thermal injury to living tissue is known to begin at 42. lethal exposure times at this temperature range from 3 to 50 hours , depending on the tissue involved ( 26 ) . at temperatures over 43 ,
lethal exposure times decrease exponentially ; at 46 , 8 minutes ' exposure is enough to cause cell death . at temperatures over 60 , denaturing of tissue collagen
begins and cell death is inevitable ( 27 , 28 ) , and for treatment in cases where injury to normal tissue is not a concern , temperatures of this magnitude are therefore desirable . in clinical practice
the tissues around the tip of a needle electrode are heated to 100 , the temperature required to induce the desirable degree of injury .
it is known , however , that rapid heating to too high a temperature ( over 100 ) dramatically increases tissue impedance , and the deposition of rf energy , heat diffusion , and further coagulation necrosis are limited ( 29 ) . using either ultrasound or ct guidance , an rf needle electrode is percutaneously introduced directly into a tumor . when the electrode is connected to a generator producing alternating electric current ,
rf is emitted from its tip , and current within the rf range ( 460 khz ) passes into surrounding tissue .
the current agitates ions of tumor tissue around the needle electrode , and the frictional heat produced by ionic agitation induces cellular death via coagulation necrosis . by changing the intensity and duration of the alternating current , and the size of the electrode
we currently limit the use of rf ablation to patients who are not considered for surgery , or who decline this option . as yet , there is no consensus as to indication , but investigators generally recommend that hccs smaller than 5 cm in diameter and fewer than four in number are ideal for rf ablation .
we are able to treat lesions larger than this by making multiple overlapping ablations with recently developed needle electrodes and powerful generators , but it is known that the larger the tumor , the greater the incidence of incomplete treatment . because rf ablation can cause bleeding , uncorrectable coagulopathy due to severe liver dysfunction is an absolute contraindication .
the prothrombin time ratio must be greater than 50% and the platelet count greater than 70,000/mm .
patients with large amounts of ascites , obstructive jaudice , evidence of extrahepatic tumors , or extensive portal venous thrombosis are not suitable candidates for the procedure .
at the moment three rf devices , all of which consist of rf generators , needle electrodes and dispersive ground pads , are commercially available . the basic principles of each are similar , but the operational techniques are different .
generator power varies between 50 and 200 watts ; some are equipped with functions that display output , tissue impedance , and temperatures in the tissue around the tip of a needle electrode . in each device
1 ) . the first device to be introduced in korea , in april 1999 , was the rita ' 500 ' model ( rita medical systems , mountain view , cal .
this consists of a 50-watt electric generator and a 15-gauge needle electrode , insulated except for 0.6 - 1 cm of its tip .
its hub is a plunger that advances 4 or 7 prongs from the tip , and when fully deployed , these and the needle electrode resemble an open umbrella 3 cm in diameter .
all the prongs and uninsulated tip of the needle are active electrodes , and each curved prong contains a thermocouple at its tip that registers the temperature of surrounding tissue . with the use of recently developed software , the temperature around a needle electrode , power , and impedance can be continuously monitored . the more recent 1500 model , manufactured by the same company , is equipped with a more powerful generator ( 150 watts ) and a larger needle electrode , 5 cm in diameter , which can induce thermal lesions of up to this size with a single ablation .
the second device ( ' rf 2000 ' system ) manufactured by radiotherapeutics corporation ( mountain view , cal .
, ) incorporates a 100-watt generator , a leveen 15-gauge , monopolar array needle electrode , and needle electrodes 2 , 3 , and 3.5 cm in diameter , the largest of which is able to induce lesions with a diameter of up to 4 cm .
the 15-gauge electrode consists of a 12- to 15-cm - long insulated cannula that advances ten individual hook - like arms which are deployed after the needle has been introduced into the tumor . the third device , manufactured by radionics corporation ( burlington , mass .
, u.s.a . ) , includes a needle electrode whose tip is internally cooled with chilled saline , a process thought to increase the size of the thermal lesion .
the device is equipped with a 200-watt generator and uses either a single 17-gauge straight electrode or clustered electrodes designed in a triangular shape . with the device
rf ablation can be performed percutaneously , laparoscopically , or during laparotomy , and involves conscious sedation or general anesthesia . for the former ,
we prefer the intramuscular injection of 50 mg pethidine hydrochloride ( pethidine ; samsung pharmaceutical , seoul , korea ) 10 - 20 minutes before the procedure .
whenever patients report intolerable pain during ablation , an additional 50 mg of the same drug is administered intravenously , with continuous monitoring of the cardiovascular and respiratory systems .
