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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.

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.

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.

The role of PET and integrated PET-CT in the diagnostic workup of suspected malignant pleural effusions is unknown. Earlier systematic reviews (published 2014 and 2015) both included pleural pathology without effusion, and reached contradictory conclusions. Five studies have been published since the latest review. This systematic review and meta-analysis aims to summarise the evidence of PET and integrated PET-CT in predicting pleural malignancy in patients suspected of having malignant pleural effusions. A meta-analysis based on a systematic literature search in Cochrane Library, Medline, EMBASE and Clinicaltrials.gov was performed. Diagnostic studies evaluating the performance of PET or PET-CT in patients with suspected malignant pleural effusion, using pleural fluid cytology or histopathology as the reference test, and presenting sufficient data for constructing a 2x2 table were included. The quality of the studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 score. Subgroup analyses on image modality, interpretation method and known malignancy status pre index-test application were planned. Seven studies with low risk of bias were included. The pooled ability to separate benign from malignant effusions varied with image modality, interpretation method and known malignancy status pre index-test application. In studies using PET-CT, visual/qualitative image analysis was superior to semi-quantitative with positive (LR + ) and negative likelihood ratio (LR-) of 9.9 (4.5–15.3) respectively 0.1 (0.1–0.2). There was considerable heterogeneity among studies. In conclusion, visual/qualitative image analysis of integrated PET-CT seems to add relevant information in the work-up of suspected malignant pleural effusions with LR + and LR- close to rigorous pre-set cut-offs of > 10 and < 0.1. However, the quality of evidence was low due to inter-study heterogeneity, and inability to assess meta-bias. Clinical Trial Registration: The protocol was uploaded to the PROSPERO database (CRD42020213319) on the 13th of October 2020.

Accurate staging of non-small cell lung cancer (NSCLC) is crucial for allocation to surgical, medical or multimodal treatment. EUS and endobronchial ultrasound (EBUS) have gained ground in the diagnosis and staging of lung cancer in addition to radiological imaging (e.g., computed tomography, fluoroscopy, and magnetic resonance imaging), nuclear medicine techniques (e.g. positron emission tomography, PET), combined techniques (e.g., fluorodesoxyglucosepositron emission tomography scanning), and sonographic imaging including conventional transcutaneous mediastinal and lung ultrasound. By using one single echoendoscope in both the trachea and the esophagus, surgical staging procedures (e.g. mediastinoscopy and video assisted thoracoscopy) can be avoided in a considerable proportion of patients with NSCLC.

Background: According to guidelines, it is possible to biopsy lung tumors “immediately adjacent to the esophagus” with EUS-B-FNA. However, it is unknown what “immediately adjacent” exactly means. Objective: to investigate the possibility of achieving EUS-B-FNA biopsies from a lung tumor depending on the distance from the esophagus and to establish the maximal allowable distance between the tumor and the esophagus. Methods: In a prospective observational study, we included patients with a lung tumor located maximum 6 cm from the esophagus and indication of EUS-B-FNA from the tumor. The tumors were of different sizes. In a plot presenting the tumor size-distance relationship in cases with (biopsy) versus without (non-biopsy) successful EUS-B-FNA, a separation line representing the threshold between the groups were identified and a biopsy-index equation established. The maximal tumor-size corrected distance (TSCD) was calculated using the residuals to the separation line. Results: In total, 70 patients were included. EUS-B-FNA from the lung tumor was possible in 46 patients. All tumors with a distance from the esophagus below 19 mm could be biopsied. The maximal allowable esophagus-tumor distance depended on tumor size. From the separation line, a biopsy-index equation was established with the sensitivity of 93.5%, a specificity of 100%, and total accuracy of 95.7%. The TSCD was 31 mm (sensitivity: 95.7%, specificity 75.0%, and accuracy: 88.6%). Conclusion: We established a biopsy-index equation to predict the achievability of a lung tumor using EUS-B-FNA depending on distance to esophagus and tumor size. A general maximal TSCD was 31 mm.

