is an Assistant Professor of Clinical Radiology,
is a Professor of Radiology
is a Visiting Resident from Columbia in the Department of
Radiology, University of Miami/Jackson Memorial Hospital, Miami,
The liver is a common site for both primary and secondary
malignancies, the most common being hepatocellular carcinoma (HCC)
and metastasis from colorectal carcinoma. Hepatocellular carcinoma
is the fourth most common cause of cancer-related deaths worldwide,
and approximately one million new cases are reported annually.
Mortality is essentially 100% when these tumors are not treated.
Surgical resection is the standard of care because it has been
shown to provide survival benefits, while systemic chemotherapy and
radiotherapy are largely ineffective.
However, only 5% to 15% of patients with HCC or hepatic metastasis
are candidates for curative surgery.
The major limiting factors for surgical treatment are too many
tumors, large lesions, tumors in unresectable locations, tumors
with major vascular invasion, insufficient hepatic reserve from
cirrhosis, and underlying medical problems that increase the
surgical risk. There is also significant peri-operative morbidity
and mortality. The average 5-year survival rate after successful
resection for both HCC and metastasis is only 20% to 40%.
A considerable number of patients will develop recurrence of tumor,
which is usually fatal.
Various minimally invasive techniques have been developed as an
alternative to surgery. The most important are percutaneous ethanol
injection (PEI), hepatic arterial chemoembolization, and thermal
ablation techniques. Percutaneous ethanol injection has been
reported to be primarily successful in small HCC and is not very
useful for treatment of metastatic tumors.
Chemoembolization is often reserved for unresectable tumors.
Recently, thermal ablation techniques have become popular. There
are two types--cold (cryoablation), and heating ablation
techniques. The latter includes radiofrequency, microwave, laser,
and high-intensity focused ultrasound (US) ablations. Cryoablation
is the most popular among surgeons with reported success rates
similar to resection surgery.
But this technique is invasive, requiring laparotomy in most cases.
Experience with microwave and laser ablations is limited and the
high-intensity focused US technique is still in the experimental
Radiofrequency (RF) ablation has gained more popularity in the
last decade and is claimed to be a very promising technique for
both primary and secondary hepatic tumors.
Radiofrequency ablation produces controlled coagulation of the
tumor by heating the tissue to temperatures above 50ºC. Recent
studies have reported favorable survival rates and excellent rates
of local tumor control by RF ablation, especially in patients with
In this article, we will discuss the historical background,
mechanism of RF ablation, optimal ablation technique, imaging
follow-up evaluation, procedural complications, and results.
Combination therapy of RF ablation with other techniques is also
The effect of RF waves was first reported by d'Arsonval in 1891.
He described heating of tissue when the RF waves pass through
living tissue. This led to the development of medical diathermy and
surgical electrocautery probes in the 1990s.
The electrocautery probe works by desiccation and charring of the
tissue at the point of contact when alternating current passes
through the patient between the cautery probe and a large grounding
pad applied usually to the thigh of the patient. Radiofrequency
ablation technique is based on this principle. Physical principle
of tissue interaction with RF waves was first described by Organ,
who demonstrated that alternating current causes agitation of ions
in the living tissue that results in frictional heat and thermal
Radiofrequency ablation in the liver was first conceptualized by
McGahan et al
and Rossie et al
in the 1990s. Using alternating current, a grounding pad, and a
stock needle insulated to the distal tip (monopolar electrode) and
inserted percutaneously, they produced focal thermal ablation at
the needle tip deep within the liver. They proposed that RF
ablation could be an effective treatment for small hepatic
Mechanism of RF ablation
An RF ablation system consists of a very high frequency (200 to
1200 KHz) alternating current generator, RF needle (monopolar
electrode), grounding pad (which serves as a large dispersive
electrode) and the patient must all be connected in series. In this
circuit, electric current enters through both the electrodes with
the patient as resistor. As the electric current alternates in
directions at high frequency, tissue ions that are attempting to
follow the direction of the current get agitated. Due to natural
high resistivity in the living tissue, ionic agitation produces
frictional heat at the immediate vicinity of electrodes. Because
the grounding pad has a very large surface area, the electrical
resistance is low; hence, the production of frictional heat is
concentrated at the needle electrode. Thus, deposition of
electromagnetic energy from electric current produces thermal
injury. The extent and nature of this injury are dependent on two
important factors: temperature and RF application duration.
