REVIEW ARTICLE Radiofrequency Ablation: Review of ... · Chin J Radiol 2001; 26: 119-134 119 Radiofrequency Ablation: Review of Mechanism, Indications, Technique, and Results JER-SHYUNG

Chin J Radiol 2001; 26: 119-134 119

Radiofrequency Ablation: Review ofMechanism, Indications, Technique, andResultsJER-SHYUNG HUANG

1,2 DEBRA A GERVAIS3 PETER R MUELLER

3

Division of Abdominal Imaging1, Department of Radiology, Kaohsiung Veterans General Hospital, Taiwan, ROC.Department of Radiology2, National Yang-Ming University, Taiwan, ROC.Division of Abdominal Imaging and Interventional Radiology3, Department of Radiology, Massachusetts GeneralHospital, USA

Radiofrequency tissue ablation is a rapidlyevolving in situ tissue ablation technique andhas received increased attention in the past fewyears. The applications evolved from ablationof cardiac aberrant conduction fiber, to tumorablation in bone, liver, kidney, breast, brain,and lung. Among them, hepatic primary andsecondary tumor ablation is the most widelystudied subject. In this article, we review themechanism, procedure, results, and theprospects of this technique, with emphasis onhepatic tumor ablation.

Key words: Radiofrequency ablation, Livertumor, Interventional procedure.

Radiofrequency (RF) ablation is a rapidlyevolving minimally invasive technique thatprovides in situ tissue ablation for a variety ofbenign and focal malignant diseases. It was firstintroduced for the ablation of the neural tissue tocontrol pain or other neurologic disorders [1-4],and to ablate the aberrant neurofibril bundle insymptomatic cardiac arrhythmia [5-7]. Recently,RF ablation has been applied percutaneously,laparoscopically, or intraoperatively into thesuperficial or deep tissue to treat a variety ofneoplasms, such as osteoid osteoma [8-10],primary and metastatic liver tumor [11-13], renalcell carcinoma [14, 15], prostate cancer [16,17],breast cancer [18,19], and metastaticlymphadenopathy.

In this article, we review the mechanism,current research and applications, clinicalexperience, as well as the prospects, of RF intumor ablation.

MECHANISM AND PROBE DESIGNS

The concept of radiofrequency tumor ablationderives from the RF electrocautery device. In1891, d'Arsonval [20], showed that theradiofrequency range alternative current whenpassed through living tissue causes an elevation intissue temperature without causing neuromuscularexcitation. The observation inspired the laterdevelopment of surgical Bovie knife [21]. Thedevice consists of an alternating electric currentgenerator operated in the range of radiofrequency,a small knifelike electrode, and a large groundingpad. When the RF current flows through thetissue, driving the ions in the tissue electrolytes to

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Reprint requests to: Peter R Mueller, MD Address: 55 Fruit Street, Boston, MA 02114-2696 U.S.A.

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Figure 1. a. Magnified view of aRadionics Triple “cool tip” probe.The needle is designed as anenclosed diamond tip with a variable2.5 or 3 cm “working” tip (arrow). b.RITA probe (RITA medical system).c. LeVeen coaccess electrode,(RadioTherapeutics)

1a 1b

1c

move back and forth between the electrode andthe ground pads, which results in localizedfrictional heat surrounding the electrode and thegrounding pad [1]. The grounding pad acts as alarge dispersive electrode that allows the currentto pass freely through the patient withoutproducing any significant heat. At the electrodepoint, desiccation and charring of the superficialtissue occurs. With the tissue desiccation andcharring, the electrocautery controls hemorrhage.

When the electrode is inserted deep into thetissue, the emitted electric current agitates theregional ions, causing frictional heat that extendsto adjacent tissue by conduction. When the localheat reaches the temperature of 50˚C for morethan 3-6 minutes, intracellular proteindenaturation and melting of lipid bilayers resultsin coagulative necrosis [22,9]. However, toproduce the same coagulation in vivo, 58˚C isnecessary due to the tissue perfusion by vesselscarrying away the delivered heat [9, 23, 65].

