Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) Samples from Advanced Non-Small Cell Lung Cancer for Whole Genome, Whole Exome and Comprehensive Panel Sequencing.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is often the only source of tumor tissue from patients with advanced, inoperable lung cancer. EBUS-TBNA aspirates are used for the diagnosis, staging, and genomic testing to inform therapy options. Here we extracted DNA and RNA from 220 EBUS-TBNA aspirates to evaluate their suitability for whole genome (WGS), whole exome (WES), and comprehensive panel sequencing. For a subset of 40 cases, the same nucleic acid extraction was sequenced using WGS, WES, and the TruSight Oncology 500 assay. Genomic features were compared between sequencing platforms and compared with those reported by clinical testing. A total of 204 aspirates (92.7%) had sufficient DNA (100 ng) for comprehensive panel sequencing, and 109 aspirates (49.5%) had sufficient material for WGS. Comprehensive sequencing platforms detected all seven clinically reported tier 1 actionable mutations, an additional three (7%) tier 1 mutations, six (15%) tier 2-3 mutations, and biomarkers of potential immunotherapy benefit (tumor mutation burden and microsatellite instability). As expected, WGS was more suited for the detection and discovery of emerging novel biomarkers of treatment response. WGS could be performed in half of all EBUS-TBNA aspirates, which points to the enormous potential of EBUS-TBNA as source material for large, well-curated discovery-based studies for novel and more effective predictors of treatment response. Comprehensive panel sequencing is possible in the vast majority of fresh EBUS-TBNA aspirates and enhances the detection of actionable mutations over current clinical testing.

Discrepancies in tumor mutation burden reporting from sequential endobronchial ultrasound transbronchial needle aspiration samples within single lymph node stations - brief report.

Introduction: Tumour Mutation Burden (TMB) is a potential biomarker for immune cancer therapies. Here we investigated parameters that might affect TMB using duplicate cytology smears obtained from endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA)-sampled malignant lymph nodes. Methods: Individual Diff-Quik cytology smears were prepared for each needle pass. DNA extracted from each smear underwent sequencing using large gene panel (TruSight Oncology 500 (TSO500 - Illumina)). TMB was estimated using the TSO500 Local App v. 2.0 (Illumina). Results: Twenty patients had two or more Diff-Quik smears (total 45 smears) which passed sequencing quality control. Average smear TMB was 8.7 ± 5.0 mutations per megabase (Mb). Sixteen of the 20 patients had paired samples with minimal differences in TMB score (average difference 1.3 ± 0.85). Paired samples from 13 patients had concordant TMB (scores below or above a threshold of 10 mutations/Mb). Markedly discrepant TMB was observed in four cases, with an average difference of 11.3 ± 2.7 mutations/Mb. Factors affecting TMB calling included sample tumour content, the amount of DNA used in sequencing, and bone fide heterogeneity of node tumour between paired samples. Conclusion: TMB assessment is feasible from EBUS-TBNA smears from a single needle pass. Repeated samples of a lymph node station have minimal variation in TMB in most cases. However, this novel data shows how tumour content and minor change in site of node sampling can impact TMB. Further study is needed on whether all node aspirates should be combined in 1 sample, or whether testing independent nodes using smears is needed.

Whole Genome Sequencing in Advanced Lung Cancer can be Performed Using Diff-Quik Cytology Smears Derived from Endobronchial Ultrasound, Transbronchial Needle Aspiration (EBUS TBNA).

INTRODUCTION: Maximising alternative sample types for genomics in advanced lung cancer is important because bronchoscopic samples may sometimes be insufficient for this purpose. Further, the clinical applications of comprehensive molecular analysis such as whole genome sequencing (WGS) are rapidly developing. Diff-Quik cytology smears from EBUS TBNA is an alternative source of DNA, but its feasibility for WGS has not been previously demonstrated. METHODS: Diff-Quik smears were collected along with research cell pellets. RESULTS: Tumour content of smears were compared to research cell pellets from 42 patients, which showed good correlation (Spearman correlation 0.85, P < 0.0001). A subset of eight smears underwent WGS, which presented similar mutation profiles to WGS of the matched cell pellet. DNA yield was predicted using a regression equation of the smears cytology features, which correctly predicted DNA yield > 1500 ng in 7 out of 8 smears. CONCLUSIONS: WGS of commonly collected Diff-Quik slides is feasible and their DNA yield can be predicted.

