CLINICAL INVESTIGATION INTERVENTIONAL ONCOLOGY

Stereotactic Radiofrequency Ablation (SRFA) of Liver Lesions:Technique Effectiveness, Safety, and Interoperator Performance

Gerlig Widmann • Peter Schullian •

Marion Haidu • Reto Bale

Received: 28 February 2011 / Accepted: 22 May 2011 / Published online: 14 June 2011

� Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2011

Abstract

Purpose To evaluate technique effectiveness, safety, and

interoperator performance of stereotactic radiofrequency

ablation (SRFA) of liver lesions.

Methods Retrospective review including 90 consecutive

patients from January 2008 to January 2010 with 106

computed tomography-guided SRFA sessions using both

single and multiple electrodes for the treatment of 177

lesions: 72 hepatocellular carcinoma (HCC) and 105

metastases with a mean size of 2.9 cm (range 0.5–11 cm).

Technique effectiveness and 1-year local recurrence were

evaluated by computed tomographic scans. Complications,

mortality, and hospital days were recorded. The perfor-

mance between an experienced and inexperienced inter-

ventional radiologist was compared.

Results The overall technique effectiveness after a single

SRFA was 95.5% (93.1% for HCC and 97.1% for metas-

tases). Four of the eight unsuccessfully treated lesions

could be retreated (secondary technique effectiveness of

97.7%). Local recurrence at 1 year was 2.9%. Technique

effectiveness was significantly different for lesions \5 cm

(96.7%) and [5 cm (87.5%) (P = 0.044) but not for

lesions \3 cm (95.9%) and 3–5 cm (100%). Compared to

clear parenchymal property (97.3%), vessel vicinity

(93.3%) (P = 0.349) and subcapsular (95.2%) (P = 0.532)

had no, but hollow viscera vicinity (83.3%) had a signifi-

cantly lower technique effectiveness (P = 0.020). Mortal-

ity rate was 0.9%. Major complications and hospital days

were higher for cirrhosis Child-Pugh B (20%, 7.2 days)

than Child-Pugh A (3.1%, 4.7 days) patients and for

metastases (5.1%, 4.3 days). There was no significant dif-

ference in interoperator performance.

Conclusion SRFA allowed for efficient, reliable, and safe

ablation of large-volume liver disease.

Keywords Ablation � Liver tumor � Hepatocellular

carcinoma (HCC) � Liver/hepatic � Navigation �Radiofrequency ablation � Image fusion

Introduction

Percutaneous image-guided radiofrequency ablation (RFA)

is increasingly used as first-line treatment of hepatocellular

carcinoma (HCC) of \5 cm that is not suitable for liver

resection or transplantation; for bridging therapy before

liver transplantation; for therapy for recurrent and nonre-

sectable HCC; for alternative treatment for resectable HCC

sized 3 cm or less; and for local ablative therapy for liver

metastases [5–8, 13, 26, 33]. RFA has proven to be a safe

procedure, with reported rates of major complications

ranging from 2 to 6% [19, 21, 27].

The success of RFA is excellent for small lesions sized

less than 3 cm [22, 28]. In contrast, the results of large

(diameter [3–5 cm) and irregularly shaped (nonspherical)

lesions as well as lesions located subcapsularly or close to

major vessels are unsatisfying and may argue for excluding

such lesions from RFA treatment. Reasons for technical

G. Widmann � P. Schullian � M. Haidu � R. Bale (&)

Department of Radiology, SIP-Department of Microinvasive

Therapy, Medical University of Innsbruck, Anichstr. 35,

6020 Innsbruck, Austria

e-mail: reto.bale@i-med.ac.at

G. Widmann

e-mail: gerlig.widmann@i-med.ac.at

P. Schullian

e-mail: peter.schullian@i-med.ac.at

M. Haidu

e-mail: marion.haidu@i-med.ac.at

123

Cardiovasc Intervent Radiol (2012) 35:570–580

DOI 10.1007/s00270-011-0200-4

failure may be poor visibility of the lesion and/or lesions

borders, imprecise electrode placement, insufficient abla-

tion size, the heat sink effect due to vicinity to large ves-

sels, and insufficient application of energy [15, 18, 28].

Lesion size and insufficient safety margin have been

identified as the most important influential factors [4, 11,

22, 24–26, 37]. The recent introduction of stereotactic

radiofrequency ablation (SRFA) combines preinterven-

tional 3D imaging, computerized 3D planning of electrode

positions, and guided electrode placement at arbitrary

angulations and orientations [1–3]. SRFA may allow for

effective and safe treatment of even large lesions, lesions in

proximity to large vessels, or lesions in subcapsular loca-

tions [2]. Our purpose was to evaluate technique effective-

ness, safety, and interoperator performance of computed

tomography (CT)-guided SRFA.

Materials and Methods

The study was approved by the institutional review board.

According to the judgment of a multidisciplinary pro-

spective tumor board, clinical subjects with primary or

secondary liver tumors who were not eligible for surgical

treatment, who had medical comorbidities precluding sur-

gery, or who refused surgical treatment were referred for

SRFA. Informed consent was obtained from all patients.