To produce irreversible cell damage, it takes several hours at
45ºC, but it takes only 4 to 5 minutes at 50°C to 55ºC. At
temperatures between 60ºC and 100ºC, there is immediate tissue
coagulation (due to irreversible damage to mitochondrial and
cytosolic enzymes by heat-induced denaturation of proteins). Above
100ºC, tissue simply vaporizes. Therefore, temperatures between
50ºC and 100ºC are ideal for RF ablation.
The U.S. Food and Drug Administration has approved RF devices
manufactured by three companies--RITA Medical Systems (Mountain
View, CA), Radiotherapeutics (Mountain View, CA), and Radionics
(Burlington, MA)--for treatment of liver tumors that are not
amenable to surgery (Table 1).
For the model 70 or model 90 Starburst XL devices (RITA Medical
Systems), the ablation protocols are based on the attainment of a
target temperature in the tissue. To perform ablation, two
grounding pads are applied to the thighs or back of the patient.
The tip of the needle is advanced with the prongs retracted, to the
desired location, and then the prongs are partially deployed. There
is an automated program that will slowly raise the generator power
from 25 W to peak within 1 to 1.5 minutes. Full deployment of the
prongs is performed when the target temperature (usually 95ºC to
105ºC) is achieved. The device automatically adjusts the power to
maintain the target temperature as the tumor is cooked. The
ablation is carried out to a preselected time in the treatment
protocol that is at least 10 minutes for smaller tumors and >20
minutes for tumors >5 cm in diameter. For satisfactory ablation,
the company recommends that after completion of the ablation cycle,
the temperature reading from the central electrode must be >50ºC
for at least 1 minute. The needle tract is ablated with a tract
ablation program, which maintains the temperature >60ºC while
removing the needle.
The ablation protocols for the LeVeen needle electrode
(Radiotherapeutics) are based on tissue impedance, unlike the
target temperature used in the RITA devices. Two grounding pads are
applied to the patient's thighs. The needle is inserted to the
desired location, and the prongs are deployed to full length. The
generator is initially set to 30 W and is then increased by 10 W
steps every minute until the peak power of 90 W is attained. At
this power, ablation is continued for 15 minutes or until the high
impedance stops current flow. If the device did not impede out in
the first 15 minutes, then the generator is switched off for 30
seconds and then restarted at maximum power and run until high
impedance again stops further ablation or until 15 minutes has
elapsed. If the ablation stops due to high impedance during the
first cycle, the machine is switched off for 30 seconds and
restarted at 70% of maximum power and run for 15 minutes or until
high impedance again stops the ablation process.
The ablation protocols for the Cool-tip RF electrode (Radionics)
are also based on tissue impedance. The needle shaft has two
internal channels connected at the tip, allowing perfusion of
chilled water. The internal cooling of the needle prevents
desiccation and charring at the needle tip, allowing better
dis-sipation of the frictional heat, which increases the size of
the thermal injury.
Recently, a clustered three-needle electrode system has been
introduced, which has three similar internally cooled needles
arranged in a parallel, triangular manner and attached to a common
hub. This arrangement is shown to produce a larger volume of
ablation than a single-electrode system produces.
Four grounding pads are applied on the patient's thighs. The
single or cluster needle is inserted to the desired location and
then connected to the generator and perfusion pump that circulates
sterile chilled water. The automated program in the generator
increases the power to a peak of 200 W within 1 minute. The power
is maintained until the impedance rises more than 20 (omega), then
the power is reduced to 10 W for 15 seconds. The power is increased
once more to maximal power until the impedance rises again above 20
(omega). This cycle is repeated for a total of 12 minutes.
Complete evaluation of the patient, including clinical history
and directed physical examination, is required. Table 2 gives a
summary of the required preprocedural investigations and their
significance. Any active infection, uncorrectable coagulopathy,
untreatable extrahepatic tumor spread, and extreme debility are
contraindications. Histopathologic confirmation of malignancy by
biopsy is essential in all patients. Written and informed consent
should be obtained.
