(Radiographics. 2001;21:S17-S35.)
© RSNA, 2001
Helping the Hepatic Surgeon |
Essential Techniques for Successful Radio-frequency Thermal Ablation of Malignant Hepatic Tumors1
Hyunchul Rhim, MD,
S. Nahum Goldberg, MD,
Gerald D. Dodd, III, MD,
Luigi Solbiati, MD,
Hyo Keun Lim, MD,
Massimo Tonolini, MD and
On Koo Cho, MD
1 From the Department of Diagnostic Radiology, Hanyang University Hospital, 17 Haengdang-Dong, Sungdong-Ku, 133-792 Seoul, Korea (H.R., O.K.C.); Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (S.N.G.); Department of Radiology, University of Texas Health Science Center, San Antonio (G.D.D.); Department of Radiology, Ospedale Generale, Busto Arsizio, Italy (L.S., M.T.); and Department of Radiology, Samsung Medical Center, Seoul, Korea (H.K.L.). Presented as an education exhibit at the 2000 RSNA scientific assembly. Received February 9, 2001; revision requested April 20 and received May 30; accepted June 7. Address correspondence to H.R. (e-mail: rhimhc@hanyang.ac.kr).
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Abstract
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Radio-frequency thermal ablation is one of the most promising minimally invasive techniques for the treatment of nonresectable hepatic tumors. Essential technical tips to successful radio-frequency ablation therapy were collected from five international experts. They were organized into five categories: understanding the mechanisms and principles of radio-frequency ablation, modulation of tissue physiologic characteristics to increase tumor destruction, strategies of overlapping ablations, strategies to improve ablation according to tumor location, and imaging strategies after ablation to ensure adequate therapy. Established factors for optimal ablation, as well as emerging technical tips, are addressed with illustrations in each section. These essential tips will be very helpful for physicians performing radio-frequency ablation of hepatic tumors.
Index Terms: Interventional prodecures, technology • Liver, interventional procedure, 761.1269 • Liver neoplasms, therapy, 761.1269 • Radiofrequency (RF) ablation
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LEARNING OBJECTIVES
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After reading this article and taking the test, the reader will be able to:
- Describe the basic mechanism of radio-frequency ablation.
- List the essential technical strategies for achieving good results from radio-frequency ablation of hepatic tumors.
- Discuss the emerging technical tips for successful radio-frequency ablation of hepatic tumors.
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Introduction
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The majority of patients with hepatic malignancy have disease that is not amenable to surgical resection (1–4). Nonsurgical, image-guided techniques for the ablation of liver tumors have generated much interest recently because they can be minimally invasive, are often performed on an outpatient basis, and may potentially be less expensive than traditional open surgery and liver resection (5). Radio-frequency ablation is one of the most promising thermal ablation techniques for the treatment of nonresectable hepatic tumors. Recent studies have reported favorable survival rates and excellent rates of local control after such ablation, especially in patients with hepatocellular carcinoma (6–9). Although much about the optimal use of radio-frequency technology remains to be determined, the importance of a fundamental understanding of the basic mechanisms, practical strategies, and technologic limitations of current radio-frequency ablation cannot be overstressed; this thorough understanding is essential to achieve successful ablation in clinical practice. Sound knowledge of these techniques will enable the clinician to minimize or avoid common errors encountered during ablation and will contribute to better long-term results and improved clinical outcomes.
Here we present essential tips for success in radio-frequency thermal ablation collected from five international experts. The tips include understanding of the radio-frequency mechanism, modulation of tissue physiologic characteristics, strategies of overlapping ablations, strategies adapted to tumor location, and imaging strategies after ablation. The established crucial factors, as well as emerging technical tips for good results of radio-frequency ablation, are addressed.
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Understanding the Radio-Frequency Mechanism: Perspectives from Hyunchul Rhim, MD, and S. Nahum Goldberg, MD
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Understanding the mechanism of radio-frequency ablation is essential to ensure reliable results of the procedure. The main tumoricidal effect of this method occurs because the deposition of electromagnetic energy induces thermal injury to the tissue. Basically, the term radio-frequency refers not to the emitted wave but rather to the alternating electric current that oscillates in the range of high frequency (200–1,200 kHz). Schematically, a closed-loop circuit is created by placing a generator, a large dispersive electrode (ground pad), a patient, and a needle electrode in series. Both the dispersive electrode and needle electrode are active, while the patient acts as a resister. Thus, an alternating electric field is created within the tissue of the patient. Given the relatively high electrical resistance of tissue in comparison with the metal electrodes, there is marked agitation of the ions present in the tumor or liver tissue that immediately surrounds the electrode. This ionic agitation creates friction within the body and thus heat, which can be tightly controlled through modulation of the amount of radio-frequency energy deposited (Fig 1). The marked discrepancy between the surface area of the needle electrode and the dispersive electrode causes the generated heat to be tightly focused and concentrated around the needle electrode (10,11). The use of multiple large grounding pads oriented to ensure maximal surface area facing the electrode maximizes dispersion of equal amounts of energy and heat at the grounding pad sites and thereby minimizes the risk of grounding pad burns (12).
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Figure 1. Schematic shows ionic agitation by alternating electric currents. The tissue ions are agitated as they attempt to follow the changes in direction of alternating electric current. The agitation results in frictional heat around the electrode.
