Yittirum-90, Transarterial radioembolization, Hepatocellular carcinoma, Pulmonary fibrosis

77 / 남자

Hepatitis B virus 보균자이며 heavy alcoholics (소주 하루 1병, 10년)로 hepatomegaly와 weight loss (7~8Kg/ 1년) 로 내원하였다. 내원 당시serum alpha-fetoprotein level은 80197 ng/ml였다. Y-90 transarterial radioembolization (TARE) 시행 약 4개월 후 cough, sputum 및 dyspnea가 발생하였다.

Pulmonary fibrosis after Y-90 transarterial radioembolization

Liver MRI상 모든 pulse sequence에서 hepatocellular carcinoma (HCC)에 합당한 영상소견을 보이는약 15 cm mass가liver right lobe에있으며 (Fig 1A) segment 6과 7에 한 개씩 intrahepatic metastatic nodule들이 있었다. TARE 1달 후 시행한 follow-up MRI에서 target lesion의 크기 및 enhancement pattern에 변화 없고 (Fig 1B) segment 4에 new intrahepatic metastasis가 생겼다. 이에 대해 drug eluting beads (DEB)- transarterial chemoembolization (TACE)를 한 차례 시행받았다. TARE 시행 약 4개월 후 respiratory symptom 발생 당시 시행한 chest CT coronal image상 양측 lung parenchyme에 multifocal patchy ground glass opacity 와 consolidation이 혼재된 병변이 보이며 right lung 이 left lung 보다 그 정도가 심했다 (Fig 2A, Radiation pneumonitis CT coronal). 호흡기 증상 지속되어 시행한follow-up (TARE 10개월 후) chest CT coronal image상 양측 lung의 volume이 감소하고 양측 central lung zones에 parenchymal distortion, traction bronchiectasis, peribronchial consolidation의 fibrosis소견을 보였으며 right lung이 left lung 보다 정도가 심했다 (Fig 2B, radiation Fibrosis CT coronal). 이러한 소견은 chest radiography에서도 확인할 수 있었다 (Fig 2C and Fig 2D). Underlying HCC는 DEB-TACE후 follow up CT 및 MRI에서 5.6cm 로 작아지고 enhancing portion은 뚜렷하지 않았다 (Fig 1C및1D).

Right lobar radioembolization을 계획하고 right hepatic artery distal portion에서 기시하는cystic artery artery를 3mm microcoil (MicroTornado, Cook incorporated, Bloomington, IN, USA)로, right inferior phrenic artery를 150~250 micrometer particle (Contour, Boston Scientific Corporation, Natick, MA, USA)로 embolization 한 후 99m-Tc 4mCi을 right hepatic artery proximal portion에서 injection 한 후 얻은 pulmonary shunt fraction은 19.86%였다. 2.5 GBq Y-90 (SIR-Spheres, Sirtex Medical, Lane Cove, Australia)을 이용 하여 right hepatic artery에서 TARE를 시행하였으며 tumor에 infusion된 dose는 약 86Gy였다. TARE 시행 2달 후 target lesion과 segment 4에 생긴 new intrahepatic metastasis에 대해 3Fr microcatheter (MicroFerret, William Cook Europe Aps, Bjaeverskov, Denmark)를 이용하여 right hepatic artery 및 A4를 selection한 후100~300 micrometer drug eluting beads (DC Bead, Biocompatibles Ltd., Farnham, United Kingdom) 에 adriamycin 100 mg을 loading하여 TACE를 시행하였다.

