CLINICAL INVESTIGATION

Stereotactic Radiofrequency Ablation for Liver Tumorsin Inherited Metabolic Disorders

Daniela Karall • Sabine Scholl-Burgi • Gerlig Widmann •

Ursula Albrecht • Katharina Niedermayr • Kathrin Maurer •

Bernd Ausserer • Martina Huemer • Reto Bale

Received: 11 July 2013 / Accepted: 21 September 2013

� Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2013

Abstract

Purpose Both glycogen storage disease type Ia (GSD Ia)

and tyrosinemia type I (TYR I) are inherited metabolic

disorders that can be complicated by formation of liver

adenomas in juvenile/young adult age and/or development

of hepatocellular carcinoma. We describe the first appli-

cation of stereotactic radiofrequency ablation (SRFA) in

focal lesions in three patients with inherited metabolic

disorders affecting the liver.

Methods SRFA was applied for removal of single large

liver adenomas in a 22-year-old woman and a 20-year-old

man with GSD Ia and of a suspicious lesion in a 16-year-

old girl with TYR I with a-fetoprotein (AFP) elevation.

Results SRFA was successful. Large scars were avoided,

and in the TYR I patient, elevated AFP values promptly

returned to normal.

Conclusion The SRFA technique is a good alternative to

surgical resection of focal liver lesions and could greatly

help patients with inherited metabolic disorders with liver

involvement, including focal liver lesions and potential

malignancy.

Keywords Glycogen storage disease type I �Hepatic adenoma/carcinoma � Stereotactic

radiofrequency ablation � Tyrosinemia type I

Abbreviations

GSD I Glycogen storage disorder type I

TYR I Tyrosinemia type I

HCC Hepatocellular carcinoma

AFP Alpha-fetoprotein

SRFA Stereotactic radiofrequency ablation

RFA Radiofrequency ablation

CT Computed tomography

FLAIR Fluid-attenuated inversion recovery

MRI Magnetic resonance imaging

T1 C ? vibe fs Name of MRI sequence

T1 Weighing

C? With contrast medium

Vibe Volume interpolated breathhold

examination

fs Fat suppression

ETT Endotracheal tube

Introduction

A number of inherited metabolic disorders affect the liver

at different ages in life, from infancy to adulthood [1]. Two

of these are glycogen storage disease type Ia (GSD Ia) and

tyrosinemia type I (TYR I).

GSD Ia is a recessively inherited metabolic disorder

caused by deficiency of glucose-6-phosphatase (G6PD,

Daniela Karall and Sabine Scholl-Burgi contributed equally to this

article.

D. Karall (&) � S. Scholl-Burgi � U. Albrecht � K. Niedermayr

Department of Pediatrics I, Inherited Metabolic Disorders,

Medical University of Innsbruck, Anichstrasse 35,

6020 Innsbruck, Austria

e-mail: daniela.karall@i-med.ac.at

G. Widmann � K. Maurer � R. Bale

Department of Radiology, Medical University of Innsbruck,

Innsbruck, Austria

B. Ausserer

Department of Pediatrics, Hospital Dornbirn, Dornbirn, Austria

M. Huemer

Department of Pediatrics, Landeskrankenhaus Bregenz, Bregenz,

Austria

123

Cardiovasc Intervent Radiol

DOI 10.1007/s00270-013-0756-2

chromosome 17q21.31, MIM 232200, E.C. 3.1.3.9), an

enzyme involved both in glycogen storage and gluconeo-

genesis. Symptoms are hypoglycemia and lifelong fasting

intolerance. Long-term complications encompass develop-

ment of renal insufficiency, osteopenia, chronic anemia, and

formation of liver adenomas in juvenile/young adult age.

The liver adenomas may cause morbidity such as abdominal

pain and bleeding as a result of their size, location, and

growth dynamics. It has been reported GSD-related adeno-

mas exhibit a particular molecular profile characterized by a

lack of HNF1A inactivation [2]. Additionally, there is a risk

of malignancy in a small percentage of patients [3–6].