Before treatment, clinical evaluation and general

anaesthetic evaluation including conventional liver bio-

chemical tests, prothrombin time, and complete blood cell

counts were performed. Exclusion criteria for SRFA were

lesions larger than 12 cm, more than 7 lesions, lesions

within 1 cm to the central bile duct, lesions infiltrating

adjacent hollow viscera, liver cirrhosis classified higher

than Child-Pugh class B, manifest ascites, prothrombin

time [23 s, prothrombin activity\40%, and platelet count

\40,000/ml. If the liver tumor had direct contact to hollow

viscera, laparoscopic liver packing with swabs immediately

before SRFA was performed in order to prevent thermal

damage (Bale et al., unpublished data).

Clinical Subjects

During the period January 1, 2008, to January 1, 2010, a

total of 90 consecutive patients (61 men, 29 women, mean

age 61.1 years, range 22–85 years) underwent a total of

106 CT-guided SRFA sessions for 177 lesions. A mean of

1.9 lesions per patient (range 1–7) were treated.

Forty patients had 72 HCCs and 47 SRFA sessions.

Twenty-eight patients (70%) with HCC had Child-Pugh A

cirrhosis, nine (22.5%) Child-Pugh B, and three (7.5%) no

cirrhosis.

Fifty patients had 105 hepatic metastases (54 colorectal,

18 mammary, 9 ovarian, 7 melanoma, 6 renal, 4 neuroen-

docrine, 3 bronchial, 3 papillary carcinoma, 1 teratoma)

and 59 SRFA sessions.

Tumors were confirmed by abdominal CT scans that

were no older than 6 weeks. The CT protocol included

native helical and contrast-enhanced scans using 90–120 ml

iodixanol 320 mg J/mg. The slice thickness for the native

and the portal venous phase were 5 mm, and for the arterial

and late phase 3 mm, respectively. For HCC, a native scan

and an arterial, portal, and late phase with a flow rate of

4 ml/s were obtained. For neuroendocrine tumors, a native,

arterial, and portal phase and for all other entities a native

and a portal venous phase were acquired with a flow rate of

3 ml/s. The mean tumor size of all 177 lesions was 2.9 cm

(range 0.5–11 cm). The HCCs had a mean size of 3 cm

(range 0.5–9.5 cm). The metastases had a mean size of

2.8 cm (range 0.5–11 cm). A total of 123 lesions (69.5%)

were \3 cm, 30 lesions (16.9%) were 3–5 cm, and 24

lesions (13.6%) were[5 cm.

Seventy-three lesions (41%) were clear parenchymal

(lesions with[1 cm distance from the liver capsule,[1 cm

distance to an adjacent hollow viscera, and[1 cm distance

vessels that sized [3 mm, 63 lesions (35.6%) were sub-

capsular (lesions \1 cm close to the liver capsule), 30

lesions (16.9%) had vessel vicinity (\1 cm close to a

vessel that sized [3 mm), and 18 lesions (10.2%) had

hollow viscera vicinity (subcapsular lesions\1 cm close to

an adjacent hollow viscera). Eleven of the 18 lesions with

hollow viscera vicinity had direct contact with the hollow

viscera, requiring separation by liver packing.

Stereotactic Radiofrequency Ablation

All patients were admitted to the referring departments of

gastroenterology, general oncology, or surgery.

All SRFAs were performed at the department of radi-

ology in an interventional suite (class II surgical room,

according to national hospital standards) with a multislice

(40) CT Siemens Somatom Sensation Open (Siemens,

Munich, Germany) that has a 82-cm sliding gantry that

provided full diagnostic image quality.

More information on SRFA is available elsewhere

[1–3]. A flowchart of the procedure is provided in Fig. 1.

Patient Preparation and Respiratory Motion Control

After general anesthesia and muscle relaxation, patients

were rigidly fixed at the table with the BlueBAG patient

fixation system (Medical Intelligence, Schwabmunchen,

Germany) [38]. For lesions in direct contact with hollow

viscera, liver packing was performed in the intervention

G. Widmann et al.: SRFA of Liver Lesions 571

123

room by surgeons with extensive experience in laparo-

scopic surgery.

In lesions of the right liver lobe, patients were posi-

tioned in slight right anterior oblique position, and the right

arm was fixed to an adjustable mechanical arm in an ele-

vated position. A patient-covering bridge was fixed at the

table for placement of the dynamic reference frame of the

navigation system.

To allow for an image-to-patient registration with the

navigation system, self-attachable skin markers (Beekley

Spots, Beekley, Bristol, CT) were placed broadly around

the region of interest.

For respiratory motion control, planning, and control CT

scans, the registration procedure and the targeting were

performed at maximal expiration during temporary dis-

connection of the endotracheal tube, which was executed

by the attending anesthetist in the intervention room [38].

Planning CT

A contrast-enhanced (90–120 ml iodixanol 320 mg J/mg,

3 ml/s) CT scan of the liver with 3-mm slice thickness was

performed in the arterial or portal phase. Three-millimeter

slice thickness provides far better targeting accuracy than

5 mm [34]. The CT data were immediately sent via

Intranet to the Treon Plus navigation system (Medtronic,

Louisville, KY).