Imaging studies form the basis for treatment. Triple-phase
computed tomography (CT) scanning or contrast-enhanced magnetic
resonance imaging (MRI) scanning is usually required. The number of
lesions, their size, location, relationship to adjacent viscera
(eg, intestines, diaphragm, gallbladder), and proximity to major
intrahepatic vessels (eg, hepatic and portal veins) should be
carefully recorded. Ideal tumors for RF ablation are <3 cm in
diameter, completely surrounded by hepatic parenchyma, >=1 cm
deep to the liver capsule, >=2 cm away from large hepatic or
portal veins, and <5 in number. Patients with too much of a
tumor burden (>5 cm in diameter and >5 lesions) are not good
candidates. Extrahepatic tumor spread should be evaluated with a
bone scan or chest CT scan, if clinically appropriate.
RF ablation procedure
The RF ablation can be performed by three different approaches,
including percutaneous, intraoperative, and laparoscopic routes.
The percutaneous approach is preferred because it is least
invasive, is associated with minimal morbidity, has a lower cost,
can be performed on an outpatient basis, and can be repeated as
necessary to treat recurrent disease. The intraoperative and
laparoscopic approaches are useful in certain special
circumstances, which will be discussed separately.
The patient should fast for 6 to 8 hours prior to the procedure.
A large peripheral intravenous (IV) access is established, and the
patient is monitored to track cardiac and respiratory rate, blood
pressure, and peripheral oxygen saturation. Although there is no
consensus about routine administration of antibiotics, we
administer a single IV dose of ampicillin and cephalosporin,
starting 30 minutes to 1 hour prior to the procedure. We continue
oral cephalosporin for 5 to 7 days after the procedure.
The procedure can be performed under IV conscious sedation or
general anesthesia, depending on the patient and operator
preferences. A preanesthetic evaluation should be performed.
Fentanyl citrate and midazolam hydrochloride are used for IV
conscious sedation. Deeper sedation can be obtained with IV
propofol infusion. General anesthesia is highly recommended if the
ablation procedure is expected to be extensive and last >=3
The actual needle insertion can be performed under US or CT
guidance, depending on which shows the tumor best and the operator
preference (Figure 1). In general, US is the most commonly used
modality because it provides good real-time guidance for needle
placement, is less expensive, and is quicker to perform.
However, during the ablation process, echogenic bubbles form that
can limit visibility, making it difficult to assess the
completeness or the extent of the coagulation necrosis. CT is
useful in monitoring the ablation process since the perimeter of
the ablated area can be better visualized.
The goal of treatment is to obtain complete tumor destruction.
If the RF ablation were to be as successful as surgical resection,
the ablation should achieve a reasonably good tumor-free margin (at
least 1 cm, preferably 2 cm).
Therefore, ablation should extend to a cuff of at least 1 cm of
normal hepatic parenchyma. Current RF devices can produce a 3-cm
sphere of ablation. Therefore, they are ideal to ablate tumors
<1 cm in diameter (subtracting 2 cm from the 3-cm diameter for
the 360š 1-cm tumor-free margin).
Technical strategy of larger tumor ablation is described below.
Ablation of lesions under special circumstances
When the tumor is >=3 cm, single ablation is not sufficient,
thus increasing the concern for under treatment and tumor
recurrence. The difficulty in achieving complete ablation of larger
tumors is not only because of the tumor volume, but also because of
poor local electrical and heat conductivity within the tumor.
The latter is attributed to the heterogeneity of tumor caused by
fibrosis and calcifications. Given these factors, the strategy to
obtain larger ablation includes overlapping of ablations, improving
electrical conductivity within the tumor by intratumoral saline
injection, and modifications of electrode design.
