Controversies in endobronchial ultrasound.

Endobronchial ultrasound (EBUS) is a minimally invasive highly accurate and safe endoscopic technique for the evaluation of mediastinal lymphadenopathy and mediastinal masses including centrally located lung tumors. The combination of transbronchial and transoesophageal tissue sampling has improved lung cancer staging, reducing the need for more invasive and surgical diagnostic procedures. Despite the high level of evidence regarding EBUS use in the aforementioned situations, there are still challenges and controversial issues such as follows: Should informed consent for EBUS and flexible bronchoscopy be different? Is EBUS able to replace standard bronchoscopy in patients with suspected lung cancer? Which is the best position, screen orientation, route of intubation, and sedation/anesthesia to perform EBUS? Is it advisable to use a balloon in all procedures? How should the operator acquire skills and how should competence be ensured? This Pro-Con article aims to address these open questions.

Patient-Reported Outcome Measures in Patients with and without Non-Expandable Lung Secondary to Malignant Pleural Effusion-A Single-Centre Observational Study.

BACKGROUND: Malignant pleural effusion (MPE) affects up to 15% of patients with malignancy, and the prevalence is increasing. Non-expandable lung (NEL) complicates MPE in up to 30% of cases. However, it is not known if patients with malignant pleural effusion and NEL are more symptomatic in activities of daily living compared to patients with MPE with expandable lung. METHODS: This was an observational study on consecutively recruited patients with MPE from our pleural clinic. Before thoracentesis, patients completed patient-reported outcomes on cancer symptoms (ESAS), health-related quality of life (5Q-5D-5L), and dyspnoea scores. Following thoracentesis, patients scored dyspnoea relief and symptoms during thoracentesis. Data on focused lung ultrasound and pleural effusion biochemistry were collected. The non-expandable lung diagnosis was made by pleural experts based on radiological and clinical information. RESULTS: We recruited 43 patients, including 12 with NEL (28%). The NEL cohort resembled those from previous studies concerning ultrasonography, pleural fluid biochemistry, and fewer cases with high volume thoracentesis. Patients with and without NEL were comparable concerning baseline demography. The 5Q-5D-5L utility scores were 0.836 (0.691-0.906) and 0.806 (0.409-0.866), respectively, for patients with and without NEL. We observed no between-group differences in symptom burden or health-related quality of life. CONCLUSION: While the presence of NEL affects the clinical management of recurrent MPE, the presence of NEL seems not to affect patients' overall symptom burden in patients with MPE.

Erratum: Local Anesthetic Thoracoscopy for Undiagnosed Pleural Effusion.

An erratum was issued for: Local Anesthetic Thoracoscopy for Undiagnosed Pleural Effusion. The Authors section was updated from: Uffe Bodtger1,2 José M. Porcel3 Rahul Bhatnagar4,5 Mohammed Munavvar6,7 Casper Jensen1 Paul Frost Clementsen1,8 Daniel Bech Rasmussen1,2 1Respiratory Research Unit PLUZ, Department of Respiratory Medicine, Zealand University Hospital 2Institute of Regional Health Research, University of Southern Denmark 3Pleural Medicine Unit, Department of Internal Medicine, Hospital Universitari Arnau de Vilanova, IRBLleida 4Respiratory Department, Southmead Hospital, North Bristol NHS Trust 5Academic Respiratory Unit, University of Bristol 6Lancashire Teaching Hospitals 7University of Central Lancashire 8Centre for HR and Education, Copenhagen Academy for Medical Education and Simulation to: Uffe Bodtger1,2 José M. Porcel3 Rahul Bhatnagar4,5 Nick Maskell4,5 Mohammed Munavvar6,7 Casper Jensen1 Paul Frost Clementsen1,8 Daniel Bech Rasmussen1,2 1Respiratory Research Unit PLUZ, Department of Respiratory Medicine, Zealand University Hospital 2Institute of Regional Health Research, University of Southern Denmark 3Pleural Medicine Unit, Department of Internal Medicine, Hospital Universitari Arnau de Vilanova, IRBLleida 4Respiratory Department, Southmead Hospital, North Bristol NHS Trust 5Academic Respiratory Unit, University of Bristol 6Lancashire Teaching Hospitals 7University of Central Lancashire 8Centre for HR and Education, Copenhagen Academy for Medical Education and Simulation.

