24 Percutaneous Ablation of Hepatic Metastases
J. Antony Goode, Tarun Sabharwal, and Andreas Adam
J. A. Goode, MD; T. Sabharwal, MD;
A. Adam, MB, BS, FRCP, FRCR, FRCS
Department of Interventional Radiology, St Thomas’
Hospital, Lambeth Palace Road, London SE1 7EH, UK CONTENTS
24.1 Introduction 337 24.2 Cryotherapy 337 24.2.1 Patient Outcome 338
24.3 Percutaneous Injection of Ethanol 338 24.4 Radiofrequency Ablation 338 24.4.1 Patient Selection and Technique 339 24.4.2 Complications 343
24.4.3 Assessment of Treatment Effectiveness 343 24.4.4 Patient Outcome 344
24.5 Laser Ablation 344
24.5.1 Patient Selection and Technique 344 24.5.2 Patient Outcome 344
24.6 Microwave Coagulation 345 24.6.1 Patient Selection and Technique 345 24.6.2 Patient Outcome 345
24.7 Conclusion 345 References 346
24.1
Introduction
The liver is the most common site of metastatic disease. Hepatic metastases most commonly occur from colorectal cancer and, less frequently, from neuroendocrine tumours, gastrointestinal sarcoma, ocular melanoma, and others. Complete evaluation of the extent of metastatic disease, both within and outside the liver, is important before considering treatment options.
Approximately 25% of patients with liver metas- tases from colorectal cancer have no other site of metastasis and can be treated with regional therapies directed towards their liver tumours. Hepatic resec- tion results in survival rates ranging from 55%–80%
at 1 year and 25%–50% at 5 years (Nagorney et al.
1989). However, because of advanced disease, unfa- vourable location of the metastases, or poor physical
condition, fewer than 20% of patients are eligible for hepatic resection (Foster 1978; Adson et al. 1984;
Cobourn et al. 1987; Fong et al. 1995; Nordlinger et al. 1987; Steele et al. 1991). In general, only patients with fewer than four or five metastases, limited to one lobe and with no evidence of extrahepatic disease, are eligible for surgery. Without resection, patients with hepatic metastases from colorectal carcinoma have a median survival of less than 1 year (Baden and Andersen 1975; Bengtsson et al. 1981; Wood et al.
1976). Recently developed minimally invasive tech- niques for local ablation of hepatic metastases may provide reasonable alternatives for patients who are not candidates for surgery. Such techniques include cryotherapy, thermal ablation, microwave therapy and intra-arterial chemoembolization.
24.2
Cryotherapy
Cryotherapy is the oldest of the local thermal ab- lation techniques. The application of cryotherapy was first suggested by Copper (1963). Since then, there have been multiple clinical reports detailing its use for the treatment of primary and secondary hepatic tumours (McPhee and Kane 1997; Haddad et al. 1998). Subfreezing temperatures are delivered through penetrating cryoprobes in which a cryogen is circulated. Thermally conducted material allows cooling of the probe tip while the shaft and delivery hoses are insulated. Irreversible destruction of tis- sue occurs at temperatures below –20 °C to –30°C.
Direct freezing, denaturation of cellular proteins, cell membrane rupture, cell dehydration, and is- chaemic hypoxia cause cell death. Cryolesions as large as 6–8 cm in diameter can be created safely.
The cost of a cryoablation unit ranges from £80,000
to £110,000. The cryoprobes are typically 2–10 mm
in diameter and cost approximately £800 for single
use. Because of the size of the probes, cryotherapy is
often used at open or laparoscopic surgery, although
smaller probes are now becoming available which may enable percutaneous cryotherapy to be carried out routinely in the future.
Generally, treatment is limited to those with four or fewer metastases, although patients with slow-growing neuroendocrine tumours may have a slightly higher number of lesions and still be can- didates for cryoablation. Contraindications include the presence of extrahepatic metastatic disease and inability to undergo general anaesthesia and laparotomy.
At present, cryoablation is primarily an open surgical technique, with fewer than 10% of patients treated laparoscopically. Ultrasound (US) is the most frequently used method of guiding the proce- dure. Depending on tumour size, one or two probes are placed centrally within the lesion with the tips of the probes touching the deep edge of the tu- mour. The cryogenic material (–196 °C) is circulated through the probes. The ice wall is visualised as an echogenic, expanding, hemispherical rim. Freezing is continued until the cryolesion extends through the tumour and into the adjacent normal tissue, with a goal of achieving a 5–10 mm ablation margin.
This first freeze takes 5–15 min and is followed by a spontaneous thaw and a second freeze to reach and slightly exceed the original cryoablation margin.
After the second freeze the cryoprobe is heated and removed and the track is packed for hemostasis.
Patients are followed up with computed tomogra- phy (CT) performed immediately before discharge, at 6 and 12 months after ablation, and yearly there- after. The thermal injury caused by cryoablation ap- pears on CT images as an avascular, low-attenuation lesion that slowly decreases in size over time. FDG- PET performed three weeks following ablation is not only able to assess the efficacy of treatment, but it may also have a future role in follow-up of patients treated with cryosurgery as it can detect recurrent disease earlier than CT (Langenhoff et al. 2002).
24.2.1
Patient Outcome
The reported survival rates are 90% at 1 year, 40%
at 3 years and 20% at 5 years, with a mean overall survival of 38 months (Dodd et al. 2000).
Major complications occur in fewer than 20%
of patients, the most common being intraperito- neal haemorrhage. No tumour seeding has been re- ported. Tumour recurrence at the cryotherapy site has been observed in 13% of patients (McPhee and
Kane 1997). Minor complications, such as fever, leu- kocytosis and transient elevation of liver function tests are seen in the majority of patients. However, when compared with radiofrequency (RF) ablation therapy, although similar rates of treatment success and complications have been obtained, local recur- rence occurred more frequently with cryoablation (Adam et al. 2002).