although lesions can be reliably localized using ct , this part of the procedure has depended mostly on sonography . for grounding , one or two
large dispersive pads are attached to the patient 's thigh or back , and after skin cleansing using a sterile technique , local anesthetic ( lidocaine ; kwang myung pharmaceutical , seoul , korea ) is injected along the expected needle pathway and a small skin nick is made .
the electrode is passed through the nick and advanced into the desired portion of the tumor , using real - time sonographic guidance .
once the needle tip is appropriately positioned in the tumor , the electrode prongs are deployed and ablation is begun .
if a rita device is used , initial ablation involves partial deployment of the curved electrodes , but once the temperature at the tip of these reaches the desired level ( usually over 95 ) , they are fully deployed .
the temperature is then maintained at 95 - 100 for ten minutes until the entire tumor or the desired portion is ablated .
after each ablation , the prongs are retracted and the needle is repositioned . at this point , the needle tract is cauterized and the needle withdrawn from the liver . with an rtc device ,
the power used for initial ablation after deployment of the multiple arrays is 50 watts . at 1 , 2 , 3 , and 4 minutes , 10-watt increments are applied , to a maximum of 90 watts , until the " roll - off " phenomena is observed ( i.e. , power output falls precipitously as tissue impedance increases markedly ) .
after a 30-second pause , ablation is restarted , at 75% of the maximum power achieved , until " roll - off " again occurs .
each tumor or area of a large tumor is ablated by the application of rf power during these two phases , and at completion the needle is removed with the multiple arrays retracted . with a radionics device either a single electrode with 2 or 3 cm of exposed metallic tip or a triple- cluster electrode , depending on the size and location of the tumor , can be employed .
after the needle electrode is introduced into the tumor , rf is usually applied for 12 minutes . to maintain a temperature of 20-25 in the tissue around the needle tip ,
a peristaltic pump is used to infuse 0 normal saline solution into the lumen of the electrodes . during ablation ,
generator output , tissue impedance and temperature around the needle tip are continuously monitored . for rf ablation to be successful and complete
the ideal goal is to ablate a peripheral margin of 0.5 - 1 cm of normal hepatic tissue surrounding the tumor , as well as the entire tumor itself : without adequate safety margins , untreated viable tumor may remain , leading to treatment failure and local recurrence
. in general , a single ablation , or two , may be adequate for tumors less than 3 cm in diameter when a needle electrode at least 3 cm in diameter is used . for larger tumors ,
however , multiple overlapping ablations should be performed , according to tumor size . with a needle electrode 3 cm in diameter
, a single ablation is applied for tumors < 2 cm in diameter , at least two ablations for those which are 2~3 cm , and multiple overlapping ablations for those > 3 cm . for tumors located in the mid - zone of the liver rather than its periphery or central zone , this treatment strategy
in addition to size , tumor location is one of the important factors influencing the likely therapeutic outcome .
if the tumor lies in the subcapsular area , no safety margin along the capsule is possible . in subcapsular tumors ,
a safety margin of normal hepatic tissue is difficult to obtain , but if the liver capsule overlying the tumor appears to be involved by the tumor , the capsule should be ablated .
subcapsular tumors can be effectively treated using either an expandable needle electrode with multiple array or a straight cooled - tip electrode .
if a tumor is small and round , the use of an expandable needle electrode is preferred because the lesions it induces tend to be more spherical in shape than those induced by one with a straight tip . for ablating fusiform tumors , a straight - tip needle electrode is better because it frequently makes elliptical lesions .
tumors located between the anterior and posterior liver capsules ( e.g. in the inferior angle of the right lobe or the lateral segment of the left ) are often difficult to ablate completely , especially when they abut on both capsules , and in this particular situation , the choice of needle electrode is important .
when an expandable electrode is used in narrow spaces , multiple overlapping ablations involving partial deployment of the hook - like electrodes are unavoidable even if the tumors are small : the full deployment of hooks can penetrate the liver capsule , and this may cause bleeding or unnecessary thermal injury to adjacent organs . because its use involves no risk of penetrating either capsule , and the entire length of active electrode
can be employed , the situation requires a straight cooled - tip electrode . additionally , the number of ablations and thus the procedure time are thereby reduced ( fig .
3 ) . if the ultrasound - guided percutaneous approach is used , subcapsular tumors exhibiting exophytic growth can also be difficult to ablate completely .
the best way to achieve effective necrosis of an exophytic tumor is to ablate the deepest portion first , thus blocking the blood supply to the exophytic portion , which is subsequently ablated ( fig .
another difficult situation arises when tumors are present in the central zone of the liver , near the hepatic hilum .
a tumor in this location is almost always surrounded by large vessels , and the resultant tissue cooling may make it difficult to ablate its periphery and the cuff of normal hepatic tissue . in this situation ,
the extent of coagulation necrosis is less than usual , and follow - up ct reveals the presence of residual perivascular tumor ( fig .