Ultrasound-guided needle aspiration via the esophagus using the endobronchial endoscope (EUS-B-FNA) is increasingly being performed by the pulmonologist for the diagnosis of lung cancer, but we have little experience and data available in the literature especially with respect to staging of the disease. We present 2 cases of EUS-B-guided aspiration of malignant pericardial effusion performed in the same setting as bronchoscopy and endobronchial ultrasound. No complications were observed. We conclude that EUS-B-FNA may be safe and efficacious in the evaluation of pericardial effusion during lung cancer workup. Thus, EUS-B-FNA may save time in the diagnostic workup, improve cancer staging, and prevent transthoracic pericardiocentesis.

Die ultraschallgestützte Feinnadelaspiration mit Zugang über den Ösophagus unter Verwendung eines endobronchialen Endoskops (EUS-B-FNA) wird von Pneumologen zunehmend für die Diagnose von Lungentumoren angewendet. Bislang liegen uns jedoch nur wenige Erfahrungen und Daten aus der Literatur über das Staging der Erkrankung vor. Wir stellen hier 2 Fälle einer EUS-B-gestützten Aspiration eines malignen Perikardergusses vor, die unter denselben Bedingungen wie eine Bronchoskopie und endobronchiale Ultraschalluntersuchung durchgeführt wurden. Es traten keine Komplikationen auf. Wir ziehen den Schluss, dass es sich bei der EUS-B-FNA vermutlich um ein sicheres und wirksames Verfahren zur Beurteilung eines Perikardergusses im Rahmen der Lungentumor-Diagnostik handelt. Somit könnte die EUS-B-FNA bei der diagnostischen Abklärung Zeit sparen, das Tumorstaging verbessern und eine transthorakale Perikardpunktion überflüssig machen.

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.

To biopsy centrally located lung tumors is a challenge, especially in patients with severe respiratory insufficiency. The endobronchial ultrasound guided fine needle aspiration performed through the esophagus (EUS-B-FNA) makes it possible to attain tissue samples without entering the airways, but safety in patients with respiratory insufficiency has not earlier been investigated.Therefore, this study aimed at assessing feasibility and safety of EUS-B-FNA from centrally located lesions suspected of lung cancer in patients with respiratory insufficiency.Method: patients with indication for EUS-B-FNA of a centrally located tumor and existing respiratory insufficiency defined as mMRC≥3, saturation ≤90% or need of continuous oxygen supply were included prospectively from three centers. Any adverse events (AE) were recorded during procedure and one-hour recovery. AEs were defined as hypoxemia (saturation

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, P0.80. 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

Background: The guidelines from the British Thoracic Society (BTS) regarding the investigation of unilateral pleural effusions recommend computed tomography (CT) in exudates. We decided to investigate if clinicians follow BTS guidelines’ recommendations with respect to CT in patients with unilateral pleural effusions. Secondly, to investigate the diagnostic consequences of following and not following this recommendation. Methods: The study was a retrospective, non-randomized study including consecutive patients referred to our tertiary centers in 2013–2016 because of unilateral pleural effusion. Patients undergoing chest CT for unilateral pleural effusion of unknown cause after thoracentesis and chest X-ray were included. Patients were categorized as having pleural exudates or transudates, according to Light’s criteria, if applicable. We registered use of CT, and calculated diagnostic values. Results: In total, 323 of the 465 included patients underwent CT (69%). CT was performed in the majority of patients not having an exudate (transudates: n=40; 54%; Light’s criteria not assessed: n=111; 67%). 18 F-FDG positron emission tomography (PET)/CT without prior CT was performed in 32 patients with an exudate (58%). The sensitivity of a non-guideline supported CT (70%) was significantly higher compared to a guideline supported CT (47%), P value

