(Radiographics. 2000;20:9-27.)
© RSNA, 2000
IMAGING & THERAPEUTIC TECHNOLOGY |
Minimally Invasive Treatment of Malignant Hepatic Tumors: At the Threshold of a Major Breakthrough1
Gerald D. Dodd, III, MD,
Michael C. Soulen, MD ,
Robert A. Kane, MD ,
Tito Livraghi, MD ,
William R. Lees, MB BS, FRCR ,
Yasuyuki Yamashita, MD ,
Alison R. Gillams, MBChB, MRCP, FRCR ,
Okkes I. Karahan, MD and
Hyunchul Rhim, MD, PhD
1 From the Departments of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78284-7800 (G.D.D., O.I.K., H.R.); University of Pennsylvania, Philadelphia (M.C.S); Beth Israel Deaconess Medical Center, Boston, Mass (R.A.K.); Ospedale Civile, Vimercate, Milan, Italy (T.L.); University College London, Middlesex Hospital, London, England (W.R.L., A.R.G.); Kumamoto University, Kumamoto, Japan (Y.Y); Erciyes University, Kayseri, Turkey (O.I.K); and Hanyang University, Seoul, South Korea (H.R). Recipient of a Summa Cum Laude award and an Excellence in Design award at the 1998 RSNA scientific assembly. Received May 17, 1999; revisions requested July 22 and received August 24; accepted August 25. Address reprint requests to G.D.D.
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Abstract
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Six existing minimally invasive techniques for the treatment of primary and secondary malignant hepatic tumors—radio-frequency ablation, microwave ablation, laser ablation, cryoablation, ethanol ablation, and chemoembolization—are reviewed and debated by noted authorities from six institutions from around the world. All of the authors currently believe that surgery remains the treatment of choice for patients with resectable hepatic tumors. However, the clinical results of each of the minimally invasive techniques presented have exceeded those obtained with conventional chemotherapy or radiation therapy. Thus, for nonsurgical patients, these techniques are becoming standard independent or adjuvant therapies. In addition, with continued improvement in technology and increasing clinical experience, one or more of these minimally invasive techniques may soon challenge surgical resection as the treatment of choice for patients with limited hepatic tumor.
Index Terms: Alcohol ablation • Cryotherapy • Interventional procedures, technology • Lasers, interstitial therapy • Liver neoplasms, chemotherapeutic infusion, 761.1266 • Liver neoplasms, therapy, 761.1266 • Radiofrequency (RF) ablation
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Introduction
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Primary and secondary malignant hepatic tumors are some of the most common tumors worldwide. Unfortunately, chemotherapy and radiation therapy are ineffective treatment methods. Surgical resection is considered the only potentially curative option; however, few patients are surgical candidates (1–3). Recent results from multiple investigations indicate that several minimally invasive treatment techniques are very effective for treating primary and secondary malignant hepatic tumors and that they may replace surgical resection in the near future (4,5).
In this article, international experts present their experience with six promising minimally invasive treatment techniques: radio-frequency ablation, microwave ablation, laser ablation, cryoablation, ethanol ablation, and chemoembolization (Fig 1). Aspects of each technique including mechanism of action, equipment, patient selection, treatment technique, and recent patient outcome are presented. The benefits and limitations of each technique are discussed.
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Radio-frequency Ablation: Perspectives from Gerald D. Dodd III, Okkes I. Karahan, and Hyunchul Rhim
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The use of radio-frequency ablation for the treatment of hepatic tumors was first suggested in separate reports by McGahan et al (6) and Rossi et al (7) in 1990. Since then, the technique has generated international interest, with multiple clinical investigations underway (8–12).
Mechanism
Alternating electric current operated in the range of radiofrequency can produce a focal thermal injury in living tissue. Shielded needle electrodes are used to concentrate the energy in selected tissue. The tip of the electrode conducts the current, which causes local ionic agitation and subsequent frictional heat (Fig 2) (13). Temperatures in excess of 50°C produce coagulative necrosis. A 2–5-cm spherical thermal injury can be produced with each ablation.
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Figure 2a. Mechanism of radio-frequency ablation. (a) Schematic depicts a four-prong needle electrode in which an alternating electric current at 460 KHz has caused ionic agitation around the electrode tip. (b) Schematic illustrates the ionic agitation, which causes frictional heat immediately around the needle. (c) Schematic shows how the heat caused by the agitation expands by conduction into the surrounding tissues to form a roughly spherical thermal injury.
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Figure 2b. Mechanism of radio-frequency ablation. (a) Schematic depicts a four-prong needle electrode in which an alternating electric current at 460 KHz has caused ionic agitation around the electrode tip. (b) Schematic illustrates the ionic agitation, which causes frictional heat immediately around the needle. (c) Schematic shows how the heat caused by the agitation expands by conduction into the surrounding tissues to form a roughly spherical thermal injury.
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Figure 2c. Mechanism of radio-frequency ablation. (a) Schematic depicts a four-prong needle electrode in which an alternating electric current at 460 KHz has caused ionic agitation around the electrode tip. (b) Schematic illustrates the ionic agitation, which causes frictional heat immediately around the needle. (c) Schematic shows how the heat caused by the agitation expands by conduction into the surrounding tissues to form a roughly spherical thermal injury.
