Molecular analysis of endobronchial ultrasound needle aspirates in patients with non-small cell lung cancer: Results from the SCOPE database.

OBJECTIVE: Molecular subtyping of non-small cell lung cancer (NSCLC) is critical in the diagnostic evaluation of patients with advanced disease. This study aimed to examine whether samples from endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) of intrathoracic lymph nodes and/or lung lesions are adequate for molecular analysis across various institutions. METHODS: We retrospectively reviewed all cases of linear EBUS-TBNA with a final bronchoscopic diagnosis of NSCLC entered in the Stather Canadian Outcomes registry for chest ProcEdures database. The primary outcome was specimen inadequacy rate for each molecular target, as defined by the local laboratory or pathologist. RESULTS: A total of 866 EBUS-TBNA procedures for NSCLC were identified. Specimen inadequacy rates were 3.8% for EGFR, 2.5% for ALK-1 and 3.5% for PD-L1. Largest target size was not different between adequate and inadequate specimens, and rapid onsite evaluation did not increase specimen adequacy rates. One centre using next-generation sequencing for EGFR had lower adequacy rates than 2 others using matrix-assisted laser desorption/ionization time-of-flight mass spectrophotometry. CONCLUSION: EBUS-TBNA specimens have a very low-specimen inadequacy rate for molecular subtyping of non-small cell lung cancer.

Sustained Clinical Benefits of Spiration Valve System in Patients with Severe Emphysema: 24-Month Follow-Up of EMPROVE.

Rationale: Follow-up of patients with emphysema treated with endobronchial valves is limited to 3-12 months after treatment in prior reports. To date, no comparative data exist between treatment and control subjects with a longer follow-up. Objectives: To assess the durability of the Spiration Valve System (SVS) in patients with severe heterogeneous emphysema over a 24-month period. Methods: EMPROVE, a multicenter randomized controlled trial, presents a rigorous comparison between treatment and control groups for up to 24 months. Lung function, respiratory symptoms, and quality-of-life (QOL) measures were assessed. Results: A significant improvement in forced expiratory volume in 1 second was maintained at 24 months in the SVS treatment group versus the control group. Similarly, significant improvements were maintained in several QOL measures, including the St. George's Respiratory Questionnaire and the COPD Assessment Test. Patients in the SVS treatment group experienced significantly less dyspnea than those in the control group, as indicated by the modified Medical Research Council dyspnea scale score. Adverse events at 24 months did not significantly differ between the SVS treatment and control groups. Acute chronic obstructive pulmonary disease exacerbation rates in the SVS treatment and control groups were 13.7% (14 of 102) and 15.6% (7 of 45), respectively. Pneumothorax rates in the SVS treatment and control groups were 1.0% (1 of 102) and 0.0% (0 of 45), respectively. Conclusions: SVS treatment resulted in statistically significant and clinically meaningful durable improvements in lung function, respiratory symptoms, and QOL, as well as a statistically significant reduction in dyspnea, for at least 24 months while maintaining an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Endobronchial Ultrasound Transbronchial Needle Aspiration With a 19-Gauge Needle vs 21- and 22-Gauge Needles for Mediastinal Lymphadenopathy.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is commonly used to evaluate mediastinal lymphadenopathy. Studies focusing on malignant lymphadenopathy have compared 21- and 22-gauge (21G and 22G, respectively) needles and have not identified an advantage of one needle size over the other in terms of diagnostic yield. RESEARCH QUESTION: Does the 19-gauge (19G) EBUS needle offer greater diagnostic yield and sensitivity vs the 21G and 22G EBUS needles for a diagnosis of sarcoidosis, lymphoma, or mediastinal lymphadenopathy not yet diagnosed? STUDY DESIGN AND METHODS: This study retrospectively examined records of 730 patients from the Stather Canadian Outcomes Registry for Chest Procedures (SCOPE) database who underwent EBUS-TBNA for a diagnosis of suspected sarcoidosis, lymphoma, or mediastinal lymphadenopathy not yet diagnosed. A propensity score analysis of two groups was performed. One group comprised patients undergoing EBUS-TBNA with a 19G needle, the other with a 21G or 22G needle. Cases for analysis were selected with a 1:2 ratio of 19G vs 21/22G using logistic regression and random matching with all eligible 19G cases included. RESULTS: There were 137 patients (312 targets) in the 19G group and 274 patients (631 targets) in the 21/22G group in the propensity score analysis. The diagnostic yield was 107 of 137 (78.1%) in the 19G group vs 194 of 274 (70.8%) in the 21/22G group (difference, 7.3%; 95% CI, -1.9 to 15.6; P = .116). The sensitivity of EBUS-TBNA for sarcoidosis was 80 of 83 (96.4%) in the 19G group vs 150 of 156 (96.2%) in the 21/22G group (difference, 0.24%; 95% CI, -6.6 to 85.1; P = .93). In patients with a final diagnosis of lymphoma, EBUS was diagnostic in 10 of 13 (76.9%) in the 19G group vs 12 of 12 (100%) in the 21/22G group (difference, 23.1%; 95% CI, -5.4 to 50.3; P = .08). INTERPRETATION: The study did not identify an advantage of the 19G EBUS needle over the 21/22G EBUS needles for diagnostic yield nor sensitivity for sarcoidosis or lymphoma.

