Journal of Gastrointestinal Cancer

, Volume 43, Issue 3, pp 396–404

Chemotherapy for the Biliary Tract Cancers: Moving Toward Improved Survival Time

  • Adriana Romiti
  • Chiara D’Antonio
  • Angelo Zullo
  • Ida Sarcina
  • Roberta Di Rocco
  • Viola Barucca
  • Valeria Durante
  • Paolo Marchetti
Review Article
  • 265 Downloads

Abstract

Background

The biliary tract carcinomas rank fifth in incidence among all gastrointestinal tumours. This group of tumours includes both cholangiocarcinoma and gallbladder carcinoma. Although surgery represents the main therapeutic option for these patients, both radiotherapy and chemotherapy could be used in a multidisciplinary approach. Several studies are currently available on the use of chemotherapy, including 5-fluorouracil, mitomycin C, methotrexate, doxorubicin and cisplatin or newer anticancer molecules, such as gemcitabine, capecitabine, oxaliplatin and irinotecan. However, the small sample size of most of these studies prevents generalization.

Discussion

We reviewed the available data on both chemotherapy and targeted therapies for biliary carcinoma. By using conventional chemotherapy, a response rate ranging from 10% to 40% has been reported. Although encouraging data emerged with the use of targeted therapies, further efforts are needed to improve treatment options for patients with biliary tract cancer.

