Transesophageal Ultrasound-guided Fine-needle Aspiration Research Articles

Combined EUS and EBUS are complementary methods in lung cancer staging: Do not forget the esophagus.

Endoscopic ultrasound (endobronchial ultrasound-guided transbronchial needle aspiration [EBUS-TBNA] and transesophageal ultrasoundguided fine needle aspiration [EUS-FNA]) can be performed in an outpatient setting under local anesthesia with mild sedation. The procedures are well established for diagnosis and staging of a variety of diseases, such as lung cancer [1–3]. Accurate staging of non-small cell lung cancer (NSCLC) is crucial for allocation to surgical treatment. By using endoscopic ultrasound, surgical staging procedures can be avoided in a considerable proportion of patients with NSCLC. In short, EUS is excellent for the left and lower paraesophageal structures plus structures under the diaphragm, whereas EBUS provides access to structures close to the large airways on both sides. Thus the two procedures are complementary (● Fig.1) [4]. Currently no single endoscope offers the benefits of both endobronchial and transbronchial access. Compared to EBUS, EUS has many advantages. EUS is better tolerated (no cough), the ultrasonic window angle is larger (150–180 versus 50–60 degrees with EBUS), the ultrasonic image is better due to higher resolution, it allows better visualization of small structures, the operator can orientate independent of an endoscopic view with secretions, and the transducer is in close contact with the target, owing to endoscopic suction with deflation of the esophageal lumen. With EUS, there are also no hard cartilage rings interposed between the needle and the target and needle maneuverability is better with improved targeting due to an “elevator.”All of these benefits are outweighed by a single disadvantage: the psychological barrier to use of EUS that exists among many—but not all—thoracic physicians. The way to overcome this barrier is to let a thoracic physician perform EUS with the smallest EBUS endoscope, that is, to perform a so-called EUS-B procedure [5, 6] even if the equipment is not designed for the purpose and therefore, in many respects, inferior compared to EUS-FNA. In their current paper, Meena and Bartter performed a retrospective comparison of EUS-B and EBUS in a total of 155 procedures and found that EUS-B was faster, patients needed less sedation and oxygen, and the time to discharge was shorter, whereas the diagnostic yield was the same. The authors conclude that EUS is the procedure of choice when applicable, meaning that, for example, EUS-B should be preferable to EBUS in a patient with a suspicious lymph node station 7 or 4L. It must be remembered, however, that in the majority of cases, choosing one method over the other is not the issue because EBUS and EUS are complementary and can be performed in a single session [4]. It should be mentioned that, for obvious reasons, several of the advantages of EUS listed above are not achievable with EUS–B. One example is superior ultrasonic visualization. It must also be noted, that in the current study, regions under the diaphragm relevant for staging of NSCLC (● Fig.1) could not be reached with the relatively short EUS–B technique, meaning that EUS does not get its full credit as a comparator in the study. Further, patient preference also have been explored by asking whether an individual preferred a foreign body in the airway or in the esophagus, although the answer seems predetermined. If thoracic physicians are not to be left behind in terms of advancements in endoscopic ultrasound, it is mandatory that necessary education and training be established for EUS as well as EBUS, including theoretical courses, simulator-based education, and clinical training plus valid assessment of all three elements [7–10]. But do not forget the esophagus!

Assessment of EGFR and K-ras mutations in fixed and fresh specimens from transesophageal ultrasound-guided fine needle aspiration in non-small cell lung cancer patients

In non-small cell lung cancer (NSCLC) patients, somatic EGFR and K-ras mutations predict therapeutic effectiveness and resistance, respectively, to EGFR tyrosine kinase inhibitors (TKIs). Transesophageal ultrasound-guided fine needle aspiration (EUS-FNA) is a validated technique for diagnosis and staging of NSCLC. In the present study, we compared the feasibility and reliability of EGFR and K-ras gene mutation analysis in fixed and fresh mediastinal lymph nodes and extra-lymph nodal samples obtained by EUS-FNA in patients suspicious for NSCLC. Thirty-six patients were enrolled into the study. For each patient, DNA was extracted from both fresh samples and fixed cytological smears. Exons 18-21 of EGFR and exon 2 of K-ras were amplified by PCR and mutation status was determined by direct sequencing and pyrosequencing. All cases were eligible for analysis. NSCLC was diagnosed in 32 patients (25 adenocarcinomas and 7 squamous cell carcinomas) and 4 patients were free of malignancy. Of the 25 patients with adenocarcinoma, EGFR mutations were detected in 2 (8%) fresh tumor samples and in 3 (12%) fixed cytological smears. K-ras mutations were detected in 8 (32%) fresh samples, and in 9 (36%) fixed cytological smears. Fixed and stained cytological samples seem to be more reliable than fresh material for molecular analysis.

