Cholangiozelluläres Karzinom und Gallenblasenkarzinom

Zusammenfassung

Risikofaktoren für Gallenblasen- und Gallengangskarzinome sind Gallensteine und chronische Entzündungen der Gallenwege.

Gallenblasenkarzinome und intrahepatische cholangiozelluläre Karzinome können zuverlässig durch Ultraschall, Computertomographie und MRT abgegrenzt werden, während perihiläre und distale cholangiozelluläre Karzinome am besten durch eine ERC oder MRC diagnostiziert werden können.

Die einzige kurative Therapieoption bei Karzinomen des Gallensystems ist die chirurgische Resektion. Es gibt zurzeit keine Indikation für neoadjuvante oder adjuvante Therapiemaßnahmen außerhalb von klinischen Studien.

Gallenblasen- und Gallengangskarzinome sind mäßig chemotherapiesensitive Tumoren. In Phase-II-Studien liegen die Ansprechraten durch eine Monochemotherapie mit 5-FU oder Gemcitabine bei ca. 10 - 30 %. Durch Kombinationschemotherapien, insbesondere durch die Kombination Gemcitabine/Cisplatin, werden in Phase-II-Studien höhere Ansprechraten von ca. 20 - 50 % erzielt. Aufgrund der geringen Inzidenz der Gallenblasen- und Gallengangskarzinome fehlen große Phase-III-Studien, die den Einfluss einer palliativen Chemotherapie auf das Überleben und die Lebensqualität der Patienten untersuchen oder unterschiedliche Chemotherapieprotokolle miteinander vergleichen. Patienten mit gutem Allgemeinzustand oder Patienten mit tumorassoziierten Symptomen sollten eine gut verträgliche palliative Chemotherapie (möglichst innerhalb von klinischen Studien) erhalten, während man bei Patienten mit nichttumorassoziiertem schlechten Allgemeinzustand mit chemotherapeutischen Maßnahmen zurückhaltend sein sollte.

Endoskopische Therapien, wie PTC- oder ERC-Stenting und photodynamische Therapie, sind wichtige palliative Maßnahmen, die den Gallenabfluss gewährleisten und zur Verlängerung des Überlebens und zur Verbesserung der Lebensqualität der Patienten beitragen.

Abstract

Risk factors for cholangiocellular and gallbladder carcinomas are bile stones and chronic inflammation of the biliary system.

Gallbladder cancer and intrahepatic cholangiocellular carcinomas can be diagnosed with a high sensitivity by ultasonography, CT and MRI, while the most sensitive diagnostic methods for perihilar or distal cholangiocellular carcinomas are ERC or MRC.

The only curative option for patients with gallbladder- or bile duct cancer is surgical resection. Outside clinical studies there is currently no indication for neoadjuvant or adjuvant chemotherapy or radiochemotherapy.

Gallbladder and bile duct carcinomas are moderately chemotherapy-sensitive tumors. The objective response rates in phase II studies with 5-FU or gemcitabine monochemotherapy are between 10 - 30 %. Higher response rates between 20 - 50 % have been observed in phase II studies with combination chemotherapy, in particular with the combination of gemcitabine/cisplatin. Because of the low incidence of gallbladder and bile duct carcinomas there are currently no large phase III trails investigating the impact of chemotherapy on survival and quality of life or comparing the activity of different chemotherapy protocols. Patients in good general physical conditions or with tumor-associated symptoms should be treated with palliative chemotherapy (whenever possible in clinical studies), while chemotherapy should be avoided in patients with severe non-tumor-associated morbidity.

Endoscopic procedures, such as PTC- or ERC-stenting and photodynamic therapy, are important supportive therapies which can help to maintain the bile flow and consequently improve survival and quality of life of patients with malignant bile duct obstructions.

