Minimally Invasive Sampling of Mediastinal Lesions.

This narrative review examines the existing literature on minimally invasive image-guided sampling techniques of mediastinal lesions gathered from international databases (Medline, PubMed, Scopus, and Google Scholar). Original studies, systematic reviews with meta-analyses, randomized controlled trials, and case reports published between January 2009 and November 2023 were included. Four authors independently conducted the search to minimize bias, removed duplicates, and selected and evaluated the studies. The review focuses on the recent advancements in mediastinal sampling techniques, including EBUS-TBNA, EUS-FNA and FNB, IFB, and nodal cryobiopsy. The review highlights the advantages of an integrated approach using these techniques for diagnosing and staging mediastinal diseases, which, when used competently, significantly increase diagnostic yield and accuracy.

Cone Beam Computed Tomography-guided Navigation Bronchoscopy with Augmented Fluoroscopy for the Diagnosis of Peripheral Pulmonary Nodules: a step-by-step guide.

Introduction Cone Beam CT-guided Navigation Bronchoscopy (CBCT-NB) with Augmented Fluoroscopy (AF) guidance represents a minimally invasive endobronchial technique for diagnosing small, peripheral pulmonary lesions. This approach is characterized by its high diagnostic accuracy and low complication risk. Current pilot trials are exploring the application of localized therapies using this innovative approach. This reportaims to provide a detailed procedural guide for performing CBCT-NB with AF guidance as the only tool for navigation and image guided biopsy. Methods We outline the procedural steps involved in the CBCT-NB procedure for diagnosing peripheral pulmonary lesions, supported by specific intra-procedural clinical video footage. The steps include (1) preprocedural considerations, (2) a detailed procedural workflow encompassing navigation to the target lesion, (3) position confirmation and tissue acquisition, and (4) postprocedural follow-up. Conclusion CBCT-NB with AF guidance is a safe and precise stand-alone navigation modality that offers high-resolution real-time 3D imaging, enhancing the diagnosis and potential treatment of peripheral pulmonary nodules.

Characterisation of pulmonary air leak measurements using a mechanical ventilator in a bench setup.

Prolonged air leakage (AL) following pulmonary resections leads to prolonged hospital stay and post-operative complications. Intra- and postoperative quantification of AL might be useful for improving treatment decisions, but these measurements have not been characterised. AL calculations based on inspiratory and expiratory tidal volumes were investigated in an Intensive Care Unit mechanical ventilator circuit (Servo-I). AL was also measured by a digital chest drainage system. This study shows that AL measurements increase in accuracy when corrected for baseline deviations (R: 0.904 > 0.997, p < 0.001). Bland-Altman analysis revealed a funnel-shape, indicative of a detection threshhold. Corrected measurements were most accurate when averaged over five breaths and AL was >500 mL/min, with an estimated mean systemic bias of 7.4% (95%-limits of agreement [LoA]: 1.1%-13.7%) at 500 mL/min air leak. Breath-by-breath analysis showed most accurate results at AL >20 mL/breath (R: 0.989-0.991, p < 0.001) at tidal volumes between 350-600 mL. The digital drain had a mean systemic bias of -11.1% (95%-LoA: -18.9% to -3.3%) with homogenous scatter in Bland-Altman analysis and a strong correlation to the control measurement over a large range (0-2000mL/min, R: 0.999, p < 0.001). This study indicates that the Servo-I can be used for air leak quantification in clinically relevant ranges (>500 mL/min), but is unsuited for small leak detection due to a detection threshold. Researchers and clinicians should be aware of varying accuracy and interoperability characteristics between AL measurement devices.

Radiation Principles, Protection, and Reporting for Interventional Pulmonology: A World Association of Bronchology and Interventional Pulmonology White Paper.