3D Treatment Planning

According to the size and geometry of the lesion, one or

multiple electrode positions were planned on the naviga-

tion software as visualized on the 2D and 3D CT recon-

structions. By using the longitudinal and orthogonal cuts

along the planned path, potential penetration of vital

structures could be prevented [2].

The following scheme was used. Electrodes were placed

in and around the lesion with an interprobe distance of a

maximum of 2 cm. Electrodes at the lesion border were

placed at the interface between tumor and normal liver

tissue to assure the goal of a safety margin of 1 cm of

healthy tissue. In lesions that were close to large vessels,

the electrodes were planned to position approximately

5 mm close to the vessel to address the so-called heat sink

effect. If a visible feeding vessel entered the tumor, this

area was ablated first to reduce tissue cooling. In subcap-

sular lesions, the liver capsule was included in the radio-

frequency necrosis. In lesions located close to adjacent

Fig. 1 Flowchart of radiofrequency ablation (SRFA)

572 G. Widmann et al.: SRFA of Liver Lesions

123

hollow viscera, a safety distance of at least 1 cm of the

electrode position to the covering liver capsule was

respected.

Image-to-Patient Registration and Stereotactic

Placement of Coaxial Needles

A paired-point registration procedure was performed that

consisted of definition of coordinates of corresponding

Beekley Spots in the image (manually on the computer)

and on the patient (with the probe of the navigation system)

and calculation of the geometrical transformation that best

aligns these points. For safety reasons, the accuracy of the

navigation was checked by touching Beekley Spots on the

patient with the probe of the navigation system and com-

paring the position as indicated by the navigation system.

After registration, the treatment area was scrubbed and

draped. The sterilized Atlas aiming device (Medtronic,

Louisville, KY) was mounted to the draped attachment

bridge on the intervention table. The device is a lockable

jointed arm with a two joints head that enables the user to

align the probe of the navigation system with the planned

trajectory. After alignment, the depth from the aiming

device to the target point was automatically calculated and

marked on a 15-gauge, 17.2-cm coaxial needle (Bard,

Covington, GA). The navigation probe was removed from

the aiming device, and the adjustable breaks on the head

were narrowed to guide the coaxial needle. One by one,

each coaxial needle was advanced through the aiming

device to the preplanned depth during short (10 s) tempo-

rary endotracheal tube disconnections [39]. A mean of 4.1

(median 3, range 1–14) coaxial needles per lesion were

positioned. A single needle positioning required approxi-

mately 2 min.

Before ablation, a native control CT with 3-mm slice

thickness (similar scan protocol as for the planning CT)

was performed to verify the needle positions and to exclude

puncture-related complications such as pneumothorax or

bleeding. The data were fused to the planning CT and

allowed the actual needle position to be checked in relation

to the planned path and target lesion [39].

Radiofrequency Ablation

The unipolar Covidien Cool-Tip radiofrequency system

(Covidien, Mansfield, MA), including the Cool-Tip radio-

frequency switching controller and a 17-gauge Cool-Tip

electrode with a length of 25 cm and a tip exposure of

3 cm, were used. The electrodes were inserted through the

17.2-cm coaxial needles and placed tip to tip. Afterward,

the shorter coaxial needles were retracted in order to

uncover the 3-cm active electrode exposure. Thus, repeat

imaging for electrode positioning control was not required.

Following the recommendations of the manufacturer, all

ablations were performed using the switching control mode

for up to three electrodes during a 16-min ablation per

cycle. For a single electrode, the recommended 12 min

were used. Mean ± SD ablation time per treatment session

(n = 106) was 64.2 ± 44.3 min (median 50 min, range

12–210 min).

Tract ablation was performed during every probe

retraction (even if the electrode was not removed from the

liver capsule) in order to prevent tumor recurrence,

bleeding and potential tumor seeding. A final portal phase

contrast-enhanced control CT (90–120 ml iodixanol

320 mg J/mg, 3 ml/s) was performed to exclude treatment-

related complications. In the case that required laparo-

scopic liver packing, the surgical team immediately

removed all glycol-saturated drapes, and the laparoscopic

sites were closed.

After regular postoperative intensive care observation,

the patients were sent to the referring departments of gas-

troenterology, general oncology, or surgery. The time point

of discharge from the hospital was decided by the referring

physicians, depending on each patient’s individual postin-

terventional recovery and general physical state. There was

neither an intention for early discharge nor an intention for

an observation longer than necessary. The interventional

radiologist had no influence on the discharge time of the

patients.

Assessment of Technique Effectiveness and Local

Recurrence

Technique effectiveness and local recurrence were evalu-

ated per treated lesion.

The following parameters were evaluated: technique

effectiveness, local tumor progression, and complications.

The parameters were evaluated on postinterventional con-

trast-enhanced abdominal CT at 1, 3, 6, and 12 months. The

CT scans were performed according to the routine diag-

nostic protocol of our university. The evaluation was per-

formed by an independent reader who did not perform the

interventions by collecting the standard radiologic reports

during follow-up in the department of radiology. Two cases

of SRFA that were hard to treat with conventional tech-

niques in a single session are illustrated in Figs. 2 and 3.

Technique effectiveness was defined as complete abla-

tion on contrast-enhanced imaging at 1 month after SRFA.

