경경정맥간내문맥정맥단락술에사용한비피막형스텐트와 eptfe 피막형스텐트의개통률과임상결과의비교 여보고하고있는피막형스텐트 VIATORR R TIPS Endoprosthesis (GORE R, Flagstaff, AZ, USA) 는현재까지국내에도입되지않아사용이불가능하며, 스텐

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1 Original Article pissn / eissn J Korean Soc Radiol 2013;69(2): Comparison of Shunt Patency and Clinical Outcomes between Bare Stents and Expanded Polytetrafluoroethylene-Covered Stents for Transjugular Intrahepatic Portosystemic Shunts 1 경경정맥간내문맥정맥단락술에사용한비피막형스텐트와 Expanded Polytetrafluoroethylene 피막형스텐트의개통률과임상결과의비교 1 Youngwoo Seo, MD 1, Young Cheol Weon, MD 1, Jae Cheol Hwang, MD 1, Byeong Seong Kang, MD 1, Woon Jung Kwon, MD 1, Shang Hun Shin, MD 1, Mi-Jeong Nam, RN 2, Chi-Youn Yang, RN 2, Seong Hoon Choi, MD 1 Departments of 1 Radiology, 2 Nursing, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea Purpose: The purpose of this study is to compare shunt patency and clinical outcomes between bare stents and expanded polytetrafluoroethylene (eptfe) covered stents in patients who had undergone transjugular intrahepatic portosystemic shunt (TIPS) creation. Materials and Methods: 43 consecutive patients with active gastroesophageal variceal bleeding who had undergone de novo TIPS creation were included in this study. For TIPS creation, bare stents were placed in twenty patients (Group 1) from January 2001 to December 2003, while eptfe-covered stents were placed in twenty-three patients (Group 2) from January 2004 to December The primary and secondary patency rates of TIPS along with the clinical outcome were assessed, and a comparison was made between the two groups. Results: The technical success rate was 100%. Cumulative primary shunt patency rate in Group 1 was 78.5%, 55.8%, and 45.8% at 6, 12, and 24 months, respectively, and in Group 2, 91.1%, 86.0%, and 79.9%, respectively (p = 0.009). Cumulative secondary shunt patency rate in Group 1 was 86.3%, 70.7%, and 64.3%, respectively, and in Group 2, 91.1%, 91.1%, and 85.0%, respectively (p = 0.022). Conclusion: The use of eptfe-covered stents particularly designed to spare the juxtacaval segment of the hepatic vein resulted in an improved patency of shunts compared to using bare stents. Index terms Transjugular Intrahepatic Portosystemic Shunt Varices Stent Covered Expanded Polytetrafluoroethylene Received March 25, 2013; Accepted June 14, 2013 Corresponding author: Jae Cheol Hwang, MD Department of Radiology, University of Ulsan College of Medicine, Ulsan University Hospital, 877 Bangeojinsunhwando-ro, Dong-gu, Ulsan , Korea. Tel Fax stent@paran.com This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 서론 경경정맥간내문맥정맥단락술 (transjugular intrahepatic portosystemic shunt; TIPS) 은정맥류출혈및치료에반응하지않는복수와같은문맥고혈압의합병증치료에효과적인시술로, 특히치명적인다량의정맥류출혈환자에서목숨을구할수있는치료방법으로알려져있다 (1-3). TIPS 의조기임상결과는매우효과적이었으나단락의협착이나폐쇄와같은기능장애로인한증상재발과재시술이문제점으로지적되었다 (4-7). 이러한장기적인단락의기능장애를극복하기위하여다양한연구가진행되었고, 최근에는 expanded polytetrafluoroethylene (eptfe) 피막형스텐트를사용한연구에서좋은성적을보고하고있다 (8-11). 피막형스텐트의초기연구에서는혈전으로인한단락의조기폐색과간정맥부위의협착으로인한단락의기능부전이문제점으로제기되었으나피막형스텐트를간정맥-하대정맥이행부를넘어서하대정맥까지연장하여설치하는기술적보완으로단락의개통률을획기적으로개선하여좋은성적을보고하고있다 (12, 13). 그러나외국에서널리사용하 Copyrights 2013 The Korean Society of Radiology 113

