Evaluating Diff-Quik cytology smears for large-panel mutation testing in lung cancer-Predicting DNA content and success with low-malignant-cellularity samples.

BACKGROUND: Cytology smears are commonly collected during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) procedures but are rarely used for molecular testing. Studies are needed to demonstrate their great potential, in particular for the prediction of malignant cell DNA content and for utility in molecular diagnostics using large gene panels. METHODS: A prospective study was performed on samples from 66 patients with malignant lymph nodes who underwent EBUS TBNA. All patients had air-dried, Diff-Quik cytology smears and formalin-fixed, paraffin-embedded cell blocks collected for cytopathology and molecular testing. One hundred eighty-five smears were evaluated by microscopy to estimate malignant cell percentage and abundance and to calculate smear size and were subjected to DNA extraction. DNA from 56 smears from 27 patients was sequenced with the TruSight Oncology 500 assay (Illumina). RESULTS: Each microscopy parameter had a significant effect on the DNA yield. An algorithm was developed that predicted a >50-ng DNA yield of a smear with an area under the curve of 0.86. Fifty DNA samples (89%) with varying malignant yields were successfully sequenced. Low-malignant-cell content (<25%) and smear area (<15%) were the main reasons for failure. All standard-of-care mutations were detected in replicate smears from individual patients, regardless of malignant cell content. Tier 1/2 mutations were discovered in two cases where standard-of-care specimens were inadequate for sequencing. Smears were scored for tumor mutation burden. CONCLUSIONS: Microscopy of Diff-Quik smears can triage samples for comprehensive panel sequencing, which highlights smears as an excellent alternative to traditional testing with cell blocks.

A randomised study of comfort during bronchoscopy comparing conscious sedation and anaesthetist-controlled general anaesthesia, including the utility of bispectral index monitoring.

BACKGROUND: The difference in patient comfort with conscious sedation versus general anaesthesia for bronchoscopy has not been adequately assessed in a randomised trial. This study aimed to assess if patient comfort during bronchoscopy with conscious sedation is noninferior to general anaesthesia. METHODS: 96 subjects were randomised to receive conscious sedation or general anaesthesia for bronchoscopy. The primary outcome was subject comfort. Secondary outcomes included willingness to undergo a repeat procedure if necessary and level of sedation assessed clinically and by bispectral index (BIS) monitoring. RESULTS: There was no significant difference between subject comfort scores (difference -0.01, 95% CI -0.63-0.61 on a 10-point scale; p=0.97) or willingness to undergo a repeat procedure (97.7% versus 91.8%, 95% CI -4.8-15.5%; p=0.37). Deeper levels of sedation in the general anaesthesia cohort was confirmed with both clinical and BIS monitoring. There was no significant difference in diagnostic accuracy (conscious sedation 93.9%, 95% CI 80.4-98.3% versus general anaesthesia 86.5%, 95% CI 72.0-94.1%; p=0.43). There were more complications (29.6%, 95% CI 18.2-44.2% versus 6.1%, 95% CI 2.1-16.5%; p<0.01) in the general anaesthesia group. There was no relationship between high BIS scores and subject discomfort. BIS levels <40 during a procedure were associated with increased complications. CONCLUSION: Conscious sedation is not inferior to general anaesthesia in providing patient comfort during bronchoscopy, despite lighter sedation, and is associated with fewer complications and comparable diagnostic accuracy. BIS monitoring may have a role in preventing complications associated with deeper sedation.

First Human Use of a New Robotic-Assisted Fiber Optic Sensing Navigation System for Small Peripheral Pulmonary Nodules.