Evaluating Diff-Quik cytology smears for large-panel mutation testing in lung cancer-Predicting DNA content and success with low-malignant-cellularity samples.

BACKGROUND: Cytology smears are commonly collected during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) procedures but are rarely used for molecular testing. Studies are needed to demonstrate their great potential, in particular for the prediction of malignant cell DNA content and for utility in molecular diagnostics using large gene panels. METHODS: A prospective study was performed on samples from 66 patients with malignant lymph nodes who underwent EBUS TBNA. All patients had air-dried, Diff-Quik cytology smears and formalin-fixed, paraffin-embedded cell blocks collected for cytopathology and molecular testing. One hundred eighty-five smears were evaluated by microscopy to estimate malignant cell percentage and abundance and to calculate smear size and were subjected to DNA extraction. DNA from 56 smears from 27 patients was sequenced with the TruSight Oncology 500 assay (Illumina). RESULTS: Each microscopy parameter had a significant effect on the DNA yield. An algorithm was developed that predicted a >50-ng DNA yield of a smear with an area under the curve of 0.86. Fifty DNA samples (89%) with varying malignant yields were successfully sequenced. Low-malignant-cell content (<25%) and smear area (<15%) were the main reasons for failure. All standard-of-care mutations were detected in replicate smears from individual patients, regardless of malignant cell content. Tier 1/2 mutations were discovered in two cases where standard-of-care specimens were inadequate for sequencing. Smears were scored for tumor mutation burden. CONCLUSIONS: Microscopy of Diff-Quik smears can triage samples for comprehensive panel sequencing, which highlights smears as an excellent alternative to traditional testing with cell blocks.

Prospective Optimization of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Lymph Node Assessment for Lung Cancer: Three Needle Agitations Are Noninferior to 10 Agitations for Adequate Tumor Cell and DNA Yield.

Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) is an important means of obtaining a tissue for advanced lung cancer. Optimizing the EBUS TBNA needling technique is important to maintain procedural simplicity and maximize sample quality for emerging molecular diagnostics. Methods: We prospectively explored three versus 10 agitations of the needle in sequential passes into the lymph node using separate needles. Resulting Diff-Quik cytology smears were quantitatively assessed using microscopic (tumor cell cellularity, abundance scores, erythrocyte contamination) and DNA yields. Microscopy was reported by two cytopathologists, and an inter-rater assessment was made by four additional cytopathologists. Results: In 86 patients confirmed as having malignant disease by EBUS TBNA (45 males, 41 females), a mean of 5.3 smears were made per patient with a total of 459 smears scored by pathologists and 168 paired smears extracted for DNA. There was no significant difference between three versus 10 agitations for smear cellularity (p = 0.44), DNA yield (p = 0.84), or DNA integrity (p = 0.20), but there was significantly less contamination by erythrocytes from three agitations (chi-square p = 0.008). There was significantly more DNA in the first pass into the node using three agitations than with other passes and with 10 agitations (pass × agitations interaction, p = 0.031). Reviewing pathologists correctly classified smears as more than or equal to 25% cellularity 86.3% of the time (κ = 0.63 [95% confidence interval: 0.55-0.71]). Conclusions: Three agitations are noninferior to 10 agitations for overall abundance of malignant cells and DNA content on smears. A smear with adequate DNA for panel sequencing could almost always be made with the first needle pass using three agitations.

Using the GenCut core biopsy tool with the radial endobronchial ultrasound guide sheath enables a high-quality histology sample capable of programmed cell death ligand 1 (PD-L1) testing.

Radial EndoBronchial UltraSound (R-EBUS)-guided biopsies are a promising biopsy technique for pulmonary nodules suspected of lung cancer with great safety profile. Programmed cell death ligand 1 (PD-L1) testing is increasingly demanded from lung biopsies. GenCut is a novel blunt tool that can be used to obtain core biopsies. This case series explores prospective performance of the GenCut core biopsy with R-EBUS. Once Peripheral Pulmonary Lesion was located, GenCut biopsy was performed followed by conventional (forceps ± cytology brush) R-EBUS biopsies. The overall diagnostic yield for the 16 patients with a mean peripheral pulmonary lesion (PPL) size of 4.1 cm was 100% from multi-modal R-EBUS sampling. The diagnostic yield for GenCut tool alone was 13/16 (81.2%) and the ability to perform PD-L1 from GenCut was 10/16 (62.5%). There were no adverse events recorded. GenCut tool is a novel blunt instrument that can be used safely to obtain a core biopsy suitable for PD-L1 in combination with R-EBUS without compromising the high safety profile.

