Comparison of electromagnetic navigation bronchoscopic localization and computed tomographic imaging-guided methylene blue localization in the resection of pulmonary nodules: a retrospective cohort study

Introduction

Lung cancer remains the most prevalent type of cancer and one of the most frequent causes of cancer death in men and women worldwide (Bade & De la Cruz, 2020). Most patients reach an advanced stage at diagnosis, which in most cases leads to poor prognosis or death. The five-year survival rate for patients with stage I disease who undergo radical resection is reported to be between 68% and 92% (Yang et al., 2021).

Detecting lung cancer early is crucial for effectively managing the disease. Surgical removal is widely considered the best treatment for early-stage lung cancer. As lung cancer screening methods like low-dose computed tomography (CT) become more widely available and accessible, the incidence of pulmonary nodules is increasing. These screening techniques allow for the quick detection and removal of identified pulmonary carcinomas, which promotes early diagnosis and treatment.

Despite the swift invention of technological methods that ease the localization of small pulmonary nodules, identifying and marking such pulmonary lesions may remain a challenge to some surgeons. Therefore, various techniques have been developed to support the localization of such lesions within the lungs. These techniques include CT imaging-guided localization via the injection of marker dye or hook wire insertion, electromagnetic bronchoscopic localization via the injection of marker dye (Xue et al., 2020; Tian et al., 2020; Mariolo et al., 2021; Xu et al., 2021; Zhu et al., 2022; Xia et al., 2024). However, there is currently no universally accepted standard for preoperative localization techniques.

Electromagnetic navigation bronchoscopy (ENB) is a recently developed localization technique that enables surgeons to reach peripheral pulmonary lesions. This innovative approach utilizes an image-guided flexible catheter and a dedicated navigation software system to facilitate precise navigation within the lungs (Xue et al., 2020; Mariolo et al., 2021; Xu et al., 2021; Yao et al., 2023; Dunn et al., 2023; Chan et al., 2023; Bondue et al., 2023; Guo et al., 2022; Lee et al., 2022; Uzbeck et al., 2022; Zhang et al., 2021; Yang et al., 2021; Jiayuan, 2021; Piao et al., 2020; Cheng & Chu, 2019; Folch et al., 2019; Hyun et al., 2019; Qian et al., 2019). After the identification of the landmark of the lesion, a marker dye (methylene blue, indocyanine green, etc.) is injected through the catheter to the localization point within the lungs. Then video-assisted thoracoscopic surgery (VATS) will be done to resect out the nodule.

In this study, we retrospectively compared the safety and efficiency of CT-guided percutaneous localization and electromagnetic navigation bronchoscopic localization via the injection of methylene blue as a marking dye to research the most accurate and safest technique for the preoperative localization of pulmonary nodules. The study assessed the success rate of dye localization by determining the proportion of patients in whom the intended lesions were accurately identified.

Patients and Methods

Results

Discussions

In this study, we realized very high success rates in using percutaneous CT-guided or ENB via dye marking for the localization of peripheral lesions with subsequent VATS resection. We utilized methylene blue as a marker dye because of its ease of convergence around the target lesion and visibility to surgeons when the thoracoscope is inserted in the patient’s thorax. These led to the high feasibility of all the two localization techniques and showed their comparability. However, CT-guided, which is an invasive technique, may require multiple insertion points when there are numerous nodules located in different lobes or located bilaterally in the two lungs of a person. Compared to the CT-guided technique, the ENB marking procedure has shown much more safety than other techniques in patients with multiple nodules, because it is less invasive and time-saving (Bondue et al., 2023; Guo et al., 2022; Fu et al., 2023; Tsai et al., 2023).

Secondly, in comparing our results with the existing literature, we found that our success rates for ENB (97.24%) and CT-guided localization (97.58%) are consistent with those reported in prior studies. For instance, Folch et al. (2019) and Khandhar et al. (2017) reported ENB success rates of 88–95%. Our observed complication rates also align with prior findings, with ENB demonstrating significantly fewer complications (0%) compared to CT-guided localization (7.3%). This is consistent with studies reporting higher rates of pneumothorax (5–15%) and hemorrhage (1–5%) for CT-guided procedures (Khandhar et al., 2017; Folch et al., 2019). This consistency of our results with existing literature has shown the dependability of our study.

Moreover, our study showed that the maximum nodule diameter of CT-guided localization was smaller than that of ENB localization, which was in contrast to the Tian et al. (2020) results, which showed that the ENB group located smaller lung nodules. Tian et al. (2020) study used hook wire instead of methylene blue in their CT-guided localization, which may have influenced their allocation of patients while a single localization marker (methylene blue) was used in our studies. This may be related to the subjective choice of the doctor who performed the localization technique, because in our hospital, CT-guided localization has been carried out for a longer time, and the doctor is more confident in locating smaller nodules than ENB. This phenomenon may disappear as the number of ENB cases increases. Our investigation suggested that the lower lobe localization failure rate increased significantly compared to the upper lobe in the ENB group, with no lobar predilection for CT-guided localization. Previous studies on ENB biopsies showed a similar trend, with their results showing higher biopsy success in the upper lobe (Bhatt et al., 2018; Makris et al., 2007). One important reason for this may be the length of the bronchoscope, that was used in the ENB procedure. Since the lower lobes are more distant in their anatomic location, bronchoscopes shorter in length may not reach them satisfactorily, which has led to a significant difference in the results as shown in our studies. This suggests that CT-guided localization has an advantage over ENB localization in the lower lobe. We recommend the extension of the length of the bronchoscopes used for ENB to address this difference. The finding that ENB is less effective for lower lobe nodules is a novel insight that warrants further investigation, therefore, a larger sample size of multicentre data may be required to confirm this suggestion.