However, there are no real guidelines regarding the man-

agement of adenomas [7]. Usually the procedure comprises

close observation of adenomas and surgical removal, if

indicated—for example, if there is large adenoma with

bleeding or suspected malignancy [8–10].

TYR I is caused by a rare recessively inherited defi-

ciency of fumarylacetoacetate hydrolase (FAH, chromo-

some 15q23–q25, MIM 276700, E.C. 3.7.1.2), an enzyme

involved in the degradation of tyrosine. Left untreated, this

deficiency leads to formation of hepatocellular carcinoma

(HCC) mediated by the toxic effect of succinylacetone.

a-Fetoprotein (AFP) is a sensitive biochemical marker

assessed during follow-up to evaluate the formation of

malignancy [11–14]. Before the 1990s, early liver trans-

plantation to prevent malignancy was the treatment of

choice. Since 1991, oral administration of nitisone (2-(2-

nitro-4-trifluormethyl-benzoyl)-1,3-cyclohexandion;

NTBC) is the standard treatment. Nitisone blocks para-

hydroxyphenylpyruvic acid dioxygenase (p-HPPD), the

second step in the tyrosine degradation pathway, prevent-

ing the accumulation of fumarylacetoacetate and its con-

version to succinylacetone. Nitisone is used in combination

with a protein-restricted diet to prevent hypertyrosinemia.

Despite treatment, HCC (characterized by an increase in

AFP) still develops in some patients and requires treatment,

such as liver transplantation [3].

Radiofrequency ablation (RFA) is a potentially local

curative ablation method, which is based on the application

of high-frequency alternating current between probes in

tissue and skin electrodes, causing targeted heat of[60 �C

and controlled tumor destruction [15]. In contrast to con-

ventional ultrasound (US)- or computed tomography (CT)-

guided RFA, stereotactic RFA (SRFA) [16–24] is not

limited by tumor size as a result of the application of

multiple probes.

To date, the application of SRFA has not been reported

to have been used in patients with inherited metabolic

disorders with potential liver tumors. Here we report what

is to our knowledge the first application of SRFA in focal

lesions in three patients with inherited metabolic disorders

affecting the liver.

Materials and Methods

SRFA is an interventional treatment of liver malignancies in

patients not eligible for surgical therapy [15–25]. Electrodes

are percutaneously placed into the tumor, and a volume of

tissue is devitalized without open resection. Stereotaxy

enables a high precision of electrode placement, which is

mandatory to assure patient safety and technical success and

to avoid major complications such as pleural and gastroin-

testinal perforations, laceration of vessels with bleeding, or

thermal collateral damage with bile duct stenosis, biloma,

gastrointestinal inflammation, and subsequent perforation.

In addition, the stereotactic multielectrode/electrode posi-

tion approach allows for generating overlapping ablations

for successful treatment of even large tumors.

The procedure can be summarized as follows. After

general anesthesia, the patient is fixed in a vacuum cushion

at the CT intervention table. Eight to 10 skin fiducials are

attached to the patient. A contrast-enhanced planning CT is

obtained during temporary endotracheal tube (ETT) dis-

connection for respiratory motion control. The CT data set

is sent to the navigation system via the hospital network.

For the ablation, one or multiple trajectories are planned on

a stereotactic navigation system using the multiplanar and

3D reconstructed images (Fig. 1A). A dynamic reference

frame is mounted to the patient table, and registration is

performed by indicating the real skin fiducials on the

patient with a navigation probe and correlation with the

virtual markers on the CT data set (Fig. 1B). After

checking the accuracy by indicating a fiducial that was not

used for registration, the skin at the target area is disin-

fected, and the entire interventional field is draped with

translucent plastic foil. A sterilized aiming device that

consists of an adjustable mechanical arm and two pivot

joints holds the probe of the navigation system and is used

for navigated trajectory alignment (Fig. 1C). The aiming

device is fixed when the calculated trajectory alignment is

correct, and the depth from the aiming device to the target

is automatically calculated by navigation software. A

coaxial needle, rigidly guided by the aiming device, is

positioned during temporary ETT disconnection without

imaging control. The coaxial needles serve as guides for

the radiofrequency electrodes. After all the needles have

been placed, a native control CT in ETT disconnection is

performed and fused with the planning CT using the nav-

igation system’s image 3D registration algorithm for veri-

fication of the correct needle placement. A biopsy sample

is obtained via the coaxial needles. Subsequently, radio-

frequency electrodes are introduced via the coaxial needles

for serial tumor ablation (Fig. 1D). After all positions are

ablated, an immediate contrast-enhanced CT scan in ETT

disconnection is fused with the planning CT for verification

of the ablation size and to exclude possible complications.

