Percutaneous Radiofrequency Ablation of Liver Tumors 

Updated: Nov 07, 2017
Author: Badar Bin Bilal Shafi, MBBS, MRCP, FRCR, CCT, EBIR; Chief Editor: Kurt E Roberts, MD 

Overview

Background

Percutaneous radiofrequency (RF) ablation (RFA) is an exciting approach to destroying inoperable primary tumors or metastases in the liver.[1, 2] In the treatment of hepatocellular carcinoma (HCC), fewer than 40% of patients are candidates for surgery, and the rate of recurrence after curative surgery is high. Percutaneous techniques like RFA are, therefore, very important. RFA is widely used for metastatic and small primary tumors.[3] It serves as a bridge for transplant candidates, especially in relation to small primary lesions.[4]

Percutaneous RFA is a minimally invasive, repeatable procedure with few complications. It is performed under radiologic guidance. Randomized controlled trials showed that RFA is superior to ethanol injection in the treatment of small HCCs.[5] RFA results in a higher rate of complete necrosis and requires fewer treatment sessions than percutaneous ethanol injection (PEI).[6, 7, 8]

Long-term survival rates are also better with RFA. A randomized clinical trial showed that RFA yields a significantly better 1-year complete response rate than does PEI.[5] RFA in combination with transcatheter arterial chemoembolization (TACE) is also an effective treatment for inoperable hepatic tumors.[9]  RFA combined with TACE also appears to be safe and effective in the treatment of breast cancer with liver metastasis.[10]

Studies comparing percutaneous RFA and percutaneous microwave coagulation therapy (PMCT) showed better results with RFA in treatment of small tumors. RFA results in better survival rates, fewer complications, and significantly lower local recurrence rates.[11, 12]

In RFA, a needle is inserted into the liver, usually under the guidance of ultrasonography or computed tomography (CT). Once the needle is placed within the tumor, a generator is used to deliver a rapidly alternating current (RF energy). This needle may be bipolar or unipolar; the latter requires grounding pads placed on the patient's thighs. Heat is generated at the site of the lesion through frictional heat produced by rapid agitation of adjacent cells and produces destruction (liquefactive necrosis) of the tumor.

This technology is used widely in Europe and the United States. Shiina et al noted that by 2007, at least 1500 institutes in Japan had introduced RFA in the treatment of liver tumors.[13]

Indications

In the treatment of HCC, the range of indications for percutaneous RFA is becoming wider than that of surgery and intra-arterial therapies, and it includes the following main categories[5, 1] :

  • HCC at an early stage [14, 15]
  • Primary treatment for small tumors [16, 17]  - A meta-analysis by Jansen et al described local ablative techniques as the treatment of choice for small HCC [18] ; the National Institute for Clinical Excellence (NICE) in the United Kingdom also recommended RFA as the treatment of choice in small tumors [19]
  • Inoperable primary liver tumor
  • Treatment of patients who cannot undergo general anesthesia or are not operative candidates because of comorbidity or advanced age
  • Liver metastasis, most commonly colorectal, especially if the patient is not an operative candidate [20]
  • Can be used for breast, [21] thyroid, [22] and neuroendocrine metastasis [23]
  • Treatment of patients who have a hepatoma or multiple small lesions and are waiting for liver transplantation [4]
  • Recurrent and progressive lesions [24]  - RFA has been used in conjunction with PEI as an alternative to repeat hepatectomy in elderly patients with recurrent HCC after initial hepatic surgery [25]

Contraindications

Contraindications for percutaneous RFA of liver tumors include the following:

  • Bile duct or major vessel invasion
  • Significant extrahepatic disease
  • Child class C cirrhosis or active infection
  • Decompensated liver disease
  • Lesions that are difficult to reach with electrodes or when electrode placement is impaired - In such cases, an open rather than percutaneous approach should be used [26] ; it should be noted, however, that RFA of liver tumors located in the caudate lobe is effective despite this segment's deep location and the proximity of the vessels [27, 28]
  • Tumors that occupy more than 40% of the volume of the liver - Tumors of this size cannot be safely ablated, because the liver reserve left after RFA might not be sufficient to preserve hepatic function
  • Proximity to vital structures like vessels and adjacent organs [29] - This is a relative contraindication; open RFA is suggested by one study [26]
  • Lesions larger than 5 cm (relative contraindication) - RFA should be used cautiously for lesions larger than 5 cm; one study suggests the use of open RFA for lesions larger than 5 cm [26]
  • Patients with metastatic lesions larger than 3 cm - These lesions are not optimally suited for RFA, because the risk of recurrence is high [20]
  • Large or numerous tumors - Multiple studies recommend RFA as a choice if there are fewer than three tumors, each of them measuring less than 3 cm [30, 31, 32]

