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1 대한내과학회지 : 제 76 권제 6 호 2009 증례 위정맥류출혈에 Histocaryl R 주입후발생한부신농양 1예 연세대학교원주의과대학내과학교실 예창진 백순구 김문영 석기태 이일영 김은미 An adrenal gland abscess after N-butyl-2-cyanoacrylate (Histoacryl ) injection therapy for gastric varices bleeding Chang Jin Yea, M.D., Soon Koo Baik, M.D., Moon Young Kim, M.D., Ki Tae Suk, M.D., Il Young Lee, M.D. and Eun Mi Kim, M.D. Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea N-butyl-2-cyanoacrylate (Histoacryl ) is used to obtain hemostasis in gastric variceal bleeding. Known complications of Histoacryl injection therapy include bleeding, perforation, stenosis, and embolism. We report a case of adrenal abscess as a very rare complication of Histoacryl injection. A 40-year-old male with liver cirrhosis was admitted with acute gastric variceal bleeding. Sclerotherapy using Histoacryl mixed with lipiodol (3 ml) was successful. Twenty-seven months later, he was readmitted complaining of left flank pain and a fever of 39 C. Abdominal computed tomography (CT) showed a heterogeneous enhancing solid and cystic mass ( cm) at the left adrenal gland. A left adrenalectomy was performed and the pathological examination confirmed a Histoacryl -related adrenal abscess. We present this case along with a brief review of the literature. (Korean J Med 76: , 2009) Key Words: Adrenal gland abscess; Gastric varices bleeding; N-butyl-2-cyanoacrylate; Sclerotherapy; Complication 서론위정맥류의발생과그에따른급성출혈은간경변증및그로인한문맥압항진증의주요합병증의하나로서전체간경변증환자의약 20~70% 에서발생한다. 위정맥류는진단후 2년이내에 30% 에서출혈을경험하며, 급성출혈의경우식도정맥류출혈에비해사망률이높아, 출혈후 6주이내에 60~70% 의사망률과매출혈시마다약 50% 의높은사망률을보인다. 따라서이러한위정맥류출혈치료의성공여부는간경변증환자의예후에중요한영향을미친다 1). 현재시행되고있는급성위정맥류출혈의치료방법으로는내시경적경화요법, 결찰요법, 경피경간색전술 (percutaneous transhepatic obliteration), 경경정맥간내문맥대순환단락술 (TIPS) 및외과적수술등이있으며, 그중에서도 n-butyl-2-cyanoa- Received: Accepted: Correspondence to Soon Koo Baik, M.D., Ph.D., Division of Gastroenterology & Hepatology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsan-dong, Wonju, Gangwon-do , Korea baiksk@medimail.co.kr

0-cm heterogeneous enhancing solid and cystic mass of the left adrenal gland. crylate ( 이하 Histoacryl ) 을이용한내시경적경화요법이가장많이시행되고있다. Histoacryl 은 1970년대초개발되어외과영역에서조직접합제로서다방면에사용되면서정맥류에도사용되었다 2).