D. Karall et al.: Stereotactic Radiofrequency Ablation

123

The patient collection was done as a retrospective, sin-

gle-center, single-arm study. The primary end point was

the removal of liver lesions with SRFA; secondary end

points included observation of metabolic parameters and

metabolic stability during and after the procedure. All three

patients in this study have been followed at our metabolic

division since infancy. The selection to SRFA technique

vs. an open surgical procedure was based on feasibility and

single-site lesions.

Results

Patient 1

This Austrian 22-year-old woman is the only child of

healthy nonconsanguineous parents, and she is regularly

followed at our center. GSD Ia had been diagnosed at the

age of 8 months, when the patient presented for hypogly-

cemic seizure and hepatomegaly. Analysis of a liver biopsy

Fig. 1 A Multiple pathways are planned on the navigation system

using multiple 2D and 3D reconstructions. B Unsterile registration by

touching the skin fiducials with the tip of the navigation probe and

correlating them with the respective markers on the CT data set on the

monitor. C The guide frame of the navigation system is positioned in

the aiming device and aligned with the preplanned pathway. The

guide frame is then removed, and the coaxial needle is introduced

through the adjusted aiming device (not visible). D Three RFA

electrodes are sequentially introduced into the coaxial needles

according to the protocol

D. Karall et al.: Stereotactic Radiofrequency Ablation

123

specimen revealed elevated glycogen (10.2 g/100 g liver;

normal 2.4–6.4 g/100 g liver) and reduced enzyme activity

of glucose-6-phosphatase (0.22 U/g liver; normal

3.7–9.6 U/g liver). She is compound heterozygous for two

mutations in the glucose-6-phophatase gene (35X in exon 1

and R170Q in exon 4). Treatment consisted of diet with

complex carbohydrates and cholesterol reduction, frequent

meals, allopurinol, and vitamins and minerals. Generally

the patient’s compliance was satisfactory, although

impaired during her teenage years. Her cognitive devel-

opment is adequate to age.

At the age of 20.5 years, liver adenomas were observed.

One lesion in segment VII/VIII quickly increased in size to

a diameter of 6.5 cm within 6 months. Because of

increasing abdominal pain, removal and histological

assessment to exclude HCC were planned.

Because of the less invasive procedure, the SRFA

method was chosen for adenoma destruction. The 6.5-cm-

diameter tumor was completely removed using 14 coaxial

needles within a total ablation time of 170 min (Fig. 2).

Analysis of samples taken via biopsy during the interven-

tion revealed hepatocellular adenoma without signs of

bleeding or malignancy. Laboratory coagulation parame-

ters were normal before, during, and after the intervention.

Because this was the first patient with an inherited

metabolic disorder treated with SRFA at our center, the

patient was observed for 48 h after intervention in the

intensive care unit. We observed an elevation of lactate to a

maximum of 15.7 mmol/l (normal range 0.5–2.2 mmol/l)

and a drop in hemoglobin to 64 g/l (normal 120–157 g/l).

SRFA-related typical temperature elevation of a maximum

of 38.5 �C was observed. Analgetics were required for

1 week for right shoulder pain, probably caused by the

subcapsular location, which is known to produce more pain

than clear intraparenchymal location. She was discharged

with her regular treatment (diet, frequent meals, allopuri-

nol) after a total observation time of 9 days. Only pointlike

scars remained at the sites of needle entry, with an overall

very satisfying cosmetic outcome (Fig. 3). Imaging follow-

up at 24 months after SRFA revealed no evidence of local

recurrence. The other adenomas remained stable.

