Endoscopic ultrasound and positron emission tomography for lung cancer staging.

BACKGROUND AND AIMS: Accurate assessment of mediastinal lymph nodes is vital for optimum treatment allocation in lung cancer patients. Currently available strategies fail to identify many patients with advanced mediastinal disease, resulting in unnecessary surgery. We prospectively compared 2 promising new modalities, positron emission tomography (PET) and endoscopic ultrasound (EUS), for staging mediastinal lymph nodes. METHODS: Consenting patients with lung cancer who also were suitable candidates for surgery were enrolled in the study. Patients underwent both PET and EUS. Outcomes were analyzed by surgery results or follow-up with serial imaging. RESULTS: Seventy-two eligible patients were enrolled, and adequate data were available for 65 patients. The final diagnosis was based on tissue analysis in 59 patients and 1-year radiologic follow-up evaluation in 6 patients. PET correctly diagnosed mediastinal lymph node status in 77% of patients, and EUS fine-needle aspiration was correct in 94% of patients (P = .012). The overall sensitivity, specificity, and accuracy of PET were 61%, 91%, and 77% compared with 87%, 100%, and 94% for EUS. We estimated that EUS obviated a surgical procedure in 55% (95% confidence interval, 40%-69%) of patients with radiologic evidence of mediastinal metastasis, and in 22% (95% confidence interval, 10%-41%) of patients without radiologic evidence of mediastinal metastasis. CONCLUSIONS: EUS fine-needle aspiration was more accurate than PET in staging mediastinal lymph nodes in lung cancer patients, and resulted in a substantial reduction in mediastinoscopy and thoracotomy.     

The prognostic significance of preoperative assessment of mediastinal lymph nodes in patients with lung cancer

In order to evaluate the prognostic significance of the preoperative assessment of mediastinal lymph nodes, 100 patients with potentially operable lung cancer underwent two-plane tomography, computed tomography (CT), transbronchial needle aspiration (TBNA; 47 patients), and cervical mediastinoscopy. Mediastinoscopy proved to be the most accurate staging procedure. Tomography was less specific, detecting only advanced mediastinal node involvement, and CT was as sensitive as mediastinoscopy but sensibly less specific. TBNA gave no false positive results but a false negative rate of 25.5 percent. Accurate preoperative staging of mediastinal nodes is mandatory to optimize the resectability rate of lung cancer. Where metastatic involvement of mediastinal nodes was preoperatively documented at more than one level, tumors were invariably unresectable. Mediastinoscopic demonstration of intracapsular metastases at only one level did not preclude complete resection. Before thoracotomy, confirmation of neoplastic spread to mediastinal nodes suggests very low survival rates, especially in patients with incomplete removal of tumors.     

Ultrasound techniques in the evaluation of the mediastinum,part I: endoscopic ultrasound (EUS), endobronchial ultrasound (EBUS) and transcutaneous mediastinal ultrasound (TMUS), introduction into ultrasound techniques

Ultrasound imaging has gained importance in pulmonary medicine over the last decades including conventional transcutaneous ultrasound (TUS), endoscopic ultrasound (EUS), and endobronchial ultrasound (EBUS). Mediastinal lymph node staging affects the management of patients with both operable and inoperable lung cancer (e.g., surgery vs. combined chemoradiation therapy). Tissue sampling is often indicated for accurate nodal staging. Recent international lung cancer staging guidelines clearly state that endosonography (EUS and EBUS) should be the initial tissue sampling test over surgical staging. Mediastinal nodes can be sampled from the airways [EBUS combined with transbronchial needle aspiration (EBUS-TBNA)] or the esophagus [EUS fine needle aspiration (EUS-FNA)]. EBUS and EUS have a complementary diagnostic yield and in combination virtually all mediastinal lymph nodes can be biopsied. Additionally endosonography has an excellent yield in assessing granulomas in patients suspected of sarcoidosis. The aim of this review, in two integrative parts, is to discuss the current role and future perspectives of all ultrasound techniques available for the evaluation of mediastinal lymphadenopathy and mediastinal staging of lung cancer. A specific emphasis will be on learning mediastinal endosonography. Part I is dealing with an introduction into ultrasound techniques, mediastinal lymph node anatomy and diagnostic reach of ultrasound techniques and part II with the clinical work up of neoplastic and inflammatory mediastinal lymphadenopathy using ultrasound techniques and how to learn mediastinal endosonography.     

