Endobronchial Ultrasound Transbronchial Needle Aspiration Research Articles

ROLE OF CONTRALATERAL HILAR NODE SAMPLING DURING NON-SMALL CELL LUNG CANCER SYSTEMATIC STAGING OF HILUM AND MEDIASTINUM WITH EBUS-TBNA

SESSION TITLE: Monday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Endobronchial ultrasound transbronchial-needle aspiration (EBUS-TBNA) for non-small cell lung cancer (NSCLC) staging has become standard of care in many centers throughout the world. Sampling starting from contralateral (N3) to ipsilateral (N1) nodes is a well-accepted strategy. Sampling ipsilateral hilar nodes offers an advantage over mediastinoscopy which can be particularly important for non-surgical candidates. However, it is unclear whether sampling of the contralateral hilar nodes with EBUS-TBNA is of any benefit. METHODS: Records from the Cleveland Clinic bronchoscopy registry were reviewed. All patients with a final diagnosis of NSCLC who underwent EBUS staging between January 2016 and December 2017 were selected. All procedures during which contralateral hilar nodes were sampled were included. It is our center’s practice to routinely sample these nodes if at least 5 mm in short axis on EBUS or suspicious for malignancy based on CT, PET-CT or EBUS imaging findings. Individuals who were considered to have M1 (stage 4) disease by any means were excluded. Descriptive analysis was performed. RESULTS: 270 patients met inclusion criteria. 145 with a right lung cancer had left hilar lymph node sampling (both stations 10L and 11L in 2, station 10L alone in 1, and the remaining 142 had sampling of station 11L only). 125 patients with a left lung lesion had right hilar sampling (stations 10R, 11s and 11i in 3, stations 10R and 11s in 5, stations 10R and 11i in 2, stations 11s and 11i in 14, station 10R alone in 5, station 11s alone in 89 and 11i alone in 7). Of the 270 patients, 42 had positive contralateral hilar nodes by PET and/or CT and all were sampled. Malignancy was identified on EBUS-TBNA in 6 contralateral hilar lymph nodes (2.2%), of which 4 (9.5%) had positive PET and/or CT. Two (0.9%) of the negative PET and CT turned out to have malignant disease and both were adenocarcinomas. Two of the malignancy findings, however, were not related to the primary contralateral lesion (one synchronous small-cell carcinoma and one small lymphocytic lymphoma). If these latter patients were to be excluded from the NSCLC analysis, the actual prevalence of contralateral hilar disease would be 1.5%. CONCLUSIONS: To our knowledge this is the first study assessing the prevalence of malignancy found on routine contralateral hilar lymph node sampling by EBUS-TBNA. CLINICAL IMPLICATIONS: These results may bring into question the actual benefit of sampling such sites, especially among patients in which PET and CT fail to demonstrate any evidence of contralateral hilar malignant involvement. DISCLOSURES: No relevant relationships by Francisco Almeida, source=Web Response No relevant relationships by Carlos Aravena Leon, source=Web Response No relevant relationships by Lucas Rathunde, source=Web Response

EP1.01-41 Feasibility of EBUS-TBNA Cytologies for an Extensive Assessment of Predictive Biomarkers in Lung Cancer

Clinical guidelines support the determination of several driver genes as well as PD-L1 to drive treatment decisions in non-small cell lung cancer (NSCLC). Endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) cytology specimens are useful for the initial diagnosis of NSCLC, although its capacity to provide enough material for a complete genotyping remains controversial. The aim of this study is to determine the yield of EBUS for a comprehensive multiplex genotyping in patients (pts) with suspected NSCLC. In this single-center, ongoing, prospective study, samples from mediastinal lymph nodes were obtained from pts undergoing EBUS-TBNA for lung cancer diagnosis/staging. Following malignant confirmation and appropriate cell content by rapid on-site evaluation, the study sample was obtained and formalin-fixed paraffin-embedded (FFPE). Three analytes were evaluated (DNA/RNA/protein). DNA and RNA were extracted and analyzed by Oncomine Solid Tumour panel (22 genes) and a customized nCounter panel (ALK, ROS; RET, NTRK, METDe14). Tumor Proportion Score (TPS) for PD-L1 protein expression was evaluated by an expert pathologist and scored into <1% (negative), 1-49% (weakly positive) and 50% (high). Twenty-five pts with NSCLC have been included and cytology samples of 20 of them molecularly characterized (5 still in progress). Overall, cytological analysis of EBUS-TBNA yield a complete characterization for the three analytes (DNA/RNA/protein) in 15 pts (75%). EBUS-TBNA sampling was sufficient for both, Nanostring and Oncomine evaluation, in a total of 18 pts (90%): 15 patients (83%) had any alteration detected by oncomine (TP53 61% [11/18],KRAS 44% [8/18], EGFRe 195.5% [1/18], BRAF V600E 5,5% [1/18], DDR2 5.5% [1/18], STK11 11% [2/18]) and 1 pt (5.5 %) by nanostring (METDex14). A total of 19 samples were sufficient for PD-L1 expression scoring (95%). TPS for PD-L1 expression was negative in 8 pts (42%), week in 4 (21%) and high in 7 pts (37%). Overall, half of the pts evaluated (10/20) would be potential candidates for an upfront personalized treatment strategy using targeted agents or immunotherapy. EBUS-TBNA is a promising alternative source of material for NSCLC genotyping and allows the identification of pts candidates for personalized therapies.