2 - Chang Jin Yea, et al. Adrenal abscess after N-butyl-2-cyanoacrylate injection - Figure 1. At endoscopy after endoscopic sclerotherapy using Histoacryl mixed with lipiodol (3 ml), a fundal varix with sealed stigmata is noted. Figure 2. Contrast enhanced abdominal spiral CT shows a cm heterogeneous enhancing solid and cystic mass of the left adrenal gland. crylate ( 이하 Histoacryl ) 을이용한내시경적경화요법이가장많이시행되고있다. Histoacryl 은 1970년대초개발되어외과영역에서조직접합제로서다방면에사용되면서정맥류에도사용되었다 2). Soehendra 3) 등이 1986년부터 Histoacryl 을이용하여내시경경화요법으로위정맥류를치료한이래로, 이약물을이용한내시경경화요법은위정맥류를폐쇄시키고소실시키는데비교적안전하고효과적인치료법으로현재가장널리이용되고있다. 그러나이시술은효과는우수하나시술시여러합병증을유발할수있다는제한점을가지고있다. Paravariceal injection이된경우궤양및천공을초래하고조기재출혈의원인이될수있으며, 도관의폐색과내시경끝에 Histoacryl 과 lipiodol 혼합액에의한유착이올수있다. 또한주사후재출혈, 발열, 색전증 ( 폐색전, 뇌경색, 비장경색 ) 등의합병증이비교적자주발생할수있는합병증들이다. 그러나 Histoacryl 을이용한내시경경화요법후이로인한누공의형성및그에따른농양의형성은매우드믄것으로이전에보고된바가없었다. 이에본저자들은위정맥류출혈로내원한환자에서 Histoacryl 주사로지혈요법을시행하고, 27개월후위와부신사이의누공의형성과이로인해발생한부신농양 1예를경험하였기에문헌고찰과함께보고하는바이다. 증례환자 : 박, 40세, 남자주소 : 좌측측복통, 발열, 오한현병력 : 상기환자는 20일전부터발생한좌측측복통과 3일전부터의발열, 오한을주소로외래를경유하여내원하였다. 환자는 10년전 B형간염바이러스감염을진단받았으며, 2년전 B형간염바이러스에의한간경변증을진단받고외래추적관찰중토혈로본원응급실에내원하였고, 응급으로시행받은상부위장관내시경검사에서급성위정맥류출혈로진단되어 Histoacryl 과 lipiodol 혼합액 (3 cc) 에의한경화요법을시행받았으며시술후위정맥류재출혈이없음이확인되어퇴원하였다 ( 그림 1). 이후환자는 2년여간특이소견없이외래추적관찰을해오던중내원 3일전부터시작된발열과좌측측복통을주소로내원하였다. 과거력 : 만성 B형간염및간경변증과이로인한급성위정맥류출혈로경화요법을받은외에특이과거력없었음. 가족력 : 특이사항없음. 사회력 : 특이사항없음. 진찰소견 : 환자내원당시의활력징후는혈압 110/70 mmhg, 맥박분당 75회, 호흡수분당 20회, 체온은 39 로, 급성병색소견을보였으나의식은명료하였다. 경도의탈수

- 대한내과학회지 : 제 76 권제 6 호통권제 586 호 2009 - Figure 3. The upper gastrointestinal series detected a radiopaque tear-drop shaped (2.

Grossly, the pathological specimen submitted for frozen section consisted of an irregular fragment of adrenal gland measuring 6 5 2 cm and weighing 38 g. There was a 1.

Under light microscopy, acute suppurative inflammation with focal ill-defined chronic granulomatous inflammation is seen (H&E stain, 100). 상치 : 1~15) 를보였다. 요검사상특이소견은없었다.

