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Endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA) is an established, minimally invasive way to sample intrathoracic abnormalities. The EBUS scope can be passed into the oesophagus to perform endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA). In cases of suspected lung cancer, a combination of the two techniques is now recommended by consensus guidelines. EBUS TBNA is usually performed by pulmonologists; however, the learning curve for EUS-B-FNA, which may be performed during the same procedure, has not been described.A multicentre, observational Australian study, using prospectively collected data from three experienced pulmonologists was conducted. Cumulative sum (cusum) analysis was used to generate visual learning curves.A total of 152 target lesions were sampled in 137 patients, with an overall sensitivity for malignancy of 94.8%. The sensitivity for malignant lesions outside of the 2009 International Association for the Study of Lung Cancer lymph node map (largely intraparenchymal lesions) was 92.9%. All three operators were competent by conventional cusum criteria. There was one case of pneumothorax, and no episodes of mediastinitis or oesophageal perforation were observed.Our data suggest that experienced pulmonologists can safely and accurately perform EUS-B-FNA, with a high diagnostic sensitivity for both lymph node and non-nodal lesions., (Copyright ©ERS 2017.)

Background: Minimally invasive techniques, including endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), yield small specimens that are adequate for cytologic diagnosis of lung cancer, but also need to provide material for molecular analysis to guide treatment. The number of EBUS-TBNA passes needed for mutation testing remains unclear. We sought to assess the adequacy of a single pass for genomic profiling of actionable mutations., Methods: In a prospective observational study, paired samples from the same lesion were obtained from patients undergoing EBUS-TBNA for lung cancer diagnosis/staging. Following tumor cell confirmation by rapid on-site evaluation, a "reference" sample comprising ≥ 3 passes was obtained and formalin-fixed paraffin-embedded. A "study" sample comprising a single pass was taken and snap-frozen. The primary outcome was DNA yield and quality from a single pass. The secondary outcome was diagnostic accuracy of a single pass for detecting actionable mutations., Results: In 40 patients, single-pass specimens yielded a mean 3.98 μg of highly intact DNA, well above the minimum threshold for targeted sequencing, which was performed in adenocarcinoma cases (n = 24). In 23 cases, there was 100% agreement in mutation status between reference and study samples. In 1 case, the reference sample failed to generate a molecular diagnosis owing to insufficient tumor cells; however, the study specimen identified a KRAS mutation. Tumor cell percentage in mutation-positive specimens was 1% to 70%, suggesting that single-pass samples detect mutations even when tumor cell content is low., Conclusion: Single EBUS-TBNA passes yield DNA of high quantity and quality with high accuracy for molecular profiling, irrespective of tumor cell content., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Transesophageal introduction of the endobronchial ultrasound (EBUS) videobronchoscope allows pulmonologists to perform endoscopic ultrasound fine-needle aspiration (EUS-B-FNA) of mediastinal lesions. Safety, diagnostic accuracy, and feasibility of EUS-B-FNA in evaluation of pulmonary parenchymal lesions are not established., Methods: All patients undergoing pulmonologist-performed EUS-B-FNA of parenchymal lung lesions at 2 tertiary centers were included in this prospective observational cohort study., Results: EUS-B-FNA sampling of parenchymal lesions was performed in 27 patients. Mean (±SD) lesion size was 36±16 mm. Seven lesions were ≤18 mm. Pneumothorax occurred in 1 patient (3.7%, 95% confidence interval, 0.001%-19%). Ten target lesions (36%) were in locations inaccessible to bronchoscopic sampling via the airways, and 9 lesions were inaccessible to EBUS-guided transbronchial needle aspiration and in locations associated with low diagnostic yield from radial EBUS. EUS-B-FNA was diagnostic in 26 patients (96%), and sensitivity of EUS-B-FNA was 100% (95% confidence interval, 87%-100%) for both lung cancer (n=21) and for pulmonary metastatic lesions (n=5)., Conclusions: Pulmonologist-performed EUS-B-FNA is safe and accurate in the evaluation parenchymal lung lesions. Diagnostic accuracy is high. EUS-B-FNA may achieve access to sites not amenable to other forms of bronchoscopic sampling, or increase diagnostic accuracy in patients where anatomic position predicts a low diagnostic yield.

Background: Transoesophageal endobronchial ultrasound (EBUS) video-bronchoscope insertion provides pulmonologists access to conduct endoscopic fine-needle aspiration (EUS-B-FNA) of mediastinal lymph node (LN) lesions and also assist in lung cancer staging by sampling left adrenal gland (LAG) lesions. Limited literature has described additional diagnostic value whilst maintaining patient safety. To elicit whether combining endoscopic transoesophageal fine-needle aspiration using convex probe bronchoscope (EUS-B-FNA) and EBUS bronchoscopy enhances the diagnostic yield of mediastinal nodal staging in lung cancer, whilst maintaining safety., Methods: All eligible patients with paraoesophageal lesions on thoracic computed tomography (CT) underwent pulmonologist-performed EUS-B-FNA at two tertiary centres and were included in this prospective observational cohort study., Results: EUS-B-FNA sampling was performed at 69 mediastinal LN lesion sites, including 17 sites inaccessible to bronchoscopic sampling. Four LAG lesions were sampled via EUS-B-FNA. There were no complications. EBUS-TBNA was augmented by EUS-B-FNA because of accessibility of sampling lesions otherwise unamenable bronchoscopically, thereby increasing diagnostic utility. Diagnostic sensitivity of EUS-B-FNA for malignancy in mediastinal LN lesions was 88% (51 of 58). For mediastinal LN lesions not amenable to EBUS-TBNA, the sensitivity for diagnosis of malignancy via EUS-B-FNA was 88% (15 of 17). Diagnostic sensitivity of EUS-B-FNA for malignancy in LAG lesions was 50% (2 of 4)., Conclusion: EUS-B-FNA is a precise and safe approach in the evaluation and staging of lung cancer when performed by a pulmonologist. It complements and increases the diagnostic utility of EBUS-TBNA by further coverage of mediastinal LN stations and access to LAG lesions., (© 2016 Royal Australasian College of Physicians.)