In abdominal tumor ablation, the procedure isperformed by inserting a 14-21 gauge partially

insulating electrode into the tumor, with 1.5-3.5cm exposed tip length, percutaneously,laparoscopically, or intraoperatively, underimaging guidance (ultrasonography [US],computed tomography [CT], or magneticresonance imaging [MR]). A 460-500 kHzalternative RF current from the generator isconnected between the electrode probe and thedispersive grounding pads at the patient’s back orthighs. A thermocouple is embedded in theelectrode tip to continuously monitor the localtemperature (Fig 1)

The final size of the heat-ablated tissuedepends on the conductive heat emitted form thetissue, which is proportional to the square of theRF current, also known as the RF power density.The RF current density decreases in proportion tothe square of the distance from the electrode.Therefore, resistive heat decreases from theablation electrode with the distance to the fourthpower [24]. The tissue temperature falls rapidlywith increasing distance away from the electrode[27]. In theory, the RF method can be used to

create the precise tumor coagulation necrosis tomatch the extent of tumor. However, a significantlimitation to the RF application is the tissueimpedance. Increased generator power (in watts),exposure time or both, results in an increasedamount of delivered energy around the electrode.When the tissue temperature surrounding theelectrode increases to more than 100˚C, theimpedance also increases significantly because ofdesiccation, tissue boiling, and carbonizationaround the electrode tip. This leads to an abruptfall in lesion current, which results in no moreadditional tissue heating in the surrounding tissueoccurs. This is an important factor in lesion sizelimitation [28, 29]. A maximal transversediameter of 10-16 mm has been typically reportedusing a conventional straight probe [30-32]. Thelongitudinal dimension, however, simply dependson the length of the uninsulated part of theelectrode [30]. Unfortunately, the elongatedcylindrical volume of necrosis created by aconventional straight probe does not approximatethe spherical shape of most metastasis andprimary liver tumor. Multiple treatments areusually needed to achieve a complete tumornecrosis. This limitation increases the proceduretime in the ablation and also limits theapplication in larger tumors. To overcome thislimitation, many technical innovations have beendeveloped to achieve a larger tumor necrosis in asingle treatment session.

Pulsed RF Deposition

Goldberg et al [33] investigated methodsdeliver the RF energy in a pulsed algorithm ratherthan a continuous manner. An automated,

programmable algorithm for pulsed-RF depositionwas designed to permit high-current deposition byperiodically reducing current for 5-30 secondsduring RF application. It allows brief periods ofheat dissipation to prevent tissue vaporization andcarbonation and to increase the current densityand hence the volume of tissue necrosis. Theyshowed a variable peak current algorithm forpulsed-RF deposition could increase coagulationnecrosis diameter over other ablation strategies.A computer chip, with thermocouple embedded inthe exposed tip of the electrode, is now availableto monitor the impedance and temperature aroundthe electrode to control the period of RF pulsedapplication, to minimize tissue carbonization andachieving maximal volume of tissue necrosis.

Intraparenchymal Saline Injection During theRadio-frequency Tissue Ablation

Livraghi et al [34] described anintraparenchymal injection of a bolus of salinebefore RF application or continuously (1 mL/min)during RF application to increase the RF lesionsize. He explained the potential benefits of salineinjection including the enlarged effectiveelectrode surface by means of augmented tissuetonicity, local cooling effect to decrease the tissueimpedance, and direct effect of the heated salinethat diffuses into the tissue. Although the authorsachieved the lesion size up to 3.9 cm, it wasnoted that the necrosis was irregular in shape andthe lesion volume was difficult to predict [34].This method was not widely used by otherinvestigators. Despite this, Miao et al [61]reported a simultaneous internal-coolingperfusion (“cooled”) and interstitial hypertonic

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Figure 2. Recurrence of tumor afterAblation of metastatic colon cancer. a.Position of probes in a difficult lesionnear the vena cava b. Contrastenhanced CT scan 3 months aftertreatment demonstrates someenhancement (arrow) suggestingrecurrence of tumor.

2a 2b

saline infusion (wet) RF system to create an exvivo lesion of 6.6-cm hepatic lesion in liver. Noin vivo study was available.