Background: In patients with suspected or proven lung cancer, assessment of regional nodal and distant metastases is key before treatment planning. By introducing the endobronchial ultrasound (EBUS)-guided scope into the esophagus and stomach (EUS-B), liver lesions and celiac nodes can be visualized. To date, the utility of EUS-B in diagnosing liver lesions and retroperitoneal lymph nodes is unknown. Objectives: To assess the feasibility, safety, and diagnostic yield of sampling of liver lesions and retroperitoneal nodes by EUS-B fine-needle aspiration (FNA) in a lung cancer staging setting. Method: Consecutive patients suspected of lung cancer in 2 Danish centers between 1 January 2015 and 31 December 2017 were included retrospectively when a lesion in the liver or a retroperitoneal lymph node was visualized and biopsied with EUS-B-FNA. Results: 23 left liver lobe lesions and 19 retroperitoneal lymph nodes were sampled by EUS-B-FNA. Sensitivity and diagnostic yield of sampled liver lesions were 86 and 83%, respectively. In 19/23 patients, there was a cytopathological diagnosis of malignancy. Sensitivity and diagnostic yield from retroperitoneal lymph node samples were 83 and 63%, respectively. In 10/19 patients, the diagnosis was malignancy. No complications were observed. Conclusion: EUS-B-FNA enables safe sampling of left liver lobe lesions and retroperitoneal lymph nodes. EUS-B should be considered as a minimally invasive technique to provide tissue proof of distant metastases lung cancer patients.

Background: Diagnosing centrally located lung tumors without endobronchial abnormalities and not located near the major airways is a diagnostic challenge. Tumors near or adjacent to the esophagus can be aspirated and detected with esophageal ultrasound (EUS) using gastrointestinal endoscopes. Objective: To assess the feasibility and diagnostic yield of endoscopic ultrasound with bronchoscope-guided fine needle aspiration (EUS-B-FNA) in paraesophageally located lung tumors and its added value to bronchoscopy and endobronchial ultrasound (EBUS). Methods: Retrospective, multicenter international study (from January 1, 2015 until January 1, 2018) of patients with suspected lung cancer, undergoing bronchoscopy, EBUS, and endoscopic ultrasound bronchoscopy (EUS-B) in one session by a single operator (pulmonologist), in whom the primary lung tumor was detected and aspirated by EUS-B. In the absence of malignancy following endoscopy, transthoracic ultrasound needle aspiration, clinical and radiological follow-up of at least 6 months was performed. The yield and sensitivity of EUS-B-FNA and its added value to bronchoscopy and EBUS was assessed. Results: 58 patients were identified with the following diagnosis: non-small-cell lung cancer (n = 43), small-cell lung cancer (n = 6), mesothelioma (n = 2), metastasis (n = 1), nonmalignant (n = 6). The yield and sensitivity of EUS-B-FNA for detecting lung cancer was 90%. In 26 patients (45%), the intrapulmonary tumor was exclusively detected by EUS-B. Adding EUS-B to conventional bronchoscopy and EBUS increased the diagnostic yield for diagnosing lung cancer in para­esophageally located lung tumors from 51 to 91%. No EUS-B-related complications were observed. Conclusion: EUS-B-FNA is a feasible and safe technique for diagnosing centrally located intrapulmonary tumors that are located near or adjacent to the esophagus. EUS-B should be considered in the same endoscopy session following nondiagnostic bronchoscopy and EBUS.

Background: Electromagnetic navigation bronchoscopy (ENB) is a relatively new and technically demanding procedure for the guidance of bronchoscopic biopsy to help locate small lung lesions. The results in experienced hands are well described. However, we do not know the results in unexperienced hands-in other words, we have no knowledge about how fast you can learn the procedure. Aim: The aim of this study was to draw learning curves for beginners in ENB using Cumulated Sum (CUSUM) analysis, a method for quantitative evaluation of the learning curves for clinical procedures. Methods: Four operators from 3 centers without prior ENB experience were enrolled. The outcome of consecutive ENB procedures was assessed and classified as either diagnostic or nondiagnostic based on sample adequacy. Learning curves were drawn based on diagnostic yield. Results: A total of 215 procedures were assessed. For 2 of the operators (operators 1 and 4), at least 25 to 30 procedures were necessary to obtain competency whereas operators 2 and 3 showed more horizontal learning curves indicating an overweight of diagnostic procedures from the beginning. Conclusion: Operators achieve competences in ENB at different paces. This must be taken in account when beginners start to learn the procedure. There is a huge need for a structured educational program and a validated test to determine competences.