Patient 2

This 20-year-old man is the second child of healthy

Turkish nonconsanguineous parents. GSD Ia was diag-

nosed at the age of 4 weeks. After birth, the patient

experienced metabolic acidosis with hypoglycemia. At age

4 months, analysis of a liver biopsy specimen revealed

elevated glycogen (8.0 g/100 g liver; normal 2.0–6.0

g/100 g liver) and reduced activity of glucose-6-phospha-

tase (0 U/g liver; normal 20–70 U/g liver). He is com-

pound heterozygous for two known mutations in the

glucose-6-phophatase gene (R83C and G270V). Treatment

consisted of diet with complex carbohydrates and choles-

terol reduction, frequent meals, allopurinol, and vitamins

and minerals. However, as a result of episodes of pro-

longed hypoglycemia in the first months of life, his cog-

nitive development is severely impaired. He lacks

Fig. 2 Patient 1, a 22-year-old woman with GSD Ia. A magnetic

resonance imaging (MRI) (T1-weighed MRI with contrast medium,

volume-interpolated breath hold examination, and fat suppression,

late enhancement) before SRFA showing hypointense liver lesion in

segment VII/VIII of 6.5 cm (white arrows). B MRI performed

3 months after SRFA showing the hypointense ablation necrosis

(white arrowheads) completely covering the ablated lesion (white

line)

Fig. 3 Cosmetic results with pointlike scars in patient 1

D. Karall et al.: Stereotactic Radiofrequency Ablation

123

expressive speech and is cared for in a home for the

handicapped during the day.

At the age of 20 years, he was admitted with acute

abdominal pain and vomiting. Hemoglobin had dropped to

85 g/l (normal 120–157 g/l). US and CT revealed ascites

and a large (7.5 cm) liver tumor in segment II of the liver.

Imaging revealed tumor adherent to the peritoneum, some

cystic and necrotic material, and blood. According to the

underlying GSD Ia and prior imaging, diagnosis of an

adenoma with secondary bleeding was assumed. After the

patient stabilized (lactate and hemoglobin), the tumor was

treated with SRFA 3 weeks later (Fig. 4). To confidently

judge the dignity of the tumor, several biopsy samples were

taken during the intervention. Histology revealed liver

adenoma without signs of malignancy. To guarantee good

pain and metabolic control in this mentally impaired

patient, he was ventilated for 7 h after intervention without

major problems and was discharged on day 3 after inter-

vention. Follow-up after 7 months revealed widespread

necrosis of the lesion, with a small remaining rim of the

original adenoma (Fig. 4). Because of the benign histology

of the tumor and the small size of the residual rim, an

observational strategy was chosen.

Patient 3

The patient is a 16-year-old Austrian girl, second of three

children of healthy nonconsanguineous parents, who was

diagnosed with TYR I at 14 months of age. Clinical

symptoms were failure to thrive, pancytopenia, and hepato-

and nephromegaly. Biochemical analysis revealed tyrosine

elevation in plasma and succinylacetone excretion in urine.

Activity of delta–amino levulinic acid dehydrogenase in

erythrocytes was significantly diminished (0.4 lmol/h/g

Hb; control 3.6 lmol/h/g Hb), suggesting tyrosinemia type

l. She had homozygosity for a known Gly337Ser missense

mutation in the fumaryl acetoacetase gene (FAH gene).

Since diagnosis in 1996, in addition to a tyrosine-defined

diet (25 mg tyrosine/kg body weight/day), she received

nitisone in a dosage of 1 mg/kg body weight/day in two

single doses without adverse effects.

At the age of 16 years, imminent rapid AFP elevation

from a base level of 10 U/l to 390 U/l was observed. A

suspicious lesion with 1.4 cm in diameter was completely

removed with SRFA using four coaxial needles and 20 min

of total ablation time (Fig. 5), and AFP levels dropped to

the base level. Histology and immune profile classified the

lesion as an inflammatory pseudotumor of the liver. It was

located within normal liver tissue, which is unusual for

HCC in TYR I. The patient was discharged in good clinical

condition the day after the intervention. Follow-up imaging

after 18 months revealed stable conditions with a small

necrotic ablation area, as expected.