3 - 대한내과학회지 : 제 76 권제 6 호통권제 586 호 Figure 3. The upper gastrointestinal series detected a radiopaque tear-drop shaped (2.6 cm) lesion (arrow) in the left upper quadrant caused by a gastro-adrenal fistula. Figure 4. Grossly, the pathological specimen submitted for frozen section consisted of an irregular fragment of adrenal gland measuring cm and weighing 38 g. There was a cm whitish hard foreign body (arrow) on the external surface and the adrenal gland contained irregular multifocal whitish yellow lesions with areas of necrosis and fibrosis. Figure 5. Under light microscopy, acute suppurative inflammation with focal ill-defined chronic granulomatous inflammation is seen (H&E stain, 100). 상치 : 1~15) 를보였다. 요검사상특이소견은없었다. 영상의학적소견 : 복부컴퓨터단층촬영에서좌측부신부위에 heterogeneous enhancing solid and cystic mass ( cm) 가발견되었다 ( 그림 2). 상부위장관조영술을시행하였으며 ( 그림 3) 위기저부에 tear drop shape (2.6 cm) 으로조영제가위벽밖으로유출되는소견이관찰되었다. 임상경과및치료 : 복부초음파및복부컴퓨터단층촬영에서 Histoacryl 시행후생긴좌측부신주위농양으로진단되어좌측부신제거술을시행하였다. 좌측부신주위농양 (6 5 2 cm) 에 Histoacryl 로추정되는단단한백색의이물질이관찰되었으며, 주위로부신피질조직과괴사및섬유화된조직이관찰되어 ( 그림 4), 병리학적소견상 Histoacryl 주입에따른급성화농성염증으로진단하였다 ( 그림 5). 소견을보였으나결막은창백하지않았고, 공막에황달은관찰되지않았다. 복부팽만과좌측측복부통증이있었다. 검사실소견 : 내원당시혈액학적검사에서혈색소 13.5 mg/dl, hematocrit 38.8%, 백혈구 37,000/mm 3 ( 호중구 94%, 림프구 3.4%), 혈소판 123,000/mL, prothrombin time 14.9초 (INR 1.33), 총빌리루빈 1.7 mg/dl, 알부민 3.1 g/dl, AST 22 IU/L, ALT 15 IU/L, ALP 106 IU/L, rgt 67 IU/L, C-reactive protein (CRP) mg/dl ( 정상치 : <0.5), ESR 98 mm/h ( 정 고찰간경병증환자에서정맥류출혈의 14~36% 가위정맥류출혈에의하며 4), 식도정맥류출혈보다발생빈도는낮지만한번발생하면심한출혈을일으키고, 재출혈률이높아사망률이 45% 에이른다 5). 해부학적으로위정맥류는좌위정맥, 비장정맥에서형성되며, 위저부와분문부일부는비정맥에서나온단위정맥 (short gastric vein) 에서위소만부와분문부의

