Rationale: The current management of advanced non–small cell lung cancer (NSCLC) requires differentiation between squamous and nonsquamous subtypes as well as epidermal growth factor receptor (EGFR) mutation status. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is increasingly used for the diagnosis and staging of lung cancer. However, it is unclear whether cytology specimens obtained with EBUS-TBNA are suitable for the subclassification and genotyping of NSCLC.

Objectives: To determine whether cytology specimens obtained from EBUS-TBNA in routine practice are suitable for phenotyping and genotyping of NSCLC.

Methods: Cytological diagnoses from EBUS-TBNA were recorded from 774 patients with known or suspected lung cancer across five centers in the United Kingdom between 2009 and 2011.

Measurements and Main Results: The proportion of patients with a final diagnosis by EBUS-TBNA in whom subtype was classified was 77% (95% confidence interval [CI], 73–80). The rate of NSCLC not otherwise specified (NSCLC-NOS) was significantly reduced in patients who underwent immunohistochemistry (adjusted odds ratio, 0.50; 95% CI, 0.28–0.82; P = 0.016). EGFR mutation analysis was possible in 107 (90%) of the 119 patients in whom mutation analysis was requested. The sensitivity, negative predictive value, and diagnostic accuracy of EBUS-TBNA in patients with NSCLC were 88% (95% CI, 86–91), 72% (95% CI, 66–77), and 91% (95% CI, 89–93), respectively.

Conclusions: This large, multicenter, pragmatic study demonstrates that cytology samples obtained from EBUS-TBNA in routine practice are suitable for subtyping of NSCLC and EGFR mutation analysis and that the use of immunohistochemistry reduces the rate of NSCLC-NOS.

Rationale

The current management of advanced non-small cell lung cancer (NSCLC) requires differentiation between squamous and non-squamous sub-types as well as epidermal growth factor receptor (EGFR) mutation status. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is increasingly used for the diagnosis and staging of lung cancer. However, it is unclear whether cytology specimens obtained with EBUS-TBNA are suitable for the sub-classification and genotyping of NSCLC.

Objectives

To determine whether cytology specimens obtained from EBUS-TBNA in routine practice are suitable for phenotyping and genotyping of NSCLC.

Methods

Cytological diagnoses from EBUS-TBNA were recorded from 774 patients with known or suspected lung cancer across 5 centres in the United Kingdom between 2009 and 2011.

Measurements and Main Results

The proportion of patients with a final diagnosis by EBUS-TBNA in whom subtype was classified was 77% (95% CI 73% - 80%). The rate of NSCLC not otherwise specified (NSCLC-NOS) was significantly reduced in patients who underwent immunohistochemistry (adjusted OR 0.50 95% CI 0.28 – 0.82, P=0.016). EGFR mutation analysis was possible in 107 (90%) of the 119 patients in whom mutation analysis was requested. The sensitivity, negative predictive value and diagnostic accuracy of EBUS-TBNA in patients with NSCLC was 88% (95% CI 86% - 91%), 72% (95% CI 66% - 77%) and 91% (95% CI 89% - 93%) respectively.

Conclusions

This large multi-centre pragmatic study demonstrates that cytology samples obtained from EBUS-TBNA in routine practice are suitable for sub-typing of NSCLC and EGFR mutation analysis and that use of immunohistochemistry reduces the rate of NSCLC-NOS.

Background and objective

Standard bronchoscopic techniques (transbronchial lung biopsy and endobronchial biopsy) provide a diagnosis in 70% of patients with pulmonary sarcoidosis. Previous data suggest that endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a high sensitivity in patients with sarcoidosis. The feasibility and utility of combining EBUS-TBNA with standard bronchoscopic techniques is unknown. The aim of this study was to evaluate the feasibility, safety and efficacy of combined EBUS-TBNA and standard bronchoscopic techniques in patients with suspected sarcoidosis and enlarged mediastinal or hilar lymphadenopathy.

Methods

Forty consecutive patients with suspected pulmonary sarcoidosis and enlarged mediastinal or hilar lymph nodes (radiographical stage I and stage II) underwent EBUS-TBNA followed by transbronchial biopsies and endobronchial biopsies under conscious sedation.