Discussion

Development of liver adenomas is a known complication in

GSD Ia. To date, surgical resection is usually recom-

mended when there is a single large adenoma or rapid

growth, before pregnancy to avoid bleeding complications,

and when a malignancy is suspected [1–10].

TYR I is a disease that inevitably affects the liver if

untreated. AFP is a sensitive marker for development of

malignancy; therefore, any elevation in an adequately

treated patient requires action to be taken, with liver

transplantation being an immediate option [1, 3, 11–14].

SRFA is a good alternative method to surgery for

treatment of liver lesions. In contrast to conventional US-

and CT-guided RFA, in SRFA [15–25], multiple probes are

planned on three-dimensional and multiplanar reconstruc-

tions of the planning CT data set using sophisticated soft-

ware. The probes are precisely placed with a frameless

stereotactic navigation system and an aiming device. In

Fig. 4 Patient 2, a 20-year-old man with GSD Ia. A Contrast-

enhanced CT before SRFA showing a hypervascular liver lesion in

segment II with 7.5 cm (white arrows). B Contrast-enhanced CT

3 months after SRFA showing the hypointense ablation necrosis

(white arrowheads) covering the ablated lesion except a small

peripheral rim of remaining tissue (white arrow)

D. Karall et al.: Stereotactic Radiofrequency Ablation

123

addition, the accuracy of probe placement and the extent of

ablation margin are verified by image fusion. In contrast to

present US-guided RFA techniques, SRFA can be effec-

tively used to treat even large or multiple liver tumors [16].

SRFA is limited only by remaining liver tissue (i.e., enough

functional liver tissue has to remain) and location such as

central tumors that are closer than 1 cm to the central bile

duct as a result of risk of biliary complications.

There is widespread experience for several indications

[15–25], but so far, there have been no reports of treatment

in patients with inherited metabolic disorders. In our study,

SRFA was especially helpful in patients 1 and 2, with

tumors measuring 6.5 and 7.5 cm, respectively. Patient 3

had only a 1.4-cm lesion and could have alternatively been

treated by conventional US- or CT-guided RFA. A single

electrode may have been sufficient. However, it has been

previously demonstrated that the recurrence rate after

SRFA is higher for very small tumors than for tumors

between 3 and 5 cm [16]. The reason for this is that only

one probe is used for the very small tumors. Because of this

observation, a minimum of three probes is used if the

tumor is larger than 1 cm.

If anatomically possible, the needles are placed between

the tumor and the surrounding tissue in order to achieve a

sufficient safety margin. This was not possible in patient 2

because of the close relationship to the stomach, leading to a

small rim of residual tumor tissue. As a result of the clear

advantages of SRFA in contrast to conventional RFA in terms

of precision and efficacy, our institution completely switched

from percutaneous RFA to SRFA as early as 2003 [24].

Recently, percutaneous US-guided image fusion tech-

niques have been introduced. These have already been

successfully used for ablation of lesions with poor con-

spicuity at conventional sonography [26]. Software

improvements may also enable these technologies to sup-

port the planning and placement of multiple probes in order

to treat large tumors [27, 28].

In GSD Ia, the development of adenomas is a known as

a long-term complication, rarely resulting in HCC. This is

different than in TYR I, where development of HCC is a

feared complication. In SRFA, during the procedure,

multiple specimens for histology can be obtained from

each lesion before ablation, and tract ablation in the biopsy

channel abolishes the risk of spreading potentially malig-

nant cells. Analysis of histological specimens was included

in the treatment protocol of the three patients treated. A

potential malignancy would have been treated with the

same SRFA intervention protocol; however, a diagnostic

assessment to detect systemic spreading of the malignant

disease would have followed the procedure.

Patients with inherited metabolic disorders require spe-

cial attention concerning their metabolic control both

during SRFA or conventional surgical interventions. Liver

resection is a surgical procedure with considerable mor-

bidity and a long hospital stay. In contrast, SRFA has a

small rate of major complications (less than 8 %), and

patients are discharged from hospital usually 2–4 days

after the intervention.

