According to the latest statistics from GLOBOCAN 2020, lung cancer accounts for 11.4% of cancer diagnoses and is the leading cause of cancer-related deaths, with an estimated 1.8 million deaths (18%). Non-small cell lung cancer (NSCLC) accounts for 85% of the confirmed cases, of which nearly one-third of the patients are early patients and have a higher overall survival rate through surgery. However, a sub-population of patients have a high risk of perioperative complications due to insufficient cardiopulmonary reserves or complications. In recent decades, percutaneous image-guided thermal ablation (IGTA) has emerged as primary or adjuvant therapeutic strategy in clinical practice. Moreover, one-third of the patients with cancer have pulmonary metastasis, and IGTA has been proved to be an effective method for the treatment of pulmonary metastases.
IGTA is an energy-based ablation technique used for treating tumors. As a precise, minimally invasive treatment technology, it utilizes the biological effects of heat to directly cause irreversible injury or necrosis of tumor cells in one or more tumor lesions located in specific organs. IGTA techniques mainly include radiofrequency ablation, microwave ablation (MWA), cryoablation, laser ablation, and high-intensity focused ultrasound ablation. MWA typically uses either 915 MHz or, more commonly, 2450 MHz frequencies. Molecules of water and protein and other polar molecules within tumor tissues vibrate at high speeds in a microwave electromagnetic field, which results in collision and mutual friction between molecules. The temperatures can be raised up to 60–150 °C in a short time, leading to coagulative necrosis of the cells. MWA has higher convection and a lower “heat-sink” effect than radiofrequency ablation. However, the use of MWA involves challenges, such as antenna design. The outer diameters of the 14G (2.0 mm) and 16G (1.6 mm) antennas are commonly used for the MWA of lung tumors, which have more “artifacts” and poor accuracy. In addition, relatively more complications, such as pneumothorax and hemorrhage, occur with the use of 14G and 16G. In this study, we compared the difference between the ablation zones of 19G (1.03 mm), 14G, and 16G, providing an experimental basis for their clinical application.
MATERIALS AND METHODS
Ex vivo standard model
We used market fresh eggs and separated the egg whites from the yolk. The yolk was mixed evenly, randomly divided into three groups, put in a plexiglass box, and placed on the test bench. The 14G, 16G, and 19G antennas were inserted 5–7 cm of yolk vertically along the box wall [Figures 123]. The same researcher used the 14G, 16G, and 19G antennas and performed 108 experiments according to the output power (50, 60, and 70 W) and ablation time (3, 6, 9, and 12 min), and then recorded the maximum long-axis (along the needle axis; length [L]) and maximum short-axis (perpendicular to the needle; [D]) diameters.
Ex vivo porcine lung stud
Forty fresh porcine lungs were obtained from a slaughterhouse on the day of the experiments. The left and right lungs were cut open as the two experimental units were randomly divided into three groups and stored in a 37 °C incubator before the experiment. The experimental unit was placed in a plexiglass scaffold and affixed tightly and smoothly to one side of the cup wall. According to the experimental unit's shape, size, and thickness, an appropriate position was selected and located in the central area of the cup wall. The path for the ablation antenna was made to avoid the main bronchus completely. The ablation antenna was inserted 5–7 cm vertically into the tissue along the cup wall and fixed to the experimental bench. MWA procedures were induced at output power settings of 50 W, 60 W, and 70 W for 3, 6, 9, and 12 min. A total of 216 ablations (six sessions per time setting in the 14G, 15G, and 19G microwave antennas) were performed by the same investigator. The research protocol was approved by the Institutional Animal Care and Use Committee of The First Affiliated Hospital of Shandong First Medical University (Jinan, China).
An MWA system (Jiuzhou Medical device Research and Development Center, Nanjing, China) was used in the studies. This system consists of an MTC-3 microwave generator (frequency: 2450 ± 50 MHz, output power: 5–100 W, time range: 1–99 s/1–99 min), a microwave coaxial cable, an implantable microwave antenna (the antenna surface is coated with polytetrafluoroethylene), and a steady-flow pump. The implantable microwave antenna can withstand the operating power of ≥80 W and has three diameters: 1.03 mm (19G), 1.60 mm (16G), and 2.0 mm (14G) [Figure 1]. The antenna shaft contains two lumina, which can deliver physiological saline at 4 °C to the tip of the shaft. The peristaltic pump is used to push saline to circulate in the cavities, and the warm solution is returned to the outside. This high-efficiency water-cooling system can generate cooled water flow at >70 mL/min.
The shape and range of the ablation zone were observed through the transparent cup wall; the long- (along the needle axis; length [L]) and short-axis (perpendicular to the needle; diameter [D]) diameters of the coagulation zone were assessed macroscopically with calipers after ablation, and the sphericity index (L/D) was subsequently calculated. The sphericity index can be simplified as long-axis/short-axis [Figures 2 and 3].
