The Korean Journal of Hepatology 2009 ; 15 : 90-95 DOI: 10.3350/kjhep.2009.15.1.90 종양의간문맥침범을경피적에탄올주입술로효과적으로극복한진행성간세포암종 1 예 고려대학교의과대학내과학교실, 영상의학교실 1 윤익 임형준 김진남 박선민 김정한이승화 1 정환훈 1 이홍식 이상우 최재현 Abstract A case of advanced hepatocellular carcinoma with portal vein tumor invasion controlled by percutaneous ethanol injection therapy Ik Yoon, M.D., Hyung Joon Yim, M.D., Jin Nam Kim, M.D., Sun Min Park, M.D., Jeong Han Kim, M.D., Seung Hwa Lee, M.D. 1, Hwan Hoon Chung, M.D. 1, Hong Sik Lee, M.D., Sang Woo Lee, M.D., Jai Hyun Choi, M.D. Department of Internal Medicine and 1 Radiology, Korea University college of Medicine, Seoul, Korea Portal vein invasion is a grave prognostic indicator in the setting of hepatocellular carcinoma (HCC). There is currently no effective method for preventing the invasion of HCC into the main portal vein. We report here a case of advanced HCC with portal vein tumor thrombosis that was effectively treated with percutaneous ethanol injection (PEI), having previously enabled subsequent successive transarterial chemoembolization (TACE). A 60-year-old male patient was diagnosed with a huge HCC, based on computed tomography and angiographic findings. Despite two sessions of TACE, the tumor invaded the right portal vein. PEI was performed on the malignant portal vein thrombosis, and three sessions thereof reduced the extent of tumor thrombi in the portal vein. Successive TACEs were performed to treat the HCC in the hepatic parenchyma. The patient was still living 19 months after the first PEI with no evidence of tumor recurrence, and his liver function remained well preserved. (Korean J Hepatol 2008;15:90-95) Key words: Carcinoma, Hepatocellular; Portal vein tumor thrombosis; Transarterial chemoembolization; Percutaneous ethanol injection therapy Received June 9, 2008; revised December 3, 2008; accepted December 10, 2008 Abbreviations: CT, computed tomography; CTAP, CT during arterio-portography; CTHA, CT during hepatic arteriography; PEI, percutaneous ethanol injection; TACE, transarterial chemoembolization. Corresponding author: Hyung Joon Yim, E-mail: gudwns21@medimail.co.kr; Phone: 031) 412-6565; Fax: 031) 412-5582 주소 : 경기도안산시단원구고잔 1 동 516 번지, 고려대학교안산병원소화기내과 ( 우 )425-707 This study was supported by the Ministry of Health and Welfare, Republic of Korea (grant A050021). - 90 -
Ik Yoon, et al. Percutaneous ethanol injection therapy for portal vein tumor invasion 서론최근영상학기법의발전과함께고위험군에대한적절한선별검사가시행되면서간세포암종 (hepatocellular carcinoma, HCC) 의조기진단이가능하게되었고이에따라간이식, 간절제술및국소치료를포함한근치적치료후간세포암종환자들의 5년생존율은 40~75% 에이르게되었다. 1 그러나이러한근치적치료는아직도간세포암종으로진단받은환자의 30% 미만에서만가능할뿐이고여전히대다수의환자들은근치적치료가불가능한진행된병기에서진단되고있다. 2 진행된간세포암종은대부분근치목적의수술치료가불가능하며, 예후가불량하여대부분의환자가 6개월이내에사망한다. 특히주문맥혈전을동반하는경우, 그예후는더욱나빠서적절한치료를받지않을경우생존중앙값이 2.7개월정도로알려져있다. 3 따라서간문맥혈전을동반한간세포암종의경우종양혈전이주문맥을침범하지않도록적극적인치료를시행하여야하나아직까지이를위한표준방법이없는실정이다. 