Internally Cooled Electrode

The key factor that prevents the delivery of RFenergy is the high temperature around theelectrode, which causes tissue charring andvaporization. To control this, Lorentzen [24]designed a 14-gauge RF needle, through whichroom temperature cool water could be circulatedwithin the needle to prevent from tissue charring.This allowed a significant increase in the durationof ablation, which resulted in a significantincrease in the delivered energy and lesion sizewhen compared with the conventional needleelectrode. Goldberg et al [25] developed a 17-gauge needle with perfusion of the electrode tipusing 0 degree Celsius saline. Both energydeposition and coagulation necrosis were found tobe significantly greater in the internally cooledelectrode than conventional electrode. Using thistechnique, Goldberg’s group achieved in vivoliver lesions of 2.4 cm.

Multiprobe Array

Many multiprobe array designs of the electrodeare now available to increase the RF lesion size inevery single treatment session. Goldberg et al[26] developed a cluster array of three 17-guage,separate internally cooled electrodes equallyspaced 0.5 cm apart (Fig 1a) (Radionics,Burlington, Mass). In their study, a single 12-15-minute application of RF to an electrode clustercan induce 4.5-7.0 cm of coagulation necrosis incolorectal metastases, and 3.1 cm in vivo liver[26]. LeVeen [35] used a 14-guage insulated

cannula that contains 10-12 individual hook-shaped electrode arms (Fig 1c)(RadioTherapeutics, Sunnyvale, CA) deployed invivo porcine liver, to produce a 3.5 cm sphericalcoagulation necrosis by applying 80 W of powerfor 10-12 minutes. Siperstein et al [36] produced3.5 to 4 cm lesions in a porcine liver by applying30 to 50 W of power for 15 minutes to a 15-guage, four to nine-pronged umbrella needlesystem (Fig 1b) (RITA Medical System, MountainView, CA). In general, the maximal lesion thatcan be created in a single treatment is about 4 cmin diameter. To date, there have been no studiesthat document a definite advantage of one needledesign over the other.

All radiofrequency generators are operated at460-500 kHz at a power setting of 50-200 W. Thecost of the generator ranges from $12,000 to30,000. The needle electrodes cost $500-1,000per needle (non-reusable) [37].

RADIOFREQUENCY ABLATION OFHEPATIC MALIGNANCY

Surgical resection is considered the onlycurative therapy for malignant hepatic tumor, butfew patients with hepatic tumor are idealcandidates for surgery. Less than 10-15% ofpatients with liver-only solid tumor metastasesare candidates for resection [38, 39]. Many in-situtumor ablation modalities, including percutaneousethanol injection (PEI), transarterialchemoembolization, cryoablation, and manythermal energy resources such as radiofrequency(RF), Laser, and microwave, have shownpromising results in those patients who areineligible for surgery due to age, the extent of

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Figure 3. Schematic representation of volumetric approach to treat# a tumor. Multiple insertions need to be performedto insure that the total volume of the tumor is treated in a 3 dimensional framework. (courtesy of Dr. Dodd III, SanAntonio, USA)

disease, or surgical morbidity. PEI is easy, safe,inexpensive, and repeatable. However, it requiresmultiple sessions to treat even the smallest tumorand has been shown ineffective in liver metastasis[40, 41]. Chemoembolization appears to offer thebest hope of controlling tumors greater than 5 cmin diameter or more than four tumors in number.However, regional therapy is not as effective aslocalized high-energy devices in killingindividual tumors [37]. Cryoablation requires alaparotomy or laparoscopy with generalanesthesia. Consequently, it is substantially moreexpensive than a percutaneous procedure. Laserablation has the advantage of being fullycompatible with MR imaging, but produce asmaller size of ablation than RF. A single ablationtime required in microwave ablation is very short(<60 seconds), but the shape of necrosis isusually elliptical [42]. In two independent studyin 1990, McGahan et al [11] and Rossi et al [12]first reported the RF ablation for the treatment ofhepatic tumor. Overall, the interest andenthusiasm for radiofrequency thermal ablationhas far exceeded that for either microwave orlaser ablation [49].