Accuracy of EUS criteria and primary tumor site for identification of mediastinal lymph node metastasis from non-small-cell lung cancer

BACKGROUND: EUS with FNA is useful for staging non-small-cell lung cancer. However, benign mediastinal adenopathy is common. The aims of this study were to identify clinical factors, especially primary tumor location, and EUS lymph nodal characteristics predictive of aortopulmonary window and subcarinal lymph node metastases of non-small-cell lung cancer. METHODS: Patients with known or suspected non-small-cell lung cancer underwent EUS staging at which EUS-FNA was performed for all identified mediastinal lymph nodes. Clinical characteristics, primary tumor data, EUS findings, and histopathology were reviewed. Exact tests were performed for both aortopulmonary window and subcarinal lymph nodes to identify factors predictive of malignant cytology. RESULTS: Ninety-two patients with non-small-cell lung cancer were included. Fifty-one had aortopulmonary window, and 73 had subcarinal lymph nodes on EUS. The EUS with FNA specimens were interpreted as suspicious or diagnostic for malignancy for 9 aortopulmonary window and 9 subcarinal lymph nodes. When comparing benign vs. malignant EUS with FNA findings for aortopulmonary window and subcarinal lymph nodes, only lymph node size of 1 cm or greater and sharp lymph nodal edges were associated with malignancy in lymph nodes at both sites, whereas primary tumor site, lymph node shape, and echogenicity were associated with malignant subcarinal nodes. When 4 classic lymph nodal features of malignancy were evaluated, the presence of 3 or more typical features had positive and negative predictive values of, respectively, 41% and 96%. CONCLUSIONS: Although tumor location and EUS lymph nodal characteristics are associated with malignant involvement of lymph nodes, the accuracy of these predictors does not obviate the need for cytologic evaluation. EUS with FNA should be performed for all lymph nodes when an abnormal finding will alter management.     

Accuracy of EUS in staging of T4 lung cancer

BACKGROUND: Increasingly, EUS is being used to stage lung cancer. Direct mediastinal invasion (T4) by lung cancer is stage IIIb disease. Patients in this stage have a 5-year survival of less than 5% and generally are offered chemotherapy without surgery. This study evaluated the accuracy of EUS in detecting T4 lung cancer. METHODS: The study included all patients with lung cancer who had EUS staging and subsequent staging at surgery, or for whom there was unequivocal confirmation of unresectability (T4) by thoracoscopy, thoracotomy or presence of malignant pleural effusion, or definite invasion of great vessels/adjacent organs on CT. RESULTS: A total of 175 of 308 patients with lung cancer who underwent EUS over a 5-year period (1997-2002) had subsequent confirmatory tumor staging. Ten patients were found by EUS to have stage T4 tumors; 7 were confirmed to be T4 by either surgical exploration (2), CT demonstration of aortic invasion (3), or documentation of malignant pleural effusion (2). Three of the 10 (30%) patients found to have stage T4 tumors by EUS had T2 disease at surgery and underwent curative resection. Of the remaining 165 patients without evidence of T4 disease at EUS, only one was found to have aortic invasion (T4) at surgery. EUS had a sensitivity of 87.5%, specificity of 98%, positive predictive value of 70%, and a negative predictive value of 99% for detecting T4 disease. CONCLUSIONS: Caution is warranted when unresectability of lung cancer is based solely on tumor invasion into mediastinal soft tissue at EUS. Overstaging occurs when a tumor appears to invade the pleural layer without mediastinal organ invasion. Confirmation of unresectability by other diagnostic modalities is warranted in such instances.     

Endoscopic ultrasonography of the mediastinum in the diagnosis of bronchial carcinoma.