24.3
Percutaneous Injection of Ethanol
Percutaneous ethanol injection (PEI) is effective in the treatment of hepatocellular carcinoma (HCC), and long-term survival rates of PEI-treated patients with HCC are similar to those of patients treated surgically (Livraghi et al. 1995).
PEI is more effective in the treatment of HCC than in that of liver metastases. This is because most hepatocellular carcinomas occur in the set- ting of cirrhosis. In this situation the tumour is
”soft”, whereas the surrounding liver parenchyma is
”hard”. This promotes the distribution of ethanol or heat within the tumour, particularly when the HCC is encapsulated. Patients with liver metastases typi- cally have normal (soft) underlying hepatic paren- chyma, whereas the metastasis is ”hard”, a situation which promotes the egress of ethanol from the le- sion into the normal liver. Metastases also tend to be more infiltrative than HCC.
24.4
Radiofrequency Ablation
Radiofrequency (RF) ablation uses radiofrequency
energy to produce local heat in tissues. Needle-like
electrodes are placed percutaneously directly into
the tumour, with the use of ultrasound, computed
tomography or magnetic resonance imaging guid-
ance. The RF electrode typically is comprised of a
metal shaft, which is insulated except for an exposed
conductive tip that is in direct electrical contact
with the targeted tissue volume. The RF generator
supplies RF power to the tissue through the elec-
trode. It is connected both to the shaft(s) of the RF
electrode and to the reference electrode, usually a
large conductive pad in contact with the patient’s
skin in an area of relatively good electrical thermal
conductivity (such as the thigh). The RF generator
produces RF voltage between the active electrode
and the reference electrode, thereby establishing an electric field within the patient’s body between the two electrodes. At the low RF frequencies used for this procedure (less than 1 MHz), the electric field pattern is governed essentially by electrostatic equa- tions and oscillates with the alternating RF current, which causes movement of ions in the tissue in pro- portion to the field intensity. The mechanism of tis- sue heating for RF ablation is frictional, or resistive, energy loss caused by the motion of the ionic current (Organ 1976; Cosman et al. 1984). All RF genera- tors are operated at 460 kHz at a power setting of 50–200 W. The cost of the generators ranges from
£8,000–£25,000. The needle electrodes cost £300–
£1000 and are not reusable. There are now several different types of RF ablation systems available.
Many of these machines differ in generator power, needle size and configuration. There are also differ- ences in the methods for monitoring of energy dep- osition and for maximising the volume of tumour coagulated.
Two systems (RITA Medical Systems, Inc.
Mountain View, CA, and RadioTherapeutics Corp.
Mountain View, CA) use coaxially deployed inner tines, which expand into the tumour after the outer needle is in place. The degree of deployment of the inner tines can be adjusted according to tumour size. The RITA system uses continuous monitor- ing of temperature to guide ablation, whereas the RadioTherapeutics machine uses monitoring of im- pedance. A third system (Radionics, Inc. Burlington, MA) has probes with either single needle or triple parallel needles; this system utilises perfusion of cold saline within the needle probe(s) to cool the electrode tip (Fig. 24.1). This minimises charring
around the needle tip thus preventing a rise in im- pedance and enabling the creation of a larger area of coagulation. The Berchtold system (Berchtold Medizinelektronik, Tuttlingen, Germany) is differ- ent from the above three in that (a) it can be used as a monopolar or a bipolar system and (b) it uses continuous infusion of saline from the needle tip into the tumour.
24.4.1
Patient Selection and Technique
Most investigators are limiting treatment with RF ablation to patients with four or fewer, 5-cm or smaller, primary or secondary malignant hepatic tumours, with no evidence of extrahepatic disease.
However, patients with a small number of pulmo- nary metastases are sometimes treated, as such me- tastases do not usually have a significant impact on survival. RF ablation is also being used in combi- nation with hepatic resection in the treatment of patients who would not be candidates for resection alone (Pawlik et al. 2003). In some centres there is a waiting period for patients prior to transplanta- tion; RF ablation is being applied to control tumour growth during this time. In addition, RF ablation is sometimes used as a test of time prior to hepatic resection in patients who are fit for surgery and in whom cross-sectional imaging reveals between one to five metastases. As new lesions can develop fairly quickly, some centres are now delaying surgery to see if this occurs. In such cases the old lesions are treated with RF ablation during the period of wait- ing (Livraghi et al. 2003a).
In some patients with a large volume of tumour in the liver, not suitable for potentially curative sur- gery or treatment with radiofrequency, RF ablation is increasingly being requested by the oncologists to reduce tumour bulk in the hope that this will increase the effectiveness of chemotherapy. The ef- fectiveness of RF for this purpose requires further investigation.
RF ablation is a good method of palliation in pa- tients who have severe pain caused by distension of the liver capsule by large tumours. In such cases, co- agulation of the tumour often provides rapid relief of pain (Fig. 24.2).
