Microwave thermal ablation is a safe novel approach to treat HCC and could serve as a \'bridge\' to OLT and down-staging for patients with HCC

1. Microwave Thermal Ablation for Hepatocarcinoma: Six Liver
Transplantation Cases
G. Zanus, R. Boetto, E. Gringeri, A. Vitale, F. D’Amico, A. Carraro, D. Bassi, P. Bonsignore, G. Noaro,
C. Mescoli, M. Rugge, P. Angeli, M. Senzolo, P. Burra, P. Feltracco, and U. Cillo
ABSTRACT
Surgical resection for malignant hepatic tumors, especially hepatocarcinoma (HCC), has
been demonstrated to increase overall survival; however, the majority of patients are not
suitable for resection. Radiofrequency ablation (RFA) is the most widely used modality for
radical treatment of small HCC (Ͻ3 cm). It improves 5-year survival compared with
standard chemotherapy and chemical ablation, allowing down-staging of unresectable
hepatic masses. Microwave ablation (MWA) has been extensively applied in Asia and was
recently introduced in the United States of America and Europe with excellent results,
especially with regard to large unresectable HCC. Our single-center experience between
May 2009 and October 2010 included application of MWA to 154 patients of median
age Ϯ standard deviation of 63.5 Ϯ 8.5 years, 6 males, and 1 female, of mean Model for
End-Stage Liver Disease (MELD) score (10.1 Ϯ 3.8). The HCC included, hepatitis C virus
(HCV)-related (n ϭ 70; 45.5%); alcool (ETOH)-related (n ϭ 42; 27%), hepatitis B virus
(HBV)-related (n ϭ 16; 10.5%); and cryptogenic cases (n ϭ 26; 17%). The cases were
performed for radical treatment down-staging for multifocal pathology or bridging liver
transplantation to orthotopic (OLT) in selected patients with single nodules. A computed
tomography (CT) scan was performed at 1 month after the surgical procedure to evalue
responses to treatment. Among 6 selected patients who underwent OLT; 5 (83.3%)
showed disease-free survival at one-year follow-up. The radical treatment achieved no
intraoperative evidence of tumor spread or of pathological signs of active HCC among the
explanted liver specimens. In conclusion, a MWA seemed to be a safe novel approach to
treat HCC and could serve as a “bridge” to OLT and down-staging for patients with HCC.
EPATOCARCINOMA (HCC) is the sixth most com- the other ablation techniques. Dong et al3 reported 216
H mon cancer and third leading cause of cancer-related
deaths with low resectability rates at the time of presenta-
patient with percutaneous ablation with MWA to treat 5 cm
(mean 40 Ϯ 24 mm) HCC with overall survival rates at 1, 3,
tion, ranging from 13%–35%.1 When surgical options are and 5 years of 94.8%, 80.4%, and 68.6%, respectively and a
precluded, image-guided tumor ablation is recommended low major complication rate (1.3%). In another experience
as the most appropriate therapeutic procedure. It is con- Liang et al4 noted the 74 patients treated with percutaneous
sidered a potentially radical treatment for selected pa-
tients.1 Given the shortage of deceased donors, hepatic
ablative procedures seem to represent a useful and effective From the General Surgery and Organ Transplantation, Hepa-
treatment for patients with HCC listed for orthotopic liver tobiliary Surgery and Liver Transplant Unit, Azienda Università di
transplantation (OLT) Bruix and Llovet in the Barcelona Padova (G.Z., R.B., E.G., A.V., F.D.A., A.C., D.B., P.B., G.N.,
U.C.) Anatomia Patologica (C.M., M.R.) Clinica Medica 5a (P.A.),
Clinic Liver Cancer (BCLC) therapeutic strategy suggested
Gastroenterologia (M.S., P.B.), and Intensive Care Unit (P.F.),
thermal ablation to be a useful procedure for unresectable Università di Padova, Padova, Italy.
