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Interventional Radiology Case Conferences Massachusetts General Hospital |
1 All authors: Division of Abdominal Imaging and Intervention, Department of Radiology–White 270, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114.
Received August 8, 2002;
accepted after revision August 29, 2002.
Address correspondence to P. R. Mueller.
Case History
 Top Case History References |
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Dr. Titton: Why was this patient thought to be a good candidate for radiofrequency tumor ablation for treatment of hepatocellular carcinoma?
Dr. Mueller: Patients are considered to be candidates for radiofrequency ablation if they have primary hepatic cancer not suitable for curative resection; hepatic metastatic disease with no extrahepatic manifestations of tumor; solitary lesions smaller than 5 cm in diameter; or a total of up to five liver lesions, with each lesion measuring as large as 3 cm in diameter [1, 2, 3, 4]. This patient had undergone two prior hepatic resections, and it was thought that any additional hepatic resection would leave the patient with insufficient hepatic reserve. The two lesions were 3 and 2 cm, which meant that they could likely be treated effectively with a single radiofrequency ablation session. Thus, this patient was considered an ideal candidate for radiofrequency ablation.
Dr. Gryzenia: What are other minimally invasive techniques for the treatment of primary and secondary hepatic malignancies?
Dr. Gervais: Because less than 15% of patients with hepatic malignancy are candidates for curative resection [3, 5], there is intense interest in developing minimally invasive curative tumor ablation techniques. For percutaneous ablation of tumors, chemical instillation techniques and thermal ablation techniques have been developed for the treatment and potential cure of hepatocellular carcinoma [2, 6, 7, 8]. One of the first tumor ablation therapies involved the chemical installation of ethanol. Percutaneous ethanol ablation causes dehydration of the cytoplasm in neoplastic cells [2, 8]. Thermal ablation therapies involve altering the local tissue temperature of the tumor in order to induce cell death. In cryoablation, a needle perfused with liquid nitrogen is used to freeze cell membranes. Microwave therapy, laser therapy, and radiofrequency ablation cause localized heating of the tumor to induce coagulation necrosis.
Another option for the treatment of hepatic malignancy is transarterial chemoembolization, which delivers regional therapy and is less efficacious than localized percutaneous treatment options in the killing of individual tumors [2].
Radiofrequency ablation holds several advantages over the other percutaneous tumor ablation techniques. For focal tumors, radiofrequency ablation therapy has proven to be more effective, easier to control, and less toxic than transarterial chemoembolization [2, 9]. Percutaneous ethanol ablation is less effective in the treatment of hepatic metastatic disease [2] because it requires more sessions than radiofrequency ablation does to treat tumors of comparable size [8]. The overall complication rate of cryoablation has been reported to be as high as 50% [2, 7, 10, 11], whereas the complication rate after radiofrequency ablation has been reported to be 2–10% [5, 9, 10]. In comparing the number of sessions required to treat tumors of similar sizes, fewer sessions of radiofrequency ablation are required than are needed with other thermal ablation therapies [2, 6]. Radiofrequency ablation systems are widely available and are relatively inexpensive [12].
Dr. Titton: How is radiofrequency ablation performed?
Dr. Arellano: Both sonography and CT may be used for imaging-guided placement of the radiofrequency electrode. In sonographically guided radiofrequency ablation, devitalized tissues become hyperechoic as a result of microbubble formation and tissue vaporization [13]. The increased echogenicity that occurs during sonographically guided radiofrequency ablation does not correspond with the actual extent of coagulation [14]. The increased echogenicity may limit the radiologist's ability to delineate the necrotic treated tissue from the adjacent tumor and may limit visualization of the needle tip if multiple ablations are performed during the same treatment session [15].
Once the lesion to be treated is evaluated with either sonography or CT, the patient is placed under conscious sedation. At some institutions, IV antibiotic prophylaxis is administered [5]. The patient's heart rate, blood pressure, pulse oximetry, and ECG readings are continuously monitored. Grounding is achieved by attaching two dispersive foil pads—each with a surface area greater than 400 cm2—to either the patient's thighs or shoulders [4, 13]. The skin is cleansed with povidone iodine, and local anesthesia of 1% Xylocaine (lidocaine; Astra USA, Marlborough, MA) is applied. The radiofrequency electrode is then placed directly into the tumor under imaging guidance. Electric current is delivered via the needle electrodes, according to specifications that vary among manufacturers. After the procedure, the patient is monitored for 4–6 hr and, if asymptomatic during the observation period, may be discharged the same day.
