Survival outcome of lobar or segmental transcatheter arterial embolization with ethanol-lipiodol mix

PO Box 2345, Beijing 100023, ChinaWorld J Gastroenterol 2005: 11(18): 2792-2795world Journal of Gastroenterology ISSN 1007-9327ELSEVIERC2005 The wG Press and Elsevier Inc. Allrights reserved.Survival outcome of lobar or segmental transcatheter arterialembolization with ethanol-lipiodol mixture in treating hepatocellularcarcinomaYun-Chung Cheung, Sheung-Fat Ko, Shu-Hang Ng, Siu-Cheung Chan, Yu-Fan ChengYun-Chung Cheung, Sheung-Fat Ko, Shu-Hang Ng, Siu- C 2005 The WJG Press and Elsevier Inc. All rights reservedCheung Can, Yu-Fan Cheng, Department of Diagnostic Radiology,Chang Gung Memorial Hospital at Keelung and at Kaohsiang, 5 Fu Key words: Liver; Hepatoma; Transcatheter arterialHsing, Street, Kwei Shan, Tao Yuan Hsien, Taiwan, Chinaembolization: Treatment: Survival outcomeCorrespondence to: Dr. Shu-Hang Ng, Department of DiagnosticRadiology, Chang Gung Memorial Hospital, 5 Fu Hsing Street, Kwei Cheung YC, Ko SF, Ng SH, Chan sC, Cheng YF SurvivalTelephone:+886-3-3281200Fa:+886-3-3330365outcome of lobar or segmental transcatheter arterialReceived: 2004-10-18 Accepted: 2004-12-08embolization with ethanol-lipiodol mixture in treatinghepatocellular carcinoma. Word J Gastroentero/ 2005; 11(18):2792-2795http://www.wignet.com/1007-9327/11/2792.aspAbstractAIM: To evaluate the dinical outcome and cost-effectivenessof transcatheter arterial ethanol-lipiodol embolotherapy INTRODUCTIONon hepatocellular carcinoma(Hcc)Hepatocellular carcinoma(HCC) had been documented asMETHODS: One hundred patients with HCc who werehe leading cause of cancer death in our country for yearstreated only by lobar or segmental transarterial Various methods of treatment including surgical andembolization(TAE)with ethanol-lipiodol mixture were non-surgical therapies have been attempted. The non-surgicalenrolled in this study. The 1st-and 2nd-year survival ratesones include transarterial embolization(TAE), transarterialwere analyzed to evaluate the feasibility of its methodchemoembolization(TACE), percutanous ethanol injection,These outcomes of our patients were individually radiofrequency ablation, systemic chemotherapy, hormonecorrelated to the Child-Pugh classification and the therapy, immunotherapy, and radiotherapy. Among them,computed tomographic features of HCC.surgery is traditionally believed to be the best treatment,offering the chance of complete cure by tumor removalRESULTS: The overall 1st-and 2nd-year survival ratesUnfortunately, most of the HCC are unresectable atwere 72% and 46%, respectively. The patients were discovery, with poor survival rate of less than 6 moA. Onclassified into three groups according to their liver functionthe other hand, the recurrence of HCC is high in a cirrhoticstatus:68 patients as Child-Pugh class A, 26 as Child B, liver secondary to infectious hepatitisand 6 as child C. child a had better survival rate than theIn those cases with cirrhotic liver, deteriorating liverChild B and/ or C. The 1st-year survival rates of patients function is a common risk factor for undertaking a largewith Child A-C were 84%, 50%, and 33.3% respectively area resection. An optimal therapy with safe procedure andand the 2nd-year survival rates were 55.5%, 28.5%, minimal interruption on liver function is essential. Under suchand 33. 3%, respectively. According to the computedcircumstances, minimal invasive nonsurgical managementtomographic features, solitary HCC with maximum rather than invasive surgical approach may be the choicediameter less than 5 cm had the best outcome with the of therapy, in which tace is one of the most commonly1st-year survival rate of 100%and the 2nd-year survival used methods. However, chemotherapeutic drugs arerate of 71.4%, while solitary HCC with maximum diameter expensive and hepatic toxic. In this study, we report theover 5 cm and multiple HCc had the 1st-year survival rates survival outcomes of TAE of HCC using the less toxicof 75%and 63. 7%, respectively, and the 2nd-year survival ethanol-lipiodol liquid mixture, in order to evaluate therates of 33. 3% and 44.4%, respectively. Only one patient feasibility of this embolization method. To our knowledge,was complicated with abscess formation and was cured this is the first report to document the therapeutic resultswith antibiotic therapy. No mortality resulted from the of TAE with ethanol-lipiodol liquid mixture in the patientprocedures performedwith中国煤化工economic, safe and feasible method for treating hcc, mAlonCNMHGspecially for the patients with smaller solitary HCC or Reviewing the records of transcatheter arterial embolizationwith liver function status of Child-Pugh class A(TAE) performed in our department from January 2000Cheung YC et a/ Outcome of ethanol -lipiodol TAE on HCC2793to December 2002, we enrolled 100 HCC patients who our patients were classified into three categories. Theyreceived lobar or segmental TAE with the mixture of included: (1)solitary HCC with maximum diameter less thanabsolute ethanol and lipiodol. There were 70 males and 30 5 cm,(2)solitary HCC with maximum diameter greaterfemales, ranging from 39 to 82 years(mean: 63. 