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Liver ablation therapy

Department of Medical Imaging, The Middlesex Hospital, Mortimer Street, London W1T 3AA, UK

	Introduction

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
The first description of percutaneous ethanol injection (PEI) was published in 1986, a small series of just 14 patients with small, non-resectable hepatocellular carcinoma (HCC) [1]. Thermal techniques were first performed in the liver at our institution in 1989, initially using single bare tip neodymium yttrium aluminium garnet (NdYAG 1064 nm) laser fibres placed under ultrasound guidance [2]. 15 years on there are hundreds of centres performing thousands of ablations mostly using radiofrequency (RF). The most common site for treatment remains the liver but ablation has been performed in many other sites including lung, renal, adrenal, pleura, bone, pelvic tumours and nodal masses. Two particularly promising areas of development are RF ablation for inoperable lung cancer and as a minimally invasive, nephron sparing technique in renal cell carcinoma. This article looks at liver ablation; the different technologies available, the clinical results and current status of ablation in patients with colorectal liver metastases, neuroendocrine metastases and non-colorectal, non-neuroendocrine metastases, e.g. breast, and HCC.

	Technical aspects

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
Energy sources can be grouped into three major categories: those employing thermal energy, either heating or cooling, direct injection therapies and photodynamic therapy.

Thermal energy
With all the heating techniques the aim is to raise the temperature of the tissue to be destroyed to between 60°C and 100°C. This is to produce coagulative necrosis yet avoid charring and vaporization of tissue. There are five thermal techniques: RF, laser, microwave, cryotherapy and high intensity focused ultrasound (HIFU) [3]. A summary of their characteristics is shown in Table 1.

Laser
Both NdYAG and solid state Lasers ( 805 nm) have been used successfully in tumour ablation. Photon absorption and heat conduction produce hyperthermia and coagulative necrosis. Laser energy is delivered through flexible thin fibres of diameter 400–600 µm or via a specially designed internally water cooled laser applicator (Somatex, Teltow, Germany). Fibre morphology can be varied depending on the area to be treated. A point source from a bare tip fibre will produce a sphere of necrosis whereas a diffuser fibre will produce an elliptical ablation. Low power (< 16 W) laser was used in the early years but output power levels were increased to 40 W in 1998. Although more expensive to set up and support than RF, Laser ablations are a little more predictable. Laser energy is deposited around the fibre tip whereas RF pathways and therefore energy deposition may vary, and are therefore more complex and less predictable. For most ablations, multiple laser applicators are used.

Microwave
Microwaves (2450 MHz) cause rotation and vibration of water molecules thus producing heat. The equipment consists of a generator and a monopolar needle electrode, which is introduced through a 14 G access needle. Multiple percutaneous electrodes are generally required. Each microwave application produces a discrete focus of necrosis, e.g. a single treatment for 120 s at 60 W provides approximately 1.6 cm of necrosis. For this reason microwave ablation has most often been used for the treatment of small (<3 cm) HCC.

Cryotherapy
Cryotherapy uses repetitive freezing and thawing of tissue to produce necrosis. Irreversible tissue destruction occurs at temperatures below –20 to –30°C. Liquid nitrogen and argon gas are used as coolants. Traditional cryotherapy probes have been large requiring laparotomy access for the treatment of liver tumours. In recent years percutaneous cryotherapy probes of less than 2.5 mm in diameter have been developed. Cryoprobes of different sizes and shape are available to map the morphology of the area to be treated. The development of the ice ball can be monitored using ultrasound or MR guidance with an accuracy of 1–5 mm.

High intensity focused ultrasound
HIFU uses frequencies of 0.8–3.2 MHz and focal peak intensities of 5000–20 000 W cm^–2. [13]. The basic mechanism is heat induced coagulative necrosis but pathological studies demonstrate particular damage to vessels including tumour microvasculature [14]. HIFU has the advantage of being a trackless technique, performed without anaesthesia and with no risk of tumour seeding. A clear acoustic path from skin to the tissue to be ablated is required. The technique has been available since the 1940s but improvements in imaging and in HIFU technology, e.g. variable focusing and electronic beam steering, have renewed interest in the technique. The main problem is the limited amount of necrosis that can be achieved per unit time. Most work has been performed in the prostate using transrectal devices.

Direct injection therapies
Ethanol, acetic acid and gel stabilized chemotherapeutic agents have all been used to ablate tumours with variable success. Gene therapy is hypothesised as the therapy of tomorrow.

Percutaneous ethanol injection
PEI was one of the first effective ablative techniques to be widely adopted for the treatment of small HCCs. Ethanol causes dehydration and subsequently necrosis [15]. Under ultrasound guidance a fine needle (21–22 G) is introduced into the tumour and 95–100% ethanol injected. To achieve complete ablation the ethanol must reach all parts of the tumour however ethanol spreads unevenly and the needle needs to be repositioned accordingly. Ethanol can reflux along the needle tract and cause pain; this limits the amount that can be injected at any one time in the conscious patient. PEI is therefore either performed as a multistage, outpatient technique under conscious sedation or as a single stage procedure under general anaesthesia. PEI is most effective in encapsulated HCC and is of little benefit in infiltrating HCC or in metastases. The scirrhous nature of liver metastases restricts the amount of ethanol that can be injected, often leading to extravasation and incomplete necrosis. Thermal techniques are therefore preferred for the treatment of metastases. In HCC, thermal techniques provide more necrosis in less time and in fewer sessions. PEI still has a role in the treatment of HCC not amenable to RF, e.g. exophytic lesions which can rupture with disastrous consequences during heating.

Photodynamic therapy (PDT)
The interaction of a photosensitizer administered systemically and light of a particular wavelength results in necrosis [16–18]. The mediator is thought to be the production of oxygen free radicles. There are several porphyrin based photosensitizing agents which vary in administration, tissue uptake, optimal wavelength of light for treatment, duration for which the patient remains photosensitized and effectiveness. In the gastrointestinal tract, oral 5 amino laevulinic acid (5ALA) works well for superficial treatments. For interstitial therapy meso-tetra-hydro-phenylchlorin (mTHPC), which optimally reacts to red light at 652 nm, is available for trials. Maximal necrosis is seen at 3 days post-treatment with mTHPC. Historically assessment of the treatment effect has not been possible during treatment but a recent paper demonstrated the possibility of using MR assessment of oxygen consumption to monitor PDT [19].