Dr. Gryzenia: Which commercially available radiofrequency ablation systems can be used to treat hepatic tumors?
Dr. Mueller: There are three commercially available radiofrequency delivery systems [16]. Each modern radiofrequency system uses a generator operated at 460–500 kHz with a power setting of 150–200 W [2, 14]. All radiofrequency generators come equipped with circuitry to evaluate generator power output and tissue impedance [15].
The design of needle electrodes ranges from the earliest single-needle electrodes to more complex systems. The single-needle electrode design creates thermal lesions measuring up to only 1.6 cm [16, 17] and is, therefore, impractical for treatment of most hepatic tumors. The modern, more complex systems use electrode arrays or clusters, resulting in larger volumes of tissue necrosis [2, 15, 16, 17].
Two commercially available multiprobe hooked electrodes are delivered via a coaxial introducer. With this design, after a single needle insertion, radiofrequency ablation can be used at multiple sites, increasing the volume of tissue necrosis [18]. RITA Medical Systems (Mountain View, CA) markets a hook array on a 15-gauge radiofrequency needle electrode. The generator displays the local tissue temperature at each electrode site in additional to displaying tissue impedance and power output. The RITA system is designed to allow the operator to monitor temperature at the tissue level to determine when the end point of the tumor ablation has been attained. After a target tissue temperature of 90–110°C is reached, it is maintained for several minutes before the procedure is terminated. RadioTherapeutics (Sunnyvale, CA) uses a hook array on a 14-gauge needle electrode [2, 16]. The RadioTherapeutics system is designed to monitor impedance. In this system, current is delivered until a rapid impedance increase occurs. This so-called roll-off phenomenon marks the end point of an ablation.
Radionics (Burlington, MA) markets a needle electrode with a different design that increases the size of the thermal injury created. The Radionics system uses a pulsed current and an internal electrode cooling system [2, 17, 18, 19]. The pulsed current uses a microchip to alternate between periods of high-energy and low-energy deposition. This technique allows preferential cooling in the tissues immediately adjacent to the electrode during periods of low-energy deposition without significantly decreasing heat deposition in deeper tissues [17, 18, 19]. Water with a temperature of 0–5°C is circulated through two hollow lumens within 17-gauge needle electrodes to maintain a tip temperature of the needle electrodes below 20–25°C to minimize tissue vaporization and carbonization adjacent to the electrode [13, 14, 17, 20]. The end point with the Radionics system is a predetermined 12-min period for each ablation.
In a study by de Baere et al. [18], the cooled-tip needle delivery system induced lesions larger than those produced by the expandable needle delivery system, but the lesions produced by the expandable needle were more reproducible. To date, we know of no studies that document a definite advantage of one needle design over another [2, 18]. The radiofrequency devices can all be used percutaneously, laparoscopically, or intraoperatively.
Dr. Titton: The patient's two lesions were treated with a 17-gauge cluster needle electrode with a 2.5-cm exposed metallic tip. The larger tumor measured 3 cm and was treated with three overlapping ablations of 12 min each (Fig. 1A). The second smaller tumor was treated with two 12-min-long ablations. What happens to the tumor on a cellular level during the procedure?
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Dr. Boland: As electric current flows from the uninsulated needle tip through the tissues, localized frictional heat in the tissues is generated due to ionic agitation. When the local temperature of the lesion exceeds 50°C, tissue necrosis occurs because of the loss of intracellular water, denaturation of intracellular proteins, tissue carbonization, and melting of the lipid bilayers [3]. Experimental studies have shown that cellular death occurs 4–6 min after exposure to temperatures exceeding 50°C, a few seconds after exposure to temperatures exceeding 55°C, and immediately after exposure to temperatures exceeding 60°C [21, 22]. The extent of coagulation necrosis induced is dependent on the overall energy deposition; the duration of radiofrequency application; and the length, configuration, and gauge of the radiofrequency electrode tip [16]. Patients with cirrhosis or well-encapsulated hepatocellular carcinomas have been shown to have increased necrosis because of the oven effect caused by heat retention in fibrotic or encapsulated tissue [8, 9].