Local recurrence was defined as evidence of newly detec-

ted tumor at the site of ablation at contrast-enhanced

imaging at 3, 6, and 12 months after CT-guided SRFA.

Complete ablation of a treated lesion was defined as cir-

cumscribed nonenhancing region within and extended

beyond the tumor borders, eventually surrounded by a

reactive rim enhancement [5]. Remaining or newly

G. Widmann et al.: SRFA of Liver Lesions 573

123

developed contrast enhancement of the ablated lesion was

considered as vital tumor tissue [5].

Subanalysis of technique effectiveness rate was per-

formed for entity (HCC vs. metastases), lesion size (\3 cm

vs. 3–5 cm vs. [5 cm; [5 cm vs. \5 cm; and [3 cm

vs. \3 cm), properties (clear parenchymal vs. vessel

vicinity; clear parenchymal vs. subcapsular; clear paren-

chymal vs. hollow viscera vicinity), and location (liver

segments I to VIII).

Assessment of Complications and Hospital Days

Complications and hospital days were evaluated per

ablation.

Major complications related to needle insertion or the

ablation procedure were defined as if they were left untreated

without invasive intervention might threaten the patient’s

life, lead to substantial morbidity and disability, or result in

an extended hospital stay.

Fig. 2 A 54-year-old man with HCC showing three lesions (whitearrows) that were simultaneously treated by a single SRFA. (1) A

3-cm lesion subcapsular segment V (3 coaxial needles/3 electrode

positions). (2) A 1.2-cm lesion segment I (1 coaxial needle/1

electrode position). (3) A 1.3-cm lesion segment IVb (2 coaxial

needles/2 electrode positions). (10), (20), and (30) refer to the

corresponding postinterventional CT scans at 1 month. Note the

sufficient larger ablation zones (white arrowheads) confirming

technique effectiveness

Fig. 3 A 70-year-old woman with HCC showing a 4.5-cm lesion

(white arrows) in segment VIII in broad contact to the middle and

right hepatic vein (8 coaxial needles/18 electrode positions). (1)

Before CT-guided SRFA. (10) Postinterventional CT at 1 month

showing sufficient larger ablation zone (white arrowheads)

confirming technique effectiveness. (100) Postinterventional CT at

12 months showing shrinkage of the ablation zone (black arrow-heads) confirming no local tumor progression. The slice positions of

the images were chosen to demonstrate the relationship of the ablation

and the adjacent vessels

574 G. Widmann et al.: SRFA of Liver Lesions

123

Minor complications were defined as complications and

relevant side effects that did not require invasive inter-

vention. Mortality rate was defined as the direct or indirect

procedure-related death rate within 6 months after

intervention.

Hospital days from the day of SRFA to the day of dis-

charge were calculated.

Complications and hospital days were compared for the

groups HCC in cirrhosis Child-Pugh A vs. Child-Pugh B

vs. metastases.

Assessment of Interoperator Performance

Interoperator performance between an experienced and

inexperienced interventional radiologist was calculated to

assess operator-dependent differences of SRFA. The

experienced radiologist (Author 1) had more than 10 years

of experience in percutaneous radiofrequency ablation and

stereotactic interventions. The inexperienced radiologist

(Author 2) had 4 years of residency training in radiology

and clinical routine in ultrasound (US)-guided and

CT-guided liver biopsies. Author 2 had no previous expe-

rience in RFA and started SRFA after a training period of

2 months. All treatment planning, electrode positioning,

and ablations were performed exclusively and completely

by either Author 1 or Author 2.

Statistical Analysis

Data analysis and descriptive statistics were performed by

PASW Statistics 17.0 (SPSS, Chicago, IL). Quantitative

data were described with mean values, standard deviation,

median, and range.

Pearson’s chi-square test was used to determine signif-

icant statistical differences between the groups ‘‘entity,’’

‘‘lesion size,’’ ‘‘properties,’’ and ‘‘location.’’ The same test

was used to determine statistically significant differences

between Author 1 and Author 2.

Student’s t-test was used to determine significant sta-

tistical differences in hospital days between HCC in cir-

rhosis Child-Pugh A vs. Child-Pugh B vs. metastases.

For all statistical tests, a P-value of less than 0.05 was

defined as statistically significant.

Results

Technique Effectiveness and Local Recurrence

All patients and lesions assigned to SRFA could be treated.

Technique effectiveness after one treatment session of

CT-guided SRFA was 95.5% per treated lesion (Table 1).

Of 177 lesions, 8 lesions in 7 patients were unsuccess-

fully treated, leading to technique effectiveness per patient

of 92.2%. Four lesions could be retreated by a second

CT-guided SRFA. One lesion showed local recurrence at

6 months after reintervention, and 4 lesions could not be

retreated as a result of progressive disease, other treatment,

or refusal of further treatment. The failed cases are pre-

sented in Table 2.

The failures of SRFA occurred in 4 lesions B2 cm in

size using only one electrode and in 3 large lesions ranging

from 6 to 8 cm, one having vessel vicinity, one subcapsular

and one having subcapsular and vessel vicinity properties.

