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Published online before print January 25, 2002, 10.1148/radiol.2223010573
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(Radiology 2002;222:805-813.)
© RSNA, 2002

Experimental Studies

Radio-frequency Tumor Ablation: Internally Cooled Electrode versus Saline-enhanced Technique in an Aggressive Rabbit Tumor Model1

Thomas Boehm, MD, Ansgar Malich, MD, S. Nahum Goldberg, MD, Jürgen R. Reichenbach, PhD, Ingrid Hilger, PhD, Peter Hauff, DVM, PhD, Michael Reinhardt, Marlies Fleck, MD and Werner A. Kaiser, MD

1 From the Department of Diagnostic Radiology, Universitätsspital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland (T.B.); Department of Diagnostic and Interventional Radiology, Friedrich-Schiller-Universität Jena, Germany (A.M., J.R.R., I.H., M.F., W.A.K.); Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass (S.N.G.); and Schering AG, Research Laboratories, Berlin, Germany (P.H., M.R.). Received March 7, 2001; revision requested April 9; revision received June 18; accepted July 24. Address correspondence to T.B. (e-mail: thomas_boehm@gmx.net).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
PURPOSE: To compare two methods of radio-frequency (RF) ablation, saline enhancement technique and internally cooled electrodes, for the treatment of small breast cancers in an animal model—highly aggressive VX2 rabbit tumors surrounded by adipose tissue.

MATERIALS AND METHODS: Twenty-seven tumors were implanted into retroperitoneal fat of 14 New Zealand White rabbits. RF ablation was performed with ultrasonographic (US) guidance after tumors had grown to 15 mm. Fourteen tumors in seven animals were treated with internally cooled electrodes (30-mm-tip single electrode, 60 W, 10 min); 13 tumors in seven animals, with saline enhancement (0.5 mL/min of saline, 25-mm tip, 30 W, 10 min). Autopsy and histopathologic assessment were performed 3 weeks after therapy.

RESULTS: Real-time US of RF ablation was not possible with either method because of obscuration by the increasing hyperechogenicity of the tumor and the surrounding adipose tissue. Equivalent efficacy was demonstrated with the two methods. Significantly greater complications were observed with the saline technique: Free retroperitoneal fluid was detected in one of seven animals with internally cooled electrodes and in all seven animals with saline enhancement (P < .01). Damage to remote structures such as the kidney, spine muscle, and skin was observed at autopsy in one of seven animals with internally cooled technique versus five of seven with saline enhancement (P < .01).

CONCLUSION: Given a lower complication rate and similar treatment efficacy in an animal tumor model, internally cooled RF electrode may be advantageous to adjuvant saline infusion for the minimally invasive treatment of breast tumors.

© RSNA, 2002

Index terms: Animals • Breast neoplasms, 00.30 • Radiofrequency (RF) ablation, 00.1269 • Ultrasound (US), guidance, 00.12986


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
For the past several years, image-guided radio-frequency (RF) ablation has become a popular method for the thermal treatment of focal tumors (1,2). When RF energy is applied to tissues via needlelike electrodes, it produces ionic resistive heating to temperatures greater than 50°C, which in turn induces focal irreversible coagulation necrosis when administered for 4–6 minutes (3). Promising initial results have been achieved, especially for the palliative treatment of liver tumors (4–9). There have been enthusiastic investigations (10–19) for the use of RF ablation for definitive treatment of tumors in other organs. One example is the breast (14), where minimally invasive procedures would be desirable because they may reduce morbidity and improve cosmesis over traditional surgical approaches. However, in contrast to the treatment of liver metastases, where incomplete local treatment of the tumor could still lead to potential palliation, the treatment of breast tumors must achieve complete definitive results. This fact substantially changes the nature of the procedure by increasing demands for complete tumor necrosis. Additionally, further research is required to establish the feasibility of RF tumor ablation in the breast, as these lesions are often embedded in fat, a tissue whose electric and thermal conductivity properties are markedly different from those of the liver (20,21).