Ideal tumours for RF ablation are smaller than 3 cm in diameter, completely surrounded by hepatic parenchyma, 1 cm or more deep to the liver capsule, and 2 cm or more away from large hepatic or portal veins. Subcapsular liver tumours can be ablated, but
Fig. 24.1. This patient has a cooled tip single electrode (Radionics) sited in a left lobe metastasis, under CT guid- ance
their treatment is usually associated with greater pro- cedural and post-procedural pain. Tumours adjacent to large blood vessels are more difficult to ablate com- pletely because the blood flow in the vessels causes cooling of the adjacent tumour, and it has been shown that vessels as small as 3 mm adjacent to a tumour can result in incomplete tumour coagulation. (Lu et al. 2003). Temporary occlusion of the hepatic arterial supply to the tumour, of the portal vein and of the he- patic veins have all been used with good effect to de- crease this cooling effect and allow tumours adjacent to large blood vessels to be ablated (Figs. 24.3, 24.4) (de Baere et al. 2002; Rossi et al. 2000; Yamasaki et al. 2002). Ablation of tumours adjacent to the large portal triads causes increased pain and poses the risk of damage to the associated bile duct. It is gen- erally recognised that treating lesions close to the gallbladder, stomach, diaphragm or colon can be as- sociated with increased risk of diaphragmatic injury, bowel perforation and peritonitis. Contraindications to treatment include sepsis, severe debilitation, and uncorrectable coagulopathies. The presence of an en- terobiliary fistula or prior sphincterotomy increases the risk of biliary sepsis after the procedure, as does the presence of intrahepatic biliary dilatation.
Percutaneous RF ablation is usually carried out with the use of conscious sedation alone and can be performed on an outpatient basis. However, many operators prefer to keep the patients in hospital overnight, partly in order to treat any discomfort and partly because of the small risk of haemorrhage accompanying the procedure.
For patients who cannot tolerate sedation or in whom multiple tumour lesions are to be treated during a single session general anaesthesia is ad- vocated. Before the procedure, adequate hydration is ensured; this is believed to reduce the incidence of the post-embolization syndrome. Antibiotics are not routinely given but in some patients at high risk of infection they should be administered prophy- lactically. These high-risk groups include patients with diabetes, immunosuppression, biliary-enteric anastomoses, ascites and biliary duct dilatation (de Baere et al. 2003; Livraghi et al. 2003b).
Fig. 24.2. a CT image of a large colorectal metastasis in the left lobe of the liver, which was causing local discomfort. b CT performed 2 weeks following RF ablation of the left lobe tumour shows reduction in size of the mass, with evidence of necrosis
Fig. 24.3. Fluoroscopic image of an occlusion balloon in- flated in hepatic vein adjacent to a metastasis to reduce cool- ing from blood flow during RF ablation with a triple, cooled electrode (Radionics)
a b
ablation requires exact placement of the electrode tip in relation to the tumour. A single ablation treat- ment raises local tissue temperatures to 60–100 °C and produces an approximate 2–5 cm spherical or oval area of coagulation.
Monitoring of thermal ablation is usually carried out by measuring parameters such as temperature Detailed study of the imaging investigations and
careful planning of the procedure are needed. Blood samples should be taken to test the renal function and coagulation status.
When using RF ablation, the operator aims to destroy the tumour and a 5–10 mm circumferential cuff of adjacent normal hepatic parenchyma. Each
Fig. 24.4. a CT image of a colorectal metastasis adjacent to the middle hepatic vein. b Under CT guidance, a needle is inserted into the metastasis to enable a coil to be sited within the tumour. c The coil is now demonstrated within the tumour. d Under fluoroscopic guidance a triple, cooled electrode (Radionics) is introduced into the tumour, using the coil as the target. An occlusion balloon is inflated in the adjacent hepatic artery to reduce cooling from blood flow. e A subsequent CT shows an area of coagulation produced by the RF ablation
a
c b
d e
and impedance. The use of imaging for this purpose has not shown to be very reliable. On ultrasound le- sions become more echogenic because of microbub- bles produced during the ablation. However, the size of the echogenic lesion does not correspond closely with the area of coagulation. On CT, air may be pro- duced due to vaporisation of tissue. However, the process of coagulation takes some hours to become complete and immediate CT is not a reliable guide.
In theory, MR thermometry provides an accurate method of monitoring thermal ablation. However, few operators rely on this method to guide treat- ment.
Tumours smaller than 2 cm in diameter can be treated with one or two ablations. Larger tumours usually require several overlapping ablations for complete coagulation. However, depending on the patient’s tolerance these may be administered in more than a single session of treatment. Each abla- tion usually lasts 12–15 min. Usually, two or three ablations are carried out during the same session when local anaesthesia is used.
The size of the coagulated area produced in a single ablation session can be increased by the use of multiple electrodes or of a ”cluster” probe (Xu et al. 2004). This may have up to nine separate elec- trode tips, which are deployed within the lesion.
One system uses a cooled tip electrode, where cold saline is used to prevent overheating of the elec- trode tip, and thus prevent local charring which would otherwise limit the energy deposition into the tumour. Another development is of saline-en- hancement during RF ablation (Kettenbach et al.
2003; Livraghi et al. 1997). In this technique, sa- line is continuously perfused through a specially designed electrode into the tumour tissue during the radiofrequency ablation. The rationale is that saline in the lesion increases conductivity of current away from the needle tip, enabling a larger volume of tissue coagulation. Neoadjuvant chemotherapy in combination with radiofrequency ablation may also result in larger areas of coagulation; intrave- nous liposomal doxorubicin has been shown to re- sult in increased coagulation diameter in an animal model (Goldberg et al. 2002). Chemoembolization in conjunction with radiofrequency ablation has also been used to achieve increased tumour necro- sis (Kitamoto et al. 2003). Chemoembolization, proposed by Kato et al. (1981), is a technique that combines intra-arterial infusion of chemothera- peutic agents with arterial embolization of the vas- cular supply to the neoplasm. The vascular occlu- sion prolongs the transit time through the tumour
vascular bed, theoretically increasing the contact time between the infusate and the neoplastic cells to increase tumour cell kill and programmed cell death.
In most patients, thermal ablation of hepatic me- tastases is guided by US or CT (Pedro et al. 2002;
Sica et al. 2002; Skjoldbye et al. 2002). However, some tumours are very poorly visible on either US or unenhanced CT. Furthermore, they may appear only transiently on CT images following enhance- ment with intravenous contrast medium, only to disappear on images obtained a few minutes later.
