Case Report Ewha Med J 2013;36(1):62-66 pissn 2234-3180 / eissn 2234-2591 http://dx.doi.org/10.12771/emj.2013.36.1.62 간세포암종에대한간동맥화학색전술후발생한급성호흡곤란증후군 조윤원ㆍ이정미ㆍ최자윤ㆍ유동훈ㆍ차라리ㆍ오혜원ㆍ김홍준ㆍ민현주ㆍ김현진ㆍ정운태ㆍ이옥재하창윤ㆍ이선영 1 경상대학교의학전문대학원내과학교실, 1 이화여자대학교의학전문대학원내과학교실 Acute Respiratory Distress Syndrome after Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Case Report Yun Won Jo, Jeong-Mi Lee, Ja Yoon Choi, Dong-Hoon Lew, Ra Ri Cha, Hye Won Oh, Hong-Jun Kim, Hyun Ju Min, Hyun Jin Kim, Woon-Tae Jung, Ok-Jae Lee, Chang Yoon Ha, Sun Young Yi 1 Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, 1 Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea Transcatheter arterial chemoembolization (TACE) has become an effective alternative treatment strategy for patients with inoperable hepatocellular carcinoma (HCC). Although TACE is relatively safe, acute respiratory distress syndrome associated with pulmonary lipiodol embolism is a rare and potentially fatal complication. We report a rare case of acute respiratory distress syndrome after TACE for inoperable HCC. A 75-year-old man, with huge HCC in right lobe, was treated by TACE for the first time. Seven hours after uneventful TACE procedure, he felt dyspneic and his oxygen saturation recorded by pulse oximetry (SpO 2) fell to 80% despite of applying non-rebreathing mask. He underwent mechanical ventilation with a protective ventilatory strategy. We experienced a case of acute respiratory distress syndrome after TACE for HCC. (Ewha Med J 2013;36(1):62-66) Key Words: Acute respiratory distress syndrome; Chemoembolization; Hepatocellular carcinoma 서론 간동맥화학색전술 (transcatheter arterial chemoembolization) 은수술이불가능한간세포암종에널리적용되는비수술적치료법이다 [1-3]. 간세포암의치료는수술적절제가가장좋은방법이지만대부분의환 Received: September 3, 2012, Accepted: October 8, 2012 Corresponding author: Chang Yoon Ha, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, 79 Gangnam-ro, Jinju 660-702, Korea Tel: 82-55-750-8057, Fax: 82-55-758-9122 E-mail: singrum@daum.net 자에서간경변을동반하고있고, 진행된상태에서발견되는경우가많아 [4] 비수술적치료법, 특히간동맥화학색전술이시행되는경우가많다. 간동맥화학색전술은약 5% 정도에서합병증이보고된다 [5,6]. 대부분의합병증은복통및발열, 오심, 구토와같은비특이적인증상과일시적인간기능의변화로나타나며대부분 3 4일이내에회복된다 [4]. 그러나급성간부전, 간경색및농양, 담낭과비장경색, 급성위장관출혈및폐색전증등과같은심각한합병증이유발할수도있으며 [4] 합병증으로인한사망률은약 1% 이내이다 [6]. 간세포암종환자에서발생한폐색전증은대부분의 62