Measurement data are expressed as the mean ± SD. The single-sample K-S was used to test whether the sample conformed to normal distribution. Levene's test was used to test the homogeneity of variance, and ANOVA was used to estimate statistical differences between long-axis diameters (L), short-axis diameters (D), and spherical indices (L/D). If statistical differences existed, LSD was used to compare the differences between groups. If variance was non-uniform, Dunnett's T3 test was used to compare the differences between groups. A P < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS (SPSS for Windows, version 22; IBM).
The egg yolk standard model
All ablation zones had good consistency in the standard model. The zones were quasi-oval, divided into an arrow-shaped, central carbonization zone and a coagulated zone from the inside to the outside. The central zone of the arrow-shaped carbonization is generally a dark brown charred band, whereas the condensation zone is a white and dense band around the central zone and has a clear boundary with the egg yolk [Figure 2].
The maximum long- and short-axis diameters and sphericity indices of the standard model ablation zones produced by the 14G, 16G, and 19G antennas heating 3, 6, 9, and 12 min at 50 W are 3.25 ± 0.05 to 4.56 ± 0.15 cm, 1.34 ± 0.14 to 1.80 ± 0.11 cm, and 2.24 ± 0.13 to 2.54 ± 0.21 cm, respectively [Table 1]. Simultaneously, the long- and short-axis diameters and sphericity indices of the ablation zone of the standard model produced by heating three types of microwave antennas at 60 W and 70 W for 3, 6, 9, or 12 min are 3.51 ± 0.09–4.72 ± 0.22 cm and 4.73 ± 0.18 cm–5.62 ± 0.17 cm, 1.36 ± 0.16–2.04 ± 0.08 cm and 1.71 ± 0.06–2.27 ± 0.06 cm, 2.23 ± 0.23–2.53 ± 0.23 cm, and 2.43 ± 0.20–2.77 ± 0.01 cm, respectively [Tables 2 and 3]. The long- and short-axis diameters and sphericity indices did not differ statistically between the 14G, 15G, and 19G groups (P < 0.05 each).
Ex vivo porcine lung
All ablation zones were ellipsoidal and had clear boundaries with surrounding tissues. The ablation zone was divided into three regions according to the color from the center to the edge [Figure 3]. First, the arrow-shaped carbonized central region generally appears as a dark brown coke burning zone. Second, the condensation zone is grossly a pale brown, hard, and dense around the central region. Third, the congestive reaction zone appeared roughly as a thick and light red circle adjacent to the coagulated zone. The sizes of the ablation zones created by the three ablation antennas were stable.
Results from the ex vivo porcine lung experiments revealed the diameters and sphericity indices for the in vitro ablation zones created by the three microwave antennas at 3, 6, 9, and 12 min (shown in [Tables 45], and [Table 6], respectively).
With the increase in ablation power (from 50 to 70 W), the maximum long-axis of ablation zone diameters of the 19G antenna increased from 3.45 ± 0.05 cm to 5.84 ± 0.67 cm, the short-axis diameters increased from 2.10 ± 0.24 cm to 3.74 ± 0.60 cm, and the sphericity indices increased from 1.49 ± 0.12 to 1.82 ± 0.37, respectively. The results for the ablation zones of the 14G and 16G antennas are as follows; the maximum long-axis of ablation zone diameters increased from 2.97 ± 0.16 cm to 5.12 ± 1.18 cm and from 3.31 ± 0.36 cm to 5.50 ± 0.89 cm, respectively. The short-axis diameters increased from 1.87 ± 0.15 cm to 3.83 ± 0.73 cm and 1.97 ± 0.35 cm to 4.23 ± 0.87 cm, respectively. The sphericity indices increased from 1.32 ± 0.11 to 1.63 ± 0.10 and 1.31 ± 0.08 to 1.70 ± 0.19, respectively. The long- and short-axis diameters did not differ statistically between the 14G, 16G, and 19G groups (P > 0.05 each). The value of the sphericity index of the 19G microwave antenna was higher than those of the 14G and 15G microwave antennas under the condition of 12 min at 70 W (P < 0.05 each). However, no statistical difference between the 14G and 15G microwave antennas was observed (P > 0.05). The curve for the length of ablation area of lung tissue with time was obtained by using 50 W, 60 W, and 70 W at 3, 6, 9, and 12 min, as shown in [Figure 4]. Figure 4a, c, and e and b, d, and f show the time-varying curves of the maximum long- and short-axis diameters created by the 14G, 16G, and 19G antennas, respectively. With the increase in ablation time, the long- and short-axis diameters of the ablation zone increased, and the trend was similar under different values of ablation power.