Endoscopic ultrasound-guided biopsies for mediastinal lesions and lymph node diagnosis and staging

OBJECTIVES:To disseminate transesophageal ultrasound-guided fine needle aspiration (EUS-FNA) as an alternative to investigate mediastinal tumoral lesions because it is an underused modality that has been available in Brazil for more than 15 years.METHODS:Descriptive analysis of a single endoscopy service's experience since 1997 in the accomplishment of EUS-FNA for mediastinal staging of previously known malignancies (Group 1) or diagnostic definition of suspect lymph nodes and masses (Group 2).RESULTS:EUS-FNA was performed in 51 patients between 26 and 87 years of age. The diameter of the lesions ranged between 1.1 and 9.8 cm (mean 3.9 cm). Their location corresponded to the following stations: higher paratracheal (4 cases), lower paratracheal (7), aortic window (12), para-aortic (6), subcarinal (9), paraesophageal (8), and hilar (5). In Group 1, 17 patients had previously diagnosed primary lung (9), breast (4), kidney (2), colon (1), and bladder (1) cancer. Fifteen of these punctures were positive for malignity. Two others were later submitted to mediastinoscopy, which identified metastases not detected by EUS-FNA. Group 2 comprised 34 patients. Among these patients, EUS-FNA diagnosed 22 neoplasms, five cases of tuberculosis and two duplication cysts. Cytology was inconclusive or without a specific diagnosis in five other cases. Mediastinoscopy identified two undiagnosed cases of oat-cell carcinoma, one lymphoma and one cryptococcosis, and confirmed one reactive lymphadenitis. There were no complications related to the method.CONCLUSIONS:EUS-FNA obviated the need for surgical procedures in 86.3% of cases. Therefore, oncologists, pulmonologists, and thoracic surgeons should always remember the technique's potential and availability.

Transesophageal Ultrasound-Guided Fine-Needle Aspiration for the Mediastinal Restaging of Non-small Cell Lung Cancer

Selected patients with stage III (N2/N3) non-small cell lung cancer (NSCLC) who are downstaged to N0 by chemoradiation therapy might benefit from subsequent surgical resection of the tumor. How mediastinal lymph nodes can be best reevaluated is subject of debate. Transesophageal ultrasound-guided fine-needle aspiration (EUS-FNA) is a minimally invasive technique to sample mediastinal nodes. We assessed sensitivity and false-negative rate of EUS-FNA for the mediastinal restaging of patients with stage III NSCLC. Fifty-eight consecutive patients with stage III NSCLC and tissue-proven lymph node metastases N2/N3) who underwent EUS-FNA for restaging purposes after chemoradiation therapy were retrospectively analyzed. Surgical-pathological staging was used as the reference standard for nodal metastases. EUS-FNA found persistent nodal metastases (N2/N3) in 15 patients (26%). Of the 43 patients without persistent mediastinal metastases at EUS, 33 patients subsequently underwent surgical verification of the mediastinal nodes in whom persistent metastases (yN2/N3) were found in 19 patients (58%), and loco-regional downstaging (yN0) was achieved in the other 14 (42%). The prevalence of persistent nodal metastases in the 48 patients who could be analyzed was 71%. Sensitivity and the false-negative rate of EUS-FNA for mediastinal restaging were 44 and 58%, respectively. For mediastinal restaging of stage III NSCLC, EUS-FNA is a minimally invasive and safe method to confirm persistent nodal metastases, but this technique has a low negative predictive value and is therefore not useful for the exclusion of mediastinal metastases. Surgical restaging is indicated in the absence of mediastinal metastases at EUS-FNA.