저자들은간문맥분지혈전을동반한간세포암종환자에서종양혈전내에경피적에탄올주입술 (percutaneous ethanol injection, 이하 PEI) 을시행함으로써주문맥으로의종양혈전의침범을효과적으로차단하고, 지속적으로경동맥항암화학색전술 (transarterial chemoembolization, 이하 TACE) 을실시하여재발또는간기능검사의악화없이임상적완해의소견을보인사례를경험하였기에이를보고한다. 사례 60세남자가우상복부통증으로내원하였다. 환자는고혈압, 당뇨병등의병력이나만성 B형또는 C형간염의병력은없었으나주 4~5회씩소주반병을 30년간음주한기왕력이있었다. 흡연은하루한갑씩을 30년간하였다. 내원시신체검진에서환자의의식은명료하였고활력징후는정상이었으 며, 결막의창백함이나공막의황달소견은관찰되지않았다. 복부는부드럽고편평하였으며, 간, 비장은촉지되지않았고, 압통이나반발통도없었다. 이동탁음이나하지의부종도관찰되지않았다. 혈구검사에서백혈구 5,820/mm 3, 혈색소 15.9 g/dl, 혈소판 233,000/mm 3 였고, 혈청생화학검사에서 aspartate aminotransferase 56 IU/L, alanine aminotransferase 28 IU/L, alkaline phosphatase 61 IU/L, gamma-glutamyl transpeptidase 189 IU/L, 총단백 7.5 g/dl, 알부민 4.6 g/dl, 총빌리루빈 0.9 mg/dl였고프로트롬빈시간은 13.5초 (INR 1.18) 였으며, 혈청알파태아단백은 102 ng/ml였다. B형간염표면항원과이에대한항체는모두음성이었으나 core 항원에대한 IgG형항체가양성이었다. C 형간염바이러스항체는음성이었다. 복부나선형전산화단층촬영 (computed tomography, CT) 에서는간의 4번분절과 6번분절에각각 65 32 mm, 64 31 mm의거대한 2개의종괴가관찰되었다. 이병변은조영제투여후동맥기에서조영증강을보이고문맥기에서는조영감쇠소견을보였다. 최초영상검사에서간문맥의혈전이나간외전이를시사하는소견은없었다. 이어서혈관조영술을실시하였고간동맥조영시간우엽에고혈관성종괴가관찰되었으며, CT동맥조영술 (CT during hepatic arteriography, 이하 CTHA) 에서고음영으로조영증강이되고, CT문맥조영술 (CT during arterioportography, 이하 CTAP) 에서저음영으로감쇠되는소견을보였다 ( 그림 1). 위와같은검사실소견및영상소견을바탕으로간세포암종으로최종진단하였고, 병변에대하여 doxorubincin 50 mg과 lipiodol 및 gelfoam을이용하여 TACE를시행하였다. 환자는 TACE 후특별한합병증은없었으며 2개월후혈청알파태아단백은 11 ng/ml로감소하였다. 그러나 TACE 최초시행후 3개월째혈청알파태아단백은 21 ng/ml로다시상승하였으며, TACE를추가시행하기위하여실시한혈관조영술및전산화단층촬영에서우엽에아직괴사되지않은암종이관찰되고, 추가로우측간문맥내에혈전이발견되었다. 이우간문맥내혈전은간 - 91 -
대한간학회지 제 15 권 제 1 호 2009 A B C D E F Figure 1. Two hepatic masses suggestive of hepatocellular carcinoma evident in segments 4 and 6 of the liver. These masses are hyperattenuating on computed tomography (CT) during hepatic arteriography (CTHA) (A, B) and hypoattenuating on CT during arterioportography (CTAP) (C, D). Angiography revealed hypervascular masses (E, F). A B Figure 2. CTHA and CTAP showing expansive thrombosis in the right portal vein (arrow). The thrombus is hyperattenuating on CTHA (A) and hypoattenuating on CTAP (B). These findings suggest invasion of the hepatocellular carcinoma into the portal vein. 실질 내에서 관찰되는 간세포암종과 마찬가지로 대해 추가적인 TACE를 실시하였고, 이틀 후 종양 CTHA에서 고음영으로 조영증강이 되고, CTAP에 혈전을 괴사시키기 위해 초음파 유도하에 PEI를 서 저음영으로 감쇠되는 소견을 보였으며, 또한 간 시행하여 문맥혈전에 직접 에탄올 9 cc를 주입하 문맥이 혈전에 의해 밖으로 팽창되는 양상을 보여 였다. 이후 간실질에 남아있는 종양에 대해 TACE 종양혈전으로 진단하였다(그림 2). 주간문맥으로의 를 계속 시행하였고 문맥 내 종양혈전에 대하여는 침범 소견은 아직 관찰되지 않아 간내 생존 종양에 PEI를 한 달 간격으로 2차례 추가 시행하였다. 3회 - 92 -
윤익외 9 인. 간암문맥침범의경피적에탄올주입치료 A B C D Figure 3. After transarterial chemoembolization, dense lipiodol uptake is noted in the main masses (A, B). After percutaneous ethanol injection therapy under CT guidance (arrow) (C), the extent of the tumor thrombosis in the portal vein has decreased, showing dense uptake of lipiodol (arrow) (D). 의간문맥내종양혈전에대한 PEI 후추적검사한복부전산화단층촬영및 CTHA와 CTAP에서간내종양은점차괴사되는소견을보였고, 문맥혈전은더이상주문맥방향으로침범하는소견이없이에탄올과함께주입한리피오돌이간문맥내에밀도있게섭취되어있는소견을보였으며간문맥의직경도 PEI 전 22 mm에서시술후에는 18 mm로감소하였다 ( 그림 3). 