Y-90 치료 후에 발생할 수 있는 adverse events에는 postradioembolization syndrome, radiation-induced liver disease, radiation-induced cholecystitis, biliary sequelae, gastrointestinal complication, radiation pneumonitis등이 있다. 이 중radiation pneumonitis는 정확한 incidence는 알려져 있지 않지만 lung shunt fraction이 13% 이상일 경우에는 생길 수 있기 때문에 추적관찰이 권고된다 (1,2). Resin-based microsphere를 사용할 경우에는 20%가 최대 허용 범위이다. 참고적으로 폐의 허용 방사선량은 treatment session당 30 Gy, cumulative dose 는50 Gy로 알려져 있다 (3). 본 증례에서는 lung shunt fraction 이 19.89%였고 이로부터 구한 lung dose는 24.67 Gy였다. 간암의 angiographic feature중 하나인 capillary bed를 by pass하는 arteriovenous shunt (AVS)가 radioembolization 후 pulmonary complication의 원인이다. AVS 통해 20~ 40 nm 크기의 Y-90 microsphere가 lung으로 도달할 수 있다. 따라서 radioembolization 전에 lung shunt fraction을 Y-90 microsphere 와 비슷한 크기의 99m-Tc macroaggregated albumin (MAA)를 이용하여 shunt fraction을 추정할 수 있다. 그러나 99m-Tc MAA의 size variability및 측정 장비 (planar vs. single photon emission CT (SPECT) gamma camaera)에 따른 오차는 있을 수 있다 (4). 진단은 pathologic evaluation에서 microsphere가 증명된 경우에 가능하다. 그러나 inflammatory, infectious, 및 cytotoxic 원인이 배제된다면 clinical, functional 및 radiologic finding을 고려하여 진단할 수도 있다. Nonproductive cough, dyspnea, fever 등의 증상이 생기며 bronchoalveolar lymphocytosis 및 eosinophilia의 소견이 동반된다. Pulmonary function test에서는 mild restrictive pattern을 보인다. Radiologic 소견은 치료 후 1~2개월 정도부터 ill-defined patchy opacities와 ground glass opacity가 양측 lungs에 비교적 symmetric distribution을 보이며 peripheral 및 hilar area 는 sparing되는 경향이 있다. 또한 lung 의 dependent portion인 posterior part가 anterior part보다 더 심한 경향이 있다 (5). 이러한 소견들은 99m-Tc MAA의 distribution과 일치한다. 치료는 corticosteroid 로 가능하며 용량은 환자의 반응 정도에 따라 20 mg/d ~ 60 mg/d로 조절할 수 있다. 치료에 반응하지 않는 경우에는 radiation pneumonitis가 localized fibrosis, traction bronchiectasis 로 진행하게 되고 pneumothorax 나 superinfection등 late complication이 생길 수 있다 (4).

1. Kim YH, Kim do Y. Yttrium-90 radioembolization for hepatocellular carcinoma: what we know and what we need to know. Oncology 2013; 84 Suppl 1:34-39. 2. Murthy R, Nunez R, Szklaruk J, et al. Yttrium-90 microsphere therapy for hepatic malignancy: devices, indications, technical considerations, and potential complications. Radiographics 2005; 25 Suppl 1:S41-55. 3. Ho S, Lau WY, Leung TW, Chan M, Johnson PJ, Li AK. Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer. Eur J Nucl Med 1997; 24:293- 298. 4. Salem R, Thurston KG. Radioembolization with 90Yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1: Technical and methodologic considerations. J Vasc Interv Radiol 2006; 17:1251-1278. 5. Lin M. Radiation pneumonitis caused by yttrium-90 microspheres: radiologic findings. AJR Am J Roentgenol 1994; 162:1300-1302.

A 77-year old man was presented with hepatomegaly and weight loss (7~8Kg/year). A. A 15 cm enhancing mass is demonstrated in the right lobe of the liver on an arterial phase image of liver MRI. B. One-month follow-up MRI after Y-90 TARE shows no significant change of a huge mass in the right lobe of the liver. A new metastatic HCC is also noted in the segment 4 (not shown). C. Three-week follow-up CT after DEB-TACE demonstrates a 9.8 cm heterogeneously enhancing mass down from 15 cm in the right lobe of the liver. D. Eight-month follow-up MRI after DEB-TACE shows a 5.6 cm mass with no enhancing portion in the right lobe of the liver.