Much of the recent success of the RF ablation technique can be attributed to the newly developed techniques that permit the induction of larger zones of coagulation, as the inability to create sufficient volumes of ablations had previously represented the key limitation to successful tumor treatment (1,22). These techniques include the use of hooked-array systems (9,11,12), adjuvant saline injection (ie, the "wet" or "virtual" electrode) (20,23–25), and single or cluster arrays of internally cooled electrodes (5). Using these techniques, several investigators reported increases in coagulation over conventional monopolar RF electrode systems, from 1.6 to 3.5–5.0 cm in diameter. However, thus far, direct comparison between these methods has been limited to studies in which hooked arrays were compared with internally cooled cluster electrodes (26). As such, the optimal method for RF ablation of the breast is currently unknown.

The purpose of this study was to compare two methods of RF ablation, a continuous adjuvant saline enhancement technique and internally cooled electrodes, for the treatment of small breast cancers in an animal model—highly aggressive VX2 rabbit tumors surrounded by adipose tissue.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Animal Preparation and Tumor Implantation Technique
The research protocol was approved by the Regional Animal Research Committee prior to the initiation of the study. Fourteen female New Zealand White rabbits (Harlan Winkelmann, Borchen, Germany) weighing 2.1–3.4 kg were used and were allowed access to food and water, as desired. The animals were anesthetized for tumor implantation and other procedures by using a mixture of 0.4 mL of ketamine hydrochloride (Ketavet 100; Upjohn, Heppenheim, Germany) and 0.2 mL of xylazine (Rompun 2%; BayerVital, Leverkusen, Germany) diluted in 5 mL of sterile saline solution. Anesthesia was administered intravenously with a 21-gauge catheter cannula (Venofix S Luer-Lok; B. Braun Melsungen, Melsungen, Germany) that was placed (T.B., A.M., P.H., M.R.) in the caudal auricular vein. Animals were shaved, and depilatory cream (Pilca extra mild; Hans Schwarzkopf, Hamburg, Germany) was applied on both sides of the spine.

To minimize the potential variation in tumor growth rate between animals, all animals were implanted with tissue from the same tumor donor. Fresh VX2 carcinoma was harvested from one carrier animal that was initially injected with cryogenically preserved tumor. This tumor material was washed in saline solution and cut into cubes of 1 mm3. B-mode ultrasonography (US) was performed to determine the optimal implantation site. By using a sterile technique, a 16-gauge cannula was advanced intravenously into the retroperitoneum with US guidance, and the prepared cubes of tumor tissue were advanced through the cannula by using a stylet and were placed with imaging guidance. The same procedure was repeated for tumor implantation on the contralateral side. Thus, 28 tumors were implanted.

Follow-up US was initially performed weekly and thereafter, once tumor growth was visible, at regular intervals of 3–4 days. Tumor treatments were performed once tumor diameters of 15 mm or greater were achieved.

RF Ablation
Animals were randomized to undergo one of two RF tumor ablation procedures by using a predefined randomization strategy (ie, even-numbered animals, cooled tip ablation; odd-numbered animals, saline-enhanced ablation). Ablation was performed with US guidance, with a single application of RF energy by using either a saline-enhanced technique (n = 14 tumors, 16.1 cm [mean ± SD] ± 0.8) or an internally cooled electrode (n = 13 tumors, 16.4 cm ± 0.9). During ablation, animals received an additional analgetic agent (Novaminsulfon Lichtenstein [0.3 ml per kilogram of body weight of metamizol-natrium]; Lichtenstein Pharmazeutica, Koblenz, Germany). US was performed for tumor localization. A small incision was made in the skin, and the ablation needle was advanced with US guidance and positioned in the center of the tumor (Fig 1). For both methods, ablation was performed for 10 minutes.



