Electromagnetic navigation bronchoscopy for localization of bilateral multiple pulmonary nodules: a comparative evaluation of safety and efficacy

Introduction

Lung cancer remains the leading cause of cancer-related deaths worldwide (1), with pulmonary nodules representing a common clinical feature of early lung cancer (2). Owing to the widespread use of low-dose spiral computed tomography (LDCT) screening, advances in diagnostic technologies, and increased awareness of health examinations, the detection rate of bilateral multiple pulmonary nodules (BMPNs) has risen significantly (3). Surgical resection is the standard treatment for pulmonary nodules with potential malignancy (4), and video-assisted thoracoscopic surgery (VATS) has become a widely accepted approach for managing this condition (5). However, intraoperative localization of nodules through tactile palpation or instruments during VATS is often challenging (6). Therefore, preoperative localization of pulmonary nodules is a crucial step to ensure precise and accurate resection. Moreover, nodules located in bilateral lungs present unique challenges for on-target localization. Conventional computed tomography-guided percutaneous dye marking (CTPDM), while widely adopted and effective, is associated with significant risks, including radiation exposure, patient discomfort, and complications such as pneumothorax and hematoma, primarily due to repeated percutaneous pulmonary punctures (7,8). And this method is particularly limited in the case of BMPNs. In recent years, electromagnetic navigation bronchoscopy (ENB) has emerged as a promising alternative that overcomes many limitations of conventional methods (9-11). By utilizing an electromagnetic field to guide instruments to the target nodule, ENB enables accurate localization without radiation exposure, making it a safer option for patients with multiple nodules or those at higher risk of procedural complications. However, to date, no studies have reported the use of electromagnetic navigation bronchoscopy-guided dye marking (ENBDM) for preoperative localization of BMPNs. This retrospective study aims to compare the safety and efficacy of ENBDM with CTPDM for localizing BMPNs. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-920/rc).

Methods

Study design

This is a single-center retrospective study comparing ENBDM versus CTPDM for preoperative localization of BMPNs conducted between January 2020 and September 2024 at The First Affiliated Hospital of Guangzhou Medical University. Preoperative localization and subsequent VATS resection were carried out in both groups by experienced thoracic surgeons. Both groups consistently used indocyanine green (ICG) as a localization dye.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments, and approved by the Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University (No. 2020K-43). Individual consent for this retrospective analysis was waived.

Patient selection

The inclusion criteria were: (I) age between 18 and 80 years; (II) BMPNs confirmed by chest computed tomography (CT) scan; (III) preoperative chest CT indicated that the lesions were difficult to localize or identify through intraoperative observation or palpation; (IV) preoperative nodule localization was performed using either ENBDM or CTPDM, with successful bilateral nodule localization achieved prior to surgery; (V) VATS was conducted to resect the nodules following localization; (VI) adequate cardiopulmonary function to tolerate surgery; (VII) absence of surgical contraindications.

Exclusion criteria included: (I) patients with compromised cardiopulmonary function unable to tolerate ENBDM, CTPDM, or VATS; (II) severe unilateral complications during initial localization preventing contralateral nodule localization.

CTPDM

The localization procedure in the CTPDM group was performed in the CT suite. Patients first underwent plain CT thorax to determine the location, size, and relationship of each nodule to surrounding anatomical structures, as well as to plan the puncture path. After disinfecting and draping the patient, the surgeon administered local anesthesia and performed percutaneous lung puncture along the planned path to the nodule region. A repeat CT scan was conducted to confirm the needle tip’s position within the target area (if unsatisfactory, the needle tip was adjusted and another CT scan was performed). Once the needle tip reached the ideal position, 0.3 mL of ICG (0.6 mg/mL) was injected into the target area. For multiple nodules on one side, the above steps were repeated, followed by a final CT scan to assess the accuracy of localization and to check for complications such as pneumothorax or hemothorax. After completing localization on one side, the patient was instructed to turn over, and the procedure was repeated until all nodules on the contralateral side were successfully localized (Figure 1A,1B). Throughout the process, patients remained awake and were exposed to repeated CT radiation. After all target nodules were localized, patients returned to the ward for short-term observation (typically less than 3 hours) before being transferred to the operating room for VATS resection.

Figure 1 Preoperative pulmonary nodule localization. (A,B) CTPDM for BMPNs (left lung, right lung). (C,D) ENBDM for BMPNs (left lung, right lung). BMPN, bilateral multiple pulmonary nodule; CTPDM, computed tomography-guided percutaneous dye marking; ENBDM, electromagnetic navigation bronchoscopy-guided dye marking.

