Cholangiocarcinoma Arising from Remnant Choledochal Cyst 증례 Todani 1 (Fig. 1), (Roux-en-Y choledochojejunostomy). 1., 118/88 mmhg, 75 /

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Case Report The Korean Journal of Pancreas and Biliary Tract 2017;22:147-151 https://doi.org/10.15279/kpba.2017.22.3.147 pissn 1976-3573 eissn 2288-0941 선천성담관낭종수술후잔류낭종에서 15 년만에발생한담관암 울산대학교의과대학서울아산병원 1 내과, 2 병리과, 3 소화기내과 이형경 1 이경민 1 김진영 1 이정선 1 안소연 2 홍승모 2 이현우 3 김명환 3 Development of Cholangiocarcinoma Arising from Remnant Intrapancreatic Cyst 15 Years after Choledochal Cyst Excision Hyeung Kyeung Lee 1, Kyoung Min Lee 1, Jinyoung Kim 1, Jungsun Lee 1, Soyeon An 2, Seung-Mo Hong 2, Hyun Woo Lee 3, Myung-Hwan Kim 3 Department of 1 Internal Medicine and 2 Pathology, 3 Division of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Among complications of choledochal cysts, malignant transformation is most concerning and management of choledochal cyst now includes complete cyst excision, whenever possible. In cases of choledochal cyst associated with pancreaticobiliary maljunction like our case, cholecystectomy along with the resection of dilatated bile duct and the biliary diversion are generally performed. However, incomplete cyst excision can result in malignant transformation within the remnant cyst. We present the case of cholangiocarcinoma arising from remnant intrapancreatic cyst 15 years after choledochal cyst excision in a patient with Todani type 1 choledochal cyst associated with pancreaticobiliary maljunction. We learn from the case that a careful long-term follow-up is needed in patients with choledochal cysts if residual cyst is remained after excision. Keywords: Choledochal cyst, Cholangiocarcinoma, Pancreatic cyst Received Mar. 2, 2017 Revised Apr. 6, 2017 Accepted Apr. 7, 2017 Corresponding author : Myung-Hwan Kim Division of Gastroenterology, Asan Medical Center, Ulsan University College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel. +82-2-3010-3183 Fax. +82-2-485-5782 E-mail; mhkim@amc.seoul.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2017 by The Korean Journal of Pancreas and Biliary Tract 서론,.,. Todani 5 ( 1, ; 2, ; 3, ; 4A, ; 4B, ; 5, ), 1 4A. 1,,,. 1,,,. 2. 3 Copyright 2017 by Korean Pancreatobiliary Association 147

Cholangiocarcinoma Arising from Remnant Choledochal Cyst 15 1. 증례 54 3. 15 Todani 1 (Fig. 1), (Roux-en-Y choledochojejunostomy). 1., 118/88 mmhg, 75 /, 16 /, 36.5.,. 5,200/mm 3, 15.5 g/dl, 285,000/mm 3, 21 IU/L, 21 IU/L, 95 IU/L, 0.6 mg/dl, carcinoembryonic antigen (CEA) 0.30 ng/ml, CA 19-9 6.7 U/mL. 3, 5 mm 7 mm (Fig. 2)., 10. standardized uptake value 2.8., A B Fig. 1. MRCP findings. (A) MRCP shows Todani type 1 choledochal cyst (a gallbladder collapses). (B) The arrow indicates the junction site of main pancreatic duct & common bile duct. The common bile duct seems to join main pancreatic duct at a right angle, sugesting the presence of pancreaticobiliary maljunction. MRCP, magnetic resonance cholangiopancreatography. A B C Fig. 2. Radiological findings of contrast-enhanced CT scan. (A) Before surgery, CT shows cystic dilatation of common bile duct without a mass or stone. (B) Remnant intrapancreatic cyst is noted after 2 months of surgery. (C) Solid portion (arrow) is seen within the remnant intrapancreatic cyst after 15 years of surgery. CT, computed tomography. 148 https://doi.org/10.15279/kpba.2017.22.3.147