Outcomes

One randomized controlled trial showed that the 2-year recurrence rate of HCC was significantly lower with RFA than with percutaneous ethanol injection (PEI). When compared with surgical resection, the recurrence rate is higher after RFA, with less time to recurrence.[33]  Recurrence is more common with the percutaneous approach as compared with open or laparoscopic RFA. The rate of recurrence is also higher with lesions larger than 3 cm.[34]

In a study by Toshimori et al, the local recurrence rates after percutaneous RFA for HCC were 2.2% at 1 year, 7.4% at 3 years, and 9.5% at 5 years.[35] Factors that predisposed to local recurrence included large tumor size (>2 cm), tumor location adjacent to the major portal branch or hepatic vein), and a small (<3 mm) ablated margin.

Shady et al assessed factors affecting outcome in patients with colorectal cancer liver metastases who were treated with percutaneous RFA.[36] On multivariate analysis, factors predictive of shorter local tumor progression-free survival were a tumor size exceeding 3 cm and a margin size of 5 mm or less; factors predictive of shorter overall survival were a tumor size exceeding 3 cm and the the presence of more than one site of extra-hepatic disease.

Yamao et al compared the survival impacts of RFA (n = 33) and hepatic resection (n = 71) as initial treatment of HCC in 104 patients with liver damage B as defined by the Liver Cancer Study Group of Japan.[37] Whereas overall survival (OS) tended to be better in the RFA group, disease-free survival (DFS) did not differ significantly between groups. Subgroup analyses found OS with RFA to be significantly better in patients with aspartate aminotransferase above 35 IU/L, serum albumin below 3.5 g/dL, and 99mTc-galactosyl human serum albumin below 0.85.

 

Periprocedural Care

Equipment

The imaging equipment needed for radiofrequency ablation (RFA) depends on the modality used. It can include the equipment necessary for ultrasonography, computed tomography (CT), or magnetic resonance imaging (MRI).

RFA equipment itself has three main components, as follows:

  • Needle electrodes
  • Electrical generator
  • Grounding pads

The needle electrodes are available in two forms. The first is a simple straight needle (see the first image below). The second is a straight needle containing multiple curved, retractable electrodes that are kept inside the needle until its tip is positioned within a tumor. Once this needle is properly positioned, a plunger on the hub of the needle is advanced so that the electrodes extend from the needle tip; when fully extended, the electrodes resemble an open umbrella (see the second image below).

Electrodes for radiofrequency ablation. Electrodes for radiofrequency ablation.
Umbrella-type electrodes for radiofrequency ablati Umbrella-type electrodes for radiofrequency ablation.

The radiofrequency (RF) generator is connected by insulated wires to the needle electrodes and to grounding pads that are placed on the patient's thighs. The generator produces alternating electrical current in the range of RF waves.

RFA systems commercially available for clinical application in the United States include the following[38] :

  • Integra Radionics (Burlington, MA) manufactures a 200W generator with internally cooled electrodes; it is available as a cluster-array system or a single-needle system and includes optional automated pulsing of the current
  • RITA Medical Systems (Mountain View, CA) produces various models of umbrella-type electrodes [39] ; these systems do not allow for pulsing of the internal current and do not have internal cooling electrodes
  • RadioTherapeutics (Mountain View, CA) produces expandable, umbrella-type electrodes, including the LeVeen RFA system; this system does not allow for pulsing of the internal current and does not have internal cooling electrodes

Patient Preparation

Anesthesia

Percutaneous RFA can be performed with local anesthesia and mild sedation. Deep sedation or general anesthesia can also be used. The modality of anesthesia depends on the patient's choice and the operator's preferences. For more information, see Local Anesthetic Agents, Infiltrative Administration and Procedural Sedation.