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Equipment
Radio-frequency devices are marketed in the United States by Rita Medical Systems (Mountain View, Calif), Radiotherapeutics (Mountain View, Calif), and Radionics (Burlington, Mass). Each device consists of an electrical generator, needle electrode, and ground pad. Each manufacturer has a different needle electrode design. The device made by Rita Medical Systems has a 15-gauge needle with four to eight retractable curved prongs (Fig 3a). Radiotherapeutics uses a 14-gauge needle with 10 retractable curved prongs (Fig 3b). Radionics uses a 17-gauge internally cooled, straight needle alone or in a three-needle cluster (Fig 3c). To date, there have been no studies that document a definite advantage of one needle design over another.
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Figure 3a. Photographs show radio-frequency ablation needle electrodes in use today, including a 15-gauge needle electrode with four retractable prongs (Rita Medical Systems) (a), a 14-gauge needle electrode with 10 retractable prongs (Radiotherapeutics) (b), and a 17-gauge internally cooled-tip needle in a three-needle cluster (Radionics) (c).
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Figure 3b. Photographs show radio-frequency ablation needle electrodes in use today, including a 15-gauge needle electrode with four retractable prongs (Rita Medical Systems) (a), a 14-gauge needle electrode with 10 retractable prongs (Radiotherapeutics) (b), and a 17-gauge internally cooled-tip needle in a three-needle cluster (Radionics) (c).
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Figure 3c. Photographs show radio-frequency ablation needle electrodes in use today, including a 15-gauge needle electrode with four retractable prongs (Rita Medical Systems) (a), a 14-gauge needle electrode with 10 retractable prongs (Radiotherapeutics) (b), and a 17-gauge internally cooled-tip needle in a three-needle cluster (Radionics) (c).
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All radio-frequency generators are operated at 460 kHz at a power setting of 50–200 W. The cost of the generators ranges from $12,000 to $30,000. The needle electrodes cost $500–$1,000 per needle (nonreusable).
Patient Selection and Technique
Most investigators are limiting treatment with radio-frequency ablation to patients with four or fewer, 5-cm or smaller, primary or secondary malignant hepatic tumors and no extrahepatic tumor. Ideal tumors are smaller than 3 cm in diameter, completely surrounded by hepatic parenchyma, 1 cm or more deep to the liver capsule, and 2 cm or more away from large hepatic or portal veins. Subcapsular liver tumors can be ablated, but their treatment is usually associated with greater procedural and postprocedural pain. Tumors adjacent to large blood vessels are more difficult to ablate completely because the blood flow in the vessels cools the adjacent tumor, thus limiting the extent of the ablation. Ablation of tumors adjacent to the larger portal triads causes increased pain and poses the risk of damage to the associated bile ducts. Contraindications to treatment include sepsis, severe debilitation, or uncorrectable coagulopathies.
Any of the radio-frequency devices can be used percutaneously or intraoperatively. Percutaneous ablation can be performed on an outpatient basis with use of conscious sedation alone. Ultrasonography (US) is the primary modality for guiding the procedure, although both computed tomography (CT) and magnetic resonance (MR) imaging can be used.
The goal of radio-frequency thermal ablation is to kill the target tumor as well as a 5–10-mm circumferential cuff of adjacent normal hepatic parenchyma. Each ablation requires exact placement of the electrode tip in the tumor. A single ablation takes 8–20 minutes, raises local tissue temperatures to 100 C, and produces an approximate 2–5-cm spherical thermal injury. The size of each ablation is delineated sonographically by echogenic microbubbles that are produced during the ablation.
Ablation strategies must vary with the size of each lesion. On the basis of a 3-cm thermal injury, tumors less than 2 cm in diameter can be treated with one or two ablations, tumors 2–3 cm require at least six overlapping ablations, and tumors greater than 3 cm require at least 12 overlapping ablations (Fig 4). The length of a single procedure depends on the number of ablations performed.
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Figure 4a. Radio-frequency ablation treatment strategies. On the basis of a 3-cm-diameter spherical thermal injury created by a single ablation, the following three ablation strategies can be used to treat most tumors. (a) Schematic illustrates how tumors less than 2 cm can easily be treated with one ablation. The active elements of the ablation needle are centered across the tumor. (b) Schematic shows how tumors 2-3 cm in diameter are treated by six overlapping ablations. Four ablations are performed in the x-y plane, and two are performed along the z axis. All ablations are positioned to touch the center of the tumor. If placed correctly, the ablations create an inner spherical injury that measures 3.7 cm in diameter. (c) Schematic depicts systematically overlapped "thermal cylinders," which are a more effective way to ablate large tumors, rather than creating random overlapping ablations (such as seen in b). Each cylinder is created by overlapping individual ablations along a single needle tract from the deepest to the most superficial portions of a tumor. Each ablation and thermal cylinder is overlapped by 50%.
