CONTEXT Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary... Show moreCONTEXT Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary thoracotomies. Current guidelines acknowledge minimally invasive endosonography followed by surgical staging (if no nodal metastases are found by endosonography) as an alternative to immediate surgical staging. OBJECTIVE To compare the 2 recommended lung cancer staging strategies. DESIGN, SETTING, AND PATIENTS Randomized controlled multicenter trial (Ghent, Leiden, Leuven, Papworth) conducted between February 2007 and April 2009 in 241 patients with resectable (suspected) NSCLC in whom mediastinal staging was indicated based on computed or positron emission tomography. INTERVENTION Either surgical staging or endosonography (combined transesophageal and endobronchial ultrasound [EUS-FNA and EBUS-TBNA]) followed by surgical staging in case no nodal metastases were found at endosonography. Thoracotomy with lymph node dissection was performed when there was no evidence of mediastinal tumor spread. MAIN OUTCOME MEASURES The primary outcome was sensitivity for mediastinal nodal (N2/N3) metastases. The reference standard was surgical pathological staging. Secondary outcomes were rates of unnecessary thoracotomy and complications. RESULTS Two hundred forty-one patients were randomized, 118 to surgical staging and 123 to endosonography, of whom 65 also underwent surgical staging. Nodal metastases were found in 41 patients (35%; 95% confidence interval [CI], 27%-44%) by surgical staging vs 56 patients (46%; 95% CI, 37%-54%) by endosonography (P = .11) and in 62 patients (50%; 95% CI, 42%-59%) by endosonography followed by surgical staging (P = .02). This corresponded to sensitivities of 79% (41/52; 95% CI, 66%-88%) vs 85% (56/66; 95% CI, 74%-92%) (P = .47) and 94% (62/66; 95% CI, 85%-98%) (P = .02). Thoracotomy was unnecessary in 21 patients (18%; 95% CI, 12%-26%) in the mediastinoscopy group vs 9 (7%; 95% CI, 4%-13%) in the endosonography group (P = .02). The complication rate was similar in both groups. CONCLUSIONS Among patients with (suspected) NSCLC, a staging strategy combining endosonography and surgical staging compared with surgical staging alone resulted in greater sensitivity for mediastinal nodal metastases and fewer unnecessary thoracotomies. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00432640. Show less
Context Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary... Show moreContext Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary thoracotomies. Current guidelines acknowledge minimally invasive endosonography followed by surgical staging (if no nodal metastases are found by endosonography) as an alternative to immediate surgical staging. Objective To compare the 2 recommended lung cancer staging strategies. Design, Setting, and Patients Randomized controlled multicenter trial (Ghent, Leiden, Leuven, Papworth) conducted between February 2007 and April 2009 in 241 patients with resectable (suspected) NSCLC in whom mediastinal staging was indicated based on computed or positron emission tomography. Intervention Either surgical staging or endosonography (combined transesophageal and endobronchial ultrasound [EUS-FNA and EBUS-TBNA]) followed by surgical staging in case no nodal metastases were found at endosonography. Thoracotomy with lymph node dissection was performed when there was no evidence of mediastinal tumor spread. Main Outcome Measures The primary outcome was sensitivity for mediastinal nodal (N2/N3) metastases. The reference standard was surgical pathological staging. Secondary outcomes were rates of unnecessary thoracotomy and complications. Results Two hundred forty-one patients were randomized, 118 to surgical staging and 123 to endosonography, of whom 65 also underwent surgical staging. Nodal metastases were found in 41 patients (35%; 95% confidence interval [CI], 27%-44%) by surgical staging vs 56 patients (46%; 95% CI, 37%-54%) by endosonography (P=.11) and in 62 patients (50%; 95% CI, 42%-59%) by endosonography followed by surgical staging (P=.02). This corresponded to sensitivities of 79% (41/52; 95% CI, 66%-88%) vs 85% (56/66; 95% CI, 74%-92%) (P=.47) and 94% (62/66; 95% CI, 85%-98%) (P=.02). Thoracotomy was unnecessary in 21 patients (18%; 95% CI, 12%-26%) in the mediastinoscopy group vs 9 (7%; 95% CI, 4%-13%) in the endosonography group (P=.02). The complication rate was similar in both groups. Conclusions Among patients with (suspected) NSCLC, a staging strategy combining endosonography and surgical staging compared with surgical staging alone resulted in greater sensitivity for mediastinal nodal metastases and fewer unnecessary thoracotomies. Trial Registration clinicaltrials.gov Identifier: NCT00432640 JAMA. 2010;304(20):2245-2252 www.jama.com Show less