5 ) . on the basis of experimental and clinical studies ( 30 - 32 )
, several investigators have found that temporary reduction of vascular flow to the liver during rf ablation by mechanical occlusion of the portal vein and/or arterial vessels , or pharmacologic modulation , increased the extent of coagulation necrosis .
when rf ablation is performed percutaneously , the use of a balloon for mechanical occlusion of the portal vein is impractical because it is invasive and time consuming . during intraoperative rf ablation after laparotomy , reduction of vascular inflow by clamping the hepatic artery and portal vein at the level of the porta hepatis ( pringle maneuver ) is very helpful in increasing the extent of coagulation necrosis .
pharmacologic modulation of hepatic blood flow has been under investigation and could be the ideal way of creating more extensive coagulation necrosis during percutaneous rf ablation .
we are able to suggest a number of ways in which the use of current rf devices for the ablation of tumors surrounded by large vessels may be efficacious .
the space between large vessels is usually small and narrow , and safe ultrasound - guided targeting may thus be difficult .
it is important not to penetrate large vessels with a needle electrode , since bleeding or pseudoaneurysm may occur .
when rf ablation involves the use of an expandable needle electrode and its hooks within the lumen of the vessel are ineffective , the hooks of the multiple array should not be placed beyond the vascular wall . to induce satisfactory coagulation necrosis in this situation , multiple overlapping ablations with partial deployment of the multiple array
even if the tumor is less than 3 cm in diameter , the recommendation applies . to avoid penetration of the vessel wall during deployment of the needle electrode , careful monitoring with real - time ultrasound is essential .
if the temperature around any tip of the multiple array fails to rise , this indicates that the tip is inside the blood vessel and should be retracted .
for ablation of a tumor surrounded by large vessels , a straight - tip internally cooled needle electrode may have advantages over the expandable needle variety .
first , because only the straight part of the active electrode is involved , penetration of the vessel wall is not a matter of concern .
second , the reduced impedance of the tissues nearest the needle electrode , induced by internal cooling with chilled saline , enables heat to diffuse more easily .
this , in turn , allows greater rf energy deposition and can lead to more extensive coagulation necrosis than is possible when an expandable needle electrode is used .
for ablation of a tumor surrounded by large vessels , it is also useful to increase the duration of rf application , regardless of the type of needle electrode employed ; one more ablation with the needle tip placed in the same position may help decrease the amount of residual perivascular tumor .
this possible outcome is , however , based on our own experience and is somewhat speculative ; firmer conclusions should be based on the findings of further studies .
the ablation procedure almost always creates numerous microbubbles in heated tissue , and these increase the echogenicity of the ablated lesion ( fig .
6 ) , a condition which is known to persist for between 15 minutes and 6 hours ( 33 , 34 ) . hyperechogenicity may be helpful for monitoring the approximate size of an ablated lesion , but makes further placement of the needle electrode difficult . for large tumors ,
one good way of treating a large tumor is to deal with the deepest portion first ; in this way increased echogenicity does not obscure its untreated portions .
no data concerning the accuracy of ct in depicting residual tumors after rf ablation have been published , and as a standard of reference , the dynamic helical mode suffers certain limitations .
nonetheless , ct has been widely used in the evaluation of therapeutic response after rf ablation .
complete tumor necrosis ( successful treatment ) is considered to have occurred when follow - up ct reveals no foci of enhancement within the ablated lesion or at its periphery ( figs . 2 , 4 ) .
any focal enhancement within the tumor or increase in size of the ablated tumor should be considered indicative of residual or recurrent lesion ( fig .
we treat residual or recurrent tumor with additional rf ablation , using three - phase helical ct to evaluate therapeutic outcome ; because reactive hyperemia in tissue surrounding the ablated lesion makes accurate assessment difficult , such evaluation does not immediately follow treatment , however ( fig . 8) .
whether ablation was successful is usually determined on the basis of ct findings obtained at least one month after the procedure . in our experience
, reactive hyperemia has usually resolved by this time . to determine the possible presence of residual or recurrent tumor , follow - up ct
dynamic mri with gd - dtpa enhancement is also a good method for evaluating therapeutic response .
areas of the tumor in which treatment was successful do not demonstrate the enhancement seen at contrast - enhanced ct .