Immunoglobulin G4 (IgG4)-related disease is a systemic fibroinflammatory disorder that can affect almost any tissue. Isolated IgG4 pleural disease is a rare manifestation and, when present, is usually described in patients presenting with dyspnoea. We present a case of asymptomatic isolated IgG4 pleural effusion and highlight that IgG4-related disease should be remembered as a differential diagnosis in patients with pleural effusion and pleural thickening, even if asymptomatic and without any other organ involvement.

Background: Flexible bronchoscopy is a core invasive procedure in pulmonary medicine and training in the procedure is mandatory. Diagnostic completeness and procedure time have been identified as useful measures of competence. No outcome measures have been developed regarding navigational path in bronchoscopy to assess whether the bronchial segments have been identified in an arbitrary or structured order. We investigated whether a new outcome measure for structured progression could be used to assess competency in flexible bronchoscopy. Methods: The study was designed as a prospective comparative study. Twelve novices, eleven intermediates, and ten expert bronchoscopy operators completed three full bronchoscopies in a simulated setting on a phantom. The following outcome measures were collected through a checklist evaluation by a trained rater: Diagnostic Completeness as amount of visualized bronchial segments, Structured Progress between the bronchial segments in ascending order, and average intersegmental time (AIT). Results: The ability to follow a structured ascending path through the bronchial tree correlated with a higher amount of identified bronchial segments (Pearson's correlation, r=0.62, P

Introduction and Background: Targeted oncological treatment of non-small cell lung cancer (NSCLC) requires assessment of oncodriver status: Epidermal growth factor receptor (EGFR), programmed death-ligand 1 (PD-L1), anaplastic lymphoma kinase (ALK) in adenocarcinomas (AC), and PD-L1 in squamous cell carcinomas (SCC). The sensitivity of thoracentesis for providing a diagnosis in malignant pleural effusion (MPE) secondary to AC is ~80% and ~15% in SSC but is not established concerning oncodriver status (1). Aims and Objectives: The study aims to clarify the prevalence of NSCLC oncodrivers in cytology-positive MPE. Methods: We retrospectively evaluated all thoracentesis performed during 2016 to 2019 at our unit. In patients with positive pleural cytology for NSCLC, we counted the prevalence of requested versus successfully measured oncodriver status. In some patients, oncodrivers were measured in biopsies from other lesions. Results: Of 191 cytology-positive MPEs, 109 were secondary to NSCLC (104 AC, 5 SCC and 0 large cell carcinomas). For AC, EGFR was requested in 49 individuals and was obtained in 41%, PD-L1 was requested in 43 individuals and obtained in 54% and ALK was requested in 53 individuals and obtained in 64%. For SCC, PD-L1 was requested in 1 of 5 individuals and was successfully obtained. Conclusions: In MPE secondary to NSCLC, there appears to be a discrepancy between the sensitivity of pleural cytology for diagnosing malignancy and identifying oncodrivers. 1: Arnold DT, De Fonseka D, Perry S, et al. Investigating unilateral pleural effusions: the role of cytology. Eur Respir J. 2018;52(5):1-9. doi:10.1183/13993003.01254-2018

The liquid-based Carbo-gel technology enables real-time multimodal image guidance for improved therapeutic precision., Diagnostic imaging often outperforms the surgeon’s ability to identify small structures during therapeutic procedures. Smart soft tissue markers that translate the sensitivity of diagnostic imaging into optimal therapeutic intervention are therefore highly warranted. This paper presents a unique adaptable liquid soft tissue marker system based on functionalized carbohydrates (Carbo-gel). The liquid state of these markers allows for high-precision placement under image guidance using thin needles. Based on step-by-step modifications, the image features and mechanical properties of markers can be optimized to bridge diagnostic imaging and specific therapeutic interventions. The performance of Carbo-gel is demonstrated for markers that (i) have radiographic, magnetic resonance, and ultrasound visibility; (ii) are palpable and visible; and (iii) are localizable by near-infrared fluorescence and radio guidance. The study demonstrates encouraging proof of concept for the liquid marker system as a well-tolerated multimodal imaging marker that can improve image-guided radiotherapy and surgical interventions, including robotic surgery.