Notably, should a patient exhibit severe complications during the localization procedure for a unilateral pulmonary nodule, the planned contralateral localization would be immediately discontinued. In such circumstances, the patient would be transferred back to the ward for close monitoring. Following clinical assessment, either expectant management with close surveillance or a unilateral surgery would be performed, while the originally scheduled bilateral thoracic procedure would be aborted.

ENBDM

The ENBDM procedure was performed in the operating room. The patient was placed supine decubitus on a special electromagnetic navigation bed and received intravenous anesthesia and a laryngeal mask airway for ventilation. Nodule localization was initiated with a flexible bronchoscope (outer diameter, 4.1 mm; working channel, 2.0 mm) integrated with an electromagnetic navigation system (Suzhou Lung-care Medical Technology Co., Ltd., Suzhou, China). The procedure involved registration of a simulated airway map, planning of a navigation trajectory, and localization of the pulmonary nodules by means of a 1.8-mm navigation guidewire used to administer a mixture of 0.3 mL of indocyanine green and 2.0 mL of air. After the patient underwent localization of BMPNs (Figure 1C,1D), they were transferred to the operating table for VATS. The specific procedural steps have been detailed in our team’s previously published manuscripts (10). It is important to note that both CTPDM and ENBDM were performed exclusively by experienced thoracic surgeons within the team. And in both groups, localization and VATS resection were completed on the same day. This workflow minimized potential dye diffusion and ensured comparable procedural timing between the two groups.

Statistical analysis

Key parameters analyzed included demographic data, nodule characteristics, procedural details (localization time, radiation exposure), pain scores, complications, and pathology outcomes. Normally distributed continuous variables were expressed as mean ± standard deviation (SD) and compared using an independent samples t-test. Non-normally distributed continuous variables were presented as median and interquartile range (IQR) and analyzed using Mann-Whitney U test. Categorical variables were reported as frequencies and percentages and compared using Pearson’s χ² test or Fisher’s exact test, as appropriate. Balance assessment was conducted using two-sided statistical tests, with P<0.05 considered statistically significant (R version 4.2.2).

Results

After excluding 8 patients who had bilateral thoracic surgery canceled due to severe localization procedure-related complications during CTPDM, this retrospective analysis enrolled 150 patients, including 79 patients with a total of 201 nodules in the ENB group and 71 patients with 169 nodules in the CT Group (Figure 2). Patient characteristics and localization details are shown in Tables 1,2. The ENB and CT groups were comparable in terms of gender distribution and BMI. Localization times were significantly shorter in the ENB group compared to the CT group (excluding anesthesia and preparation times, P<0.001). Radiation exposure was entirely absent in the ENB group, contrasting with an average of 6.6 exposure sessions in the CT group (P<0.001). Pain scores were markedly lower in the ENB group compared to the CT group (P<0.001). The ENB group reported no procedure-related complications, while the CT group experienced pneumothorax in 15.5% of cases, pulmonary hematoma in 12.7%, and hemothorax in 2.8% (P<0.001). There were no statistical differences between two groups in terms of lobe location (P=0.30) and radiological features (P=0.52). Nodules in the ENB group were smaller (P<0.001). The distance between the pulmonary nodules and the positioning points marked by ENB and CT, which were automatically calculated by the system, showed no significant difference (P=0.15). Wedge resection was the predominant surgical approach in both groups, with slightly higher rates of segmentectomy and lobectomy in the ENB group. All resections contained the target nodules, and no cases required repeat sampling.

Figure 2 The patients recruitment process. CTPDM, computed tomography-guided percutaneous dye marking; ENBDM, electromagnetic navigation bronchoscopy-guided dye marking.

Discussion

The localization strategies of pulmonary nodules for diagnostic and therapeutic purposes have undergone transformative advancements over the years. While conventional techniques, including CTPDM and hook wire localization, remain prevalent, their clinical utility is limited by procedure-related complications, such as pneumothorax and hemothorax. ENB, integrating electromagnetic field spatial tracking with three-dimensional CT reconstruction to guide the bronchoscope to the target nodule, has emerged as a promising alternative approach (12).

