Radiofrequency thermal ablation of liver tumors

Review

Radiofrequency Thermal Ablation ofLiver Tumors

Hyunchul Rhim, MD,* Gerald D. Dodd III, MD

Department of Radiology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive,San Antonio, Texas 78284-7800

Received 10 September 1998; accepted 24 November 1998

ABSTRACT: Chemotherapy and radiation therapy areineffective against primary and secondary malignanthepatic tumors. Surgical resection has been consid-ered the only potentially curative option, but few pa-tients with hepatic tumors are candidates for surgery.Recent results suggest that radiofrequency thermalablation may be an effective, minimally invasive tech-nique for treating malignant hepatic tumors. Sonog-raphy is the primary technique for guiding percutane-ous ablative procedures. We review the currentresearch and clinical experience with radiofrequencythermal ablation for treating malignant hepatic tu-mors. © 1999 John Wiley & Sons, Inc. J Clin Ultra-sound 27:221–229, 1999.

Keywords: liver neoplasms; interventional proce-dures; radiofrequency ablation; ultrasonography,guidance

Primary and secondary malignant hepatic tu-mors are some of the most common malignant

tumors in the world. Unfortunately, conventionaltherapies such as chemotherapy and radiationtherapy are ineffective against these tumors. Sur-gical resection has been considered the only po-tentially curative option, but few patients withhepatic tumors are surgical candidates.1–3 Recentresults suggest that several minimally invasivetreatment techniques are effective for treatingprimary and secondary malignant hepatic tumorsand may replace surgical resection in the fu-ture.4,5 These minimally invasive techniques in-clude cryoablation, percutaneous ethanol injec-tion, and interstitial radiofrequency (RF),

microwave, and laser ablation.6–10 The ablationtechniques are based on the ability to insert anelectrode or needle into a tumor under imagingguidance. Sonography plays the primary role inguiding electrode insertion by providing real-timemonitoring of the liver tumor being treated. Ofthe ablation techniques, RF ablation is one of themost promising.11–17 This review presents thecurrent research and clinical experience with RFtechniques for treating primary and secondarymalignant hepatic tumors.

BACKGROUND

The first experiment in RF thermal ablation ofliving tissue is credited to d’Arsonval, who in 1868demonstrated that an alternating electric currentgreater than 10 kHz could pass through livingtissue without causing neuromuscular excita-tion.18 Since then, RF thermal techniques havegained acceptance as a standard method for mak-ing well-controlled thermal lesions in the fields ofneurology and cardiology.19,20 However, until re-cently, the existing technology was inadequate forthe ablation of any but the most superficial tis-sues. In the late 1980s, modifications in the tech-nology enabled the creation of focal thermal inju-ries deep inside the body. The first publicationson the use of RF thermal ablation for the creationof deep thermal injuries in the liver were pub-lished in 1990 by Rossi et al21 and McGahan etal.22 In their publications, the authors provedthat deep thermal injuries could be created by RFthermal ablation without damaging interveningtissues. Since these publications, numerous ex-perimental and clinical studies have demon-strated the utility of this technique in treating

Correspondence to: G. D. Dodd III*Present address: Department of Diagnostic Radiology,Hanyang University Hospital, Seoul 133-792, South Korea

© 1999 John Wiley & Sons, Inc. CCC 0091-2751/99/050221-09

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hepatic tumors. Many different RF ablation sys-tems have been tested, including systems withmonopolar and bipolar electrodes, multipolarelectrodes, cooled-tip electrodes, and expandableelectrodes with multiple prongs.23–30 The advan-tages and disadvantages of each of these tech-niques are still being debated.

RADIOFREQUENCY MECHANISM

The so-called RF thermal ablation lesion is actu-ally caused by an alternating electric current op-erated in the range of RF waves (460 kHz) ratherthan by actual RF waves. The thermal ablationresults from the electric current agitating the ionsin the tissue surrounding the electrodes. The ionicagitation causes frictional heat that is distributedby conduction into the adjacent tissues. Theneedle electrode itself does not become hot. Theionic agitation and subsequent heat are directlyrelated to the intensity and duration of the alter-nating current. The heat desiccates the tissue andleads to localized coagulative necrosis.31 With ex-isting technology, lesions up to approximately 3.5cm in diameter can be produced by a single abla-tion.

