Cardiovasc Intervent Radiol (2010) 33:11–17
Quality Improvement Guidelines for RadiofrequencyAblation of Liver Tumours
Laura Crocetti • Thierry de Baere •Riccardo Lencioni
Received: 5 October 2009 / Accepted: 5 October 2009 / Published online: 19 November 2009Ó Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2009
The development of image-guided percutane-
ous techniques for local tumour ablation has been one ofthe major advances in the treatment of liver malignancies.
Among these methods, radiofrequency ablation (RFA) iscurrently established as the primary ablative modality at
This is the region ablated beyond the borders of the tumour
most institutions. RFA is accepted as the best therapeutic
to achieve complete tumour destruction. Ideally, it should
choice for patients with early-stage hepatocellular carci-
noma (HCC) when liver transplantation or surgical resec-tion are not suitable options [, ]. In addition, RFA isconsidered a viable alternate to surgery (1) for inoperable
patients with limited hepatic metastatic disease, especiallyfrom colorectal cancer, and (2) for patients deemed ineli-
This is the nonenhancing area, including the tumour and the
gible for surgical resection because of extent and location
ablative margin, on contrast-enhanced imaging modalities.
of the disease or concurrent medical conditions []. Theseguidelines were written to be used in quality-improvement
programs to assess RFA of HCC and liver metastases. Themost important processes of care are (1) patient selection,
Complications can be stratified on the basis of outcome by
(2) performing the procedure, and (3) monitoring the
using the society of interventional radiology (SIR) standard
patient. The outcome measures or indicators for these
table. Major complications result in admission to a hospital
processes are indications, success rates, and complication
for therapy (for outpatient procedures), an unplanned
increase in the level of care, prolonged hospitalization,permanent adverse sequelae, or death. Minor complicationsresult in no sequelae, and they may require nominal ther-apy or a short hospital stay for observation (generallyovernight). Major and minor complications and side effectsshould be reported on the basis of the number of ablationsessions on a per-session basis.
L. Crocetti (&) Á R. LencioniDivision of Diagnostic Imaging and Intervention,
Department of Hepatology, Liver Transplants, and InfectiousDiseases, University of Pisa, Pisa, Italye-mail: [email protected]
One or multiple electrodes are inserted directly into thetumour to deliver RF energy current. Electrodes can be
monopolar or bipolar, and they can have different designs
Department of Interventional Radiology, Institut deCance´rologie Gustave Roussy, Villejuif, France
(multitined expandable, internally cooled, perfused).
L. Crocetti et al.: Guidelines for RFA of Liver Tumours
Monopolar Electrode This has a single active electrode
applicator, with current dissipated at one or severalreturn grounding pads.
This is considered when treatment of the tumour was per-
Bipolar Electrode This consists in two electrode
formed according to protocol and complete tumour coverage
applicators or in a single array containing both the
is assessed either during or immediately after the procedure.
Multitined Expandable Electrode This has multiple
electrode tines that expand from a larger needle cannula.
Internally Cooled Electrode This electrode has an
This is the transient ([30–90 min) zone of increased ech-
internal lumen that is perfused by saline without
ogenicity seen at US within and surrounding a tumour
coming into direct contact with patient body tissue.
Perfused Electrode The tip of the electrode has smallapertures that allow the fluid (usually saline) to come incontact with the tissue.
RFA is the therapy of choice in very early and early
This is convective cooling by adjacent blood vessels, usu-
HCC according to the Barcelona Clinic Liver Cancer
ally C3 mm, when ablated tissues are heated. It can nega-
(BCLC) classification (Table ) when patients are not
tively affect the results of RFA because it can potentially
candidates for either liver resection or transplantation.
remove heat before complete tumour ablation is achieved.
Patients are required to have a single tumour smaller oras many as three nodules \3 cm each, no evidence of
vascular invasion or extrahepatic spread, performancestatus test of 0, and liver cirrhosis in Child-Pugh class A
This is the instillation of liquid (dextrose 5%, sterile water)
or gas (air, carbon dioxide) between the area of ablation andthe structure vulnerable to heating damage (usually the
RFA is generally indicated for nonsurgical patients with
This is the presence of residual unablated tumour, which is
colorectal cancer oligometastases isolated to the liver.
seen as peripheral irregular enhancement at imaging. It
Selected patients with limited hepatic and pulmonary
often grows in a scattered, nodular, or eccentric pattern.
colorectal metastatic disease, however, may qualify forpercutaneous treatment if extrahepatic disease is deemed
curable. In patients with hepatic metastases from otherprimary cancers, promising initial results have been
This is the appearance at follow-up of foci of untreated
reported in the treatment of breast and endocrine tumours.
disease in tumours that were previously considered to becompletely ablated.
