Cardiovasc Intervent Radiol DOI 10.1007/s00270-015-1168-2
LABORATORY INVESTIGATION
‘‘Edgeboost’’: A Novel Technique to Extend the Ablation Zone Lateral to a Two-Probe Bipolar Radiofrequency Device Ya Ruth Huo1,2 • Krishna Pillai1 • Javed Akhter1 • David L. Morris1,2
Received: 25 May 2015 / Accepted: 23 June 2015 Ó Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2015
Abstract Background The dual-electrode bipolar-RFA (B-RFA) is increasingly used to ablate large liver tumours (3–7 cm). However, the challenging aspect of B-RFA is the placement of the two electrodes around the tumour. Realignment often requires the electrodes to be extracted and reinserted. Aim The aim of this study is to examine ‘‘Edgeboost’’, a novel technique to increase the lateral ablation dimension without requiring any realignment of the electrodes. Methods and Materials An egg-white model and an ex vivo calf liver model were used compare the standard bipolar mode ablation to Edgeboost-1 (reaching full impedance in bipolar mode initially, then cycling in unipolar mode between left and right probes) and Edgeboost-2 (similar to Edgeboost-1 but not reaching full impedance initially in bipolar mode in order to minimize charring and, thus, to increase total ablation time). Results A significantly larger outer lateral ablation dimension to the probe was achieved with Edgeboost-1 compared to the standard method in the liver model
& David L. Morris [email protected] Ya Ruth Huo [email protected] Krishna Pillai [email protected] Javed Akhter [email protected] 1
Hepatobiliary and Surgical Oncology Unit, UNSW Department of Surgery, St George Hospital, Level 3, Pitney Building, Kogarah, Sydney, NSW 2217, Australia
2
St George Clinical School, University of New South Wales, Sydney, NSW, Australia
(1.14 cm, SD: 0.16 vs. 0.44 cm, SD: 0.24, p = 0.04). Edgeboost-2 achieved the largest outer lateral ablation dimension of 1.75 cm (SD: 0.35). A similar association was seen in the egg model. Edgeboost-2 almost doubled the mass ablated with standard bipolar alone (mass ratio: 1:1.94 in egg white and 1:1.84 in liver). Conclusion This study demonstrates that the novel ‘‘Edgeboost’’ technique can increase the outer lateral ablation dimension without requiring the two inserted electrodes to be reinserted. This would be beneficial for interventionists who use the dual B-RFA. Keywords Radiofrequency ablation Novel technique Bipolar InCircle Dual-probe Edgeboost
Introduction Mono-polar radiofrequency ablation (M-RFA) is the most widely used image-guided interventional treatment of hepatic, pulmonary and renal tumours [1–3]. However, the most restrictive factor concerning the broader applicability of M-RFA is the limited size of the radiofrequency-induced ablation (\3.0 cm) [1]. Inverse Square Law of physics applies to the use of all M-RFA devices. As a result, the current density decreases as the inverse square of the distance from the electrode, while heating decreases as the inverse of the fourth power of the distance from the electrode. [4] Therefore, heating preferentially takes place immediately adjacent to the electrode and causes irreversible dehydration and charring of the tissue near the electrode during the RFA process. Although effective methods have been developed to reduce charring and to increase the radius of ablation by the use of expandable
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electrodes, saline-infused probes or cooling with saline injections, achieving complete ablation for lesions [3 cm remains problematic with M-RFA (complete ablation: 100 % if \3 cm vs. 80 % if [3 cm; local recurrence rate: 1.6 % for tumours \3 cm vs. 8.8 % overall) [5]. Considerable differences in the local recurrence rates are reported in the literature, ranging from 6 to 39 %. [6–10]. In an effort to overcome the shortfalls of M-RFA, many centres have employed other thermocoagulative devices to treat liver tumours such as microwave ablation (MWA) and bipolar-RFA (B-RFA) [11, 12]. A few B-RFA devices have already been developed [13–16]. Some use single needles with two opposite electrical pole points at the distal end, whilst others use two separate electrodes that are placed on either side of the tumour with no direct tumour contact [13, 15]. All M-RFA devices create a core zone of ablation at the tumour site that extends radially into the adjacent tissue relying primarily on thermal conduction to ablate the tissue. In contrast, B-RFA promises the formation of a controlled and more reliable ablation area based on the geometric projection from one electrode to the other. As a result, the ablation evolves in a well-defined site delineated by the two electrodes. Referred to as a ‘line of sight’ delivery system [11], the dual-probe B-RFA involves direct penetration of radiofrequency energy through the targeted tumour (Fig. 1). Furthermore, depending on the tumour size, this approach of dual-probe B-RFA avoids the tumour being punctured and thus allows for an oncologically surgical correct ‘‘no touch’’ technique. Depending on the type of B-RFA probe used, either a rounded cube or spherical ablation distribution is achieved for up to 7 cm [17]. Fig. 1 Illustration showing differences between monopolar (A) and bipolar (B) ablation, and the InCircleTM Monarch (RFA Medical, Inc., Fremont, CA, USA) parallel electrode system for B-RFA (C)
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Furthermore, B-RFA is less affected by conductive ‘heat sinks’, compared to M-RFA and even monopolar MWA [18]. The decreased dependence on local inhomogeneities such as blood perfusion compared to M-RFA results in the ability to achieve a larger zone of ablation (finite-element models of 7.95 cm3 for monopolar and 18.79 cm3 for B-RFA) [19]. Monopolar probes require a single insertion into the tumour, allowing for thermocoagulation of tissue adjacent to deployable tines. A dispersive pad is required to close the RFA current cycle. B-RFA requires placement of dual probes 4–6 mm from the perimeter of the tumour to achieve a 1-cm margin (bipolar mode alone achieves a lateral ablation distance of 5 mm). No dispersive pad is required for B-RFA. B-RFA probe shafts are shaped like an ‘‘8’’ in cross Section (8 9 6 French Gauge for the 4 and 5 cm InCircleTM Monarch, 18 9 8 French Gauge for the 7 cm InCircleTM Monarch). The most essential, yet difficult, skill in using bipolar probes is placing the two probes 4–6 mm lateral to the perimeter of the tumour in order to achieve a margin of 1 cm (approximately 5 mm is ablated lateral to the two probes in bipolar mode). As the current stream flows between the two probes, any tumour within the two electrodes would be completely ablated until there is no electrical current (i.e. impeded out), whilst tumour lying on the outer edge of the electrodes may not receive the same treatment. In circumstances where the probes are inserted inside the tumour, the misplaced electrode would need to be removed and reinserted into the correct position otherwise the tumour outside will not be treated, or in
Y. R. Huo et al.: Novel Technique to Extend the Lateral Ablation Zone to Bipolar...
circumstances where a larger margin is desired. Removal and reinsertion of an M-RFA probe has been associated with a small risk of needle track seeding and complications such as bleeding and infections [20]. However, this risk may be slightly higher for B-RFA due to the larger probe size. Hence, the aim of this study is to examine a novel method of increasing the ablation zone lateral to the outer margin of the dual probes as to avoid the need to remove and reinsert a slightly misplaced electrode. Due to the different method of heat transfer and ablation distribution between M-RFA and B-RFA, this study hypothesizes that the novel method of using unipolar mode after bipolar mode with a dual-probe B-RFA would increase the ablation zone on the outer lateral side to the probes compared to using bipolar mode alone. Two novel techniques (Edgeboost-1 and 2) will be examined in an egg-white model and ex vivo calf liver. Various parameters such as total time to ablate, mass, volume, density and lateral and longitudinal dimensions, as well as the ablation zone on the outer lateral side to the two probes (x), will be measured and compared to the standard bipolar mode of ablation.
