Felix J.F. Herth

Real-time endobronchial ultrasound guided transbronchial needle aspiration for sampling mediastinal lymph nodes

Background: Transbronchial needle aspiration (TBNA) is an established method for sampling mediastinal lymph nodes to aid in diagnosing lymphadenopathy and in staging lung cancers. Real-time endobronchial ultrasound (EBUS) guidance is a new method of TBNA that may increase the ability to sample these nodes and hence to determine a diagnosis. A descriptive study was conducted to test this new method. Methods: Consecutive patients referred for TBNA of mediastinal lymph nodes were included in the trial. When a node was detected, a puncture was performed under real-time ultrasound control. The primary end point was the number of successful biopsy specimens. Diagnostic results from the biopsies were compared with operative findings. Lymph node stations were classified according to the recently adopted American Thoracic Society scheme. Results: From 502 patients (316 men) of mean age 59 years (range 24–82), 572 lymph nodes were punctured and 535 (94%) resulted in a diagnosis. Biopsy specimens were taken from lymph nodes in region 2L (40 nodes), 2R (53 nodes), 3 (35 nodes), 4R (86 nodes), 4L (77 nodes), 7 (127 nodes), 10R (38 nodes), 10L (43 nodes), 11R (40 nodes) and 11L (33 nodes). The mean (SD) diameter of the nodes was 1.6 (0.36) cm and the range was 0.8–3.2 cm (SD range 0.8–4.3). Sensitivity was 94%, specificity 100%, and the positive predictive value was 100% calculated per patient. No complications occurred. Conclusion: EBUS-TBNA is a promising new method for sampling mediastinal lymph nodes. It appears to permit more and smaller nodes to be sampled than conventional TBNA, and it is safe.

A Randomized Study of Endobronchial Valves for Advanced Emphysema

BACKGROUND Endobronchial valves that allow air to escape from a pulmonary lobe but not enter it can induce a reduction in lobar volume that may thereby improve lung function and exercise tolerance in patients with pulmonary hyperinflation related to advanced emphysema. METHODS We compared the safety and efficacy of endobronchial-valve therapy in patients with heterogeneous emphysema versus standard medical care. Efficacy end points were percent changes in the forced expiratory volume in 1 second (FEV1) and the 6-minute walk test on intention-to-treat analysis. We assessed safety on the basis of the rate of a composite of six major complications. RESULTS Of 321 enrolled patients, 220 were randomly assigned to receive endobronchial valves (EBV group) and 101 to receive standard medical care (control group). At 6 months, there was an increase of 4.3% in the FEV1 in the EBV group (an increase of 1.0 percentage point in the percent of the predicted value), as compared with a decrease of 2.5% in the control group (a decrease of 0.9 percentage point in the percent of the predicted value). Thus, there was a mean between-group difference of 6.8% in the FEV1 (P=0.005). Roughly similar between-group differences were observed for the 6-minute walk test. At 12 months, the rate of the complications composite was 10.3% in the EBV group versus 4.6% in the control group (P=0.17). At 90 days, in the EBV group, as compared with the control group, there were increased rates of exacerbation of chronic obstructive pulmonary disease (COPD) requiring hospitalization (7.9% vs. 1.1%, P=0.03) and hemoptysis (6.1% vs. 0%, P=0.01). The rate of pneumonia in the target lobe in the EBV group was 4.2% at 12 months. Greater radiographic evidence of emphysema heterogeneity and fissure completeness was associated with an enhanced response to treatment. CONCLUSIONS Endobronchial-valve treatment for advanced heterogeneous emphysema induced modest improvements in lung function, exercise tolerance, and symptoms at the cost of more frequent exacerbations of COPD, pneumonia, and hemoptysis after implantation. (Funded by Pulmonx; ClinicalTrials.gov number, NCT00129584.)