Overlapping ablation technique--
It is logical to expect that overlapping ablations can produce
larger ablation volumes. After a single-ablation sphere, 6
overlapping ablations (4 in x-y plane and 2 in the z-axis) produce,
geometrically, the next largest ablation. This approach will
produce a composite sphere with internal diameter of only 3.75 cm
(just 1.25 times the single-ablation sphere). This is suitable for
tumors <1.75 cm in diameter (subtracting 2 cm from the 3.75 cm
diameter for the 360š 1-cm tumor-free margin). Fourteen overlapping
ablations is the next step, and the composite sphere produced will
have a diameter of 5 cm (1.7 times that of the single-ablation
sphere). This is suitable for a 3-cm diameter tumor (subtracting 2
cm from the 5-cm diameter for the 360š 1-cm tumor-free margin). In
actual practice, it is very difficult (almost impossible) to
reproduce this model. To overcome this problem, the concept of
overlapping cylinder strategy has been advocated.
In this technique, spheres of ablation are overlapped linearly to
create cylinders, and the cylinders are then overlapped.
Geometrically, this model may produce imperfect coverage, but it
can be performed practically with greater ease and success.
Improving electrical conductivity within the tumor
Intratumoral saline injection prior to or during RF ablation
improves electrical conductivity within the tumor. This causes
greater deposition of the RF energy, leading to increased tumor
It is of interest that neither the concentration nor the volume of
the saline solution correlates linearly with the size of the RF
thermal injury. Therefore, optimal saline concentration and volume
need to be titrated carefully for each of the different devices and
Modifications of electrode design
Electrode modifications to ablate larger tumors include
clustered array electrodes, bipolar electrodes, and pulsed RF
Clustered array electrodes (such as the Radionics model) represent
an extension of the same concept as the single internally cooled
electrode described earlier. Goldberg et al
demonstrated that the sphere of coagulation necrosis produced by a
cluster of electrodes placed <1 cm apart is greater than that
created by a composite of individual electrodes. Their in vivo
experiments on liver ablation demonstrated that cluster electrodes
placed 0.5 cm apart produced an ablation sphere of 3.1 cm versus
1.8 cm produced by conventional single electrodes under otherwise
Their initial clinical experience in 10 patients with colorectal
metastasis showed ablation injury of 5.3 cm ± 0.6 using a clustered
electrode with a single 12- to 15-minute ablation.
A bipolar electrode has a different design. There is no
grounding pad; instead, there is an active electrode and a closely
placed grounding electrode. The heat is generated not only around
the active electrode, but also around the grounding electrode and
in the space between the two. This is in contrast to the monopolar
electrode, where heat is generated only at the active electrode.
Early clinical experience demonstrates that bipolar needles produce
a larger coagulation volume of 3-cm diameter by a single
Absence of a grounding pad eliminates the risk of grounding pad
Pulse RF ablation is another strategy aimed at increasing volume
of coagulation by increasing the RF energy deposition.
In this technique, higher energy deposition is alternated with
lower energy deposition. During periods of low energy deposition,
the tissue around the electrode cools down, allowing for even
higher energy deposition during the next cycle of ablation. This
method allows for deeper heat penetration, creating a larger
ablation zone. The experience is limited, but seems a promising
technique for treating larger lesions.
Tumors at difficult locations
Tumors that are subcapsular or at the liver hilum; and those
adjacent to the gallbladder, colon, intestines, and diaphragm are
of special concern because of the difficulty in achieving complete
ablation with a good tumor-free margin and increased risk of
complication. In the case of subcapsular tumors, if the tumor
involves the capsule, the latter should also be ablated with the
tumor (Figure 2). Careful selection of the needle configuration is
important. If the tumor is small and rounded, an expandable needle
system (such as the RITA and Radiotherapeutics models) is useful
because they can produce more spherical ablation injury compared
with the straight Cool-tip needles (Radionics). For tumors that are
stranded at the angles of liver, such as in the inferior angle of
right lobe or in lateral segment of left lobe, a straight
cooled-tip needle would be more useful since it can be fully
deployed for ablation. The prongs of the expandable needle systems
often penetrate the liver capsule, increasing the risk of bleeding
when they are fully deployed. If the expandable needle has to be
used, then the prongs should be partially deployed and ablation has
to be performed multiple times to cover the whole tumor.