Such lesions are difficult to treat with thermal ab- lation as accurate positioning of radiofrequency electrodes cannot always be accomplished during the short period during which they are visible on CT following i.v. contrast medium enhancement.
It is much easier to perform the procedure under CT guidance when the tumour is visible on unen- hanced images, as this allows sufficient time for accurate placement of the RF electrode. However, even when the tumour is easily visible, thermal ablation under CT guidance can be very difficult when a steeply oblique approach has to be used, for example when treating lesions located imme- diately below the dome of the diaphragm. For such tumours, ultrasound guidance is preferable, pro- vided that the tumour is reasonably well seen on ul- trasound images. Poor visualisation on ultrasound or CT images is a formidable obstacle to percutane- ous thermal ablation. Ultrasound contrast media are very helpful in visualising hepatic tumours but some masses, especially relatively avascular ones such as colorectal metastases, are not always seen clearly. Livraghi (2001) recommend transcatheter segmental chemoembolization for hepatocellular carcinomas not recognisable on US examination.
However, this approach would be unhelpful in
colorectal metastases, in which chemoembolization
has not been shown to be of benefit. MR-compatible
RF electrodes have been developed (Kettenbach
et al. 2003). However, magnetic resonance (MR) is
cumbersome and time-consuming as a method of
guidance in thermal ablation procedures. We have
developed a technique that facilitates RF ablation
of tumours poorly visualised on ultrasound or un-
enhanced CT (Adam et al. 2004). This involves in-
serting a small metallic coil into the tumour during
the short period of visualisation on enhanced CT
images. This can be accomplished by placing a nee-
dle in the vicinity of the tumour using anatomical
landmarks prior to intravenous injection of con-
trast medium. The position of the needle is then
adjusted appropriately during contrast enhance- ment and a microcoil is advanced into the centre of the tumour via the needle. This enables the radi- ofrequency electrode to be guide into position us- ing fluoroscopic guidance, usually in combination with ultrasound guidance. This technique allows accurate placement of RF electrodes irrespective of the degree of visibility of tumours on ultrasound or unenhanced CT images. Provided the mass is visible, if only transiently, on enhanced CT, it can be accessed under fluoroscopic guidance following placement of the metallic coil (Fig. 24.4).
If a tumour is visible on MR but cannot be visual- ised on ultrasound or CT images it may be possible to use MR to place an MR-compatible metallic coil, which can be used subsequently to guide the pro- cedure under fluoroscopic guidance as described above.
24.4.2
Complications
Complications are unusual. The main ones are in- traperitoneal haemorrhage, liver abscess, intestinal perforation and seeding along the tumour tract. Two recent series reported rates of major complications of 2.2% and 5.7%, with mortality of 0.3% and 1.4%
(de Baere et al. 2003; Livraghi et al. 2003b). These compare favourably to perioperative mortality of 4.4%–10% following hepatic resection for colorec- tal liver metastases.
Complications are more likely (a) where the tumour is superficial (within 1 cm of the liver capsule) or close to hilar structures, (b) with pro- longed ablation time and (c) when several lesions are treated during the same session. Perforation of a viscus is more likely in patients with advanced cirrhosis and/or poor performance status, when the tumour is adjacent to the gastrointestinal tract and when there has been previous right upper quadrant surgery or chronic cholecystitis, due to the increased development of adhesions in this lat- ter group.
A number of techniques have been used to mini- mise the risk of injury to adjacent structures. These include infusion of intrathoracic or subphrenic sa- line which has been described to limit diaphrag- matic injury for tumours high in the hepatic dome (Kapoor and Hunter 2003; Shibata et al. 2002a).
Tumours adjacent to the gastrointestinal tract have been treated with RF ablation after percutaneous interposition of a balloon between the mass and the
gastrointestinal tract, in order to prevent perforation (Yamakado et al. 2003). Percutaneous drainage of ascites and percutaneous drainage of a dilated bil- iary tree minimise the risk of haemorrhage and in- fection. Evidence from one case series suggests that RF ablation of tumours adjacent to the gallbladder can be performed safely and effectively; iatrogenic cholecystitis occurs frequently but it resolves spon- taneously (Chopra et al. 2003). As described above, antibiotics should be given to patients at increased risk of infection. ”Hot” withdrawal of the needle may reduce tumour seeding and haemorrhage. When a percutaneous approach is contraindicated, it may be possible to carry out RF during laparoscopic or open surgery.
There is often some pain after the procedure, but this usually settles within 24 h. Approximately 10%–20% of patients have a 1–3ºC rise in tempera- ture, as a response to tumour necrosis; this mild py- rexia usually begins the day after the procedure and can last up to 1 week. However, prolonged, marked pyrexia should always raise the suspicion of infec- tion and merits further investigation.
24.4.3
Assessment of Treatment Effectiveness
CT and ultrasound cannot demonstrate the re- sult of the procedure at the time of treatment.
Contrast-enhanced ultrasound has been shown in animal models to be useful in guiding and moni- toring ablation, and has been used in patients with hepatocellular carcinoma where it appears effec- tive in guiding and monitoring therapy (Liu et al. 2001; Meloni et al. 2001; Vilana et al. 2003).
However, CT is more sensitive than contrast-en- hanced ultrasound in assessing the response to ablative therapy (Meloni et al. 2001; Vilana et al. 2003). MR has the potential of measuring tem- perature and providing ”online” monitoring, but this capability is limited by several other practical considerations, including the difficulty of using RF in an MR machine.
In practice, patients are followed up with con- trast-enhanced CT or MR carried out the day after the procedure or later. Remaining viable tumour ap- pears as an enhancing area, which can be targeted at a subsequent session of treatment.
