Comparative efficacy and safety of electromagnetic navigation bronchoscopy localization and CT- guided percutaneous localization in thoracoscopic resection of pulmonary nodules: a systematic review and meta-analysis

doi:10.21203/rs.3.rs-2069587/v1

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Comparative efficacy and safety of electromagnetic navigation bronchoscopy localization and CT- guided percutaneous localization in thoracoscopic resection of pulmonary nodules: a systematic review and meta-analysis

https://doi.org/10.21203/rs.3.rs-2069587/v1

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Objectives

This study was designed to evaluate the efficacy and safety between electromagnetic navigation bronchoscopy (ENB) and CT-guided percutaneous localization prior to resection of pulmonary nodules.

Methods

Pubmed, Embase, Web of science, and the Cochrane library databases were searched from January 2000 to April 2022 for relevant studies. The primary outcome was the success rate, and the secondary outcomes were the pneumothorax rates and localization time. The meta-analysis was performed by Review Manager 5.4.

Results

Four cohort studies comprising 366 patients (ENB group: 160, CT group: 206) were analyzed. Compared with the CT-guided group, the ENB-guided group was associated with lower pneumothorax rates (relative ratio [RR] = 0.16, 95% CI 0.04–0.65, P = 0.01). No significant differences were found in success rates (relative ratio [RR] = 1.02, 95% confidence interval [CI] 0.99–1.05, P = 0.21) and localization time (mean difference [MD] = 0.99, 95% CI -5.73-7.71, P = 0.77) between the ENB- and CT-guided groups.

Conclusions

ENB-guided localization has huge prospects as a preoperative marking technique before pulmonary nodule resection.

Electromagnetic navigation bronchoscopy

CT-guided

localization

pulmonary nodule

video-assisted thoracic surgery

Lung cancer remains one of the most common causes of cancer death, with an overall 5-year survival rate lower than 20% [1]. However, the 5-year survival rate can be superior to 90% when lung cancer is detected early [2].

The latest guidelines for non-small cell lung cancer highly recommend screening with low-dose computed tomography (LDCT) to reduce lung cancer-related mortality [3]. Accordingly, the detection of lower-staged lung nodules has significantly increased[4–6]. However, these small lung nodules can be challenging to resect with minimally invasive procedures when they are impalpable or not visible[7]. Accordingly, several methods have been developed to locate these small lesions before undergoing thoracic surgery.

The oldest and most common localization method for lung resection is computed tomography (CT)-guided percutaneous localization, which has been established to be a safe and effective approach [8–10]. However, several reports have suggested that the CT-guided percutaneous marking technique leads to many complications, including pneumothorax (< 25%)[8, 11] and wire dislodgement (< 33%)[12, 13], which are rare but potentially fatal [14–17].

In recent years, electromagnetic navigation bronchoscopy (ENB)-guided localization methods have gradually replaced CT-guided percutaneous localization methods [18]. An increasing body of evidence suggests that ENB-guided marking is effective at localizing small pulmonary nodules for resection [19–21]. The advantages of ENB-guided localization include a lower risk of complications, including pneumothorax (< 10%)[19, 22], and it can be performed in the operating room.

Few studies have systematically investigated the efficacy and safety between ENB- and CT-guided percutaneous localization. Accordingly, a meta-analysis of the literature was performed in this paper.

Protocol and registration. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for systematic reviews and meta-analyses[23]. The protocol for the meta-analysis was registered at PROSPERO (Registration number: CRD42022345972).

Eligibility criteria. Included studies had to meet the following criteria: (1)prospective or retrospective studies of ≥ 20 subjects with lung nodules that reported complication and success rates associated with hook-wire and ENB before resection; (2) adequate monitoring of complications during the procedure; (3) studies were published in English; (4) either RCTs or cohort studies. Studies were excluded if they: (1) were case reports; (2) were systematic reviews or meta-analyses; (3) not published in English language. Our research was supplemented by a manual search of the references of the included articles.

Search strategy. A literature search was performed on April 20, 2022, on Pubmed, Embase, Web of science, and the Cochrane library, using the search terms: (Electromagnetic navigation) AND (Computed tomography-guided OR CT-guided) AND (pulmonary nodule OR lung nodule) AND (localization) AND (video-assisted thoracic surgery OR VATS).