Tumors at the hepatic hilum present another distinct problem
because of their proximity to main vessels, eg, the portal vein and
hepatic artery. These large vessels produce what is known as
perfusion-mediated tissue cooling or the heat-sink effect.
The rapid flow of blood in these vessels washes out the heat
quickly, preventing build-up of optimal temperature to induce
coagulation necrosis in the periphery of tumor adjacent to the
vessel. In pig liver models, Hansen et al
showed that vessels >3 mm in diameter prevent complete ablation
of liver tissue. Studies have shown that reducing hepatic perfusion
by mechanical or pharmacologic methods improves coagulation in the
This can be produced at laparotomy or during the
laparoscopic-guided approach by clamping the hepatic artery and
portal vein in the hepatoduodenal ligament (Pringle maneuver).
Although clamping can be applied safely for up to 1 hour, there is
increased risk of liver ischemia and related complications, such as
liver failure and biliary strictures. Also, resorting to open
procedures would offset the potential benefits of a minimally
invasive percutaneous approach. Alternatively, angiographic balloon
occlusion of a hepatic artery has been used during percutaneous
Hepatic artery embolization with temporary embolic agents, such as
gel foam has also been reported. However, the practical utility and
the efficacy of these additional maneuvers is questionable because
of the invasive nature of the techniques and the dual blood supply
of the liver. Other techniques for reducing blood flow, eg,
pharmacologic modulation and antiangiogenesis therapy, are largely
experimental at this time.
There is another difficulty in targeting tumors at the hepatic
hilum, since the tumor is located in the space between large
vessels, which is small and narrow. The expandable needle
electrodes should be partially deployed; otherwise they may
penetrate the large vessels, resulting in internal bleeding or
pseudoaneurysm formation. This usually necessitates multiple
ablations. Straight-tip internally cooled needles are advantageous
in this location because they can be deployed fully and there is
little concern for vessel penetration. They also have better tumor
coagulation due to internal cooling design, as discussed
The tumors located close to the diaphragm or other viscera, such
as the gallbladder and intestines, are also difficult to treat.
Diaphragmatic thermal injury can cause severe, persistent pain and
breathing difficulty, leading to lower lung atelectasis and pleural
effusion. The chronic pain may require long-term analgesics. Damage
to viscera can cause cholecystitis or ischemic bowel injury.
Therefore, treatment of tumors located at these critical locations
may be better performed using open surgical procedures, as will be
discussed in the following section.
Laparotomy and laparoscopic-guided ablations
Tumors located adjacent to the dia-phragm, gallbladder, or bowel
can be treated more easily during an open procedure because the
liver and the adjacent organs can be separated or mobilized, thus
avoiding potential injury.
These techniques also allow for more accurate tumor staging, like
detection of peritoneal or surface implants and lymphadenopathy.
They provide an opportunity to perform intraoperative US that can
detect unsuspected tumor deposits (Figure 3). These findings can
avoid an unnecessary local tumor treatment.
Both of these approaches also allow for performance of the Pringle
maneuver, which can increase the extent of tumor coagulation. But
the open techniques are invasive and more costly, and are
associated with higher morbidity and mortality than percutaneous
Monitoring of coagulation during RF ablation
Currently, imaging techniques (US, CT, and MR) are standard for
Of these, US is the most commonly used modality and the ablation is
seen as an echogenic area due to liberation of nitrogen gas during
the coagulation (Figure 4). But US is unsuitable for larger lesions
or when multiple ablations are planned because the echogenicity
from the initial ablation can obscure visibility during subsequent
needle placement. We use a combination of US and CT in these
circumstances for intraprocedural monitoring.
Both noncontrast and contrast-enhanced US, CT, and MR scans are
used for assessing the adequacy of ablation. In general,
noncontrast imaging findings are unreliable parameters for
predicting the adequacy of ablation.
The ablated area appears hyperechoic on US or hypodense on CT scan.
In experimental porcine liver models, some authors have reported
the appearance of decreased hypoattenuation on noncontrast CT as a
sensitive indicator of complete ablation.