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  		Figure 1. Schematic illustrates the positioning of the ablation electrode into the center of the tumor (left) and the oval zone of necrosis around the exposed needle tip after ablation (right), which under ideal conditions should fully envelop the implanted tumor.

 
Internally Cooled RF Ablation
Internally cooled RF ablation was performed with a 500-kHz RF generator (Cosman Coagulator CC-1; Radionics, Burlington, Mass) with integrated impedance measurement and a 30-mm-tip single electrode (Fig 2). The ablation electrode is equipped with two connectors (Luer-Lok) for inflowing and outflowing iced distilled water coolant. In contrast to the saline-enhanced technique, there is no direct contact between the treated tissue and the cooling fluid. Rather, distilled water circulates in a closed loop between the ablation electrode and a thermos filled with ice cubes. This ensures a constant temperature of the coolant of approximately 0°C (27). Circulation of the cooling fluid was maintained with a pump (PE-PM Perfusion Pump; Radionics). For the internally cooled ablation technique, 60 W of RF power was applied on the basis of our prior optimization study (unpublished data, 1999). When an increase in impedance of more than 25 {Omega} was observed, the power was reduced to maintain a constant impedance.



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  		Figure 2. Ablation electrodes for internally cooled (left) and saline-enhanced (right) techniques. On the right, the cutouts (arrowheads) in the tip serve for saline infusion through the needle into the surrounding tissue.

 
Saline-enhanced RF Ablation
For the saline-enhanced RF technique, a 500-kHz RF generator (Elektrotom 104 HF Thermo; Berchtold Medizinbelektronik, Tuttlingen, Germany) was used to apply 30 W of power, which was the optimum energy deposition for this system as determined in an in vitro study (20) of breast tissue with high fat content. The generator was modified by the manufacturer to enable real-time measurement of the electric impedance during ablation. The electrode used for the saline-enhanced technique (Fig 2) is in its distal part double walled, with the inner wall having small holes. The infused saline solution flows through the hollow shaft of the electrode and escapes through the holes into the space between the inner and outer walls of the needle tip. The outer wall is constructed with larger rectangular apertures that permit even flow of saline solution into the tissues surrounding the needle tip. Continuous interstitial perfusion of sterile saline solution (0.9% NaCl; Braun) was started 5 seconds in advance of RF ablation. Uniform saline infusion was achieved by using a pump (Perfusor Secura FT; Braun). An initial saline perfusion rate of 0.5 mL/min (30 mL/hr) was chosen on the basis of prior in vitro optimization study results (20). However, if the impedance increased, the perfusion rate increased to 40 mL/hr.

Postprocedural Follow-up
To evaluate for complications, a complete abdominal gray-scale US was performed 10 minutes after ablation, with specific attention to kidneys, liver, and bowel. The echogenicity of the tumor was assessed by means of comparison with the adjacent fat. The kidneys were additionally inspected by administering a contrast agent (0.4 mL/kg, Levovist; Schering, Berlin, Germany) with a 7.5-MHz transducer (Harmonic Imaging Power Mode HDI-5000; ATL, Bothell, Wash) to detect perfusion deficits. Free intraabdominal fluid collections were recorded. Skin at the site of probe introduction was inspected for thermal damage. Food intake and behavior of the animals were recorded on a daily basis by technicians of the Institute for Animal Research, University of Jena, Germany. Follow-up B-mode US (four to five times per animal) was performed at 3–4-day intervals for up to 3 weeks after RF ablation or until progressive local tumor growth was identified. In either of these cases, the animals were sacrificed with an overdose of ketamine hydrochloride and xylazine. Autopsy was performed to determine the extent of intratumoral and distant thermal damage. Tumors and the adjacent fatty tissues were cross-sectioned for histopathologic analysis and stained with hematoxylin and eosin. The kidneys, the adjacent bowel, the spine muscles, and the abdominal wall were inspected for thermal damage. Both kidneys were cross-sectioned, stained with eosin and hematoxylin, and examined at microscopy. In case of abnormalities at gross inspection, appropriate representative portions of the spine muscles, abdominal wall, and bowel were cross-sectioned, stained, and examined at light microscopy (T.B., A.M., I.H.).