Study selection. The retrieved articles were reviewed for eligibility by two investigators (TY and JQF) independently. After checking the title and abstract, two investigators (TY and JQF) evaluated the full text of the remaining articles for inclusion, with disagreements resolved through consensus.

Data extraction. From the eligible articles, we extracted data including publication year, country, study type, number of patients, nodule size, marking methods and outcomes of marking methods, including success rates, pneumothorax rates and localization time.

Quality assessment and risk bias. The methodological quality of the studies was assessed using the Newcastle Ottawa Scale, leading to an overall score of 0–9[24].].Two investigators (TY and JQF) independently scored the studies, and any study with a score of 5 or greater was deemed high quality[24].

Data Synthesis and Statistical Analysis. We listed the success rate of localization, pneumothorax and localization time per study. Subsequently, we calculated the pooled success rate, pneumothorax rate, localization time and the corresponding 95% CI using the random effect model. The Relative Risk (RR) and Mean Difference (MD) were used to clarify which localization method was preferable in each study. Forest plots were generated to visualize the results. Heterogeneity among studies was tested and quantified using the Q test and I² statistic[25]. I² values > 50% represented significant heterogeneity[26]. Statistical significance was set at P < 0.05. Review Manager 5.4 was utilized to conduct the present meta-analysis.

Study selection and characteristics. The initial literature retrieval process yielded 459 studies with 156 duplicates. In total, 303 titles and abstracts were reviewed for eligibility. 7 studies met the criteria for full-text assessment. Of these eligible studies, 4 cohort studies were chosen in the meta-analysis (Fig. 1). The characteristics of the included studies were compiled in Table 1.

Table 1

Characteristics of included studies
Author	Year	Country	Study Type	Participants		Nodule Mean Size(mm)		Marking Technology
Author	Year	Country	Study Type	ENB guided	CT guided	ENB guided	CT guided	ENB guided	CT guided
Tian et al. [29]	2020	China	Cohort study	52	105	Not given	Not given	Methylene blue	Hook wire
Yang et al.[30]	2020	China	Cohort study	12	35	11	7	ICG/iopamidol	ICG/iopamidol
Kuo et al.[28]	2019	Taiwan, China	Cohort study	15	30	10	11	Patent blue vital	Patent blue vital
Bolton et al.[27]	2017	American	Cohort study	81	36	15.9	12.7	Methylene blue	Hook wire

Risk of bias within the studies. According to the Newcastle-Ottawa criteria, all studies were deemed to be high quality (range: 7–9). Detailed assessments of the risk of bias are listed in Table 2.

Table 2

Quality assessment of included studies.
study	Selection				Comparability based on design and analysis	Outcome			Total
study	Representativeness of the sample	Selection of the non-intervention cohort	Ascertainment of exposure	Demonstration that outcome of interest was not present at the start of the study	Comparability based on design and analysis	Assessment of outcome	Was follow-up long enough for outcomes to occur	Adequacy of follow -up of cohorts	Total
Tian et al. [29]	1	1	0	1	2	1	0	1	7
Yang et al.[30]	1	1	1	1	2	1	1	1	9
Kuo et al.[28]	1	1	1	1	2	1	1	1	9
Bolton et al.[27]	1	1	1	1	2	1	1	1	9

Synthesis of results.

Localization success rates.

The technical success rate was the primary outcome of our study. Data pertaining to the technical success rate was reported in all studies [27–30]. The RR was 1.02(95% confidence interval [CI] 0.99–1.05, p = 0.21), with no significant heterogeneity (I² = 0, P = 0.41) (Fig. 2).

Pneumothorax rates.

Pneumothorax rate and localization time were the secondary outcomes of this study. All studies provided data on the pneumothorax rate[27–30]. The pooled RR was 0.16(95% confidence interval [CI] 0.04–0.65, P = 0 .01), with no significant heterogeneity (I² = 0, P = 0.83) (Fig. 3).

Localization time.

3 studies reported on the localization time [16–18]. The MD was 0.99(95% confidence interval [CI]-5.73-7.71, p = 0.77), with significant heterogeneity (I² = 85%, P = 0.001) (Fig. 4). We subsequently explored potential sources of heterogeneity. When one study was removed [29], the heterogeneity significantly decreased (I² = 0%, P = 0.47).

This study showed that the two preoperative localization methods yielded high successful marking rates with no significant difference in localization time. However, the ENB-guided group was associated with a lower incidence pneumothorax rate than the CT-guided group.