Ultrasound in the Diagnosis of Non-Expandable Lung: A Prospective Observational Study of M-Mode, B-Mode, and 2D-Shear Wave Elastography.

BACKGROUND: Non-expandable lung (NEL) has severe implications for patient symptoms and impaired lung function, as well as crucial implications for the management of malignant pleural effusion (MPE). Indwelling pleural catheters have shown good symptom relief for patients with NEL; hence, identifying patients early in their disease is vital. With the inability of the lung to achieve pleural apposition following thoracentesis and the formation of a hydropneumothorax, traditionally, chest X-ray and clinical symptoms have been used to make the diagnosis following thoracentesis. It is our aim to investigate whether ultrasound measurement of lung movement during respiration can predict NEL before thoracentesis, thereby aiding clinicians in their planning for the optimal treatment of affected patients. METHODS: A total of 49 patients were consecutively included in a single-centre trial performed at a pleural clinic. Patients underwent protocolled ultrasound assessment pre-thoracentesis with measurements of lung and diaphragm movement and shear wave elastography measurements of the pleura and pleural effusion at the planned site of thoracentesis. RESULTS: M-mode measurements of lung movement provided the best diagnostic ROC-curve results, with an AUC of 0.81. Internal validity showed good results utilising the calibration belt test and Brier test. CONCLUSION: M-mode measurement of lung movement shows promise in diagnosing NEL before thoracentesis in patients with known or suspected MPE. A validation cohort is needed to confirm the results.

Artificial Intelligence Improves Novices' Bronchoscopy Performance: A Randomized Controlled Trial in a Simulated Setting.

BACKGROUND: Navigating through the bronchial tree and visualizing all bronchial segments is the initial step toward learning flexible bronchoscopy. A novel bronchial segment identification system based on artificial intelligence (AI) has been developed to help guide trainees toward more effective training. RESEARCH QUESTION: Does feedback from an AI-based automatic bronchial segment identification system improve novice bronchoscopists' end-of-training performance? STUDY DESIGN AND METHODS: The study was conducted as a randomized controlled trial in a standardized simulated setting. Novices without former bronchoscopy experience practiced on a mannequin. The feedback group (n = 10) received feedback from the AI, and the control group (n = 10) trained according to written instructions. Each participant decided when to end training and proceed to performing a full bronchoscopy without any aids. RESULTS: The feedback group performed significantly better on all three outcome measures (median difference, P value): diagnostic completeness (3.5 segments, P < .001), structured progress (13.5 correct progressions, P < .001), and procedure time (-214 seconds, P = .002). INTERPRETATION: Training guided by this novel AI makes novices perform more complete, more systematic, and faster bronchoscopies. Future studies should examine its use in a clinical setting and its effects on more advanced learners.

Local Anesthetic Thoracoscopy for Undiagnosed Pleural Effusion.

Local anesthetic thoracoscopy (LAT) is a minimally invasive diagnostic procedure gaining recognition among chest physicians for managing undiagnosed pleural effusions. This single-port procedure is conducted with the patient under mild sedation and involves a contralateral decubitus position. It is performed in a sterile setting, typically a bronchoscopy suite or surgical theater, by a single operator with support from a procedure-focused nurse and a patient-focused nurse. The procedure begins with a thoracic ultrasound to determine the optimal entry point, usually in the IV-V intercostal space along the midaxillary line. Lidocaine/mepivacaine, with or without adrenaline, is used to anesthetize the skin, thoracic wall layers, and parietal pleura. A designated trocar and cannula are inserted through a 10 mm incision, reaching the pleural cavity with gentle rotation. The thoracoscope is introduced through the cannula for systematic inspection of the pleural cavity from the apex to the diaphragm. Biopsies (typically six to ten) of suspicious parietal pleura lesions are obtained for histopathological evaluation and, when necessary, microbiological analysis. Biopsies of the visceral pleura are generally avoided due to the risk of bleeding or air leaks. Talc poudrage may be performed before inserting a chest tube or indwelling pleural catheter through the cannula. The skin incision is sutured, and intrapleural air is removed using a three-compartment or digital chest drainage system. The chest tube is removed once there is no airflow, and the lung has satisfactorily re-expanded. Patients are usually discharged after 2-4 h of observation and followed up on an outpatient basis. Successful LAT relies on careful patient selection, preparation, and management, as well as operator education, to ensure safety and a high diagnostic yield.