Methods No ethics approval was required to perform this study, as it did not involve the use of any patients or live animal tissues. Livers were sourced from a commercial food supplier where the animals had been processed for human consumption. The RFA probe used in the experiment was the InCircleTM Monarch 4 cm (RFA Medical, Inc., Fremont, CA, USA) parallel electrode system for bipolar radiofrequency ablation (B-RFA). This device comprises two sets of opposing deployable electrodes, handle, plunger, guide block, power cable and generator adaptor cable. For our work, we used the nominal 4-cm needle probes with a 25-cm length probe that deploy six circular, planar-oriented electrodes (probe shafts are like an ‘‘8’’ shape in cross section; 8 9 6 French Gauge) (Fig. 1C). The generator used in the experiment was Model 1500, Rita Medical Systems, Inc (Mountain View, CA, USA). The standard dispersive pad was used from Rita Medical Systems, Inc (Mountain View, CA, USA) for monopolar application of radiofrequency energy in Edgeboost-1 and Edgeboost-2.
4-cm InCircleTM Monarch Bipolar Probe was secured in the same position for all experiments, and the two probes were placed 3 cm apart in both the egg and liver models. Edgeboost-1 and 2 were compared to Standard bipolar ablation alone at 100 W until full impedance. The ablation parameters for the two novel techniques are as follows: Edgeboost-1: (a) Bipolar mode: 100 W, time: until full impedance. (b) Unipolar mode, Right electrode: 100 W, time: 5 min egg white and 2.5 min in calf liver. (c) Unipolar mode, Left electrode: 100 W, time: 5 min egg white and 2.5 min in calf liver. (d) Repeat b and c until full impedance is reached by both electrodes. (e) Bipolar mode: 100 Watts, time: until full impedance. Edgeboost-2 (a)
Bipolar mode: 100 W, time: 8 min egg white and 3 min calf liver. (b) Unipolar mode, Right electrode: 100 W, time: 5 min egg white and 2.5 min in calf liver. (c) Unipolar mode, Left electrode: 100Watts, time: 5 min egg white and 2.5 min in calf liver. (d) Repeat b and c until full impedance is reached by both electrodes. (e) Bipolar mode: 100 W, time: until full impedance. Egg Model Fresh egg whites were separated from egg yolks and placed into a 1.8-L glass beaker with a diameter of 14 cm and a height of 19.5 cm. The egg white was equilibrated to 37 °C for each experiment. One dispersive pad was placed in the beaker, perpendicular and symmetrical to each of the two probes. Preliminary trials found no indication of coagulation on the pad surface. The set-up of the egg model is shown in Fig. 2. Coagulated egg white was recognised by the change in consistency and colour from a yellow gel to an opaque, white, firm mass. For each device, the experiment was repeated five times. The InCircleTM probes are placed in the centre of the cylindrical beaker filled with fresh egg-white (stabilised with a wooden bridge that is not shown). A dispersive pad is placed at the perimeter.
Ablation Technique Liver Model Edgeboost-1 and 2 were two novel techniques which cycled between bipolar and unipolar modes (Fig. 2). Edgeboost-1 and 2 were similar except for the first step, where Edgeboost1 reached full impedance using bipolar mode, whilst Edgeboost-2 did not reach full impedance. For all experiments, power was set at 100 W and the same generator was used. A
Fresh calf liver was equilibrated to 37 °C before beginning the experiment. The liver was placed in a rectangular polypropylene container (dimensions of 30 9 10 9 18 cm3), and 0.9 % saline (conductive media) at 37 °C was added into the container to three-quarters of the height of
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Y. R. Huo et al.: Novel Technique to Extend the Lateral Ablation Zone to Bipolar... Fig. 2 Visual representation of the egg-white model set-up
the liver. A dispersive pad was then placed at each end of the container. The InCircleTM Monarch probes were placed in the centre of the apparatus for each experiment, with each probe 13.5 cm away from the dispersive pad. The two probes were fixed 3 cm apart. The liver tissue that was ablated was recognised by the change in colour from deep brownish red to greyish pink. The tissue ablated was surgically excised from the rest of the liver. All three techniques were repeated four times. Measurements and Calculations The longitudinal dimension, lateral dimension and width of the ablated mass were measured using a linear centimetre scale, while the mass ablated was recorded in grams. The volume was measured using the displacement method by immersing only the ablated liver tissue or egg white in water. The average external lateral dimension (x) to each probe was calculated by the lateral dimension minus the distance between the two electrodes (3 cm) and then halved, as in Eq. 1 (Fig. 3). External lateral dimension ð xÞ ¼ ½Lateral dimension ðcmÞ distance between the probes ð3 cmÞ =2 ð1Þ The results are reported with mean readings and standard deviations. ANOVA was used to determine whether there was a statistically significant difference between the three techniques. The two-tailed independent t test was then used to compare the means between Standard bipolar alone with Edgeboost-1 and C, and Edgeboost-1 with Edgeboost-2. Statistically significant differences were defined as a p value less than 0.05. External lateral dimension to the two probes (x) was calculated by the lateral dimension minus the distance between the electrodes (3 cm) and then halved.