Patient Selection and Procedure

Most investigators are limiting the applicationof RF procedure to patients with unresectableprimary or secondary hepatic metastasis, fewerthan 4 or 5 lesions and up to 5 cm in diameter,and no extrahepatic tumor [43, 27, 44]. Patientswith a coagulopathy are included if thecoagulopathy is correctable. Ablation of tumoradjacent to some vital structure needs carefulconsiderations. Tumor close to the large portal

triad can cause increased pain and poses the riskof damage to the associated bile ducts. Tumorsadjacent to the large blood vessels are moredifficult to treat because that the blood flow coolthe applied heat in the adjacent tumor (heat sinkeffect) (Fig 2). Some investigators use RFablation with a Pringle maneuver (temporaryinterrupting hepatic arterial and portal venousflow during the application of RF) during theoperation to decrease the amount of heat that is“stolen” by the vessels, and to create a largerzone of necrosis [27, 64]. Tumor adjacent to theGB and bowel loop imposes the risk of post RFcholecystitis and thermal injury of the bowel loop[45]. Ablation of tumors adjacent to thediaphragm and liver capsule will cause more painduring and after the procedure.

Preprocedural evaluation including image studyto exclude extrahepatic metastasis, hematologicaland liver function evaluation to excludecontraindications such as uncorrectedcoagulopathy and severe infection. Biopsy is donebefore the procedure also. All of the RF devicescan be used percutaneously, laparoscopically, orintraoperatively. Percutaneous procedure can beperformed on an outpatient basis with the use ofconscious sedation consisting of a combination oflocal (Xylocaine 2%), intravenous benzodiazepam(midazolam 1.0-2.5 mg), and opiate (Fentanyl 50-150 µ g) [46], or more potent and short-actingagent propofol [47]. Blood pressure, respiration,pulse, and electrocardiogram are monitoredcontinuously. To prevent infection, antibioticprophylaxis with cephalosporin is given in someinstitutions [48, 49].

Ultrasonography is the most common method

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Figure 4. Successful RF ablation of ahepatoma a. CT scan demonstrates asingle probe in a small hepatoma insegment 4 (arrow). b. CT scan 6months later demonstrates a 4 cmmargin of necrosis, easilyencompassing the tumor area with awide margin. Note the parenchymalscar adjacent to the necrotic tumor(arrow).

4a 4b

used to guide percutaneous radiofrequency tumorablation because of its real-time capabilities,vascular visualization, availability, and low cost.However, the primary disadvantage of sonographyis a limited ability to assess the effectiveness, andcompleteness of an ablation. Usually, the ablationprocess produces a dense echogenic response thatobscures the margins of the tumor being treated,particularly the posterior margins, and makes theelectrode position difficult to assess. Thus, whenmultiple placements of the RF needle electrode isneeded under US-guidance, the deep junction ofthe tumor and surrounding parenchyma should betreated first. The needle then can progressively bepulled back more superficially in a 2-cm intervals[27]. Both CT and MR imaging have beenreported to be more reliable in this regard [50]. Asingle ablation takes about 8-20 minutes to raisethe local tissue temperature to above 60-degreeCelsius. The goal of the thermal ablation is toburn the target lesion with the circumferentialadjacent 5-10 mm of normal liver parenchyma.Multiple overlapping ablations are oftennecessary to achieve a complete tumor ablation(Fig 3). To treat a lesion of 3 cm in diameter, atleast six overlapping ablations are needed tocover the tumor free margin [49]. On occasion,the lesion size created by RF is greater thanexpected. This is particularly true inhepatocellular carcinoma (Fig 4). It has beendescribed as “oven effect”, whereby cirrhoticliver surrounding individual HCC nodules act as athermal insulator that increases tissue heatingwithin the tumor during RF therapy [48, 40].

Unlike metastasis, in which a 5-10-mm rim ofnormal liver around the tumor must be treated(Fig 5), for nodular HCC, it is generally sufficientto treat just the tumor itself [40]. Thus, a well-capsulated nodular HCC may need fewerablations than a metastatic lesion of the same size(Fig 6).

The RF can also be applied laparoscopically orintraoperatively. A higher-frequency US probecan be used in both techniques, which allows amore precise determination of the extent andnumber of the tumors [51]. The other advantage isthe application of Pringle maneuver in theprocedure to increase the RF lesion size.However, unlike the percutaneous approach thatallows US probe and needle to be moved to anyposition of the upper abdomen for the best angleof approach, the laparoscopic placement of needleand US probe is limited by the existinglaparoscopic ports and can not be easily mastered[49]. The increased associated morbidity,mortality and cost are also drawbacks.