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration of Lymph Nodes in the Radiologically and Positron Emission Tomography-Normal Mediastinum in Patients With Lung Cancer

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can reliably sample enlarged mediastinal lymph nodes in patients with non-small cell lung cancer (NSCLC), and in practice is mostly used to sample nodes visible on CT or positron emission tomography (PET). Few data are available on the use of endoscopic procedures to stage the mediastinum in clinical stage 1 lung cancer. The aim of the present study was to determine the results of EBUS-TBNA in sampling mediastinal lymph nodes in patients with lung cancer and a radiographically normal mediastinum and no PET activity. From January 2004 to May 2007, patients highly suspicious for NSCLC with CT scans showing no enlarged lymph nodes (no node > 1 cm) and a negative PET finding of the mediastinum underwent EBUS-TBNA. Identifiable lymph nodes at locations 2r, 2L, 4r, 4L, 7, 10r, 10L, 11r, and 11L were aspirated. All patients underwent subsequent surgical staging. Diagnoses based on aspiration results were compared with those based on surgical results. One hundred patients (mean age, 52.4 years; 59 men) were included. After surgery, 97 patients (mean age, 52.9 years; 57 men) had NSCLC confirmed and were included in the analysis. In this group, 156 lymph nodes ranging 5 to 10 mm in size were detected and sampled. Malignancy was detected in nine patients but missed in one patient. Mean diameter of the punctured lymph nodes was 7.9 mm. The sensitivity of EBUS-TBNA for detecting malignancy was 89%, specificity was 100%, and the negative predictive value was 98.9%. No complications occurred. In conclusion, EBUS-TBNA can be used to accurately sample and stage patients with clinical stage 1 lung cancer and no evidence of mediastinal involvement on CT and PET. Potentially operable patients with no signs of mediastinal involvement may benefit from presurgical staging with EBUS-TBNA.

Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop.

Introduction: Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have recently been characterized in a subset of patients with advanced non-small cell lung cancer (NSCLC). Patients harboring these mutations in their tumors show excellent response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The EGFR-TKI gefitinib has been approved in Europe for the treatment of adult patients with locally advanced or metastatic NSCLC with activating mutations of the EGFR TK. Because EGFR mutation testing is not yet well established across Europe, biomarker-directed therapy only slowly emerges for the subset of NSCLC patients most likely to benefit: those with EGFR mutations. Methods: The “EGFR testing in NSCLC: from biology to clinical practice” International Association for the Study of Lung Cancer-European Thoracic Oncology Platform multidisciplinary workshop aimed at facilitating the implementation of EGFR mutation testing. Recommendations for high-quality EGFR mutation testing were formulated based on the opinion of the workshop expert group. Results: Co-operation and communication flow between the various disciplines was considered to be of most importance. Participants agreed that the decision to request EGFR mutation testing should be made by the treating physician, and results should be available within 7 working days. There was agreement on the importance of appropriate sampling techniques and the necessity for the standardization of tumor specimen handling including fixation. Although there was no consensus on which laboratory test should be preferred for clinical decision making, all stressed the importance of standardization and validation of these tests. Conclusion: The recommendations of the workshop will help implement EGFR mutation testing in Europe and, thereby, optimize the use of EGFR-TKIs in clinical practice.

Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study

BACKGROUND Talc is the most effective chemical pleurodesis agent for patients with malignant pleural effusion. However, concerns have arisen about the safety of intrapleural application of talc, after reports of development of acute respiratory distress syndrome in 1-9% of treated patients. Our aim was to establish whether use of large-particle-size talc is safe in patients with malignant pleural effusion. METHODS We did a multicentre, open-label, prospective cohort study of 558 patients with malignant pleural effusion who underwent thoracoscopy and talc poudrage with 4 g of calibrated French large-particle talc in 13 European hospitals, and one in South Africa. The primary endpoint was the occurrence of acute respiratory distress syndrome after talc pleurodesis. FINDINGS No patients developed acute respiratory distress syndrome (frequency 0%, one-sided 95% CI 0-0.54%). 11 (2%) patients died within 30 days. Additionally, seven patients had non-fatal post-thoracoscopy complications (1.2%), including one case of respiratory failure due to unexplained bilateral pneumothorax. INTERPRETATION Use of large-particle talc for pleurodesis in malignant pleural effusion is safe, and not associated with the development of acute respiratory distress syndrome.