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Fig. 3 Measurements for egg model (A) and liver model (B) of the longitudinal dimension, lateral dimension and width
Results In bipolar mode alone, full impedance (roll-off) was always reached, requiring a mean duration of 6.1 min to ablate 3.9 9 5.0 9 5.1 cm ex vivo liver (Table 1). Similarly, for Edgeboost-1, the first step of reaching full impedance in bipolar mode required a mean time of 7.3 min. The external lateral distance of ablation to the electrodes (x) was significantly different between the three techniques
Y. R. Huo et al.: Novel Technique to Extend the Lateral Ablation Zone to Bipolar... Table 1 Comparison of ablation parameters between standard ablation, Edgeboost-1 (EB-1) and Edgeboost-2 (EB-2) Parameters
Egg-white model Standard
Edgeboost-1
Mass, g (SD)
112.0 (19.1)
Ratio
Ex vivo liver model Edgeboost-2
ANOVA
Standard
Edgeboost1
Edgeboost-2
ANOVA
185.4 (48.0)*,b
217.7 (70.9)*
0.082
95.5 (24.8)
121.6 (12.8)
180.1 (46.5)**
0.05
1
1.66
1.94
1
1.27
1.88
p valuea EB-1 versus EB-2 Volume cm3 (SD)
– 104.6 (21.4)
– 176.0 (47.8)*
0.52 216 (65.4)*
– 89.3 (28.8)
– 116.3 (11.1)
0.14 166.3 (40.1)**
Ratio
1
1.68
2.07
p value EB-1 versus EB-2
–
–
0.4085
Density, g/cm3 (SD)
1.08 (0.07)
1.06 (0.05)
1.0 (0.06)
Ratio
1
0.98
0.93
p value EB-1 versus EB-2
–
–
0.31
Ablation time (SD)
19.1 (7.9)
27.9 (6.9)
33.4 (14.0)
Ratio
1
1.46
1.74
p value EB-1 versus EB-2
–
–
0.52
Longitudinal diameter (SD)
5.5 (0.4)
6.1 90.7)
6.0 (0.9)
Ratio
1
1.1
1.1
p value EB-1 versus EB-2
–
–
0.89
Lateral diameter (SD)
6.3 (0.36)
7.7 (1.1)
8.2 (0.8)*
Ratio
1
1.22
p value EB-1 versus EB-2 Width (SD)
– 5.9 (0.6)
– 6.4 (0.77)
Ratio
1
1.1
p value EB-1 versus EB-2
–
–
0.06
0.045
1 0.26
0.19
0.38
–
–
0.13
1.09 (0.04)
1.05 (0.04)
1.08 (0.02)
1
0.96
0.99 0.25
–
–
6.1 (0.9)
15.1 (10.1)
23.3 (11.5)
1
2.48
3.81 0.48
–
–
5.0 (0.9)
4.4 (0.5)
4.9 (0.6)
1
0.88
0.98
–
–
0.01
0.015
3.9 (0.5)
5.3 (0.3)*
6.5 (0.7)***
1.30
1
1.35
1.7
0.20 7.1 (1.19)
0.23
– 5.1 (1.1)
– 5.3 (0.2)
0.08 6.4 (0.3)
1.2
1
1.04
1.25
0.45
–
–
0.02
a
Independent two-tailed t test comparing Edgeboost-1 with Edgeboost-2
b
Independent two-tailed t test comparing Edgeboost-1 or Edgeboost-2 against standard ablation
0.50
0.19
0.36
0.005
0.10
* p \ 0.05; ** p \ 0.01; ***p \ 0.001
in both the egg and liver models (ANOVA = 0.007 and 0.005, respectively). In the liver model, the x value was the highest with Edgeboost-2 (1.75 cm, SD: 0.35) followed by Edgeboost-1 (1.14 cm, SD: 0.16,) and lowest with standard bipolar mode (0.44 cm, SD: 0.24) (Fig. 4A). The x value for Edgeboost-1 and Edgeboost-2 was significantly higher than standard bipolar ablation alone. Edgeboost-1 and Edgeboost-2 were not significantly different. A similar association was seen in the egg model (Fig. 4B). The mean volume, mass, density, ablation time and dimensions using the three techniques with comparative ratios for both the liver tissue and egg-white model are shown in Table 1. In both the liver and egg models, the ablated mass was the highest using Edgeboost-2, followed by Edgeboost-1, and lowest in standard bipolar alone. Edgeboost-2 almost doubled the mass achieved using standard bipolar ablation method (standard bipolar alone) (relative increase in mass: 1.94 in egg white and 1.84 in liver). A similar correlation was seen with volume; however, density remained similar between the three techniques. In both the liver and egg models, the ablation time
was the highest in Edgeboost-2, followed by Edgeboost-1, and lowest in standard bipolar alone. The lateral and longitudinal dimensions were not statistically different between the three techniques in the egg model. In the calf liver model, the lateral and longitudinal dimensions were significantly higher in Edgeboost-2 compared to Edgeboost-1. Furthermore, the lateral and longitudinal dimensions for standard bipolar mode alone were not significantly different compared to Edgeboost-1 and Edgeboost-2 (Fig. 5). Ablated zone and healthy liver not shown to size. The conductive medium, 0.9 % saline water at 37 °C, to reach three-quarters of the height of the liver is not illustrated.
Discussion Worldwide, RFA is among the most frequently used ablation system for the local control of tumours in organs such as the liver, lung and kidneys. The use of RFA for hepatic lesions is the most widely accepted, as this
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Y. R. Huo et al.: Novel Technique to Extend the Lateral Ablation Zone to Bipolar... Fig. 4 Lateral ablation distance for the three techniques in the egg model (A, ANOVA = 0.007) and liver model (B, ANOVA = 0.005)
Fig. 5 Cross sections of bovine liver after standard bipolar ablation and Edgeboost-2 demonstrating the increased distance of ablation lateral to the bipolar electrodes (unbroken arrow)
minimally invasive treatment is attractive for patients with HCC who are unsuitable for hepatic resection and may also act as a bridging treatment to transplantation [21]. More so, many patients with secondary liver tumours are unsuitable for surgery due to comorbidities. Although M-RFA technology has significant limitations, it has been extensively described and is the most widely used thermal ablative method. In an effort to overcome the limitations of M-RFA, other thermal energy systems have been introduced for destruction of liver tumours. Dual-probe B-RFA energy delivery has the advantages of a uniform and higher current density providing rapid ablation without significant reliance on thermal conduction in the tumour target zone [18]. Animal studies comparing M-RFA to dual-probe
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B-RFA have shown superiority for the B-RFA method with respect to larger ablation zone, tissue control, haemostasis and overall efficiency [16, 22]. Clinical studies are also beginning to emerge confirming improved tumour ablation times and efficacy using dual-probe B-RFA in comparison with M-RFA [11, 23]. However, the critical yet sometimes challenging skill in using dual B-RFA can be the precise placement of the two electrodes at the perimeter of the tumour. If one or both of the electrodes are placed within the tumour, malignant cells lateral to the electrodes may not be adequately ablated as a majority of the radiofrequency current flows between the two electrodes. Realignment requires the electrodes to be extracted and reinserted, which is associated with the risk of needle track seeding and complications such as bleeding and infections [20]. A technique to increase the lateral ablation zones without requiring the two inserted electrodes to be removed would be a major benefit not only to the surgeons and interventional radiologists who may utilize the dual B-RFA in open, laparoscopic or percutaneous surgery, but also to the patients. However, it is important to highlight that the intended use of the InCircleTM technology is to have both probes inserted correctly. This study has identified two novel techniques (Edgeboost-1 and Edgeboost-2) that can increase the ablation zone lateral, externally on either side to the electrodes, as well as the volume and mass compared to standard bipolar mode. Both novel techniques are simple to implement in clinical practice, requiring only one additional dispersive pad on the patient to form a unipolar radiofrequency circuit with either of the two electrodes (Fig. 6). As expected, this study found that the use of bipolar mode alone until full impedance (Standard bipolar alone) created a spherical ablated mass with an external lateral ablation dimension (x) 0.44 cm on either side of each electrode. Edgeboost-1 was able to increase the external lateral ablation dimension (x) to 1.14 cm (additional 0.7 cm compared to bipolar
Y. R. Huo et al.: Novel Technique to Extend the Lateral Ablation Zone to Bipolar...
mode alone), whilst Edgeboost-2 was able to increase the x value further to 1.75 cm (additional 1.31 cm). If necessary, these two novel techniques can increase the lateral tumour-free margin without realignment of the B-RFA electrodes. Edgeboost-1 demonstrated that even after reaching maximum impedance in bipolar mode, each of the two probes can undergo further ablation in unipolar mode to increase the lateral ablation dimension. This highlights that complete charring of the electrodes does not occur in B-RFA when maximum impedance is reached. This is likely due to the physics of heating in B-RFA, whereby the RF current passes between the needle electrodes to produce an ionic flux in the tissue, so that the tissues, not the electrodes, are the source of heat in B-RFA [24, 25]. This ‘‘line of sight’’ energy directly penetrates the targeted tumour, and maximum impedance is reached when all of the tissue between the two electrodes undergo complete desiccation and contraction (Fig. 6).
