Photodynamic Therapy for Hilar Bile Duct Cancer,. Bismuth ,, (photodynamic therapy, PDT) ,,,. 본론 1. 광역학요법의개요 (photos

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1 Review Article The Korean Journal of Pancreas and Biliary Tract 2014;19: pissn eissn 간문부담관암의광역학요법 서울대학교의과대학내과학교실및간연구소, 서울대학교병원내과 이상협 Photodynamic Therapy for Hilar Bile Duct Cancer Sang Hyub Lee Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea Hilar cholangiocarcinoma is a fatal malignancy leading to high mortality rate despite recent therapeutic advances, and the photodynamic therapy has been noted as an emerging palliative strategy for the hilar cholangiocarcinoma. Photodynamic therapy is the treatment selectively destructing cancer tissue through the laser beam irradiation with particular wavelengths. Photosensitizer administered before the treatment is accumulated in malignant tissue, and activated in the limits of those wavelengths. The procedure is performed under percutaneous transhepatic biliary drainage or endoscopic retrograde cholangiopancreatography, and more appropriate for the periductal infiltrating type rather than mass-forming type of cholangiocarcinoma due to the shallow penetrating depth (<4.5 mm). Recent investigations demonstrated the survival gain of 4-6 months in patients with cholangiocarcinoma when it is added to palliative biliary drainage. In addition, newly developed 3rd generation photo sensitizer has enabled longer therapeutic effect with less skin phototoxicity than before. However, there are still some limitations should be concerned, including lack of large-scaled prospective studies, shallow penetrating depth of tumoricidal effects, lack of treatment response measure, and relatively expensive cost. Addressing these matters through the larger prospective studies or technical improvement may lead new era of photodynamic therapy not only for the palliative purpose but also in the therapeutic field of cholangiocarcinoma. Korean J Pancreatobiliary 2014;19(2):71-78 Keywords: Photodynamic therapy, Hilar cholangiocarcinoma, Palliative therapy, Photosensitizer Received Mar. 15, 2014 Revised Mar. 24, 2014 Accepted Apr. 10, 2014 Corresponding author : Sang Hyub Lee Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongnogu, Seoul , Korea Tel Fax ; gidoctor@korea.com This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( 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. 서론 % %, 3, 1/3. 2,. 4 Copyright 2014 by Korean Pancreatobiliary Association 71

2 Photodynamic Therapy for Hilar Bile Duct Cancer,. Bismuth ,, (photodynamic therapy, PDT) ,,,. 본론 1. 광역학요법의개요 (photosensitizer), (excitation).,, 7 TNF-α, 8 (permeability) 9,10. (porphyrin) (LDL) ,.,,, 11,.,,, 1 cm.. hematoporphyrin (HpD) Photofrin Photogem 4 6., < /L, ( /L), < /L, (INR) 1.5,, (creatinine) 1.5, (total bilirubin) 1.5, (AST, ALT) (ALP) 2.5,. 2. 광민감제 1 porphyrin Photofrin (630 nm, Axcan, Canada) Photogem (630 nm, Lomonosov Institute of Fine Chemicals, Russia) ALA 12 2 (heme) porphyrin 72

3 Sang Hyub Lee Table 1. Results of photodynamic therapy in the previous series Study Study design No. of patients Median age (y) Photosensitizer Median survival Adjuvant therapy Ortner et al. 23 Prospective single-arm 9 NR Photofrin 439 days Zoepf et al. 15 Prospective single-arm ALA NR Ortner et al. 25 RCT 39 PDT, 64 Control, 68 Dumoulin et al. 38 Historical control 44 PDT, 70 Control, 71 Cheon et al. 31 Retrospective cohort 47 PDT, 59.7 * Photofrin PDT, 493 days Control, 98 days Photofrin PDT, 9.9 mo. Control, 5.6 mo. Control, 65.8 * Control, 288 days Photofrin PDT, 558 days Wiedmann et al. 36 Prospective single-arm 7 58 Photofrin NR Nanashima et al. 35 Prospective single-arm * Photofrin NR CTX, 1; RTX, 1 Wiedmann et al. 39 Prospective cohort Photofrin 336 days Zoepf et al. 24 RCT 32 PDT, 67 Control, 71 Photosan PDT, 630 days Conrol, 210 days Shim et al. 40 Prospective cohort Photosan 558 days Witzigmann et al. 41 Controlled cohort 124 PDT, 68 Control, 71 Photofrin PDT, 12 mo. Control, 6.4 mo. CTX, 11; RTX, 3 Prasad et al. 33 Retrospective cohort Photofrin 344 days CTX, 4; RTX, 1 Kahaleh et al. 37 Historical control 48 PDT, 66 Control, 68 Quyn 29 Prospective cohort 50 PDT, 69 Control, 65 Cheon et al. 34 Non randomized 143 PDT, 63 Control, 67 Photofrin PDT, 8 mo. Control, 5 mo. Photofrin PDT, 425 days Control, 169 days Photofrin PDT, 215 days Control, 181 days Lee et al. 32 Retrospective cohort * Photofrin PDT, 215 days Control, 181 days Park et al. 30 RCT 43 PDT + S-1, 64 * * Mean. RCT, randomized controlled trial; NR, not reported; CTX, chemotherapy; RTX, radiotherapy. PDT, 68.2 * Control, 9 mo. NR PDT, 17 mo. CTX, 22; RTX, 19 CTX, 8 CTX, 21 Korean J Pancreatobiliary 2014;19(2):