	Current status of the different techniques

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
All the thermal techniques have been tried in the liver. Today PEI has largely been replaced by Laser or RF ablation in most centres. Although both of these latter techniques are effective, currently RF is the preferred technique and the one most widely practiced. Laser has the advantage of being more MR compatible permitting direct MR monitoring [20]. MR compatible RF electrodes are now available but the application of RF current and image acquisition are incompatible and have to be alternated. Comparisons of Laser and RF suggest that larger volumes of ablation and in particular the ablation of a margin of normal liver has been easier and quicker to achieve with RF [21]. Cryoablation whilst effective carries a higher complication rate. Animal work has shown that whereas cryoablation results in acute lung injury, RF does not [22]. Comparisons of laparoscopic RF with cryoablation have shown a lower complication rate with RF [23]. One study reported a 40.7% complication rate with cryotherapy compared with 3.3% with RF [24]. Comparisons of percutaneous cryotherapy and RF have shown a higher complete ablation rate with RF [25]. Microwave has been used particularly in China to treat small HCC [26, 27]. Current microwave applicators are large and several are usually required, one of the focuses of development is to produce a smaller percutaneous probe. A few centres have performed PDT. Currently PDT suffers from being a dual component technique with the additional variables of drug delivery and uptake in tissue as well as all the variables that effect light delivery. HIFU is slow requiring long treatment times, overlying ribs or lung may obscure the acoustic path and prevent access to some lesions, limited depth of penetration will exclude others. Currently RF is the preferred technique for liver tumour ablation.

	Pathological validation of RF ablation

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
Efficacy of RF has been validated in at least two cohorts of patients who subsequently underwent surgical resection [28, 29]. Pathological specimens that were resected immediately after ablation showed irreversible cell damage with absence of enzymatic activity. RF ablation induced necrosis fundamentally differs from ordinary tissue death. When cells are lethally injured membrane dysfunction and release of enzymes degrades the cellular components. The entire process takes hours to days followed by weeks of tissue repairing. In heat ablation the affected structures are subjected to instantaneous thermal fixation, equivalent to that produced by formalin. Thermally induced deactivation of the enzyme protein prevents the cell degradation seen in traditional coagulation necrosis. Consequently, with conventional staining techniques, the tissue architecture and cytological details appear well preserved, despite absence of any activity on enzymatic histochemical assays. However, the loss of enzymatic activity does not exclude antigenicity of the denatured enzyme proteins which explains positive results in RF ablated lesions on immunohistochemistry. The pronounced vascular destruction associated with RF ablation often postpones healing by blocking neutrophils with hydrolytic enzymes from access into the lesion. This can result in incomplete absorption and fibrous encapsulation of the residual lesion. Lack of cell viability can be determined early after RF ablation by a negative reaction with enzymatic histochemical stains, e.g. lactate-dehydrogenase or maleate-dehydrogenase, and nicotinamide adenine dinucleotide-diaphorase [30].

	Approach: percutaneous, laparoscopic or open?

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
RF ablation can be performed using image guidance and a percutaneous approach [31–34], laparoscopic guidance [35–37] or at open laparotomy [38–40]. At open laparotomy, RF can be combined with liver resection, i.e. resection of one area of the liver and ablation of another. Pawlik et al reported on combined resection and ablation in 172 patients and noted that the combined modality treatment was well tolerated; the mortality was 2.3% and the post-operative complication rate was 19.8% [41]. If a patient is undergoing laparotomy for another surgical procedure, which allows access to the liver, then it is reasonable to perform RF at the same time. With this exception it is difficult to justify the added morbidity, invasiveness and expense of a laparotomy compared with a percutaneous procedure. The laparoscopic approach has been used when tumour is adherent to structures that would be damaged by thermal ablation, e.g. tumour adherent to stomach, colon or duodenum. Some centres prefer the laparoscopic approach where there is poor tumour visualization transcutaneously and also for large HCCs requiring multiple punctures [42, 43]. RF ablation will most commonly be performed in the radiology department, but there is a subgroup of patients who will benefit from open or laparoscopic RF [44].

	Thermal ablation and blood flow manipulation

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
Normal liver responds to thermal injury with an increase in perfusion. Using CT we have quantified this effect in a group of 32 patients [45]. There was a mean 3.3-fold increase in hepatic arterial flow adjacent to the ablated area. Tissue perfusion has a direct impact on the volume of necrosis that can be produced. This has been confirmed using pharmacological manipulation where for example, a halothane induced reduction in blood flow of 46% resulted in a 50% increase in the diameter of the ablation [46]. Several groups have explored vascular occlusion as a method for increasing the volume of necrosis [47, 48]. Vascular occlusion either portal venous, hepatic arterial or both has been shown to be beneficial in animal models with increases in measured temperature at the treatment site and increases in the size of ablation [49, 50]. Surgeons have the option of clamping the vascular pedicle during RF ablation and percutaneous balloon occlusion is also effective. Although vascular occlusion increases the volume of ablation it also removes the protective effect of blood flow and as a result there is an associated increase in bile duct injury. An alternative approach, favoured by our group, is the use of hypotensive general anaesthesia, similar to that used at hepatic resection, i.e. maintenance of a systolic pressure of approximately 80 mmHg [51]. The above techniques are aimed at a reduction in tissue perfusion. A variant on this technique is balloon occlusion of a specific vessel during treatment of a tumour lying immediately adjacent to that vessel. This reduces the incidence of tumour recurrence but also increases the complication rate.