62*9.65 years). than 5 cm, and(3)multiple HCCs of multinodular,The technique of TAE was standardized, following the set infiltrating or mixed type. The patients were also classifiedup protocol since January 2000 in our department. In order into three other groups as Child A-C, according to theirto obtain an absolute therapeutic outcome of ethanol-lipiodol liver function status. We individually correlated the CTTAE, the patients that underwent other treatments such as presentations of HCC and the Child-Pugh classification topercutaneous ethanol injection, radiofrequency therapy or the 1st- and 2nd-year survival outcomes.TACE were excluded from our study. Those HCCs withche radiographic evidence of vascular shunts or with portalvein thrombosis were also eliminatedRESULTSAll patients were requested to sign consents after full Totally, 245 TAE procedures were successfully performedexplanation. With the coaxial angiographic technique, a Some cases of mild abdominal distension and mild feverFrench-3 microcatheter was selectively catheterized beyond were observed after the procedure, but all subsided withinthe lobar or segmental branch of the hepatic artery supplying 24 h after the procedures. No major complications wereHCC. Abte ethanol (99.5%)and lipiodol were mixed immediately noticedduring the procedures except onein emulsion as the embolize for TAE. The composition of liver abscess(1%) was found 5 d after the TAE. The abscessabsolute alcohol and lipiodol was kept at 3 to 1 ratio. was subsequently cured by antibiotic therapy. Based on theHowever, the amount of lipiodol used was proportional to finding of follow-up CT, no bilioma was complicated. Therethe maximum diameter of targeted HCC measuredwas no procedure-related mortalityomputed tomogram(CT). If the maximum diameter wasAccording to the serum data, all our patients were5 cm, the amount of lipiodol used would be 5 mL In cahepatitis-infected, including 56 patients with viral hepatitis-of multiple HCC, the amount of lipiodol (mL) used was B, 34 with viral hepatitis-C, six with both viral hepatitis Badjusted according to the sum of maximum diameters of and C, and four with non-B and non-C viral hepatitis. Atall targeted HCC in centimeters. However, the maximum the time of TAE, 68 of our 100 patients were classified asamount of lipiodol was always limited to 10 mLChild-Pugh class A, 26 as Child B and six as CIild CBefore starting the infusion of embolizing agents, each According to the morphologic presentations of HCC25 mg Demoral was given intravenously and intramuscularly, multiple HCCs were found in 69 patients, solitary HCCrespectively. To avoid the vasospasm, intra-arterial slow with maximum diameter less than 5 cm was found in 19injection of 3 mL of 2% lidocaine diluted with 10 mL patients, and that greater than 5 cm was found in thesaline were routinely administered. With the stable vital signs remaining 12 patientslipiodol mixture was connected to an adjustable pumping Post-TAE follow upmachine and was slowly infused with a set rate at 0.5-1 mL Post-TAE serum levels of aspartate aminotransferase andper minute. The TAE would be finished when the infusion alanine aminotransferase on the 3rd day increased in 195of embolizing mixture had been completed. In another procedures. of which an increment ranging from 50 to 300situation, the embolization would also be terminatedwhen the retrograde filling of the portal vein was observed IU/L was found in 123 procedures, ranging from 301 to(Figure 1), Finally, absorbable gelfoam particles were 22 procedures. Slight elevation of the total bilirubin and amedium in the supplied arteries of the embolized HCC, in of our 245 TAE procedures. All these abnormal parametersorder to delay the washout of the embolizersAccording to the findings on triphasic CT, the HCCs of returned to the initial levels within 2 wk. At that timeconsiderable decrement of alpha fetoprotein was noted in172 of our TAE procedures. The alpha fetoprotein of ourpatients with HCCs with maximum diameter less than 5 cmwas invariably improved. On the follow up triphasic CTafter the first TAE, a complete package of embolized HCCwithout evidence of