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... Show moreBackground: 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 NO 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. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Show less
Peric, R.; Schuurbiers, O.C.J.; Veselic, M.; Rabe, K.F.; Heijden, H.F.M. van der; Annema, J.T. 2010
Patients and methods: Consecutive patients with suspected mediastinal metastases (on computed tomography or positron emission tomography) and an (previous) extrathoracic malignancy underwent EUS... Show morePatients and methods: Consecutive patients with suspected mediastinal metastases (on computed tomography or positron emission tomography) and an (previous) extrathoracic malignancy underwent EUS-FNA. Results: Seventy-five patients with current (n = 14) or previously diagnosed (n = 61) extrathoracic malignancies were evaluated. EUS-FNA detected mediastinal malignancies in 43 patients (57%) [metastases of extrathoracic tumors, n = 36 (48%); second malignancy (lung cancer), n = 7 (9%)]. Mediastinal metastases were found at subsequent surgical staging in seven patients or during follow-up (one patient). In seven patients, an alternative diagnosis was established. Sensitivity, specificity, accuracy and negative predictive value of EUS-FNA for mediastinal staging were 86%, 100%, 91% and 72%, respectively. Conclusion: EUS-FNA is a minimally invasive mediastinal staging method for patients with extrathoracic malignancies to confirm nodal metastatic spread and therefore may qualify as an alternative for surgical staging. Show less
Szlubowski, A.; Zielinski, M.; Soja, J.; Annema, J.T.; Sosnicki, W.; Jakubiak, M.; ... ; Cmiel, A. 2010
Objectives: This prospective study aimed to assess the diagnostic yield of the combined approach endobronchial (EBUS) and endoscopic (EUS) ultrasound-guided needle aspiration (combined ultrasound... Show moreObjectives: This prospective study aimed to assess the diagnostic yield of the combined approach endobronchial (EBUS) and endoscopic (EUS) ultrasound-guided needle aspiration (combined ultrasound-needle aspiration (CUS-NA)) in the radiologically normal mediastinum in non-small-cell lung cancer (NSCLC) staging. Methods: CUS-NA was performed simultaneously under local anaesthesia and sedation in consecutive NSCLC patients with mediastinal nodes that were not enlarged on CT (stage IA-IIB). All patients with negative CUS-NA subsequently underwent the transcervical extended bilateral mediastinal lymphadenectomy (TEMLA) as a confirmatory test. Results: A total of 120 NSCLC patients underwent CUS-NA between 1 January 2008 and 31 December 2008. There were 318 mediastinal nodes biopsied (158EBUS-NA-stations: 2R-2, 2L-1, 4R-34, 4L-33 and 7-88 and 160 EUS-NA-stations: 4L-57, 7-101 and 9-2). CUS-NA revealed metastatic lymph node involvement in 19 of 120 patients (16%) and in 31 of 318 biopsies (10%). The prevalence was 22%. In 99 patients with negative CUS-NA, who underwent subsequent TEMLA, metastatic nodes were diagnosed in nine patients (8%) in 11 stations: 2R-2, 4R-4, 4L-1, 5-3 and 7-1. In all but one patient there were 'minimal N2' only. Diagnostic sensitivity, specificity, total accuracy, positive predictive value (PPV) and negative predictive value (NPV) of CUS-NA for normal mediastinum was 68% (95% confidence interval (CI): 48-84), 98% (95% CI: 92-100), 91% (95% CI: 86-96), 91% (95% CI: 70-99) and 91% (95% CI: 83-96), respectively. The sensitivity of CUS-NA was significantly higher than with EBUS-NA alone (p = 0.04) and higher, close to the level of significance than with EUS-NA alone (p = 0.07). The NPV of all techniques was high and that of CUS-NA was significantly higher than EBUS-NA alone and EUS-NA alone (p = 0.01, p = 0.03). No complications of CUS-NA were observed. Conclusions: In the radiologically normal mediastinum, CUS-NA is a highly effective and safe technique in NSCLC staging and, if negative, a surgical diagnostic exploration of the mediastinum may be omitted. (C) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. Show less
Bartheld, M.B. von; Veselic-Charvat, M.; Rabe, K.F.; Annema, J.T. 2010
Background and study aims: Transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of mediastinal lymph nodes is increasingly used to detect noncaseating granulomas in... Show moreBackground and study aims: Transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of mediastinal lymph nodes is increasingly used to detect noncaseating granulomas in patients with suspected sarcoidosis. The optimal needle size and tissue processing method for detecting noncaseating granulomas are debated. We assessed the value of cell-block analysis when added to conventional cytological evaluation of EUS aspirates obtained by 22-gauge needles in patients with stage I and II sarcoidosis. Patients and methods: Data from 101 consecutive patients (55% of whom had previously had a nondiagnostic bronchoscopy) with