	Colorectal metastases

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
Limited colorectal liver metastases are the most commonly treated metastatic lesion. There is good evidence that most patients will succumb from their liver metastases and therefore local control can improve life expectancy. Surgical resection is the accepted first line treatment for patients with resectable disease. 5 year survival figures range from 25% to 39% [52]. Traditionally most patients (80–90%) are not candidates for surgical resection due to extent or distribution of disease or concurrent medical disability [53]. Although historical chemotherapy results have been disappointing in the last 3–4 years the results have improved. Irinotecan has resulted in the first improvement in survival to reach significance with a median of 17.4 months and 1 year survival of 69% [54]. Improved response rates have been achieved with Oxaliplatin, 53% compared with 28% with 5FU and folinic acid [55]. More recent data suggests that sequential Oxaliplatin and Irinotecan will improve survival by a further 2–3 months [56]. There are both surgical and RF papers showing that downsizing with neoadjuvant chemotherapy followed by ablation or resection (Figure 1) is useful [57, 58]. An important caveat to this approach is that all the original sites of disease should be treated.

View larger version (114K): [in this window] [in a new window]   Figure 1. 73-year-old with multiple colorectal liver metastases previously treated with chemotherapy, referred for ablation after downsizing. (a) Contrast enhanced CT showing two small colorectal metastases (arrows). (b) CT scan just caudal to (a) showing a third metastasis (arrow). (c) Post-ablation CT scan showing three areas of ablation that encompass the whole tumour plus a margin of normal liver. (d) Follow-up CT scan 12 months later showing two of the lesions are reducing in size and healing with no evidence of recurrence. However, inferior to the third lesion there is tumour recurrence adjacent and in the left portal vein branch. Large vessels cool and protect tumour from heating and recurrence is common next to vessels. This case is unusual in that the tumour has invaded the portal vein. This was further downsized by chemotherapy and then ablated. (e) CT scan 23 months after initial ablation treatment showing continuing healing of the two smallest lesions. There is now atrophy of the left lobe of the liver and an area of absent enhancement at the ablation site around the left portal vein. There is currently no evidence of active tumour.

Our current recommendation is to accept patients with five metastases or fewer and a maximum diameter of 5 cm. Where the distribution of disease is not amenable to surgery, the use of RF or a combination of RF and resection can be considered. For those with concurrent disability, RF is a much less invasive alternative than surgery with lower complication rates. Other applications for RF include patients with limited liver disease who have insufficient residual liver to allow resection, usually post-hemihepatectomy patients with new metastases in the residual lobe and those who have been downsized but are still not surgical candidates. Randomized, controlled trials are now in process. The European Organisation for Research and Treatment of Cancer (EORTC) sponsored Chemotherapy+Local ablation versus Chemotherapy (CLOCC) trial aims to compare the effect of ablation in conjunction with systemic chemotherapy with systemic chemotherapy alone in patients with inoperable colorectal metastases. The acceptance criteria for this trial are more generous than traditional acceptance criteria. Patients can have as many as nine metastases with a maximum diameter of the largest tumour of 4 cm (Table 2).

In one study RF ablation was used to treat small tumours <4 cm in diameter prior to surgery as part of a "test-of-time" approach to treatment [69]. 60% of patients achieved complete ablation and did not require surgical resection. This approach allowed the detection of further occult metastases that would have negated the impact of surgical resection. Despite these encouraging results attempts to run a trial comparing surgical resection and ablation in surgical disease have so far failed.

	Neuroendocrine metastases

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
Although numerous treatments have been tried in this group of patients, there are very few effective therapies. Few patients are eligible for surgery and historically the other treatment modalities have produced symptomatic improvement but have had less impact on tumour load [70]. The natural history of the disease is widely variable but often these patients develop numerous, small, relatively slowly enlarging liver metastases over a period of many years. The ideal technique would be minimally invasive, have little effect on normal liver and be readily repeatable. Embolisation partly fulfils these criteria and some of the best published results are from repeated embolisation [71]. RF ablation fulfils all the desired criteria. RF can be used to reduce hormone secretion and/or to reduce tumour load [72]. Aggressive cytoreduction can reverse somatostatin analogue resistance and reduce drug requirements. Cytoreduction followed by octreotide analogues can be the best way to achieve prolonged symptom control [73].

Siperstein et al initially reported on 15 patients and more recently on 34 patients successfully treated with laparoscopic RF [35, 74]. Anders et al have treated 42 patients and achieved 90% complete ablation at a mean follow-up of 3.2 years (range 3 months to 5.5 years) (Personal communication). The same group have published their results in 21 patients treated with RF±resection [75]. In our experience in 25 patients we achieved local control of tumour volume in 14 of 19 (74%) at a median follow-up of 21 months (range 4–75) and relief or a reduction in hormone related symptoms in 9 of 14 (69%) with secreting tumours. Theoretically a reduction in tumour load could eventually translate into a survival benefit but much longer follow-up will be required to establish any improvement in survival. In our group median survival from the diagnosis of liver metastases was 53 months [76]. In Scandinavia there is an on-going trial of ablation plus biotherapy versus biotherapy alone that should provide some of the answers.

	Non-colorectal, non-neuroendocrine metastases including breast

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
Isolated liver metastases are an uncommon occurrence in breast cancer. Some surgeons will perform hepatic resection for limited liver metastases. A 22% 5-year survival post resection has been reported [77]. RF has been performed to good effect, Livraghi reported on 24 patients of whom 10 were free of disease at a mean follow-up of 10 months [78]. Our experience in 21 patients is similar. Follow-up is available in 19 of whom 6 (32%) have survived a minimum of 21–2 years, including 3 who have lived longer than 4 years (maximum 74 months), 8 have progressed and died within 12 months. Most experience has been gained by Vogl et al using Laser but they have not yet published their breast cancer data separate from other types of tumour. There is limited experience of RF in other non-colorectal, non-neuroendocrine metastases, but good surgical results have been reported when there has been an interval of more than 2 years between the primary and the development of detectable metastatic disease [79], therefore RF could be considered in these patients if they are not candidates for surgery.