2 경경정맥간내문맥정맥단락술에사용한비피막형스텐트와 eptfe 피막형스텐트의개통률과임상결과의비교 여보고하고있는피막형스텐트 VIATORR R TIPS Endoprosthesis (GORE R, Flagstaff, AZ, USA) 는현재까지국내에도입되지않아사용이불가능하며, 스텐트를하대정맥까지연장하여설치하는방법은생체간이식수혜자인경우수술시의간정맥문합및클램핑등에어떠한영향을미치는지잘알려지지않았으며잠재적인수술적어려움이예상된다 (14, 15). 이러한측면에서 TIPS 스텐트에대한연구가더필요하며, 이에저자들은간정맥-하대정맥이행부를보존하고간내에만삽입할수있도록고안하여국내에서제작한개선된 eptfe 피막형스텐트 (NITI-S R Covered Stent; 태웅, 서울, 대한민국 ) 를비피막형스텐트와비교하여피막형스텐트의유용성을알아보고자하였다. 대상과방법 의개통성을평가할수없는 1명을제외한 43명의환자가본연구에포함되었으며남자가 35명, 여자가 8명, 평균연령은 53세 (19~84 세 ) 였다. TIPS 에사용된스텐트의종류에따라대상을두군으로나누어진행하였는데 Group 1은 2001 년 1월부터 2003 년 12월까지비피막형스텐트를사용한 20명, Group 2는 2004 년 1월부터 2007 년 12월까지피막형스텐트를사용한 23명으로구성되었다. 대상환자의간경변증원인은 B형바이러스성간염 25명, C 형바이러스성간염이 2명, 알코올성 15명, Budd-Chiari syndrome 1명이었으며, 전체환자중간세포암이동반된환자는 5 명이었다. 모든환자에서위식도정맥류출혈은위내시경으로확인하였으며, 시술전간성뇌증이있었던환자는 7명이었다. 출혈이있었던정맥류의유형으로는식도정맥류출혈 4명, 위식도정맥류출혈 2명, 위정맥류출혈 37 명이었다 (Table 1). 대상본연구는후향적으로이루어졌으며본원의임상시험심의위원회 (Institutional Review Board) 승인을받았다 ( 승인번호 IRB ) 년 1월부터 2007 년 12월까지문맥고혈압의합병증으로활동성위식도정맥류출혈이있는환자중내시경적으로지혈이되지않아 de novo TIPS 를시행한환자를대상으로하였다. 총 44명이 TIPS 시술을받았으며시술이전에대량출혈에의한다발성장기손상이발생하였고, 시술직후사망하여스텐트 스텐트 Group 1의모든환자에서비피막형스텐트 Wallstent R (Boston Scientific, Natick, MA, USA) 를사용하였으며, 직경 10 mm, 길이 7 cm 스텐트를사용하였다. Group 2에서사용된피막형스텐트는 eptfe-covered stent (NITI-S R Covered stent; 태웅, 서울, 대한민국 ) 로직경 10 mm, 길이 7 cm 또는 8 cm 스텐트를사용하였다. 피막형스텐트는양측끝부위에각각 2 cm 길이의비피막부 (bare segment) 가있고중앙에 3 cm 또는 4 cm 길이의 eptfe 로피막된구조가있다. 스텐트의양측끝과 Table 1. Patient Demographics (n = 43) Detail Bare Stent Covered Stent p-value* Patient (number) Age (years) ± ± Range (years) Sex (M/F) 17/3 18/ Etiology of liver disease Alcohol 7 8 HBV HCV 1 1 Budd-Chiari Syndrome 1 0 Child-Pugh score 8.45 ± ± Child-Pugh class (A/B/C) 1/15/4 2/17/ Origin of variceal bleeding Esophageal varix 2 2 Esophagocardiac varix 0 2 Cardiac varix Fundal varix 6 4 Cardiofundal varix 1 0 Note.-*p value between Covered stent vs. Bare stent. HBV = hepatitis B virus, HCV = hepatitis C virus 114 대한영상의학회지 2013;69(2): jksronline.org

3 서영우외 피막부양측끝에는 gold marker 로표시를하여투시영상에서위치를확인할수있게하였다 (Fig. 1). 피막형스텐트는 굵기인한가닥의 nitinol 철선을나선형으로서로교차하는방식으로만들어진원주형태의금속망 (single mesh stent) 내부에 100 μm 두께의 eptfe 막을고정하여만들어졌다. eptfe 막을금속망에고정하기위하여봉에 eptfe 막을끼우고그위로 single mesh stent 를씌운다음 12% 폴리우레탄용액 (Chrono- Flex AR; Cardiotech International, Woburn, MA, USA) 에 1회담갔다가꺼내코팅하는방법으로제작되었다 (Fig. 2). TIPS 시술 TIPS 의시술은이전문헌에기술된방법으로시행하였다 (16). 초음파유도하에우측내경정맥을통하여 9 Fr sheath 를삽입하고, 5 Fr 혈관조영도관을사용하여우측간정맥을선택한뒤간정맥조영술을시행하여간정맥및간정맥-하대정맥이행부를확인하고간정맥압력을측정하였다. 이후 Ring Transjugular Intrahepatic Access Set (Cook, Bjaeverskov, Denmark) 를이용하여간실질을통해우측문맥을천자하고비장정맥-문맥조영술을시행하고문맥압을측정하였다. 간실질경로를직경 6 mm, 길이 4 cm의풍선을이용하여확장술을시행할때문맥과간정맥부위에생기는풍선허리 (balloon waist) 를확인하여간실질경로의길이를추정하고스텐트의피막부길이 (3 cm 혹은 4 cm) 를결정하였다. 모든환자에서직경 10 mm 스텐트를사용하였으며, 스텐트의전체길이는추정된간실질경로길이에따라 7 cm 혹은 8 cm였다. 