A 77-year old man was presented with hepatomegaly and weight loss (7~8Kg/year). A. A 15 cm enhancing mass is demonstrated in the right lobe of the liver on an arterial phase image of liver MRI. B. One-month follow-up MRI after Y-90 TARE shows no significant change of a huge mass in the right lobe of the liver. A new metastatic HCC is also noted in the segment 4 (not shown). C. Three-week follow-up CT after DEB-TACE demonstrates a 9.8 cm heterogeneously enhancing mass down from 15 cm in the right lobe of the liver. D. Eight-month follow-up MRI after DEB-TACE shows a 5.6 cm mass with no enhancing portion in the right lobe of the liver.

A 77-year old man was presented with hepatomegaly and weight loss (7~8Kg/year). A. A 15 cm enhancing mass is demonstrated in the right lobe of the liver on an arterial phase image of liver MRI. B. One-month follow-up MRI after Y-90 TARE shows no significant change of a huge mass in the right lobe of the liver. A new metastatic HCC is also noted in the segment 4 (not shown). C. Three-week follow-up CT after DEB-TACE demonstrates a 9.8 cm heterogeneously enhancing mass down from 15 cm in the right lobe of the liver. D. Eight-month follow-up MRI after DEB-TACE shows a 5.6 cm mass with no enhancing portion in the right lobe of the liver.

A 77-year old man was presented with hepatomegaly and weight loss (7~8Kg/year). A. A 15 cm enhancing mass is demonstrated in the right lobe of the liver on an arterial phase image of liver MRI. B. One-month follow-up MRI after Y-90 TARE shows no significant change of a huge mass in the right lobe of the liver. A new metastatic HCC is also noted in the segment 4 (not shown). C. Three-week follow-up CT after DEB-TACE demonstrates a 9.8 cm heterogeneously enhancing mass down from 15 cm in the right lobe of the liver. D. Eight-month follow-up MRI after DEB-TACE shows a 5.6 cm mass with no enhancing portion in the right lobe of the liver.

A 77-year old man experienced cough, sputum and dyspnea that started 4 months after Y-90 TARE. A. Coronal image of chest CT shows multifocal patchy consolidation and ground glass opacity in both lungs with right lung predominant. B. Seven-month follow-up chest CT demonstrates decreased lung volume, traction bronchiectasis, and parenchymal distortion which suggest pulmonary fibrosis. Characteristically fibrotic change involves central lung zones with right lung predominant. C and D. Chest radiographs taken before and after Y-90 TARE show dramatic changes of lung volume and fibrotic sequelae.

A 77-year old man experienced cough, sputum and dyspnea that started 4 months after Y-90 TARE. A. Coronal image of chest CT shows multifocal patchy consolidation and ground glass opacity in both lungs with right lung predominant. B. Seven-month follow-up chest CT demonstrates decreased lung volume, traction bronchiectasis, and parenchymal distortion which suggest pulmonary fibrosis. Characteristically fibrotic change involves central lung zones with right lung predominant. C and D. Chest radiographs taken before and after Y-90 TARE show dramatic changes of lung volume and fibrotic sequelae.

A 77-year old man experienced cough, sputum and dyspnea that started 4 months after Y-90 TARE. A. Coronal image of chest CT shows multifocal patchy consolidation and ground glass opacity in both lungs with right lung predominant. B. Seven-month follow-up chest CT demonstrates decreased lung volume, traction bronchiectasis, and parenchymal distortion which suggest pulmonary fibrosis. Characteristically fibrotic change involves central lung zones with right lung predominant. C and D. Chest radiographs taken before and after Y-90 TARE show dramatic changes of lung volume and fibrotic sequelae.

A 77-year old man experienced cough, sputum and dyspnea that started 4 months after Y-90 TARE. A. Coronal image of chest CT shows multifocal patchy consolidation and ground glass opacity in both lungs with right lung predominant. B. Seven-month follow-up chest CT demonstrates decreased lung volume, traction bronchiectasis, and parenchymal distortion which suggest pulmonary fibrosis. Characteristically fibrotic change involves central lung zones with right lung predominant. C and D. Chest radiographs taken before and after Y-90 TARE show dramatic changes of lung volume and fibrotic sequelae.