But more important morphologic features to be determined are the
size and margin (the interface between normal liver tissue and the
ablation defect) of the defect. After complete ablation, the defect
should be centered on the tumor location, it should beinitially
larger than the tumor (which ensures desired tumor-free margins),
and the interface should be sharp, smooth, and devoid of
When blood-pool contrast agents are used (iodinated contrast in CT
and gadolinium contrast in MR), there should be complete lack of
tumor enhancement with thin, smooth rim enhancement at the
The rim represents ablation-induced hyperemia (Figure 5).
Irregularity and nodularity suggests incomplete ablation with
residual tumor. Contrast-enhanced power and color Doppler US has
also been used for monitoring of coagulation. Ultrasound contrast
agents allow for better differentiation between perfused and
nonperfused tissue, which indirectly represent viable and nonviable
Therefore, adequacy of ablation can potentially be predicted in
real-time during the procedure.
The lack of general availability and operator experience are
limiting factors for universal use of US contrast agents.
Direct documentation of tissue temperature (using additional
remote temperature sensors during and immediately after ablation)
has also been used to predict adequacy of ablation.
Temperature-sensing electrodes are placed under US/CT guidance in
the periphery of the tumor or cuff of normal tissue. Temperatures
in these electrodes >55ºC indicates adequacy of tumor ablation.
However, this technique is not fully optimized and reliable systems
have yet to become available for general use.
Immediate postprocedural care
The patient needs intensive monitoring with frequent recording
of vital signs for any immediate complications like internal
bleeding. Patients usually experience significant pain and nausea
and require IV narcotic analgesics, eg, morphine sulphate and
antiemetics. Once stabilized, the patient can be moved to a regular
floor bed with routine vital monitoring. Oral fluids and regular
diet can be resumed as tolerated by the patient. Patients usually
require oral analgesics and we prescribe a combination of
acetaminophen and hydrocodone bitartrate. Patients can be
discharged home the next day. We prescribe 5 days of oral
cephalosporin tablets. If significant pain persists, oral
hydrocodone bitartrate and acetaminophen tablets are continued for
3 to 5 days.
The goal of long-term follow-up is to detect untreated residual
and recurrent tumor when it is small and potentially treatable
(Figure 6). Patients are also followed to identify development of
any extrahepatic disease. Any one or a combination of the imaging
modalities (CT, MRI, and/or US) may be used for follow-up. The
choice of modality is based on patient concerns (eg,
contrast-mediarelated allergy, renal status, and clinical
availability) and operator experience. We recommend that follow-up
should be performed with the same imaging performed prior to
treatment, as this will allow for accurate comparison of
On CT scans, complete ablation is seen as a low-attenuation area
devoid of enhancement or nodules, as described earlier. Hepatic
arterial-phase images are useful in evaluating hypervascular HCC
and portal venous-phase images are useful in evaluating metastases.
On MR imaging, the ablated tissue demonstrates low signal and there
is lack of enhancement in dynamic contrast-enhanced sequences.
Bright signal on T2-weighted images and nodular contrast
enhancement are suggestive of viable tumor tissue. In the early
postoperative period, there is contrast enhancement of the rim or
interface. The finding usually persists for a few weeks, usually
disappearing by 4 weeks on CT and possibly persisting for few
months on contrast-enhanced MR. Another important finding of
complete ablation is that the size of the defect remains stable or
decreases over time. Any increase in size is suspicious for tumor
The follow-up sequence most commonly used is to obtain scans
immediately after the procedure (within 24 hours) followed by scans
at 1 month, 3 months, and then every 3 months. It is also useful to
obtain serum alpha-fetoprotein or carcinoembryonic antigen, as
appropriate, at 3 monthly intervals in HCC and colorectal
metastasis. Ideally, the follow-up should be continued indefinitely
since tumors are known to recur even after months.
Two other imaging techniques used for follow-up need special
mention: contrast-enhanced US and functional positron emission
tomography (PET) imaging.
Unenhanced color and power Doppler US do not reliably detect
residual or recurrent tumor.
However, combining US contrast agents with the Doppler technique
improves detection of residual or recurrent tumor.
Recent studies suggest that the addition of harmonic imaging to
contrast-enhanced Doppler techniques can improve accuracy levels
comparable to that of triple-phase CT scanning.