BACKGROUND: We tested a new, investigational robotic-assisted bronchoscope system with a remotely controlled catheter to access small peripheral bronchi with real-time driving under live visualization and distal tip articulation of the catheter. The unique catheter remains stationary once located at the biopsy position. OBJECTIVES: The primary objectives of this study were to evaluate the safety and feasibility of a new shape-sensing robotic bronchoscope system to bronchoscopically approach and facilitate the sampling of small peripheral pulmonary nodules of 1-3 cm. Secondary objectives included evaluating procedural characteristics and early performance trends associated with the use of the new robotic bronchoscope system. METHODS: Subjects were enrolled according to study eligibility criteria at a single center. Navigation pathways were semi-automatically created using pre-procedure CT scans. Simultaneous (real-time) viewing of actual and virtual bronchi was used real time during navigation to the displayed target. An endobronchial ultrasound mini-probe was used to confirm lesion location. Flexible 19- to 23-G needles specifically designed to accommodate tight bend radii in transbronchial needle aspiration were used along with conventional biopsy tools. Enrolled subjects completed follow-up visits up to 6 months after the procedure. RESULTS: The study included 29 subjects with a mean lesion size of 12.2 ± 4.2, 12.3 ± 3.3, and 11.7 ± 4.1 mm in the axial, coronal, and sagittal planes, respectively. The CT bronchus sign was absent in 41.4% of cases. In 96.6% of cases, the target was reached, and samples were obtained. No device-related adverse events and no instances of pneumothorax or excessive bleeding were observed during the procedure. Early performance trends demonstrated an overall diagnostic yield of 79.3% and a diagnostic yield for malignancy of 88%. CONCLUSION: This new robotic-assisted bronchoscope system safely navigated to very small peripheral airways under continuous visualization, and through maintenance of a static position, it provides a unique sampling capability for the biopsy of small solitary pulmonary nodules.

Expiratory reactance abnormalities in patients with expiratory dynamic airway collapse: a new application of impulse oscillometry.

Expiratory dynamic airways collapse (EDAC) is a condition that affects the central airways; it is not well characterised physiologically, with relatively few studies. We sought to characterise impulse oscillometry (IOS) features of EDAC in patients with normal spirometry. Expiratory data were hypothesised to be the most revealing. In addition, we compared IOS findings in chronic obstructive pulmonary disease (COPD) patients with and without EDAC. EDAC was identified at bronchoscopy as 75-100% expiratory closure at the carina or bilateral main bronchi. Four patient groups were compared: controls with no EDAC and normal lung function; lone EDAC with normal lung function; COPD-only patients; and COPD patients with EDAC. 38 patients were studied. Mean IOS data z-scores for EDAC compared to controls showed significantly higher reactance (X) values including X at 5 Hz, resonance frequency and area under the reactance curve (AX). EDAC showed significantly greater expiratory/inspiratory differences in all IOS data compared to controls. Stepwise logistic regression showed that resonant frequency best discriminated between EDAC and normal control, whereas classification and regression tree analysis found AX ≥3.523 to be highly predictive for EDAC in cases with normal lung function (14 out of 15 cases, and none out of eight controls). These data show a new utility of IOS: detecting EDAC in patients with normal lung function.

Distinguishing Bronchoscopic Changes of Mitral Stenosis From Carcinoma In Situ With Narrow Band Imaging.

A 75-year-old woman presented with minor hemoptysis. Past history included atrial fibrillation and rheumatic mitral stenosis. Bronchoscopy revealed a striking abnormality of widespread dilated mucosal and submucosal vessels. Initially the concern was whether there was widespread endobronchial malignancy; however, narrow band imaging (NBI) demonstrated the symmetrical uniform nature of the vessels. In addition, there was a focal area of in situ carcinoma with classic NBI features of malignancy. Following external-beam radiation therapy, NBI features had dramatically changed in the treated area which was now biopsy negative. The case highlights the utility of NBI in identifying endobronchial microvessel appearance even where there are widespread nonmalignant vessel changes in the bronchial mucosa.

A new instrument to assess physician skill at chest tube insertion: the TUBE-iCOMPT.