Images Follow up

Ultrasonography provides limited informationin the follow-up study of residual or recurrenttumor. Recent preliminary study with USmicrobubbles contrast agent have been reported[52, 53] with results only slightly less thanreported with CT. Contrast-enhanced CT is themost widely used technique in the follow upstudy after RF ablation. An immediate post-RFCT is usually performed for the effectiveness andpossible complications. However, the accuracy of

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Figure 5. Pre and post treatmentimages of a metastatic colon cancer toSegment 6. a. An irregular necroticlesion is noted. b. Large lesion createdby use of a “triple probe”. Note thatthe “treated area” is much larger thanthe original lesion, thus insuring a“safety margin” around the treatedarea.

5a 5b

the completeness assessment on the CT scantaken within one month after the RF may belimited because it is difficult to distinguish theenhancing residual or recurrent tumors from theablation-induced hyperemic rim around themargin of the ablated tissue. A follow-up CTperformed at 1 month after the procedure andthen at 3- month interval is feasible. Usually, therecurrent tumor shows focal, irregular area ofenhancement both in CT (Fig 7) and MR studies.A successfully treated tumor may shows stablelow-density area or progressive decrease in size(Fig 8). Recent studies with contrast-enhancedMR imaging report a correct diagnosis ofcomplete or partial tumor necrosis was made in

32 (86%) of the 37 patients with the use ofunenhanced and dynamic gadolinium-enhancedMR images. Hypointensity on T2-weightedimages and loss of enhancement on dynamic MRimages corresponded to completely necroticlesions in all patients [54]. Tumor markers suchas α -fetoprotein and carcinoembryonic antigenlevels before and every 3 months after RFablation may be helpful in assessing the subtleimage findings.

RESULTS

There are a number of published literatureavailable for the results of RF ablation of liver

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Figure 6. Successful treatment of hepatoma inSegment 7. a. Hypervascular hepatoma noted onarterial phase image. b. CT 4 months laterdemonstrates post treatment necrosis with noevidence of recurrence.

6a 6b

Table 1. Percutaneous RF treatment Liver Malignancy

ResearcherNo. of Patients

Tumor Average Average Mean FU Complete Electrode

(Tumors) size (cm) sessions (month) necrosis % typeLivraghi [40] 42(52) HCC 2.3 1.2 >4 90% ARossi [57] 23(26) HCC 2.5 1.5 10 92% BFrancica [55] 15(20) HCC 2.8 NA 15 90% ARossi [58] 39(41) HCC <3.5 3.3 22.6 95% Bde Baere [43] 47(88) Met 2.6 1.2 17.3 90% ARossi [57] 14(19) Met 2.5 1.3 12 93% BRossi [58] 11(13) Met <3.5 3.1 11 82% DSolbiati [59] 16(31) Met 1.5-7.5 4.7 18.1 58% DSolbiati [68] 29(44) Met 1.3-5.1 1.2 10.3 66% ALivraghi [34] 14(25) Met* 3.1 NA 6 52% E* With one case of cholangiocarcinomaA: cool-tip needle (Radionics)B: four-pronged umbrella needle (RITA)C: LeVeen needle (RadioTherapeutics)D: conventional straight needleE: conventional straight needle with intraparenchymal saline injectionP: percutaneous, L: laparoscopy, O: intraoperative

tumor [34, 44, 45, 51, 55-62]. As the RF is afairly new technique, long-term results have onlybegun to be available. Most of the reports shouldbe considered as preliminary reports of short-termefficacy. As the tumor characteristics, tumorbiology, and the histology of the surroundingliver parenchyma are quite different betweenhepatocellular carcinoma and hepatic metastasis,it is feasible to discuss the results according tothe tumor types and approaching methods. Inmost percutaneous series, complete necrosis canbe achieved in 90% of lesions in hepatocellularcarcinoma with mean size less than 3cm (Table

1). In these series, follow-up period was between6 to 23 months. Livraghi et al reported the onlylong-term results of RF ablations for medium-sized and large tumors. The results in 126medium-sized (3.1-5 cm) to large (5.1-9.5 cm)hepatoma (mean 5.4 cm) in 114 patientsdemonstrated that complete necrosis can beachieved in 60 lesions (47.6%) and nearlycomplete necrosis in 40 lesions (31.7%).