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Figure 4b. Radio-frequency ablation treatment strategies. On the basis of a 3-cm-diameter spherical thermal injury created by a single ablation, the following three ablation strategies can be used to treat most tumors. (a) Schematic illustrates how tumors less than 2 cm can easily be treated with one ablation. The active elements of the ablation needle are centered across the tumor. (b) Schematic shows how tumors 2-3 cm in diameter are treated by six overlapping ablations. Four ablations are performed in the x-y plane, and two are performed along the z axis. All ablations are positioned to touch the center of the tumor. If placed correctly, the ablations create an inner spherical injury that measures 3.7 cm in diameter. (c) Schematic depicts systematically overlapped "thermal cylinders," which are a more effective way to ablate large tumors, rather than creating random overlapping ablations (such as seen in b). Each cylinder is created by overlapping individual ablations along a single needle tract from the deepest to the most superficial portions of a tumor. Each ablation and thermal cylinder is overlapped by 50%.
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Figure 4c. Radio-frequency ablation treatment strategies. On the basis of a 3-cm-diameter spherical thermal injury created by a single ablation, the following three ablation strategies can be used to treat most tumors. (a) Schematic illustrates how tumors less than 2 cm can easily be treated with one ablation. The active elements of the ablation needle are centered across the tumor. (b) Schematic shows how tumors 2-3 cm in diameter are treated by six overlapping ablations. Four ablations are performed in the x-y plane, and two are performed along the z axis. All ablations are positioned to touch the center of the tumor. If placed correctly, the ablations create an inner spherical injury that measures 3.7 cm in diameter. (c) Schematic depicts systematically overlapped "thermal cylinders," which are a more effective way to ablate large tumors, rather than creating random overlapping ablations (such as seen in b). Each cylinder is created by overlapping individual ablations along a single needle tract from the deepest to the most superficial portions of a tumor. Each ablation and thermal cylinder is overlapped by 50%.
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Patient Outcome
The results of multiple clinical series, which have used different methods of radio-frequency ablation, have been reported (8–12). The results appear promising, with a 52%–67% complete ablation rate at 1 year and survival rates of 96%, 64%, and 40% at 1, 3, and 5 years, respectively.
At our own institution, we have treated 86 patients with hepatic tumors. There is sufficient follow-up (mean, 9 months) to allow a preliminary evaluation of our results in 46 patients, 25 with hepatocellular carcinoma and 21 with metastases. These 46 patients had 76 tumor nodules ranging from 0.7 to 4.9 cm in diameter (mean, 2.8 cm). A total of 462 ablations were performed in 95 sessions. Follow-up CT scans showed complete ablation in 27 of 38 (71%) hepatocellular carcinoma nodules and 17 of 38 (45%) metastases (Fig 5). The lower complete ablation rate in our patients with hepatic metastases may have been caused by a higher frequency of regional microscopic tumor invasion into the adjacent hepatic parenchyma than is seen in patients with hepatocellular carcinoma nodules. Overall, there have been few complications in our series; two patients had intrahepatic arterial hemorrhages, a small area of one patient's diaphragm was inadvertently ablated when a subdiaphragmatic tumor was treated, and two patients developed tumor seeding along the needle tract.
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Figure 5a. CT evaluation of radio-frequency thermal ablation. (a) CT scan obtained before ablation shows a hypervascular hepatocellular carcinoma (arrow). (b) CT scan obtained after ablation shows that the tumor has become avascular. Note the prominent peritumoral hyperemia around the treated tumor (arrowheads) that is caused by the ablation process.
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Figure 5b. CT evaluation of radio-frequency thermal ablation. (a) CT scan obtained before ablation shows a hypervascular hepatocellular carcinoma (arrow). (b) CT scan obtained after ablation shows that the tumor has become avascular. Note the prominent peritumoral hyperemia around the treated tumor (arrowheads) that is caused by the ablation process.
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Microwave Ablation: Perspective from Yasuyuki Yamashita
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In 1986, the Japanese team of Tabuse et al (14) developed a small-diameter coaxial microwave system that could be applied percutaneously to ablate deep liver tissue. In the early 1990s, this technique was applied to the treatment of liver tumors. Over the past 6–7 years, refinements in equipment design and increasing operator experience have produced promising clinical results (15–19).
Mechanism
In microwave coagulation therapy or ablation, molecular dipoles are vibrated and rotated, resulting in thermal coagulation of the target tissue. The basic mechanism of heat generation in living tissue consists of rotation of water molecules (Fig 6). The rotation follows the alternating electric field component of the ultra-high-speed (2,450-MHz) microwaves (15). Microwaves emitted from the distal segment of a percutaneous probe cause the thermal coagulation of the adjacent tissues.
Equipment
The equipment for microwave ablation consists of a microwave generator and reusable needle electrodes (Fig 7). A microwave generator emits a 2,450-MHz microwave, is operated at 60 W, and costs approximately $45,000. Needle electrodes are 25 cm long, 18-gauge monopolar units that are placed through 14-gauge styleted access needles (Fig 7). Each needle electrode costs $500.