Since percutaneous needle localization before VATS was first reported in 1992 by Plunkett et al., [31]. Various localization approaches have been developed to identify small pulmonary nodules[32–35]. CT-guided localization is the most widely used method for localizing small lung nodules for resection. This approach requires percutaneous placement of metal markers, especially hook wires or microcoils [36, 37]. ENB-guided localization is a newer technique of lung nodule localization favorable for difficult-to-reach areas of the lung[38]. This technique reportedly has high accuracy in detecting and marking small pulmonary nodules and is associated with no major complications [39]. To our knowledge, no meta-analysis has hitherto compared ENB-guided versus CT-guided for localization lung nodules. We conducted this systematic review to assess the efficacy and safety of these localization methods.

Meta-analyses have shown no significant differences in localization success rate. CT-guided localization is the most common method for VATS resection, with a localization rate of 93.7–98%[38]. However, the risk of dislodgement or migration of hook-wire after localization is a major limitation of this technique [40]. In our meta-analysis, localization failure was observed in 6 patients in the CT-guided group due to deviation of the hook-wire position. ENB-guided localization is also reportedly safe and successful in localizing small lung lesions [22, 41]. Makris et al. [22]. reported success rates of 98% for ENB localization of pulmonary lesions. In our study, only one patient in the ENB group experienced pneumothorax, leading to localization failure.

Complications such as pneumothorax remain the major concern in pulmonary nodule localization. The rate of pneumothorax associated with the transthoracic procedure was 15–30% [8, 10, 42, 43]. Pneumothorax induced by pleural puncture is a major disadvantage of the percutaneous approach, which may lead to localization failure of multiple lesions. In our study, 13.6% of patients who underwent CT-guided localization developed a pneumothorax, but none required chest tube placement. The pneumothorax rate (0.6%) was significantly lower in the ENB-guided group than in the CT-guided group. The pneumothorax risk is reportedly correlated with the localization method and the lung condition of the patients [28]. Since ENB has been associated with a lower incidence of pneumothorax, it is recommended for patients with COPD or emphysematous lung disease [44, 45].

The localization time was also a secondary outcome of this study. ENB-guided localization can be performed in the operating room before surgery [27, 46, 47] and help reduce patient tension associated with invasive procedures. However, it is a newer method that requires training and specialized equipment [48]. CT-guided localization is an accurate, widely available and reproducible technique. CT-guided technology can be performed by most chest radiologists and was deemed more practical. Our analysis showed no significant difference in localization time between the two groups.

There were certain limitations in this meta-analysis. First, all studies included were retrospective cohort studies since no RCT studies have been conducted. Besides, the sample size was small, which decreased the strength of our findings to a certain extent. Moreover, the propensity matching process was only conducted in one study to minimize bias. Parameters affecting the success rate, pneumothorax rate and localization time, such as tumor operator experience, tumor depth, and tumor size, were not considered. Indeed, publication bias could have led to overestimation of the success rate, pneumothorax rate and localization time. Accordingly, well-designed randomized controlled trials are warranted to compare the effectiveness and safety between ENB and CT-guided marking.

In summary, ENB-guided localization yields outstanding safety and efficacy as a marking method before pulmonary resection. We recommend ENB as a preoperative marking technique for pulmonary nodule surgery.

Data availability

All data generated or analyzed during this study are included in this published article.

Acknowledgments

We thank Home for Researchers editorial team (www.home-for-researchers.com) for language editing service.

Authors' contributions

Qi-Feng Jing: Conceptualization; Formal analysis; Data curation; writing - original draft; Yan Tan: Conceptualization; Investigation; Methodology; Writing-review & editing; Shui-jun Shen: Data curation; Formal analysis; Methodology; Can-yun Wang: Data curation; Formal analysis; Methodology; writing - original draft; Qiao-juan Zhou: Writing-review & editing; Data curation; Investigation; Supervision.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Competing interests

The authors declare no competing interests.

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No competing interests reported.

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Comparative efficacy and safety of electromagnetic navigation bronchoscopy localization and CT- guided percutaneous localization in thoracoscopic resection of pulmonary nodules: a systematic review and meta-analysis

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Abstract

Objectives

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Results

Conclusions

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Introduction

Methods

Results

Discussion

Limitations

Conclusion

Declarations

References

Additional Declarations

Supplementary Files

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