스텐트삽입은피막형의경우에는추후생체부분간이식시에간정맥의클램핑과문합을고려하여과거문헌 (13) 과같이하대정맥까지연장시키지않고, 이행부에서 10 mm 이상의거리를두어삽입을하였다. 스텐트를삽입하고직경 8 mm, 길이 4 cm의풍선을이용하여다시확장술을시행하였다. 문맥-간정맥의압력차를재측정하여압력차가적당하지않은경우나, 비장정맥-문맥조영술에서정맥류로지속적인혈류가남아있을경우에직경 10 mm 풍선을이용하여추가적인확장술을시행하였다. 문맥-간정맥압력차가적당하지않은경우나위정맥류의형태와정도, 조영제의누출여부에따라코일색전술의여부를결정하였다 (Fig. 3). 추적검사추적검사는시술후의무기록과비주기적으로시행된위식도내시경, 컬러도플러초음파, CT, MRI, 그리고간동맥화학색전술시의간접간문맥조영술을후향적으로분석하여단락의기능부전여부를판단하였으며 TIPS 재시술환자는직접문맥조영술을통하여단락의개통성을판단하였다. 의무기록이누락 Fig. 1. The Niti-S Covered Stent: the stent consists of a covered middle portion that is 3 to 4 centimeters long and bare segments on both ends each measuring 2 centimeters in length. The diameter of the stent is 10 mm. Gold markers indicated the transition between the covered and bare segments. 된환자에서는전화조사를통하여간이식수술여부, 재출혈여 부, 생존여부, 사망원인및최종추적소실등을평가하였다. 결과측정 eptfe 의무기록과영상자료를후향적으로분석하여 TIPS 시술전 후임상적자료를수집하였다. 측정된결과는기술적성공여부, 혈역학적성공여부, 임상적성공여부, 시술후간성뇌증의발생 및악화, 단락의일차개통률, 이차개통률이다. 결과는 TIPS 를 시행한날부터간이식, 환자의사망혹은가장최근의추적관 찰이이루어진날까지자료를분석하였으며, 사망환자나추적 관찰이불가능한환자들이많은 2011 년 12 월이후의자료는수 집하지않았다. Polyurethane Stent wire Fig. 2. The schematic cross section of the Niti-S Covered Stent: the outer polyurethane layer attaches the expanded polytetrafluoroethylene graft to the stent wires (0.007 in diameter). 기술적성공은간정맥과문맥간단락의성공적인형성으로 정의하였고 (16), 혈역학적성공은시술후문맥 - 간정맥혈압차 가 12 mm Hg 이하로감압된경우로정의하였다 (17). 임상적 성공은시술후위식도정맥류출혈의지혈로정의하였으며, 이 jksronline.org 대한영상의학회지 2013;69(2):

4 경경정맥간내문맥정맥단락술에사용한비피막형스텐트와 eptfe 피막형스텐트의개통률과임상결과의비교 A B C D Fig. 3. TIPS procedure and stent placement. A 59-year-old man with hepatitis B cirrhosis and variceal bleeding. A. The direct splenoportogram shows large gasric varices. B. Tract dilatation was performed using an angioplasty balloon catheter (6 mm in diameter, 4 cm in length). The waists in the balloon indicate the location of the hepatic vein (solid arrow) and the portal vein (empty arrow), while the tract is located between the two. C. The radiograph shows the covered stent that has been placed along the shunt. The transition between the covered and bare segments of the stent can be identified by the gold markers on both proximal and distal portions of the stent (solid arrows). D. The splenoportogram acquired after stent placement shows that the hepatic end of the stent has been placed about 2 cm away from the hepatocaval junction (double arrow). Coil embolization of the varices was additionally performed after the TIPS procedure due to insufficient decompression of the varices (solid arrow). Note.-TIPS = transjugular intrahepatic portosystemic shunt 는임상적, 내시경적소견을종합하여판단하였다. 시술후간성뇌증은새로운정신상태 (mental status) 의변화가있거나, 의식수준 (level of consciousness) 의변화가있는경우로정의하였으며, 간성뇌증의발생및악화여부는임상적으로내과전문의가결정하였다. 일차개통기간은재시술없이단락의개통이유지된기간으로정의하였으며, 이차개통기간은단락의기능장애나폐색으로인하여시행한재시술과상관없이, 개통성이유지된최대기간으로정의하였다. 단락의개통은기능장애가발생하지않은상태로정의하였다. 단락의기능장애는임상적으로위식도정맥류출혈의재발이있거나, 내시경으로위식도정맥류의출혈을확인한경우, CT, MRI, 또는간동맥화학색전술시행시촬영한간접간문맥조영술에서단락의협착이있거나완전히폐색된경우, 컬러도플러초음파에서기능장애를예측할수있는소견이있는경우로정의하였다. 