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Microwave Thermal Ablation for Hepatocarcinoma: Six LiverTransplantation 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), hasbeen demonstrated to increase overall survival; however, the majority of patients are notsuitable for resection. Radiofrequency ablation (RFA) is the most widely used modality forradical treatment of small HCC (�3 cm). It improves 5-year survival compared withstandard chemotherapy and chemical ablation, allowing down-staging of unresectablehepatic masses. Microwave ablation (MWA) has been extensively applied in Asia and wasrecently introduced in the United States of America and Europe with excellent results,especially with regard to large unresectable HCC. Our single-center experience betweenMay 2009 and October 2010 included application of MWA to 154 patients of medianage � standard deviation of 63.5 � 8.5 years, 6 males, and 1 female, of mean Model forEnd-Stage Liver Disease (MELD) score (10.1 � 3.8). The HCC included, hepatitis C virus(HCV)-related (n � 70; 45.5%); alcool (ETOH)-related (n � 42; 27%), hepatitis B virus(HBV)-related (n � 16; 10.5%); and cryptogenic cases (n � 26; 17%). The cases wereperformed for radical treatment down-staging for multifocal pathology or bridging livertransplantation to orthotopic (OLT) in selected patients with single nodules. A computedtomography (CT) scan was performed at 1 month after the surgical procedure to evalueresponses 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 nointraoperative evidence of tumor spread or of pathological signs of active HCC among theexplanted 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.

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HEPATOCARCINOMA (HCC) is the sixth most com-mon cancer and third leading cause of cancer-related

deaths with low resectability rates at the time of presenta-tion, ranging from 13%–35%.1 When surgical options areprecluded, image-guided tumor ablation is recommendedas the most appropriate therapeutic procedure. It is con-sidered a potentially radical treatment for selected pa-tients.1 Given the shortage of deceased donors, hepaticblative procedures seem to represent a useful and effectivereatment for patients with HCC listed for orthotopic liverransplantation (OLT) Bruix and Llovet in the Barcelonalinic Liver Cancer (BCLC) therapeutic strategy suggested

hermal ablation to be a useful procedure for unresectableCC.2

Microwave ablation (MWA) technology with the intro-duction of the latest technical expedient (“mini-choke”) has

gained excellent therapeutic capability in comparison with

© 2011 by Elsevier Inc. All rights reserved.360 Park Avenue South, New York, NY 10010-1710

Transplantation Proceedings, 43, 1091–1094 (2011)

he other ablation techniques. Dong et al3 reported 216atient with percutaneous ablation with MWA to treat 5 cmmean 40 � 24 mm) HCC with overall survival rates at 1, 3,nd 5 years of 94.8%, 80.4%, and 68.6%, respectively and aow major complication rate (1.3%). In another experienceiang et al4 noted the 74 patients treated with percutaneous

From the General Surgery and Organ Transplantation, Hepa-tobiliary Surgery and Liver Transplant Unit, Azienda Università diPadova (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.),Gastroenterologia (M.S., P.B.), and Intensive Care Unit (P.F.),Università di Padova, Padova, Italy.

Address reprint requests to Giacomo Zanus, General Surgeryand Organ Transplantation, Hepatobiliary Surgery and LiverTransplant Unit; Azienda Università di Padova; Via Giustiniani,

2 - 35128, Padova, Italy. E-mail: zanus@unipd.it

0041-1345/–see front matterdoi:10.1016/j.transproceed.2011.02.044

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1092 ZANUS, BOETTO, GRINGERI ET AL

MWA for a median 3 cm HCC showed overall 1-, 3-, 4-, and5-year survival rates of 91%, 46%, 29%, and 29%, respec-tively with a 14% incidence local tumor recurrence. Thefirst Asian experience did not demonstrate a clear, defini-tive advantage of MWA compared with RFA, given the lackof randomized controlled trials on the safety and efficacy ofthe procedure.5

In a retrospective study comparing radiofrequency abla-tion (RFA) and MWA Lu et al6 in 2005 reported nosignificant difference in local recurrence as well as major orminor complications among 102 patients. Xu et al7 investi-gated the prognostic factors for good long-term outcomesafter MWA versus radiofrequency among 137 consecutivepatients showing a great variability in tumor size andposition. A univariate analysis demonstrated no differencesbetween RFA and MWA. We applied MWA to patientswith HCC listed for OLT seeking to decrease the risk of listdrop-out (“bridging”) and to carry patients into OLTcriteria (“down-staging”). We evaluated the macroscopicand microscopic evidences on explanted liver specimens ofprocedure efficacy.