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The nature of the thermal damage caused by radio-frequency heating is dependent on both the tissue temperature achieved and the duration of heating. Tissue cells become more susceptible to chemotherapy or radiation when their temperature is increased to 42°C (ie, hyperthermia), and heating tissues at 45°C for several hours produces irreversible cellular damage. Heating of tissue at 50°–55°C markedly shortens the duration necessary to irreversibly damage cells to 4–6 minutes. Near immediate coagulation of tissue is induced at temperatures between 60°C and 100°C and is manifest as irreversible damage to mitochondrial and cytosolic enzymes of the cells. At more than 100°–110°C, tissue vaporizes and carbonizes.
For adequate destruction of tumor tissue, the entire volume of a lesion must be subjected to cytotoxic temperatures. Hence, effective heating throughout the target volume (ie, the tumor and 5- to 10-mm thickness of normal liver tissue) is required. Thus, an essential objective of ablative therapy is achievement and maintenance of a 50°–100°C temperature throughout the entire target volume for at least 4–6 minutes (Fig 2) (12). However, the relatively slow thermal conduction from the electrode surface through the tissues increases the duration of application to 10–30 minutes. Recommendations of heating for these extended durations are based on experimental and clinical data suggesting that thermal equilibrium and, hence, complete induction of coagulation are not achieved for a given radio-frequency application until these thresholds are achieved.
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Figure 2. Graph shows tissue reaction to thermal injury. For successful ablation, the tissue temperature should be maintained in the ideal range to ablate tumor tissue adequately and avoid carbonization around the tip of the electrode due to excessive heating.
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Heat efficacy is defined as the difference between the amount of heat produced and the amount of heat lost. Therefore, effective ablation can be achieved by optimizing heat production and minimizing heat loss within the area to be ablated (12–14). The relationship between these factors has been well characterized as the "bio-heat equation" (13). Heat production is correlated with the intensity and duration of the radio-frequency energy deposited. Heat conduction or diffusion is usually explained as a factor of heat loss in regard to the electrode tip. Heat is lost mainly through convection by means of blood circulation. Therefore, the cooling of tissue by perfusion can limit the reproducible size of the ablation lesion in vivo (Fig 3) (12–14).
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Figure 3. Schematic illustrates heat efficacy. For adequate ablation, an effective heating target volume (ie, the tumor within a safety margin of normal liver parenchyma) is necessary. Heat production can be increased by increasing the amount of electric current (unidirectional arrows). The amount of conducted heat is decreased by the distance of the tissue from the tip of the electrode (bidirectional arrow), microbubbles (stars), and charring (dots) around the tip of the electrode. Convection by the adjacent vessel is a major factor of heat loss, which results in insufficient heating for ablation.
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The thermal profile of tissue heating surrounding a conventional radio-frequency electrode is unfavorable for the goal of large-volume tumor destruction. Tissues cannot be heated to greater than 100°–110°C without vaporizing, and this process produces significant gas that both serves as an insulator and retards the ability to effectively establish a radio-frequency field. This process coupled with the rapid decrease in heating at a distance from the electrode essentially limits the extent of induced coagulation to no greater than 1.6 cm in diameter. This small zone of coagulation is clearly too small to easily coagulate the typical tumors with diameters of 2.5–5.0 cm that are encountered in clinical practice.
Many investigators have explored and several corporations have manufactured new radio-frequency ablation devices based on technologic advances that increase heating efficacy (Fig 4). To accomplish this increase, the radio-frequency output of all commercially available generators has been increased to more than 150 watts, which may potentially increase the intensity of the radio-frequency current deposited at the tissue. Expandable, multitined electrodes permit the deposition of this energy over a larger volume (15,16). In addition, this design decreases the distance between the tissue and the electrode, thereby ensuring more uniform heating that relies less on heat conduction over a large distance. Alternate strategies to increase the energy deposited from a single radio-frequency electrode have also been developed. The internally cooled electrode design minimizes carbonization and gas formation around the needle tip by eliminating excess heat near the electrode. The removal of this heat by a "heat-sink" effect of flowing fluid in the electrode permits increased energy deposition and deeper tissue heating (17). Pulsing of radio-frequency energy (ie, alternation of very high radio-frequency current for several seconds followed by minimal radio-frequency deposition for a defined period) has also been described as a method that allows overall increased current deposition. Preferential cooling of the tissues near the electrode allows heating of tissues farther from the electrode when high radio-frequency current is being applied (18). A combined approach that involves use of a multiprobe cluster of internally cooled electrodes with pulsing has also been described with the claim of even greater coagulation than that achieved by any of the individual methods alone (18). Viewed in total, these technologic developments can be used to create an ablation lesion with a maximum diameter of 5.0 cm (6).
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Figure 4a. Current radio-frequency devices based on improvement in heat efficacy: (a) electrode with 10 expandable prongs (Radiotherapeutics, Mountain View, Calif), (b) electrode with nine expandable prongs (Rita Medical Systems, Mountain View, Calif), (c) generator with internal cooling system (Radionics, Burlington, Mass), and (d) multiprobe cluster of internally cooled electrodes (Radionics).