Introduction Patients with lung cancer report a lower degree of Health Related Quality of Life (HRQoL) compared with other cancer patients. HRQoL reflects how patients experience the impact of their disease and its treatment on their quality of daily living. A widely used questionnaire in lung cancer patients is the Functional Assessment of Cancer Therapy – Lung (FACT-L) questionnaire. Here we report the secondary outcomes on FACT-L data from the Postoperative Rehabilitation in Operation for Lung CAncer (PROLUCA) study, which describes the effect of early (14 days) versus late initiated (14 weeks) postoperative rehabilitation. Materials and methods The PROLUCA study was designed as a two-armed randomized controlled trial with an early rehabilitation group (14 days after surgery (ERG)) or a control arm with a late rehabilitation group (14 weeks after surgery (LRG)). The results for seven domain scores obtained using the FACT-L at the following time-points: baseline, 14 weeks, 26 weeks and 52 weeks after surgery are presented here. Results 119 patients were randomized to the ERG and 116 to the LRG. In the ERG, HRQoL measured by both FACT-L and FACT-G (general core instrument) showed a continuous improvement up to 26 weeks after which HRQoL decreased after further 26 weeks without structured intervention. In the LRG a non-significant deterioration was detected over the first 14 weeks after surgery. After participation in the 12 weeks rehabilitation program, an increase in HRQoL was seen, without reaching the same level as the early group. Conclusion Analyses of the seven domain scores obtained using FACT-L and FACT-G reflect the importance of starting exercise early after surgery since the ERG avoid a temporary decrease in HRQoL. It is therefore recommended to start up a structured rehabilitation program 14 days after surgery, containing high intensity interval training and strength exercise twice a week for 12 weeks.

Medical thoracoscopy allows the respiratory physician access to inspection and biopsy of the pleura. The method has several names, such as pleuroscopy, non-intubated thoracoscopy and exploratory thoracoscopy, all of which cover the same procedure. The main indication for medical thoracoscopy is the diagnosis of recurrent pleural effusion, where pleural biopsy is needed. Medical thoracoscopy differs from thoracic surgical surgery as patients are sedated rather than in general anaesthesia. This is a review of the state of the art of pulmonological investigations of recurrent pleural effusion and the important role of medical thoracoscopy.

Background: Several studies have reported the efficacy of esophageal ultrasound-guided fine needle aspiration (EUS-FNA) for the detection of metastases in the left adrenal gland (LAG) in patients with lung cancer. Currently we have only limited evidence based on small studies on the usefulness of EUS-B [endobronchial ultrasound (EBUS) scope into the esophagus] to provide tissue proof of suspected LAG metastases. The objectives of this study are to investigate feasibility, safety and diagnostic yield of EUS-B-FNA in LAG analysis in patients with proven or suspected lung cancer.Methods: In two Danish hospitals, a systematic search in the electronic database for patients who underwent EUS-B-FNA of the LAG for suspected or proven lung cancer was performed retrospectively between January 1st, 2015 and December 31st, 2017. Computed tomography (CT), positron emission tomography-CT, endoscopy, pathology and follow-up data were acquired.Results: One hundred and thirty-five patients were included; the prevalence of biopsy proven LAG malignancy was 30% (40/135). A total of 87% (117/135) of EUS-B-FNA samples were adequate (i.e., containing adrenal or malignant cells). No complications were observed.Conclusions: We present the largest cohort of patients ever reported showing that EUS-B-FNA of the LAG is a safe and feasible procedure and should therefore be used for staging purposes in patients with lung cancer and a suspicious LAG.