EQUIPMENT

Currently, 3 primary RF devices are commer-cially marketed in the United States. All of themfunction on the same basic principles. The differ-ences among the units are variations in electrodedesign and generator power. The device withwhich we are most familiar is manufactured byRITA Medical Systems (Mountain View, CA).This device consists of a 50-W alternating electriccurrent generator and a 15-gauge needle elec-trode (Figures 1A and 1B). The needle electrodehas a movable hub that advances and retracts 4curved electrodes from the tip of the needle. Eachcurved electrode contains a thermocouple at itstip that registers the temperature of the heatedtissue. When deployed, the needle electrode re-sembles a 4-pronged fishing hook. The diameterof the fully deployed opposing curved prongs is3 cm.

The other 2 RF ablation devices are manufac-tured by Radionics (Burlington, MA) and Radio-therapeutics (Mountain View, CA). The Radionicsdevice consists of a straight-tip internally cooledneedle electrode (Figure 1C). The tip of the needleis cooled by perfusing its inner chamber withchilled saline. Cooling the tip of the needle is be-lieved to prevent charring of the adjacent tissuesand to increase the size of the thermal injury.

This needle is coupled with a 100–200-W alter-nating electric current generator. The device canbe operated with a single electrode or up to 3 elec-trodes placed in a triangular configuration, ap-proximately 1 cm apart from each other. The3-needle configuration is believed to enhance thesize of the thermal injury, with lesions up to 4–5cm reported.24,27

The Radiotherapeutics device, similar to theRITA device, consists of a needle with a movablehub that deploys 10 curved prongs from the nee-dle’s tip (Figure 1D). The needle is coupled to a90-W alternating electric current generator. Themultiple prongs are reported to produce a moreuniform spherical injury than devices with fewerprongs produce.

The RITA device and the Radiotherapeutics de-vice differ in their operational theories. The cre-ation of the thermal injury using the RITA deviceis monitored by recording the temperature pro-duced in the heated tissues. The Radiotherapeu-tics device relies solely on impedance to gauge theextent of the thermal injury produced. Potentialdifferences in the size and configuration of thethermal injury produced by the 3 RF devices istheoretical because no comparison data are avail-able.

INDICATIONS

Most advocates of RF thermal ablation of hepatictumors limit the treatment to patients who arenot considered candidates for surgery. Nonethe-less, the types of lesions being treated by RF ther-mal ablation are similar to those being treated bysurgical resection; the most common are hepato-cellular carcinoma and metastases from colon car-cinoma. The ideal lesions for thermal ablation aresmaller than 5 cm in diameter and preferablysmaller than 3 cm in diameter. The size limitationis based on the size of the thermal injury that canbe produced by a single ablation. Although largerlesions can be treated, the task is much more dif-ficult because multiple overlapping ablationsmust be performed to ablate the tumor com-pletely. Furthermore, the chance of an incompleteablation increases with larger tumors.

Most physicians limit this treatment to adultswith 4 or fewer primary or secondary malignanthepatic tumors and no evidence of extrahepatictumors. Exclusion criteria include severe debili-tation, active infection, uncorrectable coagulopa-thy, and pregnancy.

TECHNIQUE

RF thermal ablation is performed primarily byphysicians in 2 specialties, radiology and surgery.

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222 JOURNAL OF CLINICAL ULTRASOUND

Most radiologists perform the technique percuta-neously, whereas most surgeons perform it lapa-roscopically or during laparotomy. The laparo-scopic and open surgical techniques differ fromthe percutaneous approach only by the degree ofhepatic exposure. The following discussion fo-cuses on the percutaneous technique.

We perform percutaneous RF thermal ablationusing local anesthesia and conscious sedation. Wehave an anesthesiologist administer the conscioussedation so that we can focus on the ablation pro-cess. Our anesthesiologists use short-acting intra-venous agents such as remifentanil (Ultiva; Glaxo

Wellcome, Kalamazoo, MI) and propofol (Di-privan; Zeneca Pharmaceuticals, Wilmington,DE) because they induce fairly deep sedation andanalgesia but patients recover from the effectsquickly.