Systematic Endobronchial Ultrasound - The Six Landmarks Approach.

Lung cancer is the leading cause of cancer mortality globally. To ensure the correct diagnosis and staging in relation to treatment options, it is crucial to obtain valid biopsies from suspected tumors and mediastinal lymph nodes and accurate identification of the mediastinal lymph nodes regarding the Tumor-Node-Metastasis (TNM)-classification. Flexible bronchoscopy combined with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is essential in the workup and diagnosis of patients suspected of lung cancer. EBUS-TBNA from mediastinal lymph nodes is a technically difficult procedure and has been identified as one of the most important procedures that should be integrated into a simulation-based training program for invasive pulmonologists. More specific guidelines that govern training in EBUS-TBNA are needed to meet this demand. We hereby propose a systematic, stepwise approach with specific attention to six landmarks that support the endoscopist when navigating through the bronchial maze. The stepwise approach relying on the six landmarks is used in the EBUS-certified training program offered by the European Respiratory Society (ERS).

Safety and feasibility of oesophageal ultrasound for the work-up of thoracic malignancy in patients with respiratory impairment.

Biopsying lung tumours with endobronchial access in patients with respiratory impairment is challenging. However, fine needle aspiration with the endobronchial ultrasound-endoscope via the oesophagus (EUS-B-FNA) makes it possible to obtain tissue samples without entering the airways. Safety of EUS-B-FNA in these patients has not earlier been investigated prospectively. Therefore, this study aimed at assessing feasibility and safety of EUS-B-FNA from centrally located tumours suspected of thoracic malignancy in patients with respiratory insufficiency. The study is a prospective observational study. Patients with indication of EUS-B-FNA of centrally located tumours and respiratory impairment defined as modified Medical Research Council (mMRC) dyspnoea scale score of ≥3, saturation ≤90% or need of continuous oxygen supply were included prospectively in three centres. Any adverse events (AEs) were recorded during procedure and 1-hour recovery. AEs were defined as hypoxemia (saturation <90% or need for increased oxygen supply) or any kind of events needing intervention. Late procedure-related events were recorded during 30-day follow-up. Between April 1, 2020 and January 30, 2021, 16 patients were included. No severe AEs (SAEs) occurred, but AEs were seen in 50% (n=8) and 13% (n=2) of the patients during procedure and recovery respectively. AEs included hypoxemia corrected with increased oxygen supply and in two cases reversal of sedation. Late procedure-related events were seen in 13% (n=2) and included prolonged need of oxygen and one infection treated with oral antibiotics. In this cohort, EUS-B-FNA of centrally located tumours was safe and feasible in patients with respiratory impairment, when examined in the bronchoscopy suite. A variety of mostly mild and manageable complications may occur, a few even up to 30 days post-procedure.

Systematic Bronchoscopy: the Four Landmarks Approach.

Flexible bronchoscopy is a technically difficult procedure and has been identified as the most important procedure that should be integrated into a simulation-based training program for pulmonologists. However, more specific guidelines that govern bronchoscopy training are needed to meet this demand. To ensure patients a competent examination, we propose a systematic, stepwise approach, splitting the procedure into four "landmarks" to support novice endoscopists navigating the bronchial maze. The procedure can be evaluated based on three established outcome measures to ensure a thorough and effective inspection of the bronchial tree: diagnostic completeness, structured progress, and procedure time. The stepwise approach relying on the four landmarks is used at all simulation centers in Denmark and is being implemented in the Netherlands. To provide instant feedback to novice bronchoscopists when training and to relieve time constraints from consultants, we suggest that future studies should implement artificial intelligence as a feedback and certification tool when training new bronchoscopists.

Additional Up-Front Thoracic Ultrasound in the Workup of Patients with Unilateral Pleural Effusion: A Prospective Observational Pilot Study.