따라서이후에도지속하여반복적인 TACE가가능하였다. 경과도중 TACE로완전괴사가어려웠던간내종양부분은고주파열치료를추가하였고, 현재까지총 19회의 TACE를정기적으로시행하여영상검사로관찰되는생존종양없이혈청알파태아단백은 5 ng/ml로감소된상태로유지되고있다. 고찰 TACE는근치적치료가불가능한진행성간세포암종의고식적치료법으로가장널리시행되고있으며, 최근몇몇무작위대조군연구를통해보존적치료보다유의한생존율의향상을보인다는사실이증명되었다. 4,5 또한 TACE 단독치료보다는 TACE와 PEI와같은국소치료법의병합요법이생존율의증가를보여준다는연구결과들이발표되면서 TACE와의병합치료의활용범위가점차넓어지고있다. 6-10 간세포암종의문맥침범은가장중요한예후인자중의하나로대개 TACE 시행시간부전의위험도가증가하기때문에 TACE의적응증에서제외되는것이일반적이다. 최근주문맥종양혈전을동반한진행성간세포암종에서 5-fluorouracil 과 - 93 -
The Korean Journal of Hepatology : Vol. 15. No. 1. 2009 cisplatin을병합한주입식항암화학치료를하거나방사선요법을추가하여치료하기도하나일단종양이주문맥을침범한후의생존율은아직도매우불량하다. 11-15 따라서생존율의향상이널리인정되는 TACE 를가능하면좀더유지하고자하는노력이지금까지있어왔다. 국내에서명등도주간문맥혈전을동반한간세포암종환자에서간기능이잘보존되어있고문맥주위로측부혈관의발달이좋은경우 TACE가간부전의위험을높이지않으며, 일부에서는생존율의증가도기대할수있음을보고하였다. 16 주간문맥이하의간문맥의혈전이동반되어있는경우는간기능이허락한다면문맥주위로측부혈관발달이좋지않아도 TACE가가능하며, 17 일부국내연구자들도주간문맥이하의간문맥의혈전이동반되어있는경우 TACE 만으로도진행된간세포암종에서뛰어난효과를나타냈다고보고하고있다. 18 그러나이러한경우에도간문맥내종양혈전이점차진행하여주문맥을침범하게될경우더이상의 TACE를시행하기는어려운것이일반적이다. 17 따라서간문맥내종양혈전이주문맥을침범하기전이라면보다적극적으로주문맥침범을막기위한대책을세우는것이필요하다. 과거외국에서암세포의침윤이광범위하게일어나있지않다면간문맥내종양혈전도 PEI의적용이될수있다는보고가있었다. 19 또한일부에서는원발암을수술로제거한뒤에간문맥혈전을동반하여재발한간세포암종에대해 TACE와간문맥혈전에대한 PEI를시도하여치료에성공한증례를보고하기도하였다. 20 따라서이러한보고에서처럼간문맥내종양혈전이동반된경우 TACE 단독치료보다는 PEI를병합하는것이더효과적일수있겠다. 그러나시술이상대적으로어렵고, 화학적혈전의발생이나담도계의협착등과같은합병증발생의가능성을이유로문맥내암종에대하여 PEI를실제로적용하는경우는국내에서흔하지않았으며, 따라서성공적인치료결과를보여준국내보고역시극히드물다. 본사례에서환자는진행된간세포암종으로주 문맥이하의첫번째분지인우측간문맥에서종양혈전이동반되었으나반복적으로문맥혈전내에 PEI를실시하여주문맥침범을막음으로써지속적인 TACE 시술을가능하게하였으며, 간부전이나담도협착등의합병증없이임상적완해에이르러최초진단후 21개월이지난현재까지재발없이생존하였다. 따라서간문맥혈전이동반된경우에혈전에대해 PEI와같은국소치료를배제하지말고본예와같이적극적인치료를시도할경우 TACE만으로얻을수있는효과외에문맥내종양성장억제로인한부가적인좋은결과를얻을수있을것으로판단되므로문헌고찰과함께보고한다. 요약주문맥혈전을동반하는간세포암종의예후는매우불량하므로진행성간세포암종환자에서간문맥혈전이주문맥을침범하지않도록적극적인치료를시행하여야하나아직까지이를위한적절한방법이없는실정이다. 저자들은간문맥분지혈전을동반한간세포암종환자에서간문맥종양혈전내에경피적에탄올주입술을시행하여주문맥으로의종양혈전의침범을효과적으로막음으로써지속적인경동맥항암화학색전술을가능하게하여재발또는간기능의악화없이임상적완해의소견을보인사례를경험하였다. 환자는간세포암종으로경동맥화학색전술을받은 60세의남자환자였으며, 치료도중우간문맥내종양혈전이발생하였으나주간문맥으로의침범소견은없었다. 이에 3회에걸쳐초음파유도하에문맥혈전내에경피적에탄올주입술을시행하였으며, 이후문맥혈전은더이상주문맥방향으로침범하는소견이없었으며따라서지속적인경동맥화학색전술이가능하였다. 현재까지총 19회의경동맥화학색전술을정기적으로시행하여영상검사로관찰되는생존종양없이환자는대상성간기능상태를유지하고있다. 따라서간문맥혈전이동반된경우에혈전내에경피적에탄올주입술과같은국소치료를배 - 94 -
Ik Yoon, et al. Percutaneous ethanol injection therapy for portal vein tumor invasion 제하지말고본예와같이적극적인치료를시도할경우문맥내종양성장억제로인한부가적인좋은결과를얻을수있을것으로판단한다. 색인단어 : 간세포암종, 간문맥종양혈전, 경동맥화학색전술, 경피적에탄올주입술 참고문헌 1. Liang TJ, Jeffers LJ, Reddy KR, De Medina M, Parker IT, Cheinquer H, et al. Viral pathogenesis of hepatocellular carcinoma in the United States. Hepatology 1993;18:1326-1333. 2. Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 2002;35: 519-524. 3. Llovet JM, Bustamante J, Castells A, Vilana R, Ayuso Mdel C, Sala M, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology 1999;29: 62-67. 4. Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002;359:1734-1739. 5. Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002;35:1164-1171. 