For metastatic liver tumors, complete necrosisvaries from 52 to 93% with mean follow-upperiod between 6 to 18.1 months (Table 1). Thesuccessful rate of RF ablation of HCC is higher

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Figure 7. Example of incompleteablation of a large metastatic coloncarcinoma. a. An irregular large lesionin segment 7 (arrow). b. Post ablationdemonstrates 90 % complete necrosis.There are still areas enhancing withcontrast that demonstrate incompletenecrosis (arrow).

7a 7b

Figure 8. Evolution and retraction of a treated colon carcinoma metastasis in segment 3 of the liver. a. Low densitynecrotic area after first treatment. b. CT scan 6 months later shows decrease in size of the lesion with no evidence ofenhancement. c. CT scan 2 years after first treatment demonstrating “scarring and retraction” in the area of treatment.The Patient was doing well clinically.

8a

8b

8c

than that of metastatic lesions. HCC necrosis ismore complete and uniform to the tumor shapedue to the “oven effect” [40, 48]. However, themargin of metastatic tumors is different, andmicroinvasion beyond the preoperative evaluationis common. Thus, a more aggressive ablation ofmetastatic tumor is required to minimize localtumor recurrence.

Some laparoscopic [36, 51, 63], somecombined percutaneous, laparoscopic andintraoperative [13, 27, 43, 62], or intraoperatively[60] RF ablation results had been reported (Table2). Among them, the larger series are those fromSiperstein et al [63], and Curley et al [13, 27].Siperstein et al [63] report their experience oflaparoscopic RF treatment of 43 patients with 170metastatic and 11 primary tumors. Tumorresorption in 156 (88%) of 178 lesions werereported with a mean follow up of 13.9 months.In a similar study of Curley et al. [27],radiofrequency ablation was used to treat 169tumors in 123 patients, including 48 patients withHCC and 75 with metastatic tumors. Of the 123patients, 92 (75%) were treated intraoperativelyand 31 (25%) were treated percutaneously. Alltumors were treated with LeVeen hooked-needleelectrodes, and a Pringle maneuver was used onall intraoperative cases. Overall, completenecrosis had occurred in 98% of the ablatedtumors at a median follow-up period of 15months, and 72% of the patients remained tumor-free during the same time. The authors did notanalyze the outcome difference in thepercutaneous and the intraoperative groups, nor

did they analyze the difference between theprimary and secondary tumor groups.

In the other report, Curley et al. [13] report theresult of RF ablation of 110 patients with 149HCC, including 76 patients with percutaneous, 31with intraoperative, and 3 with laparoscopicapproach. At a median follow-up period of 19months, the losal recurrence was noted in only 4(2.7%) of the 149 treated tumor. However,recurrence at other sites in liver was noted in 37(33.6%) cases.

Complications

Radiofrequency ablation of the liver isconsidered safe, with an extremely low majorcomplication rate observed by multiple groups.Livraghi et al. reports one mortality case of RF(0.8%), who developed Staphylococcus aureusperitonitis 3 days and died 8 days after theprocedure. Major complications that requiredsurgical, vascular or percutaneous interventioninclude major intraperitoneal hemorrhage (0.8%),hemothorax (2%) [40], liver abscess (6%) [43],bile leakage (3%) [57]. Minor complicationsinclude self-limited hemorrhage (1.8-8%) (Fig 9)[48], mild cholecystitis, pleural effusion,hemobilia, second degree skin burn due toinadequate ground surface or contact (3.7-10%)[26], and post-RF pain that required nonsteroidanalgesics for 2-4 days (2.6-4%). Many patientsexperienced intraprocedural pains in conscioussedation case, which is usually controllable.Treatment of peripherally located, subcapsulartumor are more likely to induce pain and

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Table 2. Surgical RF Treatment of Liver Malignancy

ResearcherNo. of Patients

Tumor ApproachMedian Tumor Mean FU Complete Electrode

(Tumors) size (cm) (months) necrosis % type

Curley [27] 123(169)Met(75)

P+O 3.4 15 98% CHCC(48)

Curley [13] 110(149) HCC P+L+O2.8 (P)

19 97% C4.6(L+O)de Baere [43] 21(33) Met O 1.3 12 94% A

Siperstein [63] 43(181)Met(170)

L NA 13.9 88% BHCC(11)