First Human Use of a New Robotic-Assisted Fiber Optic Sensing Navigation System for Small Peripheral Pulmonary Nodules.

BACKGROUND: We tested a new, investigational robotic-assisted bronchoscope system with a remotely controlled catheter to access small peripheral bronchi with real-time driving under live visualization and distal tip articulation of the catheter. The unique catheter remains stationary once located at the biopsy position. OBJECTIVES: The primary objectives of this study were to evaluate the safety and feasibility of a new shape-sensing robotic bronchoscope system to bronchoscopically approach and facilitate the sampling of small peripheral pulmonary nodules of 1-3 cm. Secondary objectives included evaluating procedural characteristics and early performance trends associated with the use of the new robotic bronchoscope system. METHODS: Subjects were enrolled according to study eligibility criteria at a single center. Navigation pathways were semi-automatically created using pre-procedure CT scans. Simultaneous (real-time) viewing of actual and virtual bronchi was used real time during navigation to the displayed target. An endobronchial ultrasound mini-probe was used to confirm lesion location. Flexible 19- to 23-G needles specifically designed to accommodate tight bend radii in transbronchial needle aspiration were used along with conventional biopsy tools. Enrolled subjects completed follow-up visits up to 6 months after the procedure. RESULTS: The study included 29 subjects with a mean lesion size of 12.2 ± 4.2, 12.3 ± 3.3, and 11.7 ± 4.1 mm in the axial, coronal, and sagittal planes, respectively. The CT bronchus sign was absent in 41.4% of cases. In 96.6% of cases, the target was reached, and samples were obtained. No device-related adverse events and no instances of pneumothorax or excessive bleeding were observed during the procedure. Early performance trends demonstrated an overall diagnostic yield of 79.3% and a diagnostic yield for malignancy of 88%. CONCLUSION: This new robotic-assisted bronchoscope system safely navigated to very small peripheral airways under continuous visualization, and through maintenance of a static position, it provides a unique sampling capability for the biopsy of small solitary pulmonary nodules.

Diff-Quik Cytology Smears from Endobronchial Ultrasound Transbronchial Needle Aspiration Lymph Node Specimens as a Source of DNA for Next-Generation Sequencing Instead of Cell Blocks.

BACKGROUND: Next-generation sequencing (NGS) in lung cancer specimens from endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is usually performed on formalin-fixed paraffin-embedded cell block material. OBJECTIVES: Since DNA can be damaged by this process, we investigated the potential of using DNA extracted from Diff-Quik cytology smears made for rapid on-site evaluation during EBUS-TBNA. METHODS: In a prospective study, 67 patients undergoing diagnostic EBUS-TBNA were ana-lysed. We compared cell blocks and smears for DNA yields and sequencing (TruSeq Amplicon Cancer Panel) outcomes. Smears were also evaluated for tumour cell fraction and overall cellularity (cell count). RESULTS: Primary lung cancer was diagnosed in 64 patients and metastatic malignancy in 3 patients. The DNA yield from smears was significantly higher than that obtained from matched cell blocks (mean 1,740 vs. 434 ng; p = 0.001). For 33 cases with matched smears and cell blocks the mutation profiles were similar. Smears with abundant malignant cells (using a cut-off of > 25% tumour cell fraction and > 1,000 cells) accurately predicted high (> 50 ng) DNA yield and therefore success in triaging samples to sequencing. In terms of tissue workflow, using only smears as source DNA for sequencing was an improvement in the use of only cell blocks (54/67 [80.6%] vs. 41/67 [61.2%]); however, the use of cell blocks when smears were not available or did not yield sufficient DNA further improved the success rate to 62/67 (92.5%) cases. CONCLUSION: We recommend smears in laboratory workflows as the primary source of DNA for NGS following an EBUS procedure.

Recurrent respiratory papillomatosis: the role of cidofovir.