Currently no tool exists to assess proceduralist skill at chest tube insertion. As inadequate doctor procedural competence has repeatedly been associated with adverse events, there is a need for a tool to assess procedural competence. This study aims to develop and examine the validity of a tool to assess competency at insertion of a chest tube, using either the Seldinger technique or blunt dissection. A 5-domain 100-point assessment tool was developed inline with British Thoracic Society guidelines and international consensus­the Chest Tube Insertion Competency Test (TUBE-iCOMPT). The instrument was used to assess chest tube insertion in mannequins and live patients. 29 participants (9 novices, 14 intermediate and 6 advanced) were tested by 2 blinded expert examiners on 2 occasions. The tool's validity was examined by demonstrating: (1) stratification of participants according to expected level of expertise (analysis of variance), and (2) test-retest and intertester reliability (intraclass correlation coefficient). The intraclass correlation coefficient of repeated scores for the Seldinger technique and blunt dissection, were 0.92 and 0.91, respectively, for test-retest results, and 0.98 and 0.95, respectively, for intertester results. Clear stratification of scores according to participant experience was seen (p<0.0001). There was no significant difference between scores obtained using mannequins or live patients. This study has validated the TUBE-iCOMPT, which could now be incorporated into chest tube insertion training programmes, providing a way to document acquisition of skill, guide individualised teaching, and assist with the assessment of the adequacy of clinician training.

Novel use of pleural ultrasound can identify malignant entrapped lung prior to effusion drainage.

BACKGROUND: The presence of entrapped lung changes the appropriate management of malignant pleural effusion from pleurodesis to insertion of an indwelling pleural catheter. No methods currently exist to identify entrapped lung prior to effusion drainage. Our objectives were to develop a method to identify entrapped lung using tissue movement and deformation (strain) analysis with ultrasonography and compare it to the existing technique of pleural elastance (PEL). METHODS: Prior to drainage, 81 patients with suspected malignant pleural effusion underwent thoracic ultrasound using an echocardiogram machine. Images of the atelectatic lower lobe were acquired during breath hold, allowing motion and strain related to the cardiac impulse to be analyzed using motion mode (M mode) and speckle-tracking imaging, respectively. PEL was measured during effusion drainage. The gold-standard diagnosis of entrapped lung was the consensus opinion of two interventional pulmonologists according to postdrainage imaging. Participants were randomly divided into development and validation sets. RESULTS: Both total movement and strain were significantly reduced in entrapped lung. Using data from the development set, the area under the receiver-operating curves for the diagnosis of entrapped lung was 0.86 (speckle tracking), 0.79 (M mode), and 0.69 (PEL). Using respective cutoffs of 6%, 1 mm, and 19 cm H2O on the validation set, the sensitivity/specificity was 71%/85% (speckle tracking), 50%/85% (M mode), and 40%/100% (PEL). CONCLUSIONS: This novel ultrasound technique can identify entrapped lung prior to effusion drainage, which could allow appropriate choice of definitive management (pleurodesis vs indwelling catheter), reducing the number of interventions required to treat malignant pleural effusion.

Achieving competency in bronchoscopy: challenges and opportunities.

Bronchoscopy education is undergoing significant changes in step with other medical and surgical specialties that seek to incorporate simulation-based training and objective measurement of procedural skills into training programmes. Low- and high-fidelity simulators are now available and allow learners to gain fundamental bronchoscopy skills in a zero-risk environment. Testing trainees on simulators is currently possible by using validated assessment tools for both essential bronchoscopy and endobronchial ultrasound skills, and more tools are under development for other bronchoscopic techniques. Educational concepts including the 'flipped classroom' model and problem-based learning exercises are increasingly used in bronchoscopy training programmes. These learner-centric teaching modalities require well-trained educators, which is possible thorough the expansion of existing faculty development programmes.

EBUS-TBNA/staging of lung cancer.

In the staging of mediastinal lymph nodes before lung cancer surgery, endobronchial ultrasound transbronchial needle aspirations (EBUS-TBNA) have proven to be highly sensitive and specific as well as safe. Although positron emission tomography/computed tomography (PET/CT) has been a major development in the preoperative workup of patients with lung cancer, EBUS-TBNA has superior test performance and PET/CT cannot be regarded as a substitute for tissue sampling with EBUS-TBNA. In general, EBUS-TBNA staging is needed for any patient with CT nodes greater than 1 cm in short axis, or PET-positive mediastinal nodes.