P1.14-45 Surgical Outcome of Non-Small Cell Lung Cancer with Clinical Single Zone N2 in Aortopulmonary Zone (LN#5 and LN#6)

Current staging work-up methodology could not exactly reflect clinical nodal status of aortopulmonary zone (AP zone) without invasive diagnostic tools. The aim of the study is to evaluate the surgical outcome of single zone clinical N2 in AP zone (LN #5 or #6). Between 2009 and 2018, a retrospective data of 7488 patients was reviewed. Patients were included when only lymph nodes in AP zone was suspected to be metastasized based on the results of computed tomography (CT), positron emission tomography (PET-CT) and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA). Patients were excluded when metastasis was detected by EBUS-TBNA in other mediastinal lymph node zones. Clinicopathologic variables such as pathologic subtype, differentiation and nodal status were evaluated to identify prognostic factors for survival rate and disease-free survival rate (DFS). Ninety-five patients were included, and median duration of follow-up was 35 months (IQR; 20 – 50). Eighty-four patients underwent upfront surgery, and their pathologic nodal staging was pN0 in 20 patients (23.8%), pN1 in 7 (8.3%), pN2a in 40 (47.6%) and pN2b in 17 (20.2%). Overall 5-year survival and 5-year DFS rate was 55.9% 54.5%, respectively. There was no survival difference between patients with pN0-1, pN2a and pN2b (p = 0.345, figure). Neither pathologic N2 nor N2b was not a risk factor for overall survival rate (p = 0.418, 0.159, respectively) and DFS (p = 0.606, 0.650, respectively). In univariate analysis, there was no other significant clinicopathologic factors for survival and DFS. Eleven patients with neoadjuvant treatment showed a similar 5-year survival rate (43.6%) compared with patients with upfront surgery. Current work-up without invasive tools for cN2a in AP zone showed relatively high false-positive rate (32.1%). However, surgical outcome of cN2a in aortopulmonary zone was comparable. Upfront surgery should be considered in highly selected patients.