컬러도플러초음파에서기능장애를예측할수있는소견은혈류가없거나, 특정부분의혈류속도가 250 cm/sec 이상, 단락의문맥부 1/3 지점의최대혈류속도가 50 cm/sec 이하, 주문맥최대혈류속도가초기측정치의 2/3 이하인경우, in-shunt flow 가초기측정치의 1/2 이하로감소한경우로정의하였다 (18). 통계두군간의환자특성비교는 t-test 와 χ 2 test 를사용하였고, Child-Pugh score 의비교는 Wilcoxon test를사용하였다. TIPS 의개통률을 Kaplan-Meier 방법으로구하였으며, log- rank test 로 Group 1과 Group 2의개통성에통계적차이를비교하였다. 단락의기능장애와임상적인자의연관성에관한다변량분석을 Cox s proportional hazards regression model 을이용하여시행하였다. 통계프로그램은 SPSS 19 version (SPSS Inc., Chicago, IL, USA) 을사용하였다. 각각의결과는 p값이 < 0.05 일때통계적으로의미있다고판정하였다. 결과 TIPS 의결과는 Table 2에요약하였다. 추적관찰기간은평균 일 (2~3273 일 ) 로 Group 1은 일, Group 2는 일로통계적차이는없었다. 비피막형스텐트를사용한환자 (Group 1) 는 20명, 피막형스텐트를사용한환자 (Group 2) 는 23명이었으며, 두군간의성별, 나이, Child-Pugh score, 간성뇌증여부는통계적차이가없었다. 출혈의원인은식도정맥류출혈이 Group 1에서 2명, Group 2 에서 2명, 위식도정맥류출혈이 Group 1에서 0명, Group 2에서 2명, 위정맥류출혈이 Group 1에서 18 명, Group 2에서 19 명으로두군간의통계적차이는없었다. 관찰기간중간이식을시행받은환자는 Group 1에서 1명, Group 2에서 5명이었으며, 간이식을받은시점까지자료분석에이용하였다. 추적관찰기간중사망한환자는 25명이며, Group 1에서 15명, Group 2에서 10명이었고, 원인은간부전 11명, 간암 3명, 패혈증 7명, 심근경색 2명, 외상성뇌출혈 1명, 자살 1명이었으나, 두군모두 116 대한영상의학회지 2013;69(2): jksronline.org

5 서영우외 Table 2. Outcome of TIPS Creation (n = 43) Outcome Bare Stent (n = 20) Covered Stent (n = 23) p-value* Follow-up period (days) Range (days) Technical success (%) 20 (100) 23 (100) Hemodynamic success (%) 19 (95.0) 22 (95.6) Clinical success (%) 19 (95.0) 21 (91.3) PSG (mm Hg) Before TIPS ± ± After TIPS 7.50 ± ± Coil embolization Hepatic encephalopathy Rebleeding within 1 month Primary patency (%) months months months Secondary patency (%) months months months Note.-*p value between Covered stent vs. Bare stent. PSG = portosystemic gradient, TIPS = transjugular intrahepatic portosystemic shunt 에서위식도정맥류출혈에의한사망은없었다. 추적관찰중소실이된환자는 6명이었다. 모든환자에서기술적성공이이루어졌으며, 시술후문맥- 간정맥압력차가 12 mm Hg 이하로감소한혈역학적성공은 Group 1에서 19명 (95.0%), Group 2에서 22명 (95.6%) 이었다 (p = 0.919). 임상적성공은 Group 1에서 19 명 (95.0%), Group 2에서 21 명 (91.3%) 이었고통계적차이는없었다 (p = 0.653). 시술전문맥-간정맥압력차는 Group 1에서 ± 5.82 mm Hg, Group 2에서 ± 6.11 mm Hg로통계적차이는없었고 (p = 0.170), 시술후압력차는 Group 1에서 7.50 ± 3.04 mm Hg, Group 2에서 7.65 ± 2.60 mm Hg로통계적으로차이가없었다 (p = 0.860). 시술중정맥류에추가적인코일색전술을시행한환자는 Group 1에서 3명, Group 2에서 6명이었다. Group 2에서 1명의환자에서는성공적으로지혈은되었으나, 다량의간신우회로혈류 (gastrorenal shunt flow) 로인한간성뇌증의발생과재출혈의가능성이높아 TIPS 시술 6일뒤역행성경정맥위정맥류폐색술 (balloon-occluded retrograde transvenous occlusion; BRTO) 을추가로시행하였다. 시술중합병증은간피막을천자하여발생한혈복강이 Group 2 환자중 1명에게있었으나, 보존적치료로조절이가능하였다. 시술후합병증중간성뇌증의발생혹은악화는 Group 1 에서 6명 (30%), Group 2에서 8명 (34.8%) 으로통계학적차 Primary patency Time (days) Fig. 4. Time-to-event analysis of TIPS primary patency: primary patency of the covered stent (91.1% at 6 m, 86.0% at 1 y, and 79.9% at 2 y) was superior to that of the bare stent (78.5% at 6 m, 55.8% at 1 y, and 45.8% at 2 y) at all time points (p = 0.009). Note.-TIPS = transjugular intrahepatic portosystemic shunt 이는없었다. 시술후 30 일내에재출혈이발생한환자는 Group 1 에서 3 명, Group 2 에서 2 명이었고, 시술후 30 일이내 에사망한환자는두군모두에서없었다. Group 2 (covered) Group 1 (bare) TIPS 를시행한환자에서일차개통률은 Group 1 에서 78.5%, 55.8%, 45.8%(6 개월, 12 개월, 24 개월 ) 이며 Group 2 에서 91.1%, 86.0%, 79.9% 이고, 두군간의일차개통률은 log-rank jksronline.org 대한영상의학회지 2013;69(2):

