Imaging modalities during navigational bronchoscopy.

INTRODUCTION: Lung nodules are commonly encountered in clinical practice. Technological advances in navigational bronchoscopy and imaging modalities have led to paradigm shift from nodule screening or follow-up to early lung cancer detection. This is due to improved nodule localization and biopsy confirmation with combined modalities of navigational platforms and imaging tools. To conduct this article, relevant literature was reviewed via PubMed from January 2014 until January 2024. AREAS COVERED: This article highlights the literature on different imaging modalities combined with commonly used navigational platforms for diagnosis of peripheral lung nodules. Current limitations and future perspectives of imaging modalities will be discussed. EXPERT OPINION: The development of navigational platforms improved localization of targets. However, published diagnostic yield remains lower compared to percutaneous-guided biopsy. The discordance between the actual location of lung nodule during the procedure and preprocedural CT chest is the main factor impacting accurate biopsies. The utilization of advanced imaging tools with navigation-based bronchoscopy has been shown to assist with localizing targets in real-time and improving biopsy success. However, it is important for interventional bronchoscopists to understand the strengths and limitations of these advanced imaging technologies.

[The role of endoscopy in the management of peripheral pulmonary nodules, part 2: Treatment]. / Place de l'endoscopie dans la gestion des nodules pulmonaires périphériques, partie 2 : traitement.

The management of peripheral lung nodules is challenging, requiring specialized skills and sophisticated technologies. The diagnosis now appears accessible to advanced endoscopy (see Part 1), which can also guide treatment of these nodules; this second part provides an overview of endoscopy techniques that can enhance surgical treatment through preoperative marking, and stereotactic radiotherapy treatment through fiduciary marker placement. Finally, we will discuss how, in the near future, these advanced endoscopic techniques will help to implement ablation strategy.

Detection of Tumor DNA in Bronchoscopic Fluids in Peripheral NSCLC: A Proof-of-Concept Study.

Introduction: DNA genotyping from plasma is a useful tool for molecular characterization of NSCLC. Nevertheless, the false-negative rate justifies the development of methods with higher sensitivity, especially in difficult-to-reach peripheral lung tumors. Methods: We aimed at comparing molecular analysis from the supernatant of guide sheath flush fluid collected during radial-EndoBronchial UltraSound (r-EBUS) bronchoscopy with plasma sampling and tumor biopsies in patients with peripheral NSCLC. The DNA was genotyped using high-throughput sequencing or the COBAS mutation test. There were 65 patients with peripheral lung tumors subjected to concomitant sampling of guide sheath flush supernatant, plasma tumor DNA, and tumor biopsy and cytology using r-EBUS. There were 33 patients (including 24 newly diagnosed with having NSCLC) with an identifiable tumor mutation in the primary lesion selected for the comparative analysis. Results: Guide sheath flush-based genotyping yielded a mutation detection rate of 61.8% (17 of 24 mutated EGFR, one of two ERBB2, one of one KRAS, one of one MAP2K, one of four MET, and zero of one STK11), compared with 33% in plasma-based genotyping (p = 0.0151). Furthermore, in eight of 34 r-EBUS without tumor cells on microscopic examination, we were able to detect the mutation in four paired guide sheath flush supernatant, compared with only two in paired plasma. Conclusion: The detection of tumor DNA in the supernatant of guide sheath flush fluid collected during r-EBUS bronchoscopy represents a sensitive and complementary method for genotyping NSCLC.

[Advanced bronchoscopic techniques for the diagnosis of peripheral lung nodule]. / Place de l'endoscopie dans les gestions des nodules périphériques. Partie 1 : diagnostic.

The endoscopic diagnosis of peripheral lung nodules is a challenging aspect of oncological practice. More often than not inaccessible by traditional endoscopy, these nodules necessitate multiple imagery tests, as well as diagnostic surgery for benign lesions. Even though transthoracic ultrasonography has a high diagnostic yield, a sizeable complication rate renders it suboptimal. Over recent years, a number of safe and accurate navigational bronchoscopic procedures have been developed. In this first part, we provide an overview of the bronchoscopic techniques currently applied for the excision and diagnostic analysis of peripheral lung nodules; emphasis is laid on electromagnetic navigation bronchoscopy and the association of virtual bronchoscopy planner with radial endobronchial ultrasound. We conclude by considering recent innovations, notably robotic bronchoscopy.

Robotic bronchoscopic needle-based confocal laser endomicroscopy to diagnose peripheral lung nodules.

