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1 The Korean Journal of Hepatology 2009 ; 15 : DOI: /kjhep 원발성간세포암종의늑골전이를경동맥화학색전술로치료한 1 예 고려대학교의과대학내과학교실 정영걸 연종은 김청호 이현정 이영선윤아일린 정은석 최종환 김지훈 변관수 bstract case of metastatic hepatocellular carcinoma of the rib, treated by transcatheter arterial chemoembolization Young Kul Jung, M.D., Jong Eun Yeon, M.D., Chung Ho Kim, M.D., Hyun Jung Lee, M.D., Young Sun Lee, M.D., Eileen L. Yoon, M.D., Jung Eun Suck, M.D., Jong Hwan Choi, M.D., Ji Hoon Kim, M.D., Kwan Soo yun, M.D. Department of Internal Medicine, Korea University of Medical College Guro Hospital, Seoul, Korea one is a common site of metastasis in patients with hepatocellular carcinoma (HCC). We report a rare case of rib metastasis from HCC treated by transcatheter arterial chemoembolization (TCE). 55-year-old man with liver cirrhosis presented with right lower chest pain. The diagnosis was an HCC with a bone metastasis in the right eighth rib. Intra-arterial injections of doxorubicin mixed with Lipiodol and Gelfoam particles were instituted through the right eighth intercostal artery. Computed tomography and a Tc 99 -labeled scan performed 2 months after the third TCE revealed no viable HCC in the right eighth rib. (Korean J Hepatol 2009; 15: ) 서론한국에서간세포암종은위암, 폐암에이어세번째로흔한악성종양이며, 전체악성종양의 16.5% 를차지한다. 1 최근에는간세포암종의진단및치료법이개선되어간세포암종의생존율이향상됨에 따라뼈를포함한간외전이의발견및치료의중요성이증가하고있다. 2 뼈는폐와부신다음으로간세포암종의전이가흔하게발생하는곳으로, 골전이를가진간세포암종환자에서약물로조절되지않는통증을동반하게되며이는삶의질과연관되는중요한문제이다. 1,2 골전이로인한통증의 Key words: Rib metastasis; Hepatocellular carcinoma; Transcatheter arterial chemoembolization Received December 10, 2008; revised pril 1, 2009; accepted pril 23, 2009 bbreviations: HCC, hepatocellular carcinoma; TCE, transcatheter arterial chemoembolization Corresponding author: Jong Eun Yeon, je_yeon@hotmail.com; Phone: 02) ; Fax: 02) 주소 : 서울시구로구구로 2 동, 고려대부속구로병원소화기내과간센터 ( 우 )

The Korean Journal of Hepatology : Vol. 15. No. 3. 2009 조절을위해서는방사선치료가일반적인고식적치료방법이며, 전이의양상에따라항암치료, 호르몬치료, 수술, 고주파열치료등이사용되기도한다.

가족력에서간염, 간종양의병력은없었다. 내원당시진찰소견에서혈압 110/60 mmhg, 맥박 90회 / 분, 호흡 20회 / 분, 체온 36.9 ㅊ 55세남자가 1개월전부터시작된우하흉부통증으로개인병원에서시행한초음파검사에서간종괴의심되어내원하였다.

C Figure 2. () Initial abdominal computed tomography (CT) scan showing contrast uptake of a mass (arrow) on segment 8 of the liver during the arterial phase.

2 The Korean Journal of Hepatology : Vol. 15. No 조절을위해서는방사선치료가일반적인고식적치료방법이며, 전이의양상에따라항암치료, 호르몬치료, 수술, 고주파열치료등이사용되기도한다. 3-6 간세포암종의늑골전이를경동맥화학색전술을이용해통증을조절하고병변을치료한예는극히일부에서보고되었으나, 국내의보고는거의없다. 7 이에저자들은원발성간세포암종의늑골전이를경동맥화학색전술로치료한 1예를경험하였기에문헌고찰과함께보고하는바이다. 사례 신음주력이있었다. 그외특별한수술이나외상의과거력은없었다. 가족력에서간염, 간종양의병력은없었다. 내원당시진찰소견에서혈압 110/60 mmhg, 맥박 90회 / 분, 호흡 20회 / 분, 체온 36.9 ㅊ 55세남자가 1개월전부터시작된우하흉부통증으로개인병원에서시행한초음파검사에서간종괴의심되어내원하였다. 환자는 20년전부터간이안좋다는얘기들었으나특별히병원에서추적관찰을받지는않았으며, 매일소주 1병을 30년간마 Figure 1. Initial rib X-ray showing bone destruction on the lateral arc of right eighth rib (arrows). C Figure 2. () Initial abdominal computed tomography (CT) scan showing contrast uptake of a mass (arrow) on segment 8 of the liver during the arterial phase. () bdominal CT scan showing contrast washout of in the mass during the delayed phase. (C) Initial abdominal CT scan showing a mass (arrowhead) on segment 6 of the liver and a soft-tissue lesion (asterisk) with bone destruction on the lateral arc of the right eighth rib