Hyeung Kyeung Lee, et al. 로 보이는 검체에서는 췌장두부의 덜 절제되어 남아있는 담 에 의한 만성 염증을 기반으로 해서 과형성-이형성-암 과정 관 낭종 표면에서 융기성 병변이 확인되었고(Fig. 3), 최종 병 (hyperplasia-dysplasia-carcinoma sequence)을 밟는 것으로 이 리조직 검사에서 선편평세포암종으로 확진되었다(Fig. 4). 해되고 있다. 이는 통상의 담도암이 선종-선암 경과를 밟거나 American joint committee on cancer 7판의 병리학적 병기는 새로이(de novo) 발암하는 것과는 차이가 있다.4 IIB (T3N1M0)였고, 림프절 12개 중 1개에 전이가 확인되었고, 일반적으로 담관 낭종 환자에서 췌담관합류이상이 동반된 절제면에서 암세포는 발견되지 않았다. 림프혈관강 침윤이 있 경우가 동반되지 않은 경우보다 담도계 암의 발생률이 유의하 어 외래에서 항암화학 방사선 치료 concurrent chemoradiation 게 높다.5 일본의 전국조사 통계에 따르면, 담관 낭종과 췌담 therapy를 시행하기로 하고, 안정적인 상태로 퇴원하였다. 관합류이상이 같이 동반된 경우는 담도계 암 발생 환자의 약 2/3이 담낭에, 약 1/3이 담도에 암이 발생하였다. 반면에 담관 고 찰 낭종이 동반되지 않은 췌담관합류이상에서는 담도계 암 발생 환자의 약 90%가 담낭에서 암이 발생하였다.6 따라서 임상에 담관 낭종은 담도암의 전구병변이며, 나이가 증가함에 따라 서는 췌담관합류이상 및 담관 낭종이 동시에 있는 환자에서 담도계 암의 발생률이 증가하므로, 담관 낭종은 증상의 유무 담도계 암의 발생을 막기 위해 예방적으로 담낭 절제술과 간 와 진단 당시의 나이에 관계없이 진단되는 대로 수술이 가능 외 담관 낭종 절제술을 시행하고, 담도상피세포가 췌액에 노 1 출되는 것을 가능한 줄여주기 위해 수술적 우회술(예를 들면, 하다면 완전 절제하는 것이 치료 원칙이다. 담관 낭종 환자에서 췌담관합류이상은 약 70%에서 확인되 간관공장문합술)을 추가로 시행한다.6 반면에 담관 낭종을 동 며,3 또한 췌담관합류이상은 담관 낭종의 발생기전 중 하나로 반하지 않은 췌담관합류이상 환자에서는 담관 절제술 없이 담 생각된다. 본 증례와 같이 췌담관합류이상이 동반된 담관 낭 낭 절제술만을 예방적으로 시행하는 것이 일반적이다.4 종 환자에서의 담도계 암 발생기전은 췌액의 담도계로의 역류 문헌에 따르면 담관 낭종 수술 후 일부 남아있는 췌장내 담 관 낭종으로 다시 수술을 받은 41명의 환자들을 추적해 본 결 과 6명의 환자(15%)에서 담관암이 발생하였고, 이들은 모두 남은 췌장내 담관 낭종에서 암이 발생하였다. 따라서 담관 낭 종 절제시 췌장내 담관 낭종 부분도 완전 절제하는 것이 중요 하다.7 담관 낭종이 췌장내 담관 부위까지 확장된 경우에는 완 전 절제를 위해 정상적인 주췌관과 합류하는 부위 바로 직상 방까지 췌장내 총담관 낭종을 절제하는 것이 원칙이다. 담관 낭종이 방추 모양으로 확대되어 있어 주췌관이 잘 보이지 않 아 주췌관을 손상시킬 위험이 크기 때문에 췌담관합류이상의 유무를 정확히 알고, 절제 전에 담관조영술, 담관내시경, 금속 Fig. 3. Bivalve image of the surgical specimen shows choledochal cyst. The cystic wall demonstrates irregular nodularity (arrowheads) and choledocholithiasis (arrow). A B 클립을 사용해 절제 부위를 정해놓는 것이 안전하다. 악성화 되지 않은 Todani 제1형 담관 낭종 환자에서 췌십이지장절제 Fig. 4. (A) Representative images of well-differentiated cholangiocarcinoma component. Cancer cells make variable sized well-formed glandular architecture, which infiltrate into bile duct wall (H&E, 40). (B) Squamous cell carcinoma component is located in advanced tumor edge. Sheets of tumor cells with abundant eosinophilic cytoplasm with pleomorphic nuclei (H&E, 200). 149