Patient Selection and Technique
Potential candidates for microwave ablation include patients with inoperable tumors that cannot be chemoembolized due to severe liver dysfunction or hypovascularity and patients with tumors that failed chemoembolization or alcohol ablation. Generally, the therapy is limited to patients with four or fewer tumors that are each less than 5 cm in diameter. Tumors located at the liver surface are difficult to treat with a percutaneous approach. A single ablation produces an elliptical coagulated area with a maximal diameter slightly greater than 2 cm near the tip of the electrode (Fig 8). Thus, ideal lesions for microwave therapy should be less than 3 cm in diameter.
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Figure 8. Microwave ablation of swine liver. Photograph of the cut surface of the liver shows an elliptical ablation (yellow arrowheads) around the distal shaft (arrow) of the monopolar electrode. Note the tip of the electrode (asterisk).
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Under US guidance, a guiding needle is inserted percutaneously toward the tumor. The microwave electrode is inserted through the outer guiding needle into the tumor. On the basis of the energy limit of the needle electrode and the patient's tolerance, microwaves are produced for 60 seconds at a power setting of 60 W. During the procedure, US demonstrates a strong hyperechoic area around the tip of the needle electrode (Fig 9). Treatments are usually repeated three times a week until the entire tumor is ablated.
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Figure 9a. CT evaluation of microwave ablation performed in a 68-year-old man with hepatocellular carcinoma who had previously been treated with arterial chemoembolization with iodized oil. (a) Enhanced CT scan obtained before embolization shows a hypervascular tumor nodule (arrowheads). (b) Unenhanced CT scan obtained 7 days after embolization shows incomplete accumulation of iodized oil in the tumor (arrow). (c) Sonogram obtained before microwave ablation (left) shows a 35-mm hypoechoic nodule in the anterior segment of the right hepatic lobe (arrows). Sonogram obtained immediately after treatment (two emissions) (right) shows a markedly echogenic region of coagulation (arrow) that has replaced the tumor. (d) Enhanced CT scan obtained 4 days after microwave ablation shows ablated tissue as unenhanced areas within and around the tumor (arrows). (e) Dynamic CT scan obtained 9 months after treatment shows that the lesion (arrow) has decreased in size, without evidence of new tumor growth.
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Figure 9b. CT evaluation of microwave ablation performed in a 68-year-old man with hepatocellular carcinoma who had previously been treated with arterial chemoembolization with iodized oil. (a) Enhanced CT scan obtained before embolization shows a hypervascular tumor nodule (arrowheads). (b) Unenhanced CT scan obtained 7 days after embolization shows incomplete accumulation of iodized oil in the tumor (arrow). (c) Sonogram obtained before microwave ablation (left) shows a 35-mm hypoechoic nodule in the anterior segment of the right hepatic lobe (arrows). Sonogram obtained immediately after treatment (two emissions) (right) shows a markedly echogenic region of coagulation (arrow) that has replaced the tumor. (d) Enhanced CT scan obtained 4 days after microwave ablation shows ablated tissue as unenhanced areas within and around the tumor (arrows). (e) Dynamic CT scan obtained 9 months after treatment shows that the lesion (arrow) has decreased in size, without evidence of new tumor growth.
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Figure 9c. CT evaluation of microwave ablation performed in a 68-year-old man with hepatocellular carcinoma who had previously been treated with arterial chemoembolization with iodized oil. (a) Enhanced CT scan obtained before embolization shows a hypervascular tumor nodule (arrowheads). (b) Unenhanced CT scan obtained 7 days after embolization shows incomplete accumulation of iodized oil in the tumor (arrow). (c) Sonogram obtained before microwave ablation (left) shows a 35-mm hypoechoic nodule in the anterior segment of the right hepatic lobe (arrows). Sonogram obtained immediately after treatment (two emissions) (right) shows a markedly echogenic region of coagulation (arrow) that has replaced the tumor. (d) Enhanced CT scan obtained 4 days after microwave ablation shows ablated tissue as unenhanced areas within and around the tumor (arrows). (e) Dynamic CT scan obtained 9 months after treatment shows that the lesion (arrow) has decreased in size, without evidence of new tumor growth.
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Figure 9d. CT evaluation of microwave ablation performed in a 68-year-old man with hepatocellular carcinoma who had previously been treated with arterial chemoembolization with iodized oil. (a) Enhanced CT scan obtained before embolization shows a hypervascular tumor nodule (arrowheads). (b) Unenhanced CT scan obtained 7 days after embolization shows incomplete accumulation of iodized oil in the tumor (arrow). (c) Sonogram obtained before microwave ablation (left) shows a 35-mm hypoechoic nodule in the anterior segment of the right hepatic lobe (arrows). Sonogram obtained immediately after treatment (two emissions) (right) shows a markedly echogenic region of coagulation (arrow) that has replaced the tumor. (d) Enhanced CT scan obtained 4 days after microwave ablation shows ablated tissue as unenhanced areas within and around the tumor (arrows). (e) Dynamic CT scan obtained 9 months after treatment shows that the lesion (arrow) has decreased in size, without evidence of new tumor growth.
