A Multicenter, Single-Arm, Prospective Trial Assessing the Diagnostic Yield of Electromagnetic Bronchoscopic and Transthoracic Navigation for Peripheral Pulmonary Nodules.

Rationale: Strict adherence to procedural protocols and diagnostic definitions is critical to understand the efficacy of new technologies. Electromagnetic navigational bronchoscopy (ENB) for lung nodule biopsy has been used for decades without a solid understanding of its efficacy, but offers the opportunity for simultaneous tissue acquisition via electromagnetic navigational transthoracic biopsy (EMN-TTNA) and staging via endobronchial ultrasound (EBUS). Objective: To evaluate the diagnostic yield of EBUS, ENB, and EMN-TTNA during a single procedure using a strict a priori definition of diagnostic yield with central pathology adjudication. Methods: A prospective, single-arm trial was conducted at eight centers enrolling participants with pulmonary nodules (<3 cm; without computed tomography [CT]- and/or positron emission tomography-positive mediastinal lymph nodes) who underwent a staged procedure with same-day CT, EBUS, ENB, and EMN-TTNA. The procedure was staged such that, when a diagnosis had been achieved via rapid on-site pathologic evaluation, the procedure was ended and subsequent biopsy modalities were not attempted. A study finding was diagnostic if an independent pathology core laboratory confirmed malignancy or a definitive benign finding. The primary endpoint was the diagnostic yield of the combination of CT, EBUS, ENB, and EMN-TTNA. Measurements and Main Results: A total of 160 participants at 8 centers with a mean nodule size of 18 ± 6 mm were enrolled. The diagnostic yield of the combined procedure was 59% (94 of 160; 95% confidence interval [CI], 51-66%). Nodule regression was found on same-day CT in 2.5% of cases (4 of 160; 95% CI, 0.69-6.3%), and EBUS confirmed malignancy in 7.1% of cases (11 of 156; 95% CI, 3.6-12%). The yield of ENB alone was 49% (74 of 150; 95% CI, 41-58%), that of EMN-TTNA alone was 27% (8 of 30; 95% CI, 12-46%), and that of ENB plus EMN-TTNA was 53% (79 of 150; 95% CI, 44-61%). Complications included a pneumothorax rate of 10% and a 2% bleeding rate. When EMN-TTNA was performed, the pneumothorax rate was 30%. Conclusions: The diagnostic yield for ENB is 49%, which increases to 59% with the addition of same-day CT, EBUS, and EMN-TTNA, lower than in prior reports in the literature. The high complication rate and low diagnostic yield of EMN-TTNA does not support its routine use. Clinical trial registered with www.clinicaltrials.gov (NCT03338049).

Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study.

BACKGROUND: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined. RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection? STUDY DESIGN AND METHODS: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria. RESULTS: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 109/L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare. INTERPRETATION: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.

A Review of Robotic-Assisted Bronchoscopy Platforms in the Sampling of Peripheral Pulmonary Lesions.

Robotic-assisted bronchoscopy is one of the newest additions to clinicians' armamentarium for the biopsy of peripheral pulmonary lesions in light of the suboptimal yields and sensitivities of conventional bronchoscopic platforms. In this article, we review the existing literature pertaining to the feasibility as well as sensitivity of available robotic-assisted bronchoscopic platforms.

Management of Pneumothorax.

Pneumothorax is a common medical condition encountered in a wide variety of clinical presentations, ranging from asymptomatic to life threatening. When symptomatic, it is important to remove air from the pleural space and provide re-expansion of the lung. Additionally, patients who experience a spontaneous pneumothorax are at high risk for recurrence, so treatment goals also include recurrence prevention. Several recent studies have evaluated less invasive management strategies for pneumothorax, including conservative or outpatient management. Future studies may help to identify who is greatest at risk for recurrence and direct earlier definitive management strategies, including thoracoscopic surgery, to those patients.

Lung Nodule Evaluation Using Robotic-Assisted Bronchoscopy at a Veteran's Affairs Hospital.