BACKGROUND: In patients with pleural effusion, specific ultrasound characteristics are associated with pleural malignancy. OBJECTIVES: This study aimed to evaluate the added value of an additional, up-front, systematic thoracic ultrasound (TUS) to standard imaging in patients with unilateral pleural effusion of unknown cause in a clinical setting. METHODS: In a prospective observational pilot study, patients referred for workup and thoracentesis of a unilateral pleural effusion received up-front TUS following a set protocol in addition to available imaging and US guiding the thoracentesis or diagnostic puncture. The primary outcome was the proportion of cases where systematic TUS changed the planned diagnostic workup. Follow-up took place 26 weeks after inclusion. RESULTS: From February to December 2020, 55 patients were included. Thirty-six (65%) patients had other chest imaging available before TUS. Twenty-one (38%) were diagnosed with malignant pleural effusion. Three patients (5%) had clinically relevant changes in the diagnostic workup after additional systematic TUS. CONCLUSIONS: Additional up-front, systematic TUS had limited clinically relevant effect on the planned diagnostic workup in patients with unilateral pleural effusion in a setting where chest CT scans often are available at referral.

Endoscopic ultrasound-guided pancreas biopsy in the hands of a chest physician.

This is the first paper to report sampling of pancreatic lesions by EUS-B-FNA. A 76 year old patient suspected of primary lung cancer presented with a 36 × 24 mm lesion in the pancreas. Thoracentesis showed malignant cells suggestive of mucinous adenocarcinoma, but immunohistochemistry was inconclusive. Due to rapid deterioration of performance status of this frail patient, the program was shortened to EUS-B-FNA of the pancreatic lesion, which showed mucinous adenocarcinoma suggestive of primary pancreatic cancer. We conclude that EUS-B-FNA from a pancreatic lesion in the hands of a chest physician is feasible and diagnostic of a tumor in pancreas.

Prediction of Time to Next Therapeutic Thoracentesis and Identification of Risk Factors of Rapid Pleural Fluid Recurrence: A Prospective Observational Study.

BACKGROUND: The value of pre-booked repeated thoracentesis in patients with recurrent pleural effusion is reliant on the estimation of time to next drainage. Identifying factors associated with rapid pleural fluid recurrence could be supportive. OBJECTIVE: We aimed to evaluate the ability of the patient and physician to predict the time to next therapeutic thoracentesis and to identify characteristics associated with rapid pleural fluid recurrence. METHOD: In a prospective, observational study, patients with recurrent unilateral pleural effusion and the physician were to predict the time to next symptom-guided therapeutic thoracentesis. Primary outcome was difference between days to actual thoracentesis and days predicted by the patient and the physician. Factors associated with pleural fluid recurrence within 60-day follow-up were assessed using Cox regression analysis. RESULTS: A total of 98 patients were included, 71% with malignant pleural effusion. Patients' and physicians' predictions numerically deviated by 6 days from the actual number of days to re-thoracentesis (IQR 2-12 and 2-13, respectively). On multivariate analyses, factors associated with increased hazard of pleural fluid recurrence included daily fluid production (HR 1.35 [1.16-1.59], p > 0.001) and large effusion size (HR 2.76 [1.23-6.19], p = 0.01). Septations were associated with decreased hazard (HR 0.48 [0.24-0.96], p = 0.04). CONCLUSION: Patients and physicians were equally unable to predict the time to next therapeutic thoracentesis. Daily fluid production and large effusion size were associated with increased risk of rapid pleural fluid recurrence, while septations were associated with a decreased risk. This may guide patients and physicians in when to expect a need for therapeutic thoracentesis.

Preparing for Reality: A Randomized Trial on Immersive Virtual Reality for Bronchoscopy Training.

