Antonini, Mario

Antonucci, Giorgio

Carpanese, Livio

Ettorre, Giuseppe Maria

Maini, Carlo L.

Miglioresi, Lucia

Puoti, Claudio

Santoro, Roberto

Sciuto, Rosa

Vennarecci, Giovanni

Transplantation

English

Giuseppe Maria Ettorre

Roberto Santoro

Claudio Puoti

Rosa Sciuto

Livio Carpanese

Mario Antonini

Giorgio Antonucci

Carlo L. Maini

Lucia Miglioresi

Giovanni Vennarecci

Crossref

Short-Term Follow-Up of Radioembolization With Yttrium-90 Microspheres Before Liver Transplantation: New Perspectives in Advanced Hepatocellular Carcinoma

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Downloadedfromhttp://journals.lww.com/transplantjournalbyBhDMf5ePHKbH4TTImqenVAHxkFJp/XpPk1L/H3vMGwqMxG9jwOd8eHu+WdxxmltmG+Y2f0aqIM4=on07/30/2018Downloadedfromhttp://journals.lww.com/transplantjournalbyBhDMf5ePHKbH4TTImqenVAHxkFJp/XpPk1L/H3vMGwqMxG9jwOd8eHu+WdxxmltmG+Y2f0aqIM4=on07/30/2018Short-Term Follow-Up of Radioembolization With Yttrium-90 MicrospheresBefore Liver Transplantation: New Perspectives in AdvancedHepatocellular CarcinomaLiver transplantation is a well-established procedure in patients af-fected by hepatocellular carcinoma(HCC) within the Milan criteria (1) orthe extended Milan criteria (2). How-ever, orthotopic liver transplantation(OLT) is not considered for patientswho exceed the extended Milan or Mi-lan criteria (i.e., size of nodule 7 cmor vascular invasion) because of thehigh risk of recurrence. In these pa-tients, OLT can only be planned afterdownstaging of the disease to within ac-ceptable limits. Patients with HCC whoare transplanted after downstaging havesimilar outcomes in terms of survivaland recurrence-free survival as thosewho meet the accepted criteria at initialpresentation (3). We report a case ofadvanced HCC with neoplastic portalvein thrombosis, which was downstagedafter radioembolization with yttrium-90(90Y) microspheres and led to a success-ful liver transplantation.In February 2007, a 62-year-oldman with hepatitis C virus-related cir-rhosis with a model for end-stage liverdisease score of 10 was diagnosed withan unresectable advanced HCC in theright lobe (7.5-cm diameter) and an in-creased -fetoprotein (AFP) level morethan 70,000 ng/mL. Macrovascular in-vasion of the right branch of the portalvein was confirmed by spiral computedtomography (CT) (Fig. 1) imaging. Theclinical case was discussed by a multidis-ciplinary panel, and it was concludedthat the patient was unsuitable for OLTbecause of the size of the tumor and vas-cular invasion.In May 2007, the patient receivedwhole-liver treatment with an intraarterialinfusion of 90Y resin microspheres (SIR-Spheres; Sirtex Medical Ltd., Sydney,Australia). The radioembolization activ-ity administered was 1702 MBq. Thetreatment was well tolerated. Follow-up1 month later revealed a positive tumorresponse. AFP level at 2 months aftertreatment was 15 ng/mL. CT imaging at3 months postradioembolisation docu-mented a complete radiologic responsewith total regression of the primary le-sion and portal thrombus.The patient was then regularlyseen in the outpatient clinic for 22months after treatment, during whichtime, no other lesions developed in theliver. In February 2009, the patient wasreassessed and considered to be a suit-able candidate for OLT. Transplantassessment performed by positron emis-sion tomography, CT, and bone scansdid not reveal new HCC lesions withinand outside the liver. In March 2009, thepatient was placed on the transplantwaiting list. While waiting for transplan-tation, a CT scan showed a suspected hy-pervascularized lesion at the site of thepreviously treated lesion, measuring lessthan 1 cm. In May 2009, a secondsegmental-liver treatment with 90Y resinmicrospheres was performed (1665MBq). The patient developed liver dys-function (ascites and cholestasis withbilirubin that peaked at 7 mg/dL), whichresolved after 2 months of conservativetreatment. In November 2009, thepatient was transplanted successfullyby the piggy-back technique withoutveno-venous bypass. Transplant sur-gery was unexpectedly more difficultthan normal because of the presence offibrous tissue between the inferiorvena cava and the caudate lobe wherethe HCC was located probably due tothe radioembolization and resultingedema. The postoperative course wasuneventful, and the patient was dis-charged on day 14 on tacrolimus (Pro-graf; Astellas Pharma, Europe, Staines,UK) and prednisone. Pathologic exam-ination of the explanted liver showed two5-mm HCC nodules surrounded by thefibrous tissue. The lymph nodes were neg-ative, and no portal vein thrombus wasfound. Eight months after OLT, the pa-tient has no signs of HCC recurrence asshowed by a CT scan, and the last AFPlevel was 10 ng/mL.In the past 10 years, different tech-niques for downstaging HCC have beenevaluated with encouraging results.However, radioembolization using in-traarterial 90Y-labeled microspheres hasproved to be one of the most effectivetechniques. Approved in Europe for