Endobronchial ultrasound in diagnosing and staging of lung cancer by Acquire 22G TBNB versus regular 22G TBNA needles: A randomized clinical trial.

OBJECTIVES: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has an important role in the diagnosis and staging of lung cancer. Evaluation of programmed death ligand 1 (PD-L1) expression and molecular profiling has become standard of care but cytological samples frequently contain insufficient tumor cells. The 22G Acquire needle with Franseen needle tip was developed to perform transbronchial needle biopsy (TBNB) with improved tissue specimens. This study evaluated if the 22G Acquire TBNB needle results in enhanced PD-L1 suitability rate compared to the regular Expect 22G TBNA needle. METHODS: in this multi-center randomized clinical trial (Netherlands Trial Register NL7701), patients with suspected (N)SCLC and an indication for mediastinal/hilar staging or lung tumor diagnosis were recruited in five university and general hospitals in the Netherlands, Poland, Italy and Czech Republic. Patients were randomized (1:1) between the two needles. Two blinded reference pathologists evaluated the samples. The primary outcome was PD-L1 suitability rate in patients with a final diagnosis of lung cancer. In case no malignancy was diagnosed, the reference standard was surgical verification or 6 month follow-up. RESULTS: 154 patients were randomized (n = 76 Acquire TBNB; n = 78 Expect TBNA) of which 92.9% (n = 143) had a final malignant diagnosis. Suitability for PD-L1 analysis was 80.0% (n = 56/70; 95 %CI 0.68-0.94) with the Acquire needle and 76.7% (n = 56/73; 95 %CI 0.65-0.85) with the Expect needle (p = 0.633). Acquire TBNB needle specimens provided more frequent superior quality (65.3% (95 %CI 0.57-0.73) vs 49.4% (95 %CI 0.41-0.57, p = 0.005) and contained more tissue cores (72.0% (95 %CI 0.60-0.81) vs 41.0% (95 %CI 0.31-0.54, p < 0.01). There were no statistically significant differences in tissue adequacy, suitability for molecular analysis and sensitivity for malignancy and N2/N3 disease. CONCLUSION: The 22G Acquire TBNB needle procured improved quality tissue specimens compared to the Expect TBNA needle but this did not result in an improved the suitability rate for PD-L1 analysis.

Endosonography and endosonography guided needle aspiration for left adrenal gland assessment in lung cancer patients - 10 years' experience.

INTRODUCTION: Lung cancer patients (LCP) require invasive evaluation of left adrenal glands (LAG) if distant metastases (M1b/1c) are suspected in CT or PET-CT. Only few studies showed utility of endosonography and particularly EUS-b-FNA as minimally invasive endoscopic method of LAG analysis. MATERIAL AND METHODS: A retrospective study of consecutive LCP was conducted in two pulmonology centers between January 2010 and December 2019. Records of complete endosonographic staging with use of single ultrasound bronchoscope or two scopes were overviewed. The analysis included cases of enlarged LAG (body size or limbs > 10 mm) examined and sampled by EUS-b-FNA or EUS-FNA. RESULTS: 142 of 2596 LCP staged by complete endosonography (M: 88, F: 54 mean age 64.7) had enlarged LAG, which were biopsied by conventional EUS-FNA (52) and/or by EUS-b-FNA (90). Strong correlation with gland diameter (P < 0.001) was observed. The incidence of LAG metastases in analyzed group was 52.1% (74/142) and regarding histology: SCLC 76.9% (10/13), adenocarcinoma 66.7% (44/66), NSCLC 56.3% (9/16) and SCC 17.5% (7/40). A specificity and PPV for both methods were 100%. A sensitivity, accuracy and NPV for EUS-FNA were 91.7%, 96.2%, 93.3% and for EUS-b-FNA 88%, 93.3% and 87%, respectively and no significant differences for both methods were noted (P = 0.62, 0.44, 0.35). No severe complications afterall biopsies were observed. A six months clinical follow up included all negative LCP with enlarged LAG. CONCLUSIONS: After our study EUS-b-FNA seems to be a reasonable method of choice for LAG assesssment in LCP.