	Hepatocellular carcinoma

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
Established experience with PEI has facilitated the introduction of RF to treat HCC (Figure 2). Trials of PEI and liver resection suggested a comparable survival. In one trial, Childs Pugh Class A patients had a 3 year survival of 71% following PEI compared with 79% following surgery and Childs Pugh Class B patients had a 3 year survival of 41% and 40%, respectively [80]. RF has been compared with PEI and been shown to have a higher complete ablation rate (90% vs 80%) in fewer treatment sessions but also a slight increase in the complication rate [81]. A similar study of 119 consecutive patients with solitary HCC <3 cm treated with either RF ablation (n=23) or ethanol ablation (n=96) showed complete tumour response in 23 patients (100%) in an average of 1.5 sessions treated with RF and in 90 patients (94%) in an average of 4 sessions treated by ethanol injection [82]. More recently a randomized controlled trial of RF and PEI in 102 patients showed a significantly longer disease free survival with RF [83]. The 1 and 2 year local recurrence-free survival rates were 98% and 96% in the RF group compared with 83% and 62% in the ethanol injection group (p=0.002). There was a trend towards increased overall survival with RF but this has not yet reached significance.

View larger version (105K): [in this window] [in a new window]   Figure 2. Hepatocellular carcinoma on a background of cirrhosis in an 80-year-old male. The tumour lies adjacent to the branches of the right portal vein branch. (a) Arterial phase CT scan showing a hypervascular lesion in the right lobe (arrow). (b) Post-ablation CT showing complete ablation with no evidence of residual tumour. (c) Follow-up CT scan 15 months later showing healing ablation with no evidence of tumour. (d) Follow-up CT scan 26 months post-ablation shows a nodule of enhancement on the medial border of the tumour inferior to the posterior branch of the right portal vein consistent with recurrent tumour (arrow). This was treated with further radiofrequency ablation. (e) Current CT scan 3 years after the initial ablation; no evidence of active tumour but worsening background cirrhosis.

Encapsulated HCC is generally easier to destroy than metastases as the heat is contained and amplified within the lesion, a phenomenon known as the "oven effect". Microwave has also been used in HCC but again comparative studies suggest that RF is more efficacious [85]. Several centres use Laser effectively in the treatment of HCC, to date there has been no comparison of Laser and RF in HCC [86]. Current recommendations for RF in HCC are Childs Pugh Class A or B cirrhosis and a single lesion <5 cm in diameter or up to three lesions, less than 3 cm in diameter (Table 2) [87]. Despite screening programmes many patients present with larger tumours. Combinations of selective transarterial chemoembolisation (TACE) and thermal ablation have been explored with some success in this group [88, 89]. Although there have been many published studies using TACE it has been difficult to show a survival benefit. A meta-analysis published in 2002 succeeded in showing a significant improvement in survival, albeit short, but could not show a benefit for TACE over embolisation alone [90]. Therefore a combined approach would appear to be reasonable. Different techniques have been used, e.g. Laser followed weeks later by TACE, or balloon occlusion of the hepatic artery during RF followed by selective catheterization of the tumour feeding vessels and chemoembolisation immediately afterwards. This technique is promising, e.g. in one study of 62 patients with a single large HCC mean diameter 4.7 cm (range 3.5–8.5 cm) the complete ablation rate at 12 months was 82% [91]. In patients with decompensated cirrhosis RF has been shown to be superior to TACE both in survival and in the number of complications [92].

	Complications

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
The complication rate following ablation varies from 2% to 10.6% and the mortality from 0.1% to 1.4% [93–97]. Needle puncture or thermal injury can result in subcapsular haematoma, occlusion or thrombosis of hepatic veins or portal vein branches, bile duct strictures or injury to adjacent viscera such as stomach, duodenum, gall bladder, colon (manifested as perforation or fistula formation) or the lung or pleura (pneumothorax or pleural effusions). More recently a technique known as "dextrose isolation" has been used to displace any vulnerable structures away from the ablation zone [98] (Figure 3). The same technique can be used to render lesions in the dome of the diaphragm that are ultrasound occult ultrasound visible by displacing overlying lung [99]. Similarly it can be used to overcome poor access to superficial lesions lying just deep to a rib.

View larger version (59K): [in this window] [in a new window]   Figure 3. 39-year-old female with multiple breast metastases (not shown). (a) Ultrasound scan performed during treatment demonstrating "Dextrose isolation". 5% dextrose has been injected through a 19 G needle into the hepatocholecystic space (thin arrow) to displace the gall bladder wall away from the metastasis to be treated (thick arrow). (b) Contrast enhanced CT scans performed the following day showing ablation of the metastasis (arrow) without damage to the gall bladder wall.

More unusual complications include hyperkalaemia in patients with chronic renal failure due to release of potassium from disrupted cells [100], rupture of exophytic HCC and pacemaker malfunction if the pacemaker lies in the path between the active electrode and the grounding pads. Grounding pad burns were reported with earlier technology but are now unusual. In patients with hip replacements the grounding pads should be moved from the thighs to the torso to avoid burns. Guide needles and hormone replacement patches may also pick up current resulting in burns.

The potential for tumour seeding has generated some discussion. Several mechanisms for tumour seeding have been proposed. Viable tumour cells that adhere to the RF electrode can be disseminated along the electrode tract during removal. Tumour cells may be carried into the tract with even a small amount of bleeding. Cells may be forced into the tract by sudden increases in intratumoural pressure such as commonly occurs during RF ablation. Finally tumour cells can be dislodged when saline is injected into the tumour. Although an early report by Llovet et al reported an extremely high rate (12.5%) [101], the incidence of tumour seeding in other multicentre studies is lower [95–97, 102]. Livraghi et al reported the incidence of tumour seeding along the course of original electrode tract as 0.5%. These seeding foci were seen 4–18 months following ablation. 75% of the tumours that developed tract seeding were superficial in location [103]. To avoid tumour seeding, the number of punctures and repeated repositioning of the RF needle electrode should be minimized, the needle tract should be selected to traverse normal liver parenchyma particularly in subcapsular tumours and the tract should be cauterized.