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Figure 4b. Current radio-frequency devices based on improvement in heat efficacy: (a) electrode with 10 expandable prongs (Radiotherapeutics, Mountain View, Calif), (b) electrode with nine expandable prongs (Rita Medical Systems, Mountain View, Calif), (c) generator with internal cooling system (Radionics, Burlington, Mass), and (d) multiprobe cluster of internally cooled electrodes (Radionics).
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Figure 4c. Current radio-frequency devices based on improvement in heat efficacy: (a) electrode with 10 expandable prongs (Radiotherapeutics, Mountain View, Calif), (b) electrode with nine expandable prongs (Rita Medical Systems, Mountain View, Calif), (c) generator with internal cooling system (Radionics, Burlington, Mass), and (d) multiprobe cluster of internally cooled electrodes (Radionics).
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Figure 4d. Current radio-frequency devices based on improvement in heat efficacy: (a) electrode with 10 expandable prongs (Radiotherapeutics, Mountain View, Calif), (b) electrode with nine expandable prongs (Rita Medical Systems, Mountain View, Calif), (c) generator with internal cooling system (Radionics, Burlington, Mass), and (d) multiprobe cluster of internally cooled electrodes (Radionics).
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In addition to the previously described devices, several other designs for radio-frequency electrodes—bipolar systems among them—are currently being developed (19). With these designs, the radio-frequency current flows from one electrode placed within the tumor to a second electrode placed less than 3.5 cm from the initial electrode. Although further work is required prior to the general availability of this type of device, contiguous coagulation of 3.5 cm in diameter has been reported.
The commercially available devices were also strategically developed to monitor the ablation process so that high-temperature coagulation may occur without exceeding a 110°C maximum temperature threshold. One device (Rita Medical Systems) relies on direct temperature measurement throughout the tissue to prevent any electrode in a multitined configuration from exceeding 110°C. The two other commercially available devices (Radionics and Radiotherapeutics) rely on an electrical measurement of tissue impedance to determine that tissue boiling is taking place. In the early phase of gas formation, although the tissue impedance increases slightly, radio-frequency current can still be deposited. These impedance rises can be detected by the generator, which can then reduce the current output to a preset level.
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Modulation of Tissue Physiologic Characteristics: Perspective from S. Nahum Goldberg, MD
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Despite technologic advances and electrode modifications that have effectively increased radio-frequency energy deposition and tissue heating, local tumor recurrence (ie, inadequate treatment) has been presented as a clinical problem for lesions greater than 2.5–3.5 cm in diameter (13). Key culprits implicated in reduced coagulation include (a) heterogeneity of tissue composition, by which differences in tumor tissue density, including fibrosis and calcification, alter electrical and thermal conductance, and (b) blood flow, by which perfusion-mediated tissue cooling (vascular flow) reduces the extent of thermally induced coagulation. In addition, vaporization or carbonization around the electrode tip can also retard heat conduction within the tissue, often in an asymmetric fashion. These limitations have led investigators to the study of adjuvant therapies that modify the underlying tumor physiologic characteristics in an attempt to improve radio-frequency thermal ablation, either in conjunction with or as an alternative to multiple ablations of a given tumor. These adjuvant therapies can be classified, on the basis of the bio-heat equation, as (a) strategies that permit an increase in the overall deposition of energy through an alteration in tissue electrical conductivity, (b) strategies that improve heat retention within the tissue, and (c) strategies that decrease the tolerance of tumor tissue to heat (13).
For a given radio-frequency current, power deposition is strongly dependent on local electrical conductivity. Intratumoral injection of saline solution (or iron compounds) prior to or during the application of radio-frequency current alters tissue conductivity and thereby allows greater deposition of radio-frequency current and increased tissue heating and coagulation (18,20). In one study, radio-frequency–induced coagulation diameter was increased in swine livers in vivo from 3.7 to 7.1 cm with the use of single internally cooled electrodes (Figs 5, 6). The magnitude of this increase in coagulation, if reproducible in tumors, would be of significant benefit for clinical applications of radio-frequency ablation. However, because both volume and concentration of saline solution influence tissue heating and the coagulation diameter in a nonlinear fashion (Fig 5) (20), optimal parameters for injection of saline solution must be determined for each type of radio-frequency apparatus used and for the different types of tumor and tissue to be treated.
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Figure 5. Graph shows tissue heating with radio-frequency current in porcine livers in vivo after pretreatment with saline solution. Each data point on the graph represents the average temperature 20 mm from a single internally cooled electrode after 12 minutes of maximal radio-frequency application. Graphic representation of the ellipsoid contour plot for tissue heating generated with Simplex optimization is also provided. This study confirms that both the concentration and volume of saline solution influence overall heating in a nonlinear fashion.
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Figure 6. Large-volume tissue coagulation with saline solution pretreatment. Photograph shows that a 6.5-cm diameter of coagulation was obtained through the application of radio-frequency current for 12 minutes after pretreatment with 12 mL of a 38.5% NaCl solution. Coagulation involves the entire thickness of the gallbladder wall (arrowheads), an injury that can lead to perforation or cholecystitis.
