A comparative study of 4-hook anchor device with methylene blue for preoperative pulmonary nodule localization
Introduction
With the widespread adoption of low-dose computed tomography (CT) technology and increased public health awareness, an increasing number of potentially malignant small pulmonary nodules (SPNs) are being detected early during lung cancer screening (1). Video-assisted thoracoscopic surgery (VATS), a minimally invasive surgical technique, has become the preferred method for treating these potentially malignant SPNs (2). However, the small size, soft texture, and deep location of SPNs make direct observation and palpation challenging during VATS, underscoring the need for accurate preoperative localization.
Various pulmonary nodule localization techniques have been developed, including hook-wire, coil, methylene blue, iodine oil, and radionuclide methods (3-6). Although the hook-wire technique is widely used in clinical practice, it has limitations because of its high rate of shedding and migration (5,7,8). To overcome this challenge, a novel 4-hook anchor device was developed to provide more stable and safer positioning (9). Although the 4-hook anchor device has demonstrated good results and safety compared with the hook-wire technique, comparative studies with other localization methods remain insufficient (10). The methylene blue injection technique, a classical localization method, offers potential advantages for specific patient populations because of its smaller injection needle size and hemostatic adhesive properties and is widely used in clinical practice (11). However, research comparing the methylene blue technique with the 4-hook anchor device is lacking.
This study aimed to fill this research gap by comparing the efficiency and safety of preoperative localization of SPNs before VATS via a 4-hook anchor device and the methylene blue technique. We anticipate that this study will provide clinicians with valuable insights to help them choose the most appropriate preoperative localization method. This will not only increase the success rate of surgery and reduce the risk of complications but also improve the overall patient experience, offering new hope for the treatment of lung cancer patients. We present this article in accordance with the STROCSS reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1535/rc).
Methods
The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College (No. 21/176-2847) and informed consent was provided by all the patients.
Patients
This single-center, retrospective study was conducted from May 2021 to April 2023. A total of 75 patients with 84 SPNs were included, with 35 patients (41 SPNs) in the 4-hook anchor group and 40 patients (43 SPNs) in the methylene blue marking group. The inclusion criteria were as follows: (I) a nodule diameter smaller than 20 mm; (II) age between 18 and 75 years; (III) safe puncture path; (IV) no emphysema or pleural adhesion; and (V) normal general condition and coagulation profile. The exclusion criteria were as follows: (I) nodules located deeper and near the hilum; (II) incomplete clinical information or lack of informed consent; and (III) severe emphysema, interstitial lung disease, extensive pleural adhesions, severe comorbidities, or those not suitable for VATS. The study cohort flow diagram is shown in Figure 1.
Clinical data and observational indicators
The primary outcome measure was the success of localization, defined by the following criteria: (I) no fracture or error of the localization device during the procedure and (II) no displacement, dislocation, or methylene blue dispersal during VATS. The secondary outcome measures included localization-related complications, puncture time, VATS operative time for SPNs, hemorrhage, and hospital costs. The overall puncture operation time was defined as the interval between the start of local anesthesia and the placement of the localizer in the pulmonary nodule. The endpoints were recorded by two independent assessors (1 interventional radiologist and 1 thoracic surgeon).
Localization techniques
Both procedures were conducted by two experienced interventional radiologists, each with a track record of more than 50 cases for their respective localization techniques. The 4-hook anchor device (SensCure Biotechnology, Ningbo, China) comprises four main components: a coaxial needle, a safety buckle, a pusher, and an anchor claw, all of which are interconnected with a suture. The detailed specifications of the device match those previously published by our team (10). The claw and sutures are inserted into a 20 G, 100 mm coaxial needle, and the pusher is used to deploy the 4-hook anchor and its sutures. After a CT scan identifies the needle puncture site, the localizer is inserted percutaneously toward the nodule, leaving the suture in the pleural space.
For the methylene blue injection group, standard CT-guided lung nodule localization steps were as follows: skin disinfection, local anesthetic application, and insertion of a 21 G needle aimed 0.5–1 cm from the nodule. After confirming needle placement, 0.2 mL of a 1:1 methylene blue and adhesive mixture was injected. A post-injection CT scan revealed a high-density area replacing the nodule, confirming success. The puncture site was then bandaged, and the patient was prepared for surgery. The 4-hook anchor device and methylene blue injection are shown in Figure 2. The localization processes of the methylene blue (Figure 3A) and 4-hook anchor device (Figure 3B) with CT guidance are shown in Figure 3.