The number of lesions should not be considered an abso-lute contraindication to RFA if successful treatment of all
This is the time from inclusion in the study to death.
metastatic deposits can be accomplished. Nevertheless,
Patients who are alive at the end of follow-up are censored.
most centres preferentially treat patients with B5 lesions.
This is coagulation induction from all electromagnetic
The target tumour should not exceed 3 cm at its longest
energy sources with frequencies \30 MHz. For tumour
axis to achieve best rates of complete ablation using most
ablation purposes, the frequency is usually in the range of
L. Crocetti et al.: Guidelines for RFA of Liver Tumours
PS 0, Child-Pugh A to B, single HCC or 3 HCCs \3 cm
PS 0, Child-Pugh A to B, multinodular HCC
PS 1 to 2, Child-Pugh A to B, portal neoplastic invasion,
includes understanding liver anatomy, liver tumour diag-nosis, and radiologic and non radiologic treatment options.
Pretreatment imaging must carefully define the location ofeach lesion with respect to surrounding structures as follows:
Lesions located on the surface of the liver can beconsidered for RFA, although their treatment requires
Targeting of the lesion can be performed with ultrasound,
adequate expertise and may be associated with a higher
computed tomography (CT), or magnetic resonance
imaging (MRI). The guidance system is chosen largely on
Thermal ablation of superficial lesions that are adjacent to
the basis of tumour visibility, operator preference, and
any part of the gastrointestinal tract must be avoided
local availability of dedicated equipment, such as CT
because of the risk of thermal injury of the gastric or bowel
fluoroscopy or open MRI systems. The transient hyper-
wall. The colon appears to be at greater risk than the
echoic zone that is seen on ultrasound within and sur-
stomach or small bowel for thermally mediated perfora-
rounding a tumour during and immediately after RFA can
tion. Gastric complications are rare, most likely owing to
be used as an approximate guide to the extent of tumour
the relatively greater wall thickness of the stomach or the
destruction. It is not sufficient to evaluate immediate
rarity of surgical adhesions along the gastrohepatic
treatment effectiveness, and follow-up imaging is manda-
ligament. Mobility of the small bowel may also provide
tory. MRI currently is the only imaging modality with
the bowel with greater protection compared with the
validated techniques for real-time temperature monitoring.
relatively fixed colon. The use of special techniques, suchas intraperitoneal injection of dextrose to displace thebowel, can be considered in such instances.
Treatment of lesions adjacent to the hepatic hilumincreases the risk of thermal injury of the biliary tract.
Thermal ablation is usually performed with the patient
This tumour location represents a relative contraindi-
under intravenous sedation or general anaesthesia with
cation to RFA. In experienced hands, thermal ablation
standard cardiac, pressure, and oxygen monitoring. Amer-
of tumours located near the gallbladder has been shown
ican Society of Anesthesiologists (ASA) score (Appendix)
to be feasible, although associated in most cases with
can be used to assess patient physical status before RFA.
self-limited iatrogenic cholecystitis.
Patients with BASA III score can be treated.
Thermal ablation of lesions adjacent to hepatic vesselsis possible because flowing blood usually protects thevascular wall from thermal injury. In this case, however,
the risk of incomplete treatment of the neoplastic tissueclose to the vessel may increase due to heat loss by
Contrast-enhanced CT or MRI are recognized as the stan-
dard modalities with which to assess treatment outcome. CTand MRI results obtained 4–6 weeks after treatment showsuccessful ablation as a nonenhancing area with or without
a peripheral enhancing rim. The enhancing rim that may beobserved along the periphery of the ablation zone appears to
Before treatment, all patients with liver tumours who are
be a relatively concentric, symmetric, and uniform process
considered for RFA should undergo a thorough clinical
in an area with smooth inner margins. This transient finding
evaluation by a multidisciplinary team, including an
represents a benign physiologic response to thermal injury
interventional radiologist, a hepatologist, an oncologist, a
(reactive hyperemia initially and fibrosis and giant cell
surgeon, and an anesthesiologist. The core of physiological
reaction subsequently). Benign periablational enhance-
knowledge required for the interventional radiologist
ment must be differentiated from irregular peripheral
L. Crocetti et al.: Guidelines for RFA of Liver Tumours
enhancement due to residual tumour that occurs at the
approximately 90% in tumours [3 cm Histological
treatment margin. Compared with benign periablational
data from explanted liver specimens in patients who have
enhancement, residual unablated tumour often grows in
undergone RFA showed that tumour size and presence of
scattered, nodular, or eccentric patterns. Contrast-enhanced
large (B3 mm) abutting vessels significantly affect local
ultrasound can be performed after the end of the procedure
treatment effect. Complete tumour necrosis was patholog-
and may allow initial evaluation of treatment effects.