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Perfusion-mediated tissue cooling reduces the extent of coagulation produced by thermal ablation (12,21,22). Modeling of the bio-heat equation shows that for a given tissue and power deposition, the effects of tissue blood flow predominate. Radio-frequency–induced coagulation is also more limited and variable in vivo, particularly in clinical practice, than ex vivo. Coagulation in vivo is often shaped by vasculature in the vicinity of the ablation. Specifically, Hansen et al (24) have shown that vessels greater than 3 mm in diameter prevent complete ablation of liver tissue. Furthermore, experiments in which hepatic perfusion is altered by mechanical or pharmacologic means during radio-frequency ablation of normal liver tissue and tumors show that blood flow is largely responsible for this reduction in observed coagulation (Figs 7, 8) (22,23).
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Figure 7. CT scan demonstrates the effect of portal inflow occlusion on radio-frequency-induced coagulation. Two 2.5-cm-diameter colorectal tumors were treated with identical radio-frequency parameters: one with (arrow) and one without portal inflow occlusion. Markedly greater coagulation (5-cm diameter vs 2.5-cm diameter) is seen with portal inflow occlusion. (Reprinted, with permission, from reference 22.)
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Figure 8. Graph shows correlation of blood flow during radio-frequency ablation with coagulation diameter. A linear regression model plots the effect of blood flow on coagulation diameter after a 10-minute application of radio-frequency current with internally cooled electrodes. The percentage of normal hepatic blood flow was measured by means of laser-Doppler US. The negative effect of blood flow on coagulation diameter is shown.
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Several strategies for reducing blood flow during ablation therapy have been proposed (12). Total portal inflow occlusion (Pringle maneuver) has been used at open laparotomy and at laparoscopy (Fig 7). Angiographic balloon occlusion can be used but may not prove adequate for intrahepatic ablation given the dual hepatic blood supply (25). Embolization prior to ablation with particulates that occlude sinusoids such as absorbable gelatin sponge or iodized oil may overcome this limitation. Pharmacologic modulation of blood flow and antiangiogenesis therapy are theoretically possible but should currently be considered experimental (23).
The ultimate goal of tumor therapy is complete eradication of all malignant cells. Given the high likelihood of incomplete treatment with heat-based modalities alone, the case for combining thermal ablation with other therapies such as chemotherapy or chemoembolization cannot be overstated. In a preliminary study, Goldberg et al (26) treated subcutaneous R3230 rat mammary adenocarcinoma nodules with radio-frequency ablation or intratumoral injection of doxorubicin chemotherapy, or both. Greater area of coagulation was observed with the combination of doxorubicin and radio-frequency therapy than with radio-frequency therapy or doxorubicin therapy alone (Fig 9). In subsequent experiments, the extent of coagulation was dependent on both the amount (0.02–2.5 mg) and the timing (2 days before to 2 days after radio-frequency therapy) of the administration of doxorubicin, with the greatest coagulation observed when doxorubicin was administered within 30 minutes of radio-frequency ablation. The findings of these experiments suggest that adjuvant chemotherapy may increase the ablation volume compared with radio-frequency ablation therapy alone. Indeed, synergy between chemotherapeutic agents and lower, hyperthermic temperatures (42°–45°C) has already been established. Further research to determine optimal methods of combining doxorubicin and other chemotherapeutic regimens (both agent and route of administration) with radio-frequency ablation is ongoing (Fig 10a).
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Figure 9. Tumor ablation by means of percutaneous instillation of intratumoral doxorubicin and radio-frequency current. Photograph shows four R3230 rat mammary adenocarcinoma tumor nodules. Specimens (from left to right) had no therapy (A) or were treated with percutaneous doxorubicin instillation alone (250 mL; 0.5 mg total) (B), radio-frequency current alone (C), or a combination of doxorubicin followed by radio-frequency current (D). Tumor tissue is stained with TTC (2,3,5-triphenyl tetrazolium chloride), a marker for mitochondrial enzymatic activity. Darker (red) peripheral regions represent residual viable tumor tissue, whereas white regions have undergone coagulation necrosis. The coagulation diameter was 6.7 mm for tumors treated with radio-frequency current alone, while intratumoral doxorubicin alone produced 2- to 3-mm-diameter patchy coagulation. Significantly increased coagulation was observed with a combination of doxorubicin and radio-frequency therapy (11.4 mm in diameter; P < .001).
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Figure 10a. Effect of doxorubicin chemotherapy on radio-frequency tumor ablation. (a) On a CT image obtained immediately after radio-frequency ablation, a 1.8-cm-diameter colorectal metastasis appears with low attenuation. Intravenous liposomal doxorubicin was administered 24 hours prior to the ablation. (b) Follow-up CT scan obtained 3 weeks later (without additional therapy) shows an enlarged region of coagulation. Over this period, coagulation volume does not usually change in size after radio-frequency ablation alone.
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Figure 10b. Effect of doxorubicin chemotherapy on radio-frequency tumor ablation. (a) On a CT image obtained immediately after radio-frequency ablation, a 1.8-cm-diameter colorectal metastasis appears with low attenuation. Intravenous liposomal doxorubicin was administered 24 hours prior to the ablation. (b) Follow-up CT scan obtained 3 weeks later (without additional therapy) shows an enlarged region of coagulation. Over this period, coagulation volume does not usually change in size after radio-frequency ablation alone.