Our previous research has systematically validated the precision and efficacy of ENBDM for unilateral pulmonary nodule localization (10). Our subsequent investigation extended this to ipsilateral multiple nodules, with ENBDM achieving simultaneous marking of multiple nodules accurately, allowing for successful surgical resection (13). The integration with ICG fluorescence imaging resulted in high localization success rates and enhanced intraoperative visualization, further supporting its utility in complex cases involving multiple nodules.

BMPNs pose significant diagnostic and therapeutic challenges due to their diverse etiologies and the technical complexities associated with their management. Simultaneous bilateral VATS has emerged as a viable minimally invasive strategy, demonstrating comparable or superior perioperative outcomes relative to staged procedures, particularly in patients with early-stage disease and favorable performance status (14,15). The precise localization of BMPNs remains a critical determinant of therapeutic success, necessitating advanced techniques for accurate intraoperative identification. In this context, ENBDM was implemented as a potential solution, with the aim of optimizing both procedural safety and localization efficacy in this complex clinical scenario.

Our novel comparative analysis of these two techniques in patients with MBPNs demonstrated that, even after excluding eight cases with severe percutaneous puncture complications, the CTPDM cohort maintained a significantly higher incidence of procedure-related complications compared to the ENBDM group. The CT-guided group exhibited markedly elevated rates of pneumothorax [15.5% (11/71) vs. 0%], hemothorax [2.8% (2/71) vs. 0%], pulmonary hematoma [12.7% (9/71) vs. 0%], and other minor complications [7% (5/71) vs. 0%], reaching statistical significance (P<0.001). These findings substantiate the safety profile of ENBDM, particularly for patients with elevated comorbidity burdens or heightened risks of procedural complications (16,17).

The CTPDM cohort demonstrated significantly higher radiation exposure metrics compared to ENBDM, both in terms of per-nodule localization attempts (2.8±0.8 vs. 0, P<0.001) and cumulative procedural doses (6.6±1.9 vs. 0, P<0.001). This disparity primarily stems from ENBDM’s utilization of a real-time electromagnetic navigation platform, which enables precise target localization without radiation exposure throughout the entire procedure. The radiation-free nature of ENBDM not only enhances operator safety but also eliminates cumulative radiation risks associated with repeated localization attempts.

In the CTPDM cohort, each radiation exposure event corresponded to a percutaneous puncture adjustment, resulting in significantly prolonged localization times [25 (IQR, 20.5–32) vs. 8 (IQR, 7–10.5) min, P<0.001]. This iterative correction process not only increased procedural duration but also induced measurable patient discomfort (pain score: 3.1±1.5 vs. 0, P<0.001) and elevated the risk of pleural-related complications. ENBDM offers significant procedural advantages by performing nodule localization under general anesthesia, thereby eliminating patient discomfort and psychological distress. The ability to conduct bilateral localization in a single supine position without repositioning requirements streamlines the workflow, while the integration of localization and surgical resection within the OR eliminates interdepartmental transfers, optimizing treatment efficiency and patient safety.

Our nodule-level analysis demonstrated comparable localization accuracy between ENBDM and CTPDM [12 (IQR, 10–15) vs. 11 (IQR, 6–18) mm, P=0.15], with no significant differences in lobe location (P=0.30) or radiological characteristics (P=0.52). Notably, ENBDM exhibited superior performance in localizing smaller nodules [6 (IQR, 5–8) vs. 7 (IQR, 6–9) mm, P<0.001] and more peripherally located lesions [distance from pleura: 3 (IQR, 2–7) vs. 5 (IQR, 3–10) mm, P<0.001], while maintaining a favorable safety profile. ENBDM demonstrated maintained localization accuracy, and an optimized safety profile compared to CTPDM. These findings further corroborate previous reports (18), demonstrating enhanced validation for the efficacy of ENBDM in the accurate localization of both unilateral and bilateral pulmonary nodules. It is noteworthy that all patients in both groups underwent the same-day surgery following localization, effectively preventing potential diffusion or positional shift of indocyanine green. Maintaining a short interval between localization and resection is critical to preserving marker visibility and positional accuracy. In clinical settings where longer delays are unavoidable, progressive dye diffusion could theoretically affect intraoperative identification, underscoring the importance of procedural coordination between radiology and surgery teams. The higher rates of segmentectomy and lobectomy in the ENBDM group reflected differences in surgical indications rather than localization accuracy. ENBDM was often used for patients requiring anatomical resection due to multiple or radiologically suspicious nodules, and all cases showed accurate intraoperative correspondence between dye marks and target lesions. Although bronchoscopy is conventionally limited in accessing the most distal airways due to progressive bronchial narrowing, several factors may explain why this limitation was not observed in our series. The use of a 4.1 mm bronchoscope combined with a 1.8 mm navigation guidewire enabled entry into higher-generation bronchi and precise dye placement near the target lesion. When a natural bronchial route was absent, a small artificial channel was created under real-time electromagnetic guidance. Furthermore, the dye was deliberately injected at the visceral pleura adjacent to the target nodule to enhance intraoperative fluorescence visualization. These technical refinements collectively contributed to the high localization success rate of ENBDM, even for nodules located within a few millimeters of the pleural surface.