ically shown in 83% of tumours \3 cm and 88% of
Later follow-up imaging studies should be aimed at
tumours located in a nonperivascular space Compari-
detecting local tumour progression, development of new
son with percutaneous ethanol injection (PEI) in five ran-
hepatic lesions, or emergence of extrahepatic disease. A
domized trials showed that RFA has a higher local
recommended follow-up protocol includes CT or MRI
anticancer effect than PEI, thus leading to better local
studies at 3, 6, 9, and 12 months after treatment and at
control of the disease (Table Consequently there is no
6-month intervals thereafter for the next 3 years.
room per PEI in HCC amenable to RFA.
Five randomized trials compared RFA with PEI for local
Contraindications for RFA are as follows:
ablation of early-stage HCC (Table The two Europeantrials failed to show a statistically significant difference in
tumour located \1 cm from the main biliary duct (due
overall survival between patients who received RFA
to risk of delayed stenosis of the main biliary tract);
compared with those receiving PEI ]. However, sur-
vival advantages were identified in three Asian studies
anterior exophytic location of the tumour (due to the
These data were recently pooled in two indepen-
dent meta-analysis, and the survival benefit of patients
with small HCCs who received RFA was confirmed [
untreatable/unmanageable coagulopathy.
]. Therefore, RFA is the preferred percutaneous treat-ment for patients with early-stage HCC on the basis ofmore consistent local tumour control and better survival
Recently, the long-term survival outcomes of RFA-
treated patients were reported (Table ) –Inpatients who underwent RFA, survival depended on the
RFA yields satisfactory local tumour control in treating
severity of underlying cirrhosis and tumour stage. Patients
small HCCs, with a complete ablation rate on imaging of
in Child-Pugh class A with early stage HCC had a 5-year
L. Crocetti et al.: Guidelines for RFA of Liver Tumours
long-term survival outcomes ofpatients with early-stage HCC
Child-Pugh A, 1 HCC \ 5 cm or 3 HCCs \ 3 cm
Child-Pugh B, 1 HCC \ 5 cm or 3 HCCs \ 3 cm
Child-Pugh A, 1 HCC \ 5 cm or 3 HCCs \ 3 cm
Child-Pugh B, 1 HCC \ 5 cm or 3 HCCs \ 3 cm
recurrent tumour after previoustreatment including resection,
Child-Pugh A, 1 HCC \ 5 cm or 3 HCCs \ 3 cm
survival rate of 61 to 77%, whereas patients with a single
Table 4 Studies reporting long-term survival outcomes of patients
tumour B2 cm had a 5-year survival rate of 68%.
with colorectal hepatic metastases who underwent percutaneous RFA
Clinical Results: Colorectal Cancer Liver Metastases
Many studies have investigated the use of RFA in the
treatment of limited colorectal cancer hepatic metastatic
disease in patients who were excluded from surgery. Two
early studies reported rates of complete response that did
not exceed 60–70% [Subsequently, owing to the
advances in RFA technique and probably to the treatmentof smaller tumours, reported rates of successful localtumour control after RFA treatment increased substantially.