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Figure 9e. CT evaluation of microwave ablation performed in a 68-year-old man with hepatocellular carcinoma who had previously been treated with arterial chemoembolization with iodized oil. (a) Enhanced CT scan obtained before embolization shows a hypervascular tumor nodule (arrowheads). (b) Unenhanced CT scan obtained 7 days after embolization shows incomplete accumulation of iodized oil in the tumor (arrow). (c) Sonogram obtained before microwave ablation (left) shows a 35-mm hypoechoic nodule in the anterior segment of the right hepatic lobe (arrows). Sonogram obtained immediately after treatment (two emissions) (right) shows a markedly echogenic region of coagulation (arrow) that has replaced the tumor. (d) Enhanced CT scan obtained 4 days after microwave ablation shows ablated tissue as unenhanced areas within and around the tumor (arrows). (e) Dynamic CT scan obtained 9 months after treatment shows that the lesion (arrow) has decreased in size, without evidence of new tumor growth.
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Patient Outcome
We have performed microwave ablation on 69 hepatocellular carcinomas, 12–50 mm in diameter (mean, 28 mm), in 60 patients. A total of one to 12 microwave emissions was required in each case. Follow-up dynamic CT performed 3 months after the procedure showed complete tumor necrosis in 50 of 69 (72%) hepatocellular carcinomas and incomplete necrosis or tumor recurrence in 19 (28%) hepatocellular carcinomas (Fig 9). The longest disease-free period was 62 months, and the earliest recurrence was seen at 3 months. The mean disease-free period was 24.2 months. The overall survival rate was 83.1% at 1 year and 68.7% at 2 years. Ascites developed in three patients, pleural effusions in two, intraperitoneal hemorrhage in one, intraperitoneal abscess in one, and needle tract seeding in two (15,16).
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Laser Ablation: Perspectives from William R. Lees and Alison R. Gillams
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The first interstitial thermal ablation of a tumor performed with laser therapy was reported by Bown in 1983 (20). Since then, experimental studies have shown that a reproducible thermal injury can be produced with neodymium yttrium aluminum garnet (Nd YAG) lasers (21). Nd YAG lasers have been used to treat tumors of the esophagus, stomach, colon, and pulmonary bronchus (22–25). The first use of lasers to treat patients with hepatomas and hepatic metastases was reported by Hashimoto et al (26) and Steger et al (27), respectively.
Mechanism
From a single, bare 400-mm laser fiber, light at optical or near-infrared wavelengths will scatter within tissue and be converted into heat. Light energy of 2.0–2.5 W will produce a spherical volume of coagulative necrosis 2 cm in diameter. Use of higher power results in charring and vaporization around the fiber tip.
Two methods have been developed for producing larger volumes of necrosis. The first consists of firing multiple bare fibers arrayed at 2-cm spacing throughout a target lesion (27). The second uses cooled-tip diffuser fibers that can deposit up to 30 W over a large surface area, thus diminishing local overheating (28).
Equipment
Portable solid-state lasers are now available with power outputs up to 30 W (Fig 10). This energy can be delivered through fibers over 10 m in length with the great advantage of being fully compatible with MR imaging. A portable laser costs $20,000–$50,000, and a set of fibers costs approximately $2,000 but can be used to treat up to 50 patients per set.
Patient Selection and Technique
The indications and contraindications for laser ablation are the same as those for radio-frequency and microwave ablation. We have used it to treat patients with colorectal metastases, neuroendocrine and other metastases with favorable biologic behavior, and hepatocellular carcinoma.
The procedure is always guided with US combined with either CT or MR imaging (Fig 11). Sonography is quick and easy if visualization is adequate, but use of CT or MR imaging can add three-dimensional precision at the expense of lengthening the procedure. The major advantages of MR imaging are enhanced lesion visualization due to use of long-acting liver-specific contrast agents, true multiplanar imaging capabilities coupled with three-dimensional navigation, and visualization of temperature change and coagulation (Fig 12) (29).
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Figure 11a. MR imaging-guided laser ablation. (a) Photograph shows a patient positioned in an MR imaging unit (0.2-T Viva [Siemens Medical Systems, Iselin, NJ]) with the radiologist performing the procedure. (b) Sagittal MR image obtained after administration of ferumoxide contrast material shows the high-signal-intensity tumor (arrow) into which two needles (arrowheads) have been inserted.
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Figure 11b. MR imaging-guided laser ablation. (a) Photograph shows a patient positioned in an MR imaging unit (0.2-T Viva [Siemens Medical Systems, Iselin, NJ]) with the radiologist performing the procedure. (b) Sagittal MR image obtained after administration of ferumoxide contrast material shows the high-signal-intensity tumor (arrow) into which two needles (arrowheads) have been inserted.
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Figure 12a. Laser ablation of colorectal metastases. (a) MR image shows needles (arrows) positioned in a high-signal-intensity tumor (arrowheads) prior to treatment. (b) MR image shows low signal intensity (arrow) within the lesion caused by laser coagulation of the tumor.