viable cancer was found in 73 patients(12 patients of HCC with maximum diameter less than 5cm,13 patients of HCC with maximum diameter greaterthan 5 cm, and 48 patients of multiple HCC). Residualviable tumors were noted in the other 27 patients(23 patients中国煤化工 ICC larger than5cm of- n order to treat residualCN MH Gence at the embolizedareas(n=8), or newly developed HCC in the otherwiseFigure 1 Post-embolization radiographic image of upper abdomenliver areas(n= 46),54 patients needed repeated TAEhomogenously packed HCC and retrograde filling of multiple parenchymalSeventeen patients underwent second TAE and the other37 patients underwent second and third TaEs2794ISSN 1007-9327 CN 14-1219/R World J Gastroenterol May 14, 2005 Volume 11 Number 18Cost-effectiveness assessmentof microcatheter system, we are able to superselectivelyThe benefits of ethanol-lipiodol TaE compared with catheterize a small angiocatheter into the tumor-feedingassessed in the cost of embolizers and the artery in order to achieve the lobar or segmental targetingduration of hospitalization In our country, the cost of embolization while avoiding arterial injury. With such a highDoxorubicin in a single TACe procedure was SUS 60 for technical performance, the embolizers can be effectively20 mg. However, the cost of the 99.5% ethanol that we injected into HCC tumor bedsused in a single TaE procedure was SUS 0.05. On the otherSince the application of TAE on unresectable HCC,hand, all patients were discharged from hospital about 3 d several reports have documented the effectiveness ofafter TAE procedures. Only one patient was admitted this treatment on unresectable HCC+. Various embolizersagain due to the complication of liver abscess 5 d after had been introduced. TACE was currently used in mostTAE and required hospitalization for antibiotic treatment centers due to the combined therapeutic effects of tumorfor 8 d. No additional systemic complication prolonging chemotoxicity and ischemia. In a report of a Chinesethe hospitalization was noticedpopulation sample of inoperable HCC with Child A and B,the 1st-and 2nd-year survival rate after TACE were 86.3%Survival outcome analysisand 78.8% respectively. In our result, the survival ratesThe overall 1st-and 2nd-year survival rates were 72% and of the patients with Child A and B were 84% and 50/o,46%, respectively. The 1st-year survival rate distinctively respectively for the 1st year, and 55.5% and 28.5%varied to Child-Pugh classification with 84% for Child A. respectively for the 2nd year. The survival rate of our50% for Child B and 33.3% for Child C. For the 2-year patients with Child C maintained at 33. 3% for the 1st-andsurvival rate, Child A was still the best but the rate decreased 2nd-year survival rates, however, due to small populationsto 55.56%. The 2-year survival rate of Child B and C were in this group, such survival rate necessitated furtherclose to the survival rate of 28.57% and 33.3%, respectively investigation with a larger seriesFigure 2). The cause of the same Ist- and 2nd-year survivalIn 1983, sonographically guided percutanous ethanolrate(33.3%)of our Child C patients was that two of ourjection therapy(PEit)was introduced as a new alternativesix Child C patients had solitary HCC less than 5 cm and approach in treating small HCCP. This method waswere well controlled by TAE in the period of 2 yearssubsequently agreed upon by many clinicians on the pointThe survival rates of patients with solitary HCC less of effectiveness in treating a small HCC1o-13 For a largethan 5 cm, and that greater than 5 cm and multiple HCCs HCC, PEIT has difficulties to fill the entire tumor tissuewere 100%,75%,and 63. 77%, respectively for the 1st year because of the complicated architecture of septa andand71.43%, 33. 33%o, and 44.44%, respectively for the second inhomogeneous infiltration of ethanol within the tumoryear(Figure 3). The patients died of the uncontrollable The combined treatment with PEIT and TACE has beenprogression of the disease including the decompensation reported as effective in causing complete tumor necrosisof liver function in 18 patients, widespread dissemination The capsular invasion or small daughter nodules can alsoof HCCs in 25, and the development of portal vein be treated 2-14. The reported 1st-and 2nd-cumulative survivalhrombosis in 9rates of combined therapy with PEIT and TACE were 78%and 54%, respectively. Such a result was similar to ourswith ethanol-lipiodol TAEDISCUSSIONCurrently, TAE or TACE are the mainstream in theIn Taiwan, most patients with HCC were cirrhotic related, treatment of unresectable HCC. Since chemotherapeuticaccompanied by liver dysfunction. The liver function drugs are hepatotoxic, we use a less toxic ethanol as animpairment or the HCC involvement often limit the surgery embolize in order to preserve the liver function as muchto be significantly higher than non-surgical cases - However, embolize that has been used to treat vascular lesions orthe survival rate had been improved by the progressive tumors. In 1997, the embolization effect of ethanol ondvances of angiographic techniques. With the development HCC was established on the basis of animal models6. 