The use of the endobronchial ultrasound (EBUS) endoscope in the oesophagus, the so‐called EUS‐B procedure, for the diagnosis and staging of thoracic malignancy is quickly gaining ground. Pleural lesions located close to the oesophagus can be inaccessible to transthoracic biopsy and endoscopic procedures can be the only option. We here present two cases demonstrating that EUS‐B‐guided fine needle aspiration (EUS‐B‐FNA) of pleural lesions is possible. The first case demonstrates a EUS‐B‐FNA with malignant mesothelioma of a pleural lesion in a 70‐year‐old patient. In the second case, EUS‐B‐FNA diagnosed a pleural metastasis from adenoid cystic adenocarcinoma in a 75‐year‐old‐patient. In conclusion, we hereby demonstrate that EUS‐B‐FNA from pleural lesions is feasible and appears to be safe., Endoscopic ultrasound (EUS) via the oesophagus can be performed either with the use of a conventional gastrointestinal endoscope (EUS‐fine needle aspiration (FNA)) or by using the endobronchial ultrasound (EBUS) endoscope in the oesophagus (EUS‐B‐FNA). The use of EUS‐B for the diagnosis and staging of thoracic malignancy is quickly gaining ground. We here present two cases demonstrating that EUS‐B‐guided FNA (EUS‐B‐FNA) of pleural lesions is possible.

Silicone from ruptured breast implants can cause lung symptoms mimicking cancer. The diagnosis may be established by transbronchial lung biopsy or surgery. We report a case of asymptomatic silicone induced granulomatous reaction in the lungs and mediastinal lymph nodes diagnosed with EBUS-TBNA. We conclude that this differential diagnosis should be kept in mind even in an asymptomatic patients and that EBUS-TBNA should be considered.

Malignant pleural effusion is an important and difficult differential diagnosis to pleural empyema. Epithelioid hemangioendothelioma is an uncommon vascular tumor, which typically occurs in liver, lung or bone. We present an extremely rare case of primary pleural epithelioid hemangioendothelioma mimicking pleural empyema. We conclude, that pleural epithelioid hemangioendothelioma should be kept in mind as a differential diagnosis in patients suspected of empyema.

Little is known about the optimal amount and timing of exercise strain in concern of the operation wound and with regard improvement of physical function and quality of life (QOL) after surgery for lung cancer. On this background, we decided to investigate the effect of early vs. late initiated postoperative rehabilitation in patients with operable lung cancer on exercise capacity, functional capacity, muscle strength, and QOL.The study was designed as a two-armed randomized controlled trial with randomization to either early initiated postoperative rehabilitation (14 days after surgery (ERG)) or a control arm with late initiated postoperative rehabilitation (14 weeks after surgery (LRG)). The primary endpoint was a change in maximum oxygen consumption (VO2peak) from baseline to post intervention 26 weeks following lung resection. Fatigue was measured with EORTC QLQ C30 LC13.From April 2013 to June 2016, 582 patients with operable NSCLC were screened for eligibility. With 119 patients randomized in the early rehabilitation group (ERG) and 116 randomized to late rehabilitation group (LRG). There was no significant difference from baseline to 26 weeks between ERG and LRG (p = 0.926). There was a significant difference from baseline to 14 weeks between groups (p = 0.0018). There was a significant difference from 14 weeks to 26 weeks between the two groups (p 0.001). We found no significant differences in QOL but we found a significant difference between ERG and LRG from baseline to 14 weeks in fatigue level in favour of ERG.This is the first randomized controlled trial to investigate the effects of early vs. late initiated postoperative rehabilitation in patients with lung cancer. There is no difference in the commencement (early vs. late) of a postoperative exercise program for patients with lung cancer on exercise capacity. But to reduce fatigue patients should be recommended to initiate early exercise programs.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) plays a key role in the staging of lung cancer, which is crucial for allocation to surgical treatment. EBUS-TBNA is a complicated procedure and simulation-based training is helpful in the first part of the long learning curve prior to performing the procedure on actual patients. New trainees should follow a structured training programme consisting of training on simulators to proficiency as assessed with a validated test followed by supervised practice on patients. The simulation-based training is superior to the traditional apprenticeship model and is recommended in the newest guidelines. EBUS-TBNA and oesophageal ultrasound-guided fine needle aspiration (EUS-FNA or EUS-B-FNA) are complementary to each other and the combined techniques are superior to either technique alone. It is logical to learn and to perform the two techniques in combination, however, for lung cancer staging solely EBUS-TBNA simulators exist, but hopefully in the future simulation-based training in EUS will be possible.