The use and availability of diverse advanced X-ray based imaging and guidance systems in the field of interventional pulmonology are rapidly growing. This popularity links inextricably to an increase in ionizing radiation use. Knowing ionizing radiation is hazardous, knowledge and competent use of X-ray imaging and guidance systems are important. The globally implemented As Low As Reasonably Achievable (ALARA) principle demands careful attention to minimize radiation exposure while achieving the precise goals of the intervention and imaging therein. To allow careful and targeted weighing of risk against reward while using X-ray based equipment, proper background knowledge of physics as well as imaging system aspects are needed. This white paper summarizes the principles of ionizing radiation which are crucial to enhance awareness and interpretation of dosimetric quantities. Consecutively, a consensus on standards for reporting radiation exposure in interventional pulmonology procedures is indicated to facilitate comparisons between different systems, approaches and results. Last but not least, it provides a list of practical measures, considerations and tips to optimize procedural imaging as well as reduce radiation dose to patients and staff.

Proof-of-principle of a lung sealant based on functionalized polyoxazolines: experiments in an ovine acute aerostasis model.

OBJECTIVES: More effective lung sealants are needed to prevent prolonged pulmonary air leakage (AL). Polyoxazoline-impregnated gelatin patch (N-hydroxysuccinimide ester functionalized poly(2-oxazoline)s; NHS-POx) was promising for lung sealing ex vivo. The aim of this study is to confirm sealing effectiveness in an in vivo model of lung injury. METHODS: An acute aerostasis model was used in healthy adult female sheep, involving bilateral thoracotomy, amputation lesions (bronchioles Ø > 1.5 mm), sealant application, digital chest tube for monitoring AL, spontaneous ventilation, obduction and bursting pressure measurement. Two experiments were performed: (i) 3 sheep with 2 lesions per lung (N = 4 NHS-POx double-layer, N = 4 NHS-POx single-layer, N = 4 untreated) and (ii) 3 with 1 lesion per lung (N = 3 NHS-POx single-layer, N = 3 untreated). In pooled linear regression, AL was analysed per lung (N = 7 NHS-POx, N = 5 untreated) and bursting pressure per lesion (N = 11 NHS-POx, N = 7 untreated). RESULTS: Baseline AL was similar between groups (mean 1.38-1.47 l/min, P = 0.90). NHS-POx achieved sealing in 1 attempt in 8/11 (72.7%) and in 10/11 (90.9%) in >1 attempt. Application failures were only observed on triangular lesions requiring 3 folds around the lung. No influences of methodological variation between experiments was detected in linear regression (P > 0.9). AL over initial 3 h of drainage was significantly reduced for NHS-POx [median: 7 ml/min, length of interquartile range: 333 ml/min] versus untreated lesions (367 ml/min, length of interquartile range: 680 ml/min, P = 0.036). Bursting pressure was higher for NHS-POx (mean: 33, SD: 16 cmH2O) versus untreated lesions (mean: 19, SD: 15 cmH2O, P = 0.081). CONCLUSIONS: NHS-POx was effective for reducing early AL, and a trend was seen for improvement of bursting strength of the covered defect. Results were affected by application characteristics and lesion geometry.

Diagnostic yield of cone beam CT based navigation bronchoscopy in patients with metastatic lesions: A propensity score matched case-control study.

