 cm) alone was 81%. The authors concluded that EUS-guided FNA of the left adrenal gland is a minimally invasive, safe, and
highly accurate method that confirms or excludes malignant adrenal involvement in patients with thoracic or GI malignancies.
The complication rate of the transgastric EUS-guided FNA approach appears to be much lower than the transcutaneous approach
since no organs are traversed except the wall of the stomach.
EUS is performed as an outpatient procedure with conscious sedation. Staging is usually performed with a radial echoendoscope
first to assess the liver and the left adrenal. The radial echoendoscope assesses the mediastinum in a 360° fashion similar to chest CT. The liver is examined from the duodenum and the antrum of the stomach. In addition, the celiac
axis is identified to assess the presence of adenopathy in that area. The left adrenal is usually found between the aorta
and the left kidney. The echoendoscope is then withdrawn slowly and the presence of adenopathy is carefully examined. The
endoscope is withdrawn in the mediastinum to about 20 cm from the incisors, where the internal carotids are usually identified in cross-section. To insure that no adenopathy is
missed, it is prudent to repeat this maneuver two to three times till the examiner is satisfied with the quality of the examination.
With the curvilinear echoendoscope, it is relatively easy to identify the left adrenal. In certain situations, where other
imaging modalities such as CT or PET suggest a high likelihood of disease in the left adrenal, the radial echoendoscope examination
can be omitted. The descending aorta is identified with the curved linear array (CLA) echoendoscope at about 35 cm from the incisor. A continuous and steady push of the CLA endoscope to about 45 cm from incisorwhile the aorta is maintained in viewleads to identification of the celiac axis bifurcation. A gentle clockwise maneuver will usually lead to identification of
the 'seagull'-shaped organ: the adrenal gland (Fig. 3). In patients with metastasis to the adrenal, the gland loses it normal shape and takes the form of a mass. Occasionally,
one limb of the adrenal is enlarged and this is usually consistent with a benign adenoma.
Certain stations are easily identified with the CLA echoendoscope. To find the subcarinal space, the echoendoscope is withdrawn
to about 2730 cm from the incisor while the endoscopist is facing the patient. The space bound by the right pulmonary artery (right of screen)
and the left atrium is the subcarinal space [Fig. 4]. Another clue is the fact that tracheal rings appear as hyperechoic bands simulating air artifacts. The area identified prior
to the bifurcation of the main trachea into the right and the left main stem bronchi is the subcarinal space. To identify
the aortopulmonary (AP) window (Station 5), the endoscope is withdrawn from the gastroesophageal junction cephalad to just
below the aortic arch while keeping the descending aorta in view. At that particular location, and by torquing 90° clockwise and tipping the up-down wheel in the upward direction, the AP window is identified. Once a target lesion is identified,
EUS-FNA is usually performed with the curvilinear echoendoscope (Olympus UC-30P or UCT 140) (Figs 3 and 4). Prior to puncture, color Doppler is used to ensure a safe path for the needle. EUS-FNA is usually performed using a 22-gauge
adjustable length Echotip needle (Wilson-Cook Inc., Winston Salem, NC). It is helpful to have a cytopathologist or a cytotechnician,
if available, at bedside to examine and determine adequacy of the specimens. The aspirate is placed on glass slides, and both
air-dried and alcohol-fixed smears are prepared. Air-dried smears are stained with a Diff Quik stain and reviewed immediately
by a cytopathologist to ensure specimen adequacy. At least four passes are obtained for each target lesion unless cytological
evaluation was diagnostic on an earlier pass. Additional passes are usually performed for flow cytometry when clinical and/or cytological features suggest the presence of a lymphoma. We do not routinely apply suction since it has been shown to result
in a bloodier specimen without an increase in accuracy. The technique for EUS-FNA of the left adrenal is similar to that of
a lymph node. If an alternative diagnosis such as lymphoma, TB, sarcoidosis, or histoplasmosis is suspected, it is possible
to obtain small core biopsies using a 19G cutting needle, but for diagnosis of bronchogenic malignancy FNA samples are usually
Limitations of EUS-FNA
Due to overlying air in lung parenchyma and bronchi, EUS cannot detect anterior mediastinal adenopathy. But since lymph node
involvement can be present in multiple stations, the choice of EUS as a first modality can be cost saving and avoids unnecessary
invasive procedures in the subgroup where EUS finds lymph node metastases. Moreover, and due to its long learning curve, these
techniques is limited to centers of expertise in many countries.
