Sight Unseen: Diagnostic Yield and Safety Outcomes of a Novel Multimodality Navigation Bronchoscopy Platform with Real-Time Target Acquisition.

BACKGROUND: Several advanced bronchoscopy platforms are currently available, but the clinical data supporting their use vary. Electromagnetic navigation bronchoscopy (ENB) remains the dominant technology; it is limited by its reliance on preoperative computed tomography, which only approximates patient anatomy during the procedure. Recently, ENB was enhanced with the (1) addition of digital tomosynthesis-based navigation correction, (2) improvements in planning algorithms, and (3) continuous real-time guidance (Illumisite™; Medtronic, Minneapolis, MN, USA). There are currently no clinical data on the diagnostic yield and safety profile of this system. OBJECTIVES: The primary objective of this study is to describe the diagnostic yield of the first 100 pulmonary parenchymal lesions sampled using the multimodality navigation bronchoscopy (MNB) platform. The secondary objective is to describe safety. METHODS: In this single-center prospective observational study, a database was maintained to track patient, procedural, and outcome data for the first 100 consecutive lesions sampled using the MNB platform at an academic quaternary referral center. Descriptive statistics and univariate and multivariate analyses are reported. RESULTS: The overall diagnostic yield of samples acquired was 79% (79/100). In the cohort where digital tomosynthesis was used, the diagnostic yield was 83% (69/83). Sensitivity for malignancy was 71% (52/73). Overall complication rates were low: pneumothorax (n = 3, 3%) and bleeding requiring intervention (n = 2, 2%). There were no procedural-related hospital admissions. CONCLUSIONS: The MNB system performed favorably. Platform superiority cannot be established without future prospective and comparative studies.

High Accuracy of Digital Tomosynthesis-Guided Bronchoscopic Biopsy Confirmed by Intraprocedural Computed Tomography.

BACKGROUND: Digital fluoroscopic tomosynthesis-guided electromagnetic navigational bronchoscopy (F-ENB) is a novel adjunct to ENB associated with higher diagnostic yield. The likelihood of F-ENB allowing accurate placement of a biopsy needle within a target remains unclear. OBJECTIVE: This study intends to determine the accuracy of F-ENB as confirmed by cone-beam computed tomography (CBCT) scan. METHODS: Patients undergoing CBCT-assisted ENB for lung nodule biopsy were prospectively enrolled. ENB was performed followed by digital tomosynthesis correction. Once optimal F-ENB alignment was achieved, and a needle was advanced into the expected location of the nodule followed by CBCT. The primary outcome was the percentage of "needle-in-lesion" hits, defined as needle tip within the nodule in 3 planes. Secondary outcomes were diagnostic yield, procedure and room time, complications, radiation, and distance between the needle tip and nodule. RESULTS: Twenty-six patients with a total of 29 nodules were enrolled. Mean nodule size was 13 mm (±4 mm) in maximal axial dimension, 83% (n = 24) were located in the peripheral third of the chest, and 17% (n = 5) had a bronchus sign. F-ENB guidance resulted in needle-in-lesion in 21 of 29 nodules (72%). Mean needle tip-to-nodule distance for nonhits was 1.75 mm (±1.35 mm). There were no complications. CONCLUSION: F-ENB resulted in a needle-in-lesion biopsy in greater than 70% of nodules despite features traditionally associated with poor diagnostic yield (size, absence of bronchus sign). Mean distance between needle tip and target for nonhits was less than 2 mm. These data suggest F-ENB alignment is accurate for small peripheral nodules.

Shape-Sensing Robotic-Assisted Bronchoscopy vs Digital Tomosynthesis-Corrected Electromagnetic Navigation Bronchoscopy: A Comparative Cohort Study of Diagnostic Performance.