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Complete ablation of an entire neoplasm with radio-frequency ablation requires the induction of large volumes of coagulation necrosis. Modification of radio-frequency energy delivery or modulation of tumor or organ biologic characteristics can markedly increase the volume of induced tumor destruction. Hence, the optimization of synergistic, adjuvant strategies may ultimately allow for improved treatment of clinically relevant tumors. However, further study is necessary to determine under which conditions particular methods will prove superior to others and whether any of these methods can improve patient outcomes.
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Strategies of Overlapping Ablation: Perspective from Gerald D. Dodd III, MD
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One of the biggest foibles in radio-frequency treatment today is targeting of the lesion. Inaccurate targeting is probably the major reason that tumors are undertreated, as opposed to inadequate energy deposition or thermal convection. Targeting can be performed with ultrasonography (US), CT, or MR imaging, and ablation may be delivered by means of open surgery, percutaneous access, or laparoscopy (27). The guidance system is chosen largely on the basis of operator preference and local experience. Although acoustic shadowing due to nitrogen bubbles and obscuration of the US image by the radio-frequency current are major disadvantages, US is still accepted as a preferable modality for guidance or monitoring during radio-frequency ablation over CT or MR imaging (6,27).
Another important factor that affects the success of radio-frequency thermal ablation is the ability to ablate all viable tumor tissue and an adequate tumor-free margin. A review of the surgical literature on the resection of malignant hepatic tumors reveals that the rate of local tumor recurrence after resection is 10%–20%. This range of rates is far less than the rate of local tumor recurrence reported in some studies of radio-frequency liver tumor ablation. The most important difference between surgical resection and radio-frequency ablation of hepatic tumors is the surgeon’s insistence on a 1-cm-wide tumor-free zone along the resection margin, which for all but the smallest of lesions can be difficult to achieve with a single radio-frequency application. However, failure to adhere to the surgical principle of obtaining at least a 1-cm-wide tumor-free margin will result in an unacceptably high rate of local tumor recurrence (28).
To achieve rates of local tumor recurrence with radio-frequency ablation that are comparable to those obtained with hepatic resection, physicians must produce a 360°, 1-cm-thick tumor-free margin around each tumor. This cuff is necessary to assure that all microscopic invasions around the periphery of a tumor have been eradicated. Thus, the target diameter of an ablation (D*) must be 2 cm larger than the diameter of the tumor (D) that undergoes treatment (Figs 11–13) (5,29,30). Three different ablation strategies will yield predictable ablation volumes (Figs 14–17).
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Figure 11. Schematic model of target ablation volume. A 360°, 1-cm-thick tumor-free margin around each tumor must be achieved for successful ablation. Thus, the diameter of the target ablation volume (D*) should be 2 cm greater than that of the tumor (D).
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Figure 12a. Adequate ablation of 5-cm-diameter liver metastases from gallbladder cancer. (a) Preablation CT scan shows a single metastatic mass in the right lobe of the liver. (b) Postablation CT scan shows thermal injury that encompasses the tumor (dotted line) and a 1- to 2-cm tumor-free margin on all sides except adjacent to the liver capsule. The asterisk indicates the superior margin of a separate tumor ablation.
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Figure 12b. Adequate ablation of 5-cm-diameter liver metastases from gallbladder cancer. (a) Preablation CT scan shows a single metastatic mass in the right lobe of the liver. (b) Postablation CT scan shows thermal injury that encompasses the tumor (dotted line) and a 1- to 2-cm tumor-free margin on all sides except adjacent to the liver capsule. The asterisk indicates the superior margin of a separate tumor ablation.
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Figure 13a. Inadequate ablation of hepatocellular carcinoma treated with a single 3-cm-diameter ablation. (a) Preablation CT scan shows a low-attenuation tumor in the higher-attenuation liver tissue. (b) Postablation CT scan shows ablation equal to the size of the tumor with no residual tumor tissue. (c) Photograph of the resected liver specimen, however, shows residual tumor tissue (arrows).
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Figure 13b. Inadequate ablation of hepatocellular carcinoma treated with a single 3-cm-diameter ablation. (a) Preablation CT scan shows a low-attenuation tumor in the higher-attenuation liver tissue. (b) Postablation CT scan shows ablation equal to the size of the tumor with no residual tumor tissue. (c) Photograph of the resected liver specimen, however, shows residual tumor tissue (arrows).
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Figure 13c. Inadequate ablation of hepatocellular carcinoma treated with a single 3-cm-diameter ablation. (a) Preablation CT scan shows a low-attenuation tumor in the higher-attenuation liver tissue. (b) Postablation CT scan shows ablation equal to the size of the tumor with no residual tumor tissue. (c) Photograph of the resected liver specimen, however, shows residual tumor tissue (arrows).
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Figure 14. Artist’s rendition of a single ablation scheme. Given the current radio-frequency devices and the need for a 1-cm-thick tumor-free margin, tumors that require only a single ablation procedure are limited. For example, a 3-cm ablation device can be used to treat a 1-cm-diameter tumor. (Reprinted, with permission, from reference 5.)
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Figure 15a. Artist’s rendition of a six-ablation scheme. (a) Six perfectly placed ablations (four along the x-y plane, two along the z plane) will yield a composite thermal sphere. (b) When 2 cm are subtracted for the 360° 1-cm-thick tumor-free margin (green circle), the size of the treated tumor nucleus (center) is limited.