BACKGROUND: Cone beam CT based Navigation Bronchoscopy (CBCT-NB) has predominantly been investigated as a diagnostic tool in (suspected) primary lung cancers. Small metastatic lesions are clinically considered more challenging to diagnose, but no study has explored the yield of navigation bronchoscopy in patients with pulmonary metastatic lesions (ML) compared to primary lung cancers (PL), correcting for known lesion characteristics affecting diagnostic yield. MATERIALS AND METHODS: This is a single-center, retrospective, propensity score-matched case-control study. We matched a subset of patients who underwent CBCT-NB and received a final diagnosis of pulmonary metastases of solid tumors between December 2017 and 2021 against confirmed primary lung cancer lesions subjected to CBCT-NB in the same time period. The lesions were propensity score matched based on known characteristics affecting yield, including location (upper lobe, lower lobe), size, bronchus sign, and lesion solidity. RESULTS: Fifty-six metastatic pulmonary lesions (mean size 14.7 mm) were individually case-matched to a selection of 297 available primary lung cancer lesions. Case-matching revealed non-significant differences in navigation success rate (PL: 89.3 % vs. ML: 82.1 %, 95%CI on differences: -21.8 to +7.5) and yield (PL: 60.7 % vs. ML: 55.4 %, 95%CI on differences: -25.4 to +14.7). The overall complication rate was comparable (5.4 % in PL vs. 5,4 % in ML). CONCLUSION: After matching primary and metastatic lesions based on CT assessable lesions characteristics, CBCT-NB showed no clinically relevant or significantly different navigation success or yield in either group. We recommend a careful assessment of CT characteristics to determine procedural difficulty rather than selecting based on the suspicion of lesion origin.

Estimating lung function from computed tomography at the patient and lobe level using machine learning.

BACKGROUND: Automated estimation of Pulmonary function test (PFT) results from Computed Tomography (CT) could advance the use of CT in screening, diagnosis, and staging of restrictive pulmonary diseases. Estimating lung function per lobe, which cannot be done with PFTs, would be helpful for risk assessment for pulmonary resection surgery and bronchoscopic lung volume reduction. PURPOSE: To automatically estimate PFT results from CT and furthermore disentangle the individual contribution of pulmonary lobes to a patient's lung function. METHODS: We propose I3Dr, a deep learning architecture for estimating global measures from an image that can also estimate the contributions of individual parts of the image to this global measure. We apply it to estimate the separate contributions of each pulmonary lobe to a patient's total lung function from CT, while requiring only CT scans and patient level lung function measurements for training. I3Dr consists of a lobe-level and a patient-level model. The lobe-level model extracts all anatomical pulmonary lobes from a CT scan and processes them in parallel to produce lobe level lung function estimates that sum up to a patient level estimate. The patient-level model directly estimates patient level lung function from a CT scan and is used to re-scale the output of the lobe-level model to increase performance. After demonstrating the viability of the proposed approach, the I3Dr model is trained and evaluated for PFT result estimation using a large data set of 8 433 CT volumes for training, 1 775 CT volumes for validation, and 1 873 CT volumes for testing. RESULTS: First, we demonstrate the viability of our approach by showing that a model trained with a collection of digit images to estimate their sum implicitly learns to assign correct values to individual digits. Next, we show that our models can estimate lobe-level quantities, such as COVID-19 severity scores, pulmonary volume (PV), and functional pulmonary volume (FPV) from CT while only provided with patient-level quantities during training. Lastly, we train and evaluate models for producing spirometry and diffusion capacity of carbon mono-oxide (DLCO) estimates at the patient and lobe level. For producing Forced Expiratory Volume in one second (FEV1), Forced Vital Capacity (FVC), and DLCO estimates, I3Dr obtains mean absolute errors (MAE) of 0.377 L, 0.297 L, and 2.800 mL/min/mm Hg respectively. We release the resulting algorithms for lung function estimation to the research community at https://grand-challenge.org/algorithms/lobe-wise-lung-function-estimation/ CONCLUSIONS: I3Dr can estimate global measures from an image, as well as the contributions of individual parts of the image to this global measure. It offers a promising approach for estimating PFT results from CT scans and disentangling the individual contribution of pulmonary lobes to a patient's lung function. The findings presented in this work may advance the use of CT in screening, diagnosis, and staging of restrictive pulmonary diseases as well as in risk assessment for pulmonary resection surgery and bronchoscopic lung volume reduction.

Rapid on-site evaluation of touch imprint cytology in navigation bronchoscopy for small peripheral pulmonary nodules.