VATS operation
VATS wedge resections of the nodules, guided by either the 4-hook anchor device or methylene blue, was performed by three experienced surgeons. Each surgeon had extensive VATS experience, having completed hundreds of procedures and at least 30 thoracoscopic resections post localization. The excised lung tissue was assessed for complete lesion removal, followed by immediate examination of frozen sections. If necessary, further procedures, such as expanded wedge resection, lobectomy, or thoracotomy, were performed. Post discharge, patients were followed up 1 month later for late complications, documented via phone calls with the patients or their relatives, with treatment provided as necessary. All patients underwent a chest CT scan and laboratory tests 1 month after discharge.
Statistical analysis
The data were analyzed via R software (version 3.6.1; http://www.Rproject.org). All the statistical tests were 2-sided, with P<0.05 considered statistically significant. The normally distributed data were expressed as the mean ± standard deviation (means ± SD), and independent sample t-tests were used for group comparisons. Nonnormally distributed data were expressed as medians and interquartile ranges [M (Q1, Q3)], with the Mann-Whitney U test used for group comparisons. The Pearson χ2 test or Fisher’s exact test was used for categorical data comparisons, and the Mann-Whitney U test was used for ordered categorical data comparisons. The standardized mean difference (SMD) was also used to compare differences between groups.
Results
The study included a total of 75 patients, including 30 males and 45 females, with an average age at diagnosis of 52.5 years. There was no significant difference in age between the methylene blue and 4-hook anchor groups. Most patients had no smoking history (82.67%), and the majority of nodules were solitary (90.67%). The median nodule diameter was 7.00 mm, and the median depth from the pleura was 7.82 mm. Ground-glass opacity (GGO) was the most common nodule type (86.90%), followed by solid nodules (13.10%). The right lower lobe (RLL) was the most common nodule location (32.14%). Clinical data of the patients are listed in Table 1.
Table 1
| Characteristic | All patients | Methylene blue | 4-hook anchor | P value | SMD |
|---|---|---|---|---|---|
| Sex | 0.345 | 0.220 | |||
| Male | 30 (40.00) | 18 (45.00) | 12 (34.29) | ||
| Female | 45 (60.00) | 22 (55.00) | 23 (65.71) | ||
| Age at diagnosis (years) | 52.5±11.6 | 54.2±12.4 | 50.5±10.4 | 0.165 | 0.331 |
| Smoking history | 0.967 | 0.009 | |||
| No | 62 (82.67) | 33 (82.50) | 29 (82.86) | ||
| Yes | 13 (17.33) | 7 (17.50) | 6 (17.14) | ||
| Nodule count | 0.297 | 0.347 | |||
| 1 | 68 (90.67) | 38 (95.00) | 30 (85.71) | ||
| 2 | 6 (8.00) | 2 (5.00) | 4 (11.43) | ||
| 3 | 1 (1.33) | 0 (0.00) | 1 (2.86) | ||
| Nodule diameter (mm) | 7.00 (5.00, 10.00) | 7.00 (5.50, 10.00) | 6.00 (5.00, 10.00) | 0.274 | 0.267 |
| Nodule depth from pleura (mm) | 7.82 (3.90, 15.48) | 7.00 (3.00, 14.00) | 10.10 (5.40, 17.40) | 0.075 | 0.329 |
| Nodule type | 0.125 | 0.341 | |||
| GGO | 73 (86.90) | 35 (81.40) | 38 (92.68) | ||
| Solid | 11 (13.10) | 8 (18.60) | 3 (7.32) | ||
| Nodule location | 0.297 | 0.480 | |||
| RUL | 24 (28.57) | 12 (27.91) | 12 (29.27) | ||
| RML | 2 (2.38) | 1 (2.33) | 1 (2.44) | ||
| RLL | 27 (32.14) | 15 (34.88) | 12 (29.27) | ||
| LUL | 19 (22.62) | 12 (27.91) | 7 (17.07) | ||
| LLL | 12 (14.29) | 3 (6.98) | 9 (21.95) |
Count data are represented as n (%). Quantitative data that conform to a normal distribution are expressed as mean ± SD, whereas quantitative data that do not conform to a normal distribution are presented as the median and interquartile range (M [Q1, Q3]). GGO, ground-glass opacity; RUL, right upper lobe; RML, right middle lobe; RLL, right lower lobe; LUL, left upper lobe; LLL, left lower lobe; SMD, standardized mean difference; SD, standard deviation.