Thoracic computed tomography (CT) is an essential component in the preoperative staging of bronchial carcinomas as is mediastinoscopy (MSC) in cases of mediastinal lymphoma. It is known that endoscopic ultrasonography (EUS), as a new diagnostic procedure, can predict lymph-node involvement in cases of tumors in the upper gastrointestinal tract with an 80% probability. In a prospective study, we examined whether EUS could be used to ascertain the presence of mediastinal lymph nodes in cases of bronchial carcinoma. Since 1990, therefore, 32 patients with operable non-small-cell bronchial carcinoma have been examined with an Olympus-Aloka EU-M2 or EU-M3 (frequency 7.5 and 12 MHz) in addition to routine diagnostics. The graded cross-sections of lymph-node dissections obtained during subsequent surgery served as evidence as to the true or false prognosis of the lymph-node status. Endoscopic ultrasonography identifies the presence and estimates the size of subcarinal, tracheobronchial, paraortal and paraesophageal lymph nodes better than computed tomography. Lymph nodes lying behind organs containing air (pretracheal lymph nodes) cannot be identified by ultrasonography. Lymph-node involvement was correctly identified by EUS in 72% of the cases, and the specificity was 86%. The poor sensitivity, at 67%, is explained by the high proportion (37%) of patients with anthracosilicosis, as the latter produces the same echo pattern as malignant infiltration. In 47% of all the cases, CT showed enlarged mediastinal lymph nodes which were not actually infiltrated in 67%. Of these lymph nodes, 33% could be classified as definitely free of metastases on the strength of their echo pattern, the rest were inflamed or really infiltrated by metastases.(ABSTRACT TRUNCATED AT 250 WORDS)     

EUS GUIDED FNA FOR MEDIASTINAL TUMORS (LUNG CANCER AND LYMPH NODES)

Trans‐esophageal endoscopic ultrasound‐guided fine needle aspiration biopsy (EUS‐FNA) has proven to be a safe and minimally invasive tissue‐sampling method which can be used to obtain a cytological diagnosis from mediastinal lesions. The aims of EUS‐FNA in the mediastinum are either to diagnose a lesion of unknown origin, to stage mediastinal lymph nodes in lung cancer patients or to diagnose other diseases involving lymph nodes of the mediastinum. In patients with non‐small cell lung cancer (NSCLC), surgery may be regarded as futile in up to 45% of patients operated, apparently because the stage of the disease is more advanced than expected preoperatively. This, combined with a stage‐dependent multimodality treatment, underlines the importance of exact staging of the disease. Conventional imaging and tissue sampling methods all have variable sensitivities. Twenty‐two studies concerning EUS‐FNA and mediastinal staging of lung cancer have been published with a total number of 1245 patients. The reported sensitivity for mediastinal malignancy range from 0.61–1.00 (median 0.90), and with specificities of 0.71–1.00 (median 1.00). The majority of the studies are retrospective and present the results of EUS‐FNA performed in lung cancer patients selected by computer tomography (CT). Recent data suggests that EUS‐FNA in addition can diagnose advanced mediastinal disease in 22–42% of NSCLC patients with normal sized lymph nodes (< 1 cm) on chest CT. EUS‐FNA may also be used as a re‐staging procedure after induction chemotherapy and it seems that EUS‐FNA is more accurate for mediastinal staging of NSCLC compared to positron emission tomography (PET). However, further studies are necessary before final conclusions can be made. At present, mediastinoscopy is still considered complementary to EUS‐FNA because EUS‐FNA cannot visualize structures anterior to the air‐filled trachea and main bronchi. Endoscopic trans‐bronchial real‐time ultrasound guided biopsy (EBUS‐TBNA) performed via the trachea and main bronchi seems to be an obvious solution. Preliminary experience with a prototype EBUS‐TBNA bronchoscope (Olympus, XBF‐UC40P, Tokyo, Japan) in 214 patients has shown promising results. Hopefully the combination of EUS‐FNA and EBUS‐TBNA will be able to replace more invasive and risky staging methods and improve the N‐staging accuracy of the mediastinum and lung hilar regions in the near future.     

