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1 대한내과학회지 : 제 77 권제 3 호 2009 특집 (Special Review) - 만성간질환치료의최신지견 간세포암종치료의최신지견 인제대학교의과대학일산백병원내과 이준성 Advances in the treatment of hepatocellular carcinoma June Sung Lee, M.D. Department of Internal Medicine, Inje University College of Medicine, Ilsanpaik Hospital, Goyang, Korea There have been recent advances in the treatment of hepatocellular carcinoma (HCC). There has been a clear change in the presentation of HCC, with an increased detection of tumors <2 cm in diameter as result of surveillance programs. In addition, the development of effective local treatment methods has led to the necessity for the selection of base therapeutic modalities on each patient s characteristics. New promising image-guided therapies and new drugs, such as sorafenib, may address the enormous need for expanded treatment options for patients with HCC. Tailored therapies are needed to improve the treatment response and, ultimately, patient survival. Here, we review these advances in the management of HCC. (Korean J Med 77: , 2009) Key Words: Hepatocellular carcinoma; Therapy 서론우리나라암발생빈도 3위인간세포암종 (Hepatocellular carcinoma, HCC) 은특히사회적으로가장활동적인 40, 50대남자의주요사망원인으로예후가아주안좋은대표적인암종이었다. 그러나비약적으로발전하는영상학적진단기법, 국가및개인이시행하는암조기검진프로그램등으로예전과다르게 2 cm 이하의소간세포암종발견빈도가많아졌으며, 새로운다양한치료기법의임상적용은간세포암종의임상상및예후를바꾸어놓았다. 간세포암종의근치적치료법은수술적절제와간이식이다. 그러나최근국소치료술도수술적절제와비슷한결과를보고하고있어 1), 일차치료법으로국소치료술도고려되고있다. 또한근치적치료를할수없는진행된간세포암종환자에서도경동맥화학색전술기법의발전, 방사선치료및표적치료제의개발등으로다양한치료가가능하게되었다. 그 런데적용될수있는치료방법이많아졌다는것은다르게표현하면가장적절한치료법선택이그만큼어려워졌다는것을의미한다. 이에본종설에서는근치적치료술이가능한소간세포암종환자및그렇지못한환자들각각에게서적용될수있는각치료법들의성적및장단점들을소개해환자진료에있어가장좋은치료법을선택하는데도움이되고자한다. 간세포암종의근치적치료 1. 간절제술종양조직을포함하여주변조직의일부까지제거하는부분간절제술 ( 이하간절제술 ) 은장기생존및완치를기대할수있는간세포암종치료의근간이다. 더욱이최근에는수술전간기능평가와예후판정이가능해지고, 수술술기및수술후환자관리의발전으로간절제술에따른합병증이나

2 - June Sung Lee. Advances in the treatment of hepatocellular carcinoma - 사망률이크게감소해간절제술을권유할수있는최소한의조건으로수술후 50% 의 5년생존율과 3% 미만의수술전후사망률이제시되고있다. 간절제술후예후는암종의크기, 숫자, 혈관침범여부, 동반된간경변및문맥압항진정도등이중요한인자로작용한다 2-7). 따라서수술전에상기의나쁜예후인자가있어수술후합병증발생가능성이높거나장기생존율이좋지않을것으로예상되는경우는절제술보다는다른치료법을우선고려하여야할것이다. 간절제술의가장큰문제는 3년 50%, 5년 70% 에이르는높은재발률과이로인한장기생존율의감소이다. 재발예측인자로는미세혈관침윤, 불량한종양세포분화도, 높은 alpha-fetoprotein, 위성결절등이제시되고있다 2,5-7). 수술후재발을줄이기위한여러실험적치료가연구되었으나효과적인것은없었다. 2. 간이식간이식은이론적으로간세포암종을완전히제거할수있는가장확실한방법인동시에새로운간기능을제공할수있는가장이상적인치료법이라할수있다. 그러나이식간부전등의수술적위험, 면역억제제를평생사용함에따른합병증및간세포암종이재발할경우예후가훨씬나쁜점, 뇌사자간이식의경우공여자가많지않아서이식할때까지시간이많이걸리는점및높은수술비용이라는단점들이있다. 