Keywords

Cholangiocarcinoma Gallbladder cancer Chemotherapy Treatment 

References

  1. 1.
    Kuwayti K, Baggenstoss AH, Stauffer MH, et al. Carcinoma of the major intrahepatic and the extrahepatic bile ducts exclusive of the papilla of Vater. Surg Ginecol Obstet. 1957;104:357–66.Google Scholar
  2. 2.
    Welzel TM, McGlynn KA, Hsing AW, et al. Impact of classification of hilar cholangiocarcinomas (Klatskin tumours) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States. J Natl Cancer Inst. 2006;98:873–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Alvaro D, Crocetti E, Ferretti S, et al. Descriptive epidemiology of cholangiocarcinoma in Italy. Digestive and Liver Disease. 2010;42:490–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Parkin DM, Muir CS. Cancer incidence in five continents. Lyon, France: International Agency for Research on Cancer; 1992. p. 45–173. IARC Scientific Publications No. 120.Google Scholar
  5. 5.
    Carriaga MT, Henson DE. Liver, gallbladder, extrahepatic bile duct and pancreas. Cancer. 1995;75:71–190.Google Scholar
  6. 6.
    Weinbren K, Mutum SS. Pathological aspects of cholangiocarcinoma. J Pathol. 1983;139:217–38.PubMedCrossRefGoogle Scholar
  7. 7.
    Henson DE, Albores-Saavadra J, Corle D. Carcinoma of the hepatic bile ducts. Cancer. 1992;70:1498–501.PubMedCrossRefGoogle Scholar
  8. 8.
    Ajiki T, Fujimori T, Onoyama H, et al. K-ras gene mutation in gall bladder carcinomas and dysplasia. Gut. 1996;38:426–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Tannapfel A, Sommerer F, Benicke M, et al. Mutations of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma. Gut. 2003;52:706–12.PubMedCrossRefGoogle Scholar
  10. 10.
    Sturm PD, Baas IO, Clement MJ, et al. Alterations of the p53 tumour-suppressor gene and K-ras oncogene in perihilar cholangiocarcinomas from a high-incidence area. Int J Cancer. 1998;78:695–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Mikami T, Yanagisawa N, Baba H, et al. Association of Bcl-2 protein expression with gallbladder carcinoma differentiation and progression and its relation to apoptosis. Cancer. 1999;85:318–25.PubMedCrossRefGoogle Scholar
  12. 12.
    Kim YT, Kim J, Jang YH, et al. Genetic alterations in gallbladder adenoma, dysplasia and carcinoma. Cancer Lett. 2001;169:59–68.PubMedCrossRefGoogle Scholar
  13. 13.
    Nakazawa K, Dobashi Y, Suzuki S, et al. Amplification and overexpression of c-erbB-2, epidermal growth factor receptor, and c-met in biliary tract cancers. J Pathol. 2005;206:356–65.PubMedCrossRefGoogle Scholar
  14. 14.
    Ukita Y, Kato M, Terada T. Gene amplification and mRNA and protein overexpression of c-erbB-2 (HER-2/neu) in human intrahepatic cholangiocarcinoma as detected by fluorescence in situ hybridization, in situ hybridization, and immunohistochemistry. J Hepatol. 2002;36:780–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Javle MM, Tan D, Yu J, et al. Nuclear survivin expression predicts poor outcome in cholangiocarcinoma. Hepatogastroenterology. 2004;51:1653–7.PubMedGoogle Scholar
  16. 16.
    De Groen PC, Gores GJ, Nicholas F, et al. Biliary tract cancers. N Engl J Med. 1999;341:1368–78.PubMedCrossRefGoogle Scholar
  17. 17.
    Alvaro D, Cannizzaro R, Labianca R, et al. Cholangiocarcinoma: a position paper by the Italian Society of Gastroenterology (SIGE), the Italian Association of Hospital Gastroenterology (AIGO), the Italian Association of Medical Oncology (AIOM) and the Italian Association of Oncological Radiotherapy (AIRO). Dig Liver Dis. 2010;42:831–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Hezel AF, Deshpande V, Zhu AX. Genetics of biliary tract cancers and emerging targeted therapies. J Clin Oncol. 2010;28:3531–40.PubMedCrossRefGoogle Scholar
  19. 19.
    Fong Y, Jarnagin W, Blumgart LH. Gallbladder cancer: comparison of patients presenting initially for definitive operation with those presenting after prior noncurative intervention. Ann Surg. 2000;232:557–69.PubMedCrossRefGoogle Scholar
  20. 20.
    Burke EC, Jarnagin WR, Hochwald SN, et al. Hilar cholangiocarcinoma: patterns of spread, the importance of hepatic resection for curative operation, and a presurgical clinical staging system. Ann Surg. 1998;228:385–94.PubMedCrossRefGoogle Scholar
  21. 21.
    Mahe M, Romestaing P, Talon B, et al. Radiation therapy in extrahepatic bile duct carcinoma. Radiother Oncol. 1991;21:121–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Kresl JJ, Schild SE, Henning GT, et al. Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallblader carcinoma. Int J Radiat Oncol Bio Phis. 2002;52:67–75.Google Scholar
  23. 23.
    Yee K, Sheppard BC, Domreis J. Cancers of the gallbladder and biliary ducts. Oncology. 2002;16:939–46.PubMedGoogle Scholar