As with cryoablation, FDP-PET may be used to
assess the efficacy of treatment and in the follow-up
of patients who have been treated with RF ablation
(Langenhoff et al. 2002).
24.4.4
Patient Outcome
In the United Kingdom, the National Institute for Clinical Excellence (2003) has recently appraised the use of radiofrequency ablation in the treatment of hepatic tumours; it has made recommendations for RF ablation in hepatocellular carcinoma and is currently working on guidelines for RF ablation in the treatment of colorectal hepatic metastases. The results of several clinical series, which have used dif- ferent methods of radiofrequency ablation appear promising, with a 52%–67% complete ablation rate at 1 year and survival rates of 96%, 64% and 40%
at 1, 3 and 5 years, respectively (Livraghi et al.
1997; Rossi et al. 1996, 1998; Solbiati et al. 1997a, 1997b, 2001). More recently, Oshowo et al. (2003) have compared RF ablation and resection for the treatment of solitary colorectal hepatic metastases in an uncontrolled study. They found comparable median survival and 3-year survival for resection (41 months and 55.4%) and RF ablation (37 months and 52.6%). Approximately 39% of lesions develop local recurrence following treatment (Solbiati et al. 2001). The frequency and time to local recur- rence are related to the size of the lesion. In a recent series of 117 patients survival was not found to be influenced by the number of metastases at the time of initial therapy (Solbiati et al. 2001). This dif- fers from the results of some surgical series, which reported that tumour recurrence and/or survival were negatively influence by the number of metas- tases resected (Cady et al. 1970; Ekberg et al. 1987;
Gayowski et al. 1994). However, authors of larger and/or more recent reports have failed to confirm this correlation and have suggested that – in the range of the analyses (generally one to eight metas- tases removed) – survival following surgical resec- tion is not correlated with the number of metastases removed (Adson et al. 1984; Butler et al. 1986;
Fong et al. 1997; Fortner et al. 1984; Hughes et al.
1986; Iwatsuki et al. 1986; Nordlinger et al. 1987;
Petrelli et al. 1991; Rosen et al. 1992; Scheele et al. 1991). These findings suggest that the decision to treat should be guided more by the likelihood of achieving tumour control than the number of lesions present.
RF ablation also appears to be a safe and effec- tive technique for the treatment of patients with systemic symptoms from neuroendocrine metas- tases, although an effect on survival has not been established in this clinical setting (Henn et al.
2003).
24.5
Laser Ablation
Laser light can be converted into heat thus lead- ing to tissue coagulation. The use of laser for thermal ablation was described by Bown (1983).
Subsequently, experimental studies showed that a reproducible thermal injury can be produced with neodymium yttrium aluminium garnet (Nd:YAG) laser (Matthewson et al. 1987). The use of laser to treat patients with hepatic metastases was described by Steger et al. (1989).
From a single, bare 400 µm laser fibre, light at optical or near-infrared wavelengths scatters within tissue and is converted into heat. Light energy of 2.0–2.5 W produces a focal volume of coagulation 2 cm in diameter. Two methods have been developed for producing larger volumes of necrosis: the first uses multiple bare fibres arrayed at 2-cm spacing throughout a target lesion (Steger et al. 1989). The second uses cooled-tip fibres that can deposit up to 30 W over a surface area, thus diminishing local overheating (Nolsoe et al. 1993). Portable solid-state lasers are now available with outputs up to 30 W.
24.5.1
Patient Selection and Technique
The indications and contraindications for laser ab- lation, and the main complications and methods of follow-up are the same as for radiofrequency abla- tion and microwave coagulation. The procedures are usually guided with CT or ultrasound although MR is sometimes used as well. By inserting up to eight fibres simultaneously it is possible to achieve confluent necrosis of 6–7 cm in diameter. The ulti- mate burn size is governed by the tumour vascular- ity and by the vasodilatory response of surrounding normal liver parenchyma.
24.5.2
Patient Outcome
The survival data for patients undergoing laser abla-
tion of hepatic metastases is similar to that following
radiofrequency ablation. Gillams and Lees (2000)
have reported a median survival rate of 27 months
and a 5-year survival rate of 26%, and more recently
Vogl et al. (2002) have published a study of 603 pa-
tients with colorectal metastases, with median sur-
vival of 3.5 years and 5-year survival of 37%. In a
further large series of 2132 laser ablations performed in 899 patients the rate of major complications was 1.8% and mortality was 0.1% (Vogl et al. 2004).
Survival of patients with colorectal metastases is governed by technical success in ablating the tu- mour and a 5- to 10-mm margin of normal liver around the tumour and by the biologic behaviour of the neoplasms .
24.6
Microwave Coagulation
In microwave coagulation therapy, molecular di- poles are vibrated and rotated, resulting in thermal coagulation of the target tissue. The basic mecha- nism of heat generation in living tissue consists of rotation of water molecules. The rotation follows the alternating electric field component of the ultra- high-speed (2450 MHz) microwaves (Murakami et al. 1995). Microwaves emitted from the distal seg- ment of the percutaneous probe cause thermal co- agulation of the adjacent tissues. The equipment for microwave ablation consists of a microwave genera- tor and reusable needle electrodes. The electrodes are 25 cm long, 18-gauge monopolar units that are placed through 14-gauge access needles. Each needle electrode costs approximately £300 and the genera- tor costs approximately £30,000.
24.6.1
Patient Selection and Technique
The technique, patient selection and main com- plications are similar to those for radiofrequency and laser ablation. The procedure is usually guided with ultrasound or CT. Microwave treatment pro- duces coagulation within 60 s at a power setting of 60 W. However, the area of coagulation is smaller than that achieved after laser or radiofrequency and it is necessary to repeat the treatments several times a week in order to achieve a sufficiently large area of tumour necrosis. As with RF ablation, oc- clusion of segmental hepatic blood flow has been used with microwave ablation in the treatment of hepatocellular carcinoma to increase the size of the ablative lesion (Ishida et al. 2002). The use of multiple antennae is another technique, which has been described to achieve an increased volume of tumour necrosis (Wright et al. 2003; Xu et al.