과거에는이식후높은재발률 (32~54%) 과불량한생존율 (5년생존율 40%) 때문에이식이꺼려져, 일부의환자에서만이루어졌으나 1990년대에들어서는 5 cm 이하의단일종양, 3 cm 이하의결절이 3개이하인경우에는 70% 대의높은 5년생존율을보고하게되었다 8). 이를 Milan criteria라명명하게되었고, 전세계적으로이기준을사용하여우수한결과들을보고하고있다. Milan criteria 즉, 5 cm 이하의단일결절혹은 3 cm 이하의결절이 3개이하이면서주혈관침습이없는경우뇌사자간이식후 5년생존율은 70% 이상, 재발률은 15% 이하의좋은결과를보고하고있는데, 이들보고들은모두상기의엄격한기준을적용하고이식대기기간이 6개월미만으로짧았다는공통점을가지고있다 9,10). 최근에는 Milan 기준을넘어더확장된기준으로이식을시행해좋은성적들이보고되고있다. 즉, UCSF 그룹은적출간병리를기준으로 6.5 cm 이하의단일결절혹은 4.5 cm 미만의 3개이하의결절 ( 단, 직경의합이 8 cm 미만 ) 인경우 1년과 5년생존율이 90%, 75% 에이른다고보고하였고 11), 나아가, 단일 결절 7 cm 이하, 3개의결절 5 cm 이하, 5개의결절 3 cm 이하혹은치료후에 6개월이상 Milan 기준으로병기가낮아진경우이식후 5년생존율이 50% 라고보고하였다 12). Milan 기준에의한것과후자의확장된기준에서의연구대상및분석방법에는차이가있어이들연구결과들을그대로비교하기에는어려움이있다. 즉, Milan 기준이이식대기당시영상소견에근거한병기를기준으로한것임에비해후자의확장된기준은적출된간의병리소견에근거한것이고 Milan 기준에의한성적은이식대기중종양진행으로인해탈락한환자의성적이반영되어있으나, 후자의연구들에서는이런환자들이모두분석에서제외된차이가있다. 이식후재발은종양의혈관침범과분화정도가중요한인자로작용한다. 간이식과부분간절제술의단기성적은서로유사하지만 3년이상경과시에는무재발생존율에있어간이식이우월한장점이있다 13). 그러나장기부족으로대기기간이길다는점에의해그장점이상쇄되고있다. 나아가이식은약 15% 의 1년사망률을보이고특히생체간이식이대부분인우리나라에서공여자의위험성을고려하지않을수없을때간기능이잘보존된환자의소간세포암종의 1차치료로간이식을권하는데에는어려움이있다고생각한다. 3. 비수술적국소치료법시술이간편하고주변간조직손상을덜주면서종양을괴사시킬수있는장점이있는국소치료법은현재고주파열치료술및에탄올주입술이표준적인치료법이다. 국소치료술의적응증은연구자나시술법에따라차이가있으나, 단발성인경우는장경 5 cm 이하, 다발성인경우는 3개이하이고, 장경이 3 cm 이하일때고려할수있다. 비적응증은조절되지않는복수가있는경우, 심한혈액응고장애, 혈소판수가 40,000~50,000/mm 3 이하, 프로트로빈활성이 40~50% 이하, 심한간기능장애, 종양혈전, 간외전이가있는경우, 영상유도가불가능한경우, 협조가안되는경우등이다. 1) 경피적에탄올주입술 (percutaneous ethanol injection therapy, PEIT) 국소치료법중에가장오래된치료법으로, 간세포암종에주입된에탄올은단백변성과소혈관혈전형성으로종양을괴사시킨다. 초음파유도하에 21게이지바늘로 95% 에탄올 2~8 ml를종양과종양주위에주입하는데종양에한번주입할수있는에탄올양이한정되어있어서크기가 1.5 cm이면한번에치료할수없고, 3 cm 정도종양의경우세차례나

3 - 대한내과학회지 : 제 77 권제 3 호통권제 589 호 누어치료하므로일주일이상의치료기간이필요하다. 시술관련사망률은거의없으며, 합병증은 1.3~2% 정도이다. 합병증으로간농양, 간부전, 복강내출혈, 담도염등이있으며, 바늘경로를통한종양의전이는 0~1% 로보고되고있다. 경피적에탄올주입술의장점은저렴한비용과낮은합병증이나, 단점은종양내격벽으로인해주입된에탄올이종양내에고루분포되지않는점, 치료시술의횟수가많다는것과 3 cm 이상의종양에서는치료효과가감소한다는것이다 14). 2) 고주파열치료술 (radiofrequency ablation, RFA) 고주파열치료술은끝부분만절연되지않은전극을통해고주파를종양으로보내면종양내조직이온들이진동하면서마찰열이발생되고, 유도된고열로인해전극을중심으로일정범위의종양에응고혹은응고괴사가일어난다. 대부분초음파를실시간보면서경피적으로시술하나, 간의횡경막직하부등에위치하여경피적접근이어려운경우에는수술장에서개복을하거나복강경을이용해실시되기도한다. 장점은적은횟수의시술로높은종양괴사효과를나타낸다는점으로, 종양의크기가 2 cm 이상인경우에탄올주입술에비하여높은종양괴사율을보인다 15-17). 단점으론간문 (hilum) 주위나대장과같은주요장기가종양에인접한경우시술합병증의위험성이높고, 큰혈관주위에종양이위치한경우열전달이충분하지않아치료효과가떨어질수있고부작용이상대적으로알코올주입술에비해많다는점이다 1,18,19). 4. 각근치적치료법의성적비교 1) 절제술과국소치료의비교수술적절제술과고주파열치료술을비교한대부분의연구는무작위대조연구가아니어서결론을내리기에는부족한실정이나, 직경 4~5 cm 이하의종양을대상으로한연구들에서고주파열치료술이절제술과비슷한치료효과와장기생존율을보고하고있다 20-23). 