Fig. 6 Increase in ablation zone lateral to the bipolar electrodes for Edgeboost-1 [complete ablation at step 1 (bipolar only)] and Edgeboost-2 (partial ablation at step 1)
Interestingly, Edgeboost-2 demonstrated that an even wider lateral ablation distance could be achieved if full impedance is not reached in bipolar mode initially. This suggests that when maximum impedance is reached in bipolar mode (Edgeboost-1), there is some charring of the two electrodes that limits the ability of each electrode to undergo further ablation in unipolar mode. However, a question then arises: Why not discard the use of bipolar initially and just use overlapping M-RFA probes? The use of overlapping ablation with M-RFA is known to be associated with a higher risk of local tumour recurrence [26]. This is likely due to the extreme difficulty of achieving complete ablation by overlapping unipolar probes, especially if the probes are placed too distant from the previous ablation or close to blood vessels [27]. A previous study required 12–13 electrodes to successfully ablate tumours 6.6–7.0 cm in diameter [26]. An explanation for this is the decrease in current density that occurs at a distance from the energy source in the monopolar RF mode, making the periphery of the lesion particularly prone to vascular cooling. In comparison, InCircleTM has been found to be able to ablate tumours up to 7.8 cm, achieve ablation sizes up to 10.3 cm [28] and to ablate giant hepatic hemangiomas ([10 cm) [29]. Haemmerich et al. reported that B-RFA (single-probe) created coagulation zones that were significantly closer to blood vessels compared to monopolar RF ablation [30]. They suggested that B-RFA allowed the lesion to be framed with higher current densities between the electrodes, which decreased the survival of tumour cells adjacent to blood vessels and decreased recurrence rates. Nevertheless, it must be emphasized that the ideal situation is when the two probes of InCircleTM B-RFA are placed 4–6 mm lateral to the perimeter of the tumour in order to achieve a margin of 1 cm (approximately 5 mm is ablated lateral to the two probes in bipolar mode) and to reach full impedance using bipolar mode alone. The use of B-RFA in bipolar mode traps heat between probes and is less prone to conductive ‘heat sinks’, compared to M-RFA and monopolar MWA [18]. This results in higher temperatures, more effective cellular destruction and a larger zone of ablation [18, 19]. The maximum volume of RF-induced coagulation necrosis can be significantly greater with B-RFA (bipolar mode) compared to M-RFA (unipolar mode) in a single ablation, reaching up to 7 cm [22, 31, 32]. There have been recent clinical studies that have shown B-RFA to be more controlled and faster than M-RFA for similarly sized tumours without an increase in complications. Recent studies report B-RFA to be more than three times faster than M-RFA (6 vs. 20 min) [11, 16], whilst having equivalent 3-year overall survival, disease-free survival and local recurrence rate in patients who had their
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ablation done laparoscopically [23]. As the laparoscopic approach remains more invasive and costlier than the percutaneous approach, future long-term studies to compare percutaneous M-RFA with B-RFA are warranted. The utilization of InCircleTM B-RFA is best suited for those with proper knowledge of hepatic anatomy and experience using this device. Guidance under real-time computed tomography is required to decrease the risk of inadvertent injury to vascular or biliary structures. The demand to find two suitable paths through the liver to the target without crossing larger vessels or hilar structures and provoking severe injury to the liver can be challenging [17]. Many studies describe a straight learning curve, where the more experience with targeting and positioning two needles is accumulated, the more time-efficient surgery is performed [17]. Additionally, the larger gauge size and the use of one additional electrode would theoretically double the risk of complications such as haemorrhage and pain compared to M-RFA. Despite these potential obstacles, the dual-probe B-RFA remains a valuable tool for experienced interventionalists with thorough knowledge of internal hepatic anatomy. B-RFA seems to be particularly useful in the treatment of tumours with sizes exceeding 3.0 cm, or in the case of local recurrence following conventional M-RFA. The current study has certain limitations since we have not correlated the present findings with in vivo studies. It is unclear whether the results obtained in ex vivo tissue identically reflect the results in human hepatic tumour because of different tissue textures, tissue impedance, blood flow and cell biology. Furthermore, the distance between the bipolar probes and the dispersive pads in these experiments is shorter than that during bipolar ablation in a human (where the dispersive pad would usually be placed on the thigh). Therefore, the extent to which the results of this experimental study can be extrapolated to the real RFA situation in humans may be limited. In spite of these limitations, however, our experiments provide preliminary evidence for the novel ‘‘Edgeboost-1’’ and ‘‘Edgeboost-2’’ techniques that can be easily implemented intra-operatively to extend the lateral ablation distances using B-RFA. In conclusion, this study demonstrates that the novel ‘‘Edgeboost’’ technique can increase the distance lateral to the two electrodes. ‘‘Edgeboost’’ would be beneficial for interventionalists who may utilize the dual-probe B-RFA in open, laparoscopic or percutaneous ablation of tumours. Compliance with Ethical Standards Conflict of interest Dr. Huo, Dr. Pillai, and Dr. Akhter have nothing to disclose. Dr. Morris reports other from RFA Medical, outside the submitted work; In addition, Dr. Morris has a patent Yes licenced to RFA Medical.
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Research Involving Human and Animal Rights This article does not contain any studies with human participants or animals performed by any of the authors.
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Y. R. Huo et al.: Novel Technique to Extend the Lateral Ablation Zone to Bipolar... 19. Haemmerich D, Staelin ST, Tungjitkusolmun S, Lee FTJ, Mahvi DM, Webster JG. Hepatic bipolar radio-frequency ablation between separated multiprong electrodes. Trans Biomed Eng. 2001;48:1145–52. 20. Jaskolka JD, Asch MR, Kachura JR, et al. Needle tract seeding after radiofrequency ablation of hepatic tumors. J Vasc Interv Radiol. 2005;16(4):485–91. 21. Nordlinger B, Benoist S. Treatment options for metastatic liver cancer. Surgical resection including perioperative chemotherapy (adjuvant and neoadjuvant). Eur J Cancer. 2003;1:181–8. 22. Jin GY, Park SH, Han YM, et al. Radio frequency ablation in the rabbit lung using wet electrodes: comparison of monopolar and dual bipolar electrode mode. Korean J Radiol. 2006;7:97–105. 23. Alemi F, Kwon E, Stewart L, Corvera CU. A comparison of monopolar to bipolar radiofrequency ablation of liver tumors. HPB. 2011;13:2–3. 24. McGahan JP, Brock JM, Tasluk H, et al. Hepatic ablation with use of radio-frequency electrocautery in the animal model. J Vasc Interv Radiol. 1992;3:291–6. 25. Organ LW. Electrophysiologic principles of radiofrequency lesion making. Appl Neurophysiol. 1976;39:69–76. 26. Chen MH, Yang W, Yan K, et al. Large liver tumors: protocol for radiofrequency ablation and its clinical application in 110 patients—mathematic model, overlapping mode, and electrode placement process. Radiology. 2004;232(1):260–71.