Sonography is used to localize the lesion to betreated. The skin is sterilely prepared anddraped, and the probe is covered with a sterilecover. The site of the needle puncture is chosen,and a local anesthetic is administered. A smallnick is made in the skin to facilitate passage ofthe needle. The initial needle placement is per-formed under local anesthetic alone to ensure

FIGURE 1. Equipment used for radiofrequency thermal ablation. (A) A 50-W alternating current (460 kHz) generator from RITA Medical Systemshas displays for the temperature of each prong, unit wattage, and total energy emitted; a countdown timer; and an impedance gauge. (B) RITAneedle electrode with 4 retractable curved electrodes that when fully deployed resemble a 4-pronged fishing hook. (C) Radionics generator andcooled-tip needle electrode. (D) Radiotherapeutics needle electrode with 10 retractable curved electrodes. (Figures 1A and 1B reprinted from DoddGD, Halff GA, Rhim HC. Thermal ablation of hepatic tumors by radiofrequency, microwave, and laser therapy. In: Clavien D-A, editor. Liver cancer:current and emerging therapies. Malden, MA: Blackwell Science, 1999. Reprinted by permission of Blackwell Science, Inc.)

RADIOFREQUENCY THERMAL ABLATION OF LIVER TUMORS

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good respiratory compliance. The initial needle/probe placement is performed through a needleguide attached to the ultrasound probe. Once theneedle is localized in the general vicinity of thetumor, the needle is detached from the guide, andthe needle tip is placed into the desired portion ofthe tumor using a freehand technique. Once theneedle position is satisfactory, the prongs are par-tially deployed, and the patient is given intrave-nous sedation. After the sedation has taken effect,the ablation is begun. The ablation is started withthe power setting at 25 W, and the setting is au-tomatically advanced to 50 W over about 30 sec-onds. As the temperature at the tips of the de-ployed prongs exceeds 95°C, the prongs are slowlydeployed completely while the temperature ismaintained at greater than 95°C. Once full de-ployment has been achieved, the temperature iskept between 95°C and 110°C for 6 minutes.

The goal of RF thermal ablation using any ofthe existing systems is to kill all of the tumor anda circumferential cuff of normal liver surroundingthe tumor to ensure an adequate tumor-free mar-gin. Based on prior surgical experience, the cuff ofablated normal liver tissue should be approxi-mately 1 cm thick. Obviously, if the tumor is sub-capsular, a margin cannot be created along thefree edge of the liver. For tumors less than 3 cm indiameter, 1 or 2 overlapping ablations are per-formed. For lesions 3–4 cm in diameter, a mini-mum of 6 overlapping ablations are performed(Figure 2). For tumors greater than 4 cm, mul-tiple overlapping ablations are created in a cylin-drical fashion until all of the tumor has been ab-lated.

When ablating small or large tumors, we at-tempt to perform the entire ablation through asingle needle puncture. The position of the needlewithin a tumor is adjusted without removing theneedle from the liver completely. The number ofcapsular penetrations is limited to minimize therisk of bleeding. The risk of bleeding is furtherdiminished by cauterization of the needle trackwhen the needle is withdrawn from the liver (Fig-ure 3). To cauterize the needle track, the needle iswithdrawn until the tip is 2 cm deep to the livercapsule. The prongs are not deployed. The gen-erator is turned on at a power setting of 25 Wuntil the impedance rises sharply and the unitshuts off.

Sonography is the most common technique forguiding the ablative process.32 During an abla-tion, numerous microbubbles are created in theheated tissue. Although these microbubbles varyin intensity from ablation to ablation, they arevisible by sonography and thus serve as a roughguide to the area of the thermal injury created(Figure 3B). However, because the exact marginof thermal injury is poorly defined, a very system-atic approach to the ablation must be used. If anyportion of the tumor is missed, recurrence at thetumor margin is inevitable. Because MRI guid-ance may provide a more accurate assessment ofthe extent of the ablated tissue, some centers arepromoting it as the guidance technique ofchoice.33,34 The advantages of sonographic overMRI guidance include shorter procedure time,real-time visualization, and utilization of less ex-pensive equipment. However, comparative stud-ies will need to be performed to determine wheth-

FIGURE 2. Treatment strategy for lesions 3–4 cm in diameter requires 6 overlapping ablations. Four ablationsare performed in the x–y plane and 2 are performed along the z axis. All ablations are positioned to touch atthe center of the tumor. If placed correctly, the ablations create an inner spherical injury that measuresapproximately 4 cm in diameter.

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er there is any significant difference in theoutcome of patients who undergo RF thermal ab-lation with MRI versus sonographic guidance.