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Figure 12b. Laser ablation of colorectal metastases. (a) MR image shows needles (arrows) positioned in a high-signal-intensity tumor (arrowheads) prior to treatment. (b) MR image shows low signal intensity (arrow) within the lesion caused by laser coagulation of the tumor.
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By inserting up to eight simultaneously energized bare fibers into the center of a tumor with a roughly 2-cm spacing, we have discovered that there is a linear relationship between burn size and the total amount of energy deposited. Thus, treatment times of 60–90 minutes yield confluent necrosis of 6–7 cm in diameter. The ultimate burn size is governed by the tumor vascularity and by the vasodilatory response of surrounding normal liver parenchyma. Hepatocellular carcinoma responds quite differently than colorectal metastases. In the former case, the capsule and surrounding cirrhotic liver clearly constrain the tumor margin so that ablating to the visible tumor margin is all that is necessary. For colorectal metastases, there is always tumor beyond the visible margin, and a 5–10-mm cuff of adjacent normal hepatic parenchyma must be ablated to achieve complete ablation. Hypervascular lesions such as hepatocellular carcinoma are first treated with ethanol ablation to devascularize the tumor as much as possible before thermal ablation is performed.
Treatment effectiveness is assessed with CT performed 18–24 hours after ablation and before discharge (Fig 13). Pain is common, and vigorous pain control is vital after the procedure. Nonsteroidal anti-inflammatory analgesics are very helpful in controlling the pain associated with the intense inflammatory response.
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Figure 13a. Imaging evaluation of laser ablation of hepatocellular carcinoma. (a) Arterial-phase CT scan obtained before ablation shows a hypervascular hepatocellular carcinoma (arrow) in the right hepatic lobe. (b) Axial T2-weighted MR image obtained immediately after laser ablation shows the low-signal-intensity tumor with a high-signal-intensity rim (arrows) caused by acute peritumoral hyperemia. (c) Portal-phase CT scan obtained 24 hours after ablation shows the avascular tumor (arrow), indicating 98% ablation.
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Figure 13b. Imaging evaluation of laser ablation of hepatocellular carcinoma. (a) Arterial-phase CT scan obtained before ablation shows a hypervascular hepatocellular carcinoma (arrow) in the right hepatic lobe. (b) Axial T2-weighted MR image obtained immediately after laser ablation shows the low-signal-intensity tumor with a high-signal-intensity rim (arrows) caused by acute peritumoral hyperemia. (c) Portal-phase CT scan obtained 24 hours after ablation shows the avascular tumor (arrow), indicating 98% ablation.
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Figure 13c. Imaging evaluation of laser ablation of hepatocellular carcinoma. (a) Arterial-phase CT scan obtained before ablation shows a hypervascular hepatocellular carcinoma (arrow) in the right hepatic lobe. (b) Axial T2-weighted MR image obtained immediately after laser ablation shows the low-signal-intensity tumor with a high-signal-intensity rim (arrows) caused by acute peritumoral hyperemia. (c) Portal-phase CT scan obtained 24 hours after ablation shows the avascular tumor (arrow), indicating 98% ablation.
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Patient Outcome
There have been several reports on the use of laser ablation to treat liver tumors (28–33). However, survival data provide the only method of determining therapeutic efficacy. At our institution, we have survival figures for patients with inoperable colorectal cancer metastases who underwent laser ablation of their liver tumors. Some of these patients have survived more than 5 years after treatment, with a median survival of 27 months and a 5-year survival rate of 26%. These figures are comparable with those for patients with operable metastases at our institution, who had a median survival of 33 months and a 5-year survival rate of 30% (cf 20%–42% in the literature) (1,2). In over 500 treatment sessions, there was only one death from a spontaneous hepatic infarction that occurred 6 days after discharge from a successful procedure. Major complications included segmental infarction in five patients, abscesses (all secondarily infected necrosis from diverticulitis or cholangitis) in three, pleural effusion in one, tumor seeding in six, and pain.
In patients with colorectal metastases, survival is governed by technical success in ablating the tumor and a 5-10-mm margin of normal liver around the tumor and by the biologic behavior of the tumor. The parameters that correlate with good outcome are the same as those for surgery: fewer than five tumors, tumors smaller than 5 cm, slow growth rate, and no extrahepatic tumor (28–33). In our own data, there is a significant difference between pre-1995 and post-1995 results because of technical improvements. Major advances in laser ablation in the past 12 months will not be reflected in outcome data for several years. Although survival rate depends on the biologic behavior of a tumor, patients with carefully selected non-colorectal metastases (eg, from breast cancer and sarcoma) show similar survival characteristics.
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Cryoablation: Perspective from Robert A. Kane
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Cryoablation is the oldest of the local thermal ablation techniques. Cooper first suggested its use for treating liver tumors in 1963 (34). Since then, there have been multiple clinical reports detailing its use for the treatment of primary and secondary malignant hepatic tumors (35–39).
Mechanism
Cryoablation is a method of in situ tumor ablation in which subfreezing temperatures are delivered through penetrating or surface cryoprobes in which a cryogen is circulated. Thermally conductive material allows cooling at the probe tip while the shaft and delivery hoses are insulated (Fig 14). Irreversible tissue destruction occurs at temperatures below -20°C to -30°C. Cell death is caused by direct freezing, denaturation of cellular proteins, cell membrane rupture, cell dehydration, and ischemic hypoxia. Cryolesions as large as 6–8 cm in diameter can be created safely.