With 18-fluorodeoxyglucose (18-FDG)-labeled PET scanning, abnormal
increased activity after ablation has been reported to represent
residual or recurrent tumor.
However, the experience is still limited, and this modality cannot
be recommended for routine follow up.
Percutaneous biopsy is another potential tool in diagnosing
tumor recurrence. Imaging findings are usually sufficient to
diagnose residual or recurrent tumor. If there is any discrepancy
between clinical and imaging findings or if the imaging findings
are not diagnostic, the suspicious area should be biopsied. Biopsy
is not routinely recommended because of its limitations, such as
sampling error and limited experience in interpretation of biopsy
specimens with heat-induced damage. Thus, a negative biopsy does
not guarantee complete treatment.
Similarly, imaging techniques also have limitations. The resolution
of the current scanners is only 2 to 3 mm, making it difficult to
diagnose microscopic residual or recurrent tumor, and to
differentiate a small recurrence from ablation-induced hyperemia in
the early postprocedural period.
Therefore, optimal follow-up protocol will include anatomic and
functional imaging, and image-guided biopsy when the imaging
findings are not definite or when a discrepancy exists between
clinical and imaging findings.
Complications of RF ablation
The incidence of clinically relevant complications following
percutaneous RF ablation is low (2% to 7%).
Although significant pain requiring IV narcotics is universal in
all patients immediately after the procedure, persistent severe
pain lasting more than 1 week is very rare. Ablation-induced injury
to the diaphragm, gallbladder, intestines, liver capsule, and major
portal veins are some of the causes of extended pain. These
patients should be evaluated carefully, and any additional causes
for acute abdominal pain should also be excluded.
Tumor ablation syndrome is another complication that results
from the release of mediators of the inflammatory response due to
ablation-induced cell death. The severity of the syndrome is
dependent on the volume of tissue ablated. Smaller ablations result
in low-grade fever (<38.8°C), malaise and leukocytosis starting
about 3 to 4 days after the procedure and lasting for 1 week to 10
days. Larger ablations result in more severe symptoms of high-grade
fever, nausea, vomiting, and lethargy. The symptoms can begin as
early as day 1 and persist for 2 to 3 weeks. The treatment for
ablation syndrome is primarily supportive, including antipyretics
and hydration. The most important differential diagnosis is abscess
at the site of ablation or septicemia. If infection is suspected,
blood cultures should be performed and IV broad-spectrum
antibiotics given. CT scanning may demonstrate gas at the ablation
site, which need not necessarily signify abscess, since gas may be
seen routinely following ablation without infection. Therefore,
drainage of the ablation cavity that is suspected to be an abscess
is purely a clinical decision.
Other reported complications are rare and include bleeding,
injury to the bile duct (resulting stricture or biliary fistula)
(Figure 7), pleural and lung injury causing pneumothorax and
pleural effusion, gallbladder injury causing cholecystitis, and
colon and intestinal injury causing ischemic bowel. Rarely, tumor
seeding in the tract of the needle may be seen (Figure 8). But
proper tract ablation can eliminate this complication (Figure 9).
Vascular complications are hepatic artery pseudoaneurysm and
arteriovenous fistula. Grounding-padrelated burns are also
Procedure-related mortality is very rare (<1%).
Complications are also seen when general anesthesia is used.
Open procedures (RF ablation at laparotomy and laparoscopy) have
additional increased morbidity and mortality related to abdominal
surgery and increased length of hospitalization.
Radiofrequency ablation is being increasingly performed
worldwide. Currently, it is predominantly performed for treatment
of hepatic tumors that are not amenable to resection. The most
common tumors treated by RF ablation are HCC and colorectal
metastases. Results of long-term survival rates from some of the
larger studies have become available recently.
These studies show that the most important determinant for
achieving complete ablation is the size of the tumor. In general,
technically successful complete ablation is possible in 90% of
tumors <2.5 cm in diameter, in approximately 70% to 90% of
tumors with 2.5- to 3.5-cm diameter, in 50% to 70% of tumors with
3.5 to 5.0 cm in diameter, and <50% of tumors >5.0 cm in
Tumor type is also shown to affect the outcome with better success
reported in treating HCC and breast metastases compared with
Studies have also shown that tumor histology directly affects the
success rate with well-differentiated HCC having better results of
ablation than infiltrating lesions.