KNOCK KNOCK, HU'S THERE? POSITIVE ANTI-HU ANTIBODY IN EXTRAPULMONARY SMALL CELL CARCINOMA OF LYMPH NODE

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: To date, small cell carcinoma (SCC) has been primarily recognized as a pulmonary malignancy and research has been skewed towards this area. Extrapulmonary SCC is rare, accounting for 2.5% of SCC, out of which lymph node SCC are far and few between. CASE PRESENTATION: A 59-year-old gentleman was initially admitted to neurology for sensory neuropathy and weight loss. He was referred to the respiratory medicine team after imaging revealed subcarinal and left hilar lymphadenopathy. He is a chronic smoker and there was a concern for malignancy. Initial endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) using 22 gauge needle showed lymphoid yield. Serum paraneoplastic panel (Hu, Yo, Ri, CV2, Amphiphysin, PNMA2/Ta, recoverin, SOX1, titin, zic4, GAD65, Tr(DNER)) was performed as part of the diagnostic work up. Anti-Hu antibody was 1:101 (strongly positive); reference titer 1:<10. Fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) scan revealed FDG avid subcarinal (SUVmax:11.1) and left hilar (SUVmax:13.2) nodes. In view of the anti-Hu antibody results and FDG-PET-CT findings, a repeat EBUS-TBNA using 19 gauge needle was performed and histology confirmed SCC. DISCUSSION: Paraneoplastic syndrome was first described by M. Auché in 1890 and is known to affect up to 8% of patients with cancer; most notably small cell lung cancer. Anti-Hu is an onconeural antibody first discovered by F. Grouse in 1985. Its moniker is type I anti-neuronal nuclear antibody (ANNA-1) and has been a signpost for paraneoplastic sensory neuropathy or encephalomyelitis. (Positive anti-Hu antibody titers have a reported specificity of 99% and sensitivity of 82%). It is recognized as a distinct clinical disease, “anti-Hu syndrome”, with characteristic clinical picture and imaging findings. A Dutch study in 2002 found that 85% of patients with positive anti-Hu antibody also have a tumor. Of note, anti-Hu antibodies can also be positive in antecedent inflammatory diseases like systemic lupus erythematosus or Sjogren’s syndrome which can confound the diagnosis. Thus, positive anti-Hu antibody levels should prompt further evaluation and follow up even in absence of concurrent malignancy. Early diagnosis of lymph node SCC has prognostic implications when compared to pulmonary and extrapulmonary SCC, thus making the distinction necessary. CONCLUSIONS: This study highlights the diagnostic implications of an abnormal paraneoplastic panel, emphasizing the role of anti-Hu antibody in its specificity for SCC. The presence of FDG avid thoracic lymph nodes with elevated anti-Hu antibody titers warrants a repeat biopsy. It is imperative for clinicians to identify occult neoplasms in the setting of paraneoplastic syndromes. Reference #1: Koike H, Sobue G. Paraneoplastic neuropathy. Handb Clin Neurol. 2013;115:713-26. Reference #2: Graus F, Cordon-Cardo C, Posner JB. Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology. 1985 Apr;35(4):538–43. Sehgal IS, Kaur H, Dhooria S, et al. Extrapulmonary small cell carcinoma of lymph node: Pooled analysis of all reported cases. World J Clin Oncol. 2016;7(3):308-20. Graus F, Keime-Guibert F, Reñe R, Benyahia B, Ribalta T, Ascaso C, Escaramis G, Delattre JY. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain. 2001;124(6):1138-1148. Senties-Madrid H, Vega-Boada F. Paraneoplastic syndromes associated with anti-Hu antibodies. Isr Med Assoc J. 2001 Feb;3(2):94-103. Reference #3: Benyahia B, Amoura Z, Rousseau A, Le Clanche C, Carpentier A, Piette JC, Delattre JY. Paraneoplastic antineuronal antibodies in patients with systemic autoimmune diseases. J Neurooncol. 2003 May;62(3):349-51. Sillevis Smitt P, Grefkens J, de Leeuw B, van den Bent M, van Putten W, Hooijkaas H, Vecht C. Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy. J Neurol. 2002 Jun;249(6):745-53. Kim KO, Lee HY, Chun SH, et al. Clinical overview of extrapulmonary small cell carcinoma. J Korean Med Sci. 2006;21(5):833-7. Kannoth S. Paraneoplastic neurologic syndrome: A practical approach. Ann Indian Acad Neurol. 2012;15(1):6-12. DISCLOSURES: No relevant relationships by John Abisheganaden, source=Web Response No relevant relationships by Caroline Choong, source=Web Response No relevant relationships by Sharlene Ho, source=Web Response No relevant relationships by Chuen Peng Lee, source=Web Response No relevant relationships by Ziqin Ng, source=Web Response No relevant relationships by Ser Hon Puah, source=Web Response No relevant relationships by HUIJIA WANG, source=Web Response No relevant relationships by Kim Hoong Yap, source=Web Response

USING LYMPH NODE SIZE AND STANDARDIZED UPTAKE UNITS TO DETERMINE DIAGNOSTIC ACCURACY OF PET-CT IN DETECTING MALIGNANT MEDIASTINAL AND HILAR DISEASE IN A REGION ENDEMIC WITH HISTOPLASMOSIS