thetreatment of unresectable liver tumors,radioembolization seems to be a safe andpossibly more effective technique thantransarterial chemoembolization for thedownstaging of HCC (4, 5). The Y90-bound microspheres remain confined tothe vascular rim of the tumor, where theydeliver a high (120 Gy) but localizedFIGURE 1. The computed tomography scan shows an hypervascular area cor-responding to hepatocellular carcinoma with neoplastic right portal vein throm-bosis before yttrium-90 microspheres treatment.930 | www.transplantjournal.com Transplantation • Volume 90, Number 8, October 27, 2010dose of -radiation to the tumor com-partment (6). The limited tissue pene-tration of -radiation (mean 2.5 mm)(6) means that most of the normal livertissue is spared (7, 8). Radioemboliza-tion can be used in the liver transplantsetting (a) as a bridge to transplant(controlling tumor progression forthose on the waiting list) or (b) for thedownstaging of tumors and resolutionof vascular invasion, thereby enablingaccess to the organ waiting list forthose outside the conventional criteriafor organ transplant.In conclusion, radioembolizationis an effective treatment of patients withunresectable HCC, allowing downstag-ing to OLT in selected cases. Althoughthe post-OLT follow-up period is stilltoo short to draw any definitive con-clusions, we would encourage liverand transplant surgeons to share ourexperience and consider radioemboli-zation as an alternative treatment ofunresectable advanced and intermedi-ate stage HCC.Giuseppe Maria Ettorre1Roberto Santoro1Claudio Puoti2Rosa Sciuto3Livio Carpanese4Mario Antonini5Giorgio Antonucci6Carlo L. Maini3Lucia Miglioresi1Giovanni Vennarecci11 General Surgery and Transplantation UnitSan Camillo HospitalRome, Italy2 Department of Internal Medicine andLiver UnitSan Giuseppe HospitalMarino, Italy3 Department of Nuclear MedicineRegina Elena Cancer InstituteRome, Italy4 Department of Interventional RadiologyRegina Elena Cancer InstituteRome, Italy5 Intensive Care UnitNational Institute for Infectious Disease “L.Spallanzani”Rome, Italy6 Department of Infectious Diseases andHepatologyNational Institute for Infectious Disease “L.Spallanzani”Rome, ItalyAddress correspondence to: Giuseppe Maria Ettorre,M.D., General Surgery and TransplantationUnit, San Camillo Hospital, Rome, Italy.E-mail: gmettorre@scamilloforlanini.rm.itG.M.E. participated in research design, perfor-mance of the research, and writing of themanuscript; R.S. participated in research de-sign and performance of the research; C.P. par-ticipated in research design; R.S., L.C., M.A.,G.A., and C.L.M. participated in performanceof the research; L.M. participated in researchdesign; and G.V. participated in research de-sign, performance of the research, and writingof the manuscript.Received 18 March 2010.Accepted 5 July 2010.Copyright © 2010 by Lippincott Williams &WilkinsISSN 0041-1337/10/9008-930DOI: 10.1097/TP.0b013e3181f10f04REFERENCES1. Mazzaferro V, Regalia E, Doci R, et al. Livertransplantation for the treatment of smallhepatocellular carcinomas in patients withcirrhosis. N Engl J Med 1996; 334: 693.2. Mazzaferro V, Llovet JM, Miceli R, et al;for the Metroticket Investigator StudyGroup. Predicting survival after liver trans-plantation in patients with hepatocellularcarcinoma beyond the Milan criteria: A ret-rospective, exploratory analysis. Lancet On-col 2009; 10: 35.3. Yao FY, Kerlan RK Jr, Hirose R, et al. Excel-lent outcome following down-staging ofhepatocellular carcinoma prior to livertransplantation: An intention-to-treat anal-ysis. Hepatology 2008; 48: 819.4. Lewandowski RJ, Kulik LM, Riaz A, et al.A comparative analysis of transarterialdownstaging for hepatocellular carcino-ma: Chemoembolization versus radio-embolization. Am J Transplant 2009; 9:1920.5. Salem R, Lewandowski RJ, Mulcahy MF, etal. Radioembolization for hepatocellular car-cinoma using yttrium-90 microspheres: Acomprehensive report of long-term out-comes. Gastroenterology 2010; 138: 52.6. Kennedy AS, Nutting C, Coldwell D, et al.Pathologic response and microdosimetry of90Y microspheres in man: Review of four ex-planted whole livers. Int J Radiat Oncol BiolPhys 2004; 60: 1552.7. Salem R, Lewandowski RJ, Atassi B, et al.Treatment of unresectable hepatocellularcarcinoma with use of 90Y microspheres(TheraSphere): Safety, tumor response,and survival. J Vasc Interv Radiol 2005; 16:1627.8. Gulec SA, Mesoloras G, Dezarn WA, et al.Safety and efficacy of Y-90 microspheretreatment in patients with primary and met-astatic liver cancer: The tumor selectivity ofthe treatment as a function of tumor to liverflow ratio. J Transl Med 2007; 5: 15.© 2010 Lippincott Williams & Wilkins 931Letters to the Editor

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Short-Term Follow-Up of Radioembolization With Yttrium-90 Microspheres Before Liver Transplantation: New Perspectives in Advanced Hepatocellular Carcinoma

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