The incidence of lung nodules has increased with improved diagnostic imaging and screening protocols. Despite improvements for diagnosing pulmonary nodules with technologies such as electromagnetic navigational bronchoscopy (ENB), several limitations still exist including adequate visualization, localization, and diagnostic yield. Robotic-assisted bronchoscopy with ENB has been introduced as a method to overcome these shortcomings. We describe our initial experience in evaluating lung nodules with robotic assisted bronchoscopy. We retrospectively reviewed data on the first 25 patients that underwent robotic-assisted bronchoscopy and biopsy. We analyzed success with localization, diagnostic yield, and post procedural morbidity. Diagnostic yield was 96% (24/25) with no periprocedural morbidity. The majority of nodules were malignant or atypical (76%) and were located in the right upper lobe. Diameter ranged between 0.8-6.9 cm (median size 1-2 cm). Seventy-five percent of patients underwent subsequent treatment for cancer based on these results, with 25% having continued surveillance. Robotic assisted bronchoscopy is safe and accurate. Studies with larger numbers will allow better understanding of the diagnostic yield and clinical utility of this approach in comparison to other diagnostic tools for lung nodules.

Interventional Therapies for Central Airways.

Central airway obstruction (CAO) is a dangerous and increasingly common problem. CAO refers to lesions causing narrowing of the trachea or mainstem bronchi and is generally divided into malignant and nonmalignant categories. These 2 entities may be caused by a variety of thoracic and extrathoracic diseases. Imaging is critical during the initial assessment of CAO and may help thoracic physicians focus the differential diagnosis and plan the safest and most appropriate diagnostic and therapeutic interventions. However, direct visualization via flexible or rigid bronchoscopy is often necessary for diagnostic and treatment purposes. A large number of procedures can be performed through bronchoscopy, with the goal of relieving the obstruction and improving patency of the airway. Deciding which procedure to perform is based both upon the type of lesion and whether the lesion is due to a malignant or nonmalignant process. Possible interventions include mechanical debridement, laser therapy, argon plasma coagulation, electrocautery, brachytherapy, and stent placement. Immediate postoperative and follow-up imaging is crucial to monitor for immediate, subacute, and chronic complications as well as disease progression and recurrence.

Prospective Multicentered Safety and Feasibility Pilot for Endobronchial Intratumoral Chemotherapy.

BACKGROUND: Malignant airway obstruction (MAO) occurs in 30% of patients with advanced-stage lung cancer, leading to debilitating dyspnea, cough, and hemoptysis. Other than recanalization of the airways, these patients lack long-lasting palliative therapy. The goal of this study was to determine the safety and feasibility of local injection of paclitaxel into the airway wall with a novel microinjection catheter. METHODS: In this multicentered prospective trial, 23 patients with non-small cell lung cancer and MAO were enrolled from July 2014 through June 2016 to undergo rigid bronchoscopy with recanalization, followed by injection of 1.5 mg of paclitaxel with a novel injection catheter. Primary end points consisted of safety (adverse events, severe adverse events, and unanticipated adverse device effects) as well as feasibility (number of injections, injection success). Secondary end points consisted of airway patency improvement, quality of life metrics, and need for further interventions and/or stenting. RESULTS: Nineteen patients underwent rigid bronchoscopy with successful recanalization and paclitaxel injection. There were no adverse events, severe adverse events, or unanticipated adverse device effects. There was an average of 3.4 injections given for a total dose of 1.5 mg of paclitaxel in all patients. There was significantly less stenosis postprocedure vs preprocedure (25%-50% vs 75%-90%; P < .001), which was unchanged at 6 weeks (25%-50%). None of the participants required further interventions or airway stenting. CONCLUSIONS: The injection of paclitaxel after recanalization of MAO in patients with non-small cell lung cancer is safe and feasible, using a novel airway injection device. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02066103; URL: www.clinicaltrials.gov.

Bronchoscopic device intervention in chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease is a heterogeneous syndrome associated with varying degrees of parenchymal emphysema and airway inflammation resulting in decreased expiratory flow, lung hyperinflation, and symptoms leading to decreased exercise tolerance and quality of life. Impairment in lung function and quality of life persists following guideline-based medical therapy, thus surgical and minimally invasive bronchoscopic approaches were developed to address this unmet need. We offer a narrative review of the available technologies. RECENT FINDINGS: Although lung volume reduction surgery has been shown to improve survival in appropriately selected patients, it is infrequently performed. Less invasive bronchoscopic procedures have thus been explored including endobronchial valves, coils, lung sealant, thermal vapor, and other airway approaches. Selection criteria including severity of physiologic and radiographic impairment, degree of lung hyperinflation, presence of intact fissures, type of symptoms, and presence of comorbidities are critical in selecting appropriate candidates. SUMMARY: Recent advances in minimally invasive approaches to lung volume reduction have offered alternatives to surgical approaches. Two endobronchial valve devices are Food and Drug Administration approved for clinical use, and investigations into alternative bronchoscopic therapies to treat both emphysema and chronic bronchitis have been performed or are currently underway. Notably, each of these treatments requires unique selection criteria and thus a personalized approach to treatment.