SESSION TITLE: Tuesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: Proper staging of the mediastinal and hilar lymph nodes is key to determining the best treatment options for patients with suspected lung cancer. Previously, two broad methods have been used in predicting malignant potential based on size and standardized uptake units (SUV) on positron emission tomography with computed tomography scans (PET-CT). Using a lymph node short axis size cut off greater than or equal to 10 mm alone may risk missing early or partially malignant nodes. While, an SUV of >2.5 has been generally accepted as being indicative of malignancy. However, this second predictive criterion is limited as lymphadenopathy secondary to inflammatory and infectious processes can also be PET-avid. Herein, we attempt to describe a method of analysis allowing greater distinction between inflammatory and malignant processes. METHODS: We retrospectively reviewed patients who had undergone endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA), mediastinoscopy, or video assisted thoracoscopy in the heart of the Ohio River Valley Basin, a region endemic for Histoplasmosis. We identified 215 biopsied lymph node stations from 69 patients (average of 3.2 stations per patient, range 1 – 8 stations), with an average size of 14.88 mm and an SUV of 1.46 (Not avid to 14.4). 116 lymph node stations had both an SUV and their short axis measured. RESULTS: A PET avid parenchymal nodule was associated with 98.7% of the biopsied nodules. The diagnostic yield in which malignancy was found was as low as 29.3%. Using a short axis size of ≥10 mm alone, the sensitivity of lymph node size for malignancy is 91.43% (95% CI 76.94-98.2%), specificity 25.93% (95% CI 16.82-36.86%), positive predictive value 34.78% (95% CI 31.16-38.54%), negative predictive value 87.5% (95% CI 69.06-95.64%), with an accuracy of 45.69% (95% CI 36.41-55.19%). Using an SUV of ≥2.5 alone, the sensitivity for lymph node metastasis through PET avidity is 67.65% (95% CI 49.47-82.61%), specificity 79.52% (95% CI 69.24-87.59%), positive predictive value 57.50% (95% CI 45.48-68.69%), negative predictive value 85.71% (95% CI 78.48-90.80%), with an accuracy of 76.07% (95% CI 67.30-83.47%). Finally, using a combination of both a short axis ≥10 mm and an SUV ≥2.5, the sensitivity is 64.71% (95% CI 46.49-80.25%), specificity 84.15% (95% CI 74.42-91.28%), positive predictive value 62.86% (95% CI 49.23-74.71%), negative predictive value 85.19% (95% CI 78.32-90.15%), with an accuracy of 78.45% (95% CI 69.85-85.54%). Of the false positive lymph nodes, 53.85% had normal lymphoid tissue, reactive/inflammatory tissue, granulomatous disease and identifiable Histoplasmosis on GMS stain each made up 23.1% of the remainder. CONCLUSIONS: Diagnostic predictive value is increased when using the above methods. CLINICAL IMPLICATIONS: Our study addresses concerns regarding PET-CT specificity for diagnosis of inflammatory versus malignant lesions. DISCLOSURES: No relevant relationships by Yousef Ahmad, source=Web Response No relevant relationships by Arjan Flora, source=Web Response No relevant relationships by Miles Hagner, source=Web Response

PULMONARY VEIN THROMBOSIS VISUALIZED BY ENDOBRONCHIAL ULTRASOUND (EBUS): A RARE FINDING

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Endobronchial ultrasound (EBUS) offers a minimally invasive tool to allow for visualization and histopathological diagnosis of mediastinal and hilar lymph nodes or masses. Simultaneously, it allows for visualization of major vasculature surrounding the tracheobronchial tree such as the pulmonary veins and arteries. Limited report exists regarding pulmonary vein thrombosis (PVT) visualization with EBUS with only one case being found after conducting a PubMed search. We are presenting an additional case of PVT incidentally diagnosed by chest computed tomography (CT) and later visualized by EBUS. CASE PRESENTATION: A 66-year-old female with a history of 30 pack-year smoking and COPD stage IVB, was found to have a sub-centimeter left lower lobe (LLL) nodule on lung cancer screening. CT chest with contrast was performed revealing new right and left hilar lymphadenopathy without extra-thoracic involvement. Due to claustrophobia PET scan was not tolerated. Repeat CT with contrast revealed that the presumed left hilar mass was actually an occlusive pulmonary vein thrombosis in the superior pulmonary vein. Few weeks later patient was admitted to the hospital with worsening fatigue and right side pleuritic chest pain. Exam was unremarkable. She was managed with therapeutic anticoagulation and antibiotics for possible infectious thrombosis. EBUS-transbronchial needle aspiration of station R10 revealed small cell lung carcinoma. Incidentally the pulmonary vein thrombosis visualized by EBUS (Figure1&2) and confirmed with Doppler mode was comparable with CT images. Chest CT repeated after 6 weeks showed minimal change in the PVT and the patient was continued on therapeutic enoxaparin without complication. DISCUSSION: PVT is a rare and fatal condition with non-specific presenting symptoms making diagnosis a challenge. There have been several case reports on PE diagnosis by EBUS, but to the best of our knowledge there has been only one other case report of PVT visualized on EBUS. No guidelines exist for the diagnosis of PE and PVT with EBUS and much of literature are the case reports only. We are presenting this case to demonstrate that EBUS could be an option to diagnose or confirm PVT when other modalities are contraindicated (e.g. CT pulmonary angiography in the presence of renal impairment or contrast allergy). Although EBUS visualization of PVT may not be applicable to the general population due to cost and invasiveness it could be considered as an alternative diagnostic modality in the right sub-population. CONCLUSIONS: PVT is a rare condition which could prove fatal if diagnosed late. Due to its nebulous presentation, diagnosis can be challenging. EBUS could be considered for the diagnosis or confirmation of PVT in the right sub-population. Reference #1: MacEachern P, Dang B, Stather D, Tremblay A. Tumor invasion into pulmonary vessels viewed by endobronchial ultrasound. J Bronchol 2008; 15:206–207. Reference #2: Swartz MA, Gillespie CT. Pulmonary emboli detected by endobronchial ultrasound. Am J Respir Crit Care Med 2011; 183:1569. Reference #3: Mohammad R. Al-Ajam et al. Endobronchial Ultrasound. When to Venture into the Vasculature. ll AnnalsATS Issues. Vol. 10, No. 4 | Aug 01, 2013. DISCLOSURES: No relevant relationships by Muhammad Bilal, source=Web Response No relevant relationships by Cynthia Callahan, source=Web Response No relevant relationships by Ameet Kumar, source=Web Response No relevant relationships by Benedicta Nnodum, source=Web Response