Jo YW, et al: ARDS after Transcatheter Arterial Chemoembolization 경우간동맥화학색전술도중리피오돌 (lipiodol) 투여로인한지질폐렴이원인인것으로알려져있다 [7]. 리피오돌로인한폐색전증은 1990년 Samejima 등 [8] 에의해처음보고되었으며, 국내에서는 1995년 Cho 등 [9] 에의해처음보고되었다. 이러한리피오돌폐색전증은대부분보존적치료로치유되는것으로알려져있고, 간동맥화학색전술후리피오돌로인한폐색전증과관련된급성호흡곤란증후군은매우드물게발생하는것으로알려져있다. 이에저자등은 75세남자환자에서간세포암치료를위해시행한간동맥화학색전술후약 7시간후에발생한급성호흡곤란증후군 1 예를경험하였기에문헌과함께보고하는바이다. 증례 75세남자가내원 3주전부터피로감이있어타병원에서혈액검사시행후간기능이상소견을보여본원으로전원되었다. 과거력상한센병외특이질환은없었으며사회력상한번에소주 1병씩한달에 2 3번마시는음주력및 15갑년의흡연력이있었다. 활력징후는안정적이었으며이학적검사에서공막의황달소견이나결막의빈혈소견등은없었으며복부진찰에서간비대소견이관찰되었다. 말초혈액검사에서혈색소 12.2 g/dl, 헤마토크리트 36%, 백혈구 7,240/mm 3, 혈소판 237,000/mm 3 였고, 혈청학적검사에서는총단백 6.8 g/dl, 알부민 3.9 g/dl, 총콜레스테롤 192 mg/dl, AST 47 IU/L, ALT 69 IU/L, Alkaline phospatase 103 IU/L, 총빌리루빈 0.85 mg/dl, 직접빌리루빈 0.12 mg/dl이었다. B형간염표지인자는 HBsAg( ), HBsAb( ) 이었으며 C형간염항체는음성이었다. 알파태아단백은 255.10 ng/ml, 프로트롬빈시간은 13.2초 (98%) 였다. 흉부X-선촬영에서양폐야에망상형음영 (reticular opacity) 과벌집모양 (honeycombing) 변화소견을보여특발성폐섬유증이의심되었다. 복부전산화단층촬영에서간우엽에 13 11 cm 크기의경계가명확한저음영의종괴가관찰되었다 (Fig. 1). 임상적소견및영상의학적검사에서간세포암이진단되었으나수술이불가능하여간동맥화학색전술을시행하였다. 간동맥혈관조영술에서간우엽에우측간동맥과위십이지장동맥에서공급받고있는거대종양병변이관찰되었다. 선별된종양간동맥으로 adriamycin 50 mg과리피오돌 30 ml를섞어서서히주입하였으며이어젤폼입자를주입하여간동맥화학색전술을시행하였다 (Fig. 2). 간동맥화학색전술 7시간경과후환자는갑작스런호흡곤란을호소하였다. 활력징후는혈압 130/80 mmhg, 맥박 116회 / 분, 호흡수 36회 / 분, 산소포화도는 71% 까지감소하여산소마스크를통해산소 10 L/ 분적용하였다. 동맥혈가스검사에서 PaO 2 58%, 산소포화도 91.6% 였으며흉부 X-선촬영에서양측폐에전반적인간유리음영 (ground glass opacity) 이증가하였다 (Fig. 3). 이학적검사에서양측폐에심한수포음이청진되었다. 심초음파및 D-dimer는정상소견이었다. 간동맥 Fig. 1. Abdomen computed tomography showes huge hepatocellular carcinoma involving right hepatic lobe. Fig. 2. Common hepatic artery angiography showes huge hypervascular tumor staining in right hepatic lobe. THE EWHA MEDICAL JOURNAL 63
Ewha Med J Vol. 36, No. 1, 2013 Fig. 3. (A) Initial chest x-ray shows reticular opacity in both lower lobes. (B) chest x-ray after TACE shows transcatheter arterial chemoembolization (TACE) multifocal bilateral patchy ground glass opacity. 촬영에서도양폐야의침윤이호전되어기관내삽관 6일후기계호흡이탈을시행하였다. 그러나이후 3일뒤환자는다시호흡곤란을호소하였으며흉부 X-선촬영에서악화소견을보여기계호흡을적용하고중환자실치료를시행하였다. 그후약 4주간스테로이드및경험적항균제치료와함께기계호흡기치료를유지했으나환자의임상증세및흉부 X-선촬영에서악화소견보이며호흡부전진행하여간동맥화학색전술시행후 40일째사망하였다. 고찰 Fig. 4. Chest computed tomography shows multifocal crazy paving pattern and interlobular septal thickening in both lung, and honeycombing in both lower lobes. 화학색전술시행 1일경과후환자의호흡부전이진행하여기관내삽관및기계호흡을적용하였다. 환자의동맥혈가스검사에서 PaO 2/FiO 2 가 200 이하였으며, 흉부전산화단층촬영에서소엽간중격이두꺼워져있고소엽중심에는간유리음영이보이는불규칙한돌조각보도모양 (crazy paving pattern) 을보여급성호흡부전증후군으로진단할수있었으며, 리이오돌이나지방이관찰되지는않았다 (Fig. 4). Methylprednisolone 60 mg을 4시간간격으로정맥주사하면서경험적항생제와이뇨제투여및호기말양압 (positiveend-expiratory pressure) 을이용한기계호흡치료를시행하였다. 기계호흡치료 2일째부터 PaO 2/FiO 2 가 250 이상으로호전되었으며흉부 X-선 간동맥화학색전술은종양의크기가크고, 상당히진행된간세포암에서시행할수있는치료법으로간동맥의폐색을유발하여간종양의허헐성괴사를초래한다. 이러한간동맥화학색전술과관련하여증상을동반하는폐합병증이발생하는경우는매우드문것으로알려져있다 [10]. 연구에따르면간동맥화학색전술을시행받은 23% 의환자에서호흡기증상을동반하지않는관류폐스캔이상소견이관찰되었고 0.05 1.8% 의환자에서는폐색전증의증상을동반하였다 [7,11]. 간세포암환자에서발생한폐색전증은종양자체에의한폐색전증도보고되어있으나 [12,13] 대부분은간동맥화학색전술도중과량의리피오돌투여로인한폐색전증이주된원인으로알려져있다. 간동맥화학색전술후발생한폐지질색전증은 1990년 Samejima 등 [8] 에의해처음보고되었다. 75세의남자환자가간세포암으로리피오돌 8 ml과 adriamycin 40 mg 혼합물로간동맥화학색전술시행후 30분후에폐부종이나타났으며저자들은동-정맥루 64 THE EWHA MEDICAL JOURNAL