Impact of EUS-guided FNA of enlarged mediastinal lymph nodes on subsequent thoracic surgery rates

BACKGROUND: A histopathologic diagnosis of metastasis in enlarged mediastinal lymph nodes usually results in non-surgical management. Cytologic specimens obtained by EUS-guided FNA can be used to detect malignancy in posterior mediastinal lymph nodes. The purpose of this study was to determine the rate of thoracic surgery after EUS-guided FNA of enlarged mediastinal lymph nodes. METHODS: A prospective observational study of patients with enlarged posterior mediastinal lymphadenopathy who were referred for EUS-guided FNA. All patients were candidates for mediastinoscopy. Patients were followed for 12 months to determine the subsequent rate of mediastinoscopy or thoracotomy and the diagnostic accuracy of EUS-guided FNA. RESULTS: Evaluation of cytologic specimens obtained by EUS-guided FNA revealed malignancy in 23 of 59 (39%) patients. The overall rate of surgery was 22% (13/59): 95% CI[0.12, 0.35]. The surgery rate for patients with a positive cytologic result was 4% (1/23) compared with 33% (12/36) for those with a negative result (p=0.009). Of patients with CT findings of a peripheral lung mass plus mediastinal lymphadenopathy, 22 of 26 (42%) underwent surgery after EUS-guided FNA, compared with two of 33 (6%) of those with mediastinal lymphadenopathy alone (p=0.0009). For cytologic evaluation of specimens obtained by EUS-guided FNA, the overall sensitivity, specificity, and accuracy for the diagnosis of malignant lymphadenopathy were 96%, 100%, and 98%, respectively. CONCLUSIONS: Few patients who undergo EUS-guided FNA of enlarged posterior mediastinal lymph nodes require subsequent thoracic surgery.     

The value of mediastinoscopy in preoperative evaluation of mediastinal involvement in non-small-cell lung cancer patients with clinical NO disease

BACKGROUND: The efficacy of mediastinal lymph node examination using cervical mediastinoscopy in operable non-small cell lung cancer patients without radiological nodal involvement on computerized tomography (CT) has been elusive. METHODS: The value of mediastinoscopy as a staging modality for assessing the mediastinal lymph node status was evaluated in 79 patients with presumed resectable non-small-cell lung cancer (NSCLC) with mediastinal nodes smaller than 1 cm (NO) form the CT scan. Sixty-one patients who did not have nodal involvement at mediastinoscopy and had complete medical records underwent complete resection. RESULTS: Negative predictive value (NPV) of the CT scan according to mediastinoscopy was 92.4 %. Histopathological examination of the surgical specimen showed the NPV of mediastinoscopy to be 93.4 %. Only 4 patients (3 patients with N2, 1 patient with N3 disease) were not correctly staged using CT scanning and mediastinoscopy. According to the pathological examination, the NPV of CT was found to be lower (76.5 %) in patients with adenocarcinoma, but the difference was not statistically significant (p > 0.128) CONCLUSION: Although the likelihood of surgical-pathological N2 is slightly higher in patients with adenocarcinoma, radiological examination of patients with cNO NSCLC disease can be as accurate as mediastinoscopy in appropriately staging mediastinal lymph node involvement.     

Endoscopic ultrasound examination for mediastinal lymph node metastases of lung cancer

Among patients with primary lung cancer who were admitted to the National Cancer Center Hospital from July 1987 to April 1988 for surgical treatments, 132 underwent preoperative transesophageal endoscopic ultrasound examination (EUS) on mediastinal lymph nodes. Of the 132 patients, 101 were pathologically evaluated and studied in this article. A GF-UM2 radial scanner with 7.5-MHz (Olympus Co Ltd) was used for image examination. The lymph nodes were diagnosed as positive for metastasis when they had thickened images, clear contours, and low echoing images of fusion or lobulation. The results obtained from 509 sites were as follows: sensitivity, 53.6 percent; specificity, 97.5 percent; positive predictive accuracy, 77.1 percent; negative predictive accuracy, 93.1 percent; and overall accuracy, 91.6 percent. The sensitivity rate was 80.6 percent excluding the result of the right superior mediastinal lymph nodes that were difficult to examine for anatomic reasons. Although EUS was considered to be an excellent method in diagnosing lymph node metastases, it had a blind angle in the field. More accurate diagnoses of mediastinal lymph node metastases could be achieved by using EUS and computed tomography (CT) together.     