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Figure 14. Photograph shows a 3-cm-long, oval ice ball developing around the conductive tip of a 5-mm cryoprobe. Note that the propagation of ice is maximal perpendicular to the probe, with very little forward propagation. This necessitates that the probe tip must reach the deep edge of the lesion for optimal treatment.
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Equipment
There are three U.S. companies marketing cryosurgical systems. Cryotech/Candela (Wayland, Mass) uses liquid nitrogen under pressure, Cryomedical Sciences (Rockville, Md) utilizes super-cooled liquid nitrogen, and Endo Care (Irvine, Calif) uses argon gas as the cryogenic material. The cost of a cryoablation unit ranges from $130,000 to $160,000. All three systems offer multiple probes in varying sizes and configurations, with trochar probes typically ranging from 2 to 10 mm in diameter (Fig 15). They cost $1,200 per probe for single use and $2,500 per probe for multiuse.
Patient Selection and Technique
For patients with unresectable primary hepatic cancer or secondary liver involvement from colorectal carcinoma, treatment is generally limited to those with four or fewer lesions. However, patients with certain other metastatic neoplasms such as those from primary neuroendocrine tumors may have a slightly higher number of lesions and still be candidates for cryoablation. Contraindications include the presence of extrahepatic metastatic disease and inability to undergo general anesthesia and laparotomy.
At present, cryoablation is primarily an open surgical technique with fewer than 10% of patients treated laparoscopically (Fig 16). US is the most predominantly used method of guiding the procedure. Depending on tumor size, one or two probes are placed centrally within the lesion with the tips of the probes touching the deep edge of the tumor. The cryogenic material (-196°C) is circulated through the probes. The ice ball is visualized as an echogenic, expanding, hemispherical rim (Fig 17). Freezing is continued until the cryolesion extends through the tumor and into the adjacent normal tissue, with the goal of achieving a 5–10-mm ablation margin. This first freeze takes 5–15 minutes and is followed by a spontaneous thaw and a second freeze to reach and slightly exceed the original cryoablation margin. After the second freeze, the cryoprobe is heated and removed, and the tract is packed for hemostasis.
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Figure 16. Intraoperative photograph of cryoablation of a large liver tumor shows two penetrating cryoprobes (open arrows) as well as a surface disc probe
(solid straight arrow) on the opposing surface. A small intraoperative US transducer (arrowhead) and a flexible rubber "fish" (curved arrow) used to protect vital structures adjacent to the frozen liver are also seen.
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Figure 17a. US guidance of hepatic cryoablation. (a) Sonogram shows an echogenic 5-mm cryoprobe (arrow) placed centrally within a relatively isoechoic colon metastasis (arrowheads). (b) Sonogram obtained at the partial freeze stage (ie, at 3 minutes) demonstrates that the ice ball (arrow) has extended to the lateral margin of the tumor, but the anterior margin (arrowheads) is still visible. (c) Sonogram obtained at the complete freeze stage (ie, at 8 minutes) shows the ice ball (arrow), which now completely encompasses and extends beyond the anterior margin of the tumor, indicating a successful ablation.
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Figure 17b. US guidance of hepatic cryoablation. (a) Sonogram shows an echogenic 5-mm cryoprobe (arrow) placed centrally within a relatively isoechoic colon metastasis (arrowheads). (b) Sonogram obtained at the partial freeze stage (ie, at 3 minutes) demonstrates that the ice ball (arrow) has extended to the lateral margin of the tumor, but the anterior margin (arrowheads) is still visible. (c) Sonogram obtained at the complete freeze stage (ie, at 8 minutes) shows the ice ball (arrow), which now completely encompasses and extends beyond the anterior margin of the tumor, indicating a successful ablation.
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Figure 17c. US guidance of hepatic cryoablation. (a) Sonogram shows an echogenic 5-mm cryoprobe (arrow) placed centrally within a relatively isoechoic colon metastasis (arrowheads). (b) Sonogram obtained at the partial freeze stage (ie, at 3 minutes) demonstrates that the ice ball (arrow) has extended to the lateral margin of the tumor, but the anterior margin (arrowheads) is still visible. (c) Sonogram obtained at the complete freeze stage (ie, at 8 minutes) shows the ice ball (arrow), which now completely encompasses and extends beyond the anterior margin of the tumor, indicating a successful ablation.
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With proper technique, a single cryoablation procedure should be adequate to completely eradicate the tumor site. Patients are followed up with CT performed immediately before discharge, at 6 and 12 months after ablation, and annually thereafter. The thermal injury caused by cryoablation appears on CT images as an avascular low-attenuation lesion that slowly decreases in size over time (Fig 18).