Schlüsselwörter

Gallengangskarzinom - Gallenblasenkarzinom - Diagnose - Chemotherapie

Key words

Bile Duct Carcinoma - Gallbladder Carcinoma - Diagnosis - Chemotherapy

Literatur

• 1 Bismuth H, Majno P E. Hepatobiliary surgery.  J Hepatol. 2000;  32 (1 Suppl) 208-224
• 2 de Groen P C, Gores G J, LaRusso N F. et al . Biliary tract cancers.  N Engl J Med. 1999;  341 (18) 1368-1378
• 3 Gores G J. Cholangiocarcinoma: current concepts and insights.  Hepatology. 2003;  37 (5) 961-969
• 4 Chalasani N, Baluyut A, Ismail A. et al . Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study.  Hepatology. 2000;  31 (1) 7-11
• 5 Chapman R W. Risk factors for biliary tract carcinogenesis.  Ann Oncol. 1999;  10 (Suppl 4) 308-311
• 6 Ramage J K, Donaghy A, Farrant J M. et al . Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis.  Gastroenterology. 1995;  108 (3) 865-869
• 7 Patel A H, Harnois D M, Klee G G. et al . The utility of CA 19 - 9 in the diagnosis of cholangiocarcinoma in patients without primary sclerosing cholangitis.  Am J Gastroenterol. 2000;  95 (1) 204-207
• 8 Lindberg B, Arnelo U, Bergquist A. et al . Diagnosis of biliary strictures in conjunction with endoscopic retrograde cholangiopancreaticography, with special reference to patients with primary sclerosing cholangitis.  Endoscopy. 2002;  34 (11) 909-916
• 9 Keiding S, Hansen S B, Rasmussen H H. et al . Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography.  Hepatology. 1998;  28 (3) 700-706
• 10 Bach A M, Loring L A, Hann L E. et al . Gallbladder cancer: can ultrasonography evaluate extent of disease?.  J Ultrasound Med. 1998;  17 (5) 303-309
• 11 Fulcher A S, Turner M A. HASTE MR cholangiography in the evaluation of hilar cholangiocarcinoma.  AJR Am J Roentgenol. 1997;  169 (6) 1501-1505
• 12 Schwartz L H, Coakley F V, Sun Y. et al . Neoplastic pancreaticobiliary duct obstruction: evaluation with breath-hold MR cholangiopancreatography.  AJR Am J Roentgenol. 1998;  170 (6) 1491-1495
• 13 Zhang Y, Uchida M, Abe T. et al . Intrahepatic peripheral cholangiocarcinoma: comparison of dynamic CT and dynamic MRI.  J Comput Assist Tomogr. 1999;  23 (5) 670-677
• 14 Glasbrenner B, Ardan M, Boeck W. et al . Prospective evaluation of brush cytology of biliary strictures during endoscopic retrograde cholangiopancreatography.  Endoscopy. 1999;  31 (9) 712-717
• 15 Khan S A, Davidson B R, Goldin R. et al . Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document.  Gut. 2002;  51 (Suppl 6) VI1-9
• 16 Yeh T S, Jan Y Y, Tseng J H. et al . Malignant perihilar biliary obstruction: magnetic resonance cholangiopancreatographic findings.  Am J Gastroenterol. 2000;  95 (2) 432-440
• 17 Zidi S H, Prat F, Le Guen O. et al . Performance characteristics of magnetic resonance cholangiography in the staging of malignant hilar strictures.  Gut. 2000;  46 (1) 103-106
• 18 Materne R, Van Beers B E, Gigot J F. et al . Extrahepatic biliary obstruction: magnetic resonance imaging compared with endoscopic ultrasonography.  Endoscopy. 2000;  32 (1) 3-9
• 19 Menzel J, Poremba C, Dietl K H. et al . Preoperative diagnosis of bile duct strictures - comparison of intraductal ultrasonography with conventional endosonography.  Scand J Gastroenterol. 2000;  35 (1) 77-82
• 20 Wehrmann T, Martchenko K, Menke D. et al . Clinical value of intraductal ultrasonography for clarification of confusing ERCP results.  Dtsch Med Wochenschr. 2003;  128 (16) 863-869
• 21 Donohue J H, Nagorney D M, Grant C S. et al . Carcinoma of the gallbladder. Does radical resection improve outcome?.  Arch Surg. 1990;  125 (2) 237-241
• 22 Klempnauer J, Ridder G J, von Wasielewski R. et al . Resectional surgery of hilar cholangiocarcinoma: a multivariate analysis of prognostic factors.  J Clin Oncol. 1997;  15 (3) 947-954
