Ralf Eberhardt

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.

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.

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 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.

Radiological and clinical outcomes of using Chartis (TM) to plan endobronchial valve treatment

One-way endobronchial valves (EBVs) have been shown to relieve symptoms of emphysema, particularly in patients without collateral ventilation (CV) between the target and adjacent lobes. In this study, we investigated the ability of the bronchoscopic Chartis™ Pulmonary Assessment System to predict treatment response by determining the presence of CV. 80 EBV patients underwent a pre-treatment Chartis assessment. Before and 30 days after implantation, high-resolution computed tomography scans were taken to determine target lobe volume reduction (TLVR). A pre- to post-treatment reduction of ≥350 mL was defined as significant. In addition, clinical outcomes (forced expiratory volume in 1 s (FEV1), 6-min walk test and St George’s Respiratory Questionnaire) were compared over the same time period. Of the 51 patients classified as having an absence of CV according to their Chartis reading, 36 showed a TLVR ≥350 mL. 29 patients were classified as having CV, and of these 24 did not meet this TLVR cut-off. Chartis showed an accuracy level of 75% in predicting whether or not the TLVR cut-off would be reached. Those predicted to respond showed significantly greater TLVR (p<0.0001) and FEV1 improvement (p=0.0013) than those predicted not to respond. Chartis is a safe and effective method of predicting response to EBV treatment.

Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: A Tuberculosis Network European Trialsgroup study

RATIONALE The rapid diagnosis of pulmonary tuberculosis (TB) is difficult when acid fast bacilli (AFB) cannot be detected in sputum smears. OBJECTIVES Following a proof of principle study, we examined in routine clinical practice whether individuals with sputum AFB smear-negative TB can be discriminated from those with latent TB infection by local immunodiagnosis with a Mycobacterium tuberculosis-specific enzyme-linked immunospot (ELISpot) assay. METHODS Subjects suspected of having active TB who were unable to produce sputum or with AFB-negative sputum smears were prospectively enrolled at Tuberculosis Network European Trialsgroup centers in Europe. ELISpot with early-secretory-antigenic-target-6 and culture-filtrate-protein-10 peptides was performed on peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage mononuclear cells (BALMCs). M. tuberculosis-specific nucleic acid amplification (NAAT) was performed on bronchoalveolar lavage fluid. MEASUREMENTS AND MAIN RESULTS Seventy-one of 347 (20.4%) patients had active TB. Out of 276 patients who had an alternative diagnosis, 127 (46.0%) were considered to be latently infected with M. tuberculosis by a positive PBMC ELISpot result. The sensitivity and specificity of BALMC ELISpot for the diagnosis of active pulmonary TB were 91 and 80%, respectively. The BALMC ELISpot (diagnostic odds ratio [OR], 40.4) was superior to PBMC ELISpot (OR, 10.0), tuberculin skin test (OR, 7.8), and M. tuberculosis specific NAAT (OR, 12.4) to diagnose sputum AFB smear-negative TB. In contrast to PBMC ELISpot and tuberculin skin test, the BALMC ELISpot was not influenced by previous history of TB. CONCLUSIONS Bronchoalveolar lavage ELISpot is an important advancement to rapidly distinguish sputum AFB smear-negative TB from latent TB infection in routine clinical practice.

Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.

Endosonography vs Conventional Bronchoscopy for the Diagnosis of Sarcoidosis: The GRANULOMA Randomized Clinical Trial

IMPORTANCE Tissue verification of noncaseating granulomas is recommended for the diagnosis of sarcoidosis. Bronchoscopy with transbronchial lung biopsies, the current diagnostic standard, has moderate sensitivity in assessing granulomas. Endosonography with intrathoracic nodal aspiration appears to be a promising diagnostic technique. OBJECTIVE To evaluate the diagnostic yield of bronchoscopy vs endosonography in the diagnosis of stage I/II sarcoidosis. DESIGN, SETTING, AND PATIENTS Randomized clinical multicenter trial (14 centers in 6 countries) between March 2009 and November 2011 of 304 consecutive patients with suspected pulmonary sarcoidosis (stage I/II) in whom tissue confirmation of noncaseating granulomas was indicated. INTERVENTIONS Either bronchoscopy with transbronchial and endobronchial lung biopsies or endosonography (esophageal or endobronchial ultrasonography) with aspiration of intrathoracic lymph nodes. All patients also underwent bronchoalveolar lavage. MAIN OUTCOMES AND MEASURES The primary outcome was the diagnostic yield for detecting noncaseating granulomas in patients with a final diagnosis of sarcoidosis. The diagnosis was based on final clinical judgment by the treating physician, according to all available information (including findings from initial bronchoscopy or endosonography). Secondary outcomes were the complication rate in both groups and sensitivity and specificity of bronchoalveolar lavage in the diagnosis of sarcoidosis. RESULTS A total of 149 patients were randomized to bronchoscopy and 155 to endosonography. Significantly more granulomas were detected at endosonography vs bronchoscopy (114 vs 72 patients; 74% vs 48%; P < .001). Diagnostic yield to detect granulomas for endosonography was 80% (95% CI, 73%-86%); for bronchoscopy, 53% (95% CI, 45%-61%) (P < .001). Two serious adverse events occurred in the bronchoscopy group and 1 in the endosonography group; all patients recovered completely. Sensitivity of the bronchoalveolar lavage for sarcoidosis based on CD4/CD8 ratio was 54% (95% CI, 46%-62%) for flow cytometry and 24% (95% CI, 16%-34%) for cytospin analysis. CONCLUSION AND RELEVANCE Among patients with suspected stage I/II pulmonary sarcoidosis undergoing tissue confirmation, the use of endosonographic nodal aspiration compared with bronchoscopic biopsy resulted in greater diagnostic yield. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00872612.

Narrow-Band Imaging Bronchoscopy Increases the Specificity of Bronchoscopic Early Lung Cancer Detection

Background: Detection of nonsmall cell lung cancer at the intraepithelial stage is believed to improve cure rates. New bronchoscopic technologies, including white light videobronchoscopy (WLB), autofluorescence imaging (AFI), and narrow band imaging (NBI), are aiming to diagnose airway neoplasia at a preinvasive stage. Objectives: To evaluate the diagnostic yields of NBI individually and in combination with WLB and AFI. Methods: A 10-month review of patients who were referred for airway screening or surveillance. Patients were randomized as to the order of AFI and NBI examinations. The airway mucosa was graded endoscopically as “normal,” “abnormal,” “suspicious,” or “tumor.” All areas that were not normal were biopsied. Biopsies with a histologic grading of moderate to severe dysplasia or carcinoma in situ were considered positive for intraepithelial neoplasia. Results: Sixty-two patients with a mean age of 56.2 ± 9.8 years were studied. Five patients had invasive cancers and were excluded from the analysis. The remaining 57 cases had a 30% prevalence of intraepithelial neoplasia. The sensitivity of WLB was 0.18 and the specificity was 0.88. The relative sensitivities (compared with WLB) of AFI and NBI were 3.7 (p = 0.005) and 3.0 (p = 0.03), respectively. The relative specificities of AFI and NBI were 0.5 (p < 0.001) and 1.0 (p = 0.72), respectively. Combining AFI and NBI did not increase diagnostic yield significantly. The sequence of performing AFI and NBI did not impact findings. Conclusions: NBI is an alternative to AFI in the detection of early lung cancers because it has a comparatively higher specificity without significantly compromising the sensitivity.