In addition to the lesion of hepatic metastatic disease, a 5- to 10-mm rim of normal tissue around the lesion also must be treated in order to treat microinvasion that may not be fully imaged [9, 13, 20]. If adequate margins are not obtained, peripheral tumor growth may occur with unfavorable geometry for retreatment [15]. As the local tissue temperature reaches more than 105°C, heating of surrounding tissue becomes severely limited because tissue charring results in increased circuit impedance [16, 21].
Dr. Gryzenia: What type of intraprocedural complications and immediate postprocedural complications have been reported with radiofrequency ablation?
Dr. Arellano: Complications requiring treatment generally develop within several days after the procedure [5]. Overall, the reported complication rates for radiofrequency ablation range from 2% to 10% [5, 9, 10]. During and immediately after the procedure, the patient's vital signs should be evaluated. A drop in blood pressure or an increase in heart rate should be viewed with suspicion because intraperitoneal or retroperitoneal hemorrhage occurs in 1.8% of patients who have undergone radiofrequency ablation [4, 9, 13]. Livraghi et al. [9] described the case of a patient with septic shock, peritonitis, and multisystem organ failure that resulted in death 8 days after radiofrequency ablation treatment of two foci of hepatocellular carcinoma. Abdominal pain may be caused by bowel perforation resulting from adhesions between the liver capsule and a loop of bowel [20, 23]. Hepatic abscess formation may occur in up to 3% of patients after radiofrequency ablation [22] and usually presents clinically within the first 2 weeks after the procedure. Shortness of breath may be related to a pneumothorax, hemothorax, or pleural effusion caused by the procedure [5]. Second- and third-degree skin burns have been reported in up to 10% of patients [4, 13]. During the first 3 days after radiofrequency ablation, the patient's transaminase levels can be expected to rise, perhaps increasing to seven times the normal values [9]. The levels generally normalize by 1 month after the procedure [13]. Fever, cholecystitis, diaphragmatic injury, myoglobinemia, rhabdomyolysis, and renal failure have been reported to occur within the first several days after radiofrequency ablation [1, 24, 25].
Dr. Titton: What are limitations of radiofrequency ablation?
Dr. Gervais: The tissue volume that can be destroyed in a single treatment is the major limitation of radiofrequency ablation. Because most radiofrequency ablation devices produce an approximately 3- to 5-cm area of ablation, the largest tumor that can be treated with a single ablation is approximately 3.5 cm [12, 15]. A tumor larger than 2.5 cm requires multiple overlapping ablations to treat the tumor itself and to create a tumor-free margin [1, 15, 26]. The overall success rate of radiofrequency ablation diminishes as the size of the tumor increases. Patients with hepatocellular carcinomas smaller than or equal to 3 cm have complete tumor necrosis at a rate approaching 90%, whereas patients with hepatocellular carcinomas larger than 3 cm have an overall response rate of approximately 50% [8, 9, 20, 23]. Patients with more than five tumors or with tumors larger than 5 cm generally require transcatheter chemoembolization, possibly combined with radiofrequency ablation [4].
Effectiveness of radiofrequency ablation treatment in patients with satellite nodules is limited because of decreased heat diffusion through peritumoral fibrotic tissue [9]. Lesion location may also limit the effectiveness of radiofrequency ablation. Lesions close to large blood vessels are difficult to treat because the local heat is dissipated by blood flow in a heat-sink phenomenon [3, 5, 27]. Goldberg et al. [27] found an inverse correlation between tissue blood flow and the diameter of coagulation necrosis. Tumors near the dome of the diaphragm are technically difficult to treat [3, 25, 28]. Tumors adjacent to the liver capsule, the gallbladder, and the loops of bowel pose an increased risk of thermal injury and possibly perforation [3, 20, 28]. Lucey et al. [28] described a case of peritonitis after radiofrequency ablation in a patient with preexisting ascites and advocated drainage of large-volume ascites before radiofrequency ablation to decrease the likelihood of seeding the peritoneal cavity with necrotic material.
Contraindications of the procedure include sepsis and uncontrolled coagulopathy [2]. Child-Pugh class C cirrhosis is considered a contraindication to radiofrequency ablation because the life expectancy of patients with this advanced cirrhosis is limited, although not by the hepatocellular carcinoma.
Dr. Gryzenia: When should the patient be scheduled for imaging after the radiofrequency ablation procedure?