The puncture operation time was significantly longer in the methylene blue group (P=0.007), with a mean time of 16.0 minutes, than in the 4-hook anchor group (15.0 minutes). However, the localizer depth from the pleura and puncture times for each nodule were not significantly different between the two groups. There were no significant differences in complications such as pneumothorax or parenchymal hemorrhage between the groups. No air embolism events were observed in any of the patients who underwent localization with either the 4-hook anchor group or methylene blue. The localization success rate was slightly greater in the 4-hook anchor group (95.122%) than in the methylene blue group (88.372%), but this difference was not statistically significant. In the methylene blue group, two patients experienced methylene blue dispersal during surgery, which was deemed unsuccessful localization. These two patients required a transition from wedge resection to segmentectomy because of unsuccessful localization. Details of the localization procedure are listed in Table 2.
Table 2
| Characteristic | All patients | Methylene blue | 4-hook anchor | P value | SMD |
|---|---|---|---|---|---|
| Overall puncture operation time (min) | 15.0 (13.0, 19.0) | 16.0 (13.8, 21.0) | 15.0 (13.0, 16.5) | 0.007* | 0.654 |
| Localizer depth from pleural (mm) | 9.0 (4.5, 15.1) | 8.0 (4.5, 13.0) | 11.8 (4.6, 16.6) | 0.314 | 0.275 |
| Puncture times of each nodule | 1.0 (1.0, 2.0) | 1.0 (1.0, 2.0) | 1.0 (1.0, 2.0) | 0.762 | 0.032 |
| Complications | 1.000 | 0.153 | |||
| None | 76 (90.48) | 38 (88.37) | 38 (92.68) | ||
| Pneumothorax | 5 (5.95) | 3 (6.98) | 2 (4.88) | ||
| Parenchymal hemorrhage | 3 (3.57) | 2 (4.65) | 1 (2.44) | ||
| Air embolism | 0 (0.00) | 0 (0.00) | 0 (0.00) | ||
| Localization success | 0.469 | 0.247 | |||
| Yes | 77 (91.67) | 38 (88.37) | 39 (95.12) | ||
| No | 7 (8.33) | 5 (11.63) | 2 (4.88) |
Count data is represented as n (%). Quantitative data that do not conform to a normal distribution are presented as the median and interquartile range [M (Q1, Q3)]. *, P<0.05. SMD, standardized mean difference.
The VATS operative time for SPNs was significantly shorter in the 4-hook anchor group (P<0.001), with an average operative time of 57.4 minutes, than in the methylene blue group (79.5 minutes). There was no significant difference in hemorrhage volume or nodule resection method between the groups. Hospital stays and costs did not differ significantly between the two groups. The most common pathology findings were minimally invasive adenocarcinoma (38.10%) and adenocarcinoma in situ (33.33%), with no significant differences between the groups in terms of pathology type. Details of the VATS and pathology are listed in Table 3.
Table 3
| Characteristic | All patients | Methylene blue | 4-hook anchor | P value | SMD |
|---|---|---|---|---|---|
| VATS operative time for SPNs (min) | 69.2±17.3 | 79.5±14.3 | 57.4±12.4 | <0.001* | 1.676 |
| Hemorrhage (mL) | 10.0 (5.0, 10.0) | 5.0 (5.0, 10.0) | 10.0 (6.5, 13.5) | 0.088 | 0.428 |
| Nodule resection under VATS | 0.26 | 0.39 | |||
| Wedge resection | 81 (96.43) | 40 (93.03) | 41 (100.00) | ||
| Segmentectomy | 3 (3.57) | 3 (6.97) | 0 (0.00) | ||
| Hospital stays (days) | 6.0 (5.0, 7.0) | 6.0 (5.0, 7.0) | 5.0 (4.0, 7.0) | 0.099 | 0.415 |
| Hospital cost (yuan) | 68,758.567±18,750.110 | 70,315.680±18,230.159 | 66,979.009±19,438.362 | 0.446 | 0.179 |
| Pathology | 0.61 | 0.56 | |||
| Minimally invasive adenocarcinoma | 32 (38.10) | 16 (37.21) | 16 (39.02) | ||
| Adenocarcinoma in situ | 28 (33.33) | 16 (37.21) | 12 (29.27) | ||
| Invasive adenocarcinoma | 10 (11.90) | 5 (11.63) | 5 (12.20) | ||
| Fibrosis scar tissue | 3 (3.57) | 1 (2.33) | 2 (4.88) | ||
| Reactive lymph node | 2 (2.38) | 0 (0.00) | 2 (4.88) | ||
| Inflammatory lesions | 7 (8.33) | 5 (11.63) | 2 (4.88) | ||
| Granuloma | 1 (1.19) | 0 (0.00) | 1 (2.44) | ||
| Hamartoma | 1 (1.19) | 0 (0.00) | 1 (2.44) |
Count data are represented as n (%). Quantitative data that conform to a normal distribution are expressed as mean ± SD, whereas quantitative data that do not conform to a normal distribution are presented as the median and interquartile range [M (Q1, Q3)]. *, P<0.05. VATS, video-assisted thoracoscopic surgery; SPN, small pulmonary nodule; SMD, standardized mean difference; SD, standard deviation.