Cholangiocarcinoma Arising from Remnant Choledochal Cyst Table 1. Reported cholangiocarcinoma cases developed within intrapancreatic remnant cyst after surgical excision of the choledochal cyst Age/sex Todani type Surgery for cyst Follow-up* (year) Cancer surgery Case #1 13 28/F I Ex, Hj 4 PD Case #2 13 23/F I Ex, Hj 6 Bypass Case #3 13 27/F IV-a Ex, Hj 13 PD Case #4 13 20/M - Ex 10 - Case #5 13 23/F IV-a Ex, Hj 12 PD Case #6 13 39/F I Ex, Hj 17 TP Case #7 13 25/M - Ex 17 - Case #8 14 42/F - Ex, Hj 17 PPPD Case #9 13 39/F IV-a Ex, Hj 17 TP Case #10 14 68/M I Ex, Hj 8 PD Case #11 13 41/F I Ex, Hj 13 TP Case #12 13 68/M I Ex, Hj 16 PD Case #13 13 62/F I Ex, Hj 8 TP Case #14 13 55/M IV-a Ex, Hj 23 PD Case #15 13 41/F I Ex, Hj 13 PPPD Case #16 13 27/F IV-a Ex, Hj 14 PD Case #17 13 58/M I Ex, Hj 26 PPPD Case #18 13 69/F I Ex, Hj 6 PPPD Case #19 13 39/F I Ex, Hj 16 PPPD Case #20 14 46/F I Ex, Hj 32 - Case #21 15 77/F I Ex, Hj 23 PPPD F, female; Ex, excision of the cyst; Hj, hepaticojejunostomy; PD, pancreatoduodenectomy; M, male; -, not described; TP, total pancreatectomy; PPPD, pylorus-preserving pancreaticoduodenectomy. *Follow-up (year), time interval between cyst excision and cancer detection.. 8. 0.7-6%,. 9-11. Todani 4A,.,. 12 17. 9 Todani 1, 5 Todani 4A, 3, 13.6 (4-26). 15 13, (CEA, CA19-9) 8 7. 13 ( 6, 4, 3 ), 3. 150 https://doi.org/10.15279/kpba.2017.22.3.147

Hyeung Kyeung Lee, et al. 1. 1 40%, 12.. 13, (Table 1).. (computed tomography) (magnetic resonance cholangiopancreatography). 15,. 요약,.,,,.. 15 1.. 국문색인 : 담관낭종, 담관암, 췌장낭종 Conflicts of Interest The authors have no conflicts to disclose. REFERENCES 1. Lee SE, Jang JY, Lee YJ, et al. Choledochal cyst and associated malignant tumors in adults: a multicenter survey in South Korea. Arch Surg 2011;146:1178-1184. 2. She WH, Chung HY, Lan LC, Wong KK, Saing H, Tam PK. Management of choledochal cyst: 30 years of experience and results in a single center. J Pediatr Surg 2009;44:2307-2311. 3. Liu YB, Wang JW, Devkota KR, et al. Congenital choledochal cysts in adults: twenty-five-year experience. Chin Med J (Engl) 2007;120:1404-1407. 4. Kamisawa T, Ando H, Suyama M, et al. Japanese clinical practice guidelines for pancreaticobiliary maljunction. J Gastroenterol 2012;47:731-759. 5. Ragot E, Mabrut JY, Ouaïssi M, et al. Pancreaticobiliary maljunctions in European patients with bile duct cysts: results of the multicenter study of the French Surgical Association (AFC). World J Surg 2017;41:538-545. 6. Morine Y, Shimada M, Takamatsu H, et al. Clinical features of pancreaticobiliary maljunction: update analysis of 2nd Japan-nationwide survey. J Hepatobiliary Pancreat Sci 2013;20:472-480. 7. Xia HT, Yang T, Liang B, Zeng JP, Dong JH. Treatment and outcomes of adults with remnant intrapancreatic choledochal cysts. Surgery 2016;159:418-425. 8. Mabrut JY, Bozio G, Hubert C, Gigot JF. Management of congenital bile duct cysts. Dig Surg 2010;27:12-18. 9. Kobayashi S, Asano T, Yamasaki M, Kenmochi T, Nakagohri T, Ochiai T. Risk of bile duct carcinogenesis after excision of extrahepatic bile ducts in pancreaticobiliary maljunction. Surgery 1999;126:939-944. 10. Watanabe Y, Toki A, Todani T. Bile duct cancer developed after cyst excision for choledochal cyst. J Hepatobiliary Pancreat Surg 1999;6:207-212. 11. Ono S, Fumino S, Shimadera S, Iwai N. Long-term outcomes after hepaticojejunostomy for choledochal cyst: a 10- to 27-year follow-up. J Pediatr Surg 2010;45:376-378. 12. Kim JW, Moon SH, Park DH, et al. Course of choledochal cysts according to the type of treatment. Scand J Gastroenterol 2010;45:739-745. 13. Mizuguchi Y, Nakamura Y, Uchida E. Subsequent biliary cancer originating from remnant intrapancreatic bile ducts after cyst excision: a literature review. Surg Today 2017;47:660-667. 14. Ishikawa K, Ogasawar S, Chiba T, et al. Cholangiocarcinoma derived from remnant intrapancreatic bile duct arising 32 years after congenital choledochal cyst excision: a case report. Case Rep Oncol 2015;8:265-273. 15. Shimada T, Sakata J, Ando T, et al. Surgical resection for carcinoma arising from the remnant intrapancreatic bile duct after excision of a congenital choledochal cyst - a case report. Gan To Kagaku Ryoho 2016;43:2101-2102. 151