27. Collyer WC, Landman J, Olweny EO, et al. Comparison of renal ablation with cryotherapy, dry radiofrequency, and saline augmented radiofrequency in a porcine model. J Am Coll Surg. 2001;193:505. 28. Meijerink MR, Van Den Tol P, Van Tilborg AAJM, Van Waesberghe JHTM, Meijer S, Van Kuijk C. Radiofrequency ablation of large size liver tumours using novel plan-parallel expandable bipolar electrodes: initial clinical experience. Eur J Radiol. 2011;77(1):167–71. 29. Van Tilborg AA, Nielsen K, Scheffer HJ, et al. Bipolar radiofrequency ablation for symptomatic giant ([10 cm) hepatic cavernous haemangiomas: initial clinical experience. Clin Radiol. 2013;68(1):e9–14. 30. Haemmerich D, Wright AW, Mahvi DM, Lee FTJ, Webster JG. Hepatic bipolar radiofrequency ablation creates coagulation zones close to blood vessels: a finite element study. Med Biol Eng Comput. 2003;41:317. 31. Al-Alem I, Pillai K, Akhter J, Chua TC, Morris DL. Heat sink phenomenon of bipolar and monopolar radiofrequency ablation observed using polypropylene tubes for vessel simulation. Surg Innov. 2014;21(3):269–76. 32. Lee JM, Han JK, Kim SH, et al. Saline-enhanced hepatic radiofrequency ablation using a perfused-cooled electrode: comparison of dual probe bipolar mode with monopolar and single probe bipolar modes. Korean J Radiol. 2004;5(2):121–7.
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LABORATORY INVESTIGATION
‘‘Edgeboost’’: A Novel Technique to Extend the Ablation Zone Lateral to a Two-Probe Bipolar Radiofrequency Device Ya Ruth Huo1,2 • Krishna Pillai1 • Javed Akhter1 • David L. Morris1,2
Received: 25 May 2015 / Accepted: 23 June 2015 Ó Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2015
Abstract Background The dual-electrode bipolar-RFA (B-RFA) is increasingly used to ablate large liver tumours (3–7 cm). However, the challenging aspect of B-RFA is the placement of the two electrodes around the tumour. Realignment often requires the electrodes to be extracted and reinserted. Aim The aim of this study is to examine ‘‘Edgeboost’’, a novel technique to increase the lateral ablation dimension without requiring any realignment of the electrodes. Methods and Materials An egg-white model and an ex vivo calf liver model were used compare the standard bipolar mode ablation to Edgeboost-1 (reaching full impedance in bipolar mode initially, then cycling in unipolar mode between left and right probes) and Edgeboost-2 (similar to Edgeboost-1 but not reaching full impedance initially in bipolar mode in order to minimize charring and, thus, to increase total ablation time). Results A significantly larger outer lateral ablation dimension to the probe was achieved with Edgeboost-1 compared to the standard method in the liver model
& David L. Morris [email protected] Ya Ruth Huo [email protected] Krishna Pillai [email protected] Javed Akhter [email protected] 1
Hepatobiliary and Surgical Oncology Unit, UNSW Department of Surgery, St George Hospital, Level 3, Pitney Building, Kogarah, Sydney, NSW 2217, Australia
2
St George Clinical School, University of New South Wales, Sydney, NSW, Australia
(1.14 cm, SD: 0.16 vs. 0.44 cm, SD: 0.24, p = 0.04). Edgeboost-2 achieved the largest outer lateral ablation dimension of 1.75 cm (SD: 0.35). A similar association was seen in the egg model. Edgeboost-2 almost doubled the mass ablated with standard bipolar alone (mass ratio: 1:1.94 in egg white and 1:1.84 in liver). Conclusion This study demonstrates that the novel ‘‘Edgeboost’’ technique can increase the outer lateral ablation dimension without requiring the two inserted electrodes to be reinserted. This would be beneficial for interventionists who use the dual B-RFA. Keywords Radiofrequency ablation Novel technique Bipolar InCircle Dual-probe Edgeboost
Introduction Mono-polar radiofrequency ablation (M-RFA) is the most widely used image-guided interventional treatment of hepatic, pulmonary and renal tumours [1–3]. However, the most restrictive factor concerning the broader applicability of M-RFA is the limited size of the radiofrequency-induced ablation (\3.0 cm) [1]. Inverse Square Law of physics applies to the use of all M-RFA devices. As a result, the current density decreases as the inverse square of the distance from the electrode, while heating decreases as the inverse of the fourth power of the distance from the electrode. [4] Therefore, heating preferentially takes place immediately adjacent to the electrode and causes irreversible dehydration and charring of the tissue near the electrode during the RFA process. Although effective methods have been developed to reduce charring and to increase the radius of ablation by the use of expandable
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electrodes, saline-infused probes or cooling with saline injections, achieving complete ablation for lesions [3 cm remains problematic with M-RFA (complete ablation: 100 % if \3 cm vs. 80 % if [3 cm; local recurrence rate: 1.6 % for tumours \3 cm vs. 8.8 % overall) [5]. Considerable differences in the local recurrence rates are reported in the literature, ranging from 6 to 39 %. [6–10]. In an effort to overcome the shortfalls of M-RFA, many centres have employed other thermocoagulative devices to treat liver tumours such as microwave ablation (MWA) and bipolar-RFA (B-RFA) [11, 12]. A few B-RFA devices have already been developed [13–16]. Some use single needles with two opposite electrical pole points at the distal end, whilst others use two separate electrodes that are placed on either side of the tumour with no direct tumour contact [13, 15]. All M-RFA devices create a core zone of ablation at the tumour site that extends radially into the adjacent tissue relying primarily on thermal conduction to ablate the tissue. In contrast, B-RFA promises the formation of a controlled and more reliable ablation area based on the geometric projection from one electrode to the other. As a result, the ablation evolves in a well-defined site delineated by the two electrodes. Referred to as a ‘line of sight’ delivery system [11], the dual-probe B-RFA involves direct penetration of radiofrequency energy through the targeted tumour (Fig. 1). Furthermore, depending on the tumour size, this approach of dual-probe B-RFA avoids the tumour being punctured and thus allows for an oncologically surgical correct ‘‘no touch’’ technique. Depending on the type of B-RFA probe used, either a rounded cube or spherical ablation distribution is achieved for up to 7 cm [17]. Fig. 1 Illustration showing differences between monopolar (A) and bipolar (B) ablation, and the InCircleTM Monarch (RFA Medical, Inc., Fremont, CA, USA) parallel electrode system for B-RFA (C)
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Furthermore, B-RFA is less affected by conductive ‘heat sinks’, compared to M-RFA and even monopolar MWA [18]. The decreased dependence on local inhomogeneities such as blood perfusion compared to M-RFA results in the ability to achieve a larger zone of ablation (finite-element models of 7.95 cm3 for monopolar and 18.79 cm3 for B-RFA) [19]. Monopolar probes require a single insertion into the tumour, allowing for thermocoagulation of tissue adjacent to deployable tines. A dispersive pad is required to close the RFA current cycle. B-RFA requires placement of dual probes 4–6 mm from the perimeter of the tumour to achieve a 1-cm margin (bipolar mode alone achieves a lateral ablation distance of 5 mm). No dispersive pad is required for B-RFA. B-RFA probe shafts are shaped like an ‘‘8’’ in cross Section (8 9 6 French Gauge for the 4 and 5 cm InCircleTM Monarch, 18 9 8 French Gauge for the 7 cm InCircleTM Monarch). The most essential, yet difficult, skill in using bipolar probes is placing the two probes 4–6 mm lateral to the perimeter of the tumour in order to achieve a margin of 1 cm (approximately 5 mm is ablated lateral to the two probes in bipolar mode). As the current stream flows between the two probes, any tumour within the two electrodes would be completely ablated until there is no electrical current (i.e. impeded out), whilst tumour lying on the outer edge of the electrodes may not receive the same treatment. In circumstances where the probes are inserted inside the tumour, the misplaced electrode would need to be removed and reinserted into the correct position otherwise the tumour outside will not be treated, or in