Rural vs urban inequalities in stage at diagnosis for lung cancer.

OBJECTIVES: Early diagnosis of lung cancer increases the chance of survival. The aim of this study was to measure the relationship between geographic residence in Saskatchewan and stage of lung cancer at the time of diagnosis. MATERIALS AND METHODS: Retrospective cohort analysis of 2,972 patients with a primary diagnosis of either non-small cell cancer (NSCLC) or small cell lung cancer (SCLC) between 2007 and 2012 was performed. Incidence proportion of early and advanced stage cancer, and relative risk of being diagnosed with advanced-stage lung cancer relative to early-stage was calculated. RESULTS: Compared to urban Saskatchewan, rural Saskatchewan lung cancer patients had a higher relative risk of advanced stage NSCLC (relative risk [RR] = 1.11, 95% confidence interval [CI]: 1.01-1.22). Rural Saskatchewan was further subdivided into north and south. The relative risk of advanced stage NSCLC in rural north Saskatchewan compared to urban Saskatchewan was even greater (RR = 1.17, 95% CI: 1.03-1.31). Although not statistically significant, there was a trend for a higher incidence of advanced stage SCLC in rural and rural north vs urban Saskatchewan (RR = 1.16, 95% CI: 0.95-1.43 and RR = 1.22; 95% CI: 0.94-1.58, respectively). There was a higher incidence proportion of advanced stage NSCLC in rural areas relative to urban (31.6-34.4 vs 29.5 per 10,000 people). CONCLUSION: Patients living in rural Saskatchewan have higher incidence proportion of and were more likely to present with advanced stage NSCLC in comparison to urban Saskatchewan patients at time of diagnosis. This inequality was even greater in rural north Saskatchewan.

Canadian Internal Medicine Ultrasound (CIMUS) Expert Consensus Statement on the Use of Lung Ultrasound for the Assessment of Medical Inpatients With Known or Suspected Coronavirus Disease 2019.

OBJECTIVES: To develop a consensus statement on the use of lung ultrasound (LUS) in the assessment of symptomatic general medical inpatients with known or suspected coronavirus disease 2019 (COVID-19). METHODS: Our LUS expert panel consisted of 14 multidisciplinary international experts. Experts voted in 3 rounds on the strength of 26 recommendations as "strong," "weak," or "do not recommend." For recommendations that reached consensus for do not recommend, a fourth round was conducted to determine the strength of those recommendations, with 2 additional recommendations considered. RESULTS: Of the 26 recommendations, experts reached consensus on 6 in the first round, 13 in the second, and 7 in the third. Four recommendations were removed because of redundancy. In the fourth round, experts considered 4 recommendations that reached consensus for do not recommend and 2 additional scenarios; consensus was reached for 4 of these. Our final recommendations consist of 24 consensus statements; for 2 of these, the strength of the recommendations did not reach consensus. CONCLUSIONS: In symptomatic medical inpatients with known or suspected COVID-19, we recommend the use of LUS to: (1) support the diagnosis of pneumonitis but not diagnose COVID-19, (2) rule out concerning ultrasound features, (3) monitor patients with a change in the clinical status, and (4) avoid unnecessary additional imaging for patients whose pretest probability of an alternative or superimposed diagnosis is low. We do not recommend the use of LUS to guide admission and discharge decisions. We do not recommend routine serial LUS in patients without a change in their clinical condition.