The disadvantage of SRFA compared to conventional

RFA is the requirement of an interventional CT suite,

general anaesthesia, training of the staff, and procedure

duration (3–5 h of operating room time). However, in our

opinion, our results justify specialized training in stereo-

taxy as well as the additional costs related to the require-

ments of infrastructure and staff. The disadvantage of

SRFA compared to surgery is the lack of a histologically

confirmed R0 resection. However, in SRFA A0 ablation, an

analogy to R0 resection may be confirmed by fusion of

postablation images with the initial planning images.

Lifelong imaging of the liver for disease surveillance is

similarly required after both procedures.

Compared to surgical interventions, thermal ablation has

other advantages. First, the percutaneous access and

reduced tissue damage causes less catabolism compared to

Fig. 5 Patient 3, a 16-year-old girl with TYR I. A Magnetic

resonance imaging (MRI) (T1-weighed MRI with contrast medium,

volume-interpolated breath hold examination, and fat suppression,

late enhancement) before SRFA showing hypointense liver lesion in

segment VI of 1.4 cm (white arrows). B MRI performed 3 months

after SRFA showing the hypointense ablation necrosis (white

arrowheads) completely covering the ablated lesion (white line)

D. Karall et al.: Stereotactic Radiofrequency Ablation

123

conventional liver surgery. This is especially important for

patients with underlying metabolic disorders that decom-

pensate more rapidly in a catabolic state. As noted in

patient 1, there was a lactate elevation to a maximum of

15.7 mmol/l (normal range 0.5–2.2 mmol/l) and a drop in

hemoglobin to 64 g/l (normal range 120–157 g/l), both

pointing to metabolic stress. Both lactate and hemoglobin

alterations resolved after metabolic stabilization (glucose

infusion to warrant an anabolic state) with no further

interventions. Second, large scars due to laparotomy are

avoided, which can result in functional problems such as

abdominal wall insufficiency and hernias. In addition, the

burden of large scars and poor cosmetic results is avoided,

which may be a major issue, especially in young adults.

In conclusion, in three patients, we have demonstrated

that SRFA is a safe and effective option for the treatment of

hepatic tumors in GSD Ia and TYR I, and that it is a good

alternative for surgical procedures. The use of the SRFA

technique could have immediate and strong consequences

and should be evaluated as an option when treating patients

with inherited metabolic disorders with potential liver

tumor formation.

Conflict of interest Reto Bale is a co-inventor of the Atlas aiming

device and a co-shareholder in its financial returns. The other authors

declare that they have no conflict of interest.