analysis of a randomized controlled trial comparing che-
In two series, RFA allowed eradication of 91% of 100
motherapy plus RFA versus chemotherapy alone in colo-
metastases and 97% of 74 metastases, respectively [
Recently, data on long-term survival of nonsurgical patientswith hepatic colorectal metastases who underwent RFA
Early major complications associated with RFA occur in
have been reported (Table ) –In particular, in three
2.2–3.1% of patients and include intraperitoneal bleeding,
series including patients with B5, each B5 cm, the 5-year
liver abscess, intestinal perforation, pneumothorax and
survival rate ranged 24–44% at 5 years [When
haemothorax, bile duct stenosis, and tumour seeding
RFA was performed in patients with small (\4 cm) solitary
(0.5%); the procedure mortality rate is 0.1–0.5% (Table
hepatic colorectal metastases, a 40% 5-year survival rate
The minor complication rate ranges from 5% to 8.9%. The
was demonstrated ]. These figures are substantially
most common causes of death are sepsis, hepatic failure,
higher than those obtained with any chemotherapy regi-
colon perforation, and portal vein thrombosis, whereas the
mens and provide indirect evidence that RFA therapy
most common complications are intraperitoneal bleeding,
improves survival in patients with limited hepatic meta-
hepatic abscess, bile duct injury, hepatic decompensation,
static disease. This conclusion is supported by the interim
and grounding pad burns. Minor complications and side
L. Crocetti et al.: Guidelines for RFA of Liver Tumours
5. Lin SM, Lin CJ, Lin CC et al (2004) Radiofrequency ablation
Table 5 Reported and acceptable rate of major complications
improves prognosis compared with ethanol injection for hepato-
cellular carcinoma B4 cm. Gastroenterology 127:1714–1723
6. Shiina S, Teratani T, Obi S et al (2005) A randomized controlled
trial of radiofrequency ablation versus ethanol injection for small
hepatocellular carcinoma. Gastroenterology 129:122–130
7. Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC (2005) Randomised
controlled trial comparing percutaneous radiofrequency thermal
ablation, percutaneous ethanol injection, and percutaneous acetic
acid injection to treat hepatocellular carcinoma of 3 cm or less.
8. Brunello F, Veltri A, Carucci P et al (2008) Radiofrequency
ablation versus ethanol injection for early hepatocellular carci-
noma: A randomized controlled trial. Scand J Gastroenterol
9. Lu DS, Yu NC, Raman SS et al (2005) Radiofrequency ablation
of hepatocellular carcinoma: treatment success as defined byhistologic examination of the explanted liver. Radiology
effects are usually transient and self-limiting []. An
uncommon late complication of RFA can be tumour
10. Orlando A, Leandro G, Olivo M, Andriulli A, Cottone M (2009)
seeding along the needle track. In patients with HCC,
Radiofrequency thermal ablation vs. percutaneous ethanol
tumour seeding occurred in 8 (0.5%) of 1,610 cases in a
injection for small hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled trials. Am J Gastroenterol
multicentre survey ] and in 1 (0.5%) of 187 cases in a
single-institution series [Lesions with subcapsular
11. Cho YK, Kim JK, Kim MY, Rhim H, Han JK (2009) Systematic
location and an invasive tumoural pattern, as shown by a
review of randomized trials for hepatocellular carcinoma treated
poor differentiation degree, seem to be at higher risk for
with percutaneous ablation therapies. Hepatology 49:453–459
12. Lencioni R, Cioni D, Crocetti L et al (2005) Early-stage hepa-
tocellular carcinoma in cirrhosis: long-term results of percuta-neous image-guided radiofrequency ablation. Radiology 234:961–967
Appendix A: American Society of Anesthesiologists
13. Tateishi R, Shiina S, Teratani T et al (2005) Percutaneous
radiofrequency ablation for hepatocellular carcinoma. Cancer
(ASA) Physical Status Classification System
14. Cabassa P, Donato F, Simeone F et al (2006) Radiofrequency
ablation of hepatocellular carcinoma: long-term experience with
expandable needle electrodes. Am J Roentgenol 185(Sup-pl):S316–S321
15. Choi D, Lim HK, Rhim H et al (2007) Percutaneous radiofre-
Patient with severe systemic disease that is a constant
quency ablation for early-stage hepatocellular carcinoma as a
first- line treatment: long-term results and prognostic factors in a
Moribund patient who is not expected to survive
large single-institution series. Eur Radiol 17:684–692
16. Takahashi S, Kudo M, Chung H et al (2007) Initial treatment
response is essential to improve survival in patients with hepa-
tocellular carcinoma who underwent curative radiofrequency
ablation therapy. Oncology 72(Suppl):S98–S103
17. Hiraoka A, Horiike N, Yamashita Y et al (2008) Efficacy of
radiofrequency ablation therapy compared to surgical resection in164 patients in Japan with single hepatocellular carcinoma
smaller than 3 cm, along with report of complications. Hepato-gastroenterology 55:2171–2174
1. Bruix J, Sherman M, Llovet JM et al (2001) EASL panel of
18. Lencioni R, Goletti O, Armillotta N et al (1998) Radio-frequency
experts on HCC. Clinical management of hepatocellular carci-
thermal ablation of liver metastases with a cooled-tip electrode
noma. Conclusions of the Barcelona-2000 EASL Conference.