Jiao [62] 35Met(27)

P+O NA 8.5 69% AHCC(8)Elias [60] 7 Met O 1.1 2 100% AA: cool-tip needle (Radionics)B: four-pronged umbrella needle (RITA)C: LeVeen needle (RadioTherapeutics)D: conventional straight needleE: conventional straight needle with intraparenchymal saline injectionP: percutaneous, L: laparoscopy, O: intraoperative

discomfort [44, 48].There are only few reports mentioning the

delayed post-ablation fever that may be seen inother type of in site tumor ablation. According toMcGahan et al. [49], the typical presentationconsists of flulike symptoms (low-grade fever upto 38.8˚C accompanied by general malaise) thatbegin 3-5 days after the ablation and persists forapproximately 5 days. With large-volumeablations, the syndrome begins almostimmediately, causing fever as high as 39.4˚C,produces severe lethargy, and lasts for as long as2-3 weeks. Appropriate treatment of thesyndrome is primarily supportive. Fever up to38.8˚C for 5 days needs a culture to rule out aseptic condition [49].

In the majority of patients, the transaminaselevels may increase to two to seven times over

baseline during the first 3 days following therapy,but will return to baseline level in most cases by7 days [27, 48, 57].

Extrahepatic Tumor Ablation

A considerable amount of reports onextrahepatic tumor ablation have been published.Rosenthal et al [8-10] treated 18 patients withosteoid osteoma with an 18 gauge conventionalRF needle through the biopsy 15-gauge Ackermancoaxial needle. Symptoms were completelyrelieved in 16 (89%) of 18 patients. In onepatient, a second procedure was required for painrelief. All but two patients underwent treatmenton outpatient basis. No complication was noted.In a subsequent study [10], the author comparedthe result of operative treatment of 87 patents andpercutaneous RF ablation of 38 patients with

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Figure 9. Example of treatment of ahepatoma in segment 7 high in thedome of the liver with a triple probe,which was successful, but resulted in asmall perihepatic hematoma. a. CTscan with probe demonstrates thetreated area encompassing theprevious tumor. b. After theprocedure, an area of necrosis isvisualized (straight arrows). A smallperihepatic hematoma (curved arrow)is also noted.

9a 9b

Figure 10. Treatment of bone pain ina patient with colon cancer metastasisto the sacrum. A single probe is usedto ablation performed with carefulattention to the temperature. Afterseveral insertions, in many patients,pain can be relieved.

osteoid osteoma. The operation recurrence was9% after 2 year, but the patient required anaverage hospital stay of 5 days. The recurrencerate in the percutaneous group was 12% with anaverage hospital stay of 0.2 day. As there is nosignificant difference between the two treatmentswith regards to the rate of recurrence, the authorsconcluded that percutaneous method is preferablefor the treatment of extraspinal osteoid osteomabecause of less hospitalization, no complication,and rapid convalescence. Palliative treatment ofmetastatic bone tumor has also been tried (Fig10).

Zlotta et al [14] first report in vivo RF

treatment of three renal cell carcinomas in 2patients before nephrectomy. Extensive necrosisthrough the tumors was noted in the pathology.McGovern et al [66] reported a successful RFablation of a 3-cm renal cell carcinoma in an 84-year-old patient. Hall et al [67] reported asuccessful combined embolization of RF ablationof a 3-cm RCC in a poor surgical candidate due tochronic debilitating disease. Gervais et al [15]reported a larger series of treatment of 9 renalcell carcinomas (mean 3.3 cm ±1.1 cm) in 8patients. According to the tumor location, theRCC was classified as exophytic, parenchymal,central and mixed lesions (Fig 11). These patientsrequired a total of 24 treatments during 14sessions. At a mean follow-up period of 10.3months, 7 (78%) tumors were completely treated(Fig 12). The smaller and exophytic tumorsnecessitated fewer treatments than did the largercentral tumors (Fig 13).

Solbiati et al [68] performed PEI and RFablation for the treatment of parathyroidhyperplasia and secondary hyperparathyroidismusing US-guidance. As compared to the controlgroup that received PEI only, the combinedtreatment allowed less treatment sessions withfavorable clinical results. In the other study,Solbiati et al treated two recurrentsupraclavicular metastatic lymph nodes frompapillary thyroid cancer in one patient that was apoor candidate for surgery. Complete necrosis ofthe lymph nodes was noted at one-year follow up[69].