직경 5 cm 이하의단일결절을지닌 180예의간세포암종환자를무작위로수술혹은고주파열치료술을시행한후비교한연구결과에서두치료간에 1, 2, 3, 4년생존율과무병생존율에차이가없으며, 종양의크기에따라서도두치료간에차이가없음이보고되었다 20). 그러나이연구에선고주파치료에배정된환자들에서동의가철회된환자가많았으며, 대상이 ICG-R 15 30% 미만, 혈소판 40,000/mm 3 이상의기준으로선정되어수술적절제가최선의치료가아닌환자들이수술을받은경우가 포함되어있을가능성이있다. 따라서향후잘계획된대규모무작위연구가필요한실정이다. 에탄올주입술과절제술을비교한연구결과를보면간기능이 Child 분류 A나 B인 3 cm 이하의단일종양인경우는두치료법간생존율에뚜렷한차이가없으며 24-26), 3 cm 이하 1~2개의결절을가진간세포암종환자를대상으로한무작위대조연구에서도두치료환자들간에생존율및재발률에차이가없다고하였다 24). 그러나에탄올주입술과절제술을비교한무작위대조연구는단한편에불과하고, 이연구조차도생존율보단재발률을기준으로표본크기를산정하였고, 두치료간에비록통계적차이는없다고하지만 5년생존율이각각 46% 와 81.8% 로큰차이가있었다. 따라서절제술과국소치료성적을비교하기에는아직임상연구결과가부족하며앞으로더많은전향적연구가필요한실정이다. 2) 에탄올주입술과고주파열치료술의비교이치료들의장점은주변간손상을최소화하여간기능을최대한보전하면서간세포암종을효과적으로치료할수있다는것과, 합병증발생이적어재발이되어도적응만된다면수차례반복적인치료가가능하다는점이다. 고주파열치료술에비교해에탄올주입술의장점은저렴한치료비와뛰어난안정성이다. 그러나국소재발률이고주파열치료술에비해높은단점이있다. 고주파열치료술은원하는치료영역을한번에치료할수있고전이암도간세포암종과마찬가지로효과적으로치료할수있다는장점이있다. 고주파열치료술과에탄올주입술성적을비교한여러무작위대조연구에서는고주파열치료술이유의하게낮은국소재발률과높은종양괴사효과를보여주었고 15,27-29), 생존율의비교에서도유의하게높거나비슷한결과를나타내었다. 특히기존에발표된무작위대조연구를메타분석한연구에서도고주파열치료술의 3년생존율이에탄올주입술에비해서유의하게높은것으로보고되었다 30). 그러나직경 2 cm 이하의종양에서는두치료법의성적에차이가없어완전한결론을내리기에는아직부족한실정이다. 따라서초음파에서잘보이는 1.5~2 cm의간세포암종의경우엔에탄올주입술이더경제적인치료방법일수도있다. 또한에탄올주입술은바늘의위치가중심에서약간벗어나더라도종양내에만바늘끝이위치해있으면에탄올이종양내부로확산되어치료가성공적으로이루어질수있는반면, 고주파열치료술의경우전극을더욱정확하게종양내부의계획된

4 - 이준성. 간세포암종치료의최신지견 - 위치에가져다놓아야하므로시술자의경험이더욱필요한치료법이다. 진행된간세포암종의치료간내다발성암종을갖고있거나, 충분한절제구역을확보하지못할정도로큰경우문맥및주혈관침범이있는경우, 혹은간기능저하가심한경우는간세포암종의근치적치료는힘들어, 부분적반응과생존율향상에치료의목표를두게된다. 1) 경동맥화학색전술 (Transcatheter Arterial Chemoembolization, TACE) 정상간은간동맥과문맥으로부터이중의혈류공급을받지만, 간세포암종은거의모든혈류를간동맥으로부터공급받는다. 따라서간동맥혈류를효과적으로차단하면정상간조직손상은최소화하면서비교적선택적으로간세포암종의허혈괴사를유발할수있다. TACE 는간세포암종에대한화학요법과선택적허혈효과를동시에보고자하는치료법이다. 종양이큰경우반복적치료에도불구하고암이완전히소실되는빈도가낮으므로근치적치료법으로분류되지는않지만종양이 4 cm보다작은경우미세도관으로혈관을초선택해 50% 이상에서완전종양괴사의항암효과가보고되기도하였다 31,32). 진행간세포암종에대한 TACE 가생존율을향상시키는지에대하여초기에는생존율에는영향을주지못한다는의견이많았으나, 절제불가능간세포암종에서 TACE 가무치료군에비해생존율을증가시킨다는무작위대조연구들이발표되었고 33,34), 이후이들의메타분석을통하여 TACE 가생존율을향상시킴이밝혀졌다 35,36). 그러나종양이주문맥을침범하거나미만성종양침윤을보이는환자에서 TACE 는효과가만족스럽지못하고오히려부작용이많이발생해다른새로운치료법개발이필요한실정이다. 수술거부나수술위험성등으로절제가능한간세포암종에시행된 TACE 치료성적은 UICC 병기 T1, T2의경우절제술이 TACE 에비해서의미있게생존율이높았으나, T3병기에서는두치료법간에생존율차이가없었다. 또한 T1, T2 병기라도 TACE 후리피오돌이조밀하게유지되어있는경우는수술과비슷한생존율을보였다 37). 따라서수술적절제가가능하지만환자가수술을거부하거나위험성이높은경우선택된일부환자에선 TACE 로서절제술과비슷한생 존율을기대할수있다. 최근에는다른국소치료와병행한연구결과들이발표되었는데, 특히수술적적응이되지않은결절크기가직경 3 cm 이상 7.5 cm 이하, 3개이하의간세포암종환자를대상으로한전향적무작위배정대조연구에서고주파열치료술과 TACE 를병용한경우중앙생존값이 37개월로고주파열치료술 22개월, TACE 단독치료 24개월에비해우수한성적을보고하였다 38). 비록본연구가고주파열치료술적응범위를벗어나는환자들이고주파열치료술단독치료군에포함되어있다는단점이있지만, TACE 에불완전한효과가예상되는환자중국소치료가가능한경우는에탄올주입술혹은고주파열치료술병용을고려해볼수있음을시사한다. 