  24. 24.
    Labianca R, Pessi MA, Zamparelli G. Treatment of colorectal cancer. Current guidelines and future prospects for drug therapy. Drugs. 1997;53:593–606.PubMedCrossRefGoogle Scholar
  25. 25.
    Chen JS, Lin YC, Jan YY, et al. Mitomycin C with weekly 24-h infusion of high dose 5-fluorouracil and leucovorin in patients with biliary tract and periampullar carcinomas. Anticancer Drugs. 2001;12:339–43.PubMedCrossRefGoogle Scholar
  26. 26.
    Harvey JH, Smith FP, Schein PS. 5-FU, mitomycin and doxorubicin [FAM] in carcinoma of the biliary tract. J Clin Oncol. 1984;2:1245–8.PubMedGoogle Scholar
  27. 27.
    Kobayashi K, Tsuji A, Morita S, et al. A phase II study of LFP therapy [5-FU[5-fluorouracil] continuous infusion and low-dose consecutive [cisplatin] CDDP] in advanced biliary tract carcinoma. BMC Cancer. 2006;6:121.PubMedCrossRefGoogle Scholar
  28. 28.
    Cantore M, Mambrini A, Fiorentini G, et al. Phase II study of hepatic intraarterial epirubicin and cisplatin, with systemic 5-fluorouracil in patients with unresectable biliary tract tumours. Cancer. 2005;103:1402–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Tajeb J, Mitry E, Boige T, et al. Optimization of 5-fluorouracil [FU]/cisplatin combination chemoterapy with a new schedule of leucovorin 5FU and cisplatin [LV5FU 2-P regimen] in patients with biliary tract carcinoma. Ann Oncol. 2002;13:1192–6.CrossRefGoogle Scholar
  30. 30.
    Ducreux M, Van Cutsen E, Van Laethem JL, et al. A randomized phase II trial of weekly high dose 5-fluorouracil with and without folinic acid and cisplatin in patients with advanced biliary tract carcinoma: results of the 40955 EORTC trial. Eur J Cancer. 2005;41:398–403.PubMedCrossRefGoogle Scholar
  31. 31.
    Sanz Altamira PM, Ferrante K, Jenkins RL, et al. A phase II trial of 5 fluorouracil, leucovorin, and carboplatin in patients with unresectable biliary tree carcinoma. Cancer. 1998;82:2321–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Patt YZ, Jones DV, Hoque A, et al. Phase II trial of intravenous flourouracil and subcutaneous interferon alfa-2b for biliary tract cancer. J Clin Oncol. 1996;14:2311–5.PubMedGoogle Scholar
  33. 33.
    Patt YZ, Hassan MM, Lozano RD, et al. Phase II trial of cisplatin, interferon alpha-2b, doxorubicin, and 5-fluorouracil for biliary tract cancer. Clin Cancer Res. 2001;7:3375–80.PubMedGoogle Scholar
  34. 34.
    Rao S, Cunningham D, Hawkins RE, et al. Phase III study of 5-FU, etoposide and leucovorin [FELV] compared to epirubicin, cisplatin and 5-FU [ECF] in previously untreated patients with advanced biliary cancer. Br J Cancer. 2005;92:1650–4.PubMedCrossRefGoogle Scholar
  35. 35.
    Patt YZ, Hassan MM, Aguayo A, et al. Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma. Cancer. 2004;101:578–86.PubMedCrossRefGoogle Scholar
  36. 36.
    Kornek GV, Schuell B, Laengle F, et al. Mitomycin C in combination with capecitabine or biweekly high dose gemcitabine in patients with advanced biliary tract cancer: a randomised phase II trial. Ann Oncol. 2004;15:478–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Kim TW, Chang HM, Kang HJ, et al. Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced biliary cancer. Ann Oncol. 2003;14:1115–20.PubMedCrossRefGoogle Scholar
  38. 38.
    Hong YS, Lee J, Lee SC, et al. Phase II study of capecitabine and cisplatin in previously untreated advanced biliary tract cancer. Cancer Chemother Pharmacol. 2007;60:321–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Park SH, Park YH, Lee JN, et al. Phase II study of epirubicin, cisplatin and capecitabine for advanced biliary tract adenocarcinoma. Cancer. 2006;106:361–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Knox JJ, Hedley D, Oza A, et al. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol. 2005;23:2332–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Cho JY, Paik YH, Chang YS, et al. Capecitabine combined with gemcitabine (CapGem) as first-line treatment in patients with advanced/metastatic biliary tract carcinoma. Cancer. 2005;104:2753–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Nehls O, Oettle H, Hartmann JT, et al. Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial. Br J Cancer. 2008;98:309–15.PubMedCrossRefGoogle Scholar
  43. 43.
    Overmann JM, Varadhachary GR, Adinin R, et al. Phase II study of capecitabine and oxaliplatin for advanced adenocarcinoma of the small bowel and ampulla of Vater. J Clin Oncol. 2009;27:2598–603.CrossRefGoogle Scholar
  44. 44.
    Tada M, Nakai Y, Sasaki T, et al. Recent progress and limitations of chemotherapy for pancreatic and biliary tract cancers. World J Clin Oncol. 2011;2:158–63.PubMedCrossRefGoogle Scholar
  45. 45.