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.

Ultrasound predictors of left adrenal metastasis in patients with lung cancer: a comparison of computed tomography, positron emission tomography-computed tomography, and endoscopic ultrasound using ultrasound bronchoscope.

INTRODUCTION: Patients with resectable lung cancer require invasive evaluation of the enlarged left adrenal gland (LAG). Few studies showed the utility of endoscopic ultrasound using ultrasound bronchoscope (EUS­B) in LAG assessment. Moreover, little is known on the combination of computed tomography (CT), positron emission tomography-computed tomography (PET­CT), and EUS­B for predicting left adrenal metastasis. PATIENTS AND METHODS: In this retrospective cohort study performed from 2012 to 2019, patients with left adrenal enlargement were evaluated by CT, PET­CT, and EUS­B, followed by complete endoscopic mediastinal staging. The adrenal glands were sampled by EUS­B-guided fine­needle aspiration. Patients were followed for 6 months. RESULTS: During the staging of lung cancer in 2176 patients, 113 enlarged LAGs (5.19%) were biopsied. Malignancy was reported in 51 LAGs (45.13%). Endoscopic ultrasound upstaged 7 patients (6.2%) and downstaged 11 patients (9.37%) after false CT or PET­CT findings. There were no biopsy­related complications. Radiologic predictors of left adrenal metastases had the highest yield at the following cutoff points: Hounsfield units >23, standardized uptake value >4.2, and LAG size >25 mm. Hypoechogenic LAGs with loss of sea­gull shape on EUS­B were associated with a 28.67­fold higher likelihood of metastases. The sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for all ultrasound predictors were 86.21%, 85.45%, 85.84%, 85.45%, and 86.21%, respectively. When combined with radiologic features, the respective values were 93.10%, 94.55%, 93.81%, 92.86%, and 94.74%. CONCLUSIONS: Hypoechogenicity and loss of sea­gull shape on EUS­B are the most reliable predictors of left adrenal metastasis. The combination of CT, PET­CT, and EUS­B improves the noninvasive diagnosis of left adrenal metastases in lung cancer patients.

Endobronchial ultrasound in diagnosing and staging of lung cancer by Acquire 22G TBNB versus regular 22G TBNA needles: study protocol of a randomised clinical trial.

INTRODUCTION: Accurate diagnosis and staging of lung cancer is crucial because it directs treatment and prognosis. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound with bronchoscope fine-needle aspiration (EUS-B-FNA) are important in this process by sampling hilar/mediastinal lymph nodes and centrally located lung tumours. With the upcoming of immunotherapy and targeted therapies, assessment of programmed death ligand 1 (PD-L1) expression and molecular profiling has become important but is often impossible in cytological samples obtained through standard 22G TBNA needles. Recently, a three-pronged cutting edge 22G needle was developed that allows for transbronchial needle biopsy (TBNB). Our objective is to determine if EBUS/EUS-B-guided nodal/lung tumour sampling with Acquire 22G TBNB needles results in an improved suitability rate for the assessment of PD-L1 expression in comparison to standard 22G TBNA needles in patients with a final diagnosis of lung cancer. METHODS AND ANALYSIS: This is an investigator-initiated, parallel group randomised clinical trial. Patients are recruited at respiratory medicine outpatient clinics of participating university and general hospitals in the Netherlands, Poland and Italy. In total 158 adult patients with (suspected) lung cancer are included if they have an indication for mediastinal/hilar lymph node or lung tumour sampling by EBUS-TBNA and/or EUS-B-FNA based on current clinical guidelines. Web-based randomisation between the two needles will be performed. Samples obtained from mediastinal/hilar lymph nodes and/or primary tumour will be processed for cytology smears and cell block analysis and reviewed by blinded reference pathologists. An intention-to-treat analysis will be applied. Patients with missing data will be excluded from analysis for that specific variable but included in the analysis of other variables. This study is financially supported by Boston Scientific. ETHICS AND DISSEMINATION: The study was approved by the local Ethics Committee (Medisch Ethische Toetsingscommissie Amsterdam Medical Center (AMC)). Dissemination will involve publication in a peer-reviewed biomedical journal. TRIAL REGISTRATION NUMBER: NL7701; Pre-results.