Waste not, want not: diagnostic material found in suction syringe aspirate during endobronchial ultrasound guided transbronchial needle aspiration.

Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a frequently performed procedure. Suction is utilized during this procedure and may occasionally result in the collection of aspirated material, the diagnostic utility of which is uncertain. This study aims to determine the contents of the suction syringe aspirate and its diagnostic value. The suction syringe aspirate was pooled in a container and sent for analysis. We retrospectively reviewed the cytological outcomes of these specimens in comparison to the diagnosis determined by EBUS-TBNA between 2015-2018. The primary outcome was the percent agreement between the diagnostic material found in the suction syringe aspirate, and the final diagnosis established by EBUS-TBNA. Forty-four patients were included. Percent agreement was calculated as the percent in which the suction syringe aspirate diagnosis agreed with the EBUS-TBNA diagnosis. The percent agreement of any diagnosis was 90.9% (95% CI: 78.7-97.2%). Two of the 44 diagnoses (4.5%) were established based solely on the suction syringe aspirate, both cases of granulomatous inflammation. Our results suggest that material collected in the suction syringe has a very high percent agreement with the final diagnosis established by EBUS-TBNA. Furthermore, the suction syringe aspirate may represent the sole diagnostic material in nearly 5% of cases. Given the additional diagnostic material in the suction syringe aspirate, it is reasonable to pool the aspirate with the primary specimen in an effort to enrich the overall diagnostic specimen. This practice may improve the likelihood that the specimen will be sufficient for additional molecular analysis, although further study is necessary. Care must be taken when more than one needle is involved to ensure that a new suction syringe is also used to avoid inadvertent upstaging by specimen contamination.

The role of endobronchial ultrasound transbronchial needle aspiration for programmed death ligand 1 testing and next generation sequencing in advanced non-small cell lung cancer.

Guidelines recommend testing for driver mutations and programmed death ligand 1 (PD-L1) expression at the time of initial diagnosis and during disease progression to help determine prognosis and initiate personalized therapy. In this article we review the updated literature and techniques of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) in obtaining adequate tissue for molecular analysis by using next-generation sequencing (NGS) and for assessing PD-L1 expression through immunohistochemistry.

Endoscopic transbronchial needle aspiration in sampling mediastinal lesions

ContextEndoscopy plays an integral part in the evaluation of mediastinum. Transbronchial sampling can be done conventionally or guided with endobronchial ultrasonography (EBUS), which is a new tool that allows seeing beyond the airway. Following its invention, the use of conventional sampling has declined.AimsTo evaluate the efficacy of EBUS-transbronchial needle aspiration (TBNA) in sampling mediastinal lesions after conventionally negative TBNA result and to compare EBUS-TBNA sampling in subcarinal and hilar sites versus paratracheal sites regarding diagnostic yield.Settings and designA prospective evaluation study was done.Patients and methodsThe study enrolled 52 patients with undiagnosed mediastinal lymphadenopathy or lesions. Subcarinal lesions were sampled by both conventional TBNA and EBUS-TBNA sampling (after negative conventional sampling results), and paratracheal lesions were sampled only with EBUS.Statistical analysisused Data were analyzed to test statistical significant difference between groups. Quantitative data were presented as mean±SD, and Student t test was used to compare between two groups.ResultsNo complications were reported. Conventional subcarinal TBNA sampling was done in 37 cases, where sufficient sampling was seen in 67.6% of cases, was diagnostic in 16.2% and had sensitivity of 20%. EBUS-TBNA was done in 22 cases after negative conventional sampling result, and in additional 15 cases as an initial procedure during the study. EBUS diagnosed 89.2% of cases, with sensitivity of 97.1%. Diagnostic percent in EBUS targeting subcarinal/hilar sites was 81.8% whereas was 100% in paratracheal EBUS sampling.ConclusionBoth modalities of sampling are safe. Diagnostic value of EBUS-TBNA exceeded much more than conventional sampling.