4 - 예창진외 5 인. N-butyl-2-cyanoacrylate injection 주입후발생한부신농양 - 일부는좌위정맥 (left gastric vein) 에서발생된다 6). 위정맥류의크기가크고간기능이저하된경우출혈률은 76% 에이르는것으로보고되고있다 7,8). Sarin 등은위치에따라분문에근접한위정맥류 (1형), 위기저부에서분문으로연결된위정맥류 (2형), 위저부에고립된위정맥류 (3형) 로분류하였을때, 고립된위정맥류에서출혈의빈도가높고, 위기저부로부터분문륜으로연결된위정맥류에서출혈률과사망률이높다고보고하였다 5). 위정맥류는점막하층에위치하며일단파열되면대량출혈의가능성이높고, 시야확보및접근에난점이있어식도정맥류출혈보다지혈이어렵다. 내시경적경화요법은정맥류내부또는주위에경화제를주입하여화학적염증반응을유발하여정맥류를폐쇄시키는방법으로신속한초기지혈효과를나타내고, 반복시행에의해정맥류의재출혈위험성을줄이고근절을가져올수있는장점이있다. 그러나위정맥류는식도정맥류와는달리직경이크고, 측부혈관이발달되어있으며, 혈류량이많고속도가빨라서식도정맥류치료에사용되는 ethanolamine oleate, polidocanol, sodium morrhuate, sodium teradecyl sulfate 등과같은경화제를이용한치료법이효과적이지못하고재출혈률이높다. Histoacryl 은 cyanoacrylate계의조직접합체로써혈액이나조직의수분과접촉하면순간적으로중합체로변환되어강력한접착제역할을하게됨으로써혈관내색적물이형성되어정맥류를폐색시키기때문에순간적으로지혈효과를나타낸다. 또한이물질반응에의한급성혈관내막괴사가일어나고혈관벽의과사와섬유화가진행되어정맥류를소멸시킨다. 주입 1주후부터중합체가빠져나가기시작하고 2~3개월경과후에는정맥류에서탈락되어대부분자연배출된다 9). Histoacryl 을이용한이러한내시경적경화요법은급성위정맥류출혈에서 93.3~100% 의우수한초기지혈성공률을보고하고있다 9,10). 그러나이치료법은내시경수기의어려움과반복적인주입으로도정맥류의완전소실이어렵다는점, 시간경과후치료부위의재출혈발생등에의해실제정맥류환자의생존율에는영향을미치지못하는한계를가지고있다 9,10). Histoacryl 치료의합병증으로는발열, 흉부불쾌감이나통증, 연하곤란, 발열등의경미한합병증이일반적이지만, 식도협착, 중합체탈락에의한재출혈, 천공등이발생할수있고, 뇌색전증, 폐색전증, 문맥및비정맥혈전증등과같은전신적인합병증이발생할수있으며, 드물게는본증례에서와같은폐혈증, 농양, 내장기관의누공이형성될수있다 11,12). 농양형성의원인은여러가지를고려할수있다. 우 선, 내시경적경화요법시술에따른 2차적세균감염이있다. Histoacryl 치료는이물질반응으로혈관벽괴사와혈관주위염증을유발할수있고, 여기에 2차적감염으로농양을형성할수있다. 일부에서는 Histoacryl 이 in vitro에서항균효과가있다는보고도있으나 13,14), Chen 등 15) 은 Histoacryl 로위정맥류출혈을치료받은환자들에게서항균효과는관찰되지않았으며, 오히려 30% 정도는일시적으로균혈증이생겼다고보고하였다. 즉, Histoacryl 주입은중합반응에의한복합체를형성하기때문에이에따른균혈증의빈도가높게된다고볼수있다. 정상적으로세균에대한노출이빈번한소화기내강으로의복합체의노출과소화기점막손상은세균감염을증가시킬수있으며 15), 본증례에서도내시경적경화요법과그에따른궤양의형성, 조기식이요법의재개등이복합적으로급성에이은만성적인염증과세균감염및이로인한만성적누공의형성을유발하고, 약 2년여간유지되던만성적누공에여러원인에의한급성세균감염이병발하고악화되므로써농양까지형성되었을것으로판단된다. 그러나 Histoacryl 을이용한위정맥류치료의경우항상이러한감염증및염증에의한합병증이발생하는것은아니며, 실제임상적으로문제가되는합병증을유발함에는경화요법술기시행자체와관련된기술적문제와의관련성을배제할수없다. 위정맥류천자시에주사침의길이가과도하게길거나너무깊게천자가된다면효과적인지혈에실패할가능성이높을뿐아니라, 인위적으로누공을형성하게할가능성이높다. 특히, 본증례와같이위정맥류가위벽자체의두께가다른부위보다얇은위저부에발생한경우, 시술과관련된이러한합병증의가능성은높다고할수있다. 또한, 과도한양의 Histoacryl 과 lipiodol 혼합액의주입은정맥류내의압력을급격히상승시켜자연적으로위장벽과외부의누공을형성할수있다. 특히, 최근에는초기지혈효과를높이기위해과거에비해사용되는 Histoacryl 과 lipiodol 혼합액의양이증가하는추세에있고, 실제본증례에있어서도총 3 cc가사용되어경화요법술기상의문제와더불어사용된 Histoacryl 과 lipiodol 혼합액의양이누공의형성과이에따른만성적농양의형성에영향을미쳤을가능성을배제할수없다. 이외에도 Histoacryl 과 lipiodol 혼합액의투여속도, 정맥류의부분적폐색과측부혈관의발달여부등이복합적으로작용하여누공과농양이발생했을가능성이높다. 식도정맥류에경화요법후에합병증으로 brain 16), 복막내 17) 에농양이생겼다는보고들은있다. 그러나위정맥류에