HCC.2 Address reprint requests to Giacomo Zanus, General Surgery
Microwave ablation (MWA) technology with the intro- and Organ Transplantation, Hepatobiliary Surgery and Liver
duction of the latest technical expedient (“mini-choke”) has Transplant Unit; Azienda Università di Padova; Via Giustiniani,
gained excellent therapeutic capability in comparison with 2 - 35128, Padova, Italy. E-mail: zanus@unipd.it
© 2011 by Elsevier Inc. All rights reserved. 0041-1345/–see front matter
360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2011.02.044
Transplantation Proceedings, 43, 1091–1094 (2011) 1091

2. 1092 ZANUS, BOETTO, GRINGERI ET AL
MWA for a median 3 cm HCC showed overall 1-, 3-, 4-, and RESULTS
5-year survival rates of 91%, 46%, 29%, and 29%, respec- Six patients of mean age Ϯ SD of 59.5 Ϯ 6.1 years and
tively with a 14% incidence local tumor recurrence. The including a M/F ratio of 4:2 underwent liver transplantation
first Asian experience did not demonstrate a clear, defini- after the procedures, HCC were HCV-related (n ϭ 3;
tive advantage of MWA compared with RFA, given the lack 50%); ETOH-related (n ϭ 2; 33.3%); and HBV-related
of randomized controlled trials on the safety and efficacy of (n ϭ 1; 16.7%). This mean MELD score was 15.3 Ϯ 16.5.
the procedure.5 Their four of them had been percutaneously and 2 laparo-
In a retrospective study comparing radiofrequency abla- scopically treated in single procedures. They underwent
tion (RFA) and MWA Lu et al6 in 2005 reported no OLT from a deceased donor at a median of 5.6 Ϯ 3.8
significant difference in local recurrence as well as major or months after the ablative procedure (Table 1).
minor complications among 102 patients. Xu et al7 investi- Four patients underwent percutaneous treatment as
gated the prognostic factors for good long-term outcomes bridge to OLT to avoid neoplastic disease diffusion and
after MWA versus radiofrequency among 137 consecutive decrease the risk of OLT list drop-out. This median age Ϯ
patients showing a great variability in tumor size and SD was 61.5 Ϯ 3.1 years and the M/F ratio of 3:1 had HCC
position. A univariate analysis demonstrated no differences that was HCV -related (1 multifocal); ETOH-related (2
between RFA and MWA. We applied MWA to patients single nodule); or HBV-related (1 single nodule). Their
with HCC listed for OLT seeking to decrease the risk of list overall mean MELD score was 13.8 Ϯ 5.8. Two patients of
drop-out (“bridging”) and to carry patients into OLT mean age Ϯ SD of 55.5 Ϯ 9.8 years and with M/F ratio of
(1:1), MELD score of 18.5 Ϯ 8.6 HCV-related (1 multifocal
criteria (“down-staging”). We evaluated the macroscopic
and 1 single nodule) underwent laparoscopic exploration
and microscopic evidences on explanted liver specimens of
and nodule ablation with down-staging to achieve OLT
procedure efficacy.
criteria.
In all 6 cases no peritoneal or nodal HCC macroscopic
and microscopic diffusion was observed intraoperatively at
METHODS
the time of laparotomy for OLT. Peritoneal adhesions were
From May 2009 to October 2010, we entered into the trial 154 detected at the sites of the ablative procedures without any
HCC patients including a male to female (M/F) ratio of 6:1 of substantial difficulty in the dissection or hepatectomy. No
mean age Ϯ standard deviation (SD) of 63.5 Ϯ 8.5 years. The HCC patient who underwent OLT suffered any complication
was hepatitis C virus (HCV)-related (n ϭ 70; 45.5%); alcool during or after the ablative procedure.
(ETOH)-related (n ϭ 42; 27%); hepatitis B virus (HBV)-related
Five of 6 transplant recipients (83.3%) are still alive
(n ϭ 16; 10.5%) cryptogenic cases (n ϭ 26; 17%). The MWA was
beyond 1 year after OLT, in the absence of a local or
performed under sonografic guidance (Esaote, Technos mix; Hita-
chi Logos Hi-Vision C) using Amica HS 14 Gauge needle with
metastatic recurrence of HCC on 1, 3, 6, and 9 month, CT
“mini-choke” technology. The operating frequency was 2450 MHz, scans. One patient (case 5) died of sepsis at 15 days after
power 20 – 80 W. The different types of treatment were as follows OLT without histological signs of active neoplastic disease
percutaneous ablation (n ϭ 73) included (M/F ratio of 5:1, 114 in the treated nodule.