2004).
24.6.2
Patient Outcome
Dong et al. (2003) report a 5-year survival of 56.7%
in 234 patients with hepatocellular carcinoma treated with microwave ablation therapy. Shibata et al. (2002b) compared RF and microwave ablation in the treatment of small hepatocellular carcino- mas and found no difference in therapeutic effect or complication rates between the two techniques, although RF ablation was completed with fewer ses- sions. There is less evidence for the therapeutic ef- fect of microwave ablation in patients with colorec- tal liver metastases. In one series of 74 patients with colorectal liver metastases a 5-year survival rate of 29% was achieved, with no major complications ob- served (Liang et al. 2003). At present, there is, how- ever no substantial series of patients with hepatic metastases treated with microwave coagulation.
24.7 Conclusion
When attempting to evaluate the benefits of inter- ventional radiological treatments for hepatic metas- tases, the questions that must be asked are:
1. Can they reliably ablate liver metastases?
2. Can they improve survival?
3. Are they safe?
Interpreting the results of methods of ablation is more difficult than assessing the outcome of hepatic resection (Primrose 2002).
Cryotherapy and radiofrequency treatment can ablate metastases in 50%–90% of cases and are relatively safe compared to hepatic resection.
With respect to overall survival, there has been no randomised comparison to show that either cryo- therapy or radiofrequency treatment alter long- term survival compared with chemotherapy alone.
However, this may be related to the fact that most
patients being referred for ablation are considered
unsuitable for hepatic resection. The ideal patient
for ablative therapy would be one who, several years
after a curative colonic resection for an early-stage
well-differentiated cancer develops a small metas-
tasis in the middle of a lobe of the liver (Primrose
2002). Such a patient is, however, also ideally suited
to surgical treatment and for such a patient the long-
term results of surgery are good. Interventional
therapy tends to be used in patients who are other- wise considered to be beyond the scope of conven- tional surgical treatment. It is possible that ablative therapy would achieve similar results to surgery if only similar patients were referred for this method of treatment.
At present, partial hepatic resection remains the method against which all interventional radiologi- cal methods of treatment have to be compared. It is important that prospective randomised trials comparing surgery with cryotherapy and radiofre- quency treatment are carried out in order to deter- mine the precise role of these modalities in patients with hepatic metastases.
References
Adam R, Hagopian EJ, Linhares M, et al (2002) A comparison of percutaneous cryosurgery and percutaneous radio- frequency for unresectable hepatic malignancies. Arch Surg 137:1332–1340
Adam A, Hatzidakis A, Hamady M, et al. (2004) Percutane- ous coil placement prior to liver radiofrequency ablation of poorly visible lesions. Eur Radiol (in press)
Adson MA, van Heerden JA, Adson MH, et al (1984) Resec- tion of hepatic metastases from colorectal cancer. Arch Surg 119:647–651
Baden H, Andersen B (1975) Survival of patients with untreated liver metastases from colorectal cancer. Scand J Gastroenterol 10:221–223
Bengtsson G, Carlsson G, Hafstrom L, et al (1981) Natural history of patients with untreated liver metastases from colorectal cancer. Am J Surg 141:586–589
Bown SG (1983) Phototherapy in tumors. World J Surg 7:700–709
Butler J, Attiyek FF, Daly JM (1986) Hepatic resection for metastases of the colon and rectum. Surg Gynecol Obstet 162:109–113
Cady B, Monson DO, Swinton NW (1970) Survival of patients after colonic resection for carcinoma with simultaneous liver metastases. Surg Gynecol Obstet 131:697–700 Chopra S, Dodd GD, Chanin MP, et al (2003) Radiofrequency
ablation of hepatic tumors adjacent to the gallbladder:
feasibility and safety. AJR Am J Roentgenol 183:697–
701
Cobourn CS, Makowka L, Langer B, et al (1987) Examination of patient selection and outcome for hepatic resection for metastatic disease. Surg Gynecol Obstet 165:239–246 Copper IS (1963) Cryogenic surgery: a new method of
destruction of extirpation of benign or malignant tis- sues. N Engl J Med 268:743–749
Cosman ER, Naswhold BS, Ovelman-Levitt J (1984) Theo- retical aspects of radiofrequency lesions in the dorsal root entry zone. Neurosurgery 15:945–950
de Baere T, Bessoud B, Dromain C, et al (2002) Percutane- ous radiofrequency ablation of hepatic tumors during temporary venous occlusion. AJR Am J Roentgenol 178:53–59
de Baere T, Risse O, Kuoch V, et al (2003) Adverse events during radiofrequency treatment of 582 hepatic tumors.
AJR Am J Roentgenol 181:695-700
Dodd GD, Soulen MC, Kane RA, et al (2000) Minimally invasive treatment of malignant hepatic tumors: at the threshold of a major breakthrough. Radiographics 20:9- 27
Dong B, Liang P, Yu X, et al (2003) Percutaneous sonographi- cally guided microwave coagulation therapy for hepa- tocellular carcinoma: results in 234 patients. AJR Am J Roentgenol 180:1547–1555
Ekberg H, Tranberg KG, Andersson R, et al (1987) Pattern of recurrence in liver resection for colorectal secondaries.