Diagnosis of Mediastinal Adenopathy—Real-Time Endobronchial Ultrasound Guided Needle Aspiration versus Mediastinoscopy

Background: Real-time endobronchial ultrasound has increased the accuracy of conventional transbronchial needle aspiration biopsy in sampling mediastinal lymph nodes. Nevertheless, direct comparisons with mediastinoscopy are not available to determine the role of endobronchial ultrasound in pathologic staging. Objectives: To compare the diagnostic yield of endobronchial ultrasound against cervical mediastinoscopy in the diagnosis and staging of radiologically enlarged mediastinal lymph nodes stations accessible by both modalities in patients with suspected nonsmall cell lung cancer. Methods: Prospective, crossover trial with surgical lymph node dissection used as the accepted standard. Biopsy results of paratracheal and subcarinal lymph nodes were compared. Results: Sixty-six patients with a mean age 60 ± 10 years were studied. The prevalence of malignancy was 89% (59/66 cases). Endobronchial ultrasound had a higher overall diagnostic yield (91%) compared with mediastinoscopy (78%; p = 0.007) in the per lymph node analysis. There was disagreement in the yield between the two procedures in the subcarinal lymph nodes (24%; p = 0.011). There were no significant differences in the yield at other lymph node stations. The sensitivity, specificity, and negative predictive value of endobronchial ultrasound were 87, 100, and 78%, respectively. The sensitivity, specificity, and negative predictive value of mediastinoscopy were 68, 100, and 59%, respectively. No significant differences were found between endobronchial ultrasound (93%) and mediastinoscopy (82%; p = 0.083) in determining true pathologic N stage (per patient analysis). Conclusions: In suspected nonsmall cell lung cancer, endobronchial ultrasound may be preferred in the histologic sampling of paratracheal and subcarinal mediastinal adenopathy because the diagnostic yield can surpass mediastinoscopy.

Endobronchial ultrasound: new insight for the diagnosis of sarcoidosis.

A diagnosis of sarcoidosis should be substantiated by pathological means in order to thoroughly exclude other diseases. The role of real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of sarcoidosis has not been reported. The purpose of the present study is to evaluate the diagnostic yield of EBUS-TBNA in demonstrating the pathological features of sarcoidosis. In total, 65 patients with suspected sarcoidosis, with enlarged hilar or mediastinal lymph nodes on computed tomography, were included in the study. Patients with a suspected or known malignancy or previously established diagnosis of sarcoidosis were excluded. Convex probe endobronchial ultrasonography integrated with a separate working channel was used for EBUS-TBNA. Surgical methods were performed in those in whom no granulomas were detected by EBUS-TBNA. Patients were followed up clinically. EBUS-TBNA was performed on a total of 77 lymph node stations in 65 patients. A final diagnosis of sarcoidosis was made for 61 (93.8%) of the patients. The remaining four patients were diagnosed as having Wegeners granulomatosis (n = 1) or indefinite (n = 3). In patients with a final diagnosis of sarcoidosis, EBUS-TBNA demonstrated noncaseating epithelioid cell granulomas in 56 (91.8%) of the patients. No complications were reported. Endobronchial ultrasound-guided transbronchial needle aspiration proved to be a safe procedure with a high yield for the diagnoses of sarcoidosis.