    Ueno H, Okusaka T, Ikeda M, et al. Phase II study of S-1 in patients with advanced biliary tract cancer. Br J Cancer. 2004;91:1769–74.PubMedCrossRefGoogle Scholar
  46. 46.
    Park I, Lee J-L, Ryu M-H, et al. Efficacy and safety of S-1 monotherapy in patients with advanced biliary tract adenocarcinoma. Oncology. 2009;76:126–32.PubMedCrossRefGoogle Scholar
  47. 47.
    Furuse J, Okusaka T, Boku N, et al. S-1 monotherapy as first-line treatment in patients with advanced biliary tract cancer: a multicenter phase II study. Cancer Chemother Pharmacol. 2008;62:849–55.PubMedCrossRefGoogle Scholar
  48. 48.
    Sasaki t, Isayama H, Yashima Y, et al. S-1 monotherapy in patients with advanced biliary tract cancer. Oncology. 2009;77:71–4.PubMedCrossRefGoogle Scholar
  49. 49.
    Sasaki T, Isayama H, Nakai Y, et al. Multicenter, phase II study of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer. Cancer Chemother Pharmacol. 2010;65:1101–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Kanai M, Yoshimura K, Tsumura T, et al. A multi-institution phase II study of gemcitabine/S-1 combination chemotherapy for patients with advanced biliary tract cancer. Cancer Chemother Pharmacol. 2011;67:1429–34.PubMedCrossRefGoogle Scholar
  51. 51.
    Kim YJ, Im S-A, Kim HG, et al. A phase II trial of S-1 and cisplatin in patients with metastatic or relapsed biliary tract cancer. Ann Oncol. 2008;19:99–103.PubMedCrossRefGoogle Scholar
  52. 52.
    Kim KP, Jang G, Hong YS, et al. Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the CYP2A6 polymorphism on pharmacokinetics and clinical activity. Br J Cancer. 2011;104:605–12.PubMedCrossRefGoogle Scholar
  53. 53.
    Scheithauer W. Review of gemcitabine in biliary tract carcinoma. Semin Oncol. 2002;29:40–5.PubMedGoogle Scholar
  54. 54.
    Burris 3rd HA, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.PubMedGoogle Scholar
  55. 55.
    Castro MP. Efficacy of gemcitabine in the treatment of patients with gallbladder carcinoma. A case report. Cancer. 1998;82:639–41.PubMedCrossRefGoogle Scholar
  56. 56.
    Gelibter A, Malaguti P, Di Cosimo S, et al. Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree. Cancer. 2005;104:1237–45.PubMedCrossRefGoogle Scholar
  57. 57.
    Doval DC, Sekham JS, Gupta SK, et al. A phase II study of gemcitabine and cisplatin in chemotherapy-naive, unresectable gall bladder cancer. Br J Cancer. 2004;19:1516–20.CrossRefGoogle Scholar
  58. 58.
    Thongprasert S, Napapan S, Charoentum C, et al. Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. Ann Oncol. 2005;16:279–81.PubMedCrossRefGoogle Scholar
  59. 59.
    Kim ST, Park JO, Lee J, et al. A phase II study of gemcitabine and cisplatin in advanced biliary tract cancer. Cancer. 2006;106:1339–46.PubMedCrossRefGoogle Scholar
  60. 60.
    Giuliani F, Gebbia V, Maiello E, et al. Gemcitabine and cisplatin for inoperable and/or metastatic biliary tree carcinomas: a multicenter phase II study of the Gruppo Oncologico dell'Italia Meridionale [GOIM]. Ann Oncol. 2006;17:vii73–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Meyerhardt JA, Zhu AX, Stuart K, et al. Phase-II study of gemcitabine and cisplatin in patients with metastatic biliary and gallbladder cancer. Dig Dis Sci. 2008;53:564–70.PubMedCrossRefGoogle Scholar
  62. 62.
    Valle J, Wasan H, Palmer DH, et al. ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–81.PubMedCrossRefGoogle Scholar
  63. 63.
    Okusaka T, Nakachi K, Fukutomi A, et al. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010;103:469–74.PubMedCrossRefGoogle Scholar
  64. 64.
    Julka PK, Puri T, Rath GK. A phase II study of gemcitabine and carboplatin combination chemotherapy in gallbladder carcinoma. Hepatobiliary Pancreat Dis Int. 2006;5:110–4.PubMedGoogle Scholar
  65. 65.
    Williams KJ, Picus J, Trinkhaus K, et al. Gemcitabine with carboplatin for advanced biliary tract cancers: a phase II single institution study. HPB [Oxford]. 2010;12:418–26.CrossRefGoogle Scholar
  66. 66.
    Harder J, Riecken B, Kummer O, et al. Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary tract cancer. Br J Cancer. 2006;95:848–52.PubMedCrossRefGoogle Scholar
  67. 67.
    André T, Reyes-Vidal JM, Fartoux L, et al. Gemcitabine and oxaliplatin in advanced biliary tract carcinoma: a phase II study. Br J Cancer. 2008;99:862–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Kim HJ, Lee NS, Lee SC, et al. A phase II study of gemcitabine in combination with oxaliplatin as first-line chemotherapy in patients with inoperable biliary tract cancer. Cancer Chemother Pharmacol. 2009;64:371–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Jang JS, Lim HY, Hwang IG, et al. Gemcitabine and oxaliplatin in patients with unresectable biliary cancer including gall bladder cancer: a Korean Cancer Study Group phase II. Cancer Chemother Pharmacol. 2010;65:641–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Sharma A, Dwary AD, Mohanti BK, et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol. 2010;28:4581–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Wagner AD, Buechner-Steudel P, Moehler M, et al. Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials. Br J Cancer. 2009;101:1846–52.PubMedCrossRefGoogle Scholar