Data Analysis
The technical aspects (ie, time needed for electrode placement and feasibility of using US to monitor the producer), efficacy (ie, frequency of local persistent tumor growth), and complications (ie, detection of free intraabdominal fluid or damage to adjacent structures as seen with US and histopathologic assessment) for both techniques were directly compared. Changes in echogenicity of the tumor prior to and after ablation were recorded. Statistical analysis was performed by using the Fisher exact test, with a P value of less than .05 indicating a statistically significant difference.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Technique
Tumor growth to sizes greater than 15 mm required 19–29 days (23 days ± 3) and was achieved for all 28 implantations. However, one tumor was implanted in the abdominal wall, and, therefore, it was ablated at an early stage of tumor growth and excluded from the present study. The positioning of both types of RF electrodes was challenging, given the substantial mobility of the tumors within the surrounding adipose tissue. However, correct placement of the internally cooled needles was more difficult because of their greater diameter (1.45 vs 1.2 mm for saline-enhanced ablation electrodes). The time required for correct needle placement ranged from 1.5 to 3.5 minutes (mean, 1.8 minutes ± 0.6) for the saline electrodes and from 3.7 to 5.5 minutes (mean, 4.3 minutes ± 0.9) for the internally cooled electrodes (P < .05).

Imaging
Prior to the procedure, tumors were highly conspicuous, as they appeared markedly hypoechoic in comparison with the surrounding adjacent fat. However, real-time monitoring of the ablation procedure was not possible, because a large area of the fatty tissue surrounding the tumor became hyperechoic shortly after starting ablation. Additionally, the hyperechoic zone did not develop the typical conical shape that was previously observed (20,27) during ablation of parenchymal organs (Fig 3). Hence, no real visual control of the procedure (beyond initial insertion) or of the lesion size was possible by using B-mode US; thus, the ablation procedure was controlled by the monitoring of impedance only. All tumors were less hypoechoic 10 minutes after ablation, and none became hyperechoic. Following internally cooled ablation, five (36%) of 14 tumors became isoechoic; after saline-enhanced ablation, four (31%) of 13 became isoechoic (difference not significant).



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  		Figure 3a. US images (US probe oriented parallel to the long axis of the kidney) obtained during a retroperitoneal tumor ablation show a small conic hyperechoic thermal lesion (arrows) around the needle tip at (a) 1 minute, (b) 5 minutes, and (c) 10 minutes of ablation. The poorly defined lesion in b and c prevents visual control of the ablation procedure.

 


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  		Figure 3b. US images (US probe oriented parallel to the long axis of the kidney) obtained during a retroperitoneal tumor ablation show a small conic hyperechoic thermal lesion (arrows) around the needle tip at (a) 1 minute, (b) 5 minutes, and (c) 10 minutes of ablation. The poorly defined lesion in b and c prevents visual control of the ablation procedure.

 


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  		Figure 3c. US images (US probe oriented parallel to the long axis of the kidney) obtained during a retroperitoneal tumor ablation show a small conic hyperechoic thermal lesion (arrows) around the needle tip at (a) 1 minute, (b) 5 minutes, and (c) 10 minutes of ablation. The poorly defined lesion in b and c prevents visual control of the ablation procedure.

 
Complications
All animals recovered rapidly within 3 hours after ablation. However, decreased food intake for up to 2 days following the procedure was observed in one (14%) of seven animals treated with internally cooled electrodes and in all seven animals (100%) treated with saline enhancement (Fisher exact test, P < .005).