This study also showed that both techniques have strengths and limitations. The CT-guided localization method is a well-established technique known for its high success rate, reaching as high as 97.58% (Table 2). However, complications stemming from pleural punctures, such as those encountered during multiple lesion localizations, remain a primary drawback of this approach (Yang et al., 2021). Additionally, there are concerns regarding the increased radiation exposure associated with bilateral pulmonary lesions because the practitioner will spend a longer period in the imaging room to localize bilateral nodules, which poses another limitation to its widespread use (Yang et al., 2021). Patients with emphysematous lung disease or chronic obstructive pulmonary disease (COPD) are not typically recommended to undergo CT-guided localization due to the higher risk of complications associated with this procedure. These complications may include hemopneumothorax, hemoptysis, and bronchial hemorrhage, which can pose significant risks to individuals with pre-existing lung conditions. Therefore, alternative localization techniques, such as electromagnetic navigation bronchoscopy (ENB), may be considered safer for patients with emphysematous lung disease or COPD (Theilig et al., 2020; Maalouf et al., 2022).

ENB offers several advantages, including enhanced patient comfort due to its performance under general anesthesia. Additionally, the procedure seamlessly transitions from localization to surgery without the need to adjust settings, thereby reducing procedure duration and associated risks (Xia et al., 2024; Khandhar et al., 2017; Gu et al., 2017; Muñoz-Largacha et al., 2017). The ENB enables access to areas that may be challenging to reach using the CT-guided approach. This encompasses nodules located close to structural reference points, for instance, the costophrenic angle, or underneath the scapula, covering areas like the side facing the mediastinum and the upper back region concealed by the scapula (Yang et al., 2021). In patients suffering from emphysematous lung conditions or chronic obstructive pulmonary disease (COPD), electromagnetic navigation bronchoscopy (ENB) is advisable because it has a proven safety record, which is supported by the absence of adverse events like hemopneumothorax, coughing up blood, and bleeding in the airways, as observed in this research (Table 3). However, ENB has its limitations. Due to its complexity and the requirements needed to perform it swiftly, it requires a high level of skill and experience from an endoscopist, an experienced anesthesiologist, and a highly developed network system to enable its performance ease, making it less readily available in many institutions. Additionally, ENB is a relatively new technique that is only feasible and affordable in high-grade hospitals, limiting its accessibility to a broader population. In addition, the lower lobe nodule localization failure rate of ENB localization was higher than that of CT-guided localization. As for centrally located tumors, the methylene blue disrupts the surgeon’s vision leading to peripheral resection that may require further resection (wedge+segmentectomy) (Table 1).

In addition, our study found that ENB had a significantly lower success rate for nodules in the lower lobes compared to the upper lobes (p = 0.005), while CT-guided localization showed no significant lobar preference (p = 0.073). This suggests that anatomical location plays a critical role in the effectiveness of ENB, particularly in the lower lobes, where longer and more tortuous bronchial pathways may pose challenges for navigation and dye placement. The higher success rate of ENB in the upper lobes may be attributed to the shorter and more straightforward bronchial pathways, which facilitate easier navigation and dye placement. In contrast, the lower success rate in the lower lobes highlights the limitations of ENB in accessing more distal and anatomically complex regions of the lung. CT-guided localization, which relies on direct percutaneous access, appears to be less affected by these anatomical challenges, making it a more reliable option for lower lobe nodules. These findings have important clinical implications. ENB may be preferred for upper lobe nodules, where its success rate is higher and the risk of complications is lower. Conversely, CT-guided localization may be more suitable for lower lobe nodules, particularly in cases where ENB is less effective due to anatomical constraints. Future research should explore the anatomical factors that contribute to these differences, such as bronchial branching patterns and nodule depth, to further refine the selection of localization techniques.

Finally, administering methylene blue provides a cost-effective, reliable, and safe technique for localizing structures within the chest cavity. This is due to the rapid convergence of the dye around or near the target lesion and its visibility to surgeons when using a thoracoscope. Consequently, this technique has found applications in the localization of pulmonary nodules. The study also provides real-world experience and calls for further large-sample studies comparing it directly with other techniques. These factors contribute to the reliability of our results and make our recommendations clear for evidence-based practice. While our study benefits from a diverse patient population drawn from various regions within China, the generalizability of our findings may be influenced by genetic, ethnic, and regional factors. For example, East Asian populations have been shown to have a higher prevalence of ground-glass nodules (GGNs) and distinct molecular profiles (e.g., epidermal growth factor Receptor (EGFR) mutations) compared to Western populations. These differences could impact the success rates and complications of localization techniques. Future multicenter studies involving diverse populations are needed to further explore these factors and enhance the external validity of our findings.

Conclusions

In conclusion, the success rate of ENB localization is similar to that of CT-guided localization. Moreover, the ENB approach allows for swift localization of pulmonary nodules without imposing patient risk, particularly regarding puncture-related complications like hemopneumothorax or hemoptysis. As such, the ENB approach may be considered comparable to the CT-guided approach for identifying and localizing pulmonary nodules. The use of CT-guided localization is more advantageous than the use of ENB localization in the lower lobes.

Supplemental Information