A comparison of cobalt (57Co) bleomycin scanning and contrast-enhanced CT scanning for assessment of the mediastinum in lung cancer.

Sixty patients with histologically proven lung cancer who had been accepted for mediastinoscopy or thoracotomy were prospectively entered into a study to evaluate computed tomographic (CT) scanning, 57Co-bleomycin scanning, and barium swallow in preoperative assessment of mediastinal lymph node metastasis. Fifty-six patients had thoracotomy at which all accessible lymph nodes were sampled. Twenty-four patients were found to have mediastinal tumor on histologic analysis of the resected mediastinal lymph nodes. Neither 57Co-bleomycin scanning nor barium swallow were clinically useful, with sensitivities of 21 percent and 11 percent respectively, whereas CT scanning was helpful. However, there was no clear cutoff point of node size to optimize sensitivity and specificity for CT scanning. When nodes greater than or equal to 15 mm were taken to indicate likely malignancy, the sensitivity was 58 percent and the specificity was 87 percent and when greater than or equal to 10 mm was used the sensitivity was 80 percent but the specificity was only 55 percent. There was no clear relationship between the size of the largest resected lymph node in each patient and the presence of malignant lymph nodes. Only 42 percent of patients with resected nodes greater than or equal to 2 cm had histologic evidence of metastases. We conclude that CT scanning should be used to indicate the presence and site of mediastinal lymph nodes, which, when visualized, should always be sampled and histologically examined prior to resection of primary tumor.     

Endoscopic ultrasound‐guided fine‐needle aspiration when combined with positron emission tomography improves specificity and overall diagnostic accuracy in unexplained mediastinal lymphadenopathy and staging of non‐small‐cell lung cancer

Background: The aim of this study was to assess the incremental value of endoscopic ultrasound (EUS)‐guided fine‐needle aspiration (FNA) to positron emission tomography (PET) in the diagnosis of unexplained mediastinal lymphadenopathy and staging of non‐small‐cell lung cancer (NSCLC). Methods: Patients who had both EUS‐guided FNA and PET were retrospectively identified from an EUS database at a tertiary hospital. All EUS‐guided FNA were carried out by one endoscopist between August 2002 and April 2005, either for the diagnosis of unexplained mediastinal lymphadenopathy or for the staging of NSCLC. Results of PET and EUS were compared with histology. A true histological positive result was defined as histological involvement in either surgery (mediastinoscopy or resection) or EUS‐guided FNA. A true histological negative result was defined as negative involvement at surgery (mediastinoscopy or resection). Results: Forty‐nine patients who had both PET scanning and EUS‐guided FNA for diagnosis of unexplained mediastinal lymphadenopathy or staging of NSCLC were identified. Of these, 33 (73% males, n = 24, age range = 44–78 years, mean = 62 years) had surgical confirmation of mediastinal lymph node pathology. In these patients, PET alone showed sensitivity, 95%; specificity, 90%; positive predictive value, 87%; negative predictive value, 90% and accuracy, 88%; whereas the addition of EUS‐guided FNA increased the overall specificity and positive predictive value to 100%, with an overall accuracy of 97%. Conclusions: This study suggests that EUS‐guided FNA complements PET by improving the overall specificity and thereby the accuracy for diagnosis of unexplained mediastinal lymphadenopathy. It provides a minimally invasive technique to assess the mediastinum in patients with NSCLC and is particularly valuable in cases in which PET findings are equivocal.     

Mediastinal staging of bronchial carcinoma: can computed tomography replace mediastinoscopy?