Combined minimally invasive staging with endoscopic ultrasound and endobronchial ultrasound
The development of real-time endoscopic transbronchial ultrasound-guided FNA (EBUS-FNA, Fig. 5) promises to have a major impact in the assessment of the anterior mediastinum , just as EUS-FNA has changed the evaluation of the posterior mediastinum. The obvious major advantage of EBUS-FNA is the
ability to proceed with nodal staging immediately after diagnostic bronchoscopy. Preliminary experiences from Denmark , Edinburgh [29,30], and Japan  suggest that EBUS-FNA is a very promising modality for staging the anterior mediastinum, particularly stations 4 and 2 [Fig. 6], areas previously only accessible by invasive procedures such as mediastinoscopy. More organized efforts have reported on
the use of combined EUS-FNA and EBUS-FNA as a minimally invasive approach to staging lung cancer patients.
Rintoul and colleagues  studied 20 patients selected by CT scanning, in which a linear-array ultrasound bronchoscope was used to visualize paratracheal
and hilar lymph nodes, and TBNA was performed under direct ultrasonic control. In seven cases, sequential EUS was used to
assess postero-inferior mediastinal lymph nodes. All procedures were performed under conscious sedation. EBUS-TBNA was undertaken
in 18 out of 20 cases and EUS-guided fine-needle aspiration in six out of seven cases. Cytology showed node (N) 2/N3 disease in 11 out of 18 EBUS-TBNA cases and provided a primary diagnosis for eight patients. EBUS-TBNA cytology was negative
in six cases, which was confirmed by mediastinoscopy or clinical follow-up in four. EUS provided additional information in
all cases. There were no procedural complications. The sensitivity, specificity, and accuracy for EBUS-TBNA were 85%, 100%,
and 89%, respectively. The authors concluded that endobronchial ultrasound with real-time transbronchial needle aspiration
offers improved sensitivity and accuracy for staging of the middle mediastinum, and, combined with endoscopic ultrasound,
should allow investigation of the majority of the mediastinum.
A recent study from Japan evaluated the role of EBUS-FNA in the evaluation of mediastinal and hilar lymph nodes . EBUS-guided TBNA was performed to obtain samples from mediastinal lymph nodes (58 nodes) and hilar lymph nodes (12 nodes).
The sensitivity, specificity, and accuracy of EBUS-guided TBNA in distinguishing benign from malignant lymph nodes were 95.7%,
100%, and 97.1%, respectively. The procedure was uneventful, and there were no complications. The authors concluded that real-time
EBUS-guided TBNA of mediastinal and hilar lymph nodes is a novel approach that is safe and has a good diagnostic yield.
More recently, Vilmann and colleagues  reported using the combined approach in staging 33 patients with either suspected or proven lung cancer. The diagnoses were
verified in 28 of 31 patients either at thoracotomy (n = 9) or during the clinical follow-up (n = 19). In the whole group of 33 patients, a total of 119 lesions were sampled by either EUS-FNA (n = 59) or EBUS-TBNA (n = 60). With a combined approach (EUS-FNA + EBUS-TBNA) in 28 of the 31 patients in whom a final diagnosis was obtained in the evaluation of mediastinal cancer, 20 patients
were found to have mediastinal involvement, whereas no mediastinal metastases were found in 8 patients. The accuracy of EUS-FNA
and EBUS-TBNA, in combination, for the diagnosis of mediastinal cancer was 100% (95% CI: 83100%). Interestingly, the two technologies were found to be complementary, and one confirmed disease missed by the other in
territories visualized by both techniques, such as the subcarina (station 7). The authors concluded that EUS-FNA and EBUS-TBNA
appear to be complementary methods.
A combined approach with both EUS-FNA and EBUS-TBNA may be able to replace more invasive methods for evaluating lung cancer
patients with suspected hilar or mediastinal metastases, as well as for evaluating unclear mediastinal or hilar lesions. It
appears that the combined approach with EUS-FNA and EBUS-FNA might preclude surgical staging in the future. Future efforts
should be directed to investigate whether this approach can obviate the need for mediastinoscopy and video-assisted thoracic
surgery (VATS), and simplify the staging of patients with lung cancer. More trials are needed to compare EBUS-FNA to conventional
bronchoscopy-guided FNA and to select the appropriate niche for each technology to further simplify the approach in each patient.