The factors affecting the prognosis of patients mainly include complete ablation rate and complications, which also restrict the development of ablation technology. The common postprocedural complications of MWA include pneumothorax, pleural effusion, hemorrhage, and infection, among which the incidence of pneumothorax is as high as 10–60%, with 3.5–40% patients needing chest-tube placement. Controlling the ablation range is most crucial for complete ablation. Establishing a standard ablation model for experimental research and development of clinical technology is of great significance. Several materials have been used in phantoms for thermal studies, including gelatin, agar, polyacrylamide gel (PAG), and PAG-containing protein. Although phantoms made of PAG and BSA can solve the problem of stability at high temperatures and have physical properties similar to the human body, there is no uniform standard in scientific research practice. Fat and protein are the main components of egg yolk. At approximately 70 °C, egg yolk coagulates and changes color, appearing as ivory-white turbidity, and the accurate visualization of the coagulation lesion without thermal hysteresis is not possible. However, the egg yolk model has many advantages, such as simple operation, high consistency, and low cost. In this study, three types of ablation antennas were used to verify the stability and observability of the model at different power settings and time.
Studies have confirmed that a thinner biopsy needle can ensure the accuracy of biopsy while significantly reducing the incidence of pneumothorax. Therefore, in this study, we have aimed to achieve equivalent ablation volumes by using thinner biopsy antennas, which is also instructive to ensure ablation quality and reduce the risk of pneumothorax and bleeding caused by punctures. To eliminate the effect of experimental lung tissue heterogeneity on ablation antennas with different diameters, we designed an in vitro standard model. The results preliminarily confirmed that there was no overall statistically significant difference in the diameters and sphericity indices of the ablation range formed by the three ablation antennas with different outer diameters. There are a few experimental and numerical studies on MWA using the ex vivo porcine lung model. Results from a study by Gao et al. showed that an increase in ablation power from 30 to 50 W increased the maximum long- and short-axis diameters of the ablation zones created by the 17G antenna from 41.1 to 66.3 mm and 29.5 to 48.9 mm, respectively. In their study, the ablation zone created by the 17G antenna is slightly more than that in our study, irrespective of whether we used the 14G, 16G, or 19G antennas. This numerical difference may be related to the experimental conditions. Interventional radiologists use ablation powers of 60–70 W and ablation times of 6–10 min for creating ablation with an average diameter of 3–3.5 cm. Therefore, our findings have more clinical reference value. Our results confirmed that there was no overall statistical difference in the long- and short-axis diameters of the ablation range formed by three diameter ablation antennas in ex vivo porcine lung. Interestingly, the ablation focus formed by the ablation antennas with diameters of 14G and 16G at 70 W and 12 min is more spherical than that formed by the ablation antenna with a diameter of 19G. We speculate that this difference may be because with the increase in ablation power and ablation time, the needle bar of the ablation antenna with a smaller diameter slows heat dissipation down compared with that of the ablation antenna with a larger diameter. Hence, it is easier to produce the “tailing phenomenon,” which makes the shape of the ablation focus closer to an ellipse. This phenomenon may be caused by the corresponding decrease in the circulation of water of the thinner ablation antenna. Therefore, 19G seems more suitable for small pulmonary lesions (1–3 cm) with a short ablation time in clinical practice.
An Ideal antenna should achieve the desired ablation zone pattern (size and shape), possess high-energy transmission efficiency, and be noninvasive to patients. Monopole, dipole, and slot antennas are three basic coaxial-based antennas from which most clinically available antennas were developed. By improving backward heating, increasing the number of antenna slots, changing the outer conductor structure, and adding a cooling system, this promising ablation technology has become an effective, safe, and widely used strategy for treating patients with cancer. Furthermore, an antenna with a small size is more desirable when considering the comfort and safety of patients during MWA procedures. For the radical treatment of early NSCLC, video-assisted thoracic surgery, SBRT, and thermal ablation, such as MWA, will be part of the “troika,” and lung surgery will likely be replaced by IGTA. A recent study confirmed that the median survival time and 5-year overall survival time of MWA for early stage NSCLC were 56.5 months and 46.7%, respectively. By contrast, Chi et al. reported that the 5-year survival rate of SABR was 30% in E-S NSCLC and 48–65% for those who underwent surgical resection. This difference depends on the type of operation and the degree of lymph node involvement. Thermal ablation can ensure the complete elimination of the lesion in a certain range and increase tumor antigen release, which is required to elicit an anticancer immune response. Thus, the use of improved ablation technology combined with immunotherapy is promising for treating lung cancer.
Our study has several limitations. First, this is an in vitro study, not an in vivo test. Second, healthy porcine lung tissue was ablated. A lung tumor model must be established to verify the experimental results. Third, because of the “heat-sink” effect caused by blood perfusion and lung ventilation, the actual ablation range in the in vivo experiment is narrow.
In conclusion, the 19G antenna could achieve the same ablation effect as the 14G and 16G antennas, which may reduce puncture risk and complication rate and provide an experimental basis for clinical applications.
Financial support and sponsorship
This study has received funding by the National Natural Science Foundation of China (81502610 and 82072028) and Shandong Provincial Natural Science Foundation, China (ZR2021MH143 and ZR2020MH143).
Conflicts of interest
There are no conflicts of interest.
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