Recurrent respiratory papillomatosis (RRP) is a rare condition that affects the respiratory system. It is caused by human papilloma virus (HPV) infection. Usually infection and papilloma growth is limited to 6-12 months duration; however, some patients have persistent disease, resulting in long-term symptoms and the need for recurrent intervention. Predominant symptoms include shortness of breath, reduced exercise tolerance and voice deterioration during flares. Current gold-standard management is through resection via microdebrider, CO2 laser, cryotherapy, electrocoagulation, Nd: YAG laser or pulse-dye laser. However, despite these therapies, approximately 20% of patients require adjuvant therapy. We discuss the use of intralesional cidofovir in the management of tracheal papillomatosis. Cidofovir's mechanism of action involves incorporating into the virus DNA chain and therefore, inhibiting the viral DNA polymerization process and hence replication.

Risk stratification in the investigation of pulmonary nodules in a high-risk cohort: positron emission tomography/computed tomography outperforms clinical risk prediction algorithms.

BACKGROUND: Clinical prediction models and 18-fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) are used for the assessment of solitary pulmonary nodules (SPN); however, a biopsy is still required before treatment, which carries risk. AIM: To determine the combined predictive benefit of one such model combined with modern PET/CT data to improve decision-making about biopsy prior to treatment and possibly reduce costs. METHODS: Patients with a SPN undergoing 18F-FDG-PET/CT from January 2011 to December 2012 were retrospectively identified; 143 patients met inclusion criteria. PET/CT studies were rated (5-point visual scale), and CT characteristics were determined. Tissue was obtained by endobronchial ultrasonography with guide sheath (EBUS-GS), CT-guided biopsy and/or surgery. EBUS-transbronchial needle aspiration (TBNA) was used instead of nodule biopsy if there were PET-positive sub-centimetre lymph nodes. RESULTS: The prediction model yielded an area under the receiver operating characteristic curve (AUC-ROC) of 64% (95% confidence interval (CI) 0.55-0.75). PET/CT increased this to 75% (95% CI 0.65-0.84). The 11% improvement is statistically significant. PET/CT score was the best single predictor for malignancy. A PET score of 1-2 had a specificity of 100% (CI 0.73-1.0), whereas a score of 4-5 had a sensitivity of only 76% (CI 0.68-0.84). No significant difference in clinical prediction scores between groups was noted. PET/CT showed the greatest benefit in true negatives and in detecting small mediastinal lymph nodes to allow EBUS-TBNA with a higher diagnostic rate. Cost analysis did not support a policy of resection-without-tissue diagnosis. CONCLUSION: PET/CT improves the clinical prediction of SPN, but its greatest use is in proving benignity. High PET scores had high false positive rates and did not add to clinical prediction. PET should be incorporated early in decision-making to allow for more effective biopsy strategies.

Grey scale texture analysis of endobronchial ultrasound mini probe images for prediction of benign or malignant aetiology.

BACKGROUND AND OBJECTIVE: Expert analysis of endobronchial ultrasound mini probe (EBUS-MP) images has established subjective criteria for discriminating benign and malignant disease. Minimal data are available for objective analysis of these images. The aim of this study was to determine if greyscale texture analysis could differentiate between benign and malignant lung lesions. METHODS: Digital EBUS-MP images with a gain setting of 10/19 and contrast setting of 4/8 from 2007 until 2012 inclusive were included. These images had an expert-defined region of interest (ROI) mapped. ROI were analysed for the following greyscale texture features: mean pixel value, difference between maximum and minimum pixel value, standard deviation of the mean pixel value, entropy, correlation, energy and homogeneity. Significant greyscale texture features differentiating benign from malignant disease were used by two physicians to assess a validation set. RESULTS: A total of 167 images were available. The first 85 lesions were used in the prediction set. Benign lesions had larger differences between maximum and minimum pixel values, larger standard deviations of the mean pixel values and higher entropy than malignant lesions (P < 0.0001 for all values). A total of 82 peripheral lesions were in the validation set. Physician 1 correctly classified 63/82 (76.8%) with a negative predictive value (NPV) for malignancy of 82% and positive predictive value (PPV) of 75%. Physician 2 correctly classified 62/82 (75.6%) with a NPV of 100% and PPV of 71.0%. CONCLUSIONS: Greyscale texture analysis of EBUS-MP images can help establish aetiology with a high NPV for malignancy.