6 경경정맥간내문맥정맥단락술에사용한비피막형스텐트와 eptfe 피막형스텐트의개통률과임상결과의비교 Secondary patency test 상통계적으로유의한차이가있었다 (p = 0.009)(Fig. 4). 재시술은 Group 1 에서 3 명, Group 2 에서 3 명의환자에서시 행하였으며, 재시술을시행한환자에서 Group 1 의모든예에 서스텐트의간실질부위의협착이관찰되었고, Group 2 의모 든예에서스텐트의간문맥말단부의협착이관찰되었다. 이차 개통률은 Group 1 에서 83.6%, 70.7%, 64.3%(6 개월, 12 개 월, 24 개월 ) 이며 Group 2 에서 91.1%, 91.1%, 85.0% 이고, 두 군간의이차개통률역시 log-rank test 상통계적으로유의한 차이가있었다 (p = 0.022)(Fig. 5). Cox s proportional hazards regression model 을이용한다변량분석에서 TIPS 시술에사용 된스텐트의종류를제외하고개통률차이에영향을주는인자 는없었다. 고찰 Time (days) Group 2 (covered) Group 1 (bare) Fig. 5. Time-to-event analysis of TIPS secondary patency: secondary patency of the covered stent (91.1% at 6 m, 91.1% at 1 y, and 85.0% at 2 y) was superior to that of the bare stent (83.6% at 6 m, 70.7% at 1 y, and 64.3% at 2 y) at all time points (p = 0.022). Note.-TIPS = transjugular intrahepatic portosystemic shunt 본연구에서저자들은문맥고혈압에의한정맥류출혈의치 료를위한 TIPS 시술시간정맥 - 하대정맥이행부를보존하면서 간내에국한하여삽입하도록고안한 eptfe 피막형스텐트는 비피막형스텐트와비교하여개통률을유의하게향상시킬수 있었으며, 기존의발표된피막형스텐트와비교하여비슷한좋 은결과를확인할수있었다. 이러한결과로간정맥 - 하대정맥 이행부를보전하여스텐트를간내에위치시킴으로써잠재적으 로간이식대상자인환자가간이식수술시 TIPS 에의한수술적 어려움과이에따른합병증을예방할수있을것이다. 기존의피막형스텐트를사용한 TIPS 시술에서간정맥부의 협착에의한단락의기능부전이문제가되었는데여러연구에 서스텐트를하대정맥까지연장시키는방법으로획기적으로개통률을높이고있다 (12, 13). 그러나피막형스텐트를하대정맥까지길게연장시키는방법은스텐트의피막부위가길어져서혈전에의한스텐트폐쇄와스텐트이동 (migration) 의위험이있다 (19). 또한스텐트가간상부하대정맥 (suprahepatic inferior vena cava) 까지연장되는경우간이식수술에서횡경막하간정맥클램핑시기술적인어려움으로부득이하게수술범위가확대되어수술시간이연장되고유병률이높아질수있기때문에스텐트설치시각별한주의를필요로한다 (14, 15, 20, 21). 이에동소성간이식 (orthotopic liver transplantation) 을고려할때 TIPS 시술시스텐트설치는위쪽은간정맥-하대정맥이행부에서 5 mm 이상여유가있어야하며, 아래쪽은간외주문맥을 1 cm 이상포함시키지않도록권장하고있다 (22). 국내는외국과비교하여생체부분간이식의비율이상대적으로높고 (23), 생체부분간이식수술은동소성간이식보다여러개의복잡한간정맥-하대정맥문합이필요하며수술후초기에는간정맥의정상적인유출이이식간의생존에중요하다 (24). 따라서간정맥의클램핑과문합의용이성, 그리고이식간의간정맥협착예방을위하여간정맥-하대정맥이행부의보존에대한중요성이더부각될수있다 (14, 15). Group 2의환자중 5명이간이식수술을받았는데 2명은생체부분간이식수술을 3명은뇌사자전간이식수술을받았다. 본원에서간이식수술을시행받은 4명에서성공적으로횡경막하간정맥클램핑및간정맥문합을시행하였다. 많은문헌에서보고하고있고주로쓰이는 VIATORR R TIPS Endoprosthesis (GORE R, Flagstaff, AZ, USA) 는문맥부에는비피막부가있지만간정맥부에는비피막부가없이구성되어있다. 비피막형스텐트를이용한 TIPS 에서단락기능부전의주원인으로여겨지는간실질경로에서담즙에의한급성혈전증과가성내막 (pseudointima) 의증식 (hyperplasia), 이동 (migration) 으로인한단락의폐쇄 (25, 26) 는피막형스텐트를사용하여간실질경로를덮어획기적으로예방할수있었으나피막형스텐트를간내간정맥에위치시킬경우간정맥부위에협착이발생하는문제점은단락기능부전의중요한원인이되었다 (13). 간정맥부위의협착발생기전은피막형스텐트의경우측면유연성이떨어져기립하려는성질에의해스텐트끝이간정맥벽에예각 (acute angle) 으로위치되는데, 이것은혈관내막의자극과와류가발생시키고, 그에따른내막증식과염증반응에의한육아조직의성장으로설명할수있다. 이는비피막형스텐트인 Wallstent 가지연성단축 (shortening) 에의해간정맥벽에자극을주는현상과유사하다고할수있다 (27). 본연구에서사용한피막형스텐트는비피막부를간정맥쪽에도 대한영상의학회지 2013;69(2): jksronline.org