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Figure 15b. Artist’s rendition of a six-ablation scheme. (a) Six perfectly placed ablations (four along the x-y plane, two along the z plane) will yield a composite thermal sphere. (b) When 2 cm are subtracted for the 360° 1-cm-thick tumor-free margin (green circle), the size of the treated tumor nucleus (center) is limited.
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Figure 16a. Artist’s rendition of a 14-ablation scheme. To ablate the untreated portions of a tumor (a, green) projected between adjacent spheres in the six-sphere model, eight additional spheres (b, blue) should be added (a total of 14 ablations). This model yields a composite spherical ablation diameter (c, green) only 1.7 times the diameter of a single ablation sphere. Incorporation of a 1-cm-thick tumor-free margin (c, green) into the model would limit the maximal diameter of a treatable tumor to 3 cm.
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Figure 16b. Artist’s rendition of a 14-ablation scheme. To ablate the untreated portions of a tumor (a, green) projected between adjacent spheres in the six-sphere model, eight additional spheres (b, blue) should be added (a total of 14 ablations). This model yields a composite spherical ablation diameter (c, green) only 1.7 times the diameter of a single ablation sphere. Incorporation of a 1-cm-thick tumor-free margin (c, green) into the model would limit the maximal diameter of a treatable tumor to 3 cm.
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Figure 16c. Artist’s rendition of a 14-ablation scheme. To ablate the untreated portions of a tumor (a, green) projected between adjacent spheres in the six-sphere model, eight additional spheres (b, blue) should be added (a total of 14 ablations). This model yields a composite spherical ablation diameter (c, green) only 1.7 times the diameter of a single ablation sphere. Incorporation of a 1-cm-thick tumor-free margin (c, green) into the model would limit the maximal diameter of a treatable tumor to 3 cm.
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Figure 17a. Artist’s rendition of a cylindrical ablation scheme. A feasible alternative strategy to the impractical 14 overlapping ablation procedures is the creation of thermal cylinders. Conceptually, spheres are overlapped to create a cylinder (a), and cylinders are overlapped (b) to systematically ablate a tumor. (Fig 17a reprinted, with permission, from reference 5.)
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Figure 17b. Artist’s rendition of a cylindrical ablation scheme. A feasible alternative strategy to the impractical 14 overlapping ablation procedures is the creation of thermal cylinders. Conceptually, spheres are overlapped to create a cylinder (a), and cylinders are overlapped (b) to systematically ablate a tumor. (Fig 17a reprinted, with permission, from reference 5.)
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Single-Ablation Scheme
Eradication of a tumor can be achieved with a single ablation if the diameter of the tumor is 2 cm less than the diameter of tissue ablated (Fig 14). For example, a 3-cm ablation device can be used to treat a 1-cm-diameter tumor. Although there have been reports of lesions as large as 5–7 cm in diameter coagulated with a single ablation, none of the existing radio-frequency devices routinely produces a thermal injury that exceeds 3–3.5 cm in diameter (30).
Six-Ablation Scheme
Six perfectly placed 3-cm-diameter ablations will yield a 3.75-cm-diameter composite thermal sphere (Fig 15). Subtracting 2 cm for the 360° 1-cm-thick tumor-free margin leaves a 1.75-cm tumor nucleus. Given the inherent error in needle placement, any attempt to use this model to treat larger tumors will result in greater local tumor recurrence owing to missed tumor tissue (30).
Fourteen-Ablation Scheme
If the six-sphere model is used to treat larger tumors, portions of untreated tumor tissue will project between adjacent spheres. Eight additional spheres must be added to cover the defects in the six-sphere model (a total of 14 ablations) (Fig 16). This model yields a composite spherical ablation diameter that is only 1.7 times the diameter of a single ablation sphere. Thus, an ablation sphere of 3 cm would yield a composite spherical ablation diameter of 5 cm. Incorporation of a 1-cm-thick tumor-free margin into the model would limit the maximal diameter of treatable tumor tissue to 3 cm (30).
Cylindrical Ablation Scheme
Because it is clear that the 14-ablation model is impossible to perform in a clinical situation, a feasible alternative strategy is the creation of thermal cylinders (Fig 17). In concept, spheres are overlapped to create a cylinder and cylinders are overlapped to systematically ablate a tumor. This model is geometrically more inefficient than the 14-ablation model; however, it can be performed with greater ease and success (30).
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Strategies According to Tumor Location: Perspective from Hyo Keun Lim, MD
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In addition to size, tumor location is one of the important factors that influence the likely outcome of therapy. For example, if the tumor lies in the subcapsular area, no safety margin along the capsule is possible. In addition, tumors in the central zone of the liver, near the hepatic hilum, are almost always surrounded by large vessels that, because of the heat-sink effect of flowing blood, make it difficult to ablate the periphery of the tumor and the cuff of normal hepatic tissue (13,22). In these situations, different strategies are needed to obtain successful treatment.