Outstanding issues and future trends
EUS-FNA and molecular markers in lung cancer
Recent preliminary work suggests that the combination of EUS-FNA and molecular markers with real-time reverse transcriptase-polymerase
chain reaction (RT-PCR) may be helpful in identifying patients with micrometastasis of cancer to lymph nodes that have benign
cytologic evaluation [33,34]. One study evaluated the capability of detecting micrometastatic disease by RT-PCR for expression of human telomerase reverse
transcriptase (hTERT) in mediastinal lymph nodes . hTERT was expressed in 0 of 14 negative control lymph nodes in 18 of 57 pathologically negative lymph nodes from cancer
patients and in 10 of 16 pathologically positive lymph nodes (p < 0.05). Five of 18 (28%) patients with no pathologically evident mediastinal disease expressed telomerase in at least one lymph
node. Approximately one-third of pathologically negative mediastinal lymph nodes in NSCLC patients express hTERT mRNA. The
authors concluded that minimally invasive EUS-FNA with RT-PCR is capable of detecting expression of cancer specific mRNA in
lymph nodes. While these results are promising, their clinical significance is yet to be determined.
In summary, EUS-FNA is an accurate, safe, and cost-effective strategy in the evaluation of patients with lung cancer. Data
support its use in groups of patients both with and without obvious mediastinal lymph node enlargement as detected by computerized
tomography or positron emission tomography. Its use in the United States, however, has been hampered by the fact that it is
available only in academic centers, its long learning curve, and the fact that it is performed predominantly by gastroenterologists.
Future studies are needed to examine its role in patients with positive and negative PET scans prior to surgical intervention.
In addition, more studies comparing EBUS-FNA and bronchoscopy with surgical gold standards are needed. Novel methods of molecular
analysis for detecting micrometastasis may further improve the sensitivity of EUS-FNA and EBUS-FNA in the preoperative evaluation
of patients with lung cancer.
1 Jemal, A, Murray, T, Samuels, A, Ghafoor, A, Ward, E & Thun, MJ. Cancer statistics. CA Cancer J Clin 2003; 53 (1): 526. PubMed
2 Dillemans, B, Deneffe, G, Verschakelen, J & Decramer, M. Value of computed tomography and mediastinoscopy in preoperative evaluation of mediastinal nodes in non-small cell lung cancer:
a study of 569 patients. Eur J Cardiothorac Surg 1994; 8 (1): 3742. PubMed CrossRef
3 Gross, BH, Glazer, GM, Orringer, MB, Spizarny, DL & Flint, A. Bronchogenic carcinoma metastatic to normal-sized lymph nodes: frequency and significance. Radiology 1988; 166 (1 Part 1): 714. PubMed
4 McLoud, TC, Bourgouin, PM, Greenberg, RW, Kosiuk, JP, Templeton, PA & Shepard, JA et al. Bronchogenic carcinoma: analysis of staging in the mediastinum with CT by correlative lymph node mapping and sampling. [Comment] Radiology 1992; 182 (2): 31923. PubMed
5 Mountain, CF. Revisions in the International System for Staging Lung Cancer. [Comment] Chest 1997; 111 (6): 171017. PubMed
6 Detterbeck, FC, DeCamp, MM Jr, Kohman, LJ & Silvestri, GA; American College of Chest Physicians. Lung cancer. Invasive staging: the guidelines. Chest 2003; 123 (1 Suppl.): 167S75S. PubMed
7 Silvestri, GA, Tanoue, LT, Margolis, ML, Barker, J & Detterbeck, F; American College of Chest Physicians. The noninvasive staging of non-small cell lung cancer: the guidelines. Chest 2003; 123 (1 Suppl.): 147S56S. PubMed
8 Toloza, EM, Harpole, L, Detterbeck, F & McCrory, DC. Invasive staging of non-small cell lung cancer: a review of the current evidence. [Review][53 refs] Chest 2003; 123 (1 Suppl.): 157S66S. PubMed
9 Toloza, EM, Harpole, L & McCrory, DC. Noninvasive staging of non-small cell lung cancer: a review of the current evidence. [Review][80 refs] Chest 2003; 123 (1 Suppl.): 137S46S. PubMed
10 Silvestri, GA, Hoffman, B & Reed, CE. One from column A: choosing between CT, positron emission tomography, endoscopic ultrasound with fine-needle aspiration, transbronchial
needle aspiration, thoracoscopy, mediastinoscopy, and mediastinotomy for staging lung cancer. [Comment] Chest 2003; 123 (2): 3335. PubMed
11 Cerfolio, RJ, Ojha, B, Bryant, AS, Bass, CS, Bartalucci, AA & Mountz, JM. The role of FDG-PET scan in staging patients with nonsmall cell carcinoma. Ann Thoracic Surg 2003; 76 (3): 8616.