	Imaging assessment and follow-up

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
The aim of treatment is complete tumour ablation with a margin of apparently normal tissue without collateral damage. Treatment efficacy is improved by intraprocedural imaging assessment. HCC can be assessed with contrast enhanced ultrasound [104]. Treatment efficacy can also be assessed by dynamic contrast enhanced CT or MR. Complete ablation is demonstrated by the absence of enhancement. Immediately after ablation it is common to see gas within the ablation zone, possibly some hyperattenuation consistent with small amounts of haemorrhage and following intravenous contrast reactive hyperaemia around the tumour. We routinely perform contrast enhanced CT 18 h after ablation to provide a baseline for further evaluation (Figure 3b). A completely ablated lesion will become homogeneous, well defined and slowly decrease in size. Despite the appearance of complete ablation, recurrence adjacent to the ablated area can occur particularly where blood flowing in adjacent vessels results in tissue cooling and protects microscopic quantities of tumour (Figures 1 and 2). The accepted definition is any evidence of hypovascular or hypervascular tumour adjacent or within the ablation zone with or without an increase in the size of the lesion. Although recurrence is most often at the edge of the ablation zone, occasionally tumour recurrence will "fill-in" an ablation zone without an increase in overall lesion size. Some groups have used size criteria to detect recurrence but this is too crude. Younger patients and patients with cirrhosis demonstrate more rapid liver regeneration. Occasionally the ablation zone will all but disappear.

In patients with colorectal metastases new tumours develop in the liver at a distance from the ablated site in 57% [64]. For HCC the 5 year recurrence rate in the liver following successful resection varies from 67.6% to 100% [105]. Therefore an important aspect of ablation is careful, structured imaging follow-up with dynamic contrast enhanced CT or MR to detect new lesions and recurrence such that further ablation can be offered as appropriate.

	Conclusions

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 
Liver ablation has become a proven and accepted part of the management of HCC. The role of ablation in colorectal metastases is still evolving. Currently it is reasonable to offer ablation to patients with limited disease who are not suitable candidates for resection. Ablation should be used in conjunction with systemic chemotherapy, the relationship between the treatments depends on the tumour load. Some tumours will need to be downsized by chemotherapy in order for ablation to be performed. For patients with ablatable disease, ablation should be performed first and followed by systemic chemotherapy. Small numbers make it harder to define the role of ablation in neuroendocrine, breast and other non-colorectal, non-neuroendocrine tumours but undoubtedly one will develop. Finally, although ablation has come a long way from the early days when only 1 cm spheres of tissue could be ablated, there are further important technical developments that are needed to improve the reliability and predictability of ablation treatments.

Received for publication April 13, 2004. Accepted for publication June 8, 2004.

	References

Top Introduction Technical aspects Current status of the... Pathological validation of RF... Approach: percutaneous,... Thermal ablation and blood... Colorectal metastases Neuroendocrine metastases Non-colorectal, non... Hepatocellular carcinoma Complications Imaging assessment and follow-up Conclusions References

 