The Challenge of Mediastinal Staging

Lung cancer staging is a crucial step in both correct prognosis and therapy. Mediastinal staging in particular is usually accomplished using imaging techniques such as computed tomography and 18F–glucose positron-emission tomography, minimally invasive techniques, i.e. transbronchial needle aspiration with or without ultrasound guidance (endobronchial ultrasound) and transoesophageal ultrasound-guided fine needle aspiration and surgical procedures, i.e. mediastinoscopy, thoracoscopy. Each of these techniques has its own sensitivities, specificities and predictive values that must be thoroughly considered within the staging route, with the aim of achieving the best result with the least resource consumption and the least discomfort to the patient; the correct evaluation of a negative result on the basis of its predictive value is essential as well. In this article we suggest a mathematical model that can predict the probability of nodal metastasis after a certain number of diagnostic procedures has been performed, providing an objective way of evaluating whether a patient is fit for surgery or, conversely, whether further investigations are required.

Cytological diagnosis of sarcoidosis revisited: A state of the art review

Diagnosis of sarcoidosis has never been an easy task. This is primarily because there is no single diagnostic test that can clinch the diagnosis. Demonstration of granulomas remains an essential criteria, but as granulomatous inflammation can be seen in host of conditions, it is necessary to exclude all possible causes, as well as to correlate with other findings, before arriving at the diagnosis of sarcoidosis. Cytology has been used effectively since the last few decades in demonstration of granulomas in various organs. Recent developments in various fields of cytodiagnosis of sarcoidosis including transesophageal ultrasound-guided fine-needle aspiration and endobronchial ultrasonograpy-guided transbronchial needle aspiration have revolutionized this field. These techniques are safe, minimally invasive, and give real-time information during aspiration. In comparision to the conventional methods, these allow easier sampling and have better sensitivity. In addition to these methods, a variety of ancillary techniques are also utilized and are reviewed here.

EUS-FNA in the preoperative staging of non-small cell lung cancer

Background According to current guidelines, transesophageal ultrasound-guided fine needle aspiration (EUS-FNA) can be performed as an alternative for surgical staging to confirm mediastinal metastases in patients with non-small cell lung cancer (NSCLC). To date however, data regarding the routine use of EUS-FNA in the preoperative staging of unselected patients with NSCLC are limited. Aims and objectives (1) To evaluate the diagnostic value of EUS-FNA in consecutive, patients with NSCLC regardless of nodal size at CT. (2) To determine the impact of EUS-FNA on the prevention of surgical staging procedures. (3) To assess the accuracy of mediastinal staging by combining EUS-FNA and mediastinoscopy. (4) To investigate whether a subgroup of patients exists that can be accurately staged by EUS-FNA alone. Methods 152 consecutive operable patients with proven or suspected NSCLC who underwent EUS-FNA were retrospectively analyzed. In the absence of mediastinal metastases, mediastinoscopy and/or thoracotomy with lymph node dissection was performed. Results The prevalence of mediastinal metastases was 49%. Sensitivity, negative predictive value (NPV) and accuracy of EUS-FNA for N2/N3 disease were 74%, 73% and 85% respectively, whereas these values for the combined staging of EUS-FNA and mediastinoscopy were 92%, 85% and 95%. Additional surgical staging in patients staged N0 at EUS-FNA reduces the false negative EUS-findings by 55%. The NPV of EUS-FNA for left-sided tumors was 68%. EUS-FNA prevented surgical staging procedures in 60 of 152 patients (39%). No major complications occurred during EUS-FNA. Conclusion Routine use of EUS-FNA in unselected patients with NSCLC reduces the need for surgical staging procedures in nearly half of patients. Additional surgical staging in patients without nodal metastases at EUS-FNA reduces the false negative EUS-FNA findings considerably regardless of the location of the primary lung tumor.

