Abstract
Background/Aim: Ablating a spherical area during hepatocellular carcinoma ablation therapy is a very important issue. We aimed to determine the ablation area of bovine liver using various radiofrequency ablation (RFA) protocols. Materials and Methods: Bovine liver (1-2 kg) was placed in an aluminum tray, which was punctured with STARmed VIVA 2.0 17-gauge (G) and 15-G electrodes using a current-carrying tip. Under the step-up or linear method, with an ablation time up to one break and RFA output stop, the size of the color change area (representing the thermally coagulated area) of the bovine liver was measured along the vertical and horizontal axes, and the ablated volume and total heat generated were calculated. Results: 5-W per minute increases protocol resulted in greater horizontal and vertical diameters of the ablated area than 10-W per minute increases protocol under the step-up method. For 5-W and 10-W per minute increases under the step-up method, the aspect ratio was 0.81 and 0.67 with a 17-G electrode, and 0.73 and 0.69 with a 15-G electrode, respectively. For 5-W and 10-W increases under the linear method, the aspect ratio was 0.89 and 0.82, respectively. Sufficient ablation was obtained, with vertical and horizontal diameters of 50 mm and 43.50 mm, respectively. Although the ablation time was long, the watt output value at the break and average watt value were low. Conclusion: Gradual increase in output (5 W) using the step-up method yielded a more spherical ablation area, and longer ablation time in the linear method with a 15-G electrode could result in a more spherical ablation area in real clinical practice in humans. Future studies should examine concerns regarding long ablation times.
As a new radiofrequency ablation (RFA) system, the STARmed VIVA RF generator® (STARmed Co. Ltd., Goyang, Republic of Korea) was approved to be covered by insurance as one of the most effective nonsurgical locoregional treatment for patients with hepatocellular carcinoma in Japan in March 2015. The STARmed system includes a variable therapeutic electrode needle, allowing for alterations of the ablation length from 5 mm to 30 mm, in 5-mm increments, by adjusting the length of the non-insulated portion of the electrode tip. Other RFA systems require the use of multiple electrodes of different sizes, although only a single electrode can be used during treatment in real clinical practice in humans (1).
An appropriate ablation area can be selected using 5-mm intervals (2). Ablation modes include a general mode, used for continuous output (current value, A); a continuance mode, used for continuous output of a set output value (power value, W); and an auto mode, in which the set output value increases each minute (power value, W). The output can be increased during ablation using the step-up method, in which output is increased each minute, or the linear method, in which the output gradually increases to the set value over a one-minute period. However, there are no specific methods for the ablation time or the number of breaks, and no studies regarding the shape of the ablation region have been reported (3).
Therefore, this study aimed to determine the shape of the ablation range under the step-up and linear methods in isolated bovine liver using a variable electrode needle in an effort to establish an optimal protocol for RFA in the auto mode.
Materials and Methods
Experimental setup. Bovine liver (1-2 kg) was placed in an aluminum tray with a return electrode attached to the bottom of each protocol three samples. The tray was punctured with a STARmed VIVA 2.0 electrode with a tip length of 30 mm. Two different electrodes were used: 15 G and 17 G. Ablation was conducted using the linear mode (initial output of 30 W, gradually increasing by 5 W or 10 W each minute) or the step-up mode (initial output of 30 W with a step-wise increase of 5 W or 10 W each minute).
The total energy, average watt output value, watt output value at the break, ablation time, and the size of the color change area (which represents the thermal coagulation area of the bovine liver), horizontal diameter, vertical diameter, and horizontal-to-vertical ratio of the thermal coagulation area were measured. The total heat generated was calculated using the output change data over time during RFA.
Statistical analysis. Categorical variables are expressed as whole numbers. Two-tailed, unpaired t-tests were performed to compare continuous variables that were normally distributed. Non-normally distributed data were compared using the Mann–Whitney U-test. Differences between the two methods in the distribution of categorical variables were evaluated using the Pearson’s Chi square test or Fisher’s exact test.