Jo YW, et al: ARDS after Transcatheter Arterial Chemoembolization 를통한과량의 adriamycin이폐동맥으로의유입이원인이라고생각했다 [8]. 이후 1995년 Chung 등 [7] 에의해간동맥화학색전술이후생기는폐합병증에대한연구가이루어졌는데, 간동맥화학색전술을받은 336명의환자중 6명에게서폐동맥지질색전증이보고되었고, 모두적어도 20 ml 이상의리피오돌이주입된경우였다. 이들의증상은주로기침, 객혈, 호흡곤란이었으며주로시술이후 2 5일사이에나타났다. 단순흉부 X선촬영에서는양폐의미만성침윤소견을보였다. 이연구에따르면저자들은폐동맥지질색전증의원인을 20 ml 이상의리피오돌주입으로결론지었다. 간동맥화학색전술이후생기는폐동맥지질색전증의기전은아직불명확하나간동맥으로의리피오돌의주입후동-정맥루를통하거나정상적인간혈류를통해서리피오돌이폐로들어가서미세색전의분해과정에서생기는고농도의 unbound free fatty acids가폐모세혈관의누출과폐부종을초래한다는것이라는가설이널리알려져있다 [7]. 간동맥화학색전술이후생기는폐동맥지질색전증의위험인자는리피오돌양이외에도리피오돌주입방법 [7,14], 리피오돌의간종양내의잔류정도 [7], 동-정맥루여부 [7,14], 하부가로막동맥 (inferior phrenic artery) 색전술 [14] 등이다. 이중가장중요한요소가투여한리피오돌의양이다 [7]. 간동맥화학색전술후생기는폐동맥지질색전증의예방법은리피오돌의양을 15 20 ml 이상투여하지않도록하며, 초선택색전술 (superselection embolization) 을시행하고 [7], 동정맥루가관찰될경우동-정맥루를가진간정맥분지를풍선을통해일시적으로막아동정맥루의정도를줄이는것이다 [15]. 그밖에 polyvinylalcohol, gelatine sponges, coils 등을통한동정맥루색전술이대안으로제시되고있다 [16,17]. 폐동맥지질색전증의명확한치료법은아직없다 [18]. 산소치료, 고용량 methylprednisolone, 헤파린, 호기말양압등의치료가효과가있다는보고가있으나입증되지는않았다 [19]. 본증례에서는 30 ml의리피오돌이투여되었고, 특발성간질성폐렴이동반되어폐동맥지질색전증에더취약했을것으로생각된다. 결론적으로폐동맥지질색전증은간동맥화학색전술의심각한합병증이며위험인자로는리피오돌의투입량, 동-정맥루의유무, 하부가로막동맥색전술등이다. 리피오돌투여양을줄이고동-정맥루의정도를줄여주는것이예방방법이며산소치료, 고용량스테로이드, 헤파린, 호기말양 압등이치료법이될수있다. 참고문헌 1. Matsui O, Kadoya M, Yoshikawa J, Gabata T, Arai K, Demachi H, et al. Small hepatocellular carcinoma: treatment with subsegmental transcatheter arterial embolization. Radiology 1993;188:79-83. 2. Wallace S, Carrasco CH, Charnsangavej C, Richli WR, Wright K, Gianturco C. Hepatic artery infusion and chemoembolization in the management of liver metastases. Cardiovasc Intervent Radiol 1990;13:153-160. 3. Yamada R, Sato M, Kawabata M, Nakatsuka H, Nakamura K, Takashima S. Hepatic artery embolization in 120 patients with unresectable hepatoma. Radiology 1983;148:397-401. 4. Jung G, Kim JW, Joe JH, Kim SJ, Lee JB, Kim JG, et al. A case of necrotizing liver abscess and bile duct necrosis following hepatic arterial chemoembolization in hepatocelluar carcinoma. Korean J Hepatol 1999;5: 348-352. 5. Sakamoto I, Aso N, Nagaoki K, Matsuoka Y, Uetani M, Ashizawa K, et al. Complications associated with transcatheter arterial embolization for hepatic tumors. Radiographics 1998;18:605-619. 6. Clark TW. Complications of hepatic chemoembolization. Semin Intervent Radiol 2006;23:119-125. 7. Chung JW, Park JH, Im JG, Han JK, Han MC. Pulmonary oil embolism after transcatheter oily chemoembolization of hepatocellular carcinoma. Radiology 1993;187:689-693. 