Transesophageal Endoscopic Ultrasound-Guided Mediastinal Lymph Node Aspiration: Does the End Justify the Means?

Abstract

Endoscopic ultrasonography (EUS) is a unique imaging modality where a high-frequency ultrasound transducer is incorporated into the tip of an endoscope to provide high-resolution images of the GI wall and structures in close proximity to the GI tract above and below the diaphragm. EUS is the most accurate method for local tumor and lymph node staging of the GI cancers, with many other applications as well in the GI tract. The development of echoendoscopes that can image parallel to the long axis of the instrument allows visualization of a needle along its length, making EUS-guided intervention a clinical reality. Endosonography has evolved from a technological accomplishment to a clinically useful procedure for sampling peri-GI lymph nodes, pancreatic masses, and submucosal GI lesions, etc.1Bhutani MS Interventional endoscopic ultrasonography. Harwood Academic Publishers, Amsterdam Holland1999Google Scholar, 2Wiersema MJ Vilmann P Giovannini M et al.Endosonography guided fine-needle aspiration biopsy: diagnostic accuracy and complication assessment.Gastroenterology. 1997; 112: 1087-1095Abstract Full Text PDF PubMed Scopus (1044) Google Scholar, 3Chang KJ Nguyen P Erickson RA et al.The clinical utility of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of pancreatic carcinoma.Gastrointest Endosc. 1997; 45: 387-393Abstract Full Text Full Text PDF PubMed Scopus (531) Google Scholar, 4Giovannini M Seitz J-F Monges G et al.Fine needle aspiration cytology guided by endoscopic ultrasonography: results in 141 patients.Endoscopy. 1995; 27: 171-177Crossref PubMed Scopus (436) Google Scholar, 5Vilmann P Hancke S Henriksen FW et al.Endoscopic ultrasonography with guided fine needle aspiration biopsy of malignant lesions in the upper gastrointestinal tract.Endoscopy. 1993; 25: 523-527Crossref PubMed Scopus (134) Google Scholar, 6Bhutani MS Hawes RH Baron PL et al.Endoscopic ultrasound guided fine needle aspiration of malignant pancreatic lesions.Endoscopy. 1997; 29: 854-858Crossref PubMed Scopus (206) Google Scholar, 7Hoffman BJ Knapple W Bhutani MS et al.Treatment of achalasia by injection of botulinum toxin under endoscopic ultrasound guidance.Gastrointest Endosc. 1997; 45: 77-79Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar, 8Wiersema MJ Wiersema LM Endosonography-guided celiac plenus neurolysis.Gastrointest Endosc. 1996; 44: 656-662Abstract Full Text Full Text PDF PubMed Scopus (363) Google Scholar, 9Gress F Ciaccia D Kiel J et al.Endoscopic ultrasound guided celiac plexus block for management of pain due to chronic pancreatitis: a large single center experience [abstract].Gastrointest Endosc. 1997; 45: 594Google Scholar, 10Chang KJ Nguyen PT Thompson JA et al.Phase I clinical trial of local immunotherapy (Cytoimplant) delivered by endoscopic ultrasound (EUS) guided fine needle injection (FNI) in patients with advanced pancreatic carcinoma [abstract].Gastrointest Endosc. 1998; 47: AB144Abstract Full Text Full Text PDF Scopus (356) Google Scholar, 11Catalano MF Sivak Jr, MV Rice T et al.Endosonographic features predictive of lymph node metastases.Gastrointest Endosc. 1994; 40: 442-446Abstract Full Text Full Text PDF PubMed Scopus (397) Google Scholar, 12Gress F Savides TJ Sandler A et al.Endoscopic ultrasonography, fine needle aspiration guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-small cell lung cancer: a comparison study.Ann Intern Med. 1997; 127: 604-616Crossref PubMed Google Scholar EUS-guided injection of therapeutic substances has also begun.7Hoffman BJ Knapple W Bhutani MS et al.Treatment of achalasia by injection of botulinum toxin under endoscopic ultrasound guidance.Gastrointest Endosc. 1997; 45: 77-79Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar, 8Wiersema MJ Wiersema LM Endosonography-guided celiac plenus neurolysis.Gastrointest Endosc. 1996; 44: 656-662Abstract Full Text Full Text PDF PubMed Scopus (363) Google Scholar, 9Gress F Ciaccia D Kiel J et al.Endoscopic ultrasound guided celiac plexus block for management of pain due to chronic pancreatitis: a large single center experience [abstract].Gastrointest Endosc. 1997; 45: 594Google Scholar, 10Chang KJ Nguyen PT Thompson JA et al.Phase I clinical trial of local immunotherapy (Cytoimplant) delivered by endoscopic ultrasound (EUS) guided fine needle injection (FNI) in patients with advanced pancreatic carcinoma [abstract].Gastrointest Endosc. 