Dr. Boland: The optimal time for the initial baseline imaging after radiofrequency ablation remains somewhat controversial [29, 30]. At our institution, we perform contrast-enhanced CT or MR imaging within 1 month of the procedure and at 3-month intervals thereafter for at least 1 year. Long-term follow-up with diagnostic imaging should be considered the most reliable tool with which to assess efficacy of radiofrequency ablation and to detect the presence of residual untreated tumor [19, 31].
Dr. Titton: Which imaging findings are signs of optimal results from radiofrequency ablation? What findings are suggestive of residual or recurrent disease?
Dr. Arellano: Evaluations of the liver performed with gray-scale, color Doppler, and contrast sonography have been reported in the literature as inferior to evaluation performed with contrast-enhanced CT or MR imaging [29, 30]. On the initial follow-up CT scans or MR images, the postablation tissue bed may appear to have slightly increased in size because of the ablation of the tumor margins. On the subsequent CT scans, the size of areas of successfully treated tumor either remain unchanged or diminish at unpredictable rates [9, 29]. Most commonly, the volume of the nonenhancing focus of treatment shrinks less than 20% [21].
At our institution, we perform helical CT of the liver during the hepatic arterial phase (30 sec), portal venous phase (70 sec), and delayed equilibrium phase (300 sec) after the IV administration of contrast material. Dynamic contrast-enhanced MR imaging with three 30-sec intervals may also reveal perfusion of the postablation tissue bed. Bulky, nodular peripheral enhancement at the treatment site is the most common appearance of an incompletely treated lesion [15]. In current practice, the most accurate predictor of induced coagulation after radiofrequency ablation is the absence of contrast enhancement in or along the periphery of the postablation tissue bed [14]. Absence of enhancement within the tumor correlates pathologically with coagulation necrosis [9, 14, 15, 20].
MR images of ablated tissues display a hyperintense appearance on T1-weighted images because of hemorrhage or proteinaceous material in the devitalized tissue and a hypointense appearance on T2-weighted images because of local dehydration within the tissues, with no enhancement after the administration of IV gadolinium [14, 29]. A recent study by Dromain et al. [29] reported that MR imaging may be slightly more sensitive than CT for the early detection of residual tumor.
Dr. Gryzenia: The patient returned 1 month after the radiofrequency ablation treatment for abdominal CT, which showed that there was no evidence of residual or recurrent disease. What complications may occur beyond the first few weeks after radiofrequency ablation treatment?
Dr. Mueller: Formation of an asymptomatic hepatic abscess resulting from an radiofrequency ablation–related injury was described by de Baere et al. [22] in two of 68 patients. The abscesses were observed at the 2-month follow-up CT examination. In both cases, the patients were discharged within 3 days after the uneventful drainage of the hepatic abscess. Overall, according to the researchers, the rate of complications from the biliary tree is low, likely due to the cooling effect of blood vessels running adjacent to the biliary tract. In theory, tumor seeding of the needle track after radiofrequency ablation can occur, but the risk of occurrence may be minimized by performing thermal coagulation of the needle track when withdrawing the electrode.
Dr. Titton: Three months after the procedure, the patient presented to the emergency department with new-onset jaundice, right upper quadrant pain, vomiting, temperature of 102.2°F, blood pressure of 120/70 mm Hg, and heart rate of 110 beats per minute. A CT scan of the abdomen and pelvis showed the segment VI lesion treated with radiofrequency ablation was nonenhancing and its maximal diameter had increased (Fig. 1B) from 3 to 7.5 cm. How was the patient managed?
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Dr. Gervais: On admission, CT findings were suspicious for abscess formation in the postablation tissue bed because the region had increased in size since the prior examination and was not displaying peripheral nodular bulky enhancement. Because of the new-onset jaundice and hepatic abscess, the patient was initially evaluated with endoscopic retrograde cholangiopancreatography (ERCP) (Fig. 1C), which revealed a paucity of bile ducts and no evidence of bile duct injury, dilatation, or obstruction. A sonographically guided percutaneous needle aspiration of the radiofrequency ablation tissue bed was then performed. The aspirate was turbid fluid that ultimately yielded Escherichia coli. A 10.5-French allpurpose percutaneous drainage catheter was then placed into the abscess collection using trocar technique. The patient was started on IV levofloxacin and metronidazole.
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Dr. Titton: A week after the abscess drainage procedure, the daily output from the abscess catheter remained high (200–400 mL per day), and the patient remained febrile. What was the next diagnostic test performed, and why was it selected?