Usefulness of combined endobronchial and endoscopic ultrasound-guided needle aspiration in the diagnosis of sarcoidosis: a prospective multicenter trial.

INTRODUCTION: Needle biopsy of enlarged lymph nodes is an accepted method for the diagnostic workup of sarcoidosis, but the optimal endosonography­guided approach is yet to be determined. OBJECTIVES: The aim of our study was to assess the relative diagnostic yield of combined ultrasound­guided needle aspiration (CUS­b­NA), which includes endobronchial ultrasound­guided transbronchial needle aspiration (EBUS­TBNA) with endoscopic ultrasound fine­needle aspiration (EUS­b­FNA), as well as the role of the cell block (CB) technique and lymph node localization in the diagnostic workup of sarcoidosis. PATIENTS AND METHODS: This was a prospective multicenter study including consecutive patients with clinical suspicion of stage I or II sarcoidosis. CUS­b­NA with smears and CB technique were performed in the whole study group. If a biopsy result was not conclusive, an invasive diagnostic workup and a 6-month follow­up were scheduled. RESULTS: Out of 77 screened patients, 54 signed written consent and 50 were enrolled for the final analysis. The overall sensitivity of EBUS­TBNA, EUS­b­FNA, and CUS­b­NA was 76.6%, 70.2%, and 91.7%, respectively. There were no differences between EBUS­TBNA and EUS­b­FNA (P = 0.52) but CUS­b­NA had a higher diagnostic yield (P = 0.005 and P = 0.001, respectively). Adding the CB method to smear technique (P = 0.008) and biopsy of the subcarinal lymph nodes increased the diagnostic yield (P = 0.001).  Conclusions: The diagnostic yield of CUS­b­NA is higher than that of endosonographic techniques alone in the diagnostic workup of stage I and II sarcoidosis. The preparation of cytological material including CB and the choice of the subcarinal lymph node station for the biopsy increase the diagnostic efficacy.

Transbronchial lung cryobiopsy guided by radial mini-probe endobronchial ultrasound in interstitial lung diseases - a multicenter prospective study.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is commonly used in diagnosing interstitial lung diseases (ILDs). Ageneral anesthesia with endotracheal intubation, balloon blockers and fluoroscopy control is the most common modality. Simplifying the procedure without decreasing it's safety could result in wider use. Prospective, observational study was conducted in three Polish pulmonology centers to evaluate safety and diagnostic yield of TBLC under conscious sedation, without intubation and bronchial blockers and with radial-EBUS guidance instead of fluoroscopy. MATERIAL AND METHODS: In patients suspected of ILD, in accordance with high resolution computer tomography (HRCT) selected lung segments were examined with radial-EBUS mini probe without aguide sheath. If the lung infiltrations were visible this locations were preferred. If not, specimens were taken from two different segments of the same lobe. Two to five biopsies with freezing time 5-8 seconds were performed. Moreover ultrasound examination was used to avoid injury of lung vessels. RESULTS: From March 2017 to September 2019 - 114 patients (M: 59, F: 55) of mean (SD) age 54 (14) years were included to the study on the basis of medical history and HRCT. Histopathology was conclusive in 90 (79%) patients and included 16 different diagnoses (sarcoidosis, EAA, COP predominantly). 24 inconclusive biopsies of unclassifiable pulmonary fibrosis were followed up. Complications included five cases (4.4%) of pneumothorax requiring achest tube drainage and aminor and moderate bleeding in few cases. There was no need for use of balloon bronchial blockers. CONCLUSIONS: TBLC under conscious sedation guided by radial EBUS mini-probe is novel, reasonable and safe technique for histological diagnosis of ILDs.