A significantly greater number of complications were observed with use of saline-enhanced techniques compared with use of internally cooled electrodes (P < .05, all comparisons). Following ablation, free retroperitoneal fluid was depicted with US in only one (14%) of seven animals with internally cooled electrodes, but in all seven animals (100%) with saline enhancement (Fig 4) (Fisher exact test, P < .005). Damage to the adjacent anatomic structures was detected at pathologic examination in six (86%) of seven animals when saline-enhancement techniques were used compared with one animal when internally cooled electrodes were used (14%) (P < .03).



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  		Figure 4. US images (US probe orientation parallel to the long axis of the kidney) obtained after RF ablation show free retroperitoneal fluid (arrows). Upper left: Fluid delineates the fascia perirenalis. Upper right: Fluid in the vicinity of an ablated tumor. Lower right and left: Two cases of fluid adjacent to the kidney.

 
Differences in collateral damage to the individual organs were not statistically significant when viewed individually by location. Nevertheless, trends toward greater complications with the saline technique were evident. Thermal damage to the kidney was observed in one (14%) of seven cases in which internally cooled electrodes were used, versus in three (43%) of seven cases with saline-enhanced ablation. In one case, US of a tumor located 3 cm away from the right kidney showed rapid fluid movement and gas bubbles around the lower pole of the kidney, which was interpreted as boiling fluid during ablation; a hyperechoic lesion in renal parenchyma became evident (Fig 5a). Contrast material–enhanced harmonic US performed 10 minutes after ablation (Fig 5b) revealed a perfusion deficit in the kidney. Gross inspection showed a pale rim of tissue at the lower pole of the kidney, and histopathologic examination revealed coagulative necrosis with neutrophilic and monocytic infiltration and beginning connective tissue growth.



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  		Figure 5a. Induced thermal lesion in the left lower pole of the kidney despite a distance of 3 cm between the ablation needle and the kidney. (a) US image shows a hyperechogenic thermal lesion (arrow) with fluid (arrowheads) around the lower pole of the kidney (US probe orientation parallel to the long axis of the kidney). (b) Contrast-enhanced harmonic US scan obtained 10 minutes after ablation shows a perfusion deficit in the cortex of the kidney (arrow). (c) Photomicrograph shows a bandlike thermal lesion in the lower pole kidney parenchyma (*), with neutrophil and macrophage infiltration toward the normal parenchyma (arrow). (Hematoxylin-eosin stain; original magnification, x40.)

 


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  		Figure 5b. Induced thermal lesion in the left lower pole of the kidney despite a distance of 3 cm between the ablation needle and the kidney. (a) US image shows a hyperechogenic thermal lesion (arrow) with fluid (arrowheads) around the lower pole of the kidney (US probe orientation parallel to the long axis of the kidney). (b) Contrast-enhanced harmonic US scan obtained 10 minutes after ablation shows a perfusion deficit in the cortex of the kidney (arrow). (c) Photomicrograph shows a bandlike thermal lesion in the lower pole kidney parenchyma (*), with neutrophil and macrophage infiltration toward the normal parenchyma (arrow). (Hematoxylin-eosin stain; original magnification, x40.)

 


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  		Figure 5c. Induced thermal lesion in the left lower pole of the kidney despite a distance of 3 cm between the ablation needle and the kidney. (a) US image shows a hyperechogenic thermal lesion (arrow) with fluid (arrowheads) around the lower pole of the kidney (US probe orientation parallel to the long axis of the kidney). (b) Contrast-enhanced harmonic US scan obtained 10 minutes after ablation shows a perfusion deficit in the cortex of the kidney (arrow). (c) Photomicrograph shows a bandlike thermal lesion in the lower pole kidney parenchyma (*), with neutrophil and macrophage infiltration toward the normal parenchyma (arrow). (Hematoxylin-eosin stain; original magnification, x40.)