12 Lardinois, DW. Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 2003; 348 (25): 25007. PubMed CrossRef
13 Pieterman, RMPJ, Meuzelaar, JJ, Mooyaart, EL, Vaalburg, W & Koeter, GH et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. [Comment] N Engl J Med 2000; 343 (4): 25461. PubMed CrossRef
14 Eloubeidi, MA, Seewald, S, Tamhane, A, Brand, B, Chen, VK & Yasuda, I et al. EUS-guided FNA of the left adrenal gland in patients with thoracic or GI malignancies. Gastrointest Endosc 2004; 59 (6): 62733. PubMed CrossRef
15 Eloubeidi, MA, Cerfolio, RJ, Chen, VK, Desmond, R, Syed, S & Ojha, B. Endoscopic ultrasound-guided fine needle aspiration of mediastinal lymph node in patients with suspected lung cancer after
positron emission tomography and computed tomography scans. Ann Thoracic Surg 2005; 79 (1): 2638. CrossRef
16 Wiersema, MJ, Edell, ES, Midthun, DE, Jondal, ML, Levy, MJ & Parakash, U et al. Prospective comparison of transbronchial needle aspiration biopsy (TBNA) and endosonography guided biopsy (EUS-FNA) of mediastinal
lymph nodes in patients with known or suspected non-small cell lung cancer. Gastrointest Endosc 2000; 55 (5): AB 79.
17 Aabakken, L, Silvestri, GA, Hawes, R, Reed, CE, Marsi, V & Hoffman, B. Cost-efficacy of endoscopic ultrasonography with fine-needle aspiration vs. mediastinotomy in patients with lung cancer and
suspected mediastinal adenopathy. Endoscopy 1999; 31 (9): 70711. PubMed CrossRef
18 Harewood, GC, Wiersema, MJ, Edell, ES & Liebow, M. Cost-minimization analysis of alternative diagnostic approaches in a modeled patient with non-small cell lung cancer and subcarinal
lymphadenopathy. Mayo Clinic Proc 2002; 77 (2): 15564.
19 Haponik, EF, Russell, GB, Beamis, JFJ, Britt, EJ, Kvale, P & Mathur, P et al. Bronchoscopy training: current fellows' experiences and some concerns for the future. [Comment] Chest 2000; 118 (3): 62530. PubMed
20 Fritscher-Ravens, A, Bohuslavizki, KH, Brandt, L, Bobrowski, C, Lund, C & Knofel, WT et al. Mediastinal lymph node involvement in potentially resectable lung cancer: comparison of CT, positron emission tomography,
and endoscopic ultrasonography with and without fine-needle aspiration. [Comment] Chest 2003; 123 (2): 44251. PubMed
21 Gress, FG, Savides, TJ, Sandler, A, Kesler, K, Conces, D & Cummings, O et al. 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. [Comment] Ann Intern Med 1997; 127 (8 Part 1): 60412. PubMed
22 Hawes, RH, Gress, F, Kesler, KA, Cummings, OW & Conces, DJ Jr Endoscopic ultrasound versus computed tomography in the evaluation of the mediastinum in patients with non-small-cell lung
cancer. Endoscopy 1994; 26 (9): 7847. PubMed
23 Wallace, MB, Silvestri, GA, Sahai, AV, Hawes, RH, Hoffman, BJ & Durkalski, V et al. Endoscopic ultrasound-guided fine needle aspiration for staging patients with carcinoma of the lung. Ann Thoracic Surg 2001; 72 (6): 18617. CrossRef
24 Wiersema, MJ, Kochman, ML, Cramer, HM & Wiersema, LM. Preoperative staging of non-small cell lung cancer: transesophageal US-guided fine-needle aspiration biopsy of mediastinal
lymph nodes. Radiology, 1994; 190 (1): 23942. PubMed
