EBUS versus EUS-B for diagnosing sarcoidosis: The International Sarcoidosis Assessment (ISA) randomized clinical trial.

BACKGROUND AND OBJECTIVE: Endosonography with intrathoracic nodal sampling is proposed as the single test with the highest granuloma detection rate in suspected sarcoidosis stage I/II. However, most studies have been performed in limited geographical regions. Studies suggest that oesophageal endosonographic nodal sampling has higher diagnostic yield than endobronchial endosonographic nodal sampling, but a head-to-head comparison of both routes has never been performed. METHODS: Global (14 hospitals, nine countries, four continents) randomized clinical trial was conducted in consecutive patients with suspected sarcoidosis stage I/II presenting between May 2015 and August 2017. Using an endobronchial ultrasound (EBUS) scope, patients were randomized to EBUS or endoscopic ultrasound (EUS)-B-guided nodal sampling, and to 22- or 25-G ProCore needle aspiration (2 × 2 factorial design). Granuloma detection rate was the primary study endpoint. Final diagnosis was based on cytology/pathology outcomes and clinical/radiological follow-up at 6 months. RESULTS: A total of 358 patients were randomized: 185 patients to EBUS-transbronchial needle aspiration (EBUS-TBNA) and 173 to EUS-B-fine-needle aspiration (FNA). Final diagnosis was sarcoidosis in 306 patients (86%). Granuloma detection rate was 70% (130/185; 95% CI, 63-76) for EBUS-TBNA and 68% (118/173; 95% CI, 61-75) for EUS-B-FNA (p = 0.67). Sensitivity for diagnosing sarcoidosis was 78% (129/165; 95% CI, 71-84) for EBUS-TBNA and 82% (115/141; 95% CI, 74-87) for EUS-B-FNA (p = 0.46). There was no significant difference between the two needle types in granuloma detection rate or sensitivity. CONCLUSION: Granuloma detection rate of mediastinal/hilar nodes by endosonography in patients with suspected sarcoidosis stage I/II is high and similar for EBUS and EUS-B. These findings imply that both diagnostic tests can be safely and universally used in suspected sarcoidosis patients.

Systematic and combined endosonographic staging of lung cancer (SCORE study).

Guidelines recommend endosonography for mediastinal nodal staging in patients with resectable nonsmall cell lung cancer (NSCLC). We hypothesise that a systematic endobronchial ultrasound (EBUS) evaluation combined with an oesophageal investigation using the same EBUS bronchoscope (EUS-B) improves mediastinal nodal staging versus the current practice of targeted positron emission tomography (PET)-computed tomography (CT)-guided EBUS staging alone.A prospective, multicentre, international study (NCT02014324) was conducted in consecutive patients with (suspected) resectable NSCLC. After PET-CT, patients underwent systematic EBUS and EUS-B. Node(s) suspicious on CT, PET, EBUS and/or EUS-B imaging and station 4R, 4L and 7 (short axis ≥8 mm) were sampled. For patients without N2/N3 disease determined on endosonography, surgical-pathological staging was the reference standard.229 patients were included in this study. The prevalence of N2/N3 disease was 103 out of 229 patients (45%). A PET-CT-guided targeted approach by EBUS identified 75 patients with N2/N3 disease (sensitivity 73%, 95% CI 63-81%; negative predictive value (NPV) 81%, 95% CI 74-87%). Four additional patients with N2/N3 disease were found by systematic EBUS (sensitivity 77%, 95% CI 67-84%; NPV 84%, 95% CI 76-89%) and five more by EUS-B (84 patients total; sensitivity 82%, 95% CI 72-88%; NPV 87%, 95% CI 80-91%). Additional clinical relevant staging information was obtained in 23 out of 229 patients (10%).Systematic EBUS followed by EUS-B increased sensitivity for the detection of N2/N3 disease by 9% compared to PET-CT-targeted EBUS alone.

Left Adrenal Gland Analysis in Lung Cancer Patients Using the Endobronchial Ultrasound Scope: A Feasibility Trial.

BACKGROUND: In lung cancer patients, the adrenal glands are predilection sites for distant metastases. Esophageal endoscopic ultrasound - fine-needle aspiration (EUS-FNA) is a minimally invasive and accurate method for left adrenal gland (LAG) analysis but requires a conventional gastrointestinal echoendoscope. Complete endobronchial and esophageal mediastinal nodal staging can be achieved by just a single endobronchial ultrasound (EBUS) scope, introducing it into the esophagus (EUS-B) following the endobronchial procedure. Whether the LAG can also be assessed with the EBUS scope is unknown. OBJECTIVES: The aim of the study was to investigate the feasibility of identifying the LAG with the EBUS scope. METHODS: We conducted a retrospective analysis of lung cancer patients who underwent EBUS and EUS-B for mediastinal staging and LAG assessment between January 2013 and May 2015. RESULTS: A total of 143 patients with (suspected) lung cancer were investigated by the combination of EBUS and EUS-B. In 68 of the 80 patients (85%) in whom an attempt was made to identify the LAG, it was feasible to transgastrically detect the LAG with the EBUS scope. In 9 patients with endosonographic signs of malignant involvement, diagnostic transgastric FNAs were obtained in all. In the 12 patients (15%) in whom the LAG was not detected, the contact between the ultrasound transducer and the gastric wall was suboptimal - the length of the scope was not a limiting factor. CONCLUSIONS: The EBUS scope allows identification of the LAG in the vast majority of lung cancer patients. IMPLICATION: In patients with (suspected) lung cancer, in addition to complete hilar and mediastinal staging, LAG assessment using just a single EBUS scope also seems feasible. Prospective studies are indicated.