Y. R. Huo et al.: Novel Technique to Extend the Lateral Ablation Zone to Bipolar...
circumstances where a larger margin is desired. Removal and reinsertion of an M-RFA probe has been associated with a small risk of needle track seeding and complications such as bleeding and infections [20]. However, this risk may be slightly higher for B-RFA due to the larger probe size. Hence, the aim of this study is to examine a novel method of increasing the ablation zone lateral to the outer margin of the dual probes as to avoid the need to remove and reinsert a slightly misplaced electrode. Due to the different method of heat transfer and ablation distribution between M-RFA and B-RFA, this study hypothesizes that the novel method of using unipolar mode after bipolar mode with a dual-probe B-RFA would increase the ablation zone on the outer lateral side to the probes compared to using bipolar mode alone. Two novel techniques (Edgeboost-1 and 2) will be examined in an egg-white model and ex vivo calf liver. Various parameters such as total time to ablate, mass, volume, density and lateral and longitudinal dimensions, as well as the ablation zone on the outer lateral side to the two probes (x), will be measured and compared to the standard bipolar mode of ablation.
Methods No ethics approval was required to perform this study, as it did not involve the use of any patients or live animal tissues. Livers were sourced from a commercial food supplier where the animals had been processed for human consumption. The RFA probe used in the experiment was the InCircleTM Monarch 4 cm (RFA Medical, Inc., Fremont, CA, USA) parallel electrode system for bipolar radiofrequency ablation (B-RFA). This device comprises two sets of opposing deployable electrodes, handle, plunger, guide block, power cable and generator adaptor cable. For our work, we used the nominal 4-cm needle probes with a 25-cm length probe that deploy six circular, planar-oriented electrodes (probe shafts are like an ‘‘8’’ shape in cross section; 8 9 6 French Gauge) (Fig. 1C). The generator used in the experiment was Model 1500, Rita Medical Systems, Inc (Mountain View, CA, USA). The standard dispersive pad was used from Rita Medical Systems, Inc (Mountain View, CA, USA) for monopolar application of radiofrequency energy in Edgeboost-1 and Edgeboost-2.
4-cm InCircleTM Monarch Bipolar Probe was secured in the same position for all experiments, and the two probes were placed 3 cm apart in both the egg and liver models. Edgeboost-1 and 2 were compared to Standard bipolar ablation alone at 100 W until full impedance. The ablation parameters for the two novel techniques are as follows: Edgeboost-1: (a) Bipolar mode: 100 W, time: until full impedance. (b) Unipolar mode, Right electrode: 100 W, time: 5 min egg white and 2.5 min in calf liver. (c) Unipolar mode, Left electrode: 100 W, time: 5 min egg white and 2.5 min in calf liver. (d) Repeat b and c until full impedance is reached by both electrodes. (e) Bipolar mode: 100 Watts, time: until full impedance. Edgeboost-2 (a)
Bipolar mode: 100 W, time: 8 min egg white and 3 min calf liver. (b) Unipolar mode, Right electrode: 100 W, time: 5 min egg white and 2.5 min in calf liver. (c) Unipolar mode, Left electrode: 100Watts, time: 5 min egg white and 2.5 min in calf liver. (d) Repeat b and c until full impedance is reached by both electrodes. (e) Bipolar mode: 100 W, time: until full impedance. Egg Model Fresh egg whites were separated from egg yolks and placed into a 1.8-L glass beaker with a diameter of 14 cm and a height of 19.5 cm. The egg white was equilibrated to 37 °C for each experiment. One dispersive pad was placed in the beaker, perpendicular and symmetrical to each of the two probes. Preliminary trials found no indication of coagulation on the pad surface. The set-up of the egg model is shown in Fig. 2. Coagulated egg white was recognised by the change in consistency and colour from a yellow gel to an opaque, white, firm mass. For each device, the experiment was repeated five times. The InCircleTM probes are placed in the centre of the cylindrical beaker filled with fresh egg-white (stabilised with a wooden bridge that is not shown). A dispersive pad is placed at the perimeter.
Ablation Technique Liver Model Edgeboost-1 and 2 were two novel techniques which cycled between bipolar and unipolar modes (Fig. 2). Edgeboost-1 and 2 were similar except for the first step, where Edgeboost1 reached full impedance using bipolar mode, whilst Edgeboost-2 did not reach full impedance. For all experiments, power was set at 100 W and the same generator was used. A
Fresh calf liver was equilibrated to 37 °C before beginning the experiment. The liver was placed in a rectangular polypropylene container (dimensions of 30 9 10 9 18 cm3), and 0.9 % saline (conductive media) at 37 °C was added into the container to three-quarters of the height of
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Y. R. Huo et al.: Novel Technique to Extend the Lateral Ablation Zone to Bipolar... Fig. 2 Visual representation of the egg-white model set-up
the liver. A dispersive pad was then placed at each end of the container. The InCircleTM Monarch probes were placed in the centre of the apparatus for each experiment, with each probe 13.5 cm away from the dispersive pad. The two probes were fixed 3 cm apart. The liver tissue that was ablated was recognised by the change in colour from deep brownish red to greyish pink. The tissue ablated was surgically excised from the rest of the liver. All three techniques were repeated four times. Measurements and Calculations The longitudinal dimension, lateral dimension and width of the ablated mass were measured using a linear centimetre scale, while the mass ablated was recorded in grams. The volume was measured using the displacement method by immersing only the ablated liver tissue or egg white in water. The average external lateral dimension (x) to each probe was calculated by the lateral dimension minus the distance between the two electrodes (3 cm) and then halved, as in Eq. 1 (Fig. 3). External lateral dimension ð xÞ ¼ ½Lateral dimension ðcmÞ distance between the probes ð3 cmÞ =2 ð1Þ The results are reported with mean readings and standard deviations. ANOVA was used to determine whether there was a statistically significant difference between the three techniques. The two-tailed independent t test was then used to compare the means between Standard bipolar alone with Edgeboost-1 and C, and Edgeboost-1 with Edgeboost-2. Statistically significant differences were defined as a p value less than 0.05. External lateral dimension to the two probes (x) was calculated by the lateral dimension minus the distance between the electrodes (3 cm) and then halved.