BACKGROUND AND OBJECTIVE: Robotic bronchoscopy has demonstrated high navigational success in small peripheral lung nodules but the diagnostic yield is discrepantly lower. Needle based confocal laser endomicroscopy (nCLE) enables real-time microscopic imaging at the needle tip. We aim to assess feasibility, safety and needle repositioning based on real-time nCLE-guidance during robotic bronchoscopy in small peripheral lung nodules. METHODS: Patients with suspected peripheral lung cancer underwent fluoroscopy and radial EBUS assisted robotic bronchoscopy. After radial EBUS nodule identification, nCLE-imaging of the target area was performed. nCLE-malignancy and airway/lung parenchyma criteria were used to identify the optimal sampling location. In case airway was visualized, repositioning of the biopsy needle was performed. After nCLE tool-in-nodule confirmation, needle passes and biopsies were performed at the same location. MEASUREMENTS AND MAIN RESULTS: Twenty patients were included (final diagnosis n = 17 (lung) cancer) with a median lung nodule size of 14.5 mm (range 8-28 mm). No complications occurred. In 19/20 patients, good quality nCLE-videos were obtained. In 9 patients (45%), real-time nCLE-imaging revealed inadequate positioning of the needle and repositioning was performed. After repositioning, nCLE-imaging provided tool-in-nodule-confirmation in 19/20 patients. Subsequent ROSE demonstrated representative material in 9/20 patients (45%) and overall diagnostic yield was 80% (16/20). Of the three patients with malignant nCLE-imaging but inadequate pathology, two were diagnosed with malignancy during follow-up. CONCLUSION: Robotic bronchoscopic nCLE-imaging is feasible and safe. nCLE-imaging in small, difficult-to-access lung nodules provided additional real-time feedback on the correct needle positioning with the potential to optimize the sampling location and diagnostic yield.

Electromagnetic navigation bronchoscopy localization of lung nodules for thoracoscopic resection.

BACKGROUND: Thoracoscopic localization of small peripheral pulmonary nodules is a concern. Failure can lead to larger parenchymal resection or conversion to thoracotomy. This study evaluates our experience in preoperative electromagnetic navigation bronchoscopy-guided localization of small peripheral lung lesions. METHODS: From January 2017 to March 2020 clinical, radiographic, surgical, and pathological data of patients who underwent electromagnetic navigation bronchoscopy (ENB)-guided methylene blue pleural marking of highly suspected pulmonary lesions before a full thoracoscopic resection were evaluated. Localization was performed for solid or mixed subpleural nodules measuring <10 mm, solid nodules measuring <20 mm located at more than 1 cm from the pleura and any pure ground glass opacity. Successful localization was defined as successful identification and thoracoscopic resection of target lesions. RESULTS: Forty-eight patients were included: 30 solid nodules (63%), 12 pure GGO (25%) and 6 mixed (13%). The median largest diameter at CT-scan was 11 mm (IQR, 9-14 mm) while the median distance from the pleural surface was 12 mm (IQR, 6-16 mm). The median ENB length was 25 min (19-33 min). Localization procedure was successful in 45 cases (94%). No procedural-related complications were reported. CONCLUSIONS: ENB is a safe and accurate preoperative procedure to localize small lung peripheral lesions. The high successful rate, the absence of related complications, the possibility of performing the procedure in the same operating room with a single general anesthesia, make ENB-guided dye marking an advantageous tool for thoracoscopic pulmonary resection.

Diagnostic yield and safety of biopsy guided by electromagnetic navigation bronchoscopy for high-risk pulmonary nodules.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) is a useful method to obtain tissue for peripheral lung nodules. We aimed to understand the diagnostic yield and safety profile in high-risk pulmonary nodules that cannot be accessed by percutaneous transthoracic needle biopsy. METHODS: In this single-center retrospective study, we reviewed patients who underwent ENB for high-risk pulmonary nodules. All procedures were performed under moderate sedation using intravenous midazolam and fentanyl. RESULTS: A total of 100 pulmonary nodules in 90 patients were subjected to ENB between October 2018 and May 2020. The median age of the study population was 66 (59-73). The mean diameter of the lung nodules was 27.9 mm. The diagnostic yield of ENB-guided biopsy was 53.0%. Although the nodule size (odds ratio: 1.055, p = 0.007) and positive bronchus sign (odds ratio: 2.918, p = 0.020) were associated with the diagnostic yield during univariate analysis, nodule size was the only independent variable on the multivariable analysis. Interestingly, the diagnostic yield showed an upward trend after 60 cases, from 45%-65%. Procedure-related complications were reported in 16 cases; among these, pneumothorax occurred in three cases, and four cases experienced moderate bleeding. No instance of major bleeding or death was linked to ENB-guided biopsy. CONCLUSION: ENB-guided biopsy for high-risk pulmonary nodules demonstrated an acceptable diagnostic yield and good safety profile. Moreover, the diagnostic yield was associated with nodule size and procedure experience.

What is the value of electromagnetic navigation in lung cancer and to what extent does it require improvement?