Comparison of objective criteria and expert visual interpretation to classify benign and malignant hilar and mediastinal nodes on 18-F FDG PET/CT.

BACKGROUND AND OBJECTIVE: There is widespread adoption of FDG-PET/CT in staging of lung cancer, but no universally accepted criteria for classifying thoracic nodes as malignant. Previous studies show high negative predictive values, but reporting criteria and positive predictive values varies. Using Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) results as gold standard, we evaluated objective FDG-PET/CT criteria for interpreting mediastinal and hilar nodes and compared this to expert visual interpretation (EVI). METHODS: A retrospective review of all patients with lung cancer who had both FDG-PET/CT and EBUS-TBNA from 2008 to 2010 was performed. Scan interpretation was blinded to histology. Patients from 2008/2009 were used for the prediction set. The validation set analysed patients from 2010. Objective FDG-PET/CT criteria were SUVmax lymph node (SUVmaxLN), ratio SUVmaxLN/SUVmax primary lung malignancy, ratio SUVmaxLN/SUVaverage liver, ratio SUVmaxLN/SUVmax liver and ratio SUVmaxLN/SUVmax blood pool. A nuclear medicine physician reviewed all scans and classified nodal stations as benign or malignant. RESULTS: Eighty-seven malignant lymph nodes and 41 benign nodes were in the prediction set. All objective FDG-PET/CT criteria analysed were significantly higher in the malignant group (P < 0.0001). EVI correctly classified 122/128 nodes (95.3%). Thirty-four malignant nodes and 19 benign nodes were in the validation set. The new proposed cut-off values of the objective criteria from the prediction set correctly classified 44/53 (83.0%) nodes: 28/34 (82.4%) malignant nodes and 16/19 (84.2%) benign nodes. EVI had 91% accuracy: 33/34 (97.1%) malignant nodes and 15/19 (79.0%) benign nodes. CONCLUSIONS: Objective analysis of 18-F FDG PET/CT can differentiate between malignant and benign nodes but is not superior to EVI.

Novel use of pleural ultrasound can identify malignant entrapped lung prior to effusion drainage.

BACKGROUND: The presence of entrapped lung changes the appropriate management of malignant pleural effusion from pleurodesis to insertion of an indwelling pleural catheter. No methods currently exist to identify entrapped lung prior to effusion drainage. Our objectives were to develop a method to identify entrapped lung using tissue movement and deformation (strain) analysis with ultrasonography and compare it to the existing technique of pleural elastance (PEL). METHODS: Prior to drainage, 81 patients with suspected malignant pleural effusion underwent thoracic ultrasound using an echocardiogram machine. Images of the atelectatic lower lobe were acquired during breath hold, allowing motion and strain related to the cardiac impulse to be analyzed using motion mode (M mode) and speckle-tracking imaging, respectively. PEL was measured during effusion drainage. The gold-standard diagnosis of entrapped lung was the consensus opinion of two interventional pulmonologists according to postdrainage imaging. Participants were randomly divided into development and validation sets. RESULTS: Both total movement and strain were significantly reduced in entrapped lung. Using data from the development set, the area under the receiver-operating curves for the diagnosis of entrapped lung was 0.86 (speckle tracking), 0.79 (M mode), and 0.69 (PEL). Using respective cutoffs of 6%, 1 mm, and 19 cm H2O on the validation set, the sensitivity/specificity was 71%/85% (speckle tracking), 50%/85% (M mode), and 40%/100% (PEL). CONCLUSIONS: This novel ultrasound technique can identify entrapped lung prior to effusion drainage, which could allow appropriate choice of definitive management (pleurodesis vs indwelling catheter), reducing the number of interventions required to treat malignant pleural effusion.

High specificity of combined narrow band imaging and autofluorescence mucosal assessment of patients with head and neck cancer.

BACKGROUND: The purpose of this study was to evaluate combined autofluorescence (AF) and narrow band imaging (NBI) for detection of mucosal lesions additional to known primary head and neck cancers and to determine impact on management. METHODS: Patients with head and neck cancer requiring preoperative screening or posttreatment surveillance had white light (WL), AF and NBI inspection of the head and neck and bronchus. Known primary cancers were not analyzed, only additional lesions. Moderate dysplasia or worse was considered significant. RESULTS: In all, 73 patients were recruited. Respectively, there were 24 and 18 additional lesions in the head and neck and bronchus that had significant histopathology. In both regions, AF and NBI were more sensitive than WL for detecting significant dysplasia with NBI demonstrating better specificity than AF (p = .003); 11 of 73 patients (15.1%) had additional findings detected by AF and NBI, which had an impact on management. CONCLUSION: Combined AF and NBI inspection is highly specific at panendoscopy and can influence management.