needle: results of a pilot clinical trial. Eur Radiol 8:1205–1211
European Association for the Study of the Liver. J Hepatol
19. Solbiati L, Goldberg SN, Ierace T et al (1997) Hepatic metasta-
ses: percutaneous radio-frequency ablation with cooled-tip elec-
2. Bruix J, Sherman M (2005) Management of hepatocellular car-
20. De Baere T, Elias D, Dromain C et al (2000) Radiofrequency
3. Stang A, Fischbach R, Teichmann W, Bokemeyer C, Braumann
ablation of 100 hepatic metastases with a mean follow-up of more
D (2009) A systematic review on the clinical benefit and role of
than 1 year. Am J Roentgenol 175:1619–1625
radiofrequency ablation as treatment of colorectal liver metasta-
21. Helmberger T, Holzknecht N, Schopf U et al (2001) Radiofre-
quency ablation of liver metastases. Technique and initial results.
4. Lencioni R, Allgaier HP, Cioni D et al (2003) Small hepatocel-
lular carcinoma in cirrhosis: randomized comparison of radio-
22. Solbiati L, Livraghi T, Goldberg SN et al (2001) Percutaneous
frequency thermal ablation versus percutaneous ethanol injection.
radio-frequency ablation of hepatic metastases from colorectal
cancer: long-term results in 117 patients. Radiology 221:159–166
L. Crocetti et al.: Guidelines for RFA of Liver Tumours
23. Lencioni R, Crocetti L, Cioni D et al (2004) Percutaneous
29. Gillams AR, Lees WR (2008) Five-year survival following
radiofrequency ablation of hepatic colorectal metastases. Tech-
radiofrequency ablation of small, solitary, hepatic colorectal
nique, indications, results, and new promises. Invest Radiol
metastases. J Vasc Interv Radiol 19:712–717
30. Ruers T, van Coevorden F, Pierie J et al (2008) Radiofrequency
24. Gillams AR, Lees WR (2004) Radio-frequency ablation of
ablation combined with chemotherapy for unresectable colorectal
colorectal liver metastases in 167 patients. Eur Radiol 14:2261–
liver metastases: interim results of a randomised phase II study
of the EORTC-NCRI CCSG-ALM Intergroup 40004 (CLOCC).
25. Machi J, Oishi AJ, Sumida K et al (2006) Long-term outcome of
radiofrequency ablation for unresectable liver metastases from
31. Livraghi T, Solbiati L, Meloni MF et al (2003) Treatment of focal
colorectal cancer: evaluation of prognostic factors and effec-
liver tumors with percutaneous radio-frequency ablation: com-
tiveness in first- and second-line management. Cancer J 12:318–
plications encountered in a multicentre study. Radiology 26:441–
26. Jackobs TF, Hoffmann RT, Trumm C et al (2006) Radiofre-
32. De Baere T, Risse O, Kuoch V et al (2003) Adverse events during
quency ablation of colorectal liver metastases: mid-term results in
radiofrequency treatment of 582 hepatic tumors. Am J Roentge-
27. Sorensen SM, Mortensen FV, Nielsen DT (2007) Radiofrequency
33. Bleicher RJ, Allegra DP, Nora DT et al (2003) Radiofrequency
ablation of colorectal liver metastases: long-term survival. Acta
ablation in 447 complex unresectable liver tumors: lessons
28. Veltri A, Sacchetto P, Tosetti I, Pagano E, Fava C, Gandini G
34. Llovet JM, Vilana R, Bru C et al (2001) Barcelona Clinic Liver
(2008) Radiofrequency ablation of colorectal liver metastases:
Cancer (BCLC) Group. Increased risk of tumor seeding after
small size favorably predicts technique effectiveness and sur-
percutaneous radiofrequency ablation for single hepatocellular
vival. Cardiovasc Intervent Radiol 31:948–956
Dear Sir or Madam! Good morning/afternoon and welcome to our hotel. We are pleased that you decided to stay with us. If you have spent at least one night in our hotel we kindly ask you to participate in a survey which will help us make your future stay here even more pleasant. The interview will take about 10-15 minutes and is conducted anonymously. 1. How did you arrive to Slovenia? (mark the ap
G. Hatano, N. Okada and H. Tanabe (Eds.), Affective Minds, pp. 101-104. ElsevierScience B. V. (2000). METALEARNING, NEUROMODULATION, AND EMOTIONInformation Sciences Division, ATR InternationalCREST, Japan Science and Technology Corporation2-2-2 Hikaridai, Seika, Soraku, Kyoto 619-0288, JapanRecent advances in machine learning and artificial neural networks have made itpossible to build rob