Results

Thirty-nine out of 40 patients successfully underwent combined EBUS-TBNA and standard bronchoscopy. Twenty-seven patients were diagnosed with sarcoidosis, eight had tuberculosis, two had reactive lymphadenopathy, two had lymphoma and one had metastatic adenocarcinoma. In patients with sarcoidosis, the sensitivity of EBUS-TBNA for detection of noncaseating granulomas was 85%, compared with a sensitivity of 35% for standard bronchoscopic techniques (P < 0.001). The diagnostic yield of combined EBUS-TBNA and bronchoscopy was 93% (P < 0.0001).

Conclusions

Combination of EBUS-TBNA with standard bronchoscopic techniques is safe and feasible, and optimizes the diagnostic yield in patients with pulmonary sarcoidosis and enlarged intrathoracic lymphadenopathy.

Background

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as an important tool for the diagnosis and staging of lung cancer but its role in the diagnosis of tuberculous intrathoracic lymphadenopathy has not been established. The aim of this study was to describe the diagnostic utility of EBUS-TBNA in patients with intrathoracic lymphadenopathy due to tuberculosis (TB).

Methods

156 consecutive patients with isolated intrathoracic TB lymphadenitis were studied across four centres over a 2-year period. Only patients with a confirmed diagnosis or unequivocal clinical and radiological response to antituberculous treatment during follow-up for a minimum of 6 months were included. All patients underwent routine clinical assessment and a CT scan prior to EBUS-TBNA. Demographic data, HIV status, pathological findings and microbiological results were recorded.

Results

EBUS-TBNA was diagnostic of TB in 146 patients (94%; 95% CI 88% to 97%). Pathological findings were consistent with TB in 134 patients (86%). Microbiological investigations yielded a positive culture of TB in 74 patients (47%) with a median time to positive culture of 16 days (range 3–84) and identified eight drug-resistant cases (5%). Ten patients (6%) did not have a specific diagnosis following EBUS; four underwent mediastinoscopy which confirmed the diagnosis of TB while six responded to empirical antituberculous therapy. There was one complication requiring an inpatient admission.

Conclusions

EBUS-TBNA is a safe and effective first-line investigation in patients with tuberculous intrathoracic lymphadenopathy.

Objective:

It is believed that off-pump coronary artery bypass grafting (OPCAB) leads to hypercoagulability, but efforts to document such a state have been unrevealing. We hypothesized that OPCAB increases the risk of developing a regional hypercoagulable state.

Methods:

Blood was obtained from the aorta and coronary sinus (CS) after CABG performed off- (N=69) or on-pump (N=35) to determine the transcardiac gradients of F1.2 (thrombin production), XIIa (coagulation activation), myoglobin (ischemia) and IL-6, IL-8 using ELISA and platelet-derived microparticles using FACS. Platelet function was measured using aggregometry. Regional myocardial pH and SVG flow were recorded intraoperatively. SVG biopsies were analyzed for endothelial integrity (EI) using immunohistochemistry and graft patency was determined by predischarge CT angiography.

Results:

Compared with on-pump, OPCAB provoked significantly higher transcardiac F1.2 (117±200 v. 31±38%), FXII-a (14±29 v. 2±4%), microparticles (14±−9.5% v. 6.4±−4.1%), IL-6 (119±183 v. 28±39%), and a trend toward increased IL-8 (67±94 v. 24±46%, P = 0.077). Myoglobin release after OPCAB, also greater than on-pump CABG (54±89 v. 8±14%, P < 0.01), correlated with regional pH change (R=−0.96, P < 0.0001), and F1.2 release (R=0.55, P = 0.0002). In contrast, systemic changes in these markers were all less after OPCAB. SVG flow was significantly reduced in OPCAB (39.4 versus 66.5 mL/min, P = 0.0002), but EI and graft patency rates were the same.

Conclusions:

Through the use of transcardiac assays, we illustrated that regional coagulation was enhanced after off- compared with on-pump CABG. If the findings of this pilot study are confirmed, OPCAB may require additional antithrombotic therapies to respond to this local hypercoagulable state.