In a day-case setting, the local anesthetic is injected into the site where the skin incision is planned, and the patient is sedated by an intravenous injection. The patient is often able to go home the same day. If general anesthesia is not used, discomfort or pain may be felt while the area is being ablated. Day-case treatments for RFA are becoming more common.

Positioning

This procedure has no set patient positioning. Positioning depends upon the modality being used, the site of the lesion, the nature of the anesthesia, and the preferences of the operator and patient. The patient should be as comfortable as possible without compromise of the operator’s ability to adequately view and treat the lesion.

 

Technique

Approach Considerations

In radiofrequency (RF) ablation (RFA), the heat is created from electrical energy. The heat is generated at a specific target from the frictional heat created by rapidly vibrating adjacent cells. The end point that defines adequate necrosis can be based on either temperature or impedance, depending on the needle manufacturer.

During an RFA procedure, an ablation needle is placed directly into the target tissue. One or more electrodes are deployed from the end of the needle into the tissue. The generator is turned on, and a target temperature is set. The RF energy flows through the electrodes and causes ionic agitation. This agitation and friction of ions creates heat, and once sufficient temperatures have been reached, the heat kills the target tissue.

Tiny thermometers (thermocouples) incorporated into the tips of the electrodes allow continuous monitoring of tissue temperatures. Power is automatically adjusted so that the target temperatures remain constant. As tissue temperature increases above 50ºC, cell protein is permanently damaged and coagulation necrosis starts. Above 60ºC, cell death occurs almost instantly. Approximately 15-30 minutes are required to perform a 3- to 5-cm ablation.

Ultrasonography is typically used to monitor the treatment process for increased echogenicity. This increase in echogenicity corresponds to the formation of tissue and water vapor bubbles from the treated tissue and is used as a rough estimate of the size of the ablation site. Multiple ablations can be overlapped to decrease the chance of local tumor recurrence.

The size of the ablated area is determined largely by the size of the electrode needle, the temperature of the tissue, and the duration of time the energy is applied. A sharp boundary separates dead tissue and unaffected surrounding tissue.

The above principles of RFA are common to most needle systems. Different types of needles and techniques necessitate some differences of approach.

Percutaneous Radiofrequency Ablation of Tumor

Multiple array electrode technique

Multiple curved, retractable electrodes are kept inside the needle until its tip is positioned within a tumor. When the needle tip is properly positioned, a plunger on the hub of the needle is advanced so that the electrodes extend from the tip. When fully extended, these electrodes resemble an open umbrella.

Multiple electrode tips of an expanding electrode are active. This results in more homogenous heat distribution within the tumor and creates a reproducible sphere of ablation every time. In addition to the more even distribution of heat, the expanding electrodes have other safety features. The hooks of the electrode are fixed within the liver tissue when deployed, so that no needle movement is possible during RFA. Also, no electrode cooling is required during ablation, making the procedure easier and quicker.

Multiple electrodes seem to be superior to single electrodes with respect to the local recurrence rate for tumors between 3 and 5 cm.[40]

An important advance in RF energy deposition was achieved with the development of internally cooled RF electrodes. These 14- to 18-gauge electrodes have an internal lumen through which chilled perfusate is circulated during RF application.[41]  By cooling the electrode tip during the application of RF energy, these electrodes prevent charring and vaporization and are capable of producing lesions of greater dimension, which assists in complete tumor destruction. This technique also enables greater generator power to be administered with less risk of tissue charring.

Bipolar electrode technique

With the bipolar electrode technique, the current returns to the generator through the electrode. This eliminates the need to have coupling pads applied to the patient’s thighs. This system was originally designed to use three separate electrodes, placed in close proximity to each other and adjacent to the tumor. Simultaneous application of three applicators is believed to achieve larger volumes of ablation than the use of three consecutively overlapped ablations; it also significantly reduces the time needed to perform the ablation.

Saline-enhanced radiofrequency ablation

RFA may be performed with saline enhancement. Hypertonic saline is injected into the tumor through a side port on the shaft of the electrode before the ablation is started. The aim is to increase ionicity and, therefore, conduction within the tumor, thereby increasing the volume of the ablation.[40] Tiny channels within the electrodes can be used to infuse very small volumes of saline into the tumor as it is being ablated. Again, the goal is not to enhance conductivity directly but to prevent desiccation and charring of the tumor that would otherwise prevent conductivity and limit the ablation volume.