References

1. Clayton PT (2003) Diagnosis of inherited disorders of liver

metabolism. J Inherit Metab Dis 26:135–146

2. Calderaro J, Labrune P, Morcrette G et al (2013) Molecular

characterization of hepatocellular adenomas developed in

patients with glycogen storage disease type I. J Hepatol

58:350–357

3. INSERM Orphanet: the portal for rare diseases and orphan drugs.

http://www.orpha.net/

4. Rake JP, Visser G, Labrune P, Participating Members of the

ESGSD I et al (2002) Guidelines for management of glycogen

storage disease type I. European Study on Glycogen Storage

Disease Type I (ESGSD I). Eur J Pediatr 161:S20–S34

5. Bianchi L (1993) Glycogen storage disease I and hepatocellular

tumours. Eur J Pediatr 152(suppl 1):S63–S70

6. Sakellariou S, Al-Hussaini H, Scalori A et al (2012) Hepatocel-

lular adenoma in glycogen storage disorder type I: a clinico-

pathological and molecular study. Histopathology 60(6B):E58–

E65

7. Froissart R, Piraud M, Mollet Boudjemline A et al (2011) Glu-

cose-6-phosphatase deficiency. Orphanet J Rare Dis 6:27–39

8. Reddy SK, Kishnani PS, Sullivan JA et al (2007) Resection of

hepatocellular adenoma in patients with glycogen storage disease

type Ia. J Hepatol 47:658–663

9. Lee PJ (2002) Glycogen storage disease type I: pathophysiology

of liver adenomas. Eur J Pediatr 161:S46–S49

10. Mollet-Boudjemline A, Hubert-Buron A, Boyer-Neumann C et al

(2011) Perioperative management of hemostasis for surgery of

benign hepatic adenomas in patients with glycogen storage dis-

ease type Ia. JIMD Rep 1:97–106

11. Sniderman King L, Trahms C, Ronald Scott C (2006) Tyrosine-

mia type 1. In: Pagon RA, Bird TD, Dolan CR et al (eds) Gen-

eReviews. University of Washington, Seattle, WA

12. Schiff M, Broue P, Chabrol B, French–Belgian study group for

HT-1 et al (2012) Heterogeneity of follow-up procedures in

French and Belgian patients with treated hereditary tyrosinemia

type 1: results of a questionnaire and proposed guidelines.

J Inherit Metab Dis 35:823–829

13. Dragani TA (2010) Risk of HCC: genetic heterogeneity and

complex genetics. J Hepatol 52:252–257

14. Tazawa Y, Kikuchi M, Kurobane I et al (1990) An acute form of

tyrosinemia type I with multiple intrahepatic mass lesions. J Pe-

diatr Gastroenterol Nutr 10:536–539

15. Bale R, Widmann G, Haidu M (2011) Stereotactic radiofrequency

ablation. Cardiovasc Intervent Radiol 34:852–856

16. Widmann G, Schullian P, Haidu M, Bale R (2012) Stereotactic

radiofrequency ablation (SRFA) of liver lesions: technique

effectiveness, safety, and interoperator performance. Cardiovasc

Intervent Radiol 35:570–580

17. Widmann G, Schullian P, Haidu M et al (2011) Targeting

accuracy of CT-guided stereotaxy for radiofrequency ablation of

liver tumours. Minim Invasive Ther Allied Technol 20:218–825

18. Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD

(2005) Cholangiocarcinoma. Lancet 366:1303–1314

19. Lau WY, Lai EC (2009) The current role of radiofrequency

ablation in the management of hepatocellular carcinoma: a sys-

tematic review. Ann Surg 249:20–25

20. Bale R, Widmann G (2007) Navigated CT-guided interventions.

Minim Invasive Ther Allied Technol 16:196–204

21. Bale R, Widmann G, Stoffner DI (2010) Stereotaxy: breaking the

limits of current radiofrequency ablation techniques. Eur J Radiol

75:32–36

22. Laeseke PF, Sampson LA, Haemmerich D et al (2006) Multiple

electrode radiofrequency ablation creates confluent areas of

necrosis: in vivo porcine liver results. Radiology 241:116–124

23. Bale R, Widmann G (2011) Can stereotactic radiofrequency

ablation replace liver resection? Mag Eur Med Oncol 4:1–4

24. Bale R, Widmann G, Schullian P et al (2012) Percutaneous ste-

reotactic radiofrequency ablation of colorectal liver metastases.

Eur Radiol 22:930–937

25. Schullian P, Widmann G, Lang TB et al (2011) Accuracy and

diagnostic yield of CT-guided stereotactic liver biopsy of primary

and secondary liver tumors. Comput Aided Surg 16:181–187

26. Lee MW, Rhim H, Cha DI et al (2012) Percutaneous radiofre-

quency ablation of hepatocellular carcinoma: fusion imaging

guidance for management of lesions with poor conspicuity at

conventional sonography. AJR Am J Roentgenol 198:1438–1444

27. Kim YS, Lee WJ, Rhim H et al (2010) The minimal ablative

margin of radiofrequency ablation of hepatocellular carcinoma

([2 and \5 cm) needed to prevent local tumor progression: 3D

quantitative assessment using CT image fusion. AJR Am J

Roentgenol 195:758–765

28. Makino Y, Imai Y, Igura T et al (2012) Usefulness of the mul-

timodality fusion imaging for the diagnosis and treatment of

hepatocellular carcinoma. Dig Dis 30:580–587

D. Karall et al.: Stereotactic Radiofrequency Ablation

123