Does prior mediastinal lymph node aspiration contribute to false-positive positron emission tomography-computed tomography?

BACKGROUND: Proper staging of the mediastinum is an essential component of lung cancer evaluation. Positron emission tomography-computed tomography (PETCT) and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) are an integral part of this process. False-positive PETCT results can occur following surgical procedures but has not been demonstrated following EBUS-TBNA. We aimed to determine whether false-positive PETCT rates increase when EBUS-TBNA is performed prior to PETCT. STUDY DESIGN AND METHODS: A retrospective review was carried out of clinical cases that underwent both PETCT and EBUS-TBNA within 30 days for the suspected malignancy. The impact of test sequence on the PETCT false-positive rate (FPR) was determined using Generalised Estimating Equation logistic regression analysis. RESULTS: A total of 675 lymph node stations were sampled and imaged on PETCT. Overall, 332 (49.2%) nodes were sampled by EBUS-TBNA before PETCT, and 343 (50.8%) afterwards, with the interval between EBUS and subsequent PETCT being a mean±sd of 11.6±6.8 days (range 1-29). The FPR on qualitative PETCT for the EBUS first group was 41 (23.2%) out of 164, and for PETCT first it was 57 (29.0%) out of 193 for a difference of 5.8% (95% CI -3.4-14.7, p=0.22). In the regression model, EBUS as the first test was associated with a lower FPR when using the clinical PETCT interpretation. INTERPRETATION: The performance of EBUS-TBNA sampling did not influence the FPR of PETCT when bronchoscopy took place in the 30 days prior to testing. Test sequence should be selected based on other clinical considerations.

Improving Lung Function in Severe Heterogenous Emphysema with the Spiration Valve System (EMPROVE). A Multicenter, Open-Label Randomized Controlled Clinical Trial.

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema.Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management.Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control).Measurements and Main Results: The primary efficacy outcome was the difference in mean FEV1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment (n = 113) or control (n = 59). Mean FEV1 showed statistically significant improvements between the treatment and control groups-between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060-0.141) and 0.099 L (95% BCI, 0.048-0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax.Conclusions: In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration With a 19-G Needle Device.

BACKGROUND: Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration is a well-established first-line minimally invasive modality for mediastinal lymph node sampling. Although results are excellent overall, the technique underperforms in certain situations. We aimed to describe our results using a new 19-G EBUS-guided transbronchial needle aspiration device to determine safety and feasibility of this approach. METHODS: We completed a retrospective chart review of all cases performed to the time of data analysis at each of 3 study sites. RESULTS: A total of 165 procedures were performed with a total of 297 individual lymph nodes or lesions sampled with the 19-G device by 10 bronchoscopists. Relatively large targets were selected for sampling with the device (mean lymph node size: 20.4 mm; lung lesions: 33.5 mm). A specific diagnosis was obtained in 77.3% of cases with an additional 13.6% of cases with benign lymphocytes, for a procedural adequacy rate of 90.9%. Procedure sample adequacy was 88.6% in suspected malignant cases, 91.0% in suspected sarcoidosis/lymphadenopathy cases, and 85.7% of cases with suspected lymphoma. On a per-node basis, a specific diagnosis was noted in 191/280 (68.2%) of samples, with an additional 61 showing benign lymphocytes for a per-node sample adequacy rate of 90%. One case (0.6%) of intraprocedure bleeding was noted. CONCLUSIONS: A new flexible 19-G EBUS needle was successfully and safely applied in a large patient cohort for sampling of lung and enlarged mediastinal lesions with high diagnostic rates across clinical indications.

Initial Clinical Experience With a Flexible Peripheral 21-G Needle Device.