Background and purpose We investigated the clinical applicability of a novel liquid fiducial marker (LFM) for image-guided pencil beam scanned (PBS) proton therapy (PBSPT) of locally advanced lung cancer (LALC). Materials and methods The relative proton stopping power (RSP) of the LFM was calculated and measured. Dose perturbations of the LFM and three solid markers, in a phantom, were measured. PBSPT treatment planning on computer tomography scans of five patients with LALC with the LFM implanted was performed with 1–3 fields. Results The RSP was experimentally determined to be 1.164 for the LFM. Phantom measurements revealed a maximum relative deviation in dose of 4.8% for the LFM in the spread-out Bragg Peak, compared to 12–67% for the solid markers. Using the experimentally determined RSP, the maximum proton range error introduced by the LFM is about 1mm. If the marker was displaced at PBSPT, the maximum dosimetric error was limited to 2 percentage points for 3-field plans. Conclusion The dose perturbations introduced by the LFM were considerably smaller than the solid markers investigated. The RSP of the fiducial marker should be corrected in the treatment planning system to avoid errors. The investigated LFM introduced clinically acceptable dose perturbations for image-guided PBSPT of LALC.

Aims To assess the prevalence of EML4–ALK rearrangement gene measured by immunohistochemistry in an unselected population-based consecutive cohort of patients with adenocarcinoma of the lung (ACL), and the correlation with smoking history, thyroid transcription factor 1 (TTF1), gender and age. Methods and results All patients diagnosed in the population of the greater Copenhagen area were included, irrespective of gender, age, smoking habits, stage or type of available diagnostic material. Tumours were stained with immunohistochemistry (clone 5A4). Immunohistochemistry-positive tumours were tested by fluorescence in-situ hybridization (FISH). During a 16-month period, 760 patients in the population were diagnosed with ACL. In 2.6% there was insufficient material for ALK testing (20 of 760). Eleven per cent of the remaining 740 ACL patients were never smokers, 43% were ex-smokers smokers and 46% were current smokers. Fourteen patients [1.9%, 95% confidence interval (CI) = 1.1–3.2] were ALK-positive by immunohistochemistry. Nine of 82 never-smokers (11%, 95% CI = 5.9–19.6) and five of 652 ex- or current smokers (0.8%, 95% CI = 0.4–2.1) were ALK-positive. Only two ALK-positive patients were found among 586 heavy smokers (> 15 pack-years) (0.3%, 95% CI = 0.09–1.2). Thirteen of the 14 immunohistochemistry-positive patients were FISH-positive. All ALK-positive tumours were TTF1-positive. The number needed to test (NNT) to identify one ALK positive patient was 9, 22 and 293 among never smokers, light and heavy smokers, respectively. Conclusions Immunohistochemical analysis of ALK rearrangement was possible in 97.4% of patients. ALK rearrangement was found primarily in never smokers. NNT to identify one ALK-positive patient was 9, 22 and 293 among never smokers, light and heavy smokers, respectively.

Background: The use of simulators in a training programme for technically challenging procedures has the advantages of lowering the risk of patient complications while helping the trainees with the initial part of their learning curve. Objectives: The aim of this study was to perform a systematic review of simulation-based training in flexible bronchoscopy and endobronchial ultrasound (EBUS). Methods: We identified 1,006 publications in the PubMed database and included publications on flexible bronchoscopy below the carina and EBUS involving hands-on simulation-based training. Publications were excluded if they were written in languages other than English, if paediatric airways were involved or if they were not journal articles. The screening process was performed by 2 individuals, and a third reviewer made the final decision in case of disagreement. Results: We included 30 publications. The studies included participants of varying experience and most commonly used a virtual reality simulator as a training modality. Assessment of the participants' skills was based on simulator metrics or on an assessment tool. Some studies included performance on patients for assessment of the operator after training on a simulator. Conclusions: Simulation-based training was demonstrated to be more efficient than the traditional apprenticeship model. Physical models and virtual reality simulators complement each other. Simulation-based education should be based on a mastery learning approach and structured as directed self-regulated learning in a distributed training programme.