METHODS

From May 2009 to October 2010, we entered into the trial 154HCC patients including a male to female (M/F) ratio of 6:1 ofmean age � standard deviation (SD) of 63.5 � 8.5 years. The HCCwas hepatitis C virus (HCV)-related (n � 70; 45.5%); alcool(ETOH)-related (n � 42; 27%); hepatitis B virus (HBV)-related(n � 16; 10.5%) cryptogenic cases (n � 26; 17%). The MWA was

erformed under sonografic guidance (Esaote, Technos mix; Hita-hi Logos Hi-Vision C) using Amica HS 14 Gauge needle withmini-choke” technology. The operating frequency was 2450 MHz,ower 20–80 W. The different types of treatment were as followsercutaneous ablation (n � 73) included (M/F ratio of 5:1, 114

nodules (1.5/patient) with mean dimension 35.6 � 18.3 mm treatedwith 85 procedures (minimum-maximum:1–4); Model for End-Stage Liver Disease 9.3 � 2.6; videolaparoscopic ablation wasperformed on 69 patients (M/F ratio of 6:1) with 89 nodules(1.3/patient) and a mean dimension of 30.1 � 15.7 mm treated witha single procedure on patient, whose overall mean MELD was 11.1� 5.1; videothoracoscopic ablation on 3 patients with posteriorlesions was related to them being not otherwise treatable with amininvasive technique; and open ablation on 9 patients was com-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 tothe reflected waves and to ohmic dissipation along the feedingcoaxial line (“comet-effect”).

Treatment efficacy was evaluated at 1 month after the ablativeprocedure for using computed tomography (CT) scan seekingabsence of contrast enhancement in the treated lesion. Six selectedpatients underwent OLT with a caval-preserving technique. Thewhole liver explanted specimens were examined both macroscopi-cally and microscopically to identify and guantify the necrotizing,effects on treated lesions. CT scans were performed on all survivedpatients at 1, 3, 6, and 9 months after OLT to detect recurrent or

metastatic disease. t

RESULTS

Six patients of mean age � SD of 59.5 � 6.1 years andincluding a M/F ratio of 4:2 underwent liver transplantationafter the procedures, HCC were HCV-related (n � 3;50%); ETOH-related (n � 2; 33.3%); and HBV-related(n � 1; 16.7%). This mean MELD score was 15.3 � 16.5.Their four of them had been percutaneously and 2 laparo-scopically treated in single procedures. They underwentOLT from a deceased donor at a median of 5.6 � 3.8

onths after the ablative procedure (Table 1).Four patients underwent percutaneous treatment as

ridge to OLT to avoid neoplastic disease diffusion andecrease the risk of OLT list drop-out. This median age �D was 61.5 � 3.1 years and the M/F ratio of 3:1 had HCChat was HCV -related (1 multifocal); ETOH-related (2ingle nodule); or HBV-related (1 single nodule). Theirverall mean MELD score was 13.8 � 5.8. Two patients ofean age � SD of 55.5 � 9.8 years and with M/F ratio of

(1:1), MELD score of 18.5 � 8.6 HCV-related (1 multifocaland 1 single nodule) underwent laparoscopic explorationand nodule ablation with down-staging to achieve OLTcriteria.

In all 6 cases no peritoneal or nodal HCC macroscopicand microscopic diffusion was observed intraoperatively atthe time of laparotomy for OLT. Peritoneal adhesions weredetected at the sites of the ablative procedures without anysubstantial difficulty in the dissection or hepatectomy. Nopatient who underwent OLT suffered any complicationduring or after the ablative procedure.

Five of 6 transplant recipients (83.3%) are still alivebeyond 1 year after OLT, in the absence of a local ormetastatic recurrence of HCC on 1, 3, 6, and 9 month, CTscans. One patient (case 5) died of sepsis at 15 days afterOLT without histological signs of active neoplastic diseasein the treated nodule.

MWA produced fixation of the tissues adjacent to theAntenna’s tip (“inner zone”) preserving cancer morphol-ogy, appearing histologically “viable-looking” (hyperchro-mic nuclei and eosinophilic cytoplasm) but destroying en-zymatic activity, showing a clear demarcation from externalcoagulation necrosis (“outer zone”). HCC were separatedfrom external non-neoplastic tissue by a fibrous tissue band(pseudo-capsule) filled with histiocytes and giant multinu-clear cells (Fig 1).