Young Kul Jung, et al. case of metastatic hepatocellular carcinoma of the rib, treated by TCE Figure 3. () Tc 99 -labeled scan showing increased uptake (arrow) at the lateral arc of the eighth rib.

두경부검진에서공막황달이나결막빈혈소견등은없었으며, 흉부검진에서국소압통이우측하부늑골에서관찰되었고, 복부검진에서간이나비장은만져지지않았다. 검사실소견에서일반혈액검사는백혈구 4,900/mm 3 ( 중성구 31.3%), 혈색소 14.6 g/dl, 혈소판 84,000/ mm 3 였다. 혈청생화학검사에서총단백 6.6 g/dl, 알부민 3.

3 Young Kul Jung, et al. case of metastatic hepatocellular carcinoma of the rib, treated by TCE Figure 3. () Tc 99 -labeled scan showing increased uptake (arrow) at the lateral arc of the eighth rib. () Positronemission tomography CT scan showing hypermetabolic activity lesions on the lateral arc of the eighth rib (arrowhead) and the right hepatic lobe. 였으며의식은명료하였다. 두경부검진에서공막황달이나결막빈혈소견등은없었으며, 흉부검진에서국소압통이우측하부늑골에서관찰되었고, 복부검진에서간이나비장은만져지지않았다. 검사실소견에서일반혈액검사는백혈구 4,900/mm 3 ( 중성구 31.3%), 혈색소 14.6 g/dl, 혈소판 84,000/ mm 3 였다. 혈청생화학검사에서총단백 6.6 g/dl, 알부민 3.2 g/dl, 아스파르테이트아미노전이효소 80 IU/L, 알라닌아미노전이효소 98 IU/L, 총빌리루빈 1.3 mg/dl, 알칼리포스파타제 133 IU/L, 감마 -글루타밀트랜스펩티다제 149 IU/L, 혈액요소질소 9.0 mg/dl, 크레아티닌 0.7 mg/dl, Na 138 mmol/l, K 4.0 mmol/l, Cl mmol/l, 프로트롬빈시간 13.0초 (international normalized ratio 1.14) 였다. 혈청간염바이러스표지자검사에서 형간염표면항원은음성이었고이에대한항체가양성이었으며, C 형간염바이러스 (HCV) 에대한항체가양성소견을보였다. 혈청 HCV RN는 222,000 IU/mL 였다. 혈청종양표지자검사에서알파태아단백 ng/ml, PIVK(protein induced by vitamin K absence)- II 79 mu/ml로각각상승되어있었다. 늑골촬영에서우측 8번늑골의골파괴소견이관찰되었고 ( 그림 1), 복부컴퓨터단층촬영에서간우엽에동맥기에조영증강되고, 지연기에저음영으로보이는각각 3.3 cm와 0.7 cm 크기의 2개의종괴가관 찰되었으며, 우측 8번늑골에골파괴를동반한연부조직음영이관찰되었다 ( 그림 2). 우측 8번늑골부위의정확한진단을위해뼈스캔과양자방출단층촬영을시행하였다. 뼈스캔에서우측 8번늑골에섭취증가를보였고 ( 그림 3), 양자방출단층촬영에서도우측 8번늑골과간우엽에대사항진을보이는부위가관찰되었다 ( 그림 3). 임상소견과영상소견으로간세포암종과이의늑골전이가의심되어혈관조영술을시행하였다. 혈관조영술에서우간동맥으로부터공급되는간우엽의과혈관성종괴와우측 8번늑간동맥으로부터공급되는늑골의종괴가관찰되어, doxorubicin 30 mg, 리피오돌 7 ml, 젤폼을혼합주입하여 1차경동맥화학색전술을시행하였다 ( 그림 4). 이후간내종괴와늑골병변의리피오돌침착이완전하지않아내원 6주후에 2차, 내원 3개월후에 3차경동맥화학색전술을시행하였다. 3차경동맥화학색전술이후 1개월과 2 개월에두차례의복부컴퓨터단층촬영을시행하였고, 우측 8번늑골종양부위에치밀한리피오돌침착이관찰되었다 ( 그림 5). 또한내원 4개월에시행한뼈스캔에서우측 8번늑골에병적섭취증가는관찰되지않았으며 ( 그림 5), 혈청종양표지자검사에서알파태아단백 30.8 ng/ml, PIVK-II 34 mu/ml로각각감소하였다. 이후환자는우하흉부통증없이외래추적관찰중이다