1998; 47: AB144Abstract Full Text Full Text PDF Scopus (356) Google Scholar Since EUS during transesophageal imaging provides high-resolution images of the posterior mediastinum, considerable interest and investigation have occurred over the last few years about its utility in the detection of mediastinal lymphadenopathy in lung cancer and other malignancies. Initially, before the development of interventional EUS techniques, the focus was on studying echo features of lymph nodes to predict malignant invasion. Lymph nodes seen by EUS that were larger than 1 cm, round, hypoechoic, and with distinct margins were considered to be malignant.11Catalano MF Sivak Jr, MV Rice T et al.Endosonographic features predictive of lymph node metastases.Gastrointest Endosc. 1994; 40: 442-446Abstract Full Text Full Text PDF PubMed Scopus (397) Google Scholar These criteria during EUS were initially described for GI cancers, eg, esophageal,11Catalano MF Sivak Jr, MV Rice T et al.Endosonographic features predictive of lymph node metastases.Gastrointest Endosc. 1994; 40: 442-446Abstract Full Text Full Text PDF PubMed Scopus (397) Google Scholar and were later applied to mediastinal lymph nodes in lung cancer. These EUS echo features of mediastinal lymph nodes in lung cancer have been shown in one study to have accuracy of 84% compared to CT scan accuracy of 49%.12Gress F Savides TJ Sandler A et al.Endoscopic ultrasonography, fine needle aspiration guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-small cell lung cancer: a comparison study.Ann Intern Med. 1997; 127: 604-616Crossref PubMed Google Scholar However, the reliance on EUS echo features to diagnose malignant lymph node invasion in lung cancer has problems of interobserver variability, lack of standardization of frequencies used to study the lymph nodes, as well as lack of uniform criteria to label a lymph node as hypoechoic or with sharp, distinct margins.13Bhutani MS Hawes RH Hoffman BJ A comparison of the accuracy of echo features during endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration for diagnosis of malignant lymph node invasion.Gastrointest Endosc. 1997; 45: 474-479Abstract Full Text Full Text PDF PubMed Scopus (343) Google Scholar In addition, it has also been shown in the study by Bhutani et at13Bhutani MS Hawes RH Hoffman BJ A comparison of the accuracy of echo features during endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration for diagnosis of malignant lymph node invasion.Gastrointest Endosc. 1997; 45: 474-479Abstract Full Text Full Text PDF PubMed Scopus (343) Google Scholar that although the presence of echo features described above could predict malignant invasion about 80% of the time; however, only 25% of nodes that had malignant invasion had all four echo features. This study that included enlarged lymph nodes in patients with esophageal, lung, and pancreatic cancers also compared the accuracy of echo features of lymph nodes with EUS-guided fine-needle aspiration (FNA) and found that EUS-guided FNA was a more reliable method for predicting lymph node invasion than echo features. Transesophageal EUS-guided real-time FNA of mediastinal lymph nodes has become a clinically useful minimally invasive method for detecting malignant lymph node invasion, as shown in this issue of CHEST (see page 339) by Fritscher-Ravens and colleagues. The accuracy of EUS-guided mediastinal lymph node FNA in this series was 97%, which is comparable to the accuracy in studies from other centers.12Gress F Savides TJ Sandler A et al.Endoscopic ultrasonography, fine needle aspiration guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-small cell lung cancer: a comparison study.Ann Intern Med. 1997; 127: 604-616Crossref PubMed Google Scholar, 13Bhutani MS Hawes RH Hoffman BJ A comparison of the accuracy of echo features during endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration for diagnosis of malignant lymph node invasion.Gastrointest Endosc. 1997; 45: 474-479Abstract Full Text Full Text PDF PubMed Scopus (343) Google Scholar, 14Silvestri GA Hoffman BJ Bhutani MS et al.Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer.Ann Thorac Surg. 1996; 61: 1441-1446Abstract Full Text PDF PubMed Scopus (254) Google Scholar, 15Huhnerbein M Ghadimi BM Haensch W et al.Transesophageal biopsy of mediastinal and pulmonary tumors by means of endoscopic ultrasound guidance.J Thorac Cardiovasc Surg. 1998; 116: 554-559Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar In addition, this procedure appears to be safe in expert hands, with no significant complications occurring in the current series. This procedure is performed under conscious sedation, similar to any other endoscopy, and the patient can be discharged from the hospital after observation in the recovery room for 45 to 60 min. Following is a summarization of the advantages and limitations of this technique, so that EUS-guided FNA of mediastinal lymph nodes could be used in the appropriate clinical setting. (1) In patients with known non-small cell lung cancer who have mediastinal lymph nodes on CT scan and who have a negative transbronchial FNA, EUS-guided FNA can be used as an accurate, minimally invasive method to stage the mediastinum. The accuracy of EUS-guided FNA in this setting is about 96%.12Gress F Savides TJ Sandler A et al.Endoscopic ultrasonography, fine needle aspiration guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-small cell lung cancer: a comparison study.Ann Intern Med. 1997; 127: 604-616Crossref PubMed Google Scholar A positive result by FNA for cancer would then obviate the need for more invasive staging modalities such as mediastinoscopy. (2) EUS-guided FNA also appears to have a cost advantage over mediastinal lymph node staging in lung cancer. Cost data in a study12Gress F Savides TJ Sandler A et al.Endoscopic ultrasonography, fine needle aspiration guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-small cell lung cancer: a comparison study.Ann Intern Med. 1997; 127: 604-616Crossref PubMed Google Scholar on EUS-guided FNA for staging lung cancer revealed that the total cost for EUS was $1,975, with mediastinoscopy and thoracotomy significantly more expensive at $7,759 and $26,028, respectively. As mentioned before, if a EUS-guided FNA result is positive for cancer, it would obviate the need for more expensive and invasive procedures, such as mediastinoscopy and thoracotomy. A decision model analysis has also been performed to calculate the average cost per year of survival in patients with lung carcinoma. This model resulted in an average cost per year of survival of EUS-guided FNA to be $3,810 and $9,757 for mediastinoscopy.16Aabaken L Silvestri G Hawes R et al.Cost effectiveness of endoscopic ultrasonography with fine needle aspiration vs mediastinoscopy in the staging of patients with lung cancer [abstract].Gastrointest Endosc. 1996; 43: 414Google Scholar (3) When a primary lung mass is suspected on CT and mediastinal lymph nodes are seen, if bronchoscopic and transbronchial methods fail to acquire a primary diagnosis, EUS-guided mediastinal FNA in these patients could potentially provide a primary diagnosis (as well as staging information). These were the inclusion criteria for the current study by Fritscher-Ravens et al, and a final diagnosis of malignancy was achieved in 25 of 35 patients. Furthermore, EUS can also play a significant role in evaluating mediastinal lymphadenopathy of unknown origin with no primary lung mass on CT. If transbronchial FNA results are negative in these patients, EUS-guided FNA can provide a diagnosis of malignancy.13Bhutani MS Hawes RH Hoffman BJ A comparison of the accuracy of echo features during endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration for diagnosis of malignant lymph node invasion.Gastrointest Endosc. 1997; 45: 474-479Abstract Full Text Full Text PDF PubMed Scopus (343) Google Scholar (4) Lymph nodes that are located in the subcarina, aortopulmonary window, and the paraesophageal area are difficult to approach during procedures such as mediastinoscopy.12Gress F Savides TJ Sandler A et al.Endoscopic ultrasonography, fine needle aspiration guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-small cell lung cancer: a comparison study.Ann Intern Med. 1997; 127: 604-616Crossref PubMed Google Scholar, 14Silvestri GA Hoffman BJ Bhutani MS et al.Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer.Ann Thorac Surg. 1996; 61: 1441-1446Abstract Full Text PDF PubMed Scopus (254) Google Scholar However, these locations are best suited and the most accessible for puncture during transesophageal EUS.12Gress F Savides TJ Sandler A et al.Endoscopic ultrasonography, fine needle aspiration guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-small cell lung cancer: a comparison study.Ann Intern Med. 1997; 127: 604-616Crossref PubMed Google Scholar, 14Silvestri GA Hoffman BJ Bhutani MS et al.Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer.Ann Thorac Surg. 1996; 61: 1441-1446Abstract Full Text PDF PubMed Scopus (254) Google Scholar (5) Previous studies on the utility of EUS-guided FNA have only included patients who have enlarged mediastinal lymph nodes by CT scan. Generally by CT scan criteria, lymph nodes that are ≥ 1 cm in size are considered to be enlarged. However, using size alone as a criteria for malignant invasion of lymph nodes by CT may not be ideal, since lymph nodes < 1 cm can potentially have malignant invasion. In a series of patients who underwent CT scan and EUS, we found a significant number of patients with thoracic malignancies who had posterior mediastinal lymphadenopathy by EUS with negative CT criteria for enlarged lymph nodes. Only 50% of patients in this series who underwent EUS-guided transesophageal FNA had enlarged nodes by CT scan.17Bhutani MS Nadella P Comparison of endoscopic ultrasound (EUS) and EUS-guided FNA with computed tomography for detection of mediastinal lymphadenopathy [abstract].Gastrointest Endosc. 1998; 93: 1664Google Scholar Early data from another group also suggest that EUS-guided FNA can diagnose malignant invasion in small mediastinal lymph nodes that are negative by CT criteria.18Ciaccia D Imperiale T Kim J et al.Operating characteristics and clinical utility of endoscopic ultrasound (EUS) guided FNA in the preoperative staging of non-small cell lung cancer (NSCLCA) in computerized tomographic patients preliminary results [abstract].Gastrointest Endosc. 1999; 49: AB155Google Scholar This concept is further strengthened by Fritscher-Ravens and colleagues. It is noteworthy that seven patients who underwent EUS-guided mediastinal lymph node FNA had lymph nodes that were < 1 cm in diameter and would not have been classified as enlarged by CT scan. Four of these aspirates revealed malignant cells. Thus, in suspected or known pulmonary malignancies, even if small (< 1 cm) lymph nodes are seen in the posterior mediastinum, it might be worthwhile to perform EUS imaging and possible FNA of these lymph nodes. However, further studies in this area are needed to establish the utility of EUS in patients who do not have enlarged nodes by CT criteria. EUS with FNA also has some limitations. Endosonography is the newest advance in GI endoscopy, with a long learning curve. Currently, this technique is generally performed by experts at some (but not all) tertiary referral centers, and the procedure is not uniformly available throughout the United States as well as around the world (although the number of centers offering EUS with FNA is steadily increasing). In contrast, transbronchial FNA and other invasive methods such as mediastinoscopy are more established modalities and more uniformly available worldwide. EUS is unable to image and sample lymph nodes that are anterior and lateral to the trachea. Early data on endobronchial ultrasound have been reported19Kurimoto N Murayama M Yoshioka S et al.Assessment of usefulness of endobronchial ultrasonography in determination of depth of tracheobronchial tumor invasion.Chest. 1999; 115: 1500-1506Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar and may be a prelude to endobronchial real-time ultrasound-guided transbronchial FNA of lymph nodes, and further development in this area may significantly improve the yield of transbronchial mediastinal sampling techniques, and potentially decrease the indications for a transesophageal approach. In conclusion, in patients with known or suspected lung cancer with mediastinal lymph nodes or in patients with mediastinal lymphadenopathy of unknown etiology, EUS-guided transesophageal FNA is a safe and minimally invasive method with high accuracy. When EUS is available, it should be used as the next logical step for mediastinal lymph node sampling if transbronchial methods are nondiagnostic, provided the lymph nodes are not located anterior and lateral to the trachea. Locations such as subcarina, aortopulmonary window, and paraesophageal area are especially suited for EUS-guided FNA, as these locations are hard to access during mediastinoscopy. Physicians performing EUS-guided transesophageal FNA can play an important role in helping pulmonary and thoracic surgery colleagues in the workup of mediastinal lymphadenopathy. Even with the development of endobronchial ultrasound-guided FNA, certain lymph node locations may be best approached transesophageally. Future research in this area should focus on the cost, complications, and technical feasibility based on the location of the lymph nodes and accuracy of current and evolving techniques for mediastinal lymph node sampling. This will allow physicians to select the most appropriate sequential application of technology on a case-to-case basis.