It is important to note that the accuracy requirements for ENB-guided dye localization differ from those for diagnostic biopsy. While the diagnostic yield of ENB for tissue sampling has been reported to be approximately 70–75% in large multicenter studies (19-21), successful localization does not necessitate direct access to the nodule center. In the context of preoperative marking, placement of the dye within an acceptable radius—typically within 20 mm of the nodule center—is sufficient to ensure intraoperative visualization and accurate wedge resection. In our cohort, the median distance between dye and target nodule was 12 (IQR, 10–15) mm, well within this safety margin, and all marked nodules were successfully resected without the need for additional sampling.

While our findings demonstrate the safety and efficacy of ENBDM, certain limitations inherent to the retrospective study design necessitate validation through prospective multicenter trials. The technical demands of ENBDM, requiring proficient operator expertise, significantly influence its localization accuracy, particularly for small or deeply situated nodules, which may subsequently impact surgical resection outcomes. Although the current availability of ENB systems and trained personnel remains limited in some institutions, these constraints should be viewed as an impetus to promote wider adoption of technologies that enhance patient safety and surgical precision. And emerging evidence regarding its learning curve appears favorable (22). The integration of advanced imaging modalities (23,24), including digital tomosynthesis and cone-beam CT, is anticipated to further enhance ENB-guided localization precision. Collectively, these developments establish ENB-guided BMPNs localization as a clinically viable alternative, offering both high success rates and an optimized safety profile.

Conclusions

This study provides evidence that ENBDM achieves comparable localization efficacy and accuracy to CTPDM in patients with BMPNs. The elimination of ionizing radiation exposure and procedural discomfort, combined with reduced localization timing and lower complication rates, establishes ENBDM as a particularly advantageous approach for patients requiring bilateral interventions or those with elevated complication risks. These findings collectively demonstrate that ENBDM represents a safe, efficient, and clinically reliable modality for preoperative BMPNs localization.

Acknowledgments

The abstract has been selected for poster display at the 2025 ESTS.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-920/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-920/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-920/prf