 
Thermal damage of the spine muscle or skin was not seen in any cases in which internally cooled electrodes were used, but spinal muscle and skin damage were observed in two (28%) and one (14%) animals, respectively, when saline was used. At gross inspection, gray discolored areas of muscle tissue with geographic borders were visible. Histopathologic assessment revealed that myofibril nuclei had become pyknotic or had undergone karyorrhexis and karyolysis. The cytoplasm and cellular borders were barely recognizable because no well-defined cross striations were seen. The cytoplasm showed intensive vacuolization. Additionally, a conglomerate pseudotumor of the adjacent bowel occurred in two (28%) cases in which saline enhancement was used, as this method induced local peritonitis. At gross inspection, several loops of the small intestine were fixed against each other and formed a conglomerate tumor. The bowel walls were hyperemic. Histopathologic assessment showed no tumor cells but thickened intestinal walls, an inflammational reaction of the mesentery with connective tissue growth.

Efficacy
No statistically significant difference in local recurrence or residual tumor was detected, as progressive tumor growth occurred in two (14%) of 14 tumors treated with internally cooled electrodes and in two (15%) of 13 tumors after saline-enhanced ablation (Fisher exact test, P = .999).

Histopathologic Assessment
The tumors were easily removed from the surrounding fat during gross sectioning, and free retroperitoneal fluid was not detected. In cases of complete tumor necrosis, histopathologic assessment showed pale eosinophilic areas with amorphous finely granular structure or areas where single cells were still visible but showed severe dystrophic changes, with partial destruction or lysis of the nucleus, severe vacuolization, and partial destruction of the cell membrane. In cases of relapse, geographic areas of vital tumor or islands of vital tumor surrounded by necrotic tissue were seen. Multiple patent blood vessels were detected centrally on the islands of incomplete tumor destruction.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
Multiple approaches have been tried to improve the efficacy and use of thermal ablation techniques. For RF ablation, two common methods are internally cooled electrodes (28) and a continuous saline infusion (29–31) into the tissues. Although both methods serve to increase the RF energy deposited in the tissues, they do so by means of different mechanisms. Internally cooled electrodes contain two internal cannulae that enable the coolant to reduce heat in tissues closest to the electrode in a manner similar to that of the perfusion-mediated tissue cooling that is observed near large vessels (12). For this method, the coolant does not leave the electrode and enter the tissues. The injection of saline into the tissues during RF ablation has been shown to increase tissue conductivity, which permits increased energy deposition without excessive heating (30). Additionally, the ongoing diffusion of the heated saline is believed to distribute the thermal energy farther from the electrode and deeper into the tissues (23,32).

In this study, we attempted to determine whether these methods of improved RF deposition are different in terms of efficacy or safety for the treatment of breast tumors. Electric impedances of fatty and glandular tissue are different from those of the liver, the tissue most commonly studied thus far (20). We have previously demonstrated that these differences lead to inhomogeneous temperature profiles owing to the liquefaction of fatty breast tissues (20). Thus, the relative equivalency of these techniques for the liver cannot be assumed to be a priori for breast tumors. Our results demonstrate equal efficacy for both of these methods, as we were able to completely ablate approximately 85% of lesions that measured 1.5 cm in diameter in the VX2 model.

Although this rate of success may be acceptable for the treatment of liver lesions, these results raise several concerns for the treatment of breast lesions with RF. Most important, considering the aim of curative tumor therapy, the rate (15%) of local untreated tumor is disappointing. Additionally, despite the fact that the sizes of tumors used in this study were small and had optimal central placement of the ablation needle, in many cases progressive tumor growth manifested as islands or nests of relapsing tumor surrounded by devitalized tumor tissue. This suggests an irregular temperature profile inside the lesion, which in many cases was likely due to the heat sink effects of the histopathologically identified tumor vessels (3,33). This finding, however, may prove less of an issue in the clinical setting, as the model studied, VX2 carcinoma, has a very strong malignant potential and is highly vascularized beyond that which is likely to occur for primary breast cancers (34). Thus, total tumor necrosis was probably more difficult to achieve than in breast carcinomas of a similar size. These techniques may still ultimately prove useful for lower-grade breast tumors, in which the lower vascularity may pose less of a problem (34). Histopathologic changes found in the present study were consistent with findings described by Miao et al (30) in ablated VX2 tumors in the liver after several weeks of follow-up.