BACKGROUND: Bronchoscopic techniques can be used to safely sample peripheral lung nodules (PLN), and transbronchial needle aspiration (TBNA) can further increase the diagnostic yield. Current needle devices not necessarily designed for this indication have limitations. We report our initial experience with a new flexible nitinol peripheral TBNA needle specifically designed for such sampling. METHODS: Retrospective case review describing the first clinical cases performed with a commercially available 21-G peripheral TBNA device in 4 centers. RESULTS: Eleven different operators performed 40 procedures for PLNs of a mean size of 35.1 mm (±18), and located 18.8 mm (±18.8) from the pleural surface, with 50% of them being present in the upper lobes. Bronchoscopists rated the use of the needle as good or excellent for reaching the PLN in 27/30 (90%) of cases. The TBNA sample was diagnostic in 18/40 cases (45%) overall and in 18/28 (64.3%) of cases where a diagnosis on bronchoscopy was possible. No episode of pneumothorax, significant bleeding, hypoxemia, escalation of care, or other complications were noted. CONCLUSION: Our initial experience with a novel peripheral TBNA device appears safe and effective, and may offer technical advantages over other available devices. Additional studies will be required to confirm the role of this device in the approach to bronchoscopic sampling of parenchymal lung nodules.

Management of malignant pleural effusion: challenges and solutions.

Malignant pleural effusion (MPE) is a sign of advanced cancer and is associated with significant symptom burden and mortality. To date, management has been palliative in nature with a focus on draining the pleural space, with therapies aimed at preventing recurrence or providing intermittent drainage through indwelling catheters. Given that patients with MPEs are heterogeneous with respect to their cancer type and response to systemic therapy, functional status, and pleural milieu, response to MPE therapy is also heterogeneous and difficult to predict. Furthermore, the impact of therapies on important patient outcomes has only recently been evaluated consistently in clinical trials and cohort studies. In this review, we examine patient outcomes that have been studied to date, address the question of which are most important for managing patients, and review the literature related to the expected value for money (cost-effectiveness) of indwelling pleural catheters relative to traditionally recommended approaches.

Flexible 19-Gauge Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Needle: First Experience.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established first-line invasive modality for mediastinal lymph node staging in lung cancer patients and in the diagnostic workup of patients with mediastinal adenopathy. With the current 21- and 22-gauge (G) EBUS-TBNA needles, the procedure can be limited by the degree of flexibility in the needle and the size of the lumen in tissue acquisition. OBJECTIVE: We report our initial experience with a first-generation flexible 19-G EBUS-TBNA (Flex 19G; Olympus Respiratory America, Redmond, WA, USA) needle with regards to efficacy and safety. METHODS: The Flex 19G EBUS-TBNA needle was used in 47 selected patients with enlarged hilar and/or mediastinal lymphadenopathy at 3 centers. The standard Olympus EBUS scope with a 2.2-mm working channel was used in all cases. RESULTS: The diagnostic yield of the Flex 19G needle according to clinical cytopathology reports was 89% (42/47). The diagnosis and their respective diagnostic yield with the Flex 19G EBUS-TBNA needle were malignancy 24/27 (89%), sarcoidosis 13/14 (93%), and reactive lymph node hyperplasia 5/6 (83%). The mean short axis of the sampled lymph nodes was 19 ± 9 mm. No complications occurred except for 1 instance of moderate bleeding, which did not require intervention beyond suctioning and subsequently resolved. All 13 patients diagnosed with adenocarcinoma by the 19-G needle had sufficient tissue for genetic testing. CONCLUSION: EBUS-TBNA using the first-generation Flex 19G needle is feasible and safe with promising diagnostic yield while providing a greater degree of flexion with the Olympus EBUS scope. Additional clinical evaluations are warranted.

Lesion heterogeneity and risk of infectious complications following peripheral endobronchial ultrasound.

BACKGROUND AND OBJECTIVE: The reported incidence of peripheral endobronchial ultrasound (pEBUS)-related infectious complications is below 1%, although studies have never focused solely on them or reported their risk factors. The goal of this study is to describe our local pEBUS infectious complication rate and characterize patient, lesion and procedural factors associated with infectious complications. METHODS: All charts, computed tomography scans and electronic records of patients who underwent a pEBUS at the Foothills Medical Center and South Health Campus Hospital in Calgary between 1 May 2014 and 1 October 2015 were reviewed. RESULTS: One hundred and ninety-nine pEBUS procedures were included in our study. The local infectious complication rate was 4.0% (8/199). Two lesion characteristics were more frequent in patients who suffered infectious complications: larger lesion diameter (P = 0.016) and lesion heterogeneity on imaging suggestive of areas of necrosis (P < 0.001). In a multivariate analysis, only the presence of lesion heterogeneity was significantly associated with infectious complications (OR = 16.74 (2.95-95.08)). The rate of infectious complications in lesions with a heterogeneous appearance was 20.7% (6/29). CONCLUSION: The rate of infectious complications after pEBUS is elevated when biopsying heterogeneous appearing lesions. This may not have previously been reported as studies of pEBUS focused on smaller and probably rarely necrotic lesions. Future studies of methods to prevent infections complications in pEBUS-guided biopsies of heterogeneous appearing lesions are warranted.