Novel approach for predicting occult lymph node metastasis in peripheral clinical stage I lung adenocarcinoma.

Occult nodal metastasis results in a poor prognosis for lung cancer patients. The aim of this study was to develop an efficient approach for predicting occult nodal metastasis in peripheral clinical stage I lung adenocarcinoma. Data for 237 peripheral clinical stage I lung adenocarcinoma patients who underwent complete resection were retrospectively reviewed. Univariate and multivariate analyses were performed to investigate predictors of occult nodal metastasis. Kaplan-Meier analysis was performed for survival. Occult nodal metastasis was detected in 26/237 (11.0%) patients. Nodule type, tumor SUVmax, whole tumor size, solid tumor size, and preoperative serum carcinoembryonic antigen (CEA) were identified as preoperative predictors of occult nodal metastasis (all P<0.05). Solid tumor size (P<0.001) and preoperative serum CEA (P=0.004) were identified as independent predictors on multivariate analysis. A prediction model was established using the independent predictors. The occult nodal metastasis rate was 2.4% with solid tumor size ≤2.3 cm (low-risk group), 17.0% with solid tumor size >2.3 cm and CEA ≤5 ng/mL (moderate-risk group), and 56.0% with solid tumor size >2.3 cm and CEA >5 ng/mL (high-risk group). The occult nodal metastasis rate was significantly higher in papillary-predominant (11.0%) and solid-predominant subtypes (28.6%; P=0.001). Patients having a micropapillary component had a significantly higher occult nodal metastasis rate (24.2%) compared with no micropapillary component (P=0.007). Histological subtype with micropapillary component and all preoperative predictors were significant prognostic factors affecting disease-free survival (DFS) (all P<0.05). A novel approach to predict occult nodal metastasis was developed for peripheral clinical stage I lung adenocarcinoma. It would be helpful for selecting candidates for stereotactic ablative radiotherapy (SABR) or wedge resection and mediastinoscopy or endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA). Complete nodal dissection should be performed for moderate to high-risk patients or patients with poor histologic subtypes.

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 ana­lysed. 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.

Diagnosis and treatment of coincident Hodgkin's lymphoma and hamartoma by endobronchial methods: A Case report

Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) is recommended for the diagnosis of malign and benign mediastinal lymphadenopathies and lesions adjacent to the central airways. However the diagnostic yield of EBUS-TBNA in diagnosis of lymphoma is weak. Additionally, the challenge of cathcing Reed-Sternberg cells in such a small sample size lowers the sensitivitiy of EBUS-TBNA for diagnosis of Hodgkin lymphoma. EBUS-TBNA can be performed with rigid bronchoscopy. A 64 years old male patient with multiple abdominal and mediastinal lymphadenopathies with coinciding hamartoma and Hodgkin lymphoma is reported for presenting diagnostic and therapeutic interventional methods performed for this unique coincidance.

Role of EBUS TBNA in Staging of Lung Cancer: A Clinician's Perspective.

The treatment of non-small cell lung cancer (NSCLC) includes surgical resection with curative intent in early-stage disease and chemoradiation in the advanced stage disease. Therefore, an accurate preoperative mediastinal lymph node staging is required not only to offer the appropriate treatment but also to avoid unnecessary invasive procedures including thoracotomy. The mediastinal lymph nodes can be sampled using several techniques including mediastinoscopy, surgery (open or video-assisted thoracoscopic surgery), endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA), or endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA). Currently, EBUS-TBNA/EUS-FNA is the preferred modality for sampling mediastinal lymph nodes because of its minimally invasive nature and high diagnostic yield. In this review, we discuss the utility of endosonographic procedures in mediastinal lymph node staging of NSCLC.