Background: Staging of lung cancer is essential to the treatment, which is curative only in cases of localized disease. Previous studies have suggested that endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is unnecessary when positron emission tomography-computed tomography (PET-CT) shows no mediastinal involvement. Objective: The aim of the study was to investigate how often EBUS-TBNA resulted in a clinically relevant upstaging in patients with lung cancer without mediastinal involvement at PET-CT. Methods: A total of 981 consecutive patients from 2009 to 2014 were referred for preoperative EBUS-TBNA. We included 167 patients with lung cancer without involvement of the mediastinum at PET-CT (115 N0 and 52 N1). Results: Of the 167 patients included, 10 (6.0%) were upstaged to N2 or N3 by EBUS-TBNA; 9 of these were originally classified as N1 at PET-CT. Therefore, 17.3% of the included N1 patients were upstaged to N2/N3 after EBUS-TBNA. This compares to only 0.9% of the N0 patients. After both EBUS-TBNA and PET-CT, 115 patients were operated, and 12 (10.4%) of these proved to be N2/N3. We calculated the sensitivity as 42.9%, the specificity as 99.0%, and the negative predictive value as 89.6%. Conclusions: The overall probability of a clinically relevant upstaging by EBUS-TBNA in patients judged as N0/N1 at PET-CT was 6.0%, compared to 0.9% in patients classified as N0 and 17.3% in patients classified as N1. The risk of overlooking N2/N3 disease after both PET-CT and EBUS-TBNA was 10.4%.

Flexible bronchoscopy and endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) are the pulmonologists´ basic procedures for the biopsy of suspicious lung lesions. If inconclusive, other guiding-modalities for tissue sampling are needed, computed tomography performed by a radiologist, or - if available - radial EBUS or electromagnetic navigation biopsy. We wanted to investigate if same-day X-ray fluoroscopy-guided transthoracic fine-needle aspiration biopsy (F-TTNAB) performed by the pulmonologist immediately after bronchoscopy and EBUS is a feasible alternative. We retrospectively identified consecutive patients in whom F-TTNAB followed a bronchoscopy and EBUS in the same séance. Patients in whom the suspicion of malignancy was invalidated after complete work up were followed for six months to identify false-negative cases. In total 125 patients underwent triple approach (bronchoscopy, EBUS and F-TTNAB) during the same séance. Malignancy was diagnosed in 86 (69%), and 77 of these (90%) were primary lung cancers. The diagnostic yield of F-TTNAB for malignancy was 77%, and sensitivity was 90%. Pneumothorax occurred in 35 (28%) patients, and was administered with pleural drainage in 22 (18% of all patients). No cases of prolonged haemoptysis were observed. The risk of pneumothorax differed insignificantly with lesion size ≤2.0 cm (27%) versus >2.0 cm (29%). We conclude that it is feasible for pulmonologist to perform F-TTNAB immediately after endoscopy as a combined triple approach in a fast-track workup of suspected lung cancer.

Background: Trocar pigtail catheter thoracentesis (TPCT) is a common procedure often performed by junior physicians. Simulation-based training may effectively train physicians in the procedure prior to performing it on patients. An assessment tool with solid validity evidence is necessary to ensure sufficient procedural competence. Objectives: Our study objectives were (1) to collect evidence of validity for a newly developed pigtail catheter assessment tool (Thoracentesis Assessment Tool [ThorAT]) developed for the evaluation of TPCT performance and (2) to establish a pass/fail score for summative assessment. Methods: We assessed the validity evidence for the ThorAT using the recommended framework for validity by Messick. Thirty-four participants completed two consecutive procedures and their performance was assessed by two blinded, independent raters using the ThorAT. We compared performance scores to test whether the assessment tool was able to discern between the two groups, and a pass/fail score was established. Results: The assessment tool was able to discriminate between the two groups in terms of competence level. Experienced physicians received significantly higher test scores than novices in both the first and second procedure. A pass/fail score of 25.2 points was established, resulting in 4 (17%) passing novices and 1 (9%) failing experienced participant in the first procedure. In the second procedure 9 (39%) novices passed and 2 (18%) experienced participants failed. Conclusions: This study provides a tool for summative assessment of competence in TPCT. Strong validity evidence was gathered from five sources of evidence. A simulation-based training program using the ThorAT could ensure competence before performing thoracentesis on patients.