BACKGROUND: Rapid on-site evaluation (ROSE) of cytopathology plays an important role in determining whether representative samples have been taken during navigation bronchoscopy. With touch imprint cytology (TIC), histologic samples can be assessed using ROSE. Although advised by guidelines, there have been almost no studies on the performance of TIC during navigation bronchoscopy. The objective of this study was to evaluate the value of TIC-ROSE (forceps/cryobiopsy) in combination with conventional ROSE (cytology needle/brush). METHODS: In this single-center, prospective cohort study, patients who had pulmonary nodules with an indication for navigation bronchoscopy were consecutively included. The primary outcome of the study was the concordance of ROSE and the procedural outcome. The concordance rates of TIC-ROSE and the combination of TIC-ROSE plus conventional ROSE were compared. RESULTS: Fifty-eight patients with 66 nodules were included. Conventional ROSE and TIC-ROSE were assessable in 61 nodules (90.9%) each. By combining both ROSE techniques, all sampled lesions were assessable. Combining conventional ROSE with TIC-ROSE showed concordant results in 51 of 66 cases (77.3%) versus 44 of 66 (66.7%) and 48 of 66 (72.8%) concordant results for conventional ROSE and TIC-ROSE alone, respectively, compared with the procedural outcome. There was no indication of tissue depletion as a result of TIC. The combined ROSE approach had a statistically significant higher concordance rate compared with conventional ROSE alone. CONCLUSIONS: TIC-ROSE is a cheap, easily implementable technique that can result in higher concordant ROSE outcomes. This could lead to more efficient procedures and possibly higher diagnostic results. In a monomodality sampling setting with only histologic samples, TIC can provide ROSE.

Intrinsic pulmonary sealing, its mechanisms and impact on validity and translational value of lung sealant studies: a pooled analysis of animal studies.

Background: No validated and standardized animal models of pulmonary air leakage (PAL) exist for testing aerostatic efficacy of lung sealants. Lack of negative control groups in published studies and intrinsic sealing mechanisms of healthy animal lungs might contribute to a translational gap, leading to poor clinical results. This study aims to address the impact of intrinsic sealing mechanisms on the validity of PAL models, and investigate the conditions required for an ovine model of PAL for lung sealant testing. Methods: An ovine acute aerostasis model was developed, consisting of a bilateral thoracotomy with lesion creation, chest tube insertion and monitoring of air leaks using digital drains (≥80 minutes), under spontaneous respiration. Healthy mixed-breed adult female sheep were used and all in vivo procedures were performed under terminal anesthesia. Superficial parenchymal lesions were tested post-mortem and in vivo, extended lesions including bronchioles (deep bowl-shaped and sequential lung amputation lesions) were tested in vivo. Experiment outcomes include air leakage (AL), minimal leaking pressure (MLP) and histology. Results: Two post-mortem (N=4 superficial parenchymal lesions) and 10 in vivo experiments (N=5 superficial parenchymal and N=16 lesions involving bronchioles) were performed. In contrast to the post-mortem model, superficial parenchymal lesions in vivo showed less air leak [mean flow ± standard deviation (SD): 760±693 vs. 42±33 mL/min, P=0.055]. All superficial parenchymal lesions in vivo sealed intrinsically within a median time of 20 minutes [interquartile range (IQR), 10-75 minutes]. Histology of the intrinsic sealing layer revealed an extended area of alveolar collapse below the incision with intra-alveolar hemorrhage. Compared to superficial parenchymal lesions in vivo, lesions involving bronchioles induced significantly higher air leak post-operatively (normalized mean flow ± SD: 459±221 mL/min, P=0.003). At termination, 5/9 (55.6%) were still leaking (median drain time: 273 minutes, IQR, 207-435 minutes), and intrinsic sealing for the remaining lungs occurred within a median of 115 minutes (IQR, 52-245 minutes). Conclusions: Lung parenchyma of healthy sheep shows a strong intrinsic sealing mechanism, explained pathologically by an extended area of alveolar collapse, which may contribute to a translational gap in lung sealant research. A meaningful ovine model has to consist of deep lesions involving bronchioles of >⌀1.5 mm. Further research is needed to develop a standardized PAL model, to improve clinical effectiveness of lung sealants.