[Advances in endoscopic diagnosis of sarcoidosis]. / Postepy w endoskopowej diagnostyce sarkoidozy.

A diagnosis of pulmonary sarcoidosis is based on the assessment of clinical outcome, radiology findings and detection of noncaseating granulomas in cytology or histology specimens. Cytological material obtained from enlarged lymph nodes and/or histological specimens from bronchial mucosa and lung tissue are examined according to sarcoidosis stage. The most available are standard bronchoscopic methods as conventional transbronchial needle aspiration (cTBNA), endobronchial biopsy (EBB) and transbronchial lung biopsy (TBLB) both performed with use of forceps. The new endoscopic techniques introduced to pulmonary diagnostics are: endobronchial ultrasoundguided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) or if used by the ultrasound bronchoscope (EUS-b-FNA) and transbronchial lung cryobiopsy (TBLC). Considering a dynamic improvement in cytology assessment techniques (processed as cytology smears and cell blocks) the endoscopic methods with use of fine needle aspiration biopsy of enlarged lymph nodes became a method of choice in sarcoidosis with lymphadenopathy, and published data suggest a higher diagnostic yield when performed under endosonographic guidance. The optimal approach (transbronchial or transesophageal) and the selection of mediastinal lymph node stations considered for biopsy still need evaluation. Also TBLC, successfully used in the diagnosis of other diffuse parenchymal lung diseases, requires more experiences and trials to establish its role in diagnosis of pulmonary sarcoidosis.

Initial Polish experience of Flexible 19 gauge Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

INTRODUCTION: EBUS is a well established minimally invasive diagnostic tool for mediastinal and hilar lymphadenopathy. The novel ViziShot Flex 19G needle (Olympus Respiratory America, Redmond, WA, USA) was introduced in 2015 in order to improve loaded scope flexion and to obtain larger tissue samples for analysis. The aims of this study were to assess diagnostic yield of Flex 19G needles and to present endoscopist's feedback about the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). MATERIAL AND METHODS: The Flex 19G needles were used in patients with hilar and/or mediastinal adenopathy in two Polish pulmonology centers. Cytology smears and cell blocks (CB) were prepared. The prospective analysis was performed due to collected data. RESULTS: Twenty two selected patients with confirmed adenopathy on chest-CT (mean age 58 ± 12) underwent EBUS-TBNA with use of Flex 19G needles. All procedures occurred to be diagnostic for smears (yield 100%). The malignancy was found in 15 cases (68.2%), and benign adenopathy in 7 (31.8%). In 12 of 14 cases of lung cancer (yield 85.7%) CB were diagnostic for immunohistochemical and molecular staining. After puncturing nodes, especially in hilar position not extensive bleeding was observed. Comparing to standard 21/22G EBUS-TBNA endoscopists underlined better flexion of loaded scope and sample adequacy and found non-significant differences in another biopsy details. CONCLUSIONS: The first Polish experience with use of Flex 19G EBUS-TBNA needle occurs to be similar in performance with standard technique with use of 22/21G needles and presents high diagnostic yield for lung cancer diagnostics, especially when preparing CB. A safety profile of the biopsy is acceptable.

The influence of lung volume reduction with intrabronchial valves on the quality of life of patients with heterogeneous emphysema - a prospective study.