Subcapsular Tumors
For subcapsular tumors, a safety margin of normal hepatic tissue is difficult to obtain, but if the liver capsule that overlies the tumor appears to be involved by the tumor, the capsule should be ablated. Subcapsular tumors can be effectively treated with either an expandable needle electrode with a multiple-array or a straight cooled-tip electrode. If a tumor is small and round, an expandable needle electrode is preferred because the ablation volume induced tends to be more spherical than those induced by cooled-tip electrodes. To ablate fusiform tumors, an internally cooled needle electrode is better because it frequently makes elliptical lesions. Tumors between the anterior and posterior liver capsules (eg, in the inferior angle of the right lobe or the lateral segment of the left lobe) are often difficult to ablate completely, especially when they abut both capsules. In this particular situation, the choice of needle electrode is particularly important. When an expandable electrode is used in narrow spaces, multiple overlapping ablations that involve partial deployment of hooklike electrodes will be unavoidable even if the tumors are small. The full deployment of hooks can penetrate the liver capsule and may cause bleeding or unnecessary thermal injury to adjacent organs. This particular situation will most likely be best approached with the straight cooled-tip electrode because its use involves substantially less risk of penetrating either capsule and the entire length of active electrode can be employed (Fig 18). In addition, the number of ablations and thus the procedure time are reduced. If the US-guided percutaneous approach is used, subcapsular tumors that show exophytic growth can also be difficult to ablate completely. The best way to achieve effective necrosis of an exophytic tumor is to ablate the deepest portion first, thus blocking the blood supply to the exophytic portion, which is subsequently ablated (Fig 19).
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Figure 18a. Hepatocellular carcinoma in a 57-year-old man. (a) Oblique US scan of the lateral segment of the left hepatic lobe shows a 2.5-cm-diameter low-echogenic hepatocellular carcinoma (arrows) located in the capsule of the anterior and posterior surface of the liver, especially where it tapers at the tips, and the 3-cm-long active tip (arrowheads) of the straight cooled-tip electrode within the mass. A single ablation lasted 12 minutes. (b) Portal-phase CT scan obtained 1 month after radio-frequency ablation reveals the presence of a round low-attenuating lesion (arrows) with no contrast enhancement in the ablated area. This finding indicates complete necrosis.
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Figure 18b. Hepatocellular carcinoma in a 57-year-old man. (a) Oblique US scan of the lateral segment of the left hepatic lobe shows a 2.5-cm-diameter low-echogenic hepatocellular carcinoma (arrows) located in the capsule of the anterior and posterior surface of the liver, especially where it tapers at the tips, and the 3-cm-long active tip (arrowheads) of the straight cooled-tip electrode within the mass. A single ablation lasted 12 minutes. (b) Portal-phase CT scan obtained 1 month after radio-frequency ablation reveals the presence of a round low-attenuating lesion (arrows) with no contrast enhancement in the ablated area. This finding indicates complete necrosis.
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Figure 19a. Hepatocellular carcinoma in a 63-year-old woman. (a) Hepatic arterial-phase CT scan depicts a 3-cm-diameter hepatocellular carcinoma (arrows) in the subcapsular area of the right hepatic lobe, which shows an outward bulge. With a 3-cm expandable needle electrode, two overlapping ablations were performed. The deep portion of the mass was treated before the exophytic portion. (b) Hepatic arterial-phase CT scan obtained 7 months after radio-frequency ablation shows an ablated lesion (arrows) with no contrast enhancement, which indicates complete necrosis.
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Figure 19b. Hepatocellular carcinoma in a 63-year-old woman. (a) Hepatic arterial-phase CT scan depicts a 3-cm-diameter hepatocellular carcinoma (arrows) in the subcapsular area of the right hepatic lobe, which shows an outward bulge. With a 3-cm expandable needle electrode, two overlapping ablations were performed. The deep portion of the mass was treated before the exophytic portion. (b) Hepatic arterial-phase CT scan obtained 7 months after radio-frequency ablation shows an ablated lesion (arrows) with no contrast enhancement, which indicates complete necrosis.
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Central Tumors Surrounded by Large Vessels
Another difficult situation arises when tumors are present in the central zone of the liver, near the hepatic hilum. A tumor in this location is almost always surrounded by large vessels, and the resultant tissue cooling may make it difficult to ablate the periphery of the tumor and the cuff of normal hepatic tissue. In this situation, the extent of coagulation necrosis is less than usual, and follow-up CT may reveal the presence of residual perivascular tumor tissue (Fig 20). While the concept of blood flow reduction during ablation has been discussed previously, clinical implementation of this strategy is currently not without difficulty. During radio-frequency ablation after laparotomy, reduction of vascular inflow by clamping of the hepatic artery and portal vein at the level of the porta hepatis (Pringle maneuver) is helpful in increasing the extent of coagulation necrosis. However, this clamping markedly increases the invasive nature of this minimally invasive technique. The Pringle maneuver can be applied safely to a normal liver for up to 1 hour. However, the safety of applying an extended Pringle maneuver during radio-frequency ablation has not been systematically studied or reported, and the technique should be used with caution, since the absence of blood flow through the liver could lead to significant damage to major vascular or biliary structures.
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Figure 20. Hepatocellular carcinoma in a 57-year-old woman. Hepatic arterial-phase CT scan obtained 7 months after radio-frequency ablation of a 4.5-cm-diameter hepatocellular carcinoma surrounded by large branches of the hepatic artery and portal vein shows a low-attenuation ablation lesion (arrows) near the hepatic hilum. A crescentic enhancing viable tumor (arrowheads) is seen along the branch of the right hepatic artery. It was not seen at 4-month follow-up CT.