Implementation of transesophageal ultrasound (EUS-FNA) for lung cancer staging

7605 Background: Transesophageal ultrasound-guided fine needle aspiration (EUS-FNA) demonstrated to be an accurate and minimally invasive method for the diagnosis and staging of lung cancer, resulting in a reduced need for surgical staging in around half of patients. Although EUS-FNA is part of lung cancer staging algorithms in recent guidelines, no data exist whether the reported EUS findings—obtained by experts—are reproducible in community hospital settings. Methods: Prospective non-randomized multicenter diagnostic implementation trial. Nine physicians from 5 hospitals participated in a dedicated EUS implementation program including indication assessment and on-site training in 45 patients. Patients with (suspected) non- small cell lung cancer in whom surgical staging of the mediastinum was indicated were eligible. Consecutive patients underwent EUS-FNA in the 5 implementation centers as well as the single expert center. In case of the absence of tissue proven N2/N3 metastases at EUS-FNA, surgical staging or thoracotomy with mediastinal dissection was performed. Primary outcomes were: 1) sensitivity and accuracy regarding mediastinal staging and 2) prevented surgical interventions. Results of implementation centers were compared to that to the expert center. Results: 527 patients were included, 334 (63%) in the implementation and 193 (37%) in the expert center. Sensitivity and accuracy for mediastinal staging (implementation vs expert centers) were 83% and 89% vs 81 and 87% respectively. Surgical staging was spared due to endosonography in 47% (implementation) vs 46% (expert) of patients. Non representative FNA samples were identical (7%) in both groups. One major complication occurred in each group. No differences in the major outcomes were found in the implementation centers comparing results of the first with the second year after introduction of EUS-FNA. Conclusions: Chest physicians without prior (endo)sonography experience obtained the same sensitivity, accuracy and impact on patient management as experts, in performing EUS-FNA for the diagnosis and staging of lung cancer. The proposed implementation program might qualify as a model to facilitate large scale dissemination of EUS-FNA for lung cancer staging. No significant financial relationships to disclose.

Why Respiratory Physicians Should Learn and Implement EUS-FNA

In their recent editorial, “EUS/EBUS—A New Dawn for the Respiratory Physician,” Janes and Spiro raise the question whether it is “really a necessity” that gastroenterologists perform transesophageal ultrasound-guided fine needle aspiration (EUSFNA) for the diagnosis and staging of lung cancer or that respiratory physicians should adopt this diagnostic method (1). We think this is indeed a relevant question. In our opinion, based on experience in investigating over 1,000 patients with lung cancer using EUS-FNA, we strongly favor the idea that EUS-FNA should be performed by respiratory physicians. The actual EUS-FNA investigation itself is just one aspect. Assessing the proper indication for EUS and weighing alternative diagnostic approaches—such as positron emission tomography (PET), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), and surgical staging—is essential. Major indications for EUS-FNA are diagnosing mediastinal or centrally located intrapulmonary lesions and mediastinal (re) staging. Nodes detected by EUS should be assigned and staged (N2/N3) according to the current lymph node map. EUS findings need to be related to further patient management to give referring physicians adequate feedback on EUS outcomes. Respiratory physicians are the experts on lung cancer staging, have the knowledge to interpret the various thoracic imaging modalities, and can best integrate all available clinical information. Obviously, gastroenterologists generally lack the specific knowledge just mentioned. Having said this just leaves the question whether respiratory physicians should enter the esophagus (cardiologists do) and implement this diagnostic method in their routine practice. Respiratory physicians are already accustomed to perform endoscopy. They should learn how to introduce a scope into the esophagus, interpret ultrasound images, and aspirate paraesophageal lesions. To address these questions, we conducted a prospective nationwide, government sponsored, implementation study (2005–2007) for EUS-FNA in lung cancer in The Netherlands (2). Based on current evidence in the literature (3), the question is no longer if but how EUS-FNA should be implemented for the care of patients with lung cancer. Now is the time for the pulmonary community to adopt EUS-FNA as a diagnostic method of our specialty. We should take up the challenge to develop standards, set up training centers, and facilitate implementation to ensure that patients with (suspected) lung cancer get access to promising minimally invasive diagnostic methodology.