대한간학회지제 15 권제 3 호 2009 Figure 4. () Hepatic arteriography showing hypervascular masses supplied by the right hepatic artery.

() Follow-up abdominal CT scan obtained after the third TCE, showing compact lipiodol-uptake lesions in segment 6 of the liver

() The follow-up Tc 99 -labeled scan shows decreased activity (asterisk) on the lateral arc of the eighth rib.

1,2 그러나최근에간세포암종의진단및치료법이개선되어간세포암종의생존율이향상됨에따라뼈를포함한간외전이의진단및치료빈도가증가하고있다.

4 대한간학회지제 15 권제 3 호 2009 Figure 4. () Hepatic arteriography showing hypervascular masses supplied by the right hepatic artery. () Intercostal arteriography showing a mass (arrow) supplied by the right eighth intercostal artery. Figure 5. () Follow-up abdominal CT scan obtained after the third TCE, showing compact lipiodol-uptake lesions in segment 6 of the liver (arrow) and in the right eighth rib (arrowhead). () The follow-up Tc 99 -labeled scan shows decreased activity (asterisk) on the lateral arc of the eighth rib. 고찰과거에는간세포암종환자의생존율이극히낮아전이에의한증상의발현이드물었기때문에진행된간세포암종의간외전이에대한임상의사들의관심이적은편이었다. 1,2 그러나최근에간세포암종의진단및치료법이개선되어간세포암종의생존율이향상됨에따라뼈를포함한간외전이의진단및치료빈도가증가하고있다. 2 뼈는폐와부신다음으로간세포암종의전이가흔하게발생하는곳으로, 간세포암종환자의부검시 3~20% 에서골전이가발견된다. 1-3 간세포암종의골전이부 위는척추가가장흔하며, 이어골반, 늑골, 장골의순으로전이가많이발생한다. 1 간세포암종의골전이는문정맥혈전이나문맥고혈압과동반된우회로인간문맥-척추정맥복합체를통해발생한다고알려져있다. 2 간세포암종의골전이진단은일반적으로뼈스캔을통해서이루어지며, 단순엑스선촬영, 컴퓨터단층촬영, 자기공명영상, 양자방출단층촬영등도진단에도움이된다. 8,9 골전이는골대사에영향을주어용해성, 경화성, 혹은혼합된형태를가지게되는데, 간세포암종의골전이는대부분골파괴를동반한골용해성병변으로나타나게된다. 골파괴를