2) 전신화학요법 (Systemic chemotherapy) 다른고형암치료처럼전신화학요법이오래전부터시도되었으나, 치료반응률은 20% 이내로낮고, 생존율의향상이없어 1990년도이후에는전신항암제에대한연구보고는별로없는실정이다 39-43). 또한보조화학요법으로간세포암종절제술후재발방지를위한전신화학요법이전체생존율, 무병생존율을증가시킬수없으며, 간경변환자에서항암제에의한부작용의위험성만높아보조화학요법은더이상치료에이용되지않고있다 12). 최근간세포암종의발병기전에대한분자생물학적연구의발전에힘입어암세포의성장, 침윤및혈관생성등과연관된신호전달체계를겨냥한분자생물학적표적치료제들이개발되고있는데이중가장주목을받는약제는 sorafenib 이다. Sorafenib은경구용 multi-kinase 억제제로 Raf-1 및 VEGF, PDGF 수용체의활성도를억제해암세포성장및혈관생성을억제해 44,45) 간세포암종에서치료효과가입증되었다 46,47). 그러나치료반응기간이대조군에비해약 3개월정도밖에차이가나지않고부작용으로피로감, 설사, 손발피부병변 (hand-foot skin reaction) 등이나타나 48) 다른치료제의개발이절실한실정이다. 현재로선전신항암화학요법의대상이되는간세포암종환자에게일차적으로 sorafenib이사용될수있다. 3) 방사선치료 (Radiotherapy) 방사선치료는컴퓨터영상기술의발전으로정상조직에노출을최소화하면서목표병변에충분한방사선조사가가능해져간세포암종치료에활용이커지고있다. 수술적절제

5 - The Korean Journal of Medicine: Vol. 77, No. 3, Table 1. Evidence-based benefits of the treatments for HCC according to the strength of the study design and endpoints Treatments assessed Benefit Level of evidence Surgical treatments Surgical resection Increased survival 3iiA Adjuvant therapies Controversial 1A-D Liver transplantation Increased survival 3iiA Neo-adjuvant treatments Treatment response 3Diii Locoregional treatments Percutaneous treatments Increased survival 3iiA Radiofrequency Better local control 1iiD Embolization/chemoembolization Increased survival 1iiA Lipiodolization Treatment response 3iiDiii Internal radiation (I 131, Y 90 ) Treatment response 3iiDiii Systemic treatments Sorafenib Increased survival 1iA Hormonal compounds, tamoxifen, anti-androgens No survival benefit 1iA Systemic chemotherapy No survival benefit 1iiA Immunotherapy No survival benefit 1iiA Study design: randomized controlled trial, meta-analysis=1 (double blind, 1i; non-double blind, 1ii); non-randomized controlled trials=2; case series=3 (population-based, 3i; non-population based, consecutive, 3ii; non-population based, non-consecutive, 3iii). Endpoints: survival (A), cause-specific mortality (B), quality of life (C). Indirect surrogates (D): disease free survival (Di), progression-free survival (Dii), tumor response (Diii). 가불가능한경우, 특히간문맥침범이동반된경우입체조형 (conformal) 혹은정위조정 (stereotactic) 방사선치료를고려해볼수있다 49-51). 간세포암의임파선, 뼈, 뇌등에로의전이에의한증상완화를위해선방사선치료가도움이된다. 4) 실험적치료간세포암종진단당시이미진행성간세포암으로발견되어, 효과가증명된상기의표준치료법이시행되지못할경우를임상에서흔하게접하게된다. 이런경우임상에서실험적치료를시행해보는경우가있는데, 아직까지실험적치료들은기존의표준치료들과대조연구결과가없고치료비용이높아표준치료를적용할수있는경우에는일반적인치료로추천되지않는다. 