nodules (1.5/patient) with mean dimension 35.6 Ϯ 18.3 mm treated MWA produced fixation of the tissues adjacent to the
with 85 procedures (minimum-maximum:1– 4); Model for End- Antenna’s tip (“inner zone”) preserving cancer morphol-
Stage Liver Disease 9.3 Ϯ 2.6; videolaparoscopic ablation was ogy, appearing histologically “viable-looking” (hyperchro-
performed on 69 patients (M/F ratio of 6:1) with 89 nodules mic nuclei and eosinophilic cytoplasm) but destroying en-
(1.3/patient) and a mean dimension of 30.1 Ϯ 15.7 mm treated with zymatic activity, showing a clear demarcation from external
a single procedure on patient, whose overall mean MELD was 11.1 coagulation necrosis (“outer zone”). HCC were separated
Ϯ 5.1; videothoracoscopic ablation on 3 patients with posterior from external non-neoplastic tissue by a fibrous tissue band
lesions was related to them being not otherwise treatable with a
(pseudo-capsule) filled with histiocytes and giant multinu-
mininvasive technique; and open ablation on 9 patients was com-
clear cells (Fig 1).
bined with other laparotomic resection procedures.
Amica HS Antenna included a new device on the tip (“mini-
choke”) as a technical remedy to back heating effects, both due to DISCUSSION
the reflected waves and to ohmic dissipation along the feeding Thermal ablation of primary or secondary liver tumors
coaxial line (“comet-effect”).
leads to the destruction of the neoplastic lesion with an at
Treatment efficacy was evaluated at 1 month after the ablative
least 0.5 mm margin of healthy liver tissue due to coagula-
procedure for using computed tomography (CT) scan seeking
absence of contrast enhancement in the treated lesion. Six selected
tion temperatures above 50°C.8 Currently, RFA is consid-
patients underwent OLT with a caval-preserving technique. The ered the treatment of choice9 for patients with HCC or
whole liver explanted specimens were examined both macroscopi- metastases that are not amenable to open surgery or
cally and microscopically to identify and guantify the necrotizing, laparoscopic treatment,10 –16 allowing satisfactory ablation
effects on treated lesions. CT scans were performed on all survived for HCC up to 30 mm in diameters. For larger lesions or
patients at 1, 3, 6, and 9 months after OLT to detect recurrent or those contiguous to vascular structures of caliber greater
metastatic disease. than 5 mm, it results in a high rate of persistence of residual

3. MICROWAVE THERMAL ABLATION 1093
Necrosis
100
100
100
100
100
100
(%)
5.6 Ϯ 3.8
Mo to OLT
4
7
13
3
5
2
CT – CE
Ͻ20%
(1 mo)
No
No
No
No
No
Watt
40
30
30
40
60
60
Fig 1. MWA produces fixation of the tissue adjacent to the
7.8 Ϯ 2.5
Antenna’s tip (“inner zone”) preserving cancer morphology,
Min
10
10
5
4
8
10
appearing hystologically “viable-looking” (Hypercromic nucleus
Table 1. Data on 6 Patients Who Underwent OLT After MWA (CT-CE‫ ؍‬CT)
and eosinophilic cytoplasm) destroying enzimatic activity in-
stead, showing a clear demarcation from external coagulative
necrosis (“outer zone”); HCC result separated from the external
Pere/VLS
Perc
Perc
Perc
Perc
non-neoplastic tissue with a fibrous tissue band (pseudo-cap-
VLS
VLS
sule) filled of histiocytes an giant multinuclear cells.
viable disease capable of progression and local recur-
Lesion
S7
S6
S6
S7
S5
S5
rence.17,18 Technological researches has therefore been
directed toward the development of new ablation tech-
niques that produce a greater volume necrosis more quickly
34.5 Ϯ 9.3
Diameter
and safely. Heat production is determined by the friction
(mm)
50
37
25
25
40
30
between the electrical charges at the molecular level sub-
jected to the action of a magnetic field. This significant fact
is due to the lack of movement and the current absence of
a delay in the propagation of heat. Therefore, the heating of
15.3 Ϯ 6.5
MELD
the target lesions is obtained more quickly and evenly,
11
12
11
23
9
26
Abbreviations: CE, contrast enhancement; Perc, percutaneous; VLS, videolaparoscopic.
regardless of the low electrical conductivity and charring
phenomena, representing main limitations of RFA.