World J Surg 11:541–547
Fong Y, Blumgart LH, Cohen AM (1995) Surgical treatment of colorectal metastases to the liver. CA Cancer J Clin 45:50–62
Fong Y, Cohen AM, Fortner JG, et al (1997) Liver resection for colorectal metastases. J Clin Oncol 15:938–946 Fortner JG, Silva JS, Cox EB, et al (1984) Multivariate analysis
of a personal series of 247 consecutive patients with liver metastases from colorectal cancer. Ann Surg 199:317–
324
Foster JH (1978) Survival after liver resection for secondary tumors. Am J Surg 135:390–394
Gayowski TJ, Iwatsuki S, Madariaga JR, et al (1994) Expe- rience in hepatic resection for metastatic colorectal cancer: analysis of clinical and pathologic risk factors.
Surgery 116:703–711
Gillams AR, Less WR (2000) Survival after percutaneous, image-guided, thermal ablation of hepatic metastases from colorectal cancer. Dis Colon Rectum 43:656–661 Goldberg SN, Girnan GD, Lukyanov AN, et al (2002) Percu-
taneous tumor ablation: increased necrosis with com- bined radio-frequency ablation and intravenous liposo- mal doxorubicin in a rat breast tumor model. Radiology 222:797–804
Haddad FF, Chapman WC, Wright JK, et al (1998) Clinical experience with cryosurgery for advanced hepatobiliary tumors. J Surg Res 75:104–108
Henn AR, Levine EA, McNulty W, et al (2003) Percutane- ous radiofrequency ablation of hepatic metastases for symptomatic relief of neuroendocrine syndromes. AJR Am J Roentgenol 181:1005–1010
Hughes KS, Simon R, Songhorabodi S, et al (1986) Resec- tion of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence. Sur- gery 100:278–284
Ishida T, Murakami T, Shibata T, et al (2002) Percutaneous microwave tumor coagulation for hepatocellular car- cinomas with interruption of segmental hepatic blood flow. J Vasc Interv Radiol 13:185–191
Iwatsuki S, Esquivel CO, Gordon RD, et al (1986) Liver resec- tion for metastatic colorectal cancer. Surgery 100:804–
810
Kapoor BS, Hunter DW (2003) Injection of subphrenic saline during radiofrequency ablation to minimize diaphrag- matic injury. Cardiovasc Interv Radiol 26:302–304 Kato T, Nemoto R, Mori H, et al (1981) Arterial chemoem-
bolization with microencapsulated anticancer drug. An approach to selective cancer chemotherapy with sus- tained effects. JAMA 245:1123–1127
Kettenbach J, Kostler W, Rucklinger E, et al (2003) Percu-
taneous saline-enhanced radiofrequency ablation of unresectable hepatic tumors: initial experience in 26 patients. AJR Am J Roentgenol 180:1537–1545
Kitamoto M, Imagawa M, Yamada H, et al (2003) Radiofre- quency ablation in the treatment of small hepatocellu- lar carcinomas: comparison of the radiofrequency effect with and without chemoembolization. AJR Am J Roent- genol 181:997–1003
Langenhoff BS, Oyen WJ, Jager GJ, et al (2002) Efficacy of fluorine-18-deoxyglucose positron emission tomogra- phy in detecting tumor recurrence after local ablative therapy for liver metastases: a prospective study. J Clin Oncol 20:4453–4458
Liang P, Dong B, Yu X, et al (2003) Prognostic factors for percutaneous microwave coagulation therapy of hepatic metastases. AJR Am J Roentgenol 181:1319-1325 Liu JB, Goldberg BB, Merton DA, et al (2001) The role of con-
trast-enhanced sonography for radiofrequency ablation of liver tumors. J Ultrasound Med 20:517–523
Livraghi T (2001) Guidelines for treatment of liver cancer.
Eur J Ultrasound 13:167–176
Livraghi T, Giorgio A, Marin G, et al (1995) Hepatocellu- lar carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection. Radiology 197:101–108
Livraghi T, Goldberg SN, Monti F, et al (1997) Saline- enhanced radiofrequency tissue ablation in the treat- ment of liver metastases. Radiology 202:205–210 Livraghi T, Solbiati L, Meloni F, et al (2003a) Percutaneous
radiofrequency ablation of liver metastases in potential candidates for resection : the ”test-of-time approach”.
Cancer 97:3027–3035
Livraghi T, Solbiati L, Meloni MF, et al (2003b) Treatment of focal liver tumors with percutaneous radio-frequency ablation: complications encountered in a multicenter study. Radiology 226:441–451
Lu DS, Raman SS, Limanond P, et al (2003) Influence of large peritumoral vessels on outcome of radiofre- quency ablation of liver tumors. J Vasc Interv Radiol 14:1267–1274
Matthewson K, Coleridge-Smith P, O’Sullivan JP, et al (1987) Biological effects of intrahepatic neodymium: yttrium- aluminum-garnet laser photocoagulation in rats. Gas- troenterology 93:550–557
McPhee MD, Kane RA (1997) Cryosurgery for hepatic tumor ablation. Semin Interv Radiol 14:285–293
Meloni MF, Goldberg SN, Livraghi T, et al (2001) Hepato- cellular carcinoma treated with radiofrequency abla- tion: comparison of pulse inversion contrast-enhanced harmonic sonography, contrast-enhanced power Dop- pler sonography, and helical CT. AJR Am J Roentgenol 177:375–380
Murakami R, Yoshimatsu S, Yamashita Y, et al (1995) Treat- ment of hepatocellular carcinoma: value of percuta- neous microwave coagulation. AJR Am J Roentgenol 164:1159–1164
Nagorney DM, van Heerden JA, Ilstrup DM, et al (1989) Pri- mary hepatic malignancy: surgical management and determinants of survival. Surgery 106:740–749
National Institute for Clinical Excellence (2003) Radiofre- quency ablation of hepatocellular carcinoma. July 2003 Nolsoe CP, Torp-Pedersen S, Burcharth F, et al (1993) Inter- stitial hyperthermia of colorectal liver metastases with
a US-guided Nd-YAG laser with a diffuser tip: a pilot clinical study. Radiology 187:333–337
Nordlinger B, Quilichini MA, Parc R, et al (1987) Hepatic resection for colorectal liver metastases. Influence on survival of preoperative factors and surgery for recur- rences in 80 patients. Ann Surg 205:256–263
Organ LW (1976) Electrophysiologic principles of radiofre- quency lesion making. Appl Neurophysiol 39:69–76 Oshowo A, Gillams A, Harrison E, et al (2003) Compari-
son of resection and radiofrequency ablation for treat- ment of solitary colorectal liver metastases. Br J Surg 90:1240–1243
Pawlik TM, Izzo F, Cohen DS, et al (2003) Combined resec- tion and radiofrequency ablation for advanced hepatic malignancies: results in 172 patients. Ann Surg Oncol 10:1059–1069
Pedro MS, Semelka RC, Braga L (2002) MR imaging of hepatic metastases. Magn Reson Imaging Clin N Am 10:15–29 Petrelli N, Gupta B, Piedmonte M, et al (1991) Morbidity
and survival of liver resection for colorectal adenocar- cinoma. Dis Colon Rectum 34:988–904
Primrose JN (2002) Treatment of colorectal metastases:
surgery, cryotherapy, or radio-frequency ablation. Gut 50:1–5
Rosen CB, Nagorney DM, Taswell HF, et al (1992) Periop- erative blood transfusion and determinants of survival after liver resection for metastatic colorectal carcinoma.