INTRODUCTION: A heterogeneous emphysema is one of the most severe forms of chronic obstructive pulmonary disease (COPD). In some cases, besides the standard pharmacotherapy, a new treatment option of emphysema can be used - bronchoscopic lung volume reduction (BLVR) with the use of intrabronchial valves. OBJECTIVES: To examine the health-related quality of life (HRQoL) of patients with severe emphysema after intrabronchial valve (IBV) implantation for the treatment of one lung. MATERIAL AND METHODS: From 2011 to 2013 a single centre prospective observational study was performed. The study assessed the effect of the therapeutic BLVR intervention, measured by St. George Respiratory Questionnaire (SGRQ). A statistical analysis by use of Wilcoxon test for dependent variables was performed. RESULTS: Twenty patients were enrolled to the study (mean age 63 ± 10 years), all ex-smokers with tobacco exposure 38 ± 11.3 packyears. After 3 months of IBV treatment the average SGRQ score improved significantly in total (-12.8; p < 0.001) and in domains and the differences were for: "symptoms" (-8.5; p < 0.001), "activity" (-13.9; p < 0.001) and "influence on life"(-13.5; p < 0.002). CONCLUSIONS: The presented study revealed a significant improvement of the quality in the life measured by SGRQ after IBV treatment for heterogeneous emphysema. For the first time our study showed the significant improvement of all three domains of SGRQ after IBV treatment.

Comparison of conventional and ultrasound-guided needle biopsy techniques in the diagnosis of sarcoidosis: a randomized trial.

INTRODUCTION: Endoscopic biopsy techniques are useful in the diagnosis of sarcoidosis. There is a need for randomized trials to establish where these procedures fit in the diagnosis of sarcoidosis. OBJECTIVES: The aim of the study was to compare the diagnostic yield of conventional transbronchial needle aspiration (TBNA) with endobronchial ultrasound-guided TBNA (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in stages I and II of pulmonary sarcoidosis. PATIENTS AND METHODS: Patients suspected of sarcoidosis were randomized to undergo TBNA or EBUS-TBNA or EUS-FNA. Patients with negative TBNA and EBUS-TBNA results underwent EUS-FNA and those with negative EUS-FNA results­EBUS-TBNA. If both tests were negative, patients in stage I were scheduled for mediastinoscopy (MS) and those in stage II­for transbronchial lung biopsy (TBLB). RESULTS: In 100 patients, 34 TBNA, 30 EBUS-TBNA, and 36 EUS-FNA procedures were performed at baseline. TBNA was positive in 20 patients (58.8%); EBUS-TBNA, in 23 (76.7%); and EUS-FNA, in 31 patients (86.1%). In patients with negative biopsy results, the second procedure was performed. The results of EUS-FNA were positive in 9 patients and of EBUS-TBNA­in none. Of 17 patients with negative results of both procedures, MS was performed in 6 patients and was positive in 2. In the remaining 11 patients, sarcoidosis was confirmed by TBLB. Sensitivity and accuracy of TBNA compared with EBUS-TBNA and EUS-FNA were 62.5% and 64.7%, 79.3% and 80%, and 88.6% and 88.9%, respectively. Sensitivity and accuracy of EBUS-TBNA were higher (P = 0.139) and of EUS-FNA were significantly higher compared with TBNA (P = 0.012). CONCLUSIONS: In stages I and II of pulmonary sarcoidosis, endoscopic ultrasound is a reasonable approach but EUS-FNA seems to be the method of choice.

Tension pneumothorax as a severe complication of endobronchial ultrasound-guided transbronchial fine needle aspiration of mediastinal lymph nodes.

This article presents a case report of a patient suffering from bullous emphysema and chronic obstructive pulmonary disease, who was diagnosed with tension pneumothorax after undergoing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Tension pneumothorax is a severe but rare complication of EBUS-TBNA. It can result from lung injury caused by the biopsy needle or, in patients suffering from bullous emphysema, from spontaneous rupture of an emphysematous bulla resulting from increased pressure in the chest cavity during cough caused by bronchofiberoscope insertion. The authors emphasize that patients should be carefully monitored after the biopsy, and, in the case of complications, provided with treatment immediately in proper hospital conditions. Patients burdened with a high risk of complications should be identified before the procedure and monitored with extreme care after its completion.