Radiofrequency ablation of HCC has been documented to provide
survival benefits, particularly for smaller lesions (<3.5 cm).
Disease-free survival on long-term follow-up, as reported by larger
studies are as follows: 64% at 23-month and 71% at 12-month mean
follow-up, according to Rossie et al
; 67% at 15-month mean follow-up, according to Francica et al
; and 92% at 1-year and 60% at 3-year follow-up, according to
Iannitti et al.
Radiofrequency ablation for liver metastases is promising but is
less effective than it is for HCC.
Colorectal metastasis is the most common metastasis treated by RF
ablation. Disease-free survival has generally been reported to be
lower than that reported for HCC. However, two recent studies show
comparable results with disease-free survival of 87% to 93% at
follow-up at 12 months, 62% to 77% at 24 months, and 41% to 50% at
Although hepatic resection is the standard of care for hepatic
malignancy, major hepatic resection is associated with significant
morbidity and mortality (2% to 10%).
Radiofrequency ablation, in comparison, is a minimally invasive and
safe procedure with lower morbidity and mortality (<2%).
Comparison with other minimally invasive techniques
Radiofrequency ablation is only one of many minimally invasive
techniques, and other techniques include PEI, chemoembolization,
and microwave, laser, or cryo-ablations. There are at least two
studies comparing the outcome of RF ablation with PEI.
They showed that complete tumor necrosis was better (90% versus 80%
to 85%) and local tumor recurrence was lower (2% versus 7%) with RF
ablation when compared with PEI. Another advantage was the fewer
number of sessions (1.2 to 1.3 versus 3.3 to 4.8) required with the
RF ablation technique. However, there is paucity of literature
providing a direct comparison between RF ablation and other
Combination therapy of hepatic tumorsThe future of RF
Complete ablation of hepatic tumor depends not only on a perfect
technique, but also on the biology of the tumor itself. There are
strategies for combining RF ablation with other minimally invasive
techniques, eg, intratumoral chemotherapeutic drug injection and
PEI, which can alter the biology of the tumor such that tumor cells
become more susceptible to heat.
It has been documented that the chemo-therapeutic agents and
hyperthermia (42ºC to 45ºC) have synergetic effects.
Goldberg et al
demonstrated in an ex-perimental rat model (R3230 mammary
adenocarcinoma) that intratumoral injection of doxorubicin
increases the volume of coagulation necrosis by RF ablation. The
ablation volume was significantly greater than the volume with RF
therapy or doxorubicin therapy alone. The extent of coagulation was
dependent on both the dose and timing of the doxorubicin, with the
greatest coagulation achieved when doxorubicin was administered
within 30 minutes of RF ablation. In another experiment (R3230
mammary adenocarcinoma, breast tumor model in rats), Goldberg et al
showed that combined therapy consisting of PEI immediately followed
by RF ablation showed significant increase in the extent of
coagulation necrosis compared with either treatment performed
alone. These combined strategies open a new venue for achieving
complete tumor ablation of smaller tumors and may make ablation of
larger tumors realistic in the future. However, further studies are
necessary to determine which combinations are more effective and if
they improve long-term outcome.
Current literature shows that RF ablation is a feasible and safe
procedure for the treatment of primary and secondary liver tumors.
Although surgical resection continues to be the standard treatment
option, RF ablation is shown to be an effective alternative for
tumors deemed not resectable. With current technology, RF ablation
is a very effective treatment for small tumors, particularly HCC
lesions. Recent advances in the device technology, including newer
electrode designs, methods of increasing tissue susceptibility to
heat, and combining with other treatment modalities, eg,
chemotherapy, may make RF ablation a realistic treatment option for
larger tumors, and may improve disease-free survival in these
patients. In view of multiple, invasive, and minimally invasive
treatment options available, further research and well-conducted,
randomized, multicenter trials are required to determine the proper
role of RF ablation in treatment of hepatic tumors.