현재국내에서실시되고있는실험적치료로는양성자치료, 간동맥내항암치료 (intraarterial chemotherapy), high-intensity focused ultrasound ablation (HIFU), sorafenib 이외의개발중인표적항암제등이있고, drug eluting bead 혹은 Yttrium microsphere 를이용한화학및방사선색전술이최근에새롭게소개되고있다. 결론진단및치료기술의발전으로과거에비해간세포암종환자에게선택할수있는치료법이다양해졌고, 근치적치료가가능한환자에선예후가향상된것이사실이다. 그러나아직까지진행된간세포암종환자들에대해선선택할수있는치료법이한정적이며그결과로아직효과가입증되지않은실험적치료들이많이시행되고있는것이현실이다. 그러나이들실험적치료는아직표준적치료가아니기때문에임상연구로서시도되어야만할것이다. 참고로현재간세포암종치료를위해시도되고있는치료법들의효과에대한증거수준 (level of evidence) 을표 1에정리하였다 52). 기존의수술, 간이식, 국소치료등의근치적치료후재발을막기위한보조치료 (adjuvant therapy) 및진행된간세포암종환자들을위한치료법개발에대해서현재많은임상연구들이진행중으로그결과들을기대해본다. 중심단어 : 간세포암종 ; 치료

6 - June Sung Lee. Advances in the treatment of hepatocellular carcinoma - REFERENCES 1) Livraghi T, Meloni F, Di Stasi M, Rolle E, Solbiati L, Tinelli C, Rossi S. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice? Hepatology 47:82-89, ) Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30: , ) Zhou XD, Tang ZY, Yang BH, Lin ZY, Ma ZC, Ye SL, Wu ZQ, Fan J, Qin LX, Zheng BH. Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma. Cancer 91: , ) Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N, Curley SA, Ellis LM, Regimbeau JM, Rashid A, Cleary KR, Nagorney DM. Simplified staging for hepatocellular carcinoma. J Clin Oncol 20: , ) Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 235: , ) Kumada T, Nakano S, Takeda I, Sugiyama K, Osada T, Kiriyama S, Sone Y, Toyoda H, Shimada S, Takahashi M, Sassa T. Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma. Hepatology 25:87-92, ) Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, Sugawara Y, Minagawa M, Takayama T, Kawasaki S, Makuuchi M. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol 38: , ) Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 25: , ) Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334: , ) Bismuth H, Majno PE, Adam R. Liver transplantation for hepatocellular carcinoma. Semin Liver Dis 19: , ) Roayaie S, Frischer JS, Emre SH, Fishbein TM, Sheiner PA, Sung M, Miller CM, Schwartz ME. Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters. Ann Surg 235: , ) Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 42: , ) Arii S, Yamaoka Y, Futagawa S, Inoue K, Kobayashi K, Kojiro M, Makuuchi M, Nakamura Y, Okita K, Yamada R. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan. Hepatology 32: , ) Beaugrand M, N'Kontchou G, Seror O, Ganne N, Trinchet JC. Local/regional and systemic treatments of hepatocellular carcinoma. Semin Liver Dis 25: , ) Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Solbiati L, Gazelle GS. Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 210: , ) Lencioni RA, Allgaier HP, Cioni D, Olschewski M, Deibert P, Crocetti L, Frings H, Laubenberger J, Zuber I, Blum HE, Bartolozzi C. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 228: , ) Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma < or =4 cm. Gastroenterology 127: , ) Rhim H, Yoon KH, Lee JM, Cho Y, Cho JS, Kim SH, Lee WJ, Lim HK, Nam GJ, Han SS, Kim YH, Park CM, Kim PN, Byun JY. Major complications after radio-frequency thermal ablation of hepatic tumors: spectrum of imaging findings. Radiographics 23: ; discussion , ) de Baere T, Risse O, Kuoch V, Dromain C, Sengel C, Smayra T, Gamal El Din M, Letoublon C, Elias D. Adverse events during radiofrequency treatment of 582 hepatic tumors. AJR Am J Roentgenol 181: , ) Chen MS, Li JQ, Zheng Y, Guo RP, Liang HH, Zhang YQ, Lin XJ, Lau WY. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 243: , ) Hong SN, Lee SY, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC, Rhee JC, Choi D, Lim HK, Lee KW, Joh JW. Comparing the outcomes of radiofrequency ablation and surgery in patients with a single small hepatocellular carcinoma and well-preserved hepatic function. J Clin Gastroenterol 39: , ) Lupo L, Panzera P, Giannelli G, Memeo M, Gentile A, Memeo V. Single hepatocellular carcinoma ranging from 3 to 5 cm: radiofrequency ablation or resection? HPB (Oxford) 9: , ) Abu-Hilal M, Primrose JN, Casaril A, McPhail MJ, Pearce NW, Nicoli N. Surgical resection versus radiofrequency ablation in the treatment of small unifocal hepatocellular carcinoma. J Gastrointest Surg 12: , ) Huang GT, Lee PH, Tsang YM, Lai MY, Yang PM, Hu RH, Chen PJ, Kao JH, Sheu JC, Lee CZ, Chen DS. Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study. Ann Surg 242:36-42,

7 - 대한내과학회지 : 제 77 권제 3 호통권제 589 호 ) Gournay J, Tchuenbou J, Richou C, Masliah C, Lerat F, Dupas B, Martin T, Nouel JF, Schnee M, Montigny P, D'Alincourt A, Hamy A, Paineau J, Le Neel JC, Le Borgne J, Galmiche JP. Percutaneous ethanol injection vs. resection in patients with small single hepatocellular carcinoma: a retrospective case-control study with cost analysis. Aliment Pharmacol Ther 16: , ) Daniele B, De Sio I, Izzo F, Capuano G, Andreana A, Mazzanti R, Aiello A, Vallone P, Fiore F, Gaeta GB, Perrone F, Pignata S, Gallo C. Hepatic resection and percutaneous ethanol injection as treatments of small hepatocellular carcinoma: a Cancer of the Liver Italian Program (CLIP 08) retrospective case-control study. J Clin Gastroenterol 36:63-67, ) Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less. Gut 54: , ) Shiina S, Teratani T, Obi S, Sato S, Tateishi R, Fujishima T, Ishikawa T, Koike Y, Yoshida H, Kawabe T, Omata M. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology 129: , ) Brunello F, Veltri A, Carucci P, Pagano E, Ciccone G, Moretto P, Sacchetto P, Gandini G, Rizzetto M. Radiofrequency ablation versus ethanol injection for early hepatocellular carcinoma: a randomized controlled trial. Scand J Gastroenterol 43: , ) Cho YK, Kim JK, Kim MY, Rhim H, Han JK. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology 49: , ) Matsui O, Kadoya M, Yoshikawa J, Gabata T, Takashima T, Demachi H. Subsegmental transcatheter arterial embolization for small hepatocellular carcinomas: local therapeutic effect and 5-year survival rate. Cancer Chemother Pharmacol 33(Suppl): S84-S88, ) Miyayama S, Matsui O, Yamashiro M, Ryu Y, Kaito K, Ozaki K, Takeda T, Yoneda N, Notsumata K, Toya D, Tanaka N, Mitsui T. Ultraselective transcatheter arterial chemoembolization with a 2-f tip microcatheter for small hepatocellular carcinomas: relationship between local tumor recurrence and visualization of the portal vein with iodized oil. J Vasc Interv Radiol 18: , ) Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359: , ) Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35: , ) Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37: , ) Camma C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P, Craxi A, Cottone M. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 224: 47-54, ) Lee HS, Kim KM, Yoon JH, Lee TR, Suh KS, Lee KU, Chung JW, Park JH, Kim CY. Therapeutic efficacy of transcatheter arterial chemoembolization as compared with hepatic resection in hepatocellular carcinoma patients with compensated liver function in a hepatitis B virus-endemic area: a prospective cohort study. J Clin Oncol 20: , ) Cheng BQ, Jia CQ, Liu CT, Fan W, Wang QL, Zhang ZL, Yi CH. Chemoembolization combined with radiofrequency ablation for patients with hepatocellular carcinoma larger than 3 cm: a randomized controlled trial. JAMA 299: , ) Chlebowski RT, Brzechwa-Adjukiewicz A, Cowden A, Block JB, Tong M, Chan KK. Doxorubicin (75 mg/m2) for hepatocellular carcinoma: clinical and pharmacokinetic results. Cancer Treat Rep 68: , ) Falkson G, MacIntyre JM, Moertel CG, Johnson