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Background : As the first sentinel lymph nodes (SLN) in lung cancer are most likely to harbor metastasis, their non-invasive identification could have a significant role in future treatments. We investigated the feasibility of adding an SLN procedure to a diagnostic navigation bronchoscopy. Methods : Thirty-one patients were included for injection of 99m Tc-nanocolloid and an iodinated contrast agent intra-/peritumorally and assessment of tracer dissipation via SPECT and CBCT imaging. Injections were performed endobronchially using a multi-modal catheter (Pioneer Plus), combining radial ultrasound and an angulated retractable needle to place injections under fluoroscopy and real-time ultrasound. Results : The injection of an imaging tracer was feasible in all cases using the catheter. Ultrasound visualized 29/30 tumors, and tracer injection was performed in 100% of patients. An SLN was subsequently identified in 10 out of 31 cases (32.3%) via SPECT/CT imaging. Iodinated contrast agent injection under CBCT imaging prior to 99m Tc nanocolloid injection visualized dissipation pathways and enabled needle relocation for subsequent 99m Tc-nanocolloid injection. Conclusions : Performing imaging tracer injections with a multi-modal catheter provided safe and local depot placement immediately following diagnostic navigation bronchoscopy. SPECT/CT imaging using 99m Tc-nanocolloid showed inconsistent results for SLN identification.

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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-2845/coif). The series “Lung Cancer Management—The Next Decade” was commissioned by the editorial office without any funding or sponsorship. RLJV reports that his institution has received unrestricted funding from Philips, AstraZeneca, Johnson & Johnson, Siemens, Pentax, Galvanize Therapeutics, and Bioncise. Besides, his institution has received funding for consultancy from Johnson & Johnson, compensation for lecturing at educational events from Medtronic. He and his institution have patents planned, issued and pending. His institution has obtained compensation for travel fees for attending meetings from Pentax. He’s an unpaid board member of the Dutch Society of Technical Physicians. SEPK reports that his institution has received unrestricted research funding from Philips, AstraZeneca, Johnson & Johnson, Pentax, and Siemens. Besides, his institution has received fees for consultancy from Johnson & Johnson. INW and DKMW report that the institution has received research funding from Philips, AstraZeneca, Johnson & Johnson, and Pentax. EHFMH reports that his institution has received unrestricted research funding from Philips, AstraZeneca, Johnson&Johnson, Pentax, Galvanize Therapeutics, and Bioncise. His institution has received fees for consultancy from Johnson & Johnson and Philips, speaker’s fees from Janssen-Cilag and Pentax, and travel support from Pentax. He and his institution have patents planned, issued and pending. He’s an unpaid board member of the WABIP and EABIP. The authors have no other conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

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 99m Tc-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 99m Tc (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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-984/coif). RLJV reports unrestricted research grants from Philips Medical, Astra Zeneca, Pentax Medical and Johnson & Johnson, consulting fees from Johnson & Johnson and Intuitive Surgical, speaker fees from Medtronic, Travel arrangements from Johnson & Johnson and Intuitive Surgical, is a board member of the Dutch Society of Technical Physicians (NVvTG) and has patents issued, pending and planned in the field of advanced and navigation bronchoscopy; EHFMvdH reports unrestricted research grants from Philips Medical, Astra Zeneca, Pentax Medical and Johnson & Johnson, consulting fees from Johnson & Johnson and Intuitive Surgical, speaker fees from Janssen-Cilag and Pentax Medical, Travel arrangements from Johnson & Johnson and Intuitive Surgical, is a board member of European Association for Bronchology and Interventional Pulmonology (ECBIP) and a board of regents member of the World Association for Bronchology and Interventional Pulmonology (WABIP) and has patents issued, pending and planned in the field of advanced and navigation bronchoscopy. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)