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Figure 18a. CT evaluation of hepatic cryoablation. (a) Pretreatment CT scan shows a colorectal metastasis (arrow) in the dome of the liver that measures 3.5 cm. (b) CT scan obtained 4 days after cryoablation shows a low-attenuation cryolesion (arrow) measuring 5 x 6 cm completely encompassing the tumor site. Small gas bubbles are also seen, a finding indicative of necrosis. (c) Follow-up CT scan obtained 8 months after cryoablation shows the residual cryolesion (arrow) markedly decreased in size as a result of healing and fibrosis.
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Figure 18b. CT evaluation of hepatic cryoablation. (a) Pretreatment CT scan shows a colorectal metastasis (arrow) in the dome of the liver that measures 3.5 cm. (b) CT scan obtained 4 days after cryoablation shows a low-attenuation cryolesion (arrow) measuring 5 x 6 cm completely encompassing the tumor site. Small gas bubbles are also seen, a finding indicative of necrosis. (c) Follow-up CT scan obtained 8 months after cryoablation shows the residual cryolesion (arrow) markedly decreased in size as a result of healing and fibrosis.
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Figure 18c. CT evaluation of hepatic cryoablation. (a) Pretreatment CT scan shows a colorectal metastasis (arrow) in the dome of the liver that measures 3.5 cm. (b) CT scan obtained 4 days after cryoablation shows a low-attenuation cryolesion (arrow) measuring 5 x 6 cm completely encompassing the tumor site. Small gas bubbles are also seen, a finding indicative of necrosis. (c) Follow-up CT scan obtained 8 months after cryoablation shows the residual cryolesion (arrow) markedly decreased in size as a result of healing and fibrosis.
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Patient Outcome
Currently, our experience in over 12 years of hepatic cryoablation has allowed a calculation of true (rather than actuarial) long-term survival rates of 90% for 1 year, 40% for 3 years, and 20% for 5 years. Mean overall survival for the entire group of 107 patients is 38 months, and the longest survival to date is 150 months after treatment (the patient is alive at this writing).
At our institution, there have been no deaths in 107 consecutive cryoablations. Others, however, have reported deaths, which occurred more often in patients in whom very large volumes of tumor were cryoablated and for whom death was related to renal failure, disseminated intravascular coagulation, and sepsis. Minor complications of fever, leukocytosis, and transient elevated values from liver function tests occurred in the majority of patients. Major complications developed in fewer than 20% of patients in our series, and most of these were related to bleeding. No tumor seeding has been reported. Local failure (ie, tumor recurrence at the cryoablation site) occurred in 13% (35).
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Ethanol Ablation: Perspective from Tito Livraghi
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Worldwide, ethanol injection therapy or ablation is probably the most accepted minimally invasive method of treating primary malignant hepatic tumors. Its acceptance is based on the ease of treatment, minimal and inexpensive therapeutic equipment required, and good clinical results.
Mechanism
Within neoplastic cells, ethanol causes dehydration of the cytoplasm and subsequent coagulation necrosis, followed by fibrous reaction. Within neoplastic vessels, ethanol induces necrosis of endothelial cells and platelet aggregation, thus causing thrombosis and tissue ischemia.
The size and shape of the induced necrosis is not always reproducible. It varies with histologic characteristics, degree of vascularization, presence of capsule or septa, and tissue consistency. Hepatocellular carcinoma is the most responsive tumor. The largest tumor treated effectively with ethanol ablation was an 8.2-cm hepatocellular carcinoma that was ablated in less than 1 hour with a one-shot technique (40).
Equipment
The materials consist of sterile ethanol 95%, a syringe, connecting tubing, and a multihole 21-gauge needle with a conical tip (PEIT needle, Hakko, Tokyo, Japan) (Fig 19). The cost of the needle, syringe, tubing, and ethanol is $45.
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Figure 19. Photograph shows ethanol ablation equipment, which consists of a syringe, sterile 95% ethanol, and a 20-cm-long, 21-gauge needle with a closed conical tip and three terminal holes (Hakko).
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Patient Selection and Technique
Ethanol ablation is generally performed in cirrhotic patients with hepatocellular carcinoma. The treatment is ineffective for liver metastases, and since 1995 radio-frequency ablation has replaced ethanol ablation for treating metastatic lesions (40–44). Candidates for ethanol ablation must have tumors whose volume is less than 30% of the total volume of the liver. Contraindications include extrahepatic disease, thrombosis of the portal vein, Child C class, prothrombin time less than 40%, and a platelet count of less than 40,000/mm3.
According to the size and number of the lesions, ethanol ablation is performed either as an outpatient multisession technique or as an inpatient one-shot technique under general anesthesia. In most instances, hepatocellular carcinomas smaller than 5 cm are treated on an outpatient basis, and larger tumors are treated with the one-shot inpatient technique. For both, ethanol is injected percutaneously under sonographic guidance. For an outpatient procedure, 1–8 mL of ethanol is injected per session, two times per week for a total of four to 12 sessions (Fig 20). In an inpatient one-shot procedure, 62 mL of ethanol is delivered in 13 injections over a mean time of 30 minutes, and the patient has a mean hospital length of stay of 3.8 days. CT is performed to evaluate the success of treatments (Fig 21) (40,41).
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Abstract
Introduction