The initial Asian experience showed the limitations of
Child
needle gauge, long periods of application, limited extent of
C
C
B
B
B
A
the necrosis and complications due to the “comet-effect”
along the needle path. These problems compromised the
Cirrhosis
ETOH
ETOH
clinical spread of the technique on a large scale. Recent
HCV
HCV
HCV
HBV
technological improvements, with the passage of the “comet-
effect” have to led studies of MWA at first experimentally
and then clinically. The feasibility studies on large animal
Multifocal
Multifocal
Multifocal
and early clinical reports of the literature showed promising
Single/
Single
Single
Single
Single
results.19 –29
MWA uses energy produced by electromagnetic fields
with frequencies around 1 GHz. The radiation is applied via
59.5 Ϯ 6.1
antennas stuck in the liver lesion under ultrasound guid-
Age (y)
ance. A new microwave generator operating at frequencies
47
66
58
62
60
64
of 2.45 GHz and equipped with an innovative device
(“mini-choke”) has been developed to trapping in the tip
energy that propagates in a retrograde fashion, responsible
M/F
for the “comet-effect.”21 The presence of a water cooling
M
M
M
M
F
F
system allows the antenna to avoid overheating due to heat
dissipation along the line of microwave transmission.
Median
Case
Both devices reproducibly and controllably by create an
ellipsoidal shaped area of tissue necrosis adjusting the
1
2
3
4
5
6

4. 1094 ZANUS, BOETTO, GRINGERI ET AL
duration and power output, as demonstrated by computer 10. Solbiati L, Livraghi T, Goldberg SN, et al: Percutaneous
simulations, ex vivo experimental studies on large animals, radiofrequency ablation of hepatic metastases from colorectal
cancer: results in 117 patients. Radiology 221:159, 2001
and clinical results obtained in vivo Phase I studies of
11. Hayashi H, Nabeshima K, Hamasaki M, et al: Presence of
benign prostatic adenomas.30 The therapeutic efficacy of microsatellite lesions with colorectal liver metastases correlate with
MWA may be evaluated similar to RFA by using imaging intrahepatic recurrence after surgical resection. Oncol Rep 212:
techniques with contrast media (magnetic resonance, tri- 601, 2009
phasic CT, and Contrast-Enhanced Ultrasound (CEUS)). 12. Livraghi T, Solbiati L, Meloni F, et al: Percutaneous radio-
frequency ablation of liver metastases in potential candidates for
We have treated 154 patients for ablative palliative or resection. Cancer 97:3027, 2003
curative purposes. As part of the transplantation program 6 13. Seki T, Wakabayashi M, Nakagawa T, et al: Ultrasonically
patients of this cohort underwent OLT with caval-preserv- guided percutaneous microwave coagulation therapy for small
ing technique. Two patients had undergone MWA down- HCC. Cancer 74:817, 1994
14. Meredith K, Lee F, Henry MB, et al: Microwave ablation of
staging with return to OLT criteria after ablative treatment;
hepatic tumours using dual-loop probes: results of a phase I clinical
4 patients underwent MWA while a waiting OLT, seeking study. J Gastrointest Surg 9:1354, 2005
to reduce the risk of list drop-out. 15. Simon CJ, Dupuy DE, Iannitti DA, et al: Intraoperative
Complete pathological analysis after OLT has enabled triple antenna hepatic microwave ablation AJR 187:333, 2006
evaluation of the effectiveness of ablation.31 Regardless of 16. Brace CL, Laeseke PF, Sampson LA, et al: Microwave
ablation with a single gauge triaxial antenna: in vivo porcine liver
how the ablation was performed percutaneously or laparo- model. Radiology 242:435, 2007
scopically the specimens showed resolution of treated nod- 17. Lam VW, Ng KK, Chok KS, et al: Incomplete ablation after
ules by histological finding with the absence at the time of radiofrequency ablation of HCC: analysis of risk factors and
OLT of peritoneal carcinomatosis and lymph node involve- prognostic factors. Ann Surg Oncol 15:782, 2008
18. Ng KK, Poon RT, Lo C, et al: Analysis of recurrence pattern
ment.
and its influence on survival outcome after radiofrequency ablation
In conclusion, MWA seemed to be a safe procedure to of HCC. J Gastrointest Surg 12:183, 2008
treat unresectable HCC, allowing satisfactory results in 19. Brace CL, Laeseke PF, Van der Weide DW, et al: Micro-
terms of ablative necrosis. The introduction of the latest wave ablation with a triaxial antenna: results in ex vivo bovine liver.
technological innovations (“mini-choke”) permits one to IEEE Trans Microw Theory Tech 53:215, 2005
20. Brace CL, Laeseke PF, Sampson LA, et al: Microwave
obtain a larger diameter figure of necrosis more quickly ablation with a single small-gauge triaxial antenna: in vivo porcine
than with RFA. liver model. Radiology 242:435, 2007
The figure of necrosis was characterized by complete 21. Longo I, Gentili GB, Cerretelli M, et al: A coaxial antenna
reproducibility and did not suffer the limitations of inherent with miniaturized choke for minimally invasive interstitial heating.