1. Livraghi T, Festi D, Monti F, Salmi A, Vettori C. US-guided percutaneous alcohol injection of small hepatic and abdominal tumors. Radiology 1986;161:309–12.[Abstract/Free Full Text]
2. Steger A, Lees W, Walmsley K, Bown S. Interstitial laser hyperthermia: a new approach to local destruction of tumours. Br Med J 1989;299:362–5.
3. Dodd G, Soulen M, Kane R, et al. Minimally invasive treatment of malignant hepatic tumors: at the threshold of a major breakthrough. Radiographics 2000;20:9–27.[Abstract/Free Full Text]
4. Curley S, Davidson B, Fleming R, et al. Laparoscopically guided bipolar RF ablation of areas of porcine liver. Surg Endosc 1997;11:729–33.[CrossRef][Medline]
5. Lorentzen T. A cooled needle electrode for RF tissue ablation: thermodynamic aspects of improved performance compared with conventional needle design. Acad Radiol 1996;3:556–63.[CrossRef][Medline]
6. Goldberg SN, Gazelle GS, Dawson SL, Rittman WJ, Mueller PR, Rosenthal DI. Tissue ablation with RF using multiprobe arrays. Acad Radiol 1995;2:670–4.[Medline]
7. Miao Y, Ni Y, Yu J, Marchal G. A comparative study on validation of a novel cooled-wet electrode for RF liver ablation. Invest Radiol 2000;35:438–44.[CrossRef][Medline]
8. Miao Y, Ni Y, Mulier S, et al. Ex-vivo experiment on RF liver ablation with saline infusion through a screw-tip cannulated electrode. J Surg Res 1997;71:19–24.[CrossRef][Medline]
9. Livraghi T, Goldberg N, Monti F, et al. Saline enhanced RF tissue ablation in the treatment of liver metastases. Radiology 1997;202:205–10.[Abstract/Free Full Text]
10. Goldberg SN, Ahmed M, Gazelle GS, et al. Radio-frequency thermal ablation with NaCl solution injection: effect of electrical conductivity on tissue heating and coagulation—phantom and porcine liver study. Radiology 2001;219:157–65.[Abstract/Free Full Text]
11. McGahan JP, Dodd GD. RF ablation of the Liver. Current status. AJR Am J Roentgenol 2001;176:3–16.[Free Full Text]
12. De Baere T, Denys A, Wood B, et al. RF liver ablation: experimental comparative study of water-cooled versus expandable systems. AJR Am J Roentgenol 2001;176:187–92.[Abstract/Free Full Text]
13. Ter Haar G. High intensity ultrasound. Semin Laparosc Surg 2001;8:77–89.[CrossRef][Medline]
14. Wu F, Chen W, Bai J, et al. Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound. Ultrasound Med Biol 2001;27:1099–106.[CrossRef][Medline]
15. Livraghi T. Percutaneous ethanol injection in the treatment of HCC in cirrhosis. Hepatogastroenterology 2001;48:20–4.[Medline]
16. Moore JV, West CML, Whitehurst C. The biology of photodynamic therapy. Phys Med Biol 1997;42:913–35.[CrossRef][Medline]
17. Dougherty TJ. Photodynamic therapy (PDT) of malignant tumors. Crit Rev Oncol Hematol 1984;2:83–116.[Medline]
18. Li JH, Guo ZH, Jin ML, et al. Photodynamic therapy in the treatment of malignant tumours: an analysis of 540 cases. J Photochem Photobiol B 1990;6:149–55.[CrossRef][Medline]
19. Gross S, Gilead A, Scherz A, Neeman M, Salomon Y. Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI. Nat Med 2003;9:1327–31.[CrossRef][Medline]
20. Vogl T, Muller P, Hammerstingl R, et al. Malignant liver tumors treated with MR imaging – guided Laser-induced thermotherapy: technique and prospective results. Radiology 1995;196:257–65.[Abstract/Free Full Text]
21. Lees WR, Gillams A. Comparison of the effectiveness of cooled tip RF and interstitial laser photocoagulation in liver tumour ablation. Radiology 1999;213P:122.
22. Chapman WC, Debelak JP, Wright-Pinson C, et al. Hepatic cryoblation, but not RF ablation, results in lung inflammation. Ann Surg 2000;231:752–61.[CrossRef][Medline]
23. Bilchik AJ, Wood TF, Allegra D, et al. Cryosurgical ablation and RF ablation for unresectable hepatic malignant neoplasms. Arch Surg 2000;135:657–64.[Abstract/Free Full Text]
24. Pearson S, Izzo F, Fleming R, et al. Intraoperative RF ablation or cryoablation for hepatic malignancies. Am J Surg 1999;178:592–9.[CrossRef][Medline]
25. Adam R, Hagopian E, Linhares M, et al. A comparison of percutaneous cryosurgery and percutaneous RF for unresectable hepatic malignancies. Arch Surg 2002;137:1332–9.[Abstract/Free Full Text]
26. Xu H, Sie X, Lu M, et al. Ultrasound-guided percutaneous thermal ablation of hepatocellular carcinoma using microwave and RF ablation. Clin Radiol 2004;59:53–61.[CrossRef][Medline]
27. Liang P, Dong B, Yu X, et al. Prognostic factors for percutaneous microwave coagulation therapy of hepatic metastases. AJR Am J Roentgenol 2003;181:1319–25.[Abstract/Free Full Text]
28. Scudamore CH, Lee SI, Patterson EJ, et al. RF ablation followed by resection of malignant liver tumors. Am J Surg 1999;177:411–7.[CrossRef][Medline]
29. Goldberg S, Scott Gazelle G, Compton C, Mueller P, Tanabe K. Treatment of intrahepatic malignancy with RF ablation. Radiologic-pathologic correlation. Cancer 2000;88:2452–63.[CrossRef][Medline]
30. Morimoto M, Sugimori K, Shirato K, et al. Treatment of hepatocellular carcinoma with RF ablation: radiologic-histologic correlation during follow-up periods. Hepatology 2002;35:1467–75.[CrossRef][Medline]
31. Solbiati L, Ierace T, Goldberg S, et al. Percutaneous US guided radio-frequency tissue ablation of liver metastases: treatment and follow-up in 16 patients. Radiology 1997;202:195–203.[Abstract/Free Full Text]
32. Solbiati L, Goldberg SN, Ierace T, et al. Hepatic metastases: percutaneous radio-frequency ablation with cooled-tip electrodes. Radiology 1997;205:367–73.[Abstract/Free Full Text]
33. Rossi S, Stasi M, Carini E, et al. Percutaneous RF Interstitial thermal ablation in the treatment of hepatic cancer. AJR Am J Roentgenol 1996;167:759–68.[Abstract/Free Full Text]
34. Lencioni R, Goletti O, Armilotta N, et al. RF thermal ablation of liver metastases with cooled tip electrode needle: results of a pilot clinical trial. Eur Radiol 1998;8:1205–11.[CrossRef][Medline]
35. Siperstein A, Rogers S, Hansen P, Gitomirsky A. Laparoscopic thermal ablation of hepatic neuroendocrine tumor metastases. Surgery 1997;122:1147–55.[CrossRef][Medline]
36. Cuschieri A, Bracken J, Boni L. Initial experience with laparoscopic ultrasound-guided RF thermal ablation of hepatic tumours. Endoscopy 1999;31:318–21.[CrossRef][Medline]