Local recurrence after technically successful SRFA was

0% at 3 months, 1.2% (2/173) at 6 months, and 2.9%

(5/173) at 12 months.

Subanalysis of technique effectiveness revealed the

following.

Entity

HCC showed no significant difference in technique effec-

tiveness rates (93.1%) compared to metastases (97.1%)

(P = 0.198).

Table 1 Characteristics of 177 liver lesions in 90 patients

Characteristic Overall Author 1 Author 2 P-value

Patients (n) 90 55 35

Tumor size (cm), mean ± SD (range) 2.9 ± 2.1 (0.5–11) 2.8 ± 1.9 (0.5–9) 3 ± 2.2 (0.5–11) 0.754

Lesions per patient (n), mean ± SD (range) 1.9 ± 1.3 (1–7) 1.9 ± 1.3 (1–7) 1.9 ± 1.2 (1–5) 0.872

Needles per lesion (n), mean ± SD (range) 4.1 ± 3 (1–14) 4 ± 3 (1–14) 4.2 ± 3.3 (1–14) 0.734

Technique effectiveness 95.5% (169/177) 95.9% (93/97) 95% (76/80) 0.780

Early local tumor progression (3 months, successfully treated) 0% 0% 0%

Local tumor progression (6 months, successfully treated) 1.1% (2/177) 2.1% (2/97) 0% 0.196

Major complications (intervention necessary) 6.6% (7/106) 6.6% (4/61) 6.7% (3/45) 0.982

Mortality 0.9% (1/106) 1.6% (1/61) 0% (0/45) 0.388

Hospital stay (days), mean ± SD (range) 4 ± 2.4 (1–11) 4 ± 2.4 (1–11) 4 ± 2.5 (1–9) 0.749

G. Widmann et al.: SRFA of Liver Lesions 575

123

Lesion Size

The analyzed groups showed no significant difference

when divided into \3 cm (95.9%) vs. 3–5 cm (100%)

vs. [5 cm (87.5%) (P = 0.083), and [3 cm (94.4%)

vs. \3 cm (95.5%) (P = 0.669). Significant differences

were found for \5 cm (96.7%) vs. [5 cm (87.5%)

(P = 0.044).

Properties

Statistical analysis revealed no significant difference of

clear parenchymal lesions (97.3%) compared to vessel

vicinity (93.3%) (P = 0.349) and subcapsular (95.2%)

(P = 0.532). In contrast, significant difference was found

for hollow viscera vicinity (83.3%) (P = 0.020).

No significant differences were observed (P = 0.125)

when comparing technique effectiveness of treatment of

lesions close to hollow viscera that did not require liver

packing (85.7%) and clear parenchymal location. How-

ever, significant differences were observed between the

treatment of lesions with clear parenchymal location and

lesions with direct contact to hollow viscera requiring

liver packing (81.8%) (P = 0.025). There was no signif-

icant difference in the size of the tumors with hollow

viscera vicinity that were treated with (mean 4.2 cm,

median 4.5 cm, range 1.3–7 cm) or without (mean

3.9 cm, median 2.8 cm, range 1.3–11 cm) liver packing

(P = 0.616).

Location

Statistical analysis of lesion location as a factor for tech-

nique effectiveness showed that there were no significant

differences among segments. Lesions located in segment II

or III did not show significant difference to the other seg-

ments (P = 0.125).

Complications and Hospital Days

Mortality rate was 0.9% (1 patient, sepsis and multiorgan

failure). Major and minor complication rates were 6.6%

and 21.7%, respectively (Table 3).

In a subanalysis including both major and minor com-

plication rates related to entity, lesion size, properties, and

location, the following statistically significant differences

were found: HCC 34.7% (25/72) vs. metastases 19% (20/

105) (P = 0.019), and [3 cm 37% (20/54) vs. \3 cm

20.5% (25/122) (P = 0.020). All other parameters did not

show statistically significant differences.

Of all 106 ablations, major complications occurred in

3.1% in HCC in cirrhosis Child-Pugh A (1/32), 20%

in HCC in cirrhosis Child-Pugh B (2/10), and in 5.1% in

metastases (3/59). (Note that 5 patients with HCC had no

cirrhosis.) Chi-square test showed P = 0.131.

Excluding the patient who died and the ablations with

liver packing, a mean of 4 and a median of 3 hospital

days (range 1–11 days) were recorded from the day of

SRFA to discharge from the hospital. In a subanalysis for

Table 2 Details of the failed cases with residual tumor after SRFA

Sex Age Entity Location Property Lesion

size (cm)

Coaxial

needles

Supplemental information Repeat

SRFA

M 78 HCC III Subcapsular 1 1 Targeting imprecision Yes

M 78 HCC VII Clear parenchymal 1.2 1 Small residual tumor and multiple

disseminated new lesions

No

M 53 HCC I Vessel vicinity 1.5 1 Previous transarterial chemoembolization

and percutaneous ethanol injection due

to vicinity to central bile duct; SRFA

after size reduction; residual tumor was

at the bile duct

No

M 75 HCC II Hollow viscera vicinity 2 1 Insufficient ablation size No

M 69 Meta CRC II Hollow viscera vicinity 2.4 3 Small residual tumor close to the stomach Yes