The unpredictability of saline perfusion in scirrhous colorectal liver metastases makes it unsafe for these lesions. However, encapsulated hepatocellular carcinoma (HCC) can become uniformly perfused without the risk of saline escaping into surrounding tissue, thus allowing ablation diameters of 6-7 cm. RFA using multiple wet electrodes shows promise as an effective method for treating inoperable HCC, especially in cases with well-preserved liver function.

Complications

Many studies have confirmed that RFA is a relatively low-risk procedure with low morbidity and mortality.[42] Few complications are associated with RFA.

Numerous factors are thought to be related to causing major complications; these factors include tumor size, number of ablation sessions, electrode type (single or cluster), and operator experience. One large study from Italy that included 41 centers showed that an increased number of RF sessions was related to a higher rate of major complications with no significant relation to tumor size or electrode type.[43]

Patients can experience discomfort immediately after the procedure; this normally settles with simple analgesia. The patient may also experience delayed pain as a part of postablation syndrome.

Postablation syndrome is a common phenomenon after RFA of solid abdominal tumors,[44] occurring in approximately one third of patients. The symptoms of postablation syndrome are flulike and include low-grade fever, delayed pain, malaise, myalgia, nausea, and vomiting. Patients should be informed about postablation syndrome and its self-limiting nature before the procedure. Most patients should be able to resume normal activity in 7-10 days.

The incidence of other complications is lower than 5%. Possible complications include the following:

  • Shoulder pain
  • Cholecystitis (normally subsides after few weeks)
  • Damage to the bile ducts, resulting in biliary obstruction
  • Damage to the bowel
  • Bleeding
  • Capsular hematoma
  • Hemoperitoneum
  • Hemothorax/hydrothorax
  • Pleural effusion
  • Intraperitoneal bleeding or ascites
  • Hemobilia
  • Infection and portal thrombosis
  • Liver abscess
  • Needle tract seeding - This is recognized as a long-term complication of RFA; it occurs mainly in lesions close to the surface or capsule of the liver
  • Collateral damage to proximal vital organs - The predictable nature of RFA generally prevents this complication
  • Self-limiting subcutaneous cellulitis

Livraghi et al found the incidence of major complications (eg, peritoneal hemorrhage, neoplastic seeding, intrahepatic abscesses, and intestinal perforation) to be 2.2% in 3554 treated lesions.[43] The incidence of minor complications was 5%, and the mortality was 0.3%.[43] Giorgio et al reported a study of 375 ablation sessions; major complications were seen in 0.9% of patients.[45] In this study, the mortality was also reported as 0.3%.[45]

Studies have shown that life-threatening acute liver failure can be considered a rare possible complication of RFA. Postablation survival depends upon Child classification, tumor multiplicity, and etiology of the HCC. Studies show that patients with HCCs that developed after viral cirrhosis had a worse prognosis than those with HCCs that occurred after alcoholic cirrhosis.[46]

Postprocedural Follow-up Imaging

RFA is usually performed in specialist centers. Radiologists and other clinicians who do not normally deal with such cases must be aware of the different aspects of post-RFA appearances, especially in view of likely recurrence. Follow-up imaging may include the use of computed tomography (CT), ultrasonography, or magnetic resonance imaging (MRI), or positron emission tomography (PET).

Contrast-enhanced computed tomography

After RFA, patient follow-up normally includes contrast-enhanced CT (CECT). At the authors’ center, a post-RFA CT study is followed by a additional study 3 months later. The usual protocol on a multidetector CT consists of precontrast and dual-phase postcontrast helical scanning. (See the images below.)

CT appearance of a liver lesion before radiofreque CT appearance of a liver lesion before radiofrequency ablation.
CT appearance of a liver lesion after radiofrequen CT appearance of a liver lesion after radiofrequency ablation.

Perihepatic collections and basal consolidation with pleural effusion are common, normal posttreatment changes. Intraperitoneal free fluid may also be seen; this normally resolves within a few days.[19] Iatrogenic arterioportal shunting and small intralesional air pockets are also seen frequently at immediate follow-up CT.[47] These usually settle within 1 month after the procedure.