E(B)US-Guided Pulmonary Interventions

Transesophageal ultrasound-guided fine needle aspiration (EUS-FNA) enables minimally invasive tissue sampling of mediastinal lymph nodes. There is convincing evidence that EUS-FNA is an accurate method for mediastinal staging of patients with non small cell lung cancer (NSCLC), and therefore EUS-FNA provides an alternative for surgical evaluation of the mediastinum. Due to the complementary reach in analyzing different mediastinal regions, additional staging by EUS-FNA to mediastinoscopy improves preoperative staging of NSCLC and therefore reduces the number of futile thoracotomies. Preliminary data suggest an important role for EUS-FNA in the assessment of mediastinal tumor invasion as well as mediastinal restaging after prior chemo (radiation) therapy. For interstitial lung diseases, EUS-FNA has been demonstrated to be an accurate method in diagnosing sarcoidosis. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a novel diagnostic method by which mediastinal, hilar, and intrapulmonary nodes can be aspirated under real-time ultrasound control from the trachea or main bronchi. EBUS-TBNA can be performed in an ambulatory setting and has been proven to be accurate in mediastinal staging of patients with NSCLC. Like EUS-FNA, EBUS-TBNA is an alternative for mediastinoscopy. EUS-FNA and EBUS-TBNA have a complementary reach for various mediastinal nodal stations, and recent studies indicate that complete and accurate locoregional staging of NSCLC can be achieved by the combination of EUS-FNA and EBUS-TBNA.

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

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 TBNA (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 ultrasound-guided 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 endobronchial ultrasound-guided transbronchial needle aspiration and transoesophageal ultrasound-guided fine needle aspiration will reduce the need for surgical staging of lung cancer significantly.

Transesophageal ultrasound-guided fine needle aspiration improves mediastinal staging in patients with non-small cell lung cancer and normal mediastinum on computed tomography

The aim of the current study was to prospectively assess the value of transesophageal ultrasound-guided fine needle aspiration (EUS-FNA) in the mediastinal staging of patients with non-small cell lung cancer (NSCLC) and CT negative for lymph node (LN) metastases, candidates for surgical resection. EUS-FNA was performed using the standard technique and LNs with at least one morphological feature suggestive of malignancy were sampled. Pathological exam of surgical specimens or tumor positive cytology was used as gold standard. Forty seven patients were included, 21% of whom had advanced disease (pN2) undetected by CT. EUS-FNA demonstrated LN metastases in 50% of them (11% of the whole series), and there were no false positives, resulting in a sensitivity, specificity, positive and negative predictive values and accuracy of 50%, 100%, 100%, 88% and 89%, respectively. In conclusion, EUS-FNA improves mediastinal staging in patients with NSCLC and CT negative for mediastinal nodes. Therefore, EUS-FNA should be considered in any patient with NSCLC and no distant metastases before any therapeutic decision is taken.

Endoscopic Ultrasound Added to Mediastinoscopy for Preoperative Staging of Patients With Lung Cancer

Up to 40% of thoracotomies performed for non-small cell lung cancer are unnecessary, predominantly due to inaccurate preoperative detection of lymph node metastases and mediastinal tumor invasion (T4). Mediastinoscopy and the novel, minimally invasive technique of transesophageal ultrasound-guided fine-needle aspiration (EUS-FNA) target different mediastinal lymph node stations. In addition, EUS can identify tumor invasion in neighboring organs if tumors are located adjacent to the esophagus. To investigate the additional value of EUS-FNA to mediastinoscopy in the preoperative staging of patients with non-small cell lung cancer. Prospective, nonrandomized multicenter trial performed in 1 referral and 5 general hospitals in the Netherlands. During a 3-year period (2000-2003), 107 consecutive patients with potential resectable non-small cell lung cancer underwent preoperative staging by both EUS-FNA and mediastinoscopy. Patients underwent thoracotomy with tumor resection if mediastinoscopy was negative. Surgical-pathological staging was compared with preoperative findings and the added benefit of the combined strategy was assessed. The EUS-FNA examination was performed as an additional staging test to mediastinoscopy in all patients. Detection of mediastinal tumor invasion (T4) and lymph node metastases (N2/N3) comparing the combined staging by both EUS-FNA and mediastinoscopy with staging by mediastinoscopy alone. The combination of EUS-FNA and mediastinoscopy identified more patients with tumor invasion or lymph node metastases (36%; 95% confidence interval [CI], 27%-46%) compared with either mediastinoscopy alone (20%; 95% CI, 13%-29%) or EUS-FNA (28%; 95% CI, 19%-38%) alone. This indicated that 16% of thoracotomies could have been avoided by using EUS-FNA in addition to mediastinoscopy. However, 2% of the EUS-FNA findings were false-positive. These preliminary findings suggest that EUS-FNA, when added to mediastinoscopy, improves the preoperative staging of lung cancer due to the complementary reach of EUS-FNA in detecting mediastinal lymph node metastases and the ability to assess mediastinal tumor invasion.