BACKGROUND: Bronchoscopy is an essential procedure in the diagnosis and treatment of pulmonary diseases. However, the literature suggests that distractions affect the quality of bronchoscopy and affect inexperienced doctors more than experienced. OBJECTIVES: The objective of the study was as follows: does simulation-based bronchoscopy training with immersive virtual reality (iVR) improve the doctors' ability to handle distractions and thereby increase the quality, measured in procedure time, structured progression score, diagnostic completeness (%), and hand motor movements of a diagnostic bronchoscopy in a simulated scenario. Exploratory outcomes were heart rate variability and a cognitive load questionnaire (Surg-TLX). METHODS: Participants were randomized. The intervention group practiced in an iVR environment with a head-mounted display (HMD) while using the bronchoscopy simulator, while the control group trained without the HMD. Both groups were tested in the iVR environment using a scenario with distractions. RESULTS: 34 participants completed the trial. The intervention group scored significantly higher in diagnostic completeness (100 i.q.r. 100-100 vs. 94 i.q.r. 89-100, p value = 0.03) and structured progress (16 i.q.r. 15-18 vs. 12 i.q.r. 11-15, p value 0.03) but not in procedure time (367 s standard deviation [SD] 149 vs. 445 s SD 219, p value = 0.06) or hand motor movements (-1.02 i.q.r. -1.03-[-1.02] versus -0.98 i.q.r. -1.02-[-0.98], p value = 0.27). The control group had a tendency toward a lower heart rate variability (5.76 i.q.r. 3.77-9.06 vs. 4.12 i.q.r. 2.68-6.27, p = 0.25). There was no significant difference in total Surg-TLX points between the two groups. CONCLUSION: iVR simulation training increases the quality of diagnostic bronchoscopy in a simulated scenario with distractions compared with conventional simulation-based training.

When Pulmonologists Are Novice to Navigational Bronchoscopy, What Predicts Diagnostic Yield?

Predicting factors of diagnostic yield in electromagnetic navigation bronchoscopy (ENB) have been explored in a number of previous studies based on data from experienced operators. However, little is known about predicting factors when the procedure is carried out by operators in the beginning of their learning curve. We here aim to identify the role of operators' experience as well as lesion- and procedure characteristics on diagnostic yield of ENB procedures in the hands of novice ENB operators. Four operators from three centers without prior ENB experience were enrolled. The outcome of consecutive ENB procedures was assessed and classified as either diagnostic or non-diagnostic and predicting factors of diagnostic yield were assessed. A total of 215 procedures were assessed. A total of 122 (57%) of the ENB procedures resulted in diagnostic biopsies. Diagnostic ENB procedures were associated with a minor yet significant difference in tumor size compared to non-diagnostic/inconclusive ENB procedures (28 mm vs. 24 mm; p = 0.03). Diagnostic ENB procedures were associated with visible lesions at either fluoroscopy (p = 0.003) or radial endobronchial ultrasound (rEBUS), (p = 0.001). In the logistic regression model, lesion visibility on fluoroscopy, but none of operator experience, the presence of a bronchus sign, lesion size, or location nor visibility on rEBUS significantly impacted the diagnostic yield. In novice ENB operators, lesion visibility on fluoroscopy was the only factor found to increase the chance of obtaining a diagnostic sample.

LINEAR ENDOSONOGRAPHY IN LUNG CANCER: A COMPREHENSIVE REVIEW.

The role of endobronchial ultrasound (EBUS) and trans-esophageal endobronchial ultrasound (EUS-B) in lung cancer is well established and scientifically validated. There is increasing data that endosonography is a crucial tool for the diagnosis of central lung lesions, and mediastinal staging and restaging of non-small cell lung cancer patients. The present article reviews the technical aspects of EBUS and EUS-B and focus on the last published research regarding its value in lung cancer.

Developing a simulation-based training curriculum in transesophageal ultrasound with the use of the endobronchial ultrasound-endoscope.

There is an increasing need to focus on how best to train respiratory physicians to perform EUS with bronchoscope-guided fine-needle aspiration biopsy (EUS-B-FNA). At current, training is mostly performed in the clinical environment under expert supervision; however, the advent of simulation-based education now provides a low-risk setting for novice trainees to learn and practice basic endosonography skills from identifying and understanding normal anatomy as well as pathology, maneuvering of endoscope, interpretation of images, and mastering of sampling techniques. In this descriptive educational paper, we used a six-step approach as a framework to describe the development of a structured training program combining EUS-B-FNA with the already well-established certification training program in endobronchial ultrasound transbronchial needle aspiration. This comprehensive training curriculum includes a theoretical course to achieve foundational knowledge, followed by simulation-based training until mastery standards are met, and supervised clinical apprenticeship. All steps should end with an objective assessment to achieve certification. This systematic development will hopefully encourage endosonography leaders and educators to collaborate and implement an evidence-based comprehensive endosonography curriculum that aims to provide the trainee with the essential EUS-B competencies to ensure that lung cancer patients are diagnosed and staged correctly.