Learning Electromagnetic Navigational Bronchoscopy and Percutaneous Transthoracic Needle Biopsy (LEAP): A Pilot Study.

BACKGROUND: Prior studies in pulmonology have examined the validity of procedural training tools, however, translation of simulation skill acquisition into real world competency remains understudied. We examine an assessment process with a simulation training course for electromagnetic navigational (EMN) bronchoscopy and percutaneous transthoracic needle aspiration (PTTNA). METHODS: A cohort study was conducted by subjects using EMN bronchoscopy and PTTNA. A procedural assessment tool was developed to measure basic competency for EMN bronchoscopy and PTTNA at 3 different time points: first simulation case, final simulation case upon reaching a competent score, and at their first live case. The assessment tool was divided into 4 domains (total score, 4 to 16; competency ≥12) with each domain requiring a passing score (1 to 4; competency ≥3.0). Complication and procedural time were collected during their first live case. RESULTS: Twenty-two serial procedures (12 EMN bronchoscopies, 10 EMN PTTNA) were observed by 14 subjects. The mean first simulation score for EMN bronchoscopy (4.66±0.89) improved after cadaver simulation (12.67±0.89, median 3 simulations attempts). The subjects' mean score for their first live case was 13.0±0.85 (self-reported score 12.5±1.07). For EMN PTTNA, the mean first simulation score (4.3±2.40) improved after cadaver simulation (12.6±1.51, median 3 simulation attempts). The subjects' mean score for their first live PTTNA case was 12.5±2.87 (self-reported score 12.1±1.05). There was only 1 minor complication. CONCLUSION: Learning EMN bronchoscopy/PTTNA is feasible using a structured simulation course with an assessment tool.

Minimally invasive palliative interventions in advanced lung cancer.

INTRODUCTION: Lung cancer is the leading cause of cancer-related deaths in the United States. Nearly 85% of all lung cancers are diagnosed at a late stage, with an associated five-year survival rate of 4%. Malignant central airway obstruction and malignant pleural effusions occur in upwards of 30% of these patients. Many of these patients are in need of palliative interventions for symptom control and to help improve their quality of life. Areas covered: This review covers the treatment modalities of malignant central airway obstruction and malignant pleural effusion. PubMed was used to search for the most up to date and clinically relevant articles that guide current treatment strategies. This review focuses on rigid bronchoscopy and the tools used for the relief of central airway obstruction, as well as intra-pleural catheter use and pleurodesis for the management of malignant pleural effusions. Expert commentary: There are multiple treatment modalities that may be used to help alleviate the symptoms of malignant central airway obstruction and pleural effusion. The modality used depends on the urgency of the situation, and specific patient's goals. An open dialog to understand the patient's end of life goals is an important factor when choosing the appropriate treatment strategy.

Study Design and Rationale: A Multicenter, Prospective Trial of Electromagnetic Bronchoscopic and Electromagnetic Transthoracic Navigational Approaches for the Biopsy of Peripheral Pulmonary Nodules (ALL IN ONE Trial).

BACKGROUND: Pulmonary nodules are a common but difficult issue for physicians as most identified on imaging are benign but those identified early that are cancerous are potentially curable. Multiple diagnostic options are available, ranging from radiographic surveillance, minimally invasive biopsy (bronchoscopy or transthoracic biopsy) to more invasive surgical biopsy/resection. Each technique has differences in diagnostic yield and complication rates with no established gold standard. Currently, the safest approach is bronchoscopic but it is limited by variable diagnostic yields. Percutaneous approaches are limited by nodule location and complications. With the recent advent of electromagnetic navigation (EMN), a combined bronchoscopic and transthoracic approach is now feasible in a single, staged procedure. Here, we present the study design and rationale for a single-arm trial evaluating a staged approach for the diagnosis of pulmonary nodules. METHODS: Participants with 1-3 cm, intermediate to high-risk pulmonary nodules will undergo a staged approach with endobronchial ultrasound (EBUS) followed by EMN-bronchoscopy (ENB), then EMN-transthoracic biopsy (EMN-TTNA) with the procedure terminated at any stage after a diagnosis is made via rapid onsite cytopathology. We aim to recruit 150 EMN participants from eight academic and community settings to show significant improvements over other historic bronchoscopic guided techniques. The primary outcome is overall diagnostic yield of the staged approach. CONCLUSION: This is the first study designed to evaluate the diagnostic yield of a staged procedure using EBUS, ENB and EMN-TTNA for the diagnosis of pulmonary nodules. If effective, the staged procedure will increase minimally invasive procedural diagnostic yield for pulmonary nodules.