Dr. Boland: An abscessogram was obtained using a catheter-injected contrast agent to investigate the cause of the persistently high outputs from the drainage catheter. This study revealed the communication of the abscess with bile ducts peripheral relative to the abscess (Fig. 1D). The central bile ducts were not opacified.
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Dr. Gryzenia: The ERCP and abscessogram each showed a separate portion of the biliary tree. Why was MR cholangiopancreatography (MRCP) then recommended?
Dr. Gervais: A recent large-scale study by Yeh et al. [32] directly compared MRCP with ERCP for detection of a suspected biliary obstruction and found MRCP to be superior in revealing the exact anatomic extent of a biliary tree obstruction and cancerous infiltration and in showing the biliary tree in its entirety. In the study, the biliary tree cephalad to the stenotic tract and the character of the intraductal filling defect could always be evaluated on MRCP but was not always well visualized on ERCP [32]. MRCP has the additional advantage over ERCP of revealing both the intraductal and extraductal anatomy [32]. In both the study by Yeh et al. [32] and another study [33], the diagnosis of malignant biliary obstruction could be made on MRCP in all patients in whom such malignancy was present.
In our patient, MRCP and gadolinium-enhanced MR imaging of the liver were performed. MR imaging of the liver displayed a new 1.5-cm enhancing mass in the central biliary tree just anterior relative to the main portal vein (Fig. 1E). This small tumor was downstream from the site of the bile leak and abscess (Fig. 1F). MRCP allowed evaluation of the obstructing mass and the more proximal portion of the biliary tree, invaluably aiding the endoscopist when the patient was sent for a repeated ERCP and endoscopic stenting. At the time of the repeated ERCP, the site of obstruction was identified, and an endoscopic stent was placed across the new obstructing focus of hepatocellular carcinoma. Subsequently, the patient's bilirubin level, liver function values, and WBC improved.
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Dr. Titton: Was the presentation of the liver abscess in this patient typical of liver abscesses that develop after radiofrequency ablation?
Dr. Arellano: Hepatic abscess formation after radiofrequency ablation is a complication that may occur in up to 3% of patients who undergo the procedure. Typically, if a hepatic abscess develops, it occurs within 2 weeks after radiofrequency ablation. In this patient, the new obstructing mass in the downstream portion of the biliary tree led to cholestasis and superinfection of the postablation tissue bed by biliary pathogens, leading to delayed abscess formation and clinical presentation 3 months after the procedure.
Radiofrequency tumor ablation with concomitant bile duct disease leading to hepatic abscess formation has been previously reported. Zagoria et al. [5] reported a case of a hepatic abscess that developed 8 days after radiofrequency ablation of a liver metastasis in a patient with a common bile duct stone that was noted at the time of the radiofrequency ablation. Patients with a biliary enteric anastamosis have been reported to be at an increased risk of hepatic abscess formation after chemoembolization, presumably because of an increased incidence of bile reflux [34]. Although there has been less clinical experience with radiofrequency ablation in this setting, it is reasonable to assume that patients with biliary enteric anastamosis would also be at an increased risk for development of hepatic abscesses after radiofrequency ablation because of increased bile reflux.
Dr. Titton: In conclusion, can you briefly summarize the role of radiofrequency ablation in treating hepatic neoplasms?
Dr. Mueller: Radiofrequency ablation of hepatocellular carcinoma or hepatic metastasis is generally a safe, well-tolerated treatment option in patients who are not surgical candidates [20, 31], with disease-free rates approaching 90% in patients treated for tumors smaller than 3 cm in diameter [8, 9]. Ideal targets for this treatment are hepatocellular carcinomas that are smaller than 3 cm in diameter, completely surrounded by normal hepatic parenchymna, at least 1 cm deep relative to the liver capsule, and at least 2 cm from the large hepatic or portal veins [2]. Radiofrequency ablation has been shown to cause increased necrosis of larger tumors over a shorter period of time compared with laser therapy, microwave therapy, and percutaneous ethanol ablation. Although three designs of radiofrequency ablation systems are available on the market, no prospective study has yet been conducted that proves a clear advantage of one particular radiofrequency delivery system. Radiofrequency ablation can generally be performed on an outpatient basis with a low overall complication rate. Patients should be monitored closely for the development of a complication or for the presence of residual or recurrent untreated disease. Patients with concomitant conditions such as ascites or preexisting biliary disease should be closely monitored to prevent a complication that may be otherwise avoided.
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