Self-expandable metallic stents in nonmalignant large airway disease.

Airway self-expandable metallic stents (SEMS) were initially studied in malignant airway obstruction; however, their use in benign airway diseases has become progressively more frequent. This may be explained by their ease of insertion compared with silicone stents, which require rigid bronchoscopy for insertion. While initial experience with SEMS in benign disease suggested efficacy and promising short-term safety profile, long-term follow-up revealed significant complication rates. In addition to a high complication rate, the management of these complications is made more difficult by the semipermanent nature of these devices. Reported complications include infection, granulation tissue formation, stent migration, stent fracture, airway perforation and fistula formation, as well as extension of the initial injury, potentially eliminating other therapeutic options such as surgical resection. Therefore, SEMS should only be used in nonmalignant large airway disease as a last resort for patients in whom other endoscopic methods, including silicone stents and dilations, as well as surgical options have failed or are technically not feasible.

Endobronchial ultrasound learning curve in interventional pulmonary fellows.

BACKGROUND AND OBJECTIVE: Little published data exist regarding the learning curve for endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). We sought to assess the improvement in skill as trainees learned EBUS-TBNA in a clinical setting. METHODS: This is a multicentre cohort study of EBUS-TBNA technical skill of interventional pulmonology (IP) fellows as assessed with EBUS-TBNA computer simulator testing every 25 clinical cases throughout IP fellowship training. RESULTS: Nine fellows from three academic centres in the United States and Canada were enrolled in the study. Ongoing improvements were seen for EBUS-TBNA efficiency score and percentage of lymph nodes correctly identified on ultrasound exam, even after 200 clinical cases. Expert-level technical skill was obtained for EBUS efficiency score and for percentage of lymph nodes correctly identified on ultrasound exam at a median of 212 and 164 procedures, respectively; however, 33% of fellows did not achieve expert-level technical skill for either metric during their fellowship training. Significant variation in learning curves of the fellows was observed. CONCLUSIONS: Significant variation is seen in the EBUS-TBNA learning curves of individual IP fellows and for individual procedure components, with ongoing improvement in EBUS-TBNA skill even after 200 clinical cases. These results highlight the need for validated, objective measures of individual competence, and can assist training programmes in ensuring adequate procedure volumes required for a majority of trainees to successfully complete these assessments.

Evaluation of a novel method of teaching endobronchial ultrasound: physician- versus respiratory therapist-proctored simulation training.

BACKGROUND: Computer endobronchial ultrasound (EBUS) simulators have been demonstrated to improve trainee procedural skills before attempting to perform EBUS procedures on patients. OBJECTIVE: To compare EBUS performance following training with computer simulation proctored by EBUS-trained respiratory therapists versus the same simulation training proctored by an interventional respirologist. METHODS: The present analysis was a prospective study of respiratory medicine trainees learning EBUS. Two cohorts of trainees were evaluated using a previously validated method using simulated cases with performance metrics measured by the simulator. Group 1 underwent EBUS training by performing 15 procedures on an EBUS simulator (n=4) proctored by an interventional respirologist. Group 2 received identical training proctored by a respiratory therapist with special training in EBUS (n=10). RESULTS: No significant differences between group 1 and group 2 were apparent for the primary outcome measures of total procedure time (15.15±1.34 min versus 14.78±2.88 min; P=0.816), the percentage of lymph nodes successfully identified (88.8±5.4 versus 80.91±8.9; P=0.092) or the percentage of successful biopsies (100.0±0.0 versus 98.75±3.95; P=0.549). The learning curves were similar between groups, and did not show an obvious plateau after 19 simulated procedures in either group. DISCUSSION: Acquisition of basic EBUS technical skills can be achieved using computer EBUS simulation proctored by specially trained respiratory therapists or by an interventional respirologist. There appeared to be no significant advantage to having an interventional respirologist proctor the computer EBUS simulation.