8. Samejima M, Tamura S, Kodama T, Yuuki Y, Takasaki J, Sekiva R, et al. Pulmonary complication following intra-arterial infusion of lipiodol-adriamycin emulsion for hepatocellular carcinoma, report of a case. Nihon Igaku Hoshasen Gakkai Zasshi 1990;50:24-28. 9. Cho SH, Kim JH, Kim BS, Jang J. A case of acute lung injury complicated by transcatheter arterial chemoembolization for hepatocellular carcinoma. Tuberc Respir Dis 1995;42:781-786. 10. Kwok PC, Lam TW, Lam CL, Lai AK, Lo HY, Chan SC. Rare pulmonary complications after transarterial chemoembolisation for hepatocellular carcinoma: two case reports. Hong Kong Med J 2003;9:457-460. 11. Xia J, Ren Z, Ye S, Sharma D, Lin Z, Gan Y, et al. Study of severe and rare complications of transarterial chemoembolization (TACE) for liver cancer. Eur J Radiol 2006;59:407-412. 12. Ozaki M, Miyagawa K, Takano H, Sekiya T, Natsuyama N, Nakano M. A case of hepatoma suspected pulmonary THE EWHA MEDICAL JOURNAL 65
Ewha Med J Vol. 36, No. 1, 2013 emboli following transcatheter arterial embolization. Rinsho Hoshasen 1989;34:165-167. 13. Kim JH, Ko GY, Yoon HK, Sung KB. Massive tumor pulmonary embolism following transcatheter arterial chemoembolization of hepatocellular carcinoma. J Korean Radiol Soc 2002;47:591-595. 14. Tajima T, Honda H, Kuroiwa T, Yabuuchi H, Okafuji T, Yosimitsu K, et al. Pulmonary complications after hepatic artery chemoembolization or infusion via the inferior phrenic artery for primary liver cancer. J Vasc Interv Radiol 2002;13(9 Pt 1):893-900. 15. Lee JH, Won JH, Park SI, Won JY, Lee do Y, Kang BC. Transcatheter arterial chemoembolization of hepatocellular carcinoma with hepatic arteriovenous shunt after temporary balloon occlusion of hepatic vein. J Vasc Interv Radiol 2007;18:377-382. 16. Kim YJ, Lee HG, Park JM, Lim YS, Chung MH, Sung MS, et al. Polyvinyl alcohol embolization adjuvant to oily chemoembolization in advanced hepatocellular carcinoma with arterioportal shunts. Korean J Radiol 2007;8:311-319. 17. Murata S, Tajima H, Nakazawa K, Onozawa S, Kumita S, Nomura K. Initial experience of transcatheter arterial chemoembolization during portal vein occlusion for unresectable hepatocellular carcinoma with marked arterioportal shunts. Eur Radiol 2009;19:2016-2023. 18. Lin MT, Kuo PH. Pulmonary lipiodol embolism after transcatheter arterial chemoembolization for hepatocellular carcinoma. JRSM Short Rep 2010;1:6. 19. Shiah HS, Liu TW, Chen LT, Chang JY, Liu JM, Chuang TR, et al. Pulmonary embolism after transcatheter arterial chemoembolization. Eur J Cancer Care (Engl) 2005;14:440-442. 66 THE EWHA MEDICAL JOURNAL