Cone-beam CT in lung biopsy: a clinical practice review on lessons learned and future perspectives.

Pulmonary nodules with intermediate to high risk of malignancy should preferably be diagnosed with image guide minimally invasive diagnostics before treatment. Several technological innovations have been developed to endobronchially navigate to these lesions and obtain tissue for diagnosis. This review addresses these technological advancements in navigation bronchoscopy in three basic steps: navigation, position confirmation and acquisition, with a specific focus on cone-beam computed tomography (CBCT). For navigation purposes ultrathin bronchoscopy combined with virtual bronchoscopy navigation, electromagnetic navigation and robotic assisted bronchoscopy all achieve good results as a navigation guidance tool, but cannot confirm location or guide biopsy positioning. Diagnostic yield has seen improvement by combining these techniques with a secondary imaging tool like radial endobronchial ultrasound (rEBUS) and fluoroscopy. For confirmation of lesion access, rEBUS provides local detailed ultrasound-imaging and can be used to confirm lesion access in combination with fluoroscopy, measure nodule-contact area length and determine catheter position for sampling. CBCT is the only technology that can provide precise 3D positioning confirmation. When focusing on tissue acquisition, there is often more than 10% difference between reaching the target and getting a diagnosis. This discrepancy is multifactorial and caused by breathing movements, small samples sizes, instrument tip displacements by tool rigidity and tumour inhomogeneity. Yield can be improved by targeting fluorodeoxyglucose (FDG)-avid regions, immediate feedback of rapid onsite evaluation, choosing sampling tools with different passive stiffnesses, by increasing the number biopsies taken and (future) catheter modifications like (robotic assisted-) active steering. CBCT with augmented fluoroscopy (CBCT-AF) based navigation bronchoscopy combines navigation guidance with 3D-image confirmation of instrument-in-lesion positioning in one device. CBCT-AF allows for overlaying the lesion and navigation pathway and the possibility to outline trans-parenchymal pathways. It can help guide and verify sampling in 3D in near real-time. Disadvantages are the learning curve, the inherent use of radiation and limited availability/access to hybrid theatres. A mobile C-arm can provide 3D imaging, but lower image quality due to lower power and lower contrast-to-noise ratio is a limiting factor. In conclusion, a multi-modality approach in experienced hands seems the best option for achieving a diagnostic accuracy >85%. Either adequate case selection or detailed 3D imaging are essential to obtain high accuracy. For current and future transbronchial treatments, high-resolution (CBCT) 3D-imaging is essential.

Sealing effectiveness of a novel NHS-POx based patch: experiments in a dynamic ex vivo porcine lung.

Background: Sealants are used to prevent prolonged pulmonary air leakage (PAL) after lung resections (incidence 5.6-30%). However, clinical evidence to support sealant use is insufficient, with an unmet need for a more effective product. We compared a novel gelatin patch impregnated with functionalized polyoxazolines (NHS-POx) (GATT-Patch) to commercially available sealant products. Methods: GATT-Patch Single/Double layers were compared to Progel®, Coseal®, Hemopatch® and TachoSil® in an ex vivo porcine lung model (first experiment). Based on these results, a second head-to-head comparison between GATT-Patch Single and Hemopatch® was performed. Air leakage (AL) was assessed in three settings using increasing ventilatory pressures (max =70 cmH2O): (I) baseline, (II) with 25 mm × 25 mm superficial pleural defect, and (III) after sealant application. Lungs floating on saline (37 ℃) were video recorded for visual AL assessment. Pressure and tidal volumes were collected from the ventilator, and bursting pressure (BP), AL and AL-reduction were determined. Results: Per sealant 10 measurements were performed (both experiments). In the first experiment, BP was superior for GATT-Patch Double (60±24 cmH2O) compared to TachoSil® (30±11 cmH2O, P<0.001), Hemopatch® (33±6 cmH2O, P=0.006), Coseal® (25±13 cmH2O, P=0.001) and Progel® (33±11 cmH2O, P=0.005). AL-reduction was superior for GATT-Patch Double (100%±1%) compared to Hemopatch® (46%±50%, P=0.010) and TachoSil® (31%±29%, P<0.001), and also for GATT-Patch Single (100%±14%, P=0.004) and Progel (89%±40%, P=0.027) compared to TachoSil®. In the second experiment, GATT-Patch Single was superior regarding BP (45±10 vs. 40±6 cmH2O, P=0.043) and AL-reduction (100%±11% vs. 68%±40%, P=0.043) when compared to Hemopatch®. Conclusions: The novel NHS-POx patch shows promise as a lung sealant, demonstrating elevated BP, good adhesive strength and a superior AL-reduction.