5 - The Korean Journal of Medicine: Vol. 76, No. 6, 대한 Histoacryl 경화요법과이로인해생긴후복막농양은매우드문경우로앞서지적한여러요건들중한가지에의해서라기보다는이들의복합적작용에의해발생했을가능성이높다. 그러므로실제내시경적경화요법을시행함에있어서시술의는이러한가능성에도주의를기울일필요가있으며, 시술시위정맥류유형에따른정확한천자의위치와깊이는물론, Histoacryl 과 lipiodol 혼합액의양, 주입속도, 식이요법의시작시점및예방적항생제요법등에대해서도세심한조절과관리가필요하다. 또한여러합병증들의조기발견을위해퇴원후에추적검사로내시경, 복부전산화단층촬영그리고 CRP를포함한혈액검사등이주기적으로시행되어야하겠다. 요 저자들은 40세간경변증환자에서위정맥류출혈치료를위해 n-butyl-2-cyanoacrylate (Histoacryl ) 와 lipidol 혼합액경화요법을시행한후발생한좌측부신농양을경험하였기에문헌고찰과함께보고하는바이다. 중심단어 : 위정맥류츨혈 ; N-butyl-2-cyanoacrylate; 부신농양 ; 경화요법 ; 합병증 약 REFERENCES 1) Graham DY, Smith JL. The course of pateints after variceal hemorrhage. Gastroenterology 80: , ) Galil KA, Schofield ID, Wright GZ. Effect of N-butyl-2-cyanoacrylate (histoacryl blue) on the healing of skin wounds. J Can Dent Assoc 50: , ) Soehendra N, Nam VC, Grimm H, Kempeneers I. Endoscopic obliteration of large esophagogastric varices with bucrylate. Endoscopy 18:25-26, ) Lo GH, Lai KH, Cheng JS, Chen MH, Chiang HT. A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices. Hepatology 33: , ) Sarin SK, Lahoti D, Saxena SP, Murthy NS, Makwana UK. Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients. Hepatology 16: , ) Haubrich WS, Schaffner F, Berk JE. Bockus gasteroenterology. 5th ed. Philadelphia, Saunders, ) Kim T, Shijo H, Kokawa H, Tokumitsu H, Kubara K, Ota K, Akiyoshi N, Iida T, Yokoyama M, Okumura M. Risk factors for hemorrhage from gastric fundal varices. Hepatology 25: , ) North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices: a prospective multicenter study. N Engl J Med 319: , ) Seewald S, Seitz U, Yang AM, Soehendra N. Variceal bleeding and portal hypertension: still a therapeutic challenge? Endoscopy 33: , ) Huang YH, Yeh HZ, Chen GH, Chang CS, Wu CY, Poon SK, Lien HC, Yang SS. Endoscopic treatment of bleeding gastric varices by N-butyl-2-cyanoacrylate (Histoacryl ) injection: longterm efficacy and safety. Gastrointest Endosc 52: , ) Nishida K, Noda T, Kawazoe S, Takahashi K, Namoto M, Yoshizaki M. Perigastric abscess after endoscopic injection sclerotherapy (EIS) using Histoacryl for bleeding from gastric varices (in Japanese with English abstract). Endosc Dig 9: , ) Verger P, Blais J, Gruau M, Haffaf Y. Retrogastric abscess secondary to gastric varices obturation with cyanoacrylate. Gastroenterol Clin Biol 22: , ) Fenzl TC, Fenzl RE, Harris L. Antimicrobial properties of alkyl-2-cyanoacrylate tissue adhesives in vitro. Am J Ophthalmol 95: , ) Eiferman RA. Snyder JW. Antibacterial effect of cyanoacrylate glue. Arch Ophthalmol 101: , ) Wahl P, Lammer F, Conen D, Schlumpf R, Bock A. Septic complications after injection of N-butyl-2-cyanoacrylate: report of two cases and review. Gastrointest Endosc 59: , ) Cohen FL, Koerner RS, Taub SJ. Solitary brain abscess following endoscopic injection sclerosis of esophageal varices. Gastrointest Endosc 31: , ) Ayub A, Linjawi T, Qadri SM, Ingemannson S, Zafar M, al-harbi A. Intraabdominal abscess after esophageal variceal sclerotherapy. J Clin Gastroenerol 18: ,

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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R