The results of the treatment of VX2 tumors achieved in other experimental studies are not directly comparable with the presented data because of different strategies of the assessment of tumor necrosis. Routine histopathologic assessment immediately after treatment is less sensitive for residual tumor detection than that after a follow-up over several weeks (35). Immediately after therapy, structural changes at the cellular level are subtle and only detectable with immunohistochemical methods (35–37). Single vital cells fully capable of reproduction may be overlooked. Therefore, the risk of incomplete tumor treatment may be underestimated with immediate posttherapeutic histopathologic assessment. On the other hand, the VX2 tumor model has the potential benefit of extremely rapid growth, which enables the detection of residual viable tumor as a detectable relapse after a follow-up of 2–3 weeks. Nevertheless, one possible shortcoming of the method is that differentiation between a relapse owing to incomplete coverage of the tumor and incomplete necrosis inside an appropriately heated zone is not possible. Hence, to minimize this possibility, a tumor size of 15 mm was deliberately chosen to facilitate complete coverage of the small tumor by the zone of elevated ablative temperatures.

Most important, our results demonstrate a significantly lower complication rate with use of internally cooled electrodes compared with use of saline enhancement techniques, particularly for the ablation of tumors embedded in fatty tissues and for injuries induced in adjacent anatomic structures. We postulate that saline-enhanced ablation may lead to distortions of the lesion shape at coagulation owing to the spread of hot fluid through the duct along the path of least resistance and causing thermal damage off target, as has been demonstrated in cow udder tissue in vitro (20). The higher complication rate observed with continuous saline enhancement can be attributed to a blend of interstitially infused heated saline solution and liquefied fat, which cause direct and uncontrollable thermal damage to adjacent and distant structures. Alternatively, the conductive saline may establish preferential electric pathways through the high-impedance fat between the targeted tumor and other anatomic structures of lower impedance, such as the kidney or the spine muscle (20). The resulting preferred current flow through fluid of low resistance leads to the heating of relatively distant anatomic structures.

In light of the equal efficacy, the detrimental aspects of the interstitial deposition of free-flowing liquid compared with internally cooled electrodes clearly outweigh any potential benefits. Consequently, these results strongly suggest that an ablation method that does not rely on free-flowing infusion should be used for tumors that are embedded in fat.

In several studies (5,12,27,38), it has been reported that thermal lesions induced by RF ablation in parenchymal organs such as liver, prostate, or kidney appear as well-defined conic hypoechoic areas around the needle tip, with shadow artifacts behind the lesion. This characteristic feature was also observed during ablation of cow udder tissue (20). However, irregular and ill-defined growth of the ablated focus has been demonstrated in vitro by using human breast specimens that contained a high percentage of adipose tissue (20). The results of the present study confirm that US will likely be an inadequate modality for monitoring lesion growth during RF ablation in the presence of fatty tissue alone or fatty tissue surrounding the ablated tumor. Thus, alternative imaging strategies may need to be considered for this procedure.

Contrast-enhanced magnetic resonance (MR) imaging of the breast appears to be a potential method of choice to define the exact extent of the tumor in a noninvasive fashion. However, typical MR enhancement features of ductal carcinoma in situ (DCIS) are not clear, because enhancement varies from a rapid rate to no enhancement at all. Soderstrom et al (39) have suggested that all DCIS can be detected by using three-dimensional rotating delivery of excitation off resonance, or RODEO, MR imaging. They were even able to differentiate between invasive carcinoma with extensive DCIS (64%) and DCIS with microinvasion (82%). Furthermore, the spatial extent of the tumor was determined accurately in 95% of cases. However, the study group was small. Other authors (40) report contrast enhancement in 96% of DCIS, but only in 50% of DCIS with an enhancement pattern typical for carcinoma. Significant differences in contrast enhancement could not be demonstrated between high-grade DCIS and non–high-grade DCIS or between comedo type DCIS and noncomedo type DCIS.