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Fig. 3 Measurements for egg model (A) and liver model (B) of the longitudinal dimension, lateral dimension and width
Results In bipolar mode alone, full impedance (roll-off) was always reached, requiring a mean duration of 6.1 min to ablate 3.9 9 5.0 9 5.1 cm ex vivo liver (Table 1). Similarly, for Edgeboost-1, the first step of reaching full impedance in bipolar mode required a mean time of 7.3 min. The external lateral distance of ablation to the electrodes (x) was significantly different between the three techniques
Y. R. Huo et al.: Novel Technique to Extend the Lateral Ablation Zone to Bipolar... Table 1 Comparison of ablation parameters between standard ablation, Edgeboost-1 (EB-1) and Edgeboost-2 (EB-2) Parameters
Egg-white model Standard
Edgeboost-1
Mass, g (SD)
112.0 (19.1)
Ratio
Ex vivo liver model Edgeboost-2
ANOVA
Standard
Edgeboost1
Edgeboost-2
ANOVA
185.4 (48.0)*,b
217.7 (70.9)*
0.082
95.5 (24.8)
121.6 (12.8)
180.1 (46.5)**
0.05
1
1.66
1.94
1
1.27
1.88
p valuea EB-1 versus EB-2 Volume cm3 (SD)
– 104.6 (21.4)
– 176.0 (47.8)*
0.52 216 (65.4)*
– 89.3 (28.8)
– 116.3 (11.1)
0.14 166.3 (40.1)**
Ratio
1
1.68
2.07
p value EB-1 versus EB-2
–
–
0.4085
Density, g/cm3 (SD)
1.08 (0.07)
1.06 (0.05)
1.0 (0.06)
Ratio
1
0.98
0.93
p value EB-1 versus EB-2
–
–
0.31
Ablation time (SD)
19.1 (7.9)
27.9 (6.9)
33.4 (14.0)
Ratio
1
1.46
1.74
p value EB-1 versus EB-2
–
–
0.52
Longitudinal diameter (SD)
5.5 (0.4)
6.1 90.7)
6.0 (0.9)
Ratio
1
1.1
1.1
p value EB-1 versus EB-2
–
–
0.89
Lateral diameter (SD)
6.3 (0.36)
7.7 (1.1)
8.2 (0.8)*
Ratio
1
1.22
p value EB-1 versus EB-2 Width (SD)
– 5.9 (0.6)
– 6.4 (0.77)
Ratio
1
1.1
p value EB-1 versus EB-2
–
–
0.06
0.045
1 0.26
0.19
0.38
–
–
0.13
1.09 (0.04)
1.05 (0.04)
1.08 (0.02)
1
0.96
0.99 0.25
–
–
6.1 (0.9)
15.1 (10.1)
23.3 (11.5)
1
2.48
3.81 0.48
–
–
5.0 (0.9)
4.4 (0.5)
4.9 (0.6)
1
0.88
0.98
–
–
0.01
0.015
3.9 (0.5)
5.3 (0.3)*
6.5 (0.7)***
1.30
1
1.35
1.7
0.20 7.1 (1.19)
0.23
– 5.1 (1.1)
– 5.3 (0.2)
0.08 6.4 (0.3)
1.2
1
1.04
1.25
0.45
–
–
0.02
a
Independent two-tailed t test comparing Edgeboost-1 with Edgeboost-2
b
Independent two-tailed t test comparing Edgeboost-1 or Edgeboost-2 against standard ablation
0.50
0.19
0.36
0.005
0.10
* p \ 0.05; ** p \ 0.01; ***p \ 0.001
in both the egg and liver models (ANOVA = 0.007 and 0.005, respectively). In the liver model, the x value was the highest with Edgeboost-2 (1.75 cm, SD: 0.35) followed by Edgeboost-1 (1.14 cm, SD: 0.16,) and lowest with standard bipolar mode (0.44 cm, SD: 0.24) (Fig. 4A). The x value for Edgeboost-1 and Edgeboost-2 was significantly higher than standard bipolar ablation alone. Edgeboost-1 and Edgeboost-2 were not significantly different. A similar association was seen in the egg model (Fig. 4B). The mean volume, mass, density, ablation time and dimensions using the three techniques with comparative ratios for both the liver tissue and egg-white model are shown in Table 1. In both the liver and egg models, the ablated mass was the highest using Edgeboost-2, followed by Edgeboost-1, and lowest in standard bipolar alone. Edgeboost-2 almost doubled the mass achieved using standard bipolar ablation method (standard bipolar alone) (relative increase in mass: 1.94 in egg white and 1.84 in liver). A similar correlation was seen with volume; however, density remained similar between the three techniques. In both the liver and egg models, the ablation time
was the highest in Edgeboost-2, followed by Edgeboost-1, and lowest in standard bipolar alone. The lateral and longitudinal dimensions were not statistically different between the three techniques in the egg model. In the calf liver model, the lateral and longitudinal dimensions were significantly higher in Edgeboost-2 compared to Edgeboost-1. Furthermore, the lateral and longitudinal dimensions for standard bipolar mode alone were not significantly different compared to Edgeboost-1 and Edgeboost-2 (Fig. 5). Ablated zone and healthy liver not shown to size. The conductive medium, 0.9 % saline water at 37 °C, to reach three-quarters of the height of the liver is not illustrated.
Discussion Worldwide, RFA is among the most frequently used ablation system for the local control of tumours in organs such as the liver, lung and kidneys. The use of RFA for hepatic lesions is the most widely accepted, as this
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Y. R. Huo et al.: Novel Technique to Extend the Lateral Ablation Zone to Bipolar... Fig. 4 Lateral ablation distance for the three techniques in the egg model (A, ANOVA = 0.007) and liver model (B, ANOVA = 0.005)
Fig. 5 Cross sections of bovine liver after standard bipolar ablation and Edgeboost-2 demonstrating the increased distance of ablation lateral to the bipolar electrodes (unbroken arrow)
minimally invasive treatment is attractive for patients with HCC who are unsuitable for hepatic resection and may also act as a bridging treatment to transplantation [21]. More so, many patients with secondary liver tumours are unsuitable for surgery due to comorbidities. Although M-RFA technology has significant limitations, it has been extensively described and is the most widely used thermal ablative method. In an effort to overcome the limitations of M-RFA, other thermal energy systems have been introduced for destruction of liver tumours. Dual-probe B-RFA energy delivery has the advantages of a uniform and higher current density providing rapid ablation without significant reliance on thermal conduction in the tumour target zone [18]. Animal studies comparing M-RFA to dual-probe
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B-RFA have shown superiority for the B-RFA method with respect to larger ablation zone, tissue control, haemostasis and overall efficiency [16, 22]. Clinical studies are also beginning to emerge confirming improved tumour ablation times and efficacy using dual-probe B-RFA in comparison with M-RFA [11, 23]. However, the critical yet sometimes challenging skill in using dual B-RFA can be the precise placement of the two electrodes at the perimeter of the tumour. If one or both of the electrodes are placed within the tumour, malignant cells lateral to the electrodes may not be adequately ablated as a majority of the radiofrequency current flows between the two electrodes. Realignment requires the electrodes to be extracted and reinserted, which is associated with the risk of needle track seeding and complications such as bleeding and infections [20]. A technique to increase the lateral ablation zones without requiring the two inserted electrodes to be removed would be a major benefit not only to the surgeons and interventional radiologists who may utilize the dual B-RFA in open, laparoscopic or percutaneous surgery, but also to the patients. However, it is important to highlight that the intended use of the InCircleTM technology is to have both probes inserted correctly. This study has identified two novel techniques (Edgeboost-1 and Edgeboost-2) that can increase the ablation zone lateral, externally on either side to the electrodes, as well as the volume and mass compared to standard bipolar mode. Both novel techniques are simple to implement in clinical practice, requiring only one additional dispersive pad on the patient to form a unipolar radiofrequency circuit with either of the two electrodes (Fig. 6). As expected, this study found that the use of bipolar mode alone until full impedance (Standard bipolar alone) created a spherical ablated mass with an external lateral ablation dimension (x) 0.44 cm on either side of each electrode. Edgeboost-1 was able to increase the external lateral ablation dimension (x) to 1.14 cm (additional 0.7 cm compared to bipolar