suspected pulmonary sarcoidosis (stage I and II), who underwent EUS-FNA of mediastinal lymph nodes with 22-gauge needles were retrospectively analyzed. Results: The sensitivity of EUS in detecting granulomas was 87% (cytology and cell-block analysis together) (stage I, 92%; stage II, 77%). In 33% of cytology negative patients (n = 6), granulomas were present in the cell block. The optimal yield for granuloma detection was reached with four needle passes. One patient developed mediastinitis after EUS-FNA. Conclusions: Cell-block analysis added to conventional cytological evaluation of 22-gauge EUS aspirates, results in a high yield in detecting granulomas in patients with suspected sarcoidosis and reduces the false-negative rate substantially. EUS has a considerably higher yield in stage I compared with stage II sarcoidosis. For an optimal yield, four needle passes are required. Show less
BACKGROUND: EUS-guided FNA is currently advocated in lung cancer staging guidelines as an alternative for surgical staging to prove mediastinal metastases. To date, training requirements for chest... Show moreBACKGROUND: EUS-guided FNA is currently advocated in lung cancer staging guidelines as an alternative for surgical staging to prove mediastinal metastases. To date, training requirements for chest physicians to obtain competency in EUS for lung cancer staging are unknown. OBJECTIVE: To test a training and implementation strategy for EUS for the diagnosis and staging of lung cancer. DESIGN: Prospective national multicenter implementation trial. Nine (chest) physicians from 5 hospitals participated in a dedicated EUS educational program (investigation of 50 patients) for the diagnosis and staging of lung cancer. EUS outcomes of trainees were compared with those of the training center. SETTING: Four general hospitals, the national cancer center (implementation centers), and a tertiary referral center (expert center). PATIENTS: This study involved 551 consecutive patients with (suspected) lung cancer, all candidates for surgical staging, who underwent EUS in 1 of the 5 implementation centers (n = 346) or the single expert center (n = 205). Surgical-pathological staging was the reference standard in case no mediastinal metastases were found. RESULTS: EUS had a sensitivity of 83% versus 82% and accuracy of 89% versus 88% for mediastinal nodal staging (implementation center vs expert center). Surgery was spared because of EUS findings in 51% versus 54% of patients. A single complication occurred in each group. LIMITATION: Surgical-pathological verification of mediastinal nodes was not available in all patients staged negative at EUS. CONCLUSION: Chest physicians who participate in a dedicated training and implementation program for EUS in lung cancer staging can obtain results similar to those of experts for mediastinal nodal staging. Show less
Background: EUS-guided FNA is currently advocated in lung cancer staging guidelines as an alternative for surgical staging to prove mediastinal metastases. To date, training requirements for chest... Show moreBackground: EUS-guided FNA is currently advocated in lung cancer staging guidelines as an alternative for surgical staging to prove mediastinal metastases. To date, training requirements for chest physicians to obtain competency in EUS for lung cancer staging are unknown. Objective: To test a training and implementation strategy for EUS for the diagnosis and staging of lung cancer. Design: Prospective national multicenter implementation trial. Nine (chest) physicians from 5 hospitals participated in a dedicated EUS educational program (investigation of 50 patients) for the diagnosis and staging of lung cancer. EUS outcomes Of trainees were compared with those of the training center. Setting: Four general hospitals, the national cancer center (implementation centers), and a tertiary referral center (expert center). Patients: This study involved 551 consecutive patients with (suspected) lung cancer, all candidates for surgical staging, who underwent EUS in 1 of the 5 implementation centers (n = 346) or the single expert center (n = 205). Surgical-pathological staging was the reference standard in case no tnediastinal metastases were found. Results: EUS had a sensitivity Of 83% versus 82% and accuracy Of 89% versus 88% For mediastinal nodal Staging (implementation center vs expert center). Surgery was spared because of EUS findings in 51% versus 54% of patients. A single complication occurred in each group. Limitation: Surgical-pathological verification Of mediastinal nodes was not available in all patients staged negative at EUS. Conclusion: Chest physicians who participate in a dedicated training and implernentation program for EUS in king Cancer Staging Call Obtain results similar to those of experts for mediastinal nodal staging. (Gastrointest Endose 2010;71:641-70.) Show less