In bronchial carcinoma the assessment of operability requires an accurate evaluation of the regional and mediastinal lymph nodes. For this, both mediastinoscopy and computed tomography are often used on a routine basis today. The present work considers the relative value of these two methods of investigation. Fifty-seven patients with bronchial carcinoma, in whom both investigations were carried out prior to surgery, were included in this prospective study. In the computed tomogram, lymph nodes with a diameter of more than 1 cm were defined as positive (i.e. suspected malignant infiltration). Sixteen of the 57 patients had histologically confirmed lymph node metastases; in 13 cases the metastases were detected by computed tomography, in 12 cases also by mediastinoscopy and in 3 cases only at thoracotomy. In 41 of the thoracotomized patients, no mediastinal metastases were found. As was to be expected, mediastinoscopy also proved negative in these cases. In 9 of these cases, however, the preoperative computed tomography findings were false-positive. For computed tomography the specificity was 78% and the sensitivity 81%; for mediastinoscopy, on the other hand, the specificity was 100% and the sensitivity 75%. The specificity of computed tomography is too low. Also, lymph nodes which are only inflamed may be considerably enlarged and cannot be differentiated in the computed tomogram from those with malignant infiltration. Mediastinal lymph nodes which appear enlarged in the computed tomogram therefore have to be further investigated by mediastinoscopy. However, in this prospective study, mediastinoscopy provided no additional information in those cases in whom the computed tomography findings were negative (lymph node diameter less than or equal to 1 cm); it did not detect the metastases in the 3 patients with false-negative computed tomography findings. Therefore, in the case of a negative computed tomogram, thoracotomy may be performed immediately, without previous mediastinoscopy.     

Accuracy and cost-effectiveness of [18F]-2-fluoro-deoxy-D-glucose-positron emission tomography scan in potentially resectable non-small cell lung cancer

STUDY OBJECTIVES: This retrospective study of patients who were referred for surgical resection of non-small cell lung cancer (NSCLC) assessed the accuracy and cost-effectiveness of positron emission tomography (PET) with radiolabeled [18F]-2-fluoro-deoxy-D-glucose (FDG) in staging mediastinal lymph nodes (MLNs). DESIGN: From January 2001 to September 2002, 90 patients with suspected or proven NSCLC who had been referred for curative resection were retrospectively reviewed. All patients were without evidence of metastatic disease. Sixty-nine of the 90 patients had undergone thoracic FDG-PET imaging as part of their evaluation and are the focus of this study. Sensitivity, specificity, accuracy, and positive and negative predictive values for metastasis to the MLN were calculated for CT scanning vs FDG-PET scanning. Four algorithms for staging MLN with mediastinoscopy and/or FDG-PET scan were compared. MEASUREMENTS AND RESULTS: Sixty-nine patients underwent preoperative CT and FDG-PET scans, and 32 of 69 patients underwent mediastinoscopy. Fifty-seven patients underwent thoracotomy with complete mediastinal lymphadenectomy. Sensitivity, specificity, accuracy, and positive and negative predictive values for CT scans and FDG-PET scans were 46%, 86%, 78%, 43%, and 87%, and 62%, 98%, 91%, 89% and 92%, respectively. Mediastinoscopy was accurate in 32 of 32 patients (100%). Routine mediastinoscopy remains the most economically reasonable strategy with excellent sensitivity. Selective FDG-PET imaging improved the sensitivity of noninvasive staging for patients with normal MLNs on CT scans. CONCLUSIONS: Selective use of FDG-PET imaging improves staging accuracy compared to CT scanning alone and makes it a cost-effective adjunct to the preoperative staging of NSCLC. However, in patients with adenocarcinoma and MLNs of < 1 cm, FDG-PET scanning cannot yet replace mediastinoscopy.     

Radiologic staging of lung cancer.

Preoperative tumor staging in patients with known or suspected non-small cell lung cancer is generally performed using contrast enhanced chest computed tomography (CT) (including the adrenal glands). Abdominal CT is generally unnecessary, given the low frequency of isolated liver metastases. The role of MRI is limited, and it is used mainly as a problem solving tool in certain specific situations. A CT showing no mediastinal lymph node enlargement usually oviates preoperative mediastinal lymph node sampling, with certain exceptions. If enlarged mediastinal lymph nodes are demonstrated at CT, then CT may be used to direct preoperative lymph node sampling via transbronchoscopic Wang needle biopsy, mediastinoscopy, mediastinotomy, or video assisted thoracoscopy.     