  72. 72.
    Alberts SR, Al-Khatib H, Mahoney MR, et al. Gemcitabine, 5-fluorouracil, and leucovorin in advanced biliary tract and gallbladder carcinoma: a North Central Cancer Treatment Group phase II trial. Cancer. 2005;103:111–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Knox JJ, Hedley D, Oza A, et al. Gemcitabine concurrent with continuous infusional 5-fluourouracil in advanced biliary cancers: a review of the Princess Margaret Hospital experience. Ann Oncol. 2004;15:770–4.PubMedCrossRefGoogle Scholar
  74. 74.
    Kuhn R, Hribaschek A, Eichelmann K, et al. Outpatient therapy with gemcitabine and docetaxel for gallbladder, biliary, and cholangio-carcinomas. Invest New Drugs. 2002;20:351–6.PubMedCrossRefGoogle Scholar
  75. 75.
    Eckel F, Schmid RM. Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer. 2007;26:896–902.CrossRefGoogle Scholar
  76. 76.
    Ennis BW, Lippman ME, Dickson RB. The EGF receptor system as a target for antitumour therapy. Cancer Invest. 1991;9:553–62.PubMedCrossRefGoogle Scholar
  77. 77.
    Lee CS, Pirdas A. Epidermal growth factor receptor immunoreactivity in gallbladder and extrahepatic biliary tract tumours. Pathol Res Pract. 1995;191:1087–91.PubMedCrossRefGoogle Scholar
  78. 78.
    Leone F, Cavalloni G, Pignochino Y, et al. Somatic mutations of epidermal growth factor receptor in bile duct and gallbladder carcinoma. Clin Cancer Res. 2006;12:1680–5.PubMedCrossRefGoogle Scholar
  79. 79.
    Zhu AX, Hezel AF. Development of molecularly targeted therapies in biliary tract cancers: reassessing the challenges and opportunities. Hepatology. 2011;53:695–704.PubMedCrossRefGoogle Scholar
  80. 80.
    Philip PA, Mahoney MR, Allmer C, et al. Phase II study of erlotinib in patients with advanced biliary cancer. J Clin Oncol. 2006;24:3069–74.PubMedCrossRefGoogle Scholar
  81. 81.
    Gruenberger B, Schueller J, Heubrandtner U, et al. Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study. Lancet Oncol. 2010;11:1142–8.PubMedCrossRefGoogle Scholar
  82. 82.
    Malka D, Trarbach T, Fartoux L, et al. A multicenter, randomized phase II trial of gemcitabine and oxaliplatin [GEMOX] alone or in combination with biweekly cetuximab in the first-line treatment of advanced biliary cancer: interim analysis of the BINGO trial. J Clin Oncol. 2009;27:15s [suppl; abstr 4520].CrossRefGoogle Scholar
  83. 83.
    Zhu AX, Meyerhardt JA, Blaszkowsky LS, et al. Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol. 2010;11:48–54.PubMedCrossRefGoogle Scholar
  84. 84.
    Lubner Sam J, Mahoney Michelle R, Kolesar Jill L, et al. Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II consortium study. J Clinical Oncol. 2010;28:3491–7.CrossRefGoogle Scholar
  85. 85.
    Bengala C, Bertolini F, Malavasi N, et al. Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial. Br J Cancer. 2010;102:68–72.PubMedCrossRefGoogle Scholar
  86. 86.
    Bekaii-Saab T, Phelps MA, Li X, et al. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol. 2011;29:2357–63.PubMedCrossRefGoogle Scholar
  87. 87.
    Su CH, Tsay SH, Wu CC, et al. Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma. Ann Surg. 1996;223:384–94.PubMedCrossRefGoogle Scholar
  88. 88.
    Liu CL, Fan ST, Lo CM, et al. Improved operative and survival outcomes of surgical treatment for hilar cholangiocarcinoma. Br J Surg. 2006;93:1488–94.PubMedCrossRefGoogle Scholar
  89. 89.
    Murakami Y, Uemura K, Sudo T, et al. Prognostic factors of patients with advanced gallbladder carcinoma following aggressive surgical resection. J Gastrointest Surg. 2011;15:1007–16.PubMedCrossRefGoogle Scholar
  90. 90.
    Hong SM, Cho H, Lee OJ, et al. The number of metastatic lymph nodes in extrahepatic bile duct carcinoma as a prognostic factor. Am J Surg Pathol. 2005;29:1177–83.PubMedCrossRefGoogle Scholar
  91. 91.
    Murakami Y, Uemura K, Hayasidani Y, et al. Indication for postoperative adjuvant therapy in biliary carcinoma based on analysis of recurrence and survival after surgical resection. Dig Dis Sci. 2009;54:1360–4.PubMedCrossRefGoogle Scholar
  92. 92.
    Kamada T, Saitou H, Takamura A, et al. The role of radiotherapy in the management of extrahepatic bile duct cancer: an analysis of 145 consecutive patients treated with intraluminal and/or external beam radiotherapy. Int J Radiat