6. Becker G, Soezgen T, Olschewski M, Laubenberger J, Blum HE, Allgaier HP. Combined TACE and PEI for palliative treatment of unresectable hepatocellular carcinoma. World J Gastroenterol 2005;11;6104-6109. 7. Dettmer A, Kirchhoff TD, Gebel M, Zender L, Malek NP, Panning B, et al. Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma. World J Gastroenterol 2006;12: 3707-3715. 8. Qian J, Feng GS, Vogl T. Combined interventional therapies of hepatocellular carcinoma. World J Gastroenterol 2003;9:1885-1891. 9. Cho JS. Interventional treatment of hepatocellular carcinoma: transcatheter arterial chemoembolization and percutaneous ethanol injection. Korean J Hepatol 1998;4:91-108. 10. Guan YS, Liu Y. Interventional treatments for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2006;5: 495-500. 11. Ando E, Tanaka M, Yamashita F, Kuromatsu R, Yutani S, Fukumori K, et al. Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases. Cancer 2002;95: 588-595. 12. Lai YC, Shih CY, Jeng CM, Yang SS, Hu JT, Sung YC, et al. Hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal vein tumor thrombosis. World J Gastroenterol 2003;9:2666-2670. 13. Song HG, Lee HC, Song BC, Chung YH, Lee YS, Yoon HK, et al. Efficacy of repeated arterial infusion of cisplatin and 5-fluorouracil via a percutaneously implantable port system in advanced hepatocellular carcinoma. Korean J Hepatol 2001;7:61-67. 14. Ahn SH, Han KH, Youn YH, Kim MH, Song KH, Lee KS, et al. Treatment outcome and prognostic factors in patients with advanced hepatocellular carcinoma (TNM Stage IVa) according to anticancer drugs of transhepatic arterial chemoinfusion. Korean J Hepatol 2000;6:456-467. 15. Kim JS, Han KH, Lee DY, Seong JS, Youn YH, Cheong JY, et al. Concurrent chemo-radiation therapy for advanced hepatocellular carcinoma with portal vein thrombosis. Korean J Hepatol 2002;8:71-79. 16. Myung SJ, Yoon JH, Gwak GY, Shin CM, Ahn DW, Yu SJ, et al. A case of infiltrative hepatocellular carcinoma with main portal vein tumor thrombosis successfully treated by transarterial chemoembolization. Korean J Hepatol 2006;12:107-111. 17. Fujii T, Takayasu K, Muramatsu Y, Moriyama N, Wakao F, Kosuqe T, et al. Hepatocellular carcinoma with portal tumor thrombus: analysis of factors determining prognosis. Jpn J Clin Oncol. 1993;23:105-109. 18. Chung JW, Park JH, Han JK, Choi BI, Han MC. Hepatocellular carcinoma and portal vein invasion: results of treatment with transcatherter oily chemoembolization. AJR Am J Roentgenol 1995;165:315-321. 19. Livraghi T, Grigioni W, Mazziotti A, Sangalli G, Vettori C, Percutaneous alcohol injection of portal thrombosis in hepatocellular carcinoma: a new possible treatment. Tumori 1990;76:394-397. 20. Chan MK, Kwok PC, Chan SC, Lam TW, Lo KK, Lam CL. Percutaneous ethanol injection as a possible curative treatment for malignant portal vein thrombosis in hepatocellular carcinoma. Cardiovasc Intervent Radiol 1999;22: 326-328. - 95 -