BACKGROUND: Electromagnetic navigational bronchoscopy has been the dominant bronchoscopic technology for targeting small peripheral lesions and now includes digital tomosynthesis-electromagnetic navigational bronchoscopy (DT-ENB), allowing near-real-time intraprocedural nodule visualization. Shape-sensing robotic-assisted bronchoscopy (ssRAB), with improved catheter stability and articulation recently became available. Although the diagnostic performance of these two methods seems higher than that of legacy systems, data remain limited. We sought to compare the diagnostic yield of these two novel platforms after their introduction at our institution. RESEARCH QUESTION: Does the diagnostic yield of ssRAB differ significantly from that of DT-ENB in patients undergoing biopsy of peripheral pulmonary lesions (PPLs)? STUDY DESIGN AND METHODS: This retrospective comparative cohort study analyzed prospectively collected data on consecutive procedures performed with DT-ENB and ssRAB in their first 6 months of use at our institution. Biopsies were considered diagnostic if histopathologic analysis revealed malignancy or specific benign features that readily explained the presence of a PPL. Nonspecific inflammation, normal lung or airway, and atypia not diagnostic of malignancy were considered nondiagnostic. RESULTS: SSRAB was used to biopsy 143 PPLs in 133 patients and DT-ENB was used to biopsy 197 PPLs in 170 patients. Diagnostic yield was 77% for ssRAB (110 of 143 PPLs) and 80% (158 of 197 PPLs) for DT-ENB (OR, 0.8; 95% CI, 0.5-1.4; P = .4). Median lesion diameters were 17 and 19 mm, respectively. No difference in diagnostic yield was found after adjustment for lesion size, bronchus sign, peripheral vs middle third location, and sex. Pneumothorax complicated 1.5% of ssRAB and 1.8% of DT-ENB procedures (P = .86). INTERPRETATION: SSRAB and DT-ENB showed comparable diagnostic yields and safety profiles in this comparative cohort study.

Navigational Bronchoscopy versus Computed Tomography-guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: protocol and rationale for the VERITAS multicenter randomized trial.

Background: Lung nodule incidence is increasing. Many nodules require biopsy to discriminate between benign and malignant etiologies. The gold-standard for minimally invasive biopsy, computed tomography-guided transthoracic needle biopsy (CT-TTNB), has never been directly compared to navigational bronchoscopy, a modality which has recently seen rapid technological innovation and is associated with improving diagnostic yield and lower complication rate. Current estimates of the diagnostic utility of both modalities are based largely on non-comparative data with significant risk for selection, referral, and publication biases. Methods: The VERITAS trial (na V igation E ndoscopy to R each Indeterminate lung nodules versus T ransthoracic needle A spiration, a randomized controlled S tudy) is a multicenter, 1:1 randomized, parallel-group trial designed to ascertain whether electromagnetic navigational bronchoscopy with integrated digital tomosynthesis is noninferior to CT-TTNB for the diagnosis of peripheral lung nodules 10-30 mm in diameter with pre-test probability of malignancy of at least 10%. The primary endpoint is diagnostic accuracy through 12 months follow-up. Secondary endpoints include diagnostic yield, complication rate, procedure duration, need for additional invasive diagnostic procedures, and radiation exposure. Discussion: The results of this rigorously designed trial will provide high-quality data regarding the management of lung nodules, a common clinical entity which often represents the earliest and most treatable stage of lung cancer. Several design challenges are described. Notably, all nodules are centrally reviewed by an independent interventional pulmonology and radiology adjudication panel relying on pre-specified exclusions to ensure enrolled nodules are amenable to sampling by both modalities while simultaneously protecting against selection bias favoring either modality. Conservative diagnostic yield and accuracy definitions with pre-specified criteria for what non-malignant findings may be considered diagnostic were chosen to avoid inflation of estimates of diagnostic utility. Trial registration: ClinicalTrials.gov NCT04250194.

Association between terminal pleural elastance and radiographic lung re-expansion after therapeutic thoracentesis in patients with symptomatic pleural effusion: a post-hoc analysis of a randomised trial.

OBJECTIVES: Recurrent symptomatic effusions can be durably managed with pleurodesis or placement of indwelling pleural catheters. Recent pleurodesis trials have largely relied on lung re-expansion on post-thoracentesis radiograph as an inclusion criterion rather than pleural elastance as determined by manometry, which is an important predictor of successful pleurodesis. We investigated the association between lung re-expansion on post-pleural drainage chest imaging and pleural physiology, with particular attention to pleural elastance over the final 200 mL aspirated. DESIGN: Post-hoc analysis of a recent randomised trial. SETTING AND PARTICIPANTS: Post-results analysis of 61 subjects at least 18 years old with symptomatic pleural effusions estimated to be at least of 0.5 L in volume allocated to manometry-guided therapeutic thoracentesis in a recent randomised trial conducted at two major university hospitals in the USA. PRIMARY OUTCOME MEASURES: The primary outcome was concordance of radiographic with normal terminal pleural elastance over the final 200 mL aspirated. We label this terminal elastance 'visceral pleural recoil', or the tendency of the maximally expanded lung to withdraw from the chest wall. RESULTS: Post-thoracentesis chest radiograph and thoracic ultrasound indicated successful lung re-expansion in 69% and 56% of cases, respectively. Despite successful radiographic lung re-expansion, visceral pleural recoil was abnormal in 71% of subjects expandable by radiograph and 77% expandable by ultrasound. The sensitivity and positive predictive value of radiographic lung re-expansion for normal visceral pleural recoil were 44% and 24%, respectively. CONCLUSION: Radiographic lung re-expansion by post-thoracentesis chest radiograph or thoracic ultrasound is a poor surrogate for normal terminal pleural elastance. Clinical management of patients with recurrent symptomatic pleural effusions guided by manometry rather than post-thoracentesis imaging might produce better outcomes, which should be investigated by future clinical trials. TRIAL REGISTRATION NUMBER: NCT02677883; Post-results.