Ultrasound techniques in the evaluation of the mediastinum,part 2: mediastinal lymph node anatomy and diagnostic reach of ultrasound techniques,clinical work up of neoplastic and inflammatory mediastinal lymphadenopathy using ultrasound techniques and how to learn mediastinal endosonography

Ultrasound imaging has gained importance in pulmonary medicine over the last decades including conventional transcutaneous ultrasound (TUS), endoscopic ultrasound (EUS), and endobronchial ultrasound (EBUS). Mediastinal lymph node (MLN) staging affects the management of patients with both operable and inoperable lung cancer (e.g., surgery vs. combined chemoradiation therapy). Tissue sampling is often indicated for accurate nodal staging. Recent international lung cancer staging guidelines clearly state that endosonography should be the initial tissue sampling test over surgical staging. Mediastinal nodes can be sampled from the airways [endobronchial ultrasound combined with transbronchial needle aspiration (EBUS-TBNA)] or the esophagus [endoscopic ultrasound fine needle aspiration (EUS-FNA)]. EBUS and EUS have a complementary diagnostic yield and in combination virtually all MLNs can be biopsied. Additionally endosonography has an excellent yield in assessing granulomas in patients suspected of sarcoidosis. The aim of this review in two integrative parts is to discuss the current role and future perspectives of all ultrasound techniques available for the evaluation of mediastinal lymphadenopathy and mediastinal staging of lung cancer. A specific emphasis will be on learning mediastinal endosonography. Part 1 deals with an introduction into ultrasound techniques, MLN anatomy and diagnostic reach of ultrasound techniques and part 2 with the clinical work up of neoplastic and inflammatory mediastinal lymphadenopathy using ultrasound techniques and how to learn mediastinal endosonography.     

EUS-guided fine needle aspiration in mediastinal lymphadenopathy of unknown etiology

BACKGROUND: EUS-guided fine needle aspiration (EUS-FNA) has significantly expanded the diagnostic capability of GI EUS. FNA technology can also be helpful in the diagnosis of non-GI disorders. The role of EUS-guided FNA in the diagnosis of mediastinal lymphadenopathy of unknown etiology has not been described. The aim of this study was to evaluate the diagnostic accuracy and impact on subsequent evaluation and therapy of EUS-FNA in mediastinal lymphadenopathy of unknown cause. METHODS: Sixty-two patients (40 men, 22 woman; mean age 56 years, range 16-91 years) with mediastinal lymphadenopathy of unknown etiology underwent EUS-FNA at 6 tertiary referral centers. Presenting symptoms included the following: dysphagia, 6 patients; night sweats, 14; cough, 8; chest pain, 10; odynophagia, 10; fever, 6; weight loss, 8; and asymptomatic/abnormal radiograph, 12. A final diagnosis by EUS-FNA, surgery, autopsy, or long-term follow-up was available for all patients. EUS-FNA results were classified under 3 disease categories: (1) benign/infectious; (2) malignant pulmonary; and (3) malignant mediastinal (e.g., lymphoma, metastatic malignancy). Four EUS features were used as criteria for lymph node metastases: size greater than 1 cm, round shape, sharp border, and homogeneous/hypoechoic echo pattern. RESULTS: Final diagnoses included benign/infectious lymph nodes, 26; malignant pulmonary, 24; and malignant mediastinal, 12. EUS-FNA established a tissue diagnosis in 56 of 62 patients (90%). EUS criteria for malignant lymph nodes were more frequently present in malignant pulmonary (mean 2.6 features) and malignant mediastinal (mean 2.8) than benign/infectious (mean 1.9) lymph nodes. EUS results influenced subsequent evaluation in 87% and therapy in 87% of patients. There was no complication of EUS-FNA. CONCLUSIONS: EUS-FNA in patients with mediastinal lymphadenopathy is safe and guides subsequent therapy in the great majority of cases. Transesophageal EUS-FNA of mediastinal lymph nodes provides minimally invasive tissue sampling, obviating the need for mediastinoscopy or bronchoscopy.     

Is lobe-specific lymph node dissection appropriate in lung cancer patients undergoing routine mediastinoscopy?