7 서영우외 cm로길게만들어피막형보다측면유연성을증가시켜단락의곡선경로를따라스텐트가평행하게위치하도록고안하였다. 이는스텐트의길이감소에따른이탈이진행되어도간정맥에스텐트가안정적으로위치할수있으며스텐트의기립현상을예방하여간정맥에대한자극을최소화할수있을것으로생각된다. 또한간정맥부에서스텐트의피막부를최소화하여단락을통한혈류와원래의간정맥의혈류를유지시켜스텐트간정맥부에혈전형성에의한단락의폐쇄를예방하기를기대하였다. 스텐트를완전히간내에설치하기위해서는 TIPS 시술시천자부위가되도록이면간정맥-하대정맥이행부로부터멀리떨어진간정맥에서이루어져야하는데이를위하여문맥과의거리를고려하여 Colapinto needle tip 의각도를원래보다예각이되도록인위적으로조작할필요가있다. 피막형스텐트를사용한 Group 2 환자중 7명의환자에서단락의기능장애가발생하였고, 그중 3명의환자에서재시술을하였다. 모든예에서간정맥의협착은관찰되지않았으며, 스텐트의간문맥-간실질이행부에서협착이관찰되었는데, 이것은스텐트의적절치못한위치선정으로피막부가간실질경로를모두포함하지못하여발생한것으로생각된다 (27). 기존의외국연구와비교할때, 본연구에서피막형스텐트를사용한군의개통률이이전피막형스텐트를사용한연구와비교해비슷한좋은결과를보이고있으며, 비피막형스텐트보다우수한성적을보이고있는데, 이는본연구에사용된스텐트는말단부를간정맥내에위치시켜간정맥-하대정맥이행부를보존해도개통률에는큰차이가없음을보여준다. 국내에는 VIA- TORR R stent 를 TIPS 에사용하여개통률을조사한연구가없고, 다른종류의피막형스텐트와비피막형스텐트를비교하여개통률을조사한연구는 Joo 등 (28) 에의한 경경정맥간내문맥정맥단락술의장기개통성 연구가유일하다. 상기연구에서는본연구와같은제조사의피막형스텐트를사용하였지만, 피막형스텐트와비피막형스텐트간의개통률차이가없다는결과를보여주었다. 본연구와결과의차이를보이는원인은스텐트형태의차이가가장가능성이높을것으로생각되나, 연구의모든요인을비교하지못해명확히알수는없다. 최근정맥류출혈의치료로 TIPS 시술이많이시행되지않고있다. 그이유로는내시경적치료기술의발전, BRTO 와같은다른치료법의발달, TIPS 후간성뇌증의유발과간기능악화등과같은합병증, 다른치료법에비해상대적으로침습적이고위험한점, 그리고예측할수없는단락의기능부전으로인한주기적인추적검사및재시술에따른경제적부담등을들수있다. 그러나다량의활동성정맥류출혈이나내시경적치료가제한적인위정맥류출혈의경우여전히 TIPS 가효과적이고구 명을위한치료법으로남아있다. 또한간기능이좋지않은위험군과급성정맥류출혈환자에서치료성공, 재출혈, 환자의생존율측면에서다른치료방법과비교하여더효과적인치료로인정되고있다 (29, 30). 본연구의대상환자들역시내시경적치료에실패하거나재출혈이발생하였던활동성정맥류출혈로 TIPS 시술후좋은임상결과를보여이러한견해를뒷받침하고있다. 최근피막형스텐트의개발과 TIPS 시술의기술적발전으로단락의기능부전을획기적으로개선하여재시술에따른경제적측면에서도긍정적인영향으로 TIPS 시술이다시주목받고있으며적응증에대한지침 (guideline) 의변경이필요하다는요구와보고들이있다 (30, 31). 본연구의한계는첫째, 기존의상품화된피막형스텐트와의개통률을직접적으로비교하지못해본연구에사용된스텐트의객관적인개통률을알기어렵다는것이다. 둘째, 대부분환자의추적관찰에서초음파및 CT 등으로간접적인개통률만측정되었고직접문맥조영술및문맥-간정맥압력차를얻은환자가적어서정확한단락의협착및기능장애여부를조사하지못했으며, 단락의기능장애가있는환자에서도정확한협착부위를확인할수없는예가많아연구에사용된피막형스텐트가간정맥부협착의예방에어느정도기여를하는지평가하기어렵다는것이다. 셋째는피막형스텐트를사용한 TIPS 시술후생체부분간이식환자가많지않아, 수술에미치는영향을평가하기힘들다는것이다. 넷째, 후향적연구의한계로주기적인추적검사와단락의개통률을파악하기위한자료들이부족하다는것이다. 결론적으로, 간실질부위만피막형으로제작하고양쪽말단부를비피막형으로제작하여하대정맥-간정맥이행부보존을위해고안된 eptfe 피막형스텐트는비피막형스텐트와비교하여우수한개통률을보였으며, 하대정맥까지확장시킨기존의피막형스텐트개통률연구와비교해서도비슷한결과를보여, 위식도정맥류출혈의치료를위한 TIPS 시술에효과적이며유용하다. 앞으로본연구에사용된스텐트가실제간정맥부의협착예방에어떤역할을하며, 간이식수술시어떤영향을주는지에대한추가적인연구가필요하다. 참고문헌 1. Rösch J, Hanafee WN, Snow H. Transjugular portal venography and radiologic portacaval shunt: an experimental study. Radiology 1969;92: Colapinto RF, Stronell RD, Birch SJ, Langer B, Blendis LM, Greig PD, et al. Creation of an intrahepatic portosystemic jksronline.org 대한영상의학회지 2013;69(2):

8 경경정맥간내문맥정맥단락술에사용한비피막형스텐트와 eptfe 피막형스텐트의개통률과임상결과의비교 shunt with a Grüntzig balloon catheter. Can Med Assoc J 1982;126: Pomier-Layrargues G, Bouchard L, Lafortune M, Bissonnette J, Guérette D, Perreault P. The transjugular intrahepatic portosystemic shunt in the treatment of portal hypertension: current status. Int J Hepatol 2012;2012: Rössle M, Richter GM, Nöldge G, Palmaz JC, Wenz W, Gerok W. New non-operative treatment for variceal haemorrhage. Lancet 1989;2: Rössle M, Siegerstetter V, Huber M, Ochs A. The first decade of the transjugular intrahepatic portosystemic shunt (TIPS): state of the art. Liver 1998;18: Saxon RS, Ross PL, Mendel-Hartvig J, Barton RE, Benner K, Flora K, et al. Transjugular intrahepatic portosystemic shunt patency and the importance of stenosis location in the development of recurrent symptoms. Radiology 1998; 207: Rösch J, Keller FS. Transjugular intrahepatic portosystemic shunt: present status, comparison with endoscopic therapy and shunt surgery, and future prospectives. World J Surg 2001;25: ; discussion Haskal ZJ. Improved patency of transjugular intrahepatic portosystemic shunts in humans: creation and revision with PTFE stent-grafts. Radiology 1999;213: Bureau C, Garcia-Pagan JC, Otal P, Pomier-Layrargues G, Chabbert V, Cortez C, et al. Improved clinical outcome using polytetrafluoroethylene-coated stents for TIPS: results of a randomized study. Gastroenterology 2004;126: Hausegger KA, Karnel F, Georgieva B, Tauss J, Portugaller H, Deutschmann H, et al. Transjugular intrahepatic portosystemic shunt creation with the Viatorr expanded polytetrafluoroethylene-covered stent-graft. J Vasc Interv Radiol 2004;15: Gaba RC, Omene BO, Podczerwinski ES, Knuttinen MG, Cotler SJ, Kallwitz ER, et al. TIPS for treatment of variceal hemorrhage: clinical outcomes in 128 patients at a single institution over a 12-year period. J Vasc Interv Radiol 2012;23: Cejna M, Peck-Radosavljevic M, Thurnher SA, Hittmair K, Schoder M, Lammer J. Creation of transjugular intrahepatic portosystemic shunts with stent-grafts: initial experiences with a polytetrafluoroethylene-covered nitinol en- doprosthesis. Radiology 2001;221: Clark TW, Agarwal R, Haskal ZJ, Stavropoulos SW. The effect of initial shunt outflow position on patency of transjugular intrahepatic portosystemic shunts. J Vasc Interv Radiol 2004;15(2 Pt 1): Tripathi D, Therapondos G, Redhead DN, Madhavan KK, Hayes PC. Transjugular intrahepatic portosystemic stentshunt and its effects on orthotopic liver transplantation. Eur J Gastroenterol Hepatol 2002;14: Guerrini GP, Pleguezuelo M, Maimone S, Calvaruso V, Xirouchakis E, Patch D, et al. Impact of tips preliver transplantation for the outcome posttransplantation. Am J Transplant 2009;9: Haskal ZJ, Martin L, Cardella JF, Cole PE, Drooz A, Grassi CJ, et al. Quality improvement guidelines for transjugular intrahepatic portosystemic shunts. SCVIR Standards of Practice Committee. J Vasc Interv Radiol 2001;12: Garcia-Tsao G, Groszmann RJ, Fisher RL, Conn HO, Atterbury CE, Glickman M. Portal pressure, presence of gastroesophageal varices and variceal bleeding. Hepatology 1985;5: Zizka J, Eliás P, Krajina A, Michl A, Lojík M, Ryska P, et al. Value of Doppler sonography in revealing transjugular intrahepatic portosystemic shunt malfunction: a 5-year experience in 216 patients. AJR Am J Roentgenol 2000;175: Hayashi PH, Mao J, Slater K, Liao R, Durham JD, Carroll J, et al. Atrial septal perforation from TIPS stent migration. J Vasc Interv Radiol 2004;15: Millis JM, Martin P, Gomes A, Shaked A, Colquhoun SD, Jurim O, et al. Transjugular intrahepatic portosystemic shunts: impact on liver transplantation. Liver Transpl Surg 1995;1: Boyer TD, Haskal ZJ; American Association for the Study of Liver Diseases. The role of transjugular intrahepatic portosystemic shunt in the management of portal hypertension. Hepatology 2005;41: Meyer C, Odeh M, Herrera JJ, Resende A, Perarnau JM, Ellero B, et al. Orthotopic liver transplantation with a suprahepatic vena caval anastomosis over a transjugular intrahepatic portosystemic shunt. J Am Coll Surg 1998;187: Hwang S, Moon DB, Lee SG. Current status and perspectives of living donor liver transplantation. J Korean Med 120 대한영상의학회지 2013;69(2): jksronline.org