• 23 Takada T, Amano H, Yasuda H. et al . Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma.  Cancer. 2002;  95 (8) 1685-1695
• 24 Todoroki T, Ohara K, Kawamoto T. et al . Benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma.  Int J Radiat Oncol Biol Phys. 2000;  46 (3) 581-587
• 25 Hejna M, Pruckmayer M, Raderer M. The role of chemotherapy and radiation in the management of biliary cancer: a review of the literature.  Eur J Cancer. 1998;  34 (7) 977-986
• 26 de Aretxabala X, Roa I, Burgos L. et al . Preoperative chemoradiotherapy in the treatment of gallbladder cancer.  Am Surg. 1999;  65 (3) 241-246
• 27 McMasters K M, Tuttle T M, Leach S D. et al . Neoadjuvant chemoradiation for extrahepatic cholangiocarcinoma.  Am J Surg. 1997;  174 (6) 605-608
• 28 Glimelius B, Hoffman K, Graf W. et al . Cost-effectiveness of palliative chemotherapy in advanced gastrointestinal cancer.  Ann Oncol. 1995;  6 (3) 267-274
• 29 Morganti A G, Trodella L, Valentini V. et al . Combined modality treatment in unresectable extrahepatic biliary carcinoma.  Int J Radiat Oncol Biol Phys. 2000;  46 (4) 913-919
• 30 Rich T A. Chemoradiation for pancreatic and biliary cancer: current status of RTOG studies.  Ann Oncol. 1999;  10 (Suppl 4) 231-233
• 31 Berr F, Wiedmann M, Tannapfel A. et al . Photodynamic therapy for advanced bile duct cancer: evidence for improved palliation and extended survival.  Hepatology. 2000;  31 (2) 291-298
• 32 Ortner M A, Liebetruth J, Schreiber S. et al . Photodynamic therapy of nonresectable cholangiocarcinoma.  Gastroenterology. 1998;  114 (3) 536-542
• 33 Mitry E, Van Cutsem E, Van Laethem J L. et al . A randomized phase II trail of weekly high dose 5FU (HD-FU) with and without folinic acid (FA) and cisplatin (P) in patients (PTS) with advanced biliary tract carcinoma: the EORTC 40 955 trial.  Proc ASCO. 2002;  21 696
• 34 Raderer M, Hejna M H, Valencak J B. et al . Two consecutive phase II studies of 5-fluorouracil/leucovorin/mitomycin C and of gemcitabine in patients with advanced biliary cancer.  Oncology. 1999;  56 (3) 177-180
• 35 Arroyo G, Gallardo J, Rubio B. et al . Gemcitabine (GEM) in advanced biliary tract cancer (ABTC). Experience from Chile and Argentina in phase II trials.  Proc ASCO. 2001;  20 626
• 36 Kubicka S, Rudolph K L, Tietze M K. et al . Phase II study of systemic gemcitabine chemotherapy for advanced unresectable hepatobiliary carcinomas.  Hepatogastroenterology. 2001;  48 (39) 783-789
• 37 Ducreux M, Rougier P, Fandi A. et al . Effective treatment of advanced biliary tract carcinoma using 5-fluorouracil continuous infusion with cisplatin.  Ann Oncol. 1998;  9 (6) 653-656
• 38 Taieb J, Mitry E, Boige V. et al . Optimization of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of leucovorin, 5-FU and cisplatin (LV5FU2-P regimen) in patients with biliary tract carcinoma.  Ann Oncol. 2002;  13 (8) 1192-1196
• 39 Nehls O, Klump B, Arkenau H T. et al . Oxaliplatin, fluorouracil and leucovorin for advanced biliary system adenocarcinomas: a prospective phase II trial.  Br J Cancer. 2002;  87 (7) 702-704
• 40 Nehls O, Oettle H, Hartmann J T. et al . Oxaliplatin plus capecitabine in advanced biliary system adenocarcinomas: a multicenter phase II trial.  Proc ASCO. 2003;  22 1126
• 41 Abid L, Oukkal M, Berkane S. et al . Phase II trial with gemcitabine and cisplatin combination in the treatment of locally advanced and metastatic gall bladder carcinoma.  Proc ASCO. 2003;  22 1302
• 42 Reyes-Vidal J, Gallardo J, Yanez E. et al . Gemcitabine (G) and cisplatin (C) in the treatment of patients (PTS) with unresectable or metastatic gallbladder cancer: results of the phase II GOCCHI study 2000 - 13.  Proc ASCO. 2003;  22 1095
• 43 Thongprasert S, Napapan S, Charoentum C. et al . Phase II study of gemcitabine plus cisplatin in biliary tract cancer.  Proc ASCO. 2003;  22 1221