Advanced Bronchoscopic Technologies for Biopsy of the Pulmonary Nodule: A 2021 Review.

The field of interventional pulmonology (IP) has grown from a fringe subspecialty utilized in only a few centers worldwide to a standard component in advanced medical centers. IP is increasingly recognized for its value in patient care and its ability to deliver minimally invasive and cost-effective diagnostics and treatments. This article will provide an in-depth review of advanced bronchoscopic technologies used by IP physicians focusing on pulmonary nodules. While most pulmonary nodules are benign, malignant nodules represent the earliest detectable manifestation of lung cancer. Lung cancer is the second most common and the deadliest cancer worldwide. Differentiating benign from malignant nodules is clinically challenging as these entities are often indistinguishable radiographically. Tissue biopsy is often required to discriminate benign from malignant nodule etiologies. A safe and accurate means of definitively differentiating benign from malignant nodules would be highly valuable for patients, and the medical system at large. This would translate into a greater number of early-stage cancer detections while reducing the burden of surgical resections for benign disease. There is little high-grade evidence to guide clinicians on optimal lung nodule tissue sampling modalities. The number of novel technologies available for this purpose has rapidly expanded over the last decade, making it difficult for clinicians to assess their efficacy. Unfortunately, there is a wide variety of methods used to determine the accuracy of these technologies, making comparisons across studies impossible. This paper will provide an in-depth review of available data regarding advanced bronchoscopic technologies.

Diagnostic Yield of Digital Tomosynthesis-assisted Navigational Bronchoscopy for Indeterminate Lung Nodules.

BACKGROUND: Navigational bronchoscopy is commonly used to sample lung nodules, with a better safety profile but lower diagnostic yield than computerized tomography-guided transthoracic needle biopsy. The addition of digital tomosynthesis to electromagnetic navigation, using intraprocedural images obtained from a C-arm fluoroscope to identify target lesion location and update navigational guidance, may improve diagnostic yield. METHODS: Consecutive bronchoscopies using tomosynthesis-assisted fluoroscopic electromagnetic navigational bronchoscopy (F-ENB) at a single institution over a 1-year period were included. The primary outcome was diagnostic yield. A bronchoscopy was defined as diagnostic if pathologic examination revealed malignancy or specific histological findings indicative of lesional sampling with confirmatory 6-month follow-up for benign lesions. RESULTS: A total of 324 patients with 363 nodules underwent F-ENB between April 25, 2018 and April 29, 2019. The average nodule size was 1.9±1.1 cm, 65% of the nodules were located in the peripheral third of the lung. A bronchus sign was present in 24% of cases. Of the 363 nodules, 299 (82.4%) had lesional findings. At 6-month follow-up, among these 299 nodules, 6 were found to be false negatives and 12 nodules were lost to follow-up. Considering all nodules lost to follow-up as false negatives, the 6-month diagnostic yield was 77.4%. Pneumothorax complicated 8 (2.5%) of cases. There was 1 episode of respiratory failure. CONCLUSION: This retrospective study suggests the diagnostic yield of F-ENB may exceed that of traditional ENB. Future prospective and comparative studies are needed to confirm these promising data.

Venovenous extracorporeal membrane oxygenation during high-risk airway interventions.