power doppler ultrasonography ( pdus ) using a microbubble contrast agent has recently been reported to be a promising noninvasive technique for assessing the therapeutic response to rf ablation in hcc ( 34 ) .
nonenhanced pdus was of little help in depicting residual intratumoral flow signals , though contrast - enhanced pdus was very sensitive in the detection of residual tumor vascularity within an ablated lesion ( fig .
several clinical series using different methods of rf application for the treatment of hcc have been reported ( 12 , 13 , 15 - 17 , 20 ) .
rossi et al . detailed their seven - year experience with rf ablation in 50 patients with hcc or hepatic metastases ( 15 ) , reporting very promising survival rates ( for hcc patients ) of 94% , 86% , 68% , and 40% at 1 , 2 , 3 and 5 years , respectively .
reported complete necrosis rates after rf ablation have varied according to the size and morphology of the hepatic lesions .
( 16 ) reported a complete necrosis rate of 90% in 42 patients with 52 small hccs ( < 3 cm in diameter ) .
this rate decreased , however , to 71% for medium hccs ( 3.1 - 5.0 cm ) and to 25% for large ones ( > 5.0 cm ) ( 17 ) . in an early experience with 51 hccs ( 1.0 - 4.0 cm in diameter ) at our institution , the complete necrosis rate was 94% ( 20 ) . during a recent one - year period , we used rf ablation alone for the treatment of 108 patients with 125 nodular hccs .
fifty - seven of these 108 , with 65 hccs , underwent follow - up helical ct not less than six months after the procedure .
forty - five tumors were small ( 0.7 - 3.0 cm ) and 20 were medium ( 3.1 - 5.0 cm ) . six - month follow - up ct showed complete necrosis of ablated tumor in 43 ( 96% ) of the 45 small lesions and in 18 ( 90% ) of the 20 that were medium - sized .
after rf ablation , we found no major but four minor complications ( one small pneumothorax and three cases of minor intraperitoneal bleeding ) which disappeared spontaneously with no specific treatment ( 35 ) .
other investigators have also reported low complication rates ( 12 - 17 ) . on the basis of several clinical studies including ours
, we believe that rf ablation is a safe and highly effective technique for the local treatment of hcc , especially for small tumors .
rf ablation has several advantages over other existing therapies : it is minimally invasive , and for the treatment of residual or recurrent tumors can be repeated .
compared with pei , rf ablation leads to a higher complete necrosis rate and requires fewer treatment sessions ( 16 ) .
the procedure is operator dependent , and for successful ablation , accurate placement of the needle electrode is imperative . in order to obtain good results , medical practicioners should therefore be familiar with sonographically - guided interventional techniques .
the other limitation is that abundant portal venous flow in normal liver tissue surrounding the tumor may act as a heat sump , making complete ablation of such tissue difficult . to decrease the effect of portal venous flow , several experimental and clinical studies are in progress .
although long - term follow - up evaluation of clinical outcome is needed , rf ablation is safe and effective , and is thus a highly promising technique for the local destruction of hcc .
further improvements in the devices and techniques employed may further increase its efficacy and safety .
on the basis of several clinical studies including ours , we believe that rf ablation is a safe and highly effective technique for the local treatment of hcc , especially for small tumors .
rf ablation has several advantages over other existing therapies : it is minimally invasive , and for the treatment of residual or recurrent tumors can be repeated .
compared with pei , rf ablation leads to a higher complete necrosis rate and requires fewer treatment sessions ( 16 ) .
the procedure is operator dependent , and for successful ablation , accurate placement of the needle electrode is imperative . in order to obtain good results , medical practicioners
the other limitation is that abundant portal venous flow in normal liver tissue surrounding the tumor may act as a heat sump , making complete ablation of such tissue difficult . to decrease the effect of portal venous flow , several experimental and clinical studies are in progress .
although long - term follow - up evaluation of clinical outcome is needed , rf ablation is safe and effective , and is thus a highly promising technique for the local destruction of hcc .
further improvements in the devices and techniques employed may further increase its efficacy and safety .
 although surgical resection remains the best option as potentially curative therapy for hepatocellular carcinoma , radiofrequency thermal ablation has begun to receive much attention as an effective minimally invasive technique for the local control of unresectable malignant hepatic tumors . 
 most recent radiofrequency devices equipped with a powerful generator and larger needle electrode permit larger thermal lesions , up to 5 cm in diameter , with a single ablation . in this article , the author reviews the technical developments and early clinical results obtained with radiofrequency ablation techniques . 
Tissue Response to Heat, and the Principle of RF Ablation
Indications and Contraindications
Equipment
Procedure and Technique
Evaluation of Therapeutic Effect
Results
Summary and Conclusion