A hypervascular area around the ablation, which represents increased arterial perfusion and possible inflammatory reaction after RFA, is the most common finding in the immediate postablation period.[48] In one study, this was noted in approximately 90% of patients in the first month and in more than 50% of cases between 1-3 months.[49]

A lesion with low attenuation and no enhancement after contrast with or without hyperattenuating rim shows a successful ablation.[48] In contrast, nodular and thick enhancement represents a tumor recurrence.[50] Another study indicated that lesion shape and non-enhanced CT attenuation are not significant parameters to differentiate between successfully and unsuccessfully treated lesions.[51] On the other hand, increase in lesion size and nodular enhancement pattern have significant relation to treatment failure.

Catalano et al described four different helical CT patterns of recurrence post RFA, as follows[52] :

  • Enhancing tissue within the edge of the ablated nodule (ingrowth)
  • Enhancing tissue around the treated nodule but continuously to its border (outgrowth)
  • Enhancing tissue within the same segment of the treated nodule on arterial phase images (spread)
  • Enhancing tissue within different segments from the treated nodule on arterial phase images (progression)

The postablation area is generally larger than the actual tumor size, for obvious reasons. An ablation area that is smaller than the tumor should be closely followed.[47] The ablated area gradually decreases in size but may also remain stable over the course of time.

Curvilinear calcification at the edge of the ablated area and fat between the ablated zone and normal parenchyma may also be seen occasionally.[19]

Ultrasonography

Grayscale

Ultrasonographic findings post RFA are variable and may show echo-poor, echogenic, or mixed appearance. (See the image below.) Grayscale ultrasonography alone is not a definite follow-up investigation and cannot differentiate between residual tumor and necrotic tissue.[47]

Ultrasound image of liver after radiofrequency abl Ultrasound image of liver after radiofrequency ablation.

Contrast-enhanced

Studies suggest that preablation use of contrast-enhanced ultrasonography (CEUS), in addition to CECT or MRI, for appropriate selection of patients improves the outcome in terms of tumor progression and efficacy of RFA therapy.[53, 54]

In images visible on ultrasonography, CEUS can be valuable post RFA as compared with CECT and MRI in terms of rapidity and cost-effectiveness. This is so because CEUS can be performed immediately after the procedure without exposing the patient to radiation and because an additional treatment can be performed in the same session.[55]

CEUS has improved patient follow-up and can provide information regarding ablation similar to that obtained with CECT.[56]  A study by Brünn et al suggested that post-RFA ablation defects tend to appear smaller on CEUS than on CECT.[57]

CEUS is more useful in known ablation zones because it has a low sensitivity in identifying the safety margin and provides incomplete coverage of the liver in patients who are at high risk of developing new tumor in the other parts of the liver.[58, 19]

Magnetic resonance imaging

Unenhanced or contrast-enhanced MRI can be used after RFA. A T1-weighted postcontrast study is more useful than the unenhanced study and is a valuable alternative to CECT.[59]

Successful ablation is denoted by no enhancement and a low signal on T2-weighted images, though increased signal on T2-weighted images does not always represent residual tumor.[60]

A study showed that MRI may have an advantage over CT in detecting early regrowth.[61] In this study, 2 of 9 local regrowths were depicted only on T2-weighted images, suggesting that MRI is a more useful sequence.

Although equally efficacious in comparison to a good CECT study, MRI is mostly used as a post-RFA problem-solving tool at present. Some studies have suggested possible use of diffusion-weighted MRI for evaluating effective treatment and recurrence.[62]

Positron emission tomography

Preliminary results from one study suggested that after RFA in patients with liver metastasis, fluorodeoxyglucose (FDG) PET-CT may detect relapse and treatment failure earlier than multidetector CT (MDCT).[63] In this study, 7 cases showed the presence of local recurrence earlier than MDCT.

Initial results of another study showed that PET-CT was significantly better than PET alone for detecting local tumor progression, whereas no significant difference was revealed between MRI and PET-CT.[64] Donckier et al showed in a study of 28 lesions that FDG-PET recognizes incomplete tumor ablation earlier than does CT.[65] This study found PET-CT to be accurate in monitoring the efficacy of RFA for treatment of liver metastases.

Further studies in a larger cohort of patients are required to establish the role of PET-CT in patients with liver metastasis who have undergone RFA.