External beam radiation therapy combined with airway stenting leads to better survival in patients with malignant airway obstruction.

BACKGROUND AND OBJECTIVE: Malignant airway obstruction (MAO), a common complication of patients with advanced lung cancer, causes debilitating dyspnoea and poor quality of life. Two common interventions used in the treatment of MAO include bronchoscopy with airway stenting and external beam radiotherapy (EBRT). Data are limited regarding their clinical effectiveness and overall effect on survival. METHODS: A retrospective chart review of patients treated with airway stenting and/or EBRT at the Johns Hopkins Hospital for MAO between July 2010 and January 2017 was reviewed. Demographics, performance status, cancer histology, therapeutic intervention and date of death were recorded. Survival was calculated using cox regression analysis. RESULTS: Of the 606 patients who were treated for MAO, 237 were identified as having MAO and included in the study. Sixty-eight patients underwent rigid bronchoscopy and stenting, 102 EBRT and 67 a combined approach. Patients who underwent stenting hand an increased hazard ratio (HR) of death in comparison to those who received combination therapy (HR: 2.12, 95% CI: 1.02, 4.39), while there was a trend towards significance in the EBRT alone group in comparison to the combination therapy group (HR: 1.62, 95% CI: 0.93, 2.83). CONCLUSION: In this retrospective analysis, combination therapy with stenting and EBRT led to better survival in comparison to stenting or EBRT alone. Prospective cohort trials are needed to confirm these results.

Procedural Learning Perspectives of Pulmonary Fellows and Practitioners.

BACKGROUND: Procedural learning requires both didactic knowledge and motor skills. Optimal teaching styles and techniques remain to be defined for pulmonary procedural learning. We investigated the preferences of learners at 2 different points in a pulmonary career; as pulmonary fellows and as clinical practitioners. METHODS: A perception survey was conducted among pulmonary fellows and practitioners from multiple institutions throughout the United States. Fellows and practitioners were immediately surveyed on procedural learning factors after completing a procedural learning course using low/high-fidelity and/or cadaver simulators. Survey questions consisting of biographical information and multiple choice, Likert style, and qualitative questions regarding learning preferences were collected. RESULTS: Seventy-five physicians (44 pulmonary fellows, 31 practitioners) from 35 centers completed the survey. Pulmonary practitioners preferred an academic expert, whereas fellows preferred familiar faculty as lecturers for procedural learning (P=0.03). There were no statistical differences between fellows/practitioners value of the use of simulators, didactics, or handouts. Both groups preferred animal/cadaver and high-fidelity simulators to low-fidelity simulators. Both groups also preferred a traditional course structure to problem-based learning/flipped classroom. The most common answer to barriers for learning a new procedure was "time" for training followed by "opportunities" to learn. CONCLUSIONS: Pulmonary fellows and practitioners we surveyed preferred a traditional course structure with cadaver/animal models and high-fidelity simulation training as compared with a flipped classroom model and low-fidelity simulators, but whether this holds true for the wider population is unknown. Larger studies are needed to validate learning perception with outcomes.

Stylet Use Does Not Improve Diagnostic Outcomes in Endobronchial Ultrasonographic Transbronchial Needle Aspiration: A Randomized Clinical Trial.