Dupuy et al [70] reported the experience of RF

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Figure 12. Successful treatment of renal cell carcinoma with RF ablation. a. Initial contrast enhanced CT demonstratesa slightly exophytic (mixed lesion). b. After initial treatment, the posterior half of the lesion still enhanced withcontrast, indicating viable tumor. c. CT scan after second treatment demonstrates complete treatment of the tumor.

12a 12b 12c

Figure 11. Classification of different appearances of renalcell carcinomas. The more “exophytic” the lesion thebetter the results and more likely the complete ablation.

ablation of 2 primary and 1 metastatic lungtumors, ranging from 2-5 cm in size. After RFablation, one patient showed residual tumor infollow up biopsy at 3 months; the second onedied of unknown cause, and the third one showedno evidence of metabolic activity at the RF lesionon a follow-up positron emission tomographyscan.

Future Strategies

Radiofrequency tumor ablation, especially forthe hepatic tumors, has been a promisingtechnique and can be a substitute for surgery inpatients not eligible for surgical treatments.However, despite the considerable progress thathas been made to date, a number of challengesremain for the future. The future strategiesinclude (a) increasing the volume of tissuedestroyed at a single treatment session (b) theintegration of RF ablation with the other in-sitetumor ablation techniques and (c) thedevelopment of more suitable and accurateimaging tests.

The key factor that limits the treatmentstrategies is the tissue volume that can bedestroyed in a single treatment. To date, thelargest range that can be ablated in a singletreatment is 3.5-4 cm [26, 35, 36]. To createtumor free margin of 5-10mm, a 3.25 cm lesionmay need up to six precisely overlapped 3-cmthermal spheres [49]. Creation of a larger volumeof tissue coagulation will ensure successfulablation of small tumors and allow us to treatpatients with larger tumors. In addition, as fewertreatments are needed for a given tumor size, the

technique would be less complex, the proceduretime can be shortened and the hemorrhagiccomplication would be decreased.

Aside from RF ablation, there are a lot of in-site tumor ablation techniques such as microwaveablation, laser ablation, cryoablation, ethanolinjection, and chemoembolization. Livraghi et al[40] compared the effectiveness of RF andpercutaneous ethanol injection (PEI) in thetreatment of small HCC. RF was shown to have ahigher rate of complete necrosis, fewer sessions,but higher complication than PEI. Morecomparative studies are needed to elucidate thecost-effectiveness of these minimally invasivetechniques for treating primary and secondarymalignant tumors. The combined treatment ofsome of these techniques may have somepromising effect in the future. For example, as theHCC receives most blood supply from the hepaticartery, the pre-RF chemoembolization of thehepatic artery may decrease the heat-sink effectin the RF procedure and create a promising tissuenecrosis [71].

A successful tumor ablation depends largely onaccurate pre-procedural planning, in which theimage diagnosis plays the most crucial role. Withrespects to tumor detection, and despiteremarkable progress in US, CT, and MR imagingover the past several years, no currently availableimaging technique is perfectly sensitive for thedetection of liver tumors. Some lesions willundoubtedly be overlooked with all imagingtechniques. To determine the treatment range, animproved imaging technique should provide notonly the tumor detection but also tumor margin

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Figure 13. Successful treatment of apurely exophytic renal cell carcinoma.a. Contrast enhanced CT scandemonstrates 2 cm enhancing lesion inthe posterior portion of the kidney.Note also the contiguous cyst. b. CTscan 6 months after treatmentdemonstrates “non-enhancement” ofthe mass, indicating obliteration of thetumor.

13a 13b

delineation. Any reliable intraprocedural imagemonitoring of the necrosis of tumor may help toachieve a complete treatment and to decrease therecurrence. Recent study of US contrast agent[52, 53] and open MR technique [72] may providea better prospect. But the efficacy remains to bedetermined.

CONCLUSION

Radiofrequency tumor ablation can beperformed safely in many locations in the bodywith promising or encouraging results. Advancesin radiofrequency equipment, technics, andcombined therapies will likely yield animprovement in the effectiveness, and allow thetreatment of larger tumors.

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