Y. R. Huo et al.: Novel Technique to Extend the Lateral Ablation Zone to Bipolar...
mode alone), whilst Edgeboost-2 was able to increase the x value further to 1.75 cm (additional 1.31 cm). If necessary, these two novel techniques can increase the lateral tumour-free margin without realignment of the B-RFA electrodes. Edgeboost-1 demonstrated that even after reaching maximum impedance in bipolar mode, each of the two probes can undergo further ablation in unipolar mode to increase the lateral ablation dimension. This highlights that complete charring of the electrodes does not occur in B-RFA when maximum impedance is reached. This is likely due to the physics of heating in B-RFA, whereby the RF current passes between the needle electrodes to produce an ionic flux in the tissue, so that the tissues, not the electrodes, are the source of heat in B-RFA [24, 25]. This ‘‘line of sight’’ energy directly penetrates the targeted tumour, and maximum impedance is reached when all of the tissue between the two electrodes undergo complete desiccation and contraction (Fig. 6).
Fig. 6 Increase in ablation zone lateral to the bipolar electrodes for Edgeboost-1 [complete ablation at step 1 (bipolar only)] and Edgeboost-2 (partial ablation at step 1)
Interestingly, Edgeboost-2 demonstrated that an even wider lateral ablation distance could be achieved if full impedance is not reached in bipolar mode initially. This suggests that when maximum impedance is reached in bipolar mode (Edgeboost-1), there is some charring of the two electrodes that limits the ability of each electrode to undergo further ablation in unipolar mode. However, a question then arises: Why not discard the use of bipolar initially and just use overlapping M-RFA probes? The use of overlapping ablation with M-RFA is known to be associated with a higher risk of local tumour recurrence [26]. This is likely due to the extreme difficulty of achieving complete ablation by overlapping unipolar probes, especially if the probes are placed too distant from the previous ablation or close to blood vessels [27]. A previous study required 12–13 electrodes to successfully ablate tumours 6.6–7.0 cm in diameter [26]. An explanation for this is the decrease in current density that occurs at a distance from the energy source in the monopolar RF mode, making the periphery of the lesion particularly prone to vascular cooling. In comparison, InCircleTM has been found to be able to ablate tumours up to 7.8 cm, achieve ablation sizes up to 10.3 cm [28] and to ablate giant hepatic hemangiomas ([10 cm) [29]. Haemmerich et al. reported that B-RFA (single-probe) created coagulation zones that were significantly closer to blood vessels compared to monopolar RF ablation [30]. They suggested that B-RFA allowed the lesion to be framed with higher current densities between the electrodes, which decreased the survival of tumour cells adjacent to blood vessels and decreased recurrence rates. Nevertheless, it must be emphasized that the ideal situation is when the two probes of InCircleTM B-RFA are placed 4–6 mm lateral to the perimeter of the tumour in order to achieve a margin of 1 cm (approximately 5 mm is ablated lateral to the two probes in bipolar mode) and to reach full impedance using bipolar mode alone. The use of B-RFA in bipolar mode traps heat between probes and is less prone to conductive ‘heat sinks’, compared to M-RFA and monopolar MWA [18]. This results in higher temperatures, more effective cellular destruction and a larger zone of ablation [18, 19]. The maximum volume of RF-induced coagulation necrosis can be significantly greater with B-RFA (bipolar mode) compared to M-RFA (unipolar mode) in a single ablation, reaching up to 7 cm [22, 31, 32]. There have been recent clinical studies that have shown B-RFA to be more controlled and faster than M-RFA for similarly sized tumours without an increase in complications. Recent studies report B-RFA to be more than three times faster than M-RFA (6 vs. 20 min) [11, 16], whilst having equivalent 3-year overall survival, disease-free survival and local recurrence rate in patients who had their
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ablation done laparoscopically [23]. As the laparoscopic approach remains more invasive and costlier than the percutaneous approach, future long-term studies to compare percutaneous M-RFA with B-RFA are warranted. The utilization of InCircleTM B-RFA is best suited for those with proper knowledge of hepatic anatomy and experience using this device. Guidance under real-time computed tomography is required to decrease the risk of inadvertent injury to vascular or biliary structures. The demand to find two suitable paths through the liver to the target without crossing larger vessels or hilar structures and provoking severe injury to the liver can be challenging [17]. Many studies describe a straight learning curve, where the more experience with targeting and positioning two needles is accumulated, the more time-efficient surgery is performed [17]. Additionally, the larger gauge size and the use of one additional electrode would theoretically double the risk of complications such as haemorrhage and pain compared to M-RFA. Despite these potential obstacles, the dual-probe B-RFA remains a valuable tool for experienced interventionalists with thorough knowledge of internal hepatic anatomy. B-RFA seems to be particularly useful in the treatment of tumours with sizes exceeding 3.0 cm, or in the case of local recurrence following conventional M-RFA. The current study has certain limitations since we have not correlated the present findings with in vivo studies. It is unclear whether the results obtained in ex vivo tissue identically reflect the results in human hepatic tumour because of different tissue textures, tissue impedance, blood flow and cell biology. Furthermore, the distance between the bipolar probes and the dispersive pads in these experiments is shorter than that during bipolar ablation in a human (where the dispersive pad would usually be placed on the thigh). Therefore, the extent to which the results of this experimental study can be extrapolated to the real RFA situation in humans may be limited. In spite of these limitations, however, our experiments provide preliminary evidence for the novel ‘‘Edgeboost-1’’ and ‘‘Edgeboost-2’’ techniques that can be easily implemented intra-operatively to extend the lateral ablation distances using B-RFA. In conclusion, this study demonstrates that the novel ‘‘Edgeboost’’ technique can increase the distance lateral to the two electrodes. ‘‘Edgeboost’’ would be beneficial for interventionalists who may utilize the dual-probe B-RFA in open, laparoscopic or percutaneous ablation of tumours. Compliance with Ethical Standards Conflict of interest Dr. Huo, Dr. Pillai, and Dr. Akhter have nothing to disclose. Dr. Morris reports other from RFA Medical, outside the submitted work; In addition, Dr. Morris has a patent Yes licenced to RFA Medical.
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Research Involving Human and Animal Rights This article does not contain any studies with human participants or animals performed by any of the authors.
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