INTRODUCTION: Lung nodules are being identified with increasing frequency. With this growing burden of nodules comes a growing need for diagnostic technologies extending beyond the current reach of conventional bronchoscopy. One such method for diagnosing peripheral lung lesions is electromagnetic navigational bronchoscopy (ENB), which comprises a set of tools designed to aid the bronchoscopist in identifying, accessing, and sampling peripheral lung lesions under virtual guidance. AREAS COVERED: Herein we present an in-depth review of ENB, including commercially available electromagnetic navigation platforms, factors influencing diagnostic yield, adjunctive imaging and biopsy tools, potential risks, cost, technical shortcomings, and competing technologies. A review of the scientific literature was conducted primarily through PubMed, ScienceDirect, and Google Scholar, and pertinent publications and abstracts from the inception of electromagnetic navigation through early 2020 were considered. We also share our perspective on the future of ENB from both a diagnostic and a therapeutic standpoint. EXPERT OPINION: ENB is currently a leading tool in the diagnostic evaluation of peripheral lung lesions. The future of ENB rests not only on its potential to expand into the therapeutic realm but also on its ability to keep pace with competing diagnostic and therapeutic technologies.

Robotic assisted-bronchoscopy: technical tips and lessons learned from the initial experience with sampling peripheral lung lesions.

BACKGROUND: Peripheral pulmonary nodules are increasingly detected in patients screened for lung cancer or during disease progression of thoracic or extrathoracic malignancies. Sampling these lesions requires surgery, computed tomography (CT)-guided biopsy or bronchoscopic interventions. Bronchoscopic interventions are preferable because they have lower complications and often patients may not be ideal candidates for surgical or CT-guided biopsy. In addition, guidelines recommend diagnosis and staging in one single procedure. The diagnostic yield of existing advanced bronchoscopic techniques including electromagnetic navigation, radial probe ultrasonography, ultrathin bronchoscopy or virtual bronchoscopy remains suboptimal. The purpose of this paper is to codify the technique whereby a diagnostic bronchoscopy is performed using the new robotic platform. METHODS: In the present report, I describe the technique for performing robotic-assisted bronchoscopy (RAB) using the Monarch™ platform (Auris Health, Inc., Redwood City, CA). RESULTS: Appropriate team training, patient selection, anesthesia settings, optimal tissue acquisition and processing, and prevention of complications are described and illustrated. CONCLUSIONS: RAB may be beneficial for patients with peripheral lung lesions that require biopsy prior to surgical resection, stereotactic radiation, targeted or immunotherapy.

Diagnostic yield of electromagnetic navigational bronchoscopy: results of initial 35 cases in a Japanese institute.

BACKGROUND: Electromagnetic navigational bronchoscopy (ENB) is a new bronchoscopic technique for navigational transbronchial lung biopsy (TBLB) that guides the sheath to the target lesion in real time. Herein, we report our experience with this navigational system, its diagnostic yields, and associated complications. METHODS: A single-center, single-operator retrospective chart review was performed. We included 35 consecutive patients who underwent ENB with superDimensionTM (Medtronic, MN, USA) for the diagnosis of pulmonary lesions from February 2016 to May 2017 in Kyoto University Hospital. The size of the target lesion varied from 8 to 25 mm (median, 15.28±5.48 mm). All ENB procedures were performed under conscious sedation using 2 to 10 mg midazolam and 1 to 10 mg morphine hydrochloride. No fluoroscopic guide was employed except in three cases. RESULTS: A total of 25 patients were diagnosed via ENB, yielding a diagnostic rate of 71.4% (25/35). The average lesion size of the diagnosed group was 16.44±5.44 mm (range, 8-25 mm). Eighteen cases were diagnosed as primary lung cancer, 3 were metastatic lung cancer, and 4 were inflammatory diseases. The average lesion size of the 10 undiagnosed cases was 12.40±5.21 mm (range, 8-24 mm). The lesion size of the undiagnosed group was significantly smaller than that of the diagnosed group (P=0.02). The average time required for the procedure was 16.78±9.57 minutes (range, 3-46 minutes), independent of the diagnosis, the lesion size, and the tumor location. We encountered one pneumothorax which required chest drainage and one hemopneumothorax which required non-elective thoracotomy and wedge resection. One patient developed high fever over 38 °C for one day following the procedure. CONCLUSIONS: In our initial series of 35 cases, ENB-guided TBLB showed an acceptable diagnostic yield.

Pleural Dye Marking Using Radial Endobronchial Ultrasound and Virtual Bronchoscopy before Sublobar Pulmonary Resection for Small Peripheral Nodules.