7.◆ child a0942Child B(26)-<5 cm solitary(19)77143-·<5 cm solitary(12)8261Overall (100)6078Multinodular(69)中国煤化工△44CNMHG0M0.5Y1YFigure 2 Survival rates of HCC in Child-Pugh classificationFigure 3 Survival rates of HCC in different morphology.Cheung YC et a/ Outcome of ethanol-lipiodol TAE on HCC2795Kan et al, reported the pathways of iodized oil and silicon 7 Wheeler PG, Melia W, Dubbins P. Non-operative arterialrubber solution shunting from the hepatic artery to theembolization in primary liver tumors. BM/1979; 2: 242-244ortal veinna. and the mechanism of sinusoid embolization8 Yuen MF, Chan AO, Wong BC, Hui CK, Ooi GC, Tso WK,by iodized oill). On the other hand, two reports haveYuar H], Wong DK, Lai CL. Transarterial chemoembolizationfor inoperable, early stage hepatocellular carcinodocumented the clinical efficacy of this ethanol-lipiodoltients with Child Pugh grade A and B: results of aTAE on HCCi20 211. The results showed successful liver lobarive study in 96 Chinese patients. Am J Gastroenterolmablation with only minimal side effects.1181-1185From the fluoroscopic observation on an animal model, 9 Sugiura N, Takara k, ohto N Percutaneous intratumoraldual embolization will be induced by slow infusion ofinsoluble substance, such as a mixture of ethiodol andSf small hepatocellular carcinoma. Acta Hepatol Jpn 1983;thanol, which appears as small droplets passing through 10 Fujimoto T. The experimental and clinical studies of percu-the hepatic sinusoids(the bridges between the hepatic artertaneous ethanol injection therapy(PEIT)urand the portal vein) to the portal vein. This achieves completeny for small hepatocellular carcinoma. Acta Hepatol Jpn 1988:9:52-55hrombotic effect with embolizers package in both the 11 Ebara M, Ohto N, Sugiura N, Kita K, Yoshikawa M,Okudaarteries supplying the tumor and its adjacent parenchymalK, Kondo F, Kondo Y Percutaneous ethanol injection for theportal veins 2. A slow infusion of embolizers is the keytreatment of small hepatocellular carcinoma. Study of 95atients. Gastroenterol Hepatol 1990; 5: 616-626technique not only prevents the spasmodic change of the 12 hina S, Tagawa k. Unuma T Takanashi g, Yoshiura K,feeding artery, but also allows the embolizers to floweous ethanol injection for the therapy for hepatocellularprimarily to the fast stream tumor vessels. Once the tumorcarcinoma. A histopathologic study. Cancer 1991; 68: 1524-vessels have been filled up, the liquid, insoluble embolizerswill then start to deposit along the feeding hepatic artery 13 Tanaka M, Okazaki H, Nakamura S, Endo o, Inoue S,and the parenchymal portal veinsIn our results, tumor morphologic features and patientreatment with a combination therapy of transcatheter arte-liver function status affected the survival rates of HCCrial embolization and percutaneous ethanol injection. Radiol-oy1991;179:713-717patients after TAE with ethanol-lipiodol mixture. Better 14 Yamamoto K, Masuzawa M, Kato M, Kurosawa K,Kanekosurvival rates were observed in patients with solitary smallerA, Ishida H, Imamura E, Park NJ, Shirai Y, Fujimoto K,HCC or with liver function status of Child A. The outcomeMichida T, hayashi N, Ikeda M. Evaluation of combinedof our study was similar to that of traditional TACEtherapy with chemoembolization and ethanol injection forNevertheless, ethanol-lipiodol TAE is a cheap and less toxicadvanced hepatocellular carcinoma. Seminars Oncol 1997: 24(2 Suppl 6): $6-55alterative treatment feasible for HCC15 Li YH, Wang CS, Liao LY, Wang CK, Shih LS, Chen RC, ChenPH. Long-term survival of Taiwaness patients with hepato-ACKNOWLEDGMENTScellular carcinoma after combination therapy with transcatheterarterial chemoembolization and percutaneous ethanolWe sincerely thank Miss Stephanie Cheung, a student ofinjection. Formos Med Assoc 2003: 102: 141-146Cell Biology and Genetics at the University of British16 Kan Z wallace S. Transcatheter liver lobar ablation:experimental trial in a animal model. Eur Radiol 1997; 7:Columbia, Canada for manuscript preparation1071-107517 Ito K, Kusunoki H, Okamoto E, Ozawa M, Ishikawa AREFERENCESMatsuura M, Nakajima N. 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