4 Photodynamic Therapy for Hilar Bile Duct Cancer protoporphyrin (PpIX) ferrochelatase. 13,14 PpIX,, Chlorophyll (CpD) 16,17,. CpD-a pheophorbide-a (Ph-a). Ph-a 2-1-hexyloxyethyl-2-devinyl pyropheophorbide-a 18 Photofrin, bacteriochlorophyll bacteriochlorin 간문부담관암에서의광역학요법의적용 , ,27 (Photofrin ) 48 2 mg/kg.,., ( mm) ( nm) , 1 cm J/cm 2..,.., 3 4, mm (sclerosing variant). (superficial spreading type with the papillary variant). (Mass-forming type) (intraductal mass form), 간문부담관암에서의광역학요법의치료성적 (Table 1)., 1998 Ortner 23 Bismuth 3 4 Phtofrin II (Axan, Mont- Saint-Hilaire, Canada), 630 nm, (median survival) 438 (Karnofsky index) 32.3% 68.9%. Ortner

5 Sang Hyub Lee, 400., 50% ( ) Bismuth type 4 16, 16, 630, Quyn ,278, , 21 fluoropyrimidine S-1 9 S-I 17. (2.9 vs. 2.2 ) (6.7 mg/dl vs. 8.4 mg/dl) %, 52%. 288, , (244±66 vs. 177±45 ) (356±213 vs. 230±73 ).. Prasad 33 25,,,. Cheon , bilirubin,, % 2 disease free. Wiedmann 36. Bismuth % 5 71%.. 5. 간문부담관암에서의광역학요법의제한점과향후과제,..., Ortner 25 ( ). Zoepf 24 25%. Korean J Pancreatobiliary 2014;19(2):

6 Photodynamic Therapy for Hilar Bile Duct Cancer Kahaleh 37 (MELD) (18.3 vs. 14.6), 4.5 mg/dl.,.. Photofrin 4 mm. Foscan 7 mm. (infiltrative type). probe.,. probe.... (IDUS). 3 cm.... probe.,,,,. 결론.,,,.,,..,,.,,,,. 국문색인 : 광역학요법, 간문부담관암, 고식적치료, 광민감제 Conflicts of Interest The author has no conflicts to disclose. 76

7 Sang Hyub Lee REFERENCES 1. Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 2013;145: Khan SA, Davidson BR, Goldin RD, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut 2012;61: Rosen CB, Heimbach JK, Gores GJ. Liver transplantation for cholangiocarcinoma. Transplant International 2010;23: Ito F, Cho CS, Rikkers LF, Weber SM. Hilar cholangiocarcinoma: current management. Ann Surg 2009;250: Hayata Y, Kato H, Konaka C, et al. Photoradiation therapy with hematoporphyrin derivative in early and stage 1 lung cancer. Chest 1984;86: McCaughan JS Jr, Mertens BF, Cho C, Barabash RD, Payton HW. Photodynamic therapy to treat tumors of the extrahepatic biliary ducts. A case report. Arch Surg 1991;126: Fingar VH, Taber SW, Haydon PS, Harrison LT, Kempf SJ, Wieman TJ. 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8 Photodynamic Therapy for Hilar Bile Duct Cancer photodynamic therapy with external drainage. Korean J Gastroenterol 2004;44: Lee TY, Cheon YK, Shim CS, Cho YD. Photodynamic therapy prolongs metal stent patency in patients with unresectable hilar cholangiocarcinoma. World Journal of Gastroenterology 2012;18: Prasad GA, Wang KK, Baron TH, et al. Factors associated with increased survival after photodynamic therapy for cholangiocarcinoma. Clinical Gastroenterology and Hepatology 2007;5: Cheon YK, Lee TY, Lee SM, Yoon JY, Shim CS. Longterm outcome of photodynamic therapy compared with biliary stenting alone in patients with advanced hilar cholangiocarcinoma. HPB: the official journal of the International Hepato Pancreato Biliary Association. 2012;14: Nanashima A, Yamaguchi H, Shibasaki S, et al. Adjuvant photodynamic therapy for bile duct carcinoma after surgery: a preliminary study. J Gastroenterol 2004;39: Wiedmann M, Caca K, Berr F, et al. Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma: a phase II pilot study. Cancer 2003;97: Kahaleh M, Mishra R, Shami VM, et al. Unresectable cholangiocarcinoma: comparison of survival in biliary stenting alone versus stenting with photodynamic therapy. Clinical Gastroenterology and Hepatology 2008;6: Dumoulin FL, Gerhardt T, Fuchs S, et al. Phase II study of photodynamic therapy and metal stent as palliative treatment for nonresectable hilar cholangiocarcinoma. Gastrointestinal. Endoscopy 2003;57: Wiedmann M, Berr F, Schiefke I, et al. Photodynamic therapy in patients with non-resectable hilar cholangiocarcinoma: 5-year followup of a prospective phase II study. Gastrointestinal Endoscopy 2004;60: Shim CS, Cheon YK, Cha SW, et al. Prospective study of the effectiveness of percutaneous transhepatic photodynamic therapy for advanced bile duct cancer and the role of intraductal ultrasonography in response assessment. Endoscopy 2005;37: Witzigmann H, Berr F, Ringel U, et al. Surgical and palliative management and outcome in 184 patients with hilar cholangiocarcinoma: palliative photodynamic therapy plus stenting is comparable to r1/r2 resection. Ann Surg 2006;244:

의학강좌_전상훈

의학강좌_전상훈 Continuing Education Column Photodynamic Therapy Sanghoon Jheon, MD Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine E-mail: jheon@snu.ac.kr J Korean Med