M 74 HCC VIII Subphrenic 6 5 Insufficient ablation size Yes

M 59 Meta RCC VI Vessel vicinity, subcapsular,

hollow viscera vicinity

6 9 Small residual tumor close to the VCI and

lateral subcapsular

No

M 58 Meta CRC VIII

(main)

Vessel vicinity 8 12 Central lesion surrounding and attaching

right, middle and left hepatic vein, VCI,

and portal vein; small residual tumor at

the portal vein

No

RCC Renal cell carcinoma, CRC colorectal carcinoma

576 G. Widmann et al.: SRFA of Liver Lesions

123

longer hospital stays ([5 hospital days) related to the

above parameters, the following statistically significant

differences were found: \3 cm 23% (28/122) vs. 3–5 cm

53.3% (16/30) vs. [5 cm 62.5% (15/24) (P = 0.000). All

other parameters did not show statistically significant

differences.

The corresponding hospital days for SRFA of HCC in

cirrhosis Child-Pugh A (n = 32) showed mean 4.7 ±

3.8 days (median 4 days); for Child-Pugh B (n = 10)

showed mean 7.2 ± 6 days (median 5.5 days); and for

metastases (n = 59) showed mean 4.3 ± 2.5 days (median

4 days). The t-tests showed the following: HCC in cirrhosis

Child-Pugh B vs. metastases, P = 0.187; HCC in cirrhosis

Child-Pugh B vs. Child-Pugh A, P = 0.135; and HCC in

cirrhosis Child-Pugh A vs. metastases, P = 0.538.

For the ablations with liver packing, a mean of 7.76 and

a median of 6 hospital days (range 4–20 days) were found,

which was significantly higher than without liver packing

(P = 0.002).

Interoperator Performance

A total of 55 patients were treated by Author 1 and 35

patients by Author 2 (Table 1). There were no significant

differences in patient characteristics for age (P = 0.822),

sex (P = 0.898), lesion size (P = 0.754), number of

lesions per patient (P = 0.872), and number of coaxial

needles per lesion (P = 0.734) for the two operators.

There were no significant differences in technique

effectiveness (P = 0.780), major complications (P =

0.889), and hospital days (P = 0.749).

Discussion

In the presented SRFA protocol, one or multiple cooled

monopolar electrodes were placed at one or multiple

electrode positions via coaxial needles at a maximum

interelectrode distance of 2 cm, depending on the tumor

size and shape. If multiple electrodes were used, they were

activated by the switching control mode, where the power

is automatically switched from one electrode to up to three

others depending on the impedance. Lee et al. [14] showed

that when using three cooled-tip monopolar electrodes, the

circularity (isometric ratio) of the ablation zone decreased

with increasing interelectrode distance, and that interelec-

trode distances of larger than 3 cm could not create con-

fluent coagulation necrosis. Multitined expandable

electrodes may not be useful in our approach to position

multiple electrodes very close to vessels, the diaphragm,

and the liver capsule [4, 10, 16, 26, 30]. Multipolar elec-

trodes are feasible but require strict parallelism of the

electrode positions to ensure confluent necroses [31]. In

conventional RFA, usually only one electrode or clusters of

three electrodes are used. For larger tumors, repeat abla-

tions are performed. The multielectrode/electrode position

approach in SRFA allowed for generation of arbitrary large

overlapping ablation necroses. Thus, unlike conventional

RFA, individual features and ablation sizes of different

electrode systems do not influence the success of SRFA.

However, in principle, the procedure may be adapted to

any radiofrequency electrode system, as well as to cryo-

ablation and microwave technologies.

By using conventional US-guided RFA for treatment of

HCC in 42 patients with 52 lesions B3 cm, with a mean of

Table 3 Details of mortality

and complications of 106

ablations in 90 patients

Characteristic Value Therapy

Mortality 0.9% (1/106)

Sepsis and organ failure 0.9% (1/106)

Major complications (intervention necessary) 7.5% (8/106)

Pneumothorax 2.8% (3/106) Drainage

Pleural effusion 0.9% (1/106) Drainage

Liver abscess 0.9% (1/106) Drainage and antibiotics

Perihepatic bleeding 0.9% (1/106) Coiling

Multiple organ dysfunction syndrome 0.9% (1/106) Intensive care unit

Minor complications (no intervention necessary) 21.7% (23/106)

Pleural effusion 12.3% (13/106)

Pneumothorax 2.8% (3/106)

Subcapsular hematoma 1.9% (2/106)

Perihepatic bleeding 1.9% (2/106)

Temporary blood pressure increase 0.9% (1/106)

Small pulmonary embolism 0.9% (1/106)

Skin burn 0.9% (1/106)

G. Widmann et al.: SRFA of Liver Lesions 577

123

1.2 treatment sessions, Livraghi et al. [17] achieved a

technique effectiveness rate of 90% (47/52). However, in

126 HCC lesions 3.1 cm or larger in diameter in 114

consecutive patients, the same authors reported technique

effectiveness of only 47.6% (60/126) [18]. In the series

of Seror et al. [31] with US-guided multipolar RFA of

HCC [5 cm (median size 5.7 cm, range 5.0–8.5 cm), a

technique effectiveness of 81% (22/27) was achieved after

a mean of 1.2 treatment sessions. Tumors larger than 8 cm

could not be successfully ablated.