Statistical significance was defined as p<0.05. All statistical analyses were performed using EZR (Saitama Medical Centre, Jichi Medical University, Shimotsuke, Japan), a graphical user interface for R version 3.2.2 (The R Foundation for Statistical Computing, Vienna, Austria) (4).
Results
During step-up-mode RFA using a 17-G electrode, longer horizontal and vertical diameters were observed when the output was increased by 5 W each minute than when it was increased by 10 W each minute. The aspect ratio was 0.81 when 5-W increases were used and 0.67 when 10-W increases were used (p=0.121). However, the ablation time was longer when 5-W increases were used than when 10-W increases were used (p=0.121) (Table I).
Step-up-mode of radiofrequency ablation using a 17-G, 30-mm electrode.
During the step-up-mode RFA using a 15-G electrode, longer horizontal and vertical diameters were observed when the output was increased by 5 W each minute than when it was increased by 10 W each minute. The aspect ratio was 0.73 when 5-W increases were used and 0.69 when 10-W increases were used (p=0.683). However, the ablation time was longer when 5-W increases were used than when 10-W increases were used (p=0.121) (Table II).
Step-up-mode of radiofrequency ablation using a 15-G, 30-mm electrode.
During the linear-mode RFA using a 17-G electrode, the ablation time was longer when the output was increased by 5 W per minute than when it was increased by 10 W per minute (p=0.05). The watt output value at the break and the average watt value were higher when the output was increased by 5 W per minute than when it was increased by 10 W per minute (p=0.507), while the aspect ratio was same, at 0.75 (Table III).
Linear mode of radiofrequency ablation using a 17 G, 30-mm electrode.
During linear-mode RFA using a 15-G electrode, the aspect ratio was significantly higher when 5-W increases were used (at 0.89) than when 10-W increases were used (at 0.82) (p=0.035). The vertical and horizontal diameters were higher when 5-W increases were used (50 mm and 43.50 mm, respectively) than when 10-W increases were used (45.00 mm and 37.80 mm, respectively) (p=0.5, p=0.077, respectively). Although the ablation time was longer (p=0.05), the watt value at the break and average watt value were significantly lower (p=0.046) when 5-W increases were used than when 10-W increases were used (Table IV).
Linear-mode radiofrequency ablation using a 15-G, 30-mm electrode.
Discussion
RFA is a therapeutic technique that utilizes the principle of conductive heating, in which heat is generated by friction from moving electrons when current is passed through a conductor (5). RFA uses conductive heating to coagulate and necrotize diseased tissue, as a treatment for malignant neoplasms (6-8). In the present study, the ablation area of bovine liver was determined for several RFA protocols. We found that gradual increases in output (5 W) using the step-up method yielded a more spherical ablation area, and longer ablation time used in the linear method with a 15 G electrode increased the ablation in the horizontal direction, resulting in a more spherical ablation area.
RFA generates heat via high-frequency current applied to biological tissue between an electrode and a counter electrode. The heat is generated within all of the tissues through which the current flows; however, although the tissue near the electrode, where the current density is high, becomes hot, less heat is generated in the tissue distant from the electrode because of the cooling effect (radiator effect) that occurs with decreased current density and blood flow. In addition, the electrical conductivity of the tissue is reduced by the outflow of micro-bubbles generated in the thermal coagulation zone by the blood flow, resulting in insufficient thermal coagulation of the target area. When energization is initiated at a high output, the tissue in the area of the electrodes may be carbonized, which affects the ability to induce induction heating. Therefore, conductive heat must be generated efficiently to obtain a sufficient ablation range. According to the liver cancer treatment algorithm used in Japan, resection and ablation occur concurrently, and ablation is an effective treatment according to the results of the SURF trial (9). However, the aspect ratio of unipolar needle RFA is inferior to that of microwaves (10-12). Hepatocellular carcinoma lesions are often spherical (13, 14). The recurrence rate of hepatocellular carcinoma is low when ablation is achieved in a uniform area. Therefore, the optimal coagulated area during RFA is spherical. A previous study regarding RFA using a variable electrode in excised liver tissue reported that the long axis length of the ablated area was approximately 71% of the length of the short axis, resulting in an elliptical ablation area.
