Microwave Thermal Ablation for Hepatocarcinoma: Six LiverTransplantation CasesG. Zanus, R. Boetto, E. Gringeri, A. Vitale,...
1092                                                                                            ZANUS, BOETTO, GRINGERI ET...
MICROWAVE THERMAL ABLATION                                                                                                ...
1094                                                                                                  ZANUS, BOETTO, GRING...
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Microwave Thermal Ablation For Hepatocarcinoma Six Liver Transplantation Cases


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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

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Microwave Thermal Ablation For Hepatocarcinoma Six Liver Transplantation Cases

  1. 1. Microwave Thermal Ablation for Hepatocarcinoma: Six LiverTransplantation CasesG. 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 216H mon cancer and third leading cause of cancer-relateddeaths 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 aprecluded, image-guided tumor ablation is recommended low major complication rate (1.3%). In another experienceas the most appropriate therapeutic procedure. It is con- Liang et al4 noted the 74 patients treated with percutaneoussidered a potentially radical treatment for selected pa-tients.1 Given the shortage of deceased donors, hepaticablative 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 ditransplantation (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 Liverduction 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 matter360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2011.02.044Transplantation Proceedings, 43, 1091–1094 (2011) 1091
  2. 2. 1092 ZANUS, BOETTO, GRINGERI ET ALMWA for a median 3 cm HCC showed overall 1-, 3-, 4-, and RESULTS5-year survival rates of 91%, 46%, 29%, and 29%, respec- Six patients of mean age Ϯ SD of 59.5 Ϯ 6.1 years andtively with a 14% incidence local tumor recurrence. The including a M/F ratio of 4:2 underwent liver transplantationfirst 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-relatedof 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 underwenttion (RFA) and MWA Lu et al6 in 2005 reported no OLT from a deceased donor at a median of 5.6 Ϯ 3.8significant 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 asgated the prognostic factors for good long-term outcomes bridge to OLT to avoid neoplastic disease diffusion andafter MWA versus radiofrequency among 137 consecutive decrease the risk of OLT list drop-out. This median age Ϯpatients 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 HCCposition. A univariate analysis demonstrated no differences that was HCV -related (1 multifocal); ETOH-related (2between RFA and MWA. We applied MWA to patients single nodule); or HBV-related (1 single nodule). Theirwith HCC listed for OLT seeking to decrease the risk of list overall mean MELD score was 13.8 Ϯ 5.8. Two patients ofdrop-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 multifocalcriteria (“down-staging”). We evaluated the macroscopic and 1 single nodule) underwent laparoscopic explorationand microscopic evidences on explanted liver specimens of and nodule ablation with down-staging to achieve OLTprocedure efficacy. criteria. In all 6 cases no peritoneal or nodal HCC macroscopic and microscopic diffusion was observed intraoperatively atMETHODS the time of laparotomy for OLT. Peritoneal adhesions wereFrom May 2009 to October 2010, we entered into the trial 154 detected at the sites of the ablative procedures without anyHCC patients including a male to female (M/F) ratio of 6:1 of substantial difficulty in the dissection or hepatectomy. Nomean age Ϯ standard deviation (SD) of 63.5 Ϯ 8.5 years. The HCC patient who underwent OLT suffered any complicationwas 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 orperformed 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 afterpower 20 – 80 W. The different types of treatment were as follows OLT without histological signs of active neoplastic diseasepercutaneous 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 thewith 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 externala single procedure on patient, whose overall mean MELD was 11.1 coagulation necrosis (“outer zone”). HCC were separatedϮ 5.1; videothoracoscopic ablation on 3 patients with posterior from external non-neoplastic tissue by a fibrous tissue bandlesions 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 DISCUSSIONthe reflected waves and to ohmic dissipation along the feeding Thermal ablation of primary or secondary liver tumorscoaxial 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 seekingabsence 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 orwhole liver explanted specimens were examined both macroscopi- metastases that are not amenable to open surgery orcally and microscopically to identify and guantify the necrotizing, laparoscopic treatment,10 –16 allowing satisfactory ablationeffects on treated lesions. CT scans were performed on all survived for HCC up to 30 mm in diameters. For larger lesions orpatients at 1, 3, 6, and 9 months after OLT to detect recurrent or those contiguous to vascular structures of caliber greatermetastatic disease. than 5 mm, it results in a high rate of persistence of residual
  3. 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. 4. 1094 ZANUS, BOETTO, GRINGERI ET ALduration and power output, as demonstrated by computer 10. Solbiati L, Livraghi T, Goldberg SN, et al: Percutaneoussimulations, ex vivo experimental studies on large animals, radiofrequency ablation of hepatic metastases from colorectal cancer: results in 117 patients. Radiology 221:159, 2001and clinical results obtained in vivo Phase I studies of 11. Hayashi H, Nabeshima K, Hamasaki M, et al: Presence ofbenign prostatic adenomas.30 The therapeutic efficacy of microsatellite lesions with colorectal liver metastases correlate withMWA 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, 2009phasic 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 forWe have treated 154 patients for ablative palliative or resection. Cancer 97:3027, 2003curative purposes. As part of the transplantation program 6 13. Seki T, Wakabayashi M, Nakagawa T, et al: Ultrasonicallypatients of this cohort underwent OLT with caval-preserv- guided percutaneous microwave coagulation therapy for smalling technique. Two patients had undergone MWA down- HCC. Cancer 74:817, 1994 14. Meredith K, Lee F, Henry MB, et al: Microwave ablation ofstaging with return to OLT criteria after ablative treatment; hepatic tumours using dual-loop probes: results of a phase I clinical4 patients underwent MWA while a waiting OLT, seeking study. J Gastrointest Surg 9:1354, 2005to 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, 2006evaluation 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 liverhow the ablation was performed percutaneously or laparo- model. Radiology 242:435, 2007scopically the specimens showed resolution of treated nod- 17. Lam VW, Ng KK, Chok KS, et al: Incomplete ablation afterules by histological finding with the absence at the time of radiofrequency ablation of HCC: analysis of risk factors andOLT 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 patternment. 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, 2008treat 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: Microwaveobtain a larger diameter figure of necrosis more quickly ablation with a single small-gauge triaxial antenna: in vivo porcinethan 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 antennareproducibility and did not suffer the limitations of inherent with miniaturized choke for minimally invasive interstitial heating. IEEE Trans Biomed Eng 50:82, 2003heat transfer by conduction or “heat-sink” effects due to 22. Awad MM, Devgan L, Kamel IR, et al: Microwave ablationproximity to the vascular structures. in a hepatic porcine model: correlation of CT and histopathologic findings. HPB (Oxford) 9:357, 2007REFERENCES 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: Microwave52:762, 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, 2003of 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, 2005taneous microwave coagulation therapy of hepatic metastases. 27. Kuang M, Lu MD, Xie XY, et al: Liver cancer: increasedAm 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 (Epubcoagulation 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, 2007study. 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 Oncollong-term outcome after percutaneous thermal ablation for HCC: 96:481, 2007a 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-chokedtumour ablation standardization of terminology and reporting microwave applicator. J Endourol 22:1509, 2008criteria. 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 withversus resection for resectable colorectal liver metastases: time for hepatocellular carcinoma: review of 15 explanted livers. Am Ja randomized trial? An update. Dig Surg 25:445, 2008 Gastroenterol 98:2052, 2003