Ann Surg 216:493–505
Rossi S, Di Stasi M, Buscarini E, et al (1996) Percutaneous RF interstitial thermal ablation in the treatment of hepatic cancer. AJR Am J Roentgenol 167:759–768
Rossi S, Buscarini E, Garbagnati F, et al (1998) Percutaneous treatment of small hepatic tumors by an expandable RF needle electrode. AJR Am J Roentgenol 170:1015–1022 Rossi S, Garbagnati F, Lencioni R, et al (2000) Percutane-
ous radio-frequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply. Radiology 217:119–126
Scheele J, Stangl R, Altendorf-Hofmann A, et al (1991) Indi- cators of prognosis after hepatic resection for colorectal secondaries. Surgery 110:13–29
Shibata T, Iimuro Y, Ikai I, et al (2002a) Percutaneous radio- frequency ablation therapy after intrathoracic saline solution infusion for liver tumor in the hepatic dome. J Vasc Interv Radiol 13:313–315
Shibata T, Iimuro Y, Yamamoto Y, et al (2002b) Small hepa- tocellular carcinoma: comparison of radio-frequency ablation and percutaneous microwave coagulation therapy. Radiology 223:331–337
Sica GT, Ji H, Ros PR (2002) Computed tomography and magnetic resonance imaging of hepatic metastases. Clin Liver Dis 6:165–179
Skjoldbye B, Pedersen MH, Struckmann J, et al (2002) Improved detection and biopsy of solid liver lesions using pulse-inversion ultrasound scanning and contrast agent infusion. Ultrasound Med Biol 28:439–444 Solbiati L, Goldberg SN, Ierace T, et al (1997a) Hepatic metas-
tases: percutaneous radio-frequency ablation with cooled-tip electrodes. Radiology 205:367–373
Solbiati L, Ierace T, Goldberg SN, et al (1997b) Percutane- ous US-guided radio-frequency tissue ablation of liver metastases: treatment and follow-up in 16 patients.
Radiology 202:195–203
Solbiati L, Livraghi T, Goldberg SN, et al (2001) Percutane- ous radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients.
Radiology 221:159–166
Steele G Jr, Bleday R, Mayer RJ, et al (1991) A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: gastrointestinal tumor study group protocol 6584. J Clin Oncol 9:1105–1112
Steger AC, Lees WR, Walmsley K, et al (1989) Interstitial laser hyperthermia: a new approach to local destruction of tumors. BMJ 299:362–365
Vilana R, Llovet JM, Bianchi L, et al (2003) Contrast- enhanced power Doppler sonography for assessment of vascularity of small hepatocellular carcinomas before and after percutaneous ablation. J Clin Ultrasound 31:119–128
Vogl TJ, Straub R, Eichler K, et al (2002) Malignant liver tumors treated with MR imaging-guided laser-induced thermotherapy: experience with complications in 899 patients (2,520 lesions). Radiology 225:367–377
Vogl TJ, Straub R, Eichler K, et al (2004) Colorectal carci- noma metastases in liver: laser-induced interstitial ther-
motherapy-local tumor control rate and survival data.
Radiology 230:450–458
Wood CB, Gillis CR, Blumgart LH (1976) A retrospective study of the natural history of patients with liver metas- tases from colorectal cancer. Clin Oncol 2:285–288 Wright AS, Lee FT, Mahvi DM (2003) Hepatic microwave
ablation with multiple antennae results in synergisti- cally larger zones of coagulation necrosis. Ann Surg Oncol 10:275–283
Xu HX, Xie XY, Lu MD, et al (2004) Ultrasound-guided per- cutaneous thermal ablation of hepatocellular carcinoma using microwave and radiofrequency ablation. Clin Radiol 59:53–61
Yamakado K, Nakatsuka A, Akeboshi M, et al (2003) Per- cutaneous radiofrequency ablation of liver neoplasms adjacent to the gastrointestinal tract after balloon cath- eter interposition. J Vasc Interv Radiol 14:1183–1186 Yamasaki T, Kurokawa F, Shirahashi H, et al (2002) Percuta-
neous radiofrequency ablation therapy for patients with hepatocellular carcinoma during occlusion of hepatic blood flow. Comparison with standard percutaneous radiofrequency ablation therapy. Cancer 95:2353–2360