Discussion
The aim of this study was to compare the safety and efficacy of a 4-hook anchor device with methylene blue for the preoperative localization of SPNs in VATS. By retrospectively analyzing data from 75 patients, we found that the VATS operative time was significantly shorter in the 4-hook anchor device group than in the methylene blue group. There were no significant differences between the two groups in terms of locator depth, complications, localization success, bleeding, hospital stay, or hospital costs.
The design of the 4-hook anchor device provides more stable fixation and reduces the risk of intraoperative displacement. By increasing the number of anchoring points compared with the hook-wire technique, the 4-hook anchor device improves the accuracy and reliability of nodule localization. Our preceding randomized controlled trial (RCT) underscored the superior safety and efficacy of the 4-hook wire over the conventional hook-wire in the localization of pulmonary nodules (10). The methylene blue technique is favored for its simplicity and cost-effectiveness; however, it may exhibit dye diffusion in some cases, compromising the accuracy of surgical localization (12). The scarcity of comparative studies between the two localization methods is a significant gap that our research aimed to address.
In a previous study, Chu et al. (13) compared 135 patients with preoperative localization of SPNs via hook-wire and 151 patients with the methylene blue technique. They reported that the methylene blue technique significantly reduced patient localization and hospitalization time. However, the hook-wire technique is associated with a greater risk of complications, particularly pneumothorax. Wang et al. (14) conducted a meta-analysis of seven studies including a total of 933 patients and compared the efficacy and safety of the methylene blue technique with those of the microcoil technique for CT-guided preoperative localization of SPNs. This study revealed that the methylene blue technique had a slightly higher technical success rate than did the microcoil method. In terms of postoperative complications, the methylene blue group had a lower complication rate than did the microcoil group. Methylene blue has advantages over traditional microcoil and hook-wire techniques because it causes minimal damage to surrounding tissues and has a lower complication rate. However, methylene blue still has drawbacks, such as inaccurate localization of deeper nodules and the risk of dispersal during surgery.
The 4-hook anchor device is an advancement of the traditional hook-wire technique. Our results revealed that the VATS procedure time was shorter in the 4-hook anchor device group than in the methylene blue group; we think that the reasons for this are multifaceted (15). Its superior stability upon deployment minimizes nodule displacement, while its optimized visibility under thoracoscopy allows for precise and efficient targeting. Additionally, the reliability of the 4-hook anchor device could increase the confidence of the surgical team, leading to more decisive actions. The surgical team’s extensive experience and proficiency with the 4-hook anchor device contribute to the overall expedited procedure time, underscoring its practical advantages in clinical settings.
Our study also revealed that complication rates and intraoperative bleeding rates were similar between the two groups. In this study, although no patients experienced the serious complication of air embolism, it is imperative to emphasize the potential risk of air embolism during puncture procedures, as its occurrence poses a significant challenge to clinical practice. The occurrence of air embolism is a critical concern due to its potential to cause rapid and life-threatening deterioration in a patient’s condition. It requires immediate recognition and swift intervention to mitigate its effects (16,17). Although two patients in the methylene blue group experienced dispersal during surgery, dispersal did not significantly affect the overall success rate, indicating that both techniques are acceptable in terms of safety. Despite the shorter puncture time in the 4-hook group, there was no statistically significant difference in overall clinical outcomes, hospital stay, or hospital costs, suggesting that there was no difference in cost-effectiveness between the two groups. The 4-hook anchor device may be more advantageous for accurate localization of deeper nodules and stability of the localization.
This study has several limitations. First, the data are based on a single-center retrospective study, which may introduce selection and information bias. Second, the relatively small sample size may have limited the validity of the statistical analysis. Future studies should consider prospective, multicenter, RCTs to further validate the comparative effectiveness of the 4-hook anchor device and methylene blue techniques. Additionally, cost-effectiveness analyses should focus on the impact of different technologies on long-term patient prognosis.
Conclusions
Compared with the methylene blue technique, the 4-hook anchor device is safe and reliable and offers a shorter VATS operative time.
Acknowledgments
We would like to thank the investigators at all participating study sites.
Funding: This work was supported by
Footnote
Reporting Checklist: The authors have completed the STROCSS reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-1535/rc
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1535/coif). The authors have no 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 (as revised in 2013). The study was approved by the Institutional Review Board of the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College (No. 21/176-2847) and informed consent was provided by all the patients.
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/.
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