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When radio-frequency ablation is performed percutaneously, the use of a balloon for mechanical occlusion of the portal vein has been viewed as impractical in many centers because it is invasive and time-consuming (25). Nevertheless, we are able to suggest a number of ways in which the use of current radio-frequency devices for the ablation of tumors surrounded by large vessels may be efficacious. The space between large vessels is usually small and narrow, and safe US-guided targeting may thus be difficult. It is important not to penetrate large vessels with a needle electrode, since bleeding or pseudoaneurysm may occur. When radio-frequency ablation involves the use of an expandable needle electrode and its hooks within the lumen of the vessel are ineffective, the hooks of the multiple array should not be placed beyond the vascular wall. To induce satisfactory coagulation necrosis in this situation, multiple overlapping ablations with partial deployment of the multiple array are recommended, rather than a single ablation with the needle electrode fully deployed. Even if the tumor is less than 3 cm in diameter, the recommendation applies. For ablation of a tumor surrounded by large vessels, a straight-tip internally cooled needle electrode may have advantages over the expandable needle variety. First, because only the straight part of the active electrode is involved, penetration of the vessel wall is not a matter of concern. Second, the reduced impedance of the tissues nearest the needle electrode, induced by internal cooling with chilled saline solution, allows heat to diffuse more easily. This reduced impedance, in turn, allows greater deposition of radio-frequency energy and can lead to more extensive coagulation necrosis than is possible when an expandable needle electrode is used.
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Imaging of Treatment Response: Perspectives from Luigi Solbiati, MD, and Massimo Tonolini, MD
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To achieve complete treatment of hepatic tumors, accurate imaging techniques are needed for close patient follow-up. US is valuable for providing widely available real-time guidance of the ablation procedure, but gray-scale sonographic findings may under- or overestimate size and completeness of induced necrosis, because the hyperechogenic focus that appears around the distal probe during the application of thermal energy represents formation of gas microbubbles in the heated liver tissue and not coagulated tissue per se (31–39).
For both hepatocellular carcinoma and metastatic lesions, the most universally accepted imaging finding that suggests complete treatment of a focal liver tumor is the elimination of previously seen vascular enhancement on contrast-enhanced images (13,27). Radiologic-pathologic correlation in experimental and clinical studies shows that findings of both contrast-enhanced CT and MR imaging examinations can be predictive of the extent of this nonperfusing area of coagulation to within 2-3 mm (ie, the current degree of imaging resolution) (40). Thus, CT or MR baseline imaging should be performed no more than 1–2 weeks prior to ablation to permit accurate comparison with postablation images. To optimize the chances of complete tumor destruction, CT or MR imaging, or both, should be performed within 1 week after the radio-frequency ablation session to detect possible residual viable tumor tissue that requires immediate retreatment (5–10). However, since findings of current imaging modalities underestimate the presence of small foci of residual, previously undetected neoplastic tissue, close imaging follow-up should be performed every 3–4 months. Given that local progressive tumor growth has been observed more than 18 months after ablation, we strongly recommend that this intensity of short-interval imaging be continued indefinitely.
Multiphasic helical CT plays a central role in the assessment of therapeutic response because it allows confident discrimination between ablated and residual viable tumor tissue (Fig 21) (5–7). Adequate coagulation necrosis appears as a homogeneously hypoattenuating area with well-defined borders and should have a volume equal to or, in the ideal situation, greater than that of the original nodules and be devoid of characteristic neoplastic or parenchymal enhancement. Lack of enhancement throughout the entire lesion is considered the hallmark of a complete response, while in partial necrosis, margins are ill-defined and peripheral viable tumor tissue maintains the characteristic enhancement behavior of native nodules. Hepatic arterial–phase images are most useful for evaluating hypervascular hepatomas, whereas differentiation of coagulated areas from hypoattenuating tumor tissue is usually easiest with images obtained during the portal venous and equilibrium (3-minute delayed) phases in patients who undergo treatment for hepatic metastases. At CT evaluation within the first few days of treatment, a hyperattenuating rim is often visible during the arterial phase of scanning. This finding corresponds at histopathologic evaluation to an inflammatory reaction to the thermal damage that generally regresses during the first month after treatment (10).
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Figure 21a. Hepatocellular carcinoma, 3.5 cm in diameter in segment 8, in a 64-year-old man. Contrast-enhanced helical CT and US harmonic scans obtained after injection of 2.4 mL of microbubble contrast agent (Sonovue; Bracco Diagnostics, Milan, Italy) were studied before and after single-session cool-tip radio-frequency ablation. (a, b) Pretreatment contrast-enhanced US (a) and CT (b) scans show the hypervascular tumor during the arterial phase. (c-e) Postablation US scan (c) obtained during the arterial phase and CT scans obtained during the arterial (d) and portal (e) phases show complete necrosis of the carcinoma and excellent correspondence between the two imaging modalities.
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Figure 21b. Hepatocellular carcinoma, 3.5 cm in diameter in segment 8, in a 64-year-old man. Contrast-enhanced helical CT and US harmonic scans obtained after injection of 2.4 mL of microbubble contrast agent (Sonovue; Bracco Diagnostics, Milan, Italy) were studied before and after single-session cool-tip radio-frequency ablation. (a, b) Pretreatment contrast-enhanced US (a) and CT (b) scans show the h | |
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Abstract
LEARNING OBJECTIVES