Optimal Endobronchial Ultrasound Strain Elastography Assessment Strategy: An Explorative Study

Background: In lung cancer staging, mediastinal lymph nodes are currently aspirated using endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) based on size and FDG-PET avidity. EBUS strain elastography (SE) is a new technique that may help predict the presence of malignancy. However, a standardized assessment strategy for EBUS-SE measurement is lacking. Objectives: The aim of this study was to determine the optimal assessment strategy for investigating the predictive value of EBUS-SE in mediastinal lymph nodes. Methods: Two qualitative visual analogue scale strain scores and two semiquantitative strain elastography measurements (a strain histogram and strain ratio) were acquired in 120 lymph nodes of 63 patients with (suspected) lung cancer. The dataset was randomized into an 80% training dataset to determine cut-off values. Performance was consecutively tested on the remaining 20% and the overall dataset. Results: The semiquantitative mean histogram scoring strategy with a cut-off value of 78 (range 0–255) showed the best and most reproducible performance in prediction of malignancy with 93% overall sensitivity, 75% specificity, 69% positive predictive value, 95% negative predictive value, and 82% accuracy. Combining the EBUS-SE mean histogram scoring outcome with PET-CT information increased the post-test probability of disease in relevant clinical scenarios, having a positive test likelihood ratio of 4.16 (95% CI 2.98–8.13) and a negative test likelihood ratio of 0.14 (95% CI 0.04–2.81) in suspicious lymph nodes based on FDG-PET or CT imaging. Conclusions: EBUS-SE can potentially help predict lymph node malignancy in patients with lung cancer. The best semiquantitative assessment method is the mean strain histogram technique.

Endobronchial ultrasound transbronchial needle aspiration in elderly patients: safety and performance outcomes EBUS-TBNA in elderly

Aim Complication rates are low and endobronchial ultrasound guided needle aspiration (EBUS-TBNA) is generally regarded as a safe procedure, but there is a very limited number of studies evaluating the efficacy and safety of the procedure in advanced ages. The aim of this study is to assess the safety and performance outcomes of EBUS-TBNA in elderly. Methods It was a retrospective observational study; patients who received EBUS-TBNA between September 2016 and January 2018 were evaluated. We analyzed patient’s characteristics, doses of midazolam, and lidocaine used, regions of lymph node biopsies, and complications. Also, functionality and general physical status of patients over 65 years of age were evaluated. Results During study period 132 cases of EBUS-TBNA were evaluated. 39 (29.5%) cases were aged 70 years, and over. There were more comorbidities in older group. Performance status of older group was worse. Furthermore, when evaluated according to American College of Cardiology (ACC)/American Heart Association (AHA) and American Society of Anesthesiologists (ASA), the older group was found to be composed of the riskier patients. When patients aged between 65 and 69, and over 70 compared, older patient’s Barthel, EQ 5-D, SGA, and G8 scores were found to be worse. Despite that, there was no difference in the frequency, and types of complications between both groups. Diagnostic performance was not different between age groups. Conclusions Independent from comorbidities, general health status, and functionality EBUS-TBNA procedure in 70-year-old and over patients is a safe minimally invasive procedure.

Changes in non-small cell lung cancer diagnosis, molecular testing and prognosis 2011-2016.

Non-small cell lung cancer (NSCLC) is a leading cause of death all over the world. Diagnostic and therapeutic arsenals have improved in recent years, but we are unsure as to whether these advances have been transferred to clinical practice. The aim of this study was to evaluate differences in NSCLC diagnostic processes and short-term survival rates between two recent cohorts. A prospective, observational study was conducted with patients diagnosed with NSCLC in the period of 2011-2016. Patients were divided into two cohorts (2011-2013 and 2014-2016), and monitored for up to 1 year after diagnosis. A total of 713 patients with lung cancer were selected, 500 of whom had NSCLC (222 patients in the 2011-2013 cohort, and 278 in the 2014-2016 cohort). We observed a chronological increase in the use of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and ultrasound-guided transthoracic puncture (US-TTP) between the cohorts. Overall short-term survival was similar between the two groups, both for locally and for advanced disease. Treatment with tyrosine kinase inhibitors (TKI) was the only therapeutic factor associated with an improved likelihood of survival. Changes in diagnostic process in NSCLC have been observed towards a more precise stratification. Although short-term survival has not changed for advanced NSCLC, some of the newer therapeutic options are associated with increased survival in real-world scenarios.

Ultrasonography of the Mediastinum: Techniques, Current Practice, and Future Directions.