To sufficiently heat and coagulate the target area, the linear method of increasing RFA system output has been proposed. In the present study, the effects of each RFA protocol on excised bovine liver tissue were investigated. When the step-up RFA method was used with a 15-G or 17-G electrode, the horizontal and vertical diameters of the coagulated area were greater when the output was increased by 5 W per minute than when the output was increased by 10 W per minute. Increases of 5 W resulted in a higher aspect ratio than increases of 10 W. When the linear RFA method was used, the coagulated area was more similar to a sphere than that obtained when the step-up method was used. Sufficient ablation was obtained, with vertical and horizontal diameters of 50 mm and 43.50 mm, respectively, when the 15-G linear method was used, and the watt value at the break and average watt value were low, even though the ablation time was long. This may be due to the fact that the output is automatically increased after energization has started using a generator in the linear mode. When an impedance increase is detected, a break is automatically generated, allowing for responses to subtle impedance changes. Accordingly, a gradual linear mode (increases of 5 W per minute) can better adjust as a result of more subtle impedance changes than a less gradual linear mode (increases of 10 W per minute).
When the linear method is used, the area under the curve for the wattage is larger than that when the step-up method is used. The system output is gradually increased. The suppression of popping and pain in clinical settings of RFA using the linear method require further investigation. When the ablation time is lengthened, the amount of work that can be performed increases and the coagulation zone expands. However, the linear method, which performs ablation at a low power, elongates the short axis direction to form a spherical coagulation area. A larger coagulation area may be attainable as low-power ablation suppresses increased impedance, resulting in an expanded coagulation area.
The present study has several limitations. The most important limitation was the absence of blood flow. In vivo, the volume of coagulation is smaller and the amount of applied energy is higher due to the removal of heat by the presence of blood flow. This ex vivo procedure cannot be directly adopted for use in a clinical setting. Future studies to determine if a spherical coagulation area can be obtained using the linear method in actual RFA are necessary.
In the present study, linear mode STARmed VIVA 2.0 RFA was used to keep the initial output low and achieve a spherical coagulation region after a longer energization time. This protocol of RFA may suppress local recurrence by obtaining a sufficient spherical ablation area. In addition, popping and pain are reduced using this protocol, which may reduce the complications of clinical RFA. However, more research is necessary to determine if a similar coagulation area can be obtained using these methods clinically.
Acknowledgements
We would like to thank Editage (www.editage.com) for English language editing.
Footnotes
Authors’ Contributions
Conceptualization: Toru Ishikawa; Data curation: Toru Ishikawa, Iori Hasegawa, Hiroshi Hirosawa, Tsubasa Honmou, Nobuyuki Sakai; Formal analysis: Toru Ishikawa; Investigation: Toru Ishikawa, Iori Hasegawa, Hiroshi Hirosawa, Tsubasa Honmou, Nobuyuki Sakai, Takanori Igarashi, Shun Yamazaki, Takamasa Kobayashi, Toshifumi Sato, Akito Iwanaga, Tomoe Sano, Junji Yokoyama, Terasu Honma; Methodology: Toru Ishikawa; Project administration: Toru Ishikawa; Resources: Toru Ishikawa; Software: Toru Ishikawa; Visualization: Toru Ishikawa; Writing – original draft: Toru Ishikawa; Writing – review & editing: Iori Hasegawa, Hiroshi Hirosawa, Tsubasa Honmou, Nobuyuki Sakai, Takanori Igarashi, Shun Yamazaki, Takamasa Kobayashi, Toshifumi Sato, Akito Iwanaga, Tomoe Sano, Junji Yokoyama, Terasu Honma.
Conflicts of Interest
The Authors declare no conflicts of interest.
- Received March 15, 2023.
- Revision received March 31, 2023.
- Accepted April 7, 2023.
- Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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