BACKGROUND: Minimally invasive surgery of pulmonary nodules allows suboptimal palpation of the lung compared to open thoracotomy. OBJECTIVE: The objective of this study was to assess endoscopic pleural dye marking using radial endobronchial ultrasound (r-EBUS) and virtual bronchoscopy to localize small peripheral lung nodules immediately before minimally invasive resection. METHODS: The endoscopic procedure was performed without fluoroscopy, under general anesthesia in the operating room immediately before minimally invasive surgery. Then, 1 mL of methylene blue (0.5%) was instilled into the guide sheath, wedged in the subpleural space. Wedge resection or segmentectomy were guided by visualization of the dye on the pleural surface. Contribution of dye marking to the surgical procedure was rated by the surgeon. RESULTS: Twenty-five nodules, including 6 ground glass opacities, were resected in 22 patients by video-assisted thoracoscopic wedge resection (n = 11) or robotic-assisted thoracoscopic surgery (10 segmentectomies and 1 wedge resection). The median greatest diameter of nodules was 8 mm. No conversion to open thoracotomy was needed. The endoscopic procedure added an average 10 min to surgical resection. The dye was visible on the pleural surface in 24 cases. Histological diagnosis and free margin resection were obtained in all cases. Median skin-to-skin operating time was 90 min for robotic segmentectomy and 40 min for video-assisted wedge resection. The same operative precision was considered impossible by the surgeon without dye marking in 21 cases. CONCLUSIONS: Dye marking using r-EBUS and virtual bronchoscopy can be easily and safely performed to localize small pulmonary nodules immediately before minimally invasive resection.

Gaining access to the periphery of the lung: Bronchoscopic and transthoracic approaches.

Globally, lung cancer remains the leading cause of cancer-related death. Annual low-dose computed tomography has been recommended as a screening test for early detection of lung cancers. Implementing this screening strategy is expected to challenge pulmonologist to confirm the nature of the increasing number of detected pulmonary nodules. Clinicians are obliged to use the less invasive and most efficient and safe means to set diagnoses. Hence, the field of diagnostic modalities, especially the advanced diagnostic bronchoscopy is witnessing rapid evolution to fulfill these unmet needs. This review highlights the available diagnostic modalities, describes their advantages and discusses the limitations of each technique. It also suggests an integrated diagnostic algorithm based on the best available evidence. A search of the PubMed database was conducted using relevant terms described at methodology; only articles in English were reviewed by November 2016.

Role of electromagnetic navigational bronchoscopy in pulmonary nodule management.

The incidence of pulmonary nodules and lung cancer is rising. Some of this increase in incidence is due to improved pick up by newer imaging modalities. However, the goal is to diagnose these lesion, many of which are located in the periphery, by safe and relatively non-invasive methods. This has led to the emergence of numerous techniques such as electromagnetic navigational bronchoscopy (ENB). Current evidence supports a role for these techniques in the diagnostic pathway. However, numerous factor influence the diagnostic accuracy. Thus despite significant advances, more research needs to be undertaken to further improve the currently available diagnostic technologies.

Molecular analysis of peripheral non-squamous non-small cell lung cancer sampled by radial EBUS.

BACKGROUND AND OBJECTIVE: Treatment optimization of non-squamous non-small-cell lung cancers (nonSq-NSCLC) relies on the molecular analysis of the tumour. We aimed to assess the predictive factors of molecular analysis feasibility (MAF) from samples of peripheral nonSq-NSCLC obtained by radial endobronchial ultrasound bronchoscopy (r-EBUS) and 1.5 mm microbiopsy forceps. METHODS: We reviewed data from consecutive peripheral lung nodules sampled with r-EBUS between January 2012 and July 2014 at a single French University Hospital. nonSq-NSCLC were systematically analysed for EGFR, KRAS, ALK, HER2, PI3K and BRAF throughout the study, and c-MET and ROS1 alterations for the last 10 months. RESULTS: Of 111 nonSq-NSCLC diagnosed by r-EBUS (113 procedures, mean nodule diameter 28 ± 15 mm), 88 were analysed for EGFR and ALK, 87 for KRAS, 86 for HER2, PI3K and BRAF and 14 for c-MET. Forty-one mutations were identified (23 KRAS, 10 EGFR, 2 BRAF, 1 HER2 and 5 ALK rearrangements). Four c-MET overexpressions were noted. MAF rose from 67% for the first 57 procedures to 89% for the last 56 procedures (P = 0.02) likely due to a higher number of biopsies performed (2 ± 1 vs 3 ± 2, P = 0.005). Upper or middle lobe location (OR 1.19, 95% CI: 1.02-1.38, P = 0.03), and at least three biopsies (OR 1.20, 95% CI: 1.04-1.40, P = 0.02) were predictive factors of MAF. Percentage of tumour cells, size of lesion and distance to the pleura did not correlate with MAF. CONCLUSION: Multi-gene molecular analysis could be performed in nearly 80% of paraffin-embedded biopsies or smear specimens sampled by r-EBUS assisted bronchoscopy of peripheral tumoral lung nodules.