9 서영우외 Assoc 2008;51: Ko GY, Sung KB, Yoon HK, Kim KR, Kim JH, Gwon DI, et al. Early posttransplant hepatic venous outflow obstruction: long-term efficacy of primary stent placement. Liver Transpl 2008;14: LaBerge JM, Ferrell LD, Ring EJ, Gordon RL. Histopathologic study of stenotic and occluded transjugular intrahepatic portosystemic shunts. J Vasc Interv Radiol 1993;4: Saxon RR, Mendel-Hartvig J, Corless CL, Rabkin J, Uchida BT, Nishimine K, et al. Bile duct injury as a major cause of stenosis and occlusion in transjugular intrahepatic portosystemic shunts: comparative histopathologic analysis in humans and swine. J Vasc Interv Radiol 1996;7: Cura M, Cura A, Suri R, El-Merhi F, Lopera J, Kroma G. Causes of TIPS dysfunction. AJR Am J Roentgenol 2008; 191: Joo SM, Park JH, Kim HC, Jae HJ, Chung JW. Long term follow-up of a transjugular intrahepatic portosystemic shunt: a comparison of covered and uncovered stents. J Korean Soc Radiol 2009;60: García-Pagán JC, Caca K, Bureau C, Laleman W, Appenrodt B, Luca A, et al. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med 2010;362: Fidelman N, Kwan SW, LaBerge JM, Gordon RL, Ring EJ, Kerlan RK Jr. The transjugular intrahepatic portosystemic shunt: an update. AJR Am J Roentgenol 2012;199: Riggio O, Ridola L, Lucidi C, Angeloni S. Emerging issues in the use of transjugular intrahepatic portosystemic shunt (TIPS) for management of portal hypertension: time to update the guidelines? Dig Liver Dis 2010;42: 경경정맥간내문맥정맥단락술에사용한비피막형스텐트와 Expanded Polytetrafluoroethylene 피막형스텐트의개통률과임상결과의비교 1 서영우 1 원영철 1 황재철 1 강병성 1 권운정 1 신상훈 1 남미정 2 양지연 2 최성훈 1 목적 : 위식도정맥류출혈치료를위한 transjugular intrahepatic portosystemic shunt (TIPS) 시술시, 간정맥-하대정맥이행부보존을위해사용된 expanded polytetrafluoroethylene (eptfe) 피막형스텐트와비피막형스텐트의개통률을비교하여 eptfe 피막형스텐트의유용성을알아보고자한다. 대상과방법 : 위식도정맥류출혈을치료하기위해 de novo TIPS 를시행한 43명의환자가대상이며, 2001 년 1월부터 2003 년 12월까지 20명의환자는비피막형스텐트를사용하였고 (Group 1), 2004 년 1월부터 2007 년 12월까지 23명의환자는스텐트양측끝에 2 cm의비피막부가있는 eptfe 피막형스텐트를사용하였다 (Group 2). 두군간의일차개통률, 이차개통률및임상결과를비교하였다. 결과 : 평균추적관찰기간은 985 일이었으며, 모든환자에서기술적성공을하였다. 30일내재출혈은 Group 1에서 3명, Group 2에서 2명이있었으나통계적차이는없었다. 일차개통률은 Group 1에서 78.5%, 55.8%, 45.8%(6 개월, 12개월, 24개월 ) 였고, Group 2에서 91.1%, 86.0%, 79.9% 로통계적으로유의한차이가있었으며 (p = 0.009), 이차개통률은 Group 1에서 83.6%, 70.7%, 64.3% 였고, Group 2에서 91.1%, 91.1%, 85.0% 로통계적으로유의한차이가있었다 (p = 0.022). 결론 : 간정맥-하대정맥이행부를보존하기위하여제작된 eptfe 피막형스텐트는비피막형스텐트와비교하여우수한개통률을보여주며, 위식도정맥류출혈의치료를위한 TIPS 시술에효과적이며유용하다. 울산대학교의과대학울산대학교병원 1 영상의학과, 2 간호부 jksronline.org 대한영상의학회지 2013;69(2):

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