DISCUSSION

Thermal ablation of primary or secondary liver tumorsleads to the destruction of the neoplastic lesion with an atleast 0.5 mm margin of healthy liver tissue due to coagula-tion temperatures above 50°C.8 Currently, RFA is consid-red the treatment of choice9 for patients with HCC or

metastases that are not amenable to open surgery orlaparoscopic treatment,10–16 allowing satisfactory ablationor HCC up to 30 mm in diameters. For larger lesions orhose contiguous to vascular structures of caliber greater

han 5 mm, it results in a high rate of persistence of residual

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MICROWAVE THERMAL ABLATION 1093

viable disease capable of progression and local recur-rence.17,18 Technological researches has therefore beendirected toward the development of new ablation tech-niques that produce a greater volume necrosis more quicklyand safely. Heat production is determined by the frictionbetween the electrical charges at the molecular level sub-jected to the action of a magnetic field. This significant factis due to the lack of movement and the current absence ofa delay in the propagation of heat. Therefore, the heating ofthe target lesions is obtained more quickly and evenly,regardless of the low electrical conductivity and charringphenomena, representing main limitations of RFA.

The initial Asian experience showed the limitations ofneedle gauge, long periods of application, limited extent ofthe necrosis and complications due to the “comet-effect”along the needle path. These problems compromised theclinical spread of the technique on a large scale. Recenttechnological improvements, with the passage of the “comet-effect” have to led studies of MWA at first experimentallyand then clinically. The feasibility studies on large animaland early clinical reports of the literature showed promisingresults.19–29

MWA uses energy produced by electromagnetic fieldswith frequencies around 1 GHz. The radiation is applied viaantennas stuck in the liver lesion under ultrasound guid-ance. A new microwave generator operating at frequenciesof 2.45 GHz and equipped with an innovative device(“mini-choke”) has been developed to trapping in the tipenergy that propagates in a retrograde fashion, responsiblefor the “comet-effect.”21 The presence of a water coolingsystem allows the antenna to avoid overheating due to heatdissipation along the line of microwave transmission.

Both devices reproducibly and controllably by create an

Fig 1. MWA produces fixation of the tissue adjacent to theAntenna’s tip (“inner zone”) preserving cancer morphology,appearing hystologically “viable-looking” (Hypercromic nucleusand eosinophilic cytoplasm) destroying enzimatic activity in-stead, showing a clear demarcation from external coagulativenecrosis (“outer zone”); HCC result separated from the externalnon-neoplastic tissue with a fibrous tissue band (pseudo-cap-sule) filled of histiocytes an giant multinuclear cells.

ellipsoidal shaped area of tissue necrosis adjusting theC

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1094 ZANUS, BOETTO, GRINGERI ET AL

duration and power output, as demonstrated by computersimulations, ex vivo experimental studies on large animals,and clinical results obtained in vivo Phase I studies ofbenign prostatic adenomas.30 The therapeutic efficacy of

WA may be evaluated similar to RFA by using imagingechniques with contrast media (magnetic resonance, tri-hasic CT, and Contrast-Enhanced Ultrasound (CEUS)).e have treated 154 patients for ablative palliative or

urative purposes. As part of the transplantation program 6atients of this cohort underwent OLT with caval-preserv-

ng technique. Two patients had undergone MWA down-taging with return to OLT criteria after ablative treatment;patients underwent MWA while a waiting OLT, seeking

o reduce the risk of list drop-out.Complete pathological analysis after OLT has enabled

valuation of the effectiveness of ablation.31 Regardless ofhow the ablation was performed percutaneously or laparo-scopically the specimens showed resolution of treated nod-ules by histological finding with the absence at the time ofOLT of peritoneal carcinomatosis and lymph node involve-ment.

In conclusion, MWA seemed to be a safe procedure totreat unresectable HCC, allowing satisfactory results interms of ablative necrosis. The introduction of the latesttechnological innovations (“mini-choke”) permits one toobtain a larger diameter figure of necrosis more quicklythan with RFA.

The figure of necrosis was characterized by completereproducibility and did not suffer the limitations of inherentheat transfer by conduction or “heat-sink” effects due toproximity to the vascular structures.

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