In the everyday practice of respiratory physicians, ultrasound techniques play a key role by enabling several diagnostic and interventional procedures. The application of ultrasound to endoscopic procedures allows both a visualization and a guided sampling of mediastinal and hilar lymph nodes. Endobronchial ultrasound can be combined with transbronchial needle aspiration, and, similarly, endoscopic ultrasound can be combined with fine-needle aspiration to sample virtually all mediastinal nodal stations from the airways and the esophagus. Endobronchial ultrasound-transbronchial needle aspiration and endoscopic ultrasound-fine needle aspiration showed a complementary diagnostic yield, and, recently, endoscopic ultrasound with bronchoscope was introduced in clinical practice to perform a transesophageal needle aspiration by using an ultrasound bronchoscope. This technique allows a single operator to perform both transbronchial and transesophageal needle sampling with the same instrument during a single bronchoscopic procedure. Mediastinal staging impacts the management of patients affected by lung cancer, and the most recent guidelines clearly state that endobronchial ultrasound and endoscopic ultrasound should be the initial tissue sampling procedure over surgical staging. In addition, endoscopic ultrasound techniques demonstrated an excellent yield in diagnosing lymphoma and benign diseases, for example, sarcoidosis. The aim of this review was to discuss the current role and future perspectives of endosonography techniques available for the evaluation of the mediastinum. Special emphasis was placed on equipment and technical aspects, the diagnostic role, and future directions of development.

Comparison of Programmed Death Ligand-1 Immunohistochemical Staining Between Endobronchial Ultrasound Transbronchial Needle Aspiration and Resected Lung Cancer Specimens

In advanced non-small cell lung cancer (NSCLC), small biopsy specimens from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are often the only available material from cancer tissue for the analysis of programmed death ligand-1 (PD-L1) expression. We aim to assess the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PD-L1 expression at≥ 1%and≥ 50%on EBUS-TBNA samples compared with their corresponding surgically resected tumor. We retrospectively reviewed all patients who underwent EBUS-TBNA followed by surgical resection of NSCLC between July 2006 and September 2016. Demographic information and periprocedural/surgical data were collected. The archived specimens were retrieved and assessed for PD-L1. A positive PD-L1 stain was defined using two separate cutoff points:≥ 1%and≥ 50%of tumor cell positivity. EBUS-TBNA aspirates were compared with the surgically resected specimen to calculate the sensitivity, specificity, PPV, and NPV. Sixty-one patients were included. For PD-L1≥ 1%, the sensitivity, specificity, PPV, and NPV were 72%, 100%, 100%, and 80%, respectively. For PD-L1≥ 50%, the sensitivity, specificity, PPV, and NPV were 47%, 93%, 70%, and 84%, respectively. The concordance rates for PD-L1≥ 1%and≥ 50%were 87%and 82%, respectively. A PD-L1 cutoff of≥ 1%on EBUS-TBNA has a strong correlation with resected tumor specimen. For PD-L1≥ 50%, there is a significant decrease in the sensitivity and PPV of EBUS-TBNA specimen when compared with resected tumor. When analyzing for PD-L1 expression using a cutoff of≥ 50%, EBUS-TBNA specimens may misclassify the status of PD-L1.

Diagnosing Lung Cancer: The Complexities of Obtaining a Tissue Diagnosis in the Era of Minimally Invasive and Personalised Medicine.

The role of the respiratory physician in diagnosing lung cancer has increased in complexity over the last 20 years. Adenocarcinoma is now the prevailing histopathological sub-type of non-small cell lung cancer (NSCLC) resulting in more peripheral cancers. Conventional bronchoscopy is often not sufficient to obtain adequate tissue samples for diagnosis. Radiologically guided transthoracic biopsy is a sensitive alternative, but carries significant risks. These limitations have driven the development of complimentary bronchoscopic navigation techniques for peripheral tumour localisation and sampling. Furthermore, linear endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is increasingly being chosen as the initial diagnostic procedure for those with central lesions and/or radiological evidence of node-positive disease. This technique can diagnose and stage patients in a single, minimally invasive procedure with a diagnostic yield equivalent to that of surgical mediastinoscopy. The success of molecular targeted therapies and immune checkpoint inhibitors in NSCLC has led to the increasing challenge of obtaining adequate specimens for accurate tumour subtyping through minimally invasive procedures. This review discusses the changing epidemiology and treatment landscape of lung cancer and explores the utility of current diagnostic options in obtaining a tissue diagnosis in this new era of precision medicine.

A novel prediction model for the probability of mediastinal lymph node metastases detected by endobronchial ultrasound-transbronchial needle aspiration in non-small cell lung cancer: possible applications in clinical decision-making

A novel prediction model for the probability of mediastinal lymph node metastases detected by endobronchial ultrasound-transbronchial needle aspiration in non-small cell lung cancer: possible applications in clinical decision-making