For treatment of colorectal liver metastases using con-

ventional US-guided RFA in 88 consecutive patients with

134 lesions (mean size 2.1 cm, range 0.6–4 cm) and 119

ablations, Livraghi et al. [20] reported a technique effec-

tiveness of 63% (85/134), and Solbiati et al. [32] reported a

technical success of 98% (176/179) when treating 117

patients with 179 lesions (mean size 2.8 cm, range

0.6–9.6 cm). Chen et al. [4] used a mathematical model for

creation of overlapping necroses with US-guided RFA in a

total of 332 patients with 503 liver lesions (mean size

4.0 cm, range 1–8 cm) who were treated in a mean of

1.2–1.6 sessions; they reported technique effectiveness

rates of 95.8% (295/308) for HCC and 94.9% (185/195) for

liver metastases. The technique effectiveness in large

([3.5 cm) and small lesions was 91.3% (189/207) and

98.3% (291/296), respectively.

Livraghi et al. [17, 18, 20], Solbiati et al. [32], Seror

et al. [31], and Chen et al. [4] each performed repeat ses-

sions (up to 11) of conventional US-guided RFA, if pos-

sible, when residual tumor was identified on initial

posttreatment CT. Thus, reported technique effectiveness

often refers to secondary technique effectiveness [9].

SRFA provided a technique effectiveness after a single

treatment session (=primary technique effectiveness rate)

of 95.5% (169/177). For 54 lesions [3 cm, technique

effectiveness was 94.4%, and for the 24 lesions [5 cm,

87.5%. Compared to present techniques, SRFA allowed for

successful ablation of lesions [8 cm with a maximum

lesion size of 11 cm. Four of the 8 incompletely ablated

lesions could be treated by a second SRFA and were

completely ablated. Thus, SRFA finally showed a sec-

ondary technique effectiveness of 97.7%. One year after

successful CT-guided SRFA, a total of 2.9% (5/173) local

recurrences were found.

HCC vs. metastases did not show statistically significant

differences (93.1% vs. 97.1%). Remarkably, vessel vicinity

and subcapsular did not significantly influence technique

effectiveness compared to clear parenchymal, which is a

clear difference from a previous meta-analysis of RFA

[22]. Obviously, following the concept of placing elec-

trodes very close to vessels successfully overcame the heat

sink effects [2, 3, 35]. Only the hollow viscera vicinity

showed significantly lower technique effectiveness of

83.3% (15/18) compared to clear parenchymal with

97.3% (71/73). Compared to the mean overall tumor size

of 2.9 cm, the group of hollow viscera vicinity had a

mean tumor size of 4 cm. Remarkably, hollow viscera

vicinity that did not require liver packing (7/18) had no

significant different technique effectiveness compared to

clear parenchymal. However, lesions that required laparo-

scopic liver packing still were difficult to treat and had

worse results. In sum, the most important sources of failure

in the presented series of SRFA were insufficient targeting

and insufficient ablation size related to using only one

electrode, and very large tumor size with vessel vicinity

and subcapsular and hollow viscera vicinity. The impor-

tance of large ablation margins of healthy tissue sur-

rounding the tumors cannot be overemphasized.

In conventional RFA, the ablations were mostly treated

as outpatients or with one night’s stay. A multicenter study

of complications of percutaneous RFA of 3554 lesions in

2320 patients showed a mortality rate and major compli-

cation rate of 0.3 and 2.2%, respectively [19]. In the pre-

sented SRFA series, the mortality rate and major

complication rates of 0.9 and 6.6%, respectively, were

higher. The multineedle/needle position approach for sin-

gle-session treatment of up to 7 lesions per patient and a

mean of 4.1 coaxial needles per lesion (the largest lesions

with 14 coaxial needles) while the patient was under gen-

eral anaesthesia was certainly more aggressive than con-

ventional RFA techniques. With these considerations, the

complication rate and hospital days were still small,

and substantially smaller than that of surgical resection.

Most major complications, including pneumothorax, pleu-

ral effusion, liver abscess, and hepatic bleeding, could be

successfully treated by interventional therapy. Significantly

higher overall complication rates were found for

lesions[3 cm (37%) compared to lesions\3 cm (20.5%),

but remarkably, vessel vicinity, and subcapsular and hol-

low viscera vicinity did not show significant differences to

clear parenchymal. The overall complication rates were

significantly higher for HCC (34.7%) than for metastases

(19%), and major complications were substantially higher

for cirrhosis Child-Pugh B (20%) compared to Child-Pugh

A (3.1%) and metastases (5.1%). Patients were discharged

from the hospital after a mean and median of 4 and 3 days,

respectively. Patients needed a significantly longer hospital

stay of more than 5 days in correlation to tumor size in

62.5% of lesions [5 cm and only 23% of lesions \3 cm,

but not for other lesion properties. This may reflect the

consequences of the increasing aggressiveness that is

required for successful treatment of large lesions during

one treatment session. Cirrhosis Child-Pugh B had more

median hospital days (5 days) than Child-Pugh A and

metastases (4 days each). Obviously, patients who required

laparoscopic liver packing for treatment of lesions with

578 G. Widmann et al.: SRFA of Liver Lesions

123

contact to hollow viscera needed more hospital days than

patients without liver packing.