37. Siperstein A, Garland A, Engle K, et al. Local recurrence after laparoscopic RF thermal ablation of hepatic tumours. Ann Surg Oncol 2000;7:106–13.[Abstract]
38. Curley SA, Izzo F, Delrio P, et al. RF ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Ann Surg 1999;230:1–8.[CrossRef][Medline]
39. Jiao L, Hansen P, Havlik R, et al. Clinical short-term results of RF ablation in primary or secondary liver tumors. Am J Surg 1999;177:303–6.[CrossRef][Medline]
40. Wood TF, Rose DM, Chung M, et al. RF ablation of 231 unresectable hepatic tumours: indications, limitations and complications. Ann Surg Oncol 2000;7:593–600.[Abstract]
41. Pawlik T, Izzo F, Cohen D, Morris J, Curley S. Combined resection and RF ablation for advanced hepatic malignancies: results in 172 patients. Ann Surg Oncol 2003;10:1002–4.[Free Full Text]
42. Montorsi M, Santambrogio R, Bianchi P, et al. RF interstitial thermal ablation of HCC in liver cirrhosis: role of the laparoscopic approach. Surg Endosc 2001;15:141–5.[CrossRef][Medline]
43. Podnos YD, Henry G, Ortiz JA, et al. Laparoscopic ultrasound with RF ablation in cirrhotic patients with HCC: technique and technical considerations. Am Surg 2001;67:1181–4.[Medline]
44. Yokohama T, Egami K, Miyamoto M, et al. Percutaneous and laparoscopic approaches of RF ablation treatment for liver cancer. J Hepatobiliary Pancreat Surg 2003;10:425–7.[CrossRef][Medline]
45. Gillams AR, Lees WR. Thermal ablation induced changes in hepatic arterial perfusion. Radiology 1999;213P:382.
46. Goldberg S, Hahn P, Halpern E, Fogle R, Scott Gazelle G. RF tissue ablation: effect of pharmacological modulation of blood flow on coagulation diameter. Radiology 1998;209:761–7.[Abstract/Free Full Text]
47. Patterson EJ, Scudamore CH, Owen DA, Nagy AG, Buczkowski AK. RF ablation of porcine liver in vivo: effects of blood flow and treatment time on lesion size. Ann Surg 1998;227:559–65.[CrossRef][Medline]
48. Goldberg SN, Hahn PF, Tanabe KK, et al. Percutaneous RF tissue ablation: does perfusion-mediated tissue cooling limit coagulation necrosis? J Vasc Interv Radiol 1998;9:101–11.[Medline]
49. de Baere T, Bessoud B, Dromain C, et al. Percutaneous RF ablation of hepatic tumors during temporary venous occlusion. AJR Am J Roentgenol 2002;178:53–9.[Abstract/Free Full Text]
50. Denys A, Portier F, Lamarre A, Wicky S. Hepatic vascular occlusions and RF liver ablation: from animal experiment to clinical observation? AJR Am J Roentgenol 2001;177:1215–6.[Free Full Text]
51. Lees WR, Schumillian C, Gillams AR. Hypotensive anaesthesia improves the effectiveness of RF ablation in the liver. Radiology 2000;217:228.[Abstract/Free Full Text]
52. Fong Y, Cohen AM, Fortner JG, et al. Liver resection for colorectal metastases. J Clin Oncol 1997;15:938–94.[Abstract/Free Full Text]
53. Steele G, Ravikumar T. Resection of hepatic metastases from colorectal cancer. Ann Surg 1989;210:127–38.[Medline]
54. Douillard JY; V303 Study Group. Irinotecan and high dose fluorouracil/leucovroin for metastatic colorectal cancer. Oncology 2000;14:51–5.[Medline]
55. Giacchetti S, Perpoint B, Zidani R, et al. Phase III multicenter trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first line treatment of metastatic colorectal cancer. J Clin Oncol 2000;18:136–47.[Abstract/Free Full Text]
56. Moehler M, Hoffman T, Hildner K, et al. Weekly oxaliplatin, high-dose folinic acid and 24h-5-fluorouracil (FUFOX) as salvage therapy in metastatic colorectal cancer patients pretreated with irinotecan and folinic acid/5-fluorouracil regimens. Z Gastroenterol 2002;40:957–64.[CrossRef][Medline]
57. Bismuth H, Adam R, Levi F, et al. Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg 1996;224:509–22.[CrossRef][Medline]
58. Shankar A, Leonard P, Renaut AJ, et al. Neoadjuvant therapy improves respectability rates for colorectal cancer. Ann R Coll Surg Engl 2001;83:85–8.[Medline]
59. Gillams A, Lees WR. Survival after percutaneous, image guided thermal ablation of hepatic metastases from colorectal cancer. Dis Colon Rectum 2000;43:656–61.[CrossRef][Medline]
60. Gillams A, Lees WR. Image guided ablation of colorectal liver metastases: time for a randomized controlled trial versus hepatic resection. Radiology 1999;213P:212.
61. Gillams A. Thermal ablation of liver metastases. Abdominal Imaging 2001;26:361–8.[CrossRef][Medline]
62. Jenkins LT, Millikan KW, Bines SD, Staren ED, Doolas A. Hepatic resection for metastatic colorectal cancer. Am Surg 1997;63:605–10.[Medline]
63. Nordlinger B, Guiguet M, Vaillant C, et al. Surgical resection of colorectal carcinoma metastases to the liver. Cancer 1996;77:1254–62.[CrossRef][Medline]
64. Solbiati L, Livraghi T, Goldberg SN, et al. Percutaneous RF ablation of hepatic metastases from colorectal cancer: long term results in 117 patients. Radiology 2001;221:159–66.[Abstract/Free Full Text]
65. Vogl T, Muller P, Meck M, et al. Liver metastases: interventional therapeutic techniques and results, state of the art. Eur Radiol 1999;9:675–84.[CrossRef][Medline]
66. Vogl T, Straub R, Eichler K, Sollner O, Mack M. Colorectal carcinoma metastases in liver: laser-induced interstitial thermotherapy-local tumor control rate and survival data. Radiology 2004;230:450–8.[Abstract/Free Full Text]
67. Elias D, de Baere T, Smayra T, et al. Percutaneous RF thermoablation as an alternative to surgery for treatment of liver tumour recurrence after hepatectomy. Br J Surg 2002;89:752–6.[CrossRef][Medline]
68. Oshowo A, Gillams A, Harrison E, Lees W, Taylor I. Comparison of resection and RF ablation for treatment of solitary colorectal liver metastases. Br J Surg 2003;90:1240–3.[CrossRef][Medline]
69. Livraghi T, Solbiati L, Meloni F, et al. Percutaneous radio-frequency ablation of liver metastases in potential candidates for resection: "the test-of-time" approach. Cancer 2003;15:3027–35.
70. Clouse ME, Perry L, Stuart K, Tokes KR. Hepatic arterial chemoembolization for metastatic neuroendocrine tumours. Digestion 1994;55:92–7.
71. Roche A, Girish B, de Baere T, et al. Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumours. Eur Radiol 2003;13:136–40.[Medline]
72. Henn A, Levine E, McNulty W, Zagoria R. Percutaneous RF ablation of hepatic metastases for symptomatic relief of neuroendocrine syndromes. AJR Am J Roentgenol 2003;181:1005–10.[Abstract/Free Full Text]