Proposed quality indicators and recommended standard reporting items in performance of EBUS bronchoscopy: An official World Association for Bronchology and Interventional Pulmonology Expert Panel consensus statement.

BACKGROUND: Since their introduction, both linear and radial endobronchial ultrasound (EBUS) have become an integral component of the practice of Pulmonology and Thoracic Oncology. The quality of health care can be measured by comparing the performance of an individual or a health service with an ideal threshold or benchmark. The taskforce sought to evaluate quality indicators in EBUS bronchoscopy based on clinical relevance/importance and on the basis that observed significant variation in outcomes indicates potential for improvement in health care outcomes. METHODS: A comprehensive literature review informed the composition of a comprehensive list of candidate quality indicators in EBUS. A multiple-round modified Delphi consensus process was subsequently performed with the aim of reaching consensus over a final list of quality indicators and performance targets for these indicators. Standard reporting items were developed, with a strong preference for items where evidence demonstrates a relationship with quality indicator outcomes. RESULTS: Twelve quality Indicators are proposed, with performance targets supported by evidence from the literature. Standardized reporting items for both radial and linear EBUS are recommended, with evidence supporting their utility in assessing procedural outcomes presented. CONCLUSION: This statement is intended to provide a framework for individual proceduralists to assess the quality of EBUS they provide their patients through the identification of clinically relevant, feasible quality measures. Emphasis is placed on outcome measures, with a preference for consistent terminology to allow communication and benchmarking between centres.

Diagnostic yield and safety of navigation bronchoscopy: A systematic review and meta-analysis.

BACKGROUND: Navigation bronchoscopy has seen rapid development in the past decade in terms of new navigation techniques and multi-modality approaches utilizing different techniques and tools. This systematic review analyses the diagnostic yield and safety of navigation bronchoscopy for the diagnosis of peripheral pulmonary nodules suspected of lung cancer. METHODS: An extensive search was performed in Embase, Medline and Cochrane CENTRAL in May 2022. Eligible studies used cone-beam CT-guided navigation (CBCT), electromagnetic navigation (EMN), robotic navigation (RB) or virtual bronchoscopy (VB) as the primary navigation technique. Primary outcomes were diagnostic yield and adverse events. Quality of studies was assessed using QUADAS-2. Random effects meta-analysis was performed, with subgroup analyses for different navigation techniques, newer versus older techniques, nodule size, publication year, and strictness of diagnostic yield definition. Explorative analyses of subgroups reported by studies was performed for nodule size and bronchus sign. RESULTS: A total of 95 studies (n = 10,381 patients; n = 10,682 nodules) were included. The majority (n = 63; 66.3%) had high risk of bias or applicability concerns in at least one QUADAS-2 domain. Summary diagnostic yield was 70.9% (95%-CI 68.4%-73.2%). Overall pneumothorax rate was 2.5%. Newer navigation techniques using advanced imaging and/or robotics(CBCT, RB, tomosynthesis guided EMN; n = 24 studies) had a statistically significant higher diagnostic yield compared to longer established techniques (EMN, VB; n = 82 studies): 77.5% (95%-CI 74.7%-80.1%) vs 68.8% (95%-CI 65.9%-71.6%) (p < 0.001).Explorative subgroup analyses showed that larger nodule size and bronchus sign presence were associated with a statistically significant higher diagnostic yield. Other subgroup analyses showed no significant differences. CONCLUSION: Navigation bronchoscopy is a safe procedure, with the potential for high diagnostic yield, in particular using newer techniques such as RB, CBCT and tomosynthesis-guided EMN. Studies showed a large amount of heterogeneity, making comparisons difficult. Standardized definitions for outcomes with relevant clinical context will improve future comparability.