Endobronchial Ultrasound With Transbronchial Needle Aspiration for Restaging the Mediastinum in Lung Cancer

PURPOSE To investigate the sensitivity and accuracy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for restaging the mediastinum after induction chemotherapy in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS One hundred twenty-four consecutive patients with tissue-proven stage IIIA-N2 disease who were treated with induction chemotherapy and who had undergone mediastinal restaging by EBUS-TBNA were reviewed. On the basis of computed tomography, 58 patients were classified as having stable disease and 66 were judged to have had a partial response. All patients subsequently underwent thoracotomy with attempted curative resection and a lymph node dissection regardless of EBUS-TBNA findings. RESULTS Persistent nodal metastases were detected by using EBUS-TBNA in 89 patients (72%). Of the 35 patients in whom no metastases were assessed by EBUS-TBNA, 28 were found to have residual stage IIIA-N2 disease at thoracotomy. The majority (91%) of these false negative results were due to nodal sampling error rather than detection error. Overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of EBUS-TBNA for mediastinal restaging after induction chemotherapy were 76%, 100%, 100%, 20%, and 77%, respectively. CONCLUSION EBUS-TBNA is a sensitive, specific, accurate, and minimally invasive test for mediastinal restaging of patients with NSCLC. However, because of the low negative predictive value, tumor-negative findings should be confirmed by surgical staging before thoracotomy.

Combined endoscopic-endobronchial ultrasound-guided fine-needle aspiration of mediastinal lymph nodes through a single bronchoscope in 150 patients with suspected lung cancer.

BACKGROUND For mediastinal lymph nodes, biopsies must often be performed to accurately stage lung cancer. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) allows real-time guidance in sampling paratracheal, subcarinal, and hilar lymph nodes, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) can sample mediastinal lymph nodes located adjacent to the esophagus. Nodes can be sampled and staged more completely by combining these procedures, but to date use of two different endoscopes has been required. We examined whether both procedures could be performed with a single endobronchial ultrasound bronchoscope. METHODS Consecutive patients with a presumptive diagnosis of non-small cell lung cancer (NSCLC) underwent endoscopic staging by EBUS-TBNA and EUS-FNA through a single linear ultrasound bronchoscope. Surgical confirmation and clinical follow-up was used as the reference standard. RESULTS Among 150 evaluated patients, 139 (91%; 83 men, 56 women; mean age 57.6 years) were diagnosed with NSCLC. In these 139 patients, 619 nodes were endoscopically biopsied: 229 by EUS-FNA and 390 by EBUS-TBNA. Sensitivity was 89% for EUS-FNA and 92% for EBUS-TBNA. The combined approach had a sensitivity of 96% and a negative predictive value of 95%, values higher than either approach alone. No complications occurred. CONCLUSIONS The two procedures can easily be performed with a dedicated linear endobronchial ultrasound bronchoscope in one setting and by one operator. They are complementary and provide better diagnostic accuracy than either one alone. The combination may be able to replace more invasive methods as a primary staging method for patients with lung cancer.

Efficacy predictors of lung volume reduction with zephyr valves in a european cohort

The Endobronchial Valve for Emphysema Palliation Trial (VENT) was a multi-centre, prospective, randomised, controlled trial conducted to evaluate the safety and effectiveness of unilateral endobronchial valve (EBV) treatment. The purpose of this analysis was to assess outcomes in the previously unreported European VENT study cohort. Patients with advanced emphysema were randomly assigned (2:1) to receive Zephyr® (Pulmonx Inc., Redwood City, CA, USA) EBV treatment (n=111) or medical management (n=60). At 6 months, EBV patients demonstrated a significant improvement compared with the controls for mean±sd change in forced expiratory volume in 1 s (7±20% versus 0.5±19%; p=0.067), cycle ergometry (2±14 W versus -3±10 W; p=0.04) and St George’s Respiratory Questionnaire (-5±14 points versus 0.3±13 points; p=0.047). At 12 months, the magnitude of the difference between groups for change from baseline was of similar magnitude to the differences seen at 6 months. Rates for complications did not differ significantly. EBV patients with computed tomography (CT) scans suggestive of complete fissure and lobar occlusion had a mean±sd lobar volume reduction of -80±30% and >50% met minimal clinical difference thresholds. The degree of emphysema heterogeneity did not preclude excellent outcomes. Unilateral lobar volume reduction using EBV treatment is safe and superior clinical results correlated with CT suggestive of complete fissures and successful lobar occlusion. Emphysema heterogeneity was not critical for determining positive outcomes.