LA, Scherman RC. Primary liver cancer: an Eastern Cooperative Oncology Group Trial. Cancer 54: , ) Melia WM, Johnson PJ, Williams R. Induction of remission in hepatocellular carcinoma: a comparison of VP 16 with adriamycin. Cancer 51: , ) Falkson G, Ryan LM, Johnson LA, Simson IW, Coetzer BJ, Carbone PP, Creech RH, Schutt AJ. A random phase II study of mitoxantrone and cisplatin in patients with hepatocellular carcinoma: an ECOG study. Cancer 60: , ) Patt YZ, Hassan MM, Lozano RD, Brown TD, Vauthey JN, Curley SA, Ellis LM. Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2b for treatment of hepatocellular carcinoma. J Clin Oncol 21: , ) Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA. BAY exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64: , ) Chang YS, Adnane J, Trail PA, Levy J, Henderson A, Xue D, Bortolon E, Ichetovkin M, Chen C, McNabola A, Wilkie D, Carter CA, Taylor IC, Lynch M, Wilhelm S. Sorafenib (BAY )

8 - 이준성. 간세포암종치료의최신지견 - inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol 59: , ) Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359: , ) Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10:25-34, ) Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Lathia C, Schwartz B, Taylor I, Moscovici M, Saltz LB. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24: , ) Park W, Lim DH, Paik SW, Koh KC, Choi MS, Park CK, Yoo BC, Lee JE, Kang MK, Park YJ, Nam HR, Ahn YC, Huh SJ. Local radiotherapy for patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 61: , ) Kim TH, Kim DY, Park JW, Kim YI, Kim SH, Park HS, Lee WJ, Park SJ, Hong EK, Kim CM. Three-dimensional conformal radiotherapy of unresectable hepatocellular carcinoma patients for whom transcatheter arterial chemoembolization was ineffective or unsuitable. Am J Clin Oncol 29: , ) Seong J, Lee IJ, Shim SJ, Lim do H, Kim TH, Kim JH, Jang HS, Kim MS, Chie EK, Nam TK, Lee HS, Han CJ. A multicenter retrospective cohort study of practice patterns and clinical outcome on radiotherapy for hepatocellular carcinoma in Korea. Liver Int 29: , ) Llovet JM, Bruix J. Novel advancements in the management of hepatocellular carcinoma in J Hepatol 48(Suppl 1):S20- S37,

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김범수 Analysis of Outcomes after Resection of Sarcomatous Hepatocellular Carcinoma Purpose: Sarcomatous hepatocellular carcinoma (HCC) is rare. Therefore, the clinicopathologic characteristics and prognosis