Real-time virtual sonography, synchronizing preinter-

ventional multiplanar reformatted CT, or magnetic reso-

nance imaging to B-mode US may improve targeting and

allows for the treatment of liver lesions that are undetect-

able by US [23, 29].

However, conventional approaches may not be practi-

cable for lesions requiring multiple electrode positions as a

result of the three-dimensional problem considering opti-

mal ablation criteria, safety, and access routes surrounded

by anatomic obstacles [22, 28]. In the presented series of

SRFA, all liver lesions in all locations could be treated with

no limitations concerning access or number and complexity

of electrode positions. In contrast to reports that enforce the

role of the experience of the interventional radiologist

performing RFA [5, 28], SRFA did not reveal significant

differences of treatment success and morbidity rates if it

was executed by an experienced or inexperienced inter-

ventionalist, and the procedure seemed to greatly enhance

our outcomes. Because both operators had similar patients,

lesion characteristics, and technical characteristics, a bias

related to size and complexity could be ruled out.

A drawback of the optical navigation system was the line-

of-sight problem, which may constrain navigation after

insertion of a large number of needles and which may

require repositioning of the stereoscopic camera. In contrast,

electromagnetic navigation has no line-of-sight problem, but

position measuring is less stable and significantly influenced

by metallic distortion [36, 40, 41].

Disadvantages of this high-end guidance technology are

the increased requirements on infrastructure, staff, and

specialized training in 3D-navigated stereotaxy [1, 2, 12].

A multifunctional intervention room with full anesthesia

equipment is required. Large gantry diameters for inter-

ventional radiology are not widely available but should be.

Sliding gantries allow moving the CT between two sepa-

rable rooms and may not block the CT scanner during the

entire intervention.

Limitations of the study are as follows. The study is a

retrospective review of consecutive patients treated with

SRFA in a single center. Unfortunately, worldwide, no

other center performs SRFA or any other form of stereo-

tactic ablative therapy, and we could not compare our

results to others. We could not conduct a prospective

randomized, controlled study comparing SRFA with

US-guided RFA because at our university hospital,

US-guided RFA is no longer accepted, the result of the

substantial technical advantages of SRFA.

Although data from consecutive patients during a

period of 2 years were reviewed, the number of patients

(n = 90) and number of treated lesions (n = 177) are

small—perhaps too small to show significant differences

in some of the parameters for subanalysis. Related to the

inhomogeneous group of metastases and small numbers, a

differentiated subanalysis of metastases was not per-

formed. The wide range of sizes (0.5–11 cm) makes

definite conclusions difficult, and it is hard to draw major

conclusions from one experienced vs. one less experi-

enced interventional radiologist. The results should be

confirmed by others at different medical centers.

The main purpose of the study was to evaluate tech-

nique effectiveness and safety of liver lesions treated by

SRFA. We did not perform a statistical multivariable

evaluation for technical failure and local recurrence

because we had only 8 failures and 5 local recurrences.

The reasons for the technical failures were discussed in

detail. We did not evaluate the potential influence of

systemic therapy on technique effectiveness and local

recurrence. The local recurrence during 1 year was

included in our evaluation; however, Kaplan–Meier

analysis on overall and recurrence-free survival was not

the purpose of this study.

It is difficult to draw a clear line between incomplete

ablation determined as ‘‘technically ineffective’’ and ‘‘local

recurrence.’’ In the presented study, 1 month’s control was

used to determine technique effectiveness, and the sub-

sequent 3, 6, and 12 months’ control was used to determine

local recurrence. Local recurrence (not distant recurrence

of a new clone near the ablated lesion) may always be the

result of an insufficient ablation margin and thus incom-

plete ablation. However, at 3 months, local recurrence after

technical successful SRFA was not noted.

In conclusion, compared to conventional image-guided

percutaneous RFA, SRFA is a technically advanced pro-

cedure that integrates interventional 3D imaging, 3D

computerized treatment planning, and 3D stereotactic

guidance. Technique effectiveness after a single session of

SRFA for even multiple lesions per patient was 95.5%.

There were no significant performance differences between

an experienced radiologist and a less experienced radiolo-

gist. Because of careful 3D planning and stereotactic

placement of multiple electrodes/electrode positions,

SRFA allowed for safe and effective treatment of large-

volume liver disease. Long-term clinical results of SRFA

remain to be determined.

Acknowledgments The authors thank the radiation technicians:

Bob Lang, RT, Martin Fasser, RT, Martin Knoflach, RT, Julia

Mahlknecht, RT, and Florian Schanda, RT.

Conflict of interest Gerlig Widmann, Peter Schullian, and Marion

Haidu have no conflict of interest. Reto Bale is a coinventor of the

stereotactic aiming device used in this study (Atlas, Medical Intelli-

gence GesmbH, Schwabmunchen, Germany) and a coshareholder in

its financial returns.

G. Widmann et al.: SRFA of Liver Lesions 579

123

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