73. Chung MH, Pisegna J, Spirt M, et al. Hepatic cytoreduction followed by a novel long-acting somatostatin analogue: a paradigm for intractable neuroendocrine tumors metastatic to the liver. Surgery 2001;130:954–62.[CrossRef][Medline]
74. Berber E, Flesher N, Siperstein A. Laparoscopic RF ablation of neuroendocrine liver metastases. World J Surg 2002;26:985–90.[CrossRef][Medline]
75. Hellman P, Ladjevardi S, Skogseid B, et al. RF tissue ablation using cooled tip for liver metastases of endocrine tumors. World J Surg 2002;26:1052–6.[CrossRef][Medline]
76. Gillams AR, Lees WR. Thermal ablation of neuroendocrine liver metastases: long term results. Eur Radiol 2004;14 (Suppl 2):144.
77. Selzner M, Morse M, Vredenburgh J, Meyers W, Clavien P. Liver metastases from breast cancer: long term survival after curative resection. Surgery 2000;127:383–9.[CrossRef][Medline]
78. Livraghi T, Goldberg N, Solbiati L, et al. Percutaneous RF ablation of liver metastases from breast cancer: initial experience in 24 patients. Radiology 2001;220:145–9.[Abstract/Free Full Text]
79. Laurent C, Rullier E, Feyler A, Masson B, Saric J. Resection of non-colorectal and non-neuroendocrine liver metastases: late metastases are the only chance of cure. World J Surg 2001;25:1532–6.[Medline]
80. Livraghi T, Bolondi L, Buscarini L, et al. No treatment, resection and ethanol injection in HCC: a retrospective analysis of survival in 391 patients with cirrhosis. Italian Cooperative HCC Study Group. J Hepatol 1995;22:522–6.[CrossRef][Medline]
81. Livraghi T, Goldberg SN, Lazzaroni S, et al. Small HCC: treatment with RF ablation versus ethanol injection. Radiology 1999;210:655–61.[Abstract/Free Full Text]
82. Ikeda M, Okada S, Ueno H, Okusaka T, Kuriyama H. RF ablation and percutaneous ethanol injection in patients with small hepatocellular carcinoma: a comparative study. Jpn J Clin Oncol 2001;31:322–6.[Abstract/Free Full Text]
83. Lencioni R, Allgaier HP, Cioni D, et al. Small hepatocellular carcinoma in cirrhosis: randomized comparison of RF thermal ablation versus percutaneous ethanol injection. Radiology 2003;228:235–40.[Abstract/Free Full Text]
84. Lencioni R, Cioni D, Crocetti L, DellaPina C, Franchini C, Bartolozzi C. Small hepatocellular carcinoma in cirrhosis: long-term results of percutaneous RF ablation. Radiology 2003;229(P):411.
85. Shibata T, Iimuro Y, Yamamoto Y, et al. Small HCC: comparison of radio-frequency ablation and percutaneous microwave coagulation therapy. Radiology 2002;223:331–7.[Abstract/Free Full Text]
86. Pacella CM, Bizzarri G, Magnolfi F, et al. Laser thermal ablation in the treatment of small HCC; results in 74 patients. Radiology 2001;221:712–20.[Abstract/Free Full Text]
87. Livraghi T, Goldberg N, Lazzaroni S, et al. HCC: RF ablation of medium and large lesions. Radiology 2000;214:761–8.[Abstract/Free Full Text]
88. Pacella CM, Bizzarri G, Cecconi O, et al. Hepatocellular carcioma: long term results of combined treatment with Laser thermal ablation and transcatheter arterial chemoembolization. Radiology 2001;219:669–78.[Abstract/Free Full Text]
89. Lencioni R, Cioni D, Donati F, Bartolozzi C. Combination of interventional therapies in HCC. Hepatogastroenterology 2001;48:8–14.[Medline]
90. Camma C, Schepis F, Orlando A, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 2002;224:47–54.[Abstract/Free Full Text]
91. Rossi S, Garbagnati F, Lencioni R, et al. Percutaneous radio-frequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply. Radiology 2000;217:119–26.[Abstract/Free Full Text]
92. Hsieh C, Chang H, Chen TW, et al. Comparison of transarterial chemoembolisation, laparoscopic RF ablation and conservative treatment for decompensated cirrhotic patients with hepatocellular carcinoma. World J Gastroenterol 2004;10:505–8.[Medline]
93. Mulier S, Mulier P, Ni Y, et al. Complications of RF coagulation of liver tumours. Br J Surg 2002;89:1206–22.[CrossRef][Medline]
94. Rhim H, Dodd GD. RF thermal ablation of liver tumours. J Clin Ultrasound 1999;27:221–9.[CrossRef][Medline]
95. Rhim H, Yoon K, Lee J, et al. Major complications after radio-frequency thermal ablation of hepatic tumors: spectrum of imaging findings. Radiographics 2003;23:123–34; discussion 134–6.[Abstract/Free Full Text]
96. Rhim H, Dodd G, Chintapalli K, et al. RF thermal ablation of abdominal tumors: lessons learned from complications. Radiographics 2004;24:41–52.[Abstract/Free Full Text]
97. de Baere T, Risse O, Kuoch V, et al. Adverse events during RF treatment of 582 hepatic tumors. AJR Am J Roentgenol 2003;181:695–700.[Abstract/Free Full Text]
98. Gillams A, Lees W. Liver isolation during RF ablation. Radiology 2003;9(P):589.
99. Minami Y, Kudo M, Kawasaki T, et al. Percutaneous ultrasound-guided RF ablation with artificial pleural effusion for hepatocellular carcinoma in the hepatic dome. J Gastroenterol 2003;38:1066–70.[CrossRef][Medline]
100. Verhoeven B, Haagsma E, Appeltans B, Slooff M, De Jong K. Hyperkalaemia after RF ablation of hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2002;14:1023–4.[CrossRef][Medline]
101. Llovet JM, Vilana R, Bru C, et al. Increased risk of tumor seeding after percutaneous RF ablation for single hepatocellular carcinoma. Hepatology 2001;33:1124–9.[CrossRef][Medline]
102. Liu C, Frilling A, Dereskewitz C, Broelsch CE. Tumor seeding after fine needle aspiration biopsy and percutaneous RF thermal ablation of hepatocellular carcinoma. Dig Surg 2003;20:460–3.[CrossRef]
103. Livraghi T, Solbiati L, Meloni MF, et al. Treatment of focal liver tumors with percutaneous radio-frequency ablation: complications encountered in a multicenter study. Radiology 2003;226:441–51.[Abstract/Free Full Text]
104. Cioni D, Lencioni R, Rossi S, et al. RF ablation of HCC: using contrast enhanced harmonic power Doppler sonography to assess treatment outcome. AJR Am J Roentgenol 2001;177:783–8.[Abstract/Free Full Text]
105. Izumi N, Asahina Y, Noguchi O, Uchihara M, Kanazawa N, Itakura J, et al. Risk factors for distant recurrence of hepatocellular carcinoma in the liver after complete coagulation by microwave or radiofrequency ablation. Cancer 2001;91:949–56.[CrossRef][Medline]

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