Background: Confirmation of mediastinal disease (N2/3) in non-small cell lung cancer (NSCLC) generally precludes curative surgical management. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become a routine first test in mediastinal staging of NSCLC; however, it remains unclear whether a negative EBUS-TBNA should be followed by mediastinoscopy before proceeding to surgery. Understanding the prevalence of metastases in lymph nodes with benign findings on EBUS-TBNA will inform decision making following negative EBUS-TBNA., Methods: We examined a retrospective cohort of patients who underwent EBUS-TBNA before resection with mediastinal lymph node sampling for NSCLC between December 2009 and June 2014 in 3 hospitals in Melbourne, Australia. All patients had integrated positron emission tomography/computed tomography (PET/CT) before EBUS-TBNA., Results: Eighty-two matched mediastinal lymph node stations were sampled in 57 patients by both EBUS-TBNA and surgical resection, 47 nodes in patients staged cN0/1 by PET/CT and 35 nodes in patients staged cN2/3. All patients had a negative EBUS-TBNA. Four malignant nodes were identified surgically (4.9% of lymph nodes). The mean size of malignant deposits was 5.5 mm. Per-node negative predictive value was 78/82=0.95. All malignant nodes were located in patients with moderate-high risk disease (cN2/3), giving a disease prevalence in cN2/3 patients of 11%, and 0% in cN0/1. In patients staged cN2, per-node NVP was 0.89., Conclusion: The prevalence of mediastinal nodal disease following negative EBUS-TBNA is very low, at 4.9%. The per-node NVP of EBUS-TBNA is 0.95, decreasing to 0.89 in moderate-high risk patients. We suggest that a negative EBUS-TBNA of mediastinal nodes does not need to be confirmed by mediastinoscopy of those nodal stations, regardless of PET/CT findings.

Patient-derived xenograft (PDX) models generated from surgical specimens are gaining popularity as preclinical models of cancer. However, establishment of PDX lines from small cell lung cancer (SCLC) patients is difficult due to very limited amount of available biopsy material. We asked whether SCLC cells obtained from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) could generate PDX lines that maintained the phenotypic and genetic characteristics of the primary tumor. Following successful EBUS-TBNA sampling for diagnostic purposes, we obtained an extra sample for cytologic analysis and implantation into the flanks of immunodeficient mice. Animals were monitored for engraftment for up to 6 months. Histopathologic and immunohistochemical analysis, and targeted next-generation re-sequencing, were then performed in both the primary sample and the derivative PDX line. A total of 12 patients were enrolled in the study. EBUS-TBNA aspirates yielded large numbers of viable tumor cells sufficient to inject between 18,750 and 1,487,000 cells per flank, and to yield microgram quantities of high-quality DNA. Of these, samples from 10 patients generated xenografts (engraftment rate 83%) with a mean latency of 104 days (range 63-188). All but one maintained a typical SCLC phenotype that closely matched the original sample. Identical mutations that are characteristic of SCLC were identified in both the primary sample and xenograft line. EBUS-TBNA has the potential to be a powerful tool in the development of new targeting strategies for SCLC patients by providing large numbers of viable tumor cells suitable for both xenografting and complex genomic analysis.

Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) may diagnose suspected lung cancer. Determination of non-small cell lung cancer (NSCLC) subtype may guide therapy in select patients. Small-volume biopsies may be subject to significant interobserver variability in subtype determination. Three pathologists independently reviewed specimens from 60 patients who underwent EBUS-TBNA for diagnosis/staging of suspected/known NSCLC. Smear, haematoxylin and eosin (H&E) and immunohistochemistry (IHC) specimens were reviewed without reference to other specimen types obtained from the same patient. Final diagnoses, and degree of confidence in the diagnosis, were recorded for each specimen. Almost perfect agreement was seen for distinguishing between small cell lung cancer and NSCLC for all specimen types. Agreement in determination of NSCLC subtype for smear, H&E and IHC specimens was slight (κ=0.095, 95% CI -0.164-0.355), fair (κ=0.278, 95% CI 0.075-0.481) and moderate (κ=0.564, 95% CI 0.338-0.740), respectively. Perfect agreement was seen when all three observers were confident of diagnoses made on IHC specimens. Interobserver agreement in interpretation of EBUS-TBNA specimens is moderate for determination of NSCLC subtype. Agreement is highest following examination of IHC specimens. Clinicians should be aware of the degree of pathologist confidence in the tissue diagnosis prior to commencement of subtype-specific therapy for NSCLC.