Funding: This study was supported by National Key R&D Program of China (No. 2017YFC0112700).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-920/coif). S.L. serves as an unpaid editorial board member of Translational Lung Cancer Research from February 2025 to January 2026. All authors report that this study was supported by National Key R&D Program of China (No. 2017YFC0112700). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments, and approved by the Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University (No. 2020K-43). Individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424. [Crossref] [PubMed]
2. Smith RA, Andrews KS, Brooks D, et al. Cancer screening in the United States, 2019: A review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin 2019;69:184-210. [Crossref] [PubMed]
3. Zhang Y, Fu F, Chen H. Management of Ground-Glass Opacities in the Lung Cancer Spectrum. Ann Thorac Surg 2020;110:1796-804. [Crossref] [PubMed]
4. International Early Lung Cancer Action Program Investigators. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006;355:1763-71. [Crossref] [PubMed]
5. Klapper J, D'Amico TA. VATS versus open surgery for lung cancer resection: moving toward a minimally invasive approach. J Natl Compr Canc Netw 2015;13:162-4. [Crossref] [PubMed]
6. Tamura M, Oda M, Fujimori H, et al. New indication for preoperative marking of small peripheral pulmonary nodules in thoracoscopic surgery. Interact Cardiovasc Thorac Surg 2010;11:590-3. [Crossref] [PubMed]
7. Li X, Xu K, Cen R, et al. Preoperative computer tomography-guided indocyanine green injection is associated with successful localization of small pulmonary nodules. Transl Lung Cancer Res 2021;10:2229-36. [Crossref] [PubMed]
8. Voulaz E, Giudici VM, Lanza E, et al. Percutaneous Computed Tomography (CT)-Guided Localization with Indocyanine Green for the Thoracoscopic Resection of Small Pulmonary Nodules. J Clin Med 2023;12:6149. [Crossref] [PubMed]
9. Kuo SW, Tseng YF, Dai KY, et al. Electromagnetic Navigation Bronchoscopy Localization Versus Percutaneous CT-Guided Localization for Lung Resection via Video-Assisted Thoracoscopic Surgery: A Propensity-Matched Study. J Clin Med 2019;8:379. [Crossref] [PubMed]
10. Zhang J, He J, Chen J, et al. Application of indocyanine green injection guided by electromagnetic navigation bronchoscopy in localization of pulmonary nodules. Transl Lung Cancer Res 2021;10:4414-22. [Crossref] [PubMed]
11. Song JW, Park IK, Bae SY, et al. Electromagnetic Navigation Bronchoscopy-Guided Dye Marking for Localization of Pulmonary Nodules. Ann Thorac Surg 2022;113:1663-9. [Crossref] [PubMed]
12. Folch EE, Labarca G, Ospina-Delgado D, et al. Sensitivity and Safety of Electromagnetic Navigation Bronchoscopy for Lung Cancer Diagnosis: Systematic Review and Meta-analysis. Chest 2020;158:1753-69. [Crossref] [PubMed]
13. Wang R, Chen Y, Wang C, et al. A better option for localization of multiple pulmonary nodules in the ipsilateral lung: electromagnetic navigation bronchoscopy-guided preoperative localization. Transl Lung Cancer Res 2025;14:775-84. [Crossref] [PubMed]
14. Zhou JJ, Song XY, Huang BY, et al. A retrospective analysis of simultaneous bilateral uniportal thoracoscopic surgeries for multiple primary bilateral pulmonary nodules. J Cardiothorac Surg 2024;19:566. [Crossref] [PubMed]
15. Yang L, Guo C, Zhang Y, et al. Simultaneous bilateral video-assisted thoracic surgery is safe and feasible for multiple primary lung cancers. J Cardiothorac Surg 2024;19:436. [Crossref] [PubMed]
16. Chen YC, Huang TW, Hsu HH, et al. Simultaneous Patent Blue Dye Injections Aid in the Preoperative CT-Guided Localization of Multiple Pulmonary Nodules. Medicina (Kaunas) 2022;58:405. [Crossref] [PubMed]
17. Xu L, Wang J, Liu L, et al. Computed tomography-guided cyanoacrylate injection for localization of multiple ipsilateral lung nodules. Eur Radiol 2022;32:184-93. [Crossref] [PubMed]
18. Kops SEP, Heus P, Korevaar DA, et al. Diagnostic yield and safety of navigation bronchoscopy: A systematic review and meta-analysis. Lung Cancer 2023;180:107196. [Crossref] [PubMed]
19. Ost DE, Ernst A, Lei X, et al. Diagnostic Yield and Complications of Bronchoscopy for Peripheral Lung Lesions. Results of the AQuIRE Registry. Am J Respir Crit Care Med 2016;193:68-77. [Crossref] [PubMed]
20. Seijo LM, de Torres JP, Lozano MD, et al. Diagnostic yield of electromagnetic navigation bronchoscopy is highly dependent on the presence of a Bronchus sign on CT imaging: results from a prospective study. Chest 2010;138:1316-21. [Crossref] [PubMed]
21. Yarmus L, Akulian J, Wahidi M, et al. A Prospective Randomized Comparative Study of Three Guided Bronchoscopic Approaches for Investigating Pulmonary Nodules: The PRECISION-1 Study. Chest 2020;157:694-701. [Crossref] [PubMed]
22. Xue M, Lan K, Yan X, et al. Electromagnetic navigation bronchoscopy-guided preoperative lung nodule localization in video-assisted thoracic surgery (VATS): a learning curve analysis. Transl Lung Cancer Res 2024;13:2561-72. [Crossref] [PubMed]
23. Dunn BK, Blaj M, Stahl J, et al. Evaluation of Electromagnetic Navigational Bronchoscopy Using Tomosynthesis-Assisted Visualization, Intraprocedural Positional Correction and Continuous Guidance for Evaluation of Peripheral Pulmonary Nodules. J Bronchology Interv Pulmonol 2023;30:16-23. [Crossref] [PubMed]
24. Patrucco F, Daverio M, Airoldi C, et al. 4D Electromagnetic Navigation Bronchoscopy for the Sampling of Pulmonary Lesions: First European Real-Life Experience. Lung 2021;199:493-500. [Crossref] [PubMed]