Although sonography is the primary techniquefor guiding thermal ablation, it is not particularlyuseful for assessing the completeness of the abla-tion or detecting tumor recurrence.15–17 We usedynamic contrast-enhanced helical CT for thesepurposes (Figures 4 and 5). We routinely performhelical CT within 2 hours of the ablation to assessthe completeness of the ablation and to look forpossible complications. If the immediate post-treatment CT scans show obvious residual tumor,the patient is scheduled for a repeat ablationwithin 1 week. After each ablative session, ourpatients are observed for 4–6 hours in the outpa-tient recovery area. If stable and without signifi-cant pain, they are discharged on the same day asthe procedure. All patients return 1 month after

the ablation for repeat CT to assess the complete-ness of the ablation and to look for new tumor. Ifthere is no evidence of residual or recurrent tu-mor, the patient is followed at 3-month intervalsby repeat CT. If at any time recurrent tumor isdetected, the patient is contacted and scheduledfor reablation.

The interpretation of the follow-up CT scansrequires experience to prevent both overdiagnosisand underdiagnosis of residual or recurrent tu-mor. The ablation process causes a hyperemic re-sponse in the liver parenchyma surrounding theablation site.13 This hyperemia prevents an accu-rate assessment of the completeness of the abla-tion in the early post-ablation period (Figure 4B).The hyperemia usually resolves within 1 monthafter the procedure. After this time, persistent ornew peritumoral hyperemia is considered an in-dication of recurrent tumor. Recurrent hypovas-

FIGURE 3. Use of sonography to guide and monitor the radiofre-quency thermal ablation procedure. (A) Pretreatment sonogramshows a hypoechoic hepatocellular carcinoma (arrowheads) in theright lobe of the liver. (B) During the ablation, the echogenicity of thetumor is increased by the presence of microbubbles (arrowheads). (C)

After the procedure, the needle track is cauterized (arrowheads) toprevent bleeding.


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cular tumors such as colon carcinoma are de-tected as an enlargement of the ablated area, asatellite nodule in the margin of the treated area(Figure 5C), or a subtle double-density halo de-veloping around the margins of the treated area.All areas suspicious for tumor recurrence shouldbe assessed by percutaneous biopsy. The goal offollow-up after ablation should be the early detec-tion and treatment of all new tumors, unless theextent of tumor is overwhelming. Patients whodevelop tumors outside the liver are no longerconsidered candidates for repeat ablations of livertumors unless the extrahepatic disease can be re-sected.

RESULTS

Since 1996, 5 clinical studies detailing the out-come of RF thermal ablation of malignant hepatictumors have been reported. Rossi et al13 reportedtheir 7-year experience with RF thermal ablationwith mono- or bipolar electrodes in 50 patientswith hepatocellular carcinoma or hepatic metas-tases. The reported overall survival rates for pa-tients with hepatocellular carcinoma were 94%,86%, 68%, and 40% at 1, 2, 3, and 5 years, respec-tively. However, the outcomes in patients withhepatic metastases were much less promising,with well over 50% of patients experiencing tu-mor recurrence within 1 year. The same groupalso reported their experience with the RITA

needle.15 Contrasting this needle with the mono-and bipolar electrode devices used in their earlierstudy, they found that use of the RITA needlemade it possible to treat the same size nodules infewer sessions. Patient outcome, however, did notappear to differ with the type of electrode deviceused. Livraghi et al12 reported their experienceusing the cooled-tip needle (Radionics) to treat atotal of 24 nodules in patients with liver metas-tases. At 6 months, 52% of the treated tumorswere completely necrotic. Solbiati et al11 reportedno evidence of local tumor growth in 67% of 31ablated metastatic tumor nodules less than 3 cmin diameter. Shortly thereafter, this group re-ported that 94% of their patients with hepatic me-tastases treated using the cooled-tip needle werealive at 12 months, with 50% appearing to be dis-ease-free.17

To date, we have used RF thermal ablation totreat 52 patients with hepatic tumors at The Uni-versity of Texas Health Science Center at San An-tonio. Forty-four of these patients were treated inclinical trials, and 8 were treated outside of clini-cal trials. We have sufficient follow-up (mean, 8months) for 42 patients to make a preliminarystatement regarding our results. Of these 42 pa-tients, 25 had hepatocellular carcinomas and 17had hepatic metastases, the majority of whichwere from colon carcinomas. The 42 patients hada total of 72 tumor nodules with a mean diameterof 2.7 cm. The treatment of these patients re-

FIGURE 4. (A) CT scan before ablation shows a hypervascular metastatic tumor (arrowhead). (B) The tumor became avascular (arrowhead) on theCT scan taken immediately after ablation. The ablation was thus deemed complete. Note the prominent peritumoral hyperemia around the treatedarea (arrow).