Further improvements in the depiction of tumor margins and DCIS in breast MR imaging, as well as in temperature mapping techniques (41,42), may make it possible to treat the tumors reliably. Nevertheless, a better understanding of the types of tumors, as characterized with specific MR imaging morphology and enhancement, that might be treated locally versus the types that should remain in the domain of surgery is crucial for clinical implementation of local tumor treatment of breast cancer. The potential for losing vital direct information about histopathologic tumor margins, as is currently clinically required, may be solved by using local minimally invasive excision of the tumors prior to ablation (43). Strategies for neoadjuvant and adjuvant therapy of these types of breast cancer have to be redefined as well. Therefore, implementation of these methods will probably not only depend on technical feasibility and long-term results but also on appropriate interdisciplinary coordination.

The rapid pace of the technologic development of thermal ablation therapies and the rapid increase in our understanding of the underlying mechanisms suggest that additional improvements to RF techniques that will enable better and more reliable tumor destruction are possible. Given the issue of fat liquefaction at higher ablative temperatures, a feedback control of the applied RF power that is based on direct temperature measurements in the center of the lesion could be implemented to allow temperature adjustments below the melting point of fat. This may be ultimately achieved by using additional temperature sensors or thermally sensitive MR imaging techniques. Such a feedback regulation of the applied RF power would be crucial to prevent large-scale fatty tissue necrosis and charring. Under these conditions, RF ablation should provide a reduced and equivalent level of collateral tissue damage, compared with focused ultrasound (44), but at much lower costs of implementation and at reduced time needed for treatment.

Practical application: Findings in the current study demonstrate that RF ablation of tumors embedded in fat can be performed with a significantly lower complication rate by using internally cooled electrodes, compared with ablation with interstitial saline infusion. This is owing to the better control of tissue heating that is limited to the local tumor target. Further reduction of complications and better lesion targeting may be possible with the newer generation of RF and imaging technologies, which may ultimately allow the definition of a target temperature and maintenance of that constant temperature during ablation. When such RF equipment and further achievements in margin definition with breast MR imaging ablation become readily available, minimally invasive imaging-guided thermal ablation may become a suitable alternative to surgery for breast tumors.


   ACKNOWLEDGMENTS
 
The authors thank Burkhardt Seifert, PhD, University of Zurich, Switzerland, for his contribution to the statistical assessment, Rosemarie Kühne-Heid, MD, Institute of Pathology, Friedrich-Schiller-Universität, Germany, for her help in the interpretation of histopathologic findings due to collateral damage of adjacent organs, and Wolfgang Müller of Berchtold GmbH, Tuttlingen, Germany, for his technical and intellectual support.


   FOOTNOTES
 
Abbreviations: DCIS = ductal carcinoma in situ, RF = radio frequency

Author contributions: Guarantor of integrity of entire study, T.B.; study concepts, T.B.; study design, T.B., J.R.R., A.M., M.F., W.A.K., I.H., P.H., M.R.; literature research, T.B., J.R.R., P.H.; experimental studies, T.B., A.M., M.F., P.H., M.R.; data acquisition, T.B., A.M.; data analysis/interpretation, T.B., J.R.R., S.N.G., A.M., I.H.; statistical analysis, T.B.; manuscript preparation and definition of intellectual content, T.B., S.N.G.; manuscript editing, T.B., S.N.G., A.M.; manuscript revision/review, J.R.R., S.N.G., A.M., M.F., W.A.K., I.H.; manuscript final version approval, all authors.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 

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