BACKGROUND: Endobronchial ultrasonographically guided transbronchial needle aspiration (EBUS-TBNA) of thoracic structures is a commonly performed tissue sampling technique. The use of an inner-stylet in the EBUS needle has never been rigorously evaluated and may be unnecessary. METHODS: In a prospective randomized single-blind controlled clinical trial, patients with a clinical indication for EBUS-TBNA underwent lymph node sampling using both with-stylet and without-stylet techniques. Sample adequacy, diagnostic yield, and various cytologic quality measures were compared. RESULTS: One hundred twenty-one patients were enrolled, with 194 lymph nodes sampled, each using both with-stylet and without-stylet techniques. There was no significant difference in sample adequacy or diagnostic yield between techniques. The without-stylet technique resulted in adequate samples in 87% of the 194 study lymph nodes, which was no different from the with-stylet adequacy rate (82%; P = .371). The with-stylet technique resulted in a diagnosis in 50 of 194 samples (25.7%), which was similar to the without-stylet group (49 of 194 [25.2%]; P = .740). There was a high degree of concordance in the determination of adequacy (84.0%; 95% CI, 78.1-88.9) and diagnostic sample generation (95.4%; 95% CI, 91.2-97.9) between the two techniques. A similar qualitative number of lymphocytes, malignant cells, and bronchial respiratory epithelia were recovered using each technique. CONCLUSIONS: Omitting stylet use during EBUS-TBNA does not affect diagnostic outcomes and reduces procedural complexity. TRIAL REGISTRY: ClinicalTrials.Gov: No. NCT 02201654; URL:www.clinicaltrials.gov.

A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer: HAL.

RATIONALE: Estimating the probability of finding N2 or N3 (prN2/3) malignant nodal disease on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with non-small cell lung cancer (NSCLC) can facilitate the selection of subsequent management strategies. OBJECTIVES: To develop a clinical prediction model for estimating the prN2/3. METHODS: We used the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) registry to identify patients with NSCLC with clinical radiographic stage T1-3, N0-3, M0 disease that had EBUS-TBNA for staging. The dependent variable was the presence of N2 or N3 disease (vs. N0 or N1) as assessed by EBUS-TBNA. Univariate followed by multivariable logistic regression analysis was used to develop a parsimonious clinical prediction model to estimate prN2/3. External validation was performed using data from three other hospitals. MEASUREMENTS AND MAIN RESULTS: The model derivation cohort (n = 633) had a 25% prevalence of malignant N2 or N3 disease. Younger age, central location, adenocarcinoma histology, and higher positron emission tomography-computed tomography N stage were associated with a higher prN2/3. Area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.82-0.89), model fit was acceptable (Hosmer-Lemeshow, P = 0.62; Brier score, 0.125). We externally validated the model in 722 patients. Area under the receiver operating characteristic curve was 0.88 (95% confidence interval, 0.85-0.90). Calibration using the general calibration model method resulted in acceptable goodness of fit (Hosmer-Lemeshow test, P = 0.54; Brier score, 0.132). CONCLUSIONS: Our prediction rule can be used to estimate prN2/3 in patients with NSCLC. The model has the potential to facilitate clinical decision making in the staging of NSCLC.

Same-Day Computed Tomographic Chest Imaging for Pulmonary Nodule Targeting with Electromagnetic Navigation Bronchoscopy May Decrease Unnecessary Procedures.

RATIONALE: Bronchoscopy is commonly used for the diagnosis of suspicious pulmonary nodules discovered on computed tomographic (CT) imaging of the chest. Procedural CT imaging for bronchoscopy planning is often completed weeks to months before the date of a scheduled bronchoscopy, which may not allow discovery of a decrease in nodule size or resolution before the bronchoscopic procedure. OBJECTIVES: To determine whether same-day CT imaging of the chest discovers partial or total resolution of some lung nodules and thereby reduces unnecessary bronchoscopic procedures. METHODS: We performed a prospective case series study of patients undergoing navigational bronchoscopy using a new technology requiring same-day preprocedural CT imaging at one university teaching hospital. Patients scheduled to undergo bronchoscopy who were found to have partial or complete resolution of their lesion on the same-day CT exam leading to the cancellation of their procedure were identified and further characterized. MEASUREMENTS AND MAIN RESULTS: From January 2015 to June 2016, 116 patients were scheduled for navigational bronchoscopy for the diagnosis of a pulmonary lesion. Of the 116 patients scheduled, 8 (6.9%) had a decrease in size or resolution of their lesion, leading to the cancellation of their procedure. The number needed to screen to prevent one unnecessary procedure was 15. For cancelled cases, the average time from initial CT prompting referral for bronchoscopy to the day of procedure scan was 53 days. CONCLUSIONS: Time from initial imaging to day of procedure is variable, occasionally allowing enough time for lesions to resolve, thereby obviating the need for biopsy. Same-day imaging may decrease unnecessary procedural risk.