OBJECTIVES: Practice patterns for the use of extracorporeal membrane oxygenation (ECMO) during high-risk airway interventions vary, and data are limited. We aim to characterize our recent experience using ECMO for procedural support during whole-lung lavage (WLL) and high-risk bronchoscopy for central airway obstruction (CAO). METHODS: We performed a retrospective cohort study of adults who received ECMO during WLL and high-risk bronchoscopy from 1 July 2018 to 30 March 2020. Our primary end point was successful completion of the intervention. Secondary end points included ECMO-associated complications and hospital survival. RESULTS: Eight patients received venovenous ECMO for respiratory support during 9 interventions; 3 WLLs for pulmonary alveolar proteinosis were performed in 2 patients, and 6 patients underwent 6 bronchoscopic interventions for CAO. We initiated ECMO prior to the intervention in 8 cases and during the intervention in 1 case for respiratory decompensation. All 9 interventions were successfully completed. Median ECMO duration was 17.8 h (interquartile range, 15.9-26.6) for the pulmonary alveolar proteinosis group and 1.9 h (interquartile range, 1.4-8.1) for the CAO group. There was 1 cannula-associated deep vein thrombosis; there were no other ECMO complications. Seven patients (87.5%) and 4 (50.0%) patients survived to discharge and 1 year postintervention, respectively. CONCLUSIONS: Use of venovenous ECMO to facilitate high-risk airway interventions is safe and feasible. Planned preprocedural ECMO initiation may prevent avoidable respiratory emergencies and extend therapeutic airway interventions to patients otherwise considered too high-risk to treat. Guidelines are needed to inform the utilization of ECMO during high-risk bronchoscopy and other airway interventions.

Bronchoscopic biopsy of peripheral pulmonary lesions in 2020: a review of existing technologies.

There are over 200,000 new cases of lung cancer diagnosed annually in the United States resulting in nearly 150,000 deaths, making lung cancer the most lethal of all forms of cancer. Only 1 in 6 lung cancers are diagnosed at an early stage an over half are diagnosed with distant metastasis. Despite advances in screening and treatment, the 5-year survival rate for all lung cancers remains low, around 20%. The advent of effective lung cancer screening with low-dose computed tomography has started to shift diagnosis to earlier stages. Screening, along with the ever-increasing use of chest CT, have led to an exponential increase in the detection of indeterminate lung nodules. For many nodules, effective diagnosis relies on invasive tissue sample collection. Advances in bronchoscopic technology have allowed for safe and increasingly effective tissue diagnosis of these nodules; however, inconsistencies across studies evaluating diagnostic yield remain. This review will provide an overview of the advanced bronchoscopic technologies currently in wide use, the quality of data supporting their use, some of the perceived weaknesses and strengths of each technology, and introduce promising emerging diagnostic platforms poised to advance the field. Ultimately, quality comparative research is needed to accurately characterize the diagnostic test performance of currently available bronchoscopic platforms, improve the efficacy of bronchoscopy-generated diagnostic yields while maintaining, their strong safety profile.

Minimal clinically important difference for chest discomfort in patients undergoing pleural interventions.

RATIONALE: Therapeutic thoracentesis is among the most frequently performed medical procedures. Chest discomfort is a common complication and has been associated with increasingly negative pleural pressure as fluid is withdrawn in the setting of non-expendable lung. Visual analogue scales (VASs) are commonly employed to measure changes in discomfort and dyspnoea related to pleural interventions. The minimal clinically important difference (MCID), defined as the smallest change in VAS score associated with patient report of significant change in a symptom, is required to interpret the results of studies using VAS scores and is used in clinical trial power calculations. The MCID for chest discomfort in patients undergoing pleural interventions has not been determined. METHODS: Prospectively collected data from two recent randomised trials of therapeutic thoracentesis were used for this investigation. Adult patients with symptomatic pleural effusions referred for therapeutic thoracentesis were enrolled across ten US academic medical centres. Patients were asked to rate their level of chest discomfort on 100 mm VAS before, during and following thoracentesis. Patients then completed a 7-point Likert scale indicating the significance of any change in chest discomfort from preprocedure to postprocedure. The mean difference between discomfort 5 min postprocedure and discomfort just prior to the start of pleural fluid drainage was categorised by Likert scale response. RESULTS: Data from a total of 262 thoracenteses were included in the analysis. Thirty-four of 262 patients experienced a 'small but significant increase' or a 'large or moderate increase' in discomfort following thoracentesis. The mean increase in VAS score in those reporting a 'small but significant increase' in chest discomfort (n=23) was 16 mm (SD 22.44, 95% CI 6.87 to 25.21). CONCLUSIONS: The MCID for thoracentesis-related chest discomfort measured by 100 mm VAS is 16 mm. This MCID specific to discomfort resulting from pleural fluid interventions can inform the design and analysis of future pleural intervention studies.