25 Wallace, MB, Ravenel, J, Block, MI, Fraig, M, Silvestri, G & Wildi, S et al. Endoscopic ultrasound in lung cancer patients with a normal mediastinum on computed tomography. Ann Thoracic Surg 2004; 77 (5): 17638. CrossRef
26 Chang, KJ, Erickson, RA & Nguyen, P. Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration of the left adrenal gland. Gastrointest Endosc 1996; 44 (5): 56872. PubMed
27 Dietrich, CF, Wehrmann, T, Hoffmann, C, Herrmann, G, Caspary, WF & Seifert, H. Detection of the adrenal glands by endoscopic or transabdominal ultrasound. Endoscopy 1997; 29 (9): 85964. PubMed
28 Krasnik, M, Vilmann, P, Larsen, SS & Jacobsen, GK. Preliminary experience with a new method of endoscopic transbronchial real time ultrasound guided biopsy for diagnosis of
mediastinal and hilar lesions. Thorax 2003; 58 (12): 10836. PubMed CrossRef
29 Rintoul, RC, Skwarski, KM, Murchison, JT, Hill, A, Walker, WS & Penman, ID. Endoscopic and endobronchial ultrasound real-time fine-needle aspiration for staging of the mediastinum in lung cancer. Chest 2004; 126 (6): 20202. PubMed
30 Rintoul, RC, Skwarski, KM, Murchison, JT, Wallace, WA, Walker, WS & Penman, ID. Endobronchial and endoscopic ultrasound-guided real-time fine-needle aspiration for mediastinal staging. Eur Respir J 2005; 25 (3): 41621. PubMed CrossRef
31 Vilmann, P, Krasnik, M, Larsen, SS, Jacobsen, GK & Clementsen, P. Transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial
needle aspiration (EBUS-TBNA) biopsy: a combined approach in the evaluation of mediastinal lesions. Endoscopy 2005; 37 (9): 8339. PubMed CrossRef
32 Yasufuku, K, Chiyo, M, Sekine, Y, Chhajed, PN, Shibuya, K & Iizasa, T et al. Real-time endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal and hilar lymph nodes. Chest 2004; 126 (1): 1228. PubMed
33 Mitas, M, Cole, DJ, Hoover, L, Fraig, MM, Mikhitarian, K & Block, MI et al. Real-time reverse transcription-PCR detects KS1/4 mRNA in mediastinal lymph nodes from patients with non-small cell lung cancer. Clin Chem 2003; 49 (2): 31215. PubMed CrossRef
34 Wallace, MBB. Detection of telomerase expression in mediastinal lymph nodes of patients with lung cancer. Am J Respir Crit Care Med 1900; 167 (12): 16705. CrossRef
35 Wiersema, MJ, Vazquez-Sequeiros, E & Wiersema, LM. Evaluation of mediastinal lymphadenopathy with endoscopic US-guided fine-needle aspiration biopsy. Radiology 2001; 219 (1): 2527. PubMed
36 Fritscher-Ravens, A, Sriram, PV, Bobrowski, C, Pforte, A, Topalidis, T & Krause, C et al. Mediastinal lymphadenopathy in patients with or without previous malignancy: EUS-FNA-based differential cytodiagnosis in 153
patients. Am J Gastroenterol 2000; 95 (9): 227884. PubMed CrossRef
37 Hunerbein, M, Ghadimi, BM, Haensch, W & Schlag, PM. Transesophageal biopsy of mediastinal and pulmonary tumors by means of endoscopic ultrasound guidance. J Thorac Cardiovasc Surg 1998; 116 (4): 5549. PubMed
38 Silvestri, GA, Hoffman, BJ, Bhutani, MS, Hawes, RH, Coppage, L & Sanders-Cliette, A et al. Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer. Ann Thorac Surg 1996; 61 (5): 14415. PubMed CrossRef
Copyright © Blackwell Publishing, 2005