5 정영걸외 9 인. 원발성간세포암종의늑골전이를경동맥화학색전술로치료한 1 예 동반해서골외로확장하는종괴형태가간세포암종골전이의특징적인모양이다. 8 간세포암종환자의골전이에대한치료목표는통증을없애고안정화시키는것이다. 5 약물로조절되지않는통증의조절을위해방사선치료가흔히사용되지만단독전이의경우수술치료가고려되기도한다. 1,4,5 방사선치료는국소종양성장을억제하며종양수축을유도하고, 주위조직의압력을감소시키는효과가있으며, 골전이환자의 80% 정도에서통증조절에효과가있는것으로알려져있다. 10 이외에도간세포암종골전이의치료에항암치료, 호르몬치료, 고주파열치료, 시멘트주입성형술등이사용된다. 4-6,11 간세포암종의치료에널리사용되는경동맥화학색전술은종양의주요동맥을차단해서종양의허혈성괴사를유발하는방법이다. 12 경동맥화학색전술을이용해간세포암종의늑골전이병변을치료한예는국외에 Fukushima 등에의해 1예가보고되었으나, 국내에보고된적은없다. 7 Fukushima 등에의해보고된사례와같이본사례에서도혈관조영술에서늑간동맥으로부터혈액을공급받는종괴가관찰되어이를경동맥화학색전술로치료하였다. 치료후비교적단기간의추적관찰중에있지만늑골전이및간내병변은안정적인상태로통증및삶의질이향상되었다. 따라서원발성간세포암종의진단이나치료과정에서늑골전이가발견되면혈관조영술을시행하여늑간동맥이나병변을공급하는동맥을선택하여경동맥화학색전술로치료하는방법도고려해볼수있겠다. 요약뼈는간세포암종의전이장소중세번째로흔하게발생하는곳으로이에대한치료는제한적이다. 55세남자환자가우하흉부통증으로내원하여원발성간세포암종과우측 8번늑골전이로진단되었다. 혈관조영술에서우측 8번늑간동맥으로부터공급되는늑골의종양이관찰되어총 3회의경동맥화학색전술을시행하였고, 이후두차례의컴퓨터단층촬영에서는우측 8번늑골종양부위에치밀 한리피오돌침착이관찰되었으며, 통증은소실되었다. 이에저자들은경동맥화학색전술로치료한원발성간세포암종환자의늑골전이 1예를경험하였기에문헌고찰과함께보고하는바이다. 색인단어 : 늑골전이, 간세포암종, 경동맥화학색전술 참고문헌 1. Kim SU, Kim DY, Park JY, hn SH, Nah HJ, Chon CY, et al. Hepatocellular carcinoma presenting with bone metastasis: clinical characteristics and prognostic factors. J Cancer Res Clin Oncol 2008;134: ttili VS, abu KG, Lokanatha D, apsy PP, Ramachandra C, Rajshekar H. one metastasis in hepatocellular carcinoma: need for reappraisal of treatment. J Cancer Res Ther 2008;4: Okazaki N, Yoshino M, Yoshida T, Hirohashi S, Kishi K, Shimosato Y. one metastasis in hepatocellular carcinoma. Cancer 1985;55: Nakamura N, Igaki H, Yamashita H, Shiraishi K, Tago M, Sasano N, et al. retrospective study of radiotherapy for spinal bone metastases from hepatocellular carcinoma. Jpn J Clin Oncol 2007;37: Seong J, Koom WS, Park HC. Radiotherapy for painful bone metastases from hepatocellular carcinoma. Liver Int 2005;25: Maruyama M, sano T, Kenmochi T, Kainuma O, Iwasaki K, Miyauchi H, et al. Radiofrequency ablation therapy for bone metastasis from hepatocellular carcinoma: case report. nticancer Res 2003;23: Fukushima H, Hirai K, Shimada M, oki Y, Iwai I, Yamashita K, et al. Hepatocellular carcinoma with a complete remission of bone metastasis achieved by arterial chemotherapy. Gan No Rinsho 1990;36: Fukutomi M, Yokota M, Chuman H, Harada H, Zaitsu Y, Funakoshi, et al. Increased incidence of bone metastases in hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2001;13: Yoon KT, Kim JK, Kim do Y, hn SH, Lee JD, Yun M, et al. Role of 18F-fluorodeoxyglucose positron emission tomography in detecting extrahepatic metastasis in pretreatment staging of hepatocellular carcinoma. Oncology 2007;72(Suppl 1): Porter T, Fontanesi J. Palliative irradiation for bone metastasis--a new paradigm. Int J Radiat Oncol iol Phys 1994;29: Kodama H, ikata H, Uka K, Takaki S, Mori N, Waki K, et al. Efficacy of percutaneous cementoplasty for bone metastasis from hepatocellular carcinoma. Oncology 2007; 72: Lee KH, Sung K, Lee DY, Park SJ, Kim KW, Yu JS. Transcatheter arterial chemoembolization for hepatocellular carcinoma: anatomic and hemodynamic considerations in the hepatic artery and portal vein. Radiographics 2002;22:

김범수

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