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quired 71 separate sessions and a total of 364individual ablations. Sixty-seven of the sessionswere performed percutaneously, and 4 were per-formed intraoperatively. The mean proceduraltime per session was 62 minutes. Follow-up CTscans showed complete ablation of 50 nodules(69%), incomplete ablation of 13 nodules (18%),and complete ablation with recurrence of 9 nod-ules (13%) (Figures 4 and 5). To date, there hasbeen no significant difference in the rate of com-plete ablation by tumor size or type. We have seenonly 4 major complications caused by the proce-

dure: hepatic bleed in 2 patients (both recoveredfully), tumor seeding along the needle track in 1patient with pancreatic carcinoma, and diaphrag-matic thermal injury that caused shoulder painfor 3 months after the procedure in 1 patient.

ADVANTAGES

RF thermal ablation has several advantages overother therapies for primary and secondary malig-nant hepatic tumors. As a percutaneous proce-dure, RF thermal ablation can be performed on an

FIGURE 5. (A) CT scan before ablation shows a hypovascular metastatic tumor (arrowhead). (B) The tumor became avascular (arrowhead) 1 monthafter ablation. The ablation was thus deemed complete. (C) However, the follow-up CT scan at 3 months shows recurrence (black arrowhead) atthe treatment margin adjacent to the involuting area of tumor (white arrowhead). (D) The recurrent tumor became avascular (arrowheads) afterrepeat ablation.


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outpatient basis using conscious sedation. As aresult, patients are not subjected to the attendantmorbidity of hepatic resection or cryosurgery.1–5

If tumor recurs at the treatment margin or a newtumor develops elsewhere in the liver, RF ther-mal ablation can be repeated. Compared with per-cutaneous ethanol injection,7 RF thermal abla-tion requires fewer treatment sessions to ablate atumor completely.15 For example, most tumorssmaller than 3 cm in diameter can be treated byRF ablation in 1 or 2 sessions, whereas ethanolablation usually requires 3 or 4 sessions. RF ther-mal ablation also appears to be more effectivethan percutaneous ethanol injection as a treat-ment for metastatic hepatic tumors.35

LIMITATIONS

As with all procedures, the outcome of RF ther-mal ablation will be related to the skill of thephysician performing the procedure. Exact place-ment of the ablation needles requires consider-able skill and some degree of guesswork by eventhe most experienced interventional radiologist orsurgeon.32 Recurrence at the treatment marginmay result from an inability to adequately kill thehepatic parenchyma adjacent to the treated tu-mor(s). The abundant portal venous blood flowpresent in normal hepatic parenchyma acts as aheat sump, which makes the creation of a thermalinjury in normal liver more difficult than it is ineither primary or secondary malignant hepatictumors. Experimental studies have shown thatthe size of a hepatic thermal injury can be in-creased by reducing portal venous flow,16,30 andminimally invasive techniques of diminishing he-patic perfusion are being investigated.

OTHER INTERSTITIAL THERAPIES

Two other interstitial therapies used to treat he-patic tumors are microwave and laser ablation.8,9

To date, however, there are not enough data toenable comparison of the therapeutic efficacy ofthese ablative techniques with that of RF thermalablation. Several clinical studies of microwaveand laser ablation have been performed, but thetotal number of treated patients is small, the pa-tient populations are unmatched, and the resultsof the studies are uncertain because of the con-comitant use of other oncologic treatments.36,37

Nonetheless, it is apparent that each technique ishighly effective, at least for debulking small he-patic tumors. The ultimate success of these tech-niques as definitive ablative therapies will be

based on the ability of each to ablate all visibletumor and an adequate margin of normal tissue.

CONCLUSIONS

RF thermal ablation is a promising minimally in-vasive technique for the treatment of small pri-mary or secondary malignant hepatic tumors. Itis often used alone, but at some institutions, suchas ours, RF thermal ablation is used in conjunc-tion with surgical resection and/or chemotherapy.Long-term studies assessing the clinical outcomeof RF thermal ablation are ongoing. Large-scalerandomized clinical studies will be necessary todetermine the effectiveness of this therapy com-pared with microwave ablation, laser ablation,and conventional treatment techniques.

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Radiofrequency thermal ablation of liver tumors