Effectiveness of Flexible Bronchoscopy Simulation-Based Training: A Systematic Review.

BACKGROUND: The implementation of simulation-based training (SBT) to teach flexible bronchoscopy (FB) skills to novice trainees has increased during the last decade. However, it is unknown whether SBT is effective to teach FB to novices and which instructional features contribute to training effectiveness. RESEARCH QUESTION: How effective is FB SBT and which instructional features contribute to training effectiveness? STUDY DESIGN AND METHODS: We searched Embase, PubMed, Scopus, and Web of Science for articles on FB SBT for novice trainees, considering all available literature until November 10, 2022. We assessed methodological quality of included studies using a modified version of the Medical Education Research Study Quality Instrument, evaluated risk of bias with relevant tools depending on study design, assessed instructional features, and intended to correlate instructional features to outcome measures. RESULTS: We identified 14 studies from an initial pool of 544 studies. Eleven studies reported positive effects of FB SBT on most of their outcome measures. However, risk of bias was moderate or high in eight studies, and only six studies were of high quality (modified Medical Education Research Study Quality Instrument score ≥ 12.5). Moreover, instructional features and outcome measures varied highly across studies, and only four studies evaluated intervention effects on behavioral outcome measures in the patient setting. All of the simulation training programs in studies with the highest methodological quality and most relevant outcome measures included curriculum integration and a range in task difficulty. INTERPRETATION: Although most studies reported positive effects of simulation training programs on their outcome measures, definitive conclusions regarding training effectiveness on actual bronchoscopy performance in patients could not be made because of heterogeneity of training features and the sparse evidence of training effectiveness on validated behavioral outcome measures in a patient setting. TRIAL REGISTRATION: PROSPERO; No.: CRD42021262853; URL: https://www.crd.york.ac.uk/prospero/.

Evaluating and developing sealants for the prevention of pulmonary air leakage: A systematic review of animal models.

Sealants may provide a solution for pulmonary air leakage (PAL), but their clinical application is debatable. For sealant comparison, standardized animal models are lacking. This systematic review aims to assess methodology and quality of animal models for PAL and sealant evaluation. All animal models investigating lung sealing devices (e.g., staplers, glues, energy devices) to prevent or treat PAL were retrieved systematically from Embase, Pubmed and Web of science. Methodological study characteristics, risk of bias, reporting quality and publication bias were assessed. A total of 71 studies were included (N = 75 experiments, N = 1659 animals). Six different species and 18 strains were described; 92% of experiments used healthy animals, disease models were used in only six studies. Lesions to produce PAL were heterogenous, and only 11 studies used a previously reported technique, encompassing N = 5 unique lesions. Clinically relevant outcomes were used in the minority of studies (imaging 16%, air leak 10.7%, air leak duration 4%). Reporting quality was poor, but revealed an upward trend per decade. Overall, high risk of bias was present, and only 18.7% used a negative control group. All but one study without control groups claimed positive outcomes (95.8%), in contrast to 84.3% using positive or negative control groups, which also concluded equivocal, adverse or inconclusive outcomes. In conclusion, animal studies evaluating sealants for prevention of PAL are heterogenous and of poor reporting quality. Using negative control groups, disease models and quantifiable outcomes seem important to increase validity and relevance. Further research is needed to reach consensus for model development and standardization.

Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer: A Randomized Clinical Trial.

PURPOSE: Resectable non-small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking. METHODS: Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, Pnoninferior < .0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality. RESULTS: Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; Pnoninferior = .0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior = .0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first (P = .4940). CONCLUSION: On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.

Ex-vivo exploration of an endobronchial sentinel lymph node procedure in lung cancer for optimizing workflow and evaluating feasibility of novel imaging tools.

Background: Early-stage lung cancer is treated with curative intent by surgery or radiotherapy. However, upstaging is frequently seen after surgery in clinical N0 lung cancer patients, and despite curative intent, 2-year recurrence rates of 9-28% are reported. A sentinel lymph node (SLN) procedure could improve the staging accuracy. We explored the feasibility of performing a navigation bronchoscopy based SLN procedure in human ex-vivo lung cancer specimens to optimize procedural parameters and assess a novel injection tool. Methods: Ten lung resection specimens were included and allocated to either peri- or intratumoral injection of a tracer combining 99mTc-nanocolloid and indocyanine green (ICG) while varying the injection volume. A Pioneer Plus catheter with a pre-angulated 24G needle and an ultrasound (US)-element was used to perform real-time US guided transbronchial injections at multiple locations. Thereafter, single photon emission computed tomography/computed tomography (SPECT/CT)-scanning was performed to image injection depots and to assess their location relative to the tumor. Results: An average volume of 0.7 mL (range, 0.3-1.2 mL) with an average activity of 89.5 MBq 99mTc (range, 35.4-188.0 MBq) was injected. Intratumoral injections in non-solid and solid tumors were successful in 100% and 64.3% respectively, while 100% of peritumoral injections in solid tumors were successful. The US-element of the catheter allowed real-time imaging and was able to visualize all tumors and 67.4% of all injections. SPECT/CT-scanning visualized 76.7% of the injection depots. Conclusions: A navigation bronchoscopy mediated SLN procedure seems technically feasible. The Pioneer Plus is a suitable catheter to place tracer depots at multiple intra-/peri-tumoral sites, while receiving real-time feedback on the needle localization in relation to the tumor. The next step of in-vivo injections will determine if tracer drainage to the SLN can also be detected on pre- and per-operative imaging.

Case report: multiple lesions during navigation bronchoscopy; seen one, seen them all?

Background: Peripheral pulmonary nodules are often detected as multiple nodules in one patient. Computed tomography (CT) guided transthoracic biopsy (TTNB) is the most widely implemented method for minimal invasive biopsy of pulmonary nodules, but generally only one nodule is sampled per procedure. Navigation bronchoscopy is an endobronchial procedure with very low complication rates, and uses high-end image guidance which allows for the sampling of multiple nodules in one session, while also allowing inspection of the central airways and endobronchial ultrasound (EBUS) guided staging in one session. This report presents a unique case with three different synchronous primary tumors treated with three different treatment modalities that highlights the added value of cone-beam CT guided navigation bronchoscopy (CBCT-NB) in the diagnostic work-up of suspected early-stage lung cancer. Case Description: This case describes an asymptomatic patient with no history of prior lung cancer referred because of a shadow seen on a screening X-ray. CT and positron emission tomography (PET) showed two nodules for which a navigation procedure was performed. Both nodules were sampled, and on inspection, a third occult endobronchial lesion was also found. Pathology revealed three separate primary tumors, which were treated with three different treatment modalities: surgery, radiotherapy and endobronchial cryoablation. Current follow-up at 12 months shows no signs of recurrence. Conclusions: This case highlights that synchronous primary malignancies do occur and require a patient tailored approach to minimize treatment related morbidity and optimize survival. To this goal, image guided navigation bronchoscopy allows for a full and complete diagnostic evaluation and can be combined with a staging EBUS in one single session.