Rapid cytological analysis of endobronchial ultrasound-guided aspirates in sarcoidosis.

Rapid on-site evaluation (ROSE) of endobronchial ultrasound-guided transbronchial needle aspirates (EBUS-TBNA) has not been compared to final detailed cytological analysis in patients with suspected sarcoidosis. To assess the diagnostic accuracy of EBUS-TBNA with ROSE in patients with suspected sarcoidosis, a prospective two-centre study performed EBUS-TBNA with ROSE of cellular material followed by transbronchial lung biopsy (TBLB) and endobronchial biopsy (EBB). The diagnostic accuracy of EBUS-TBNA with ROSE was compared to the final cytological assessment and to TBLB and EBB. Analysis confirmed 49 out of 60 cases of sarcoidosis. ROSE sensitivity was 87.8% (specificity 91%, positive predictive value 97.7%). ROSE slide interpretation in combination with the final fixed slide and cell block preparations had a sensitivity of 91.8% (specificity 100%, positive predictive value 100%). 67% of patients were confirmed as having sarcoidosis on TBLB and 29% on EBB. Interobserver agreement between cytotechnologists and pathologists was very good (κ=0.91, 95% CI 0.80-1.0 and κ=0.91, 95% CI 0.79-1.0, respectively). EBUS-TBNA with ROSE has high diagnostic accuracy and interobserver agreement and informs the bronchoscopist in theatre whether additional diagnostic procedures need to be undertaken. EBUS-TBNA with ROSE should therefore be considered as the first-line investigation of sarcoidosis.

Optical differentiation between malignant and benign lymphadenopathy by grey scale texture analysis of endobronchial ultrasound convex probe images.

BACKGROUND: Morphologic and sonographic features of endobronchial ultrasound (EBUS) convex probe images are helpful in predicting metastatic lymph nodes. Grey scale texture analysis is a well-established methodology that has been applied to ultrasound images in other fields of medicine. The aim of this study was to determine if this methodology could differentiate between benign and malignant lymphadenopathy of EBUS images. METHODS: Lymph nodes from digital images of EBUS procedures were manually mapped to obtain a region of interest and were analyzed in a prediction set. The regions of interest were analyzed for the following grey scale texture features in MATLAB (version 7.8.0.347 [R2009a]): mean pixel value, difference between maximal and minimal pixel value, SEM pixel value, entropy, correlation, energy, and homogeneity. Significant grey scale texture features were used to assess a validation set compared with fluoro-D-glucose (FDG)-PET-CT scan findings where available. RESULTS: Fifty-two malignant nodes and 48 benign nodes were in the prediction set. Malignant nodes had a greater difference in the maximal and minimal pixel values, SEM pixel value, entropy, and correlation, and a lower energy (P < .0001 for all values). Fifty-one lymph nodes were in the validation set; 44 of 51 (86.3%) were classified correctly. Eighteen of these lymph nodes also had FDG-PET-CT scan assessment, which correctly classified 14 of 18 nodes (77.8%), compared with grey scale texture analysis, which correctly classified 16 of 18 nodes (88.9%). CONCLUSIONS: Grey scale texture analysis of EBUS convex probe images can be used to differentiate malignant and benign lymphadenopathy. Preliminary results are comparable to FDG-PET-CT scan.

Review of the role of EBUS-TBNA for the pulmonologist, including lung cancer staging.

This review focuses on the role of endobronchial ultrasound-guided transbronchial needle aspiration in day-to-day pulmonology practice. Case examples are given of the common indications for endobronchial ultrasound-guided transbronchial needle aspiration which are: (i) lung cancer staging; (ii) confirming a diagnosis of malignancy in thoracic lymph nodes; (iii) diagnosing central pulmonary masses; (iv) sarcoidosis; and (v) inflammatory/benign thoracic lymph nodes. The technique is widely used, and after appropriate training by experienced bronchoscopists can be easily integrated into a bronchoscopy service.