The prevalence of tumour markers in malignant pleural effusions associated with primary pulmonary adenocarcinoma: a retrospective study.

BACKGROUND: Oncological treatment of primary pulmonary adenocarcinoma (AC) includes drugs targeting the pathways involving programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK). The aim of the study was to report the prevalence of these tumour markers in pleural fluid with cytology positive for pulmonary AC and the potential influence of volume pleural fluid tested. METHODS: We retrospectively reviewed all thoracenteses performed in a two-year period at our interventional unit at Department of Respiratory Medicine at Zealand University Hospital Naestved, Denmark. ALK and PD-L1 testing was done using immunohistochemistry and EGFR testing using next-generation sequencing. We included pleural fluid specimens containing malignant cells originating from primary pulmonary AC and with at least one tumour marker requested by the clinicians. RESULTS: When screening 927 pleural fluid specimens, we identified 57 in accordance with the inclusion criteria. PD-L1, ALK and EGFR were obtained in 35/55 (64%), 38/57 (67%) and 26/47 (55%), respectively. The prevalence did not increase when analysing volumes > 50 mL (p = 0.21-0.58). CONCLUSION: Tumour markers in pleural fluid specimens containing cells from pulmonary AC can be demonstrated in more than half of the cases. Therefore, supplementary invasive procedures than thoracentesis could potentially await these analyses.

Adult pulmonary blastoma in an adult with urothelial cancer: A case report.

Pulmonary blastoma is an aggressive lung cancer with incidence ranging from 0.25-0.5 of all the reported lung cancers. Although, pulmonary blastoma is seen commonly in childhood its very rare in adults. Surgical treatment is often the treatment of choice, but benefits of neoadjuvant chemotherapy are unclear. People with DICER1 syndrome commonly develop Pulmonary blastoma and do have concomitant or previous history of benign or malignant tumours in extra pulmonary site like kidney, thyroid, ovary cervix testicle and eye. As per our knowledge, this is the first case of adult pulmonary blastoma previously diagnosed with urothelial cancer and a strong familial predilection of malignancy, with negative genetic test for DICER1 mutations.

Assessment of competence in local anaesthetic thoracoscopy: development and validity investigation of a new assessment tool.

BACKGROUND: The aims of the study were to develop an assessment tool in local anaesthetic thoracoscopy (LAT), investigate validity evidence, and establish a pass/fail standard. METHODS: Validity evidence for the assessment tool was gathered using the unified Messick framework. The tool was developed by five experts in respiratory medicine and medical education. Doctors with varying experience performed two consecutive procedures in a standardized, simulation-based setting using a newly developed thorax/lung silicone model. Performances were video-recorded and assessed by four expert raters using the new tool. Contrasting groups' method was used to set a pass/fail standard. RESULTS: Nine novices and 8 experienced participants were included, generating 34 recorded performances and 136 expert assessments. The tool had a high internal consistency (Cronbach's alpha =0.94) and high inter-rater reliability (Cronbach's alpha =0.91). The total item score significantly correlated with the global score (rs=0.86, P<0.001). Participants' first performance correlated to second performance (test-retest reliability) with a Pearson's r of 0.93, P<0.001. Generalisability (G) study showed a G-coefficient of 0.92 and decision (D) study estimated that one performance assessed by two raters or four performances assessed by one rater are needed to reach an acceptable reliability, i.e., G-coefficient >0.80. The tool was able to discriminate between the two groups in both performances: experienced mean score =30.8±4.2; novice mean score =15.8±2.3, P<0.001. Pass/fail standard was set at 22 points. CONCLUSIONS: The newly developed assessment tool showed solid evidence of validity and can be used to ensure competence in LAT.