IEEE Trans Biomed Eng 50:82, 2003
heat transfer by conduction or “heat-sink” effects due to
22. Awad MM, Devgan L, Kamel IR, et al: Microwave ablation
proximity to the vascular structures. in a hepatic porcine model: correlation of CT and histopathologic
findings. HPB (Oxford) 9:357, 2007
REFERENCES 23. Brace CL: Microwave ablation technology: what every user
should know. Curr Probl Diagn Radiol 38:61, 2009
1. Lencioni R: Loco-regional treatment of HCC. Hepatology, 24. Durick NA, Laeseke PF, Broderick LS, et al: Microwave
52:762, 2010 ablation with triaxial antennas tuned for lung: results in an in vivo
2. Bruix J, Llovet JM: Prognostic prediction and treatment porcine model. Radiology 247:80, 2008 (Epub Feburary 21, 2008)
strategy in HCC. Hepatology 35:519, 2002 25. Fan QY, Ma BA, Zhou Y, et al: Bone tumors of the
3. Dong BW, Liang P, Yu XL, et al: Longterm results of extremities or pelvis treated by microwave-induced hyperthermia.
percutaneous sonographically-guided microwave ablation therapy Clin Orthop Relat Res 406:165, 2003
of early-stage HCC. Zhonghua Yi Xue Za Zhi 86:797, 2006 26. Furukawa K, Miura T, Kato Y, et al: Microwave coagulation
4. Liang P, Dong B, Yu X, et al: Prognostic factors for percu- therapy in canine peripheral lung tissue. J Surg Res 123:245, 2005
taneous microwave coagulation therapy of hepatic metastases. 27. Kuang M, Lu MD, Xie XY, et al: Liver cancer: increased
Am J Roentgenol 181:1319, 2003 microwave delivery to ablation zone with cooled-shaft antenna-
5. Boutros C, Somasundar P, Garrean S, et al: Microwave experimental and clinical studies. Radiology 242:914, 2007 (Epub
coagulation therapy for hepatic tumors: review of the literature and January 17, 2007)
critical analysis. Surg Oncol 19:e22, 2010 (Epub March 6, 2009) 28. lannitti DA, Martin RC, Simon CJ, et al: Hepatic tumor
6. Lu MD, Xu HX, Xie XY, et al: Percutaneous microwave and ablation with clustered microwave antennae: the US Phase II trial.
radiofrequency ablation for HCC: a retrospective comparative HPB (Oxford) 9:120, 2007
study. J Gastroenterol 40:1054, 2005 29. Martin RC, Scoggins CR, McMasters KM: Microwave he-
7. Xu HX, Lu MD, Xie XY, et al: Prognostic factors for patic ablation: initial experience of safety and efficacy. J Surg Oncol
long-term outcome after percutaneous thermal ablation for HCC: 96:481, 2007
a survival analysis of 137 consecutive patients. Clin Radiol 60:1018, 30. Bartoletti R, Cai T, Tinacci G, et al: Transperineal micro-
2005 wave termal ablation in patients with obstructive benign prostatic
8. Goldberg SN, Grassi CJ, Cardella JF, et al: Image-guided hyperplasia: a phase I clinical study with a new micro-choked
tumour ablation standardization of terminology and reporting microwave applicator. J Endourol 22:1509, 2008
criteria. Radiology 235:728, 2005 31. Yamashiki N, Kato T, Bejarano PA, et al: Histopathological
9. Mulier S, Ruers T, Jamart J, et al: Radiofrequency ablation changes after microwave coagulation therapy for patients with
versus resection for resectable colorectal liver metastases: time for hepatocellular carcinoma: review of 15 explanted livers. Am J
a randomized trial? An update. Dig Surg 25:445, 2008 Gastroenterol 98:2052, 2003