EUS-B-FNA vs conventional EUS-FNA for left adrenal gland analysis in lung cancer patients.

INTRODUCTION: In patients with lung cancer, left adrenal glands (LAG) suspected for distant metastases (M1b) based on imaging require further evaluation for a definitive diagnosis. Tissue acquisition is regularly performed using conventional EUS-FNA. The aim of this study was to investigate the success rate of endoscopic ultrasound guided fine-needle aspiration using the EBUS scope (EUS-B-FNA) for LAG analysis. METHODS: This is a prospective multicenter study in consecutive patients with (suspected) lung cancer and suspected mediastinal and LAG metastases. Following complete mediastinal staging using the EBUS scope (EBUS+EUS-B), the LAG was evaluated and sampled by both EUS-B (experimental procedure) and conventional EUS (current standard of care). RESULTS: The success rate for LAG analysis (visualized, sampled and adequate tissue obtained) was 89% (39/44; 95% CI 76-95%) for EUS-B-FNA, and 93% (41/44; 95%CI 82-98%) for EUS-FNA. In the absence of metastases at EUS-B and/or EUS, surgical verification of the LAG or 6 months clinical and radiological follow-up was obtained, but missing for 5 patients. The prevalence of LAG metastases was 54% (21/39). In patients in whom LAG was seen and sampled, sensitivity for LAG metastases was at least 87% (95%CI 65-97%) for EUS-B, and at least 83% (95%CI 62-95%) for conventional EUS. CONCLUSION: LAG analysis by EUS-B shows a similar high success rate in comparison to conventional EUS. IMPLICATION: Both a mediastinal nodal and LAG evaluation can be adequately performed with just an EBUS scope and single endoscopist. This staging strategy is likely to reduce patient-burden and costs.

Added value of combined endobronchial and oesophageal endosonography for mediastinal nodal staging in lung cancer: a systematic review and meta-analysis.

BACKGROUND: Guidelines recommend endosonography with fine-needle aspiration for mediastinal nodal staging in non-small-cell lung cancer, but most do not specify whether this should be through endobronchial endoscopy (EBUS), oesophageal endoscopy (EUS), or both. We assessed the added value and diagnostic accuracy of the combined use of EBUS and EUS. METHODS: For this systematic review and random effects meta-analysis, we searched MEDLINE, Embase, BIOSIS Previews, and Web of Science, without language restrictions, for studies published between Jan 1, 2000, and Feb 25, 2016. We included studies that assessed the accuracy of the combined use of EBUS and EUS in detecting mediastinal nodal metastases (N2/N3 disease) in patients with lung cancer. For each included study, we extracted data on the age and sex of participants, inclusion criteria regarding tumour stage on imaging, details of the endoscopic testing protocol, duration of each endoscopic procedure, number of lymph nodes sampled, serious adverse events occurring during the endoscopic procedures, the reference standard, and 2 × 2 tables for EBUS, EUS, and the combined approach. We evaluated the added value (absolute increase in sensitivity and in detection rate) of the combined use of EBUS and EUS in detecting mediastinal nodal metastases over either test alone, and the diagnostic accuracy (sensitivity and negative predictive value) of the combined approach. This study is registered with PROSPERO, number CRD42015019249. FINDINGS: We identified 2567 unique manuscripts by database search, of which 13 studies (including 2395 patients) were included in the analysis. Median prevalence of N2/N3 disease was 34% (range 23-71). On average, addition of EUS to EBUS increased sensitivity by 0·12 (95% CI 0·08-0·18) and addition of EBUS to EUS increased sensitivity by 0·22 (0·16-0·29). Mean sensitivity of the combined approach was 0·86 (0·81-0·90), and the mean negative predictive value was 0·92 (0·89-0·93). The mean negative predictive value was significantly higher in studies with a prevalence of 34% or less (0·93 [95% CI 0·91-0·95]) compared with studies with a prevalence of more than 34% (0·89 [0·85-0·91]; p=0·013). We found no significant differences in mean sensitivity and negative predictive value between studies that did EBUS first or EUS first, or between studies that used an EBUS-scope or a regular echoendoscope to do EUS. INTERPRETATION: The combined use of EBUS and EUS significantly improves sensitivity in detecting mediastinal nodal metastases, reducing the need for surgical staging procedures. FUNDING: No external funding.