BACKGROUND: The extent and the necessity of lymph node dissection has yet to be defined after resectional surgery for lung cancer. We aimed to analyze the lobe-specific extent of lymph node positivity in patients who underwent preoperative mediastinoscopy as a routine strategy. METHODS: A total of 280 patients with non-small cell lung cancer with negative mediastinoscopy were operated on in our center between January 1997 and June 2003. Hilar and mediastinal lymphadenectomy was performed in every patient. RESULTS: The most commonly involved lymph nodes were found to be paratracheal station lymph nodes (n = 83; 96.5 %) for right upper lobe tumors, subcarinal station lymph nodes (n = 52; 88.1 %) for right lower lobe carcinomas, aorticopulmonary lymph nodes (n = 62; 92.5 %) for left upper lobe and subcarinal station lymph nodes (n = 49; 96.0 %) for left lower lobe tumors. In the patients with right upper lobe, right lower lobe and left lower lobe tumors, the presence of a tumor at these stations was found to be an indicator for poor prognosis ( P = 0.033, P = 0.0038 and P = 0.0016, respectively). Patients with multiple station N2 disease did not survive beyond 3 years. CONCLUSIONS: In patients who underwent routine mediastinoscopy, lobe-specific lymph node dissection could be recommended. Patients with multilevel N2 involvement did not seem to benefit from resectional surgery.     

Endoscopic ultrasound in non-small cell lung cancer and negative mediastinum on computed tomography

Despite technical advances in staging non-small cell lung cancer (NSCLC), accurate staging remains a challenge. Endoscopic ultrasound is useful in staging NSCLC when lymphadenopathy is present on a computed tomography (CT), but its role in the absence of lymphadenopathy on CT has not been well defined. Therefore, we sought to determine the clinical impact of endoscopic ultrasound (EUS) in staging NSCLC in absence of mediastinal lymphadenopathy on CT. Seventy-six patients with NSCLC with absence of mediastinal lymphadenopathy on CT were enrolled and followed prospectively. EUS-guided fine-needle aspiration was performed on sites that were suspicious for metastases. Surgical pathology after thoracotomy was used as the reference standard for assessing accuracy. Sixty-two (86%) patients underwent surgery, and 10 (13%) did not. EUS precluded surgery in 9 patients (12%) and influenced management in 18 (25%) of all patients in this study. EUS detected malignant mediastinal lymphadenopathy more frequently in patients with lower lobe and hilar cancers combined compared with upper lobe cancers (p = 0.004). EUS played a significant role in identifying patients with unresectable (N3) NSCLC when adenopathy was not present on CT imaging and appears to be more sensitive in detecting lymph node metastases in lower lobe and hilar NSCLC compared with upper lobe NSCLC.     

Endoscopic ultrasound-guided fine-needle aspiration for non-small cell lung cancer staging: A systematic review and metaanalysis

BACKGROUND: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a minimally invasive alternative technique for mediastinal staging of non-small cell lung cancer. A metaanalysis was performed to estimate the diagnostic accuracy of EUS-FNA for staging mediastinal lymph nodes (N2/N3 disease) in patients with lung cancer. METHODS: Relevant studies were identified using Medline (1966 to November 2005), CINAHL, and citation indexing. Included studies used histology or adequate clinical follow-up (> 6 months) as the "gold standard," and provided sufficient data for calculating sensitivity and specificity. Summary receiver operating characteristic curves metaanalysis was performed to estimate the pooled sensitivity and specificity. RESULTS: In 18 eligible studies, EUS-FNA identified 83% of patients (95% confidence interval [CI], 78 to 87%) with positive mediastinal lymph nodes (pooled sensitivity) and 97% of patients (95% CI, 96 to 98%) with negative mediastinal lymph nodes (pooled specificity). In eight studies that were limited to patients who had abnormal mediastinal lymph nodes seen on CT scans, the sensitivity was 90% (95% CI, 84 to 94%) and the specificity was 97% (95% CI, 95 to 98%). In patients without abnormal mediastinal lymph nodes seen on CT scans (four studies), the pooled sensitivity was 58% (95% CI, 39 to 75%). Minor complications were reported in 10 cases (0.8%). There were no major complications. CONCLUSIONS: EUS-FNA is a safe modality for the invasive staging of lung cancer that is highly sensitive when used to confirm metastasis to mediastinal lymph nodes seen on CT scans. In addition, among lung cancer patients with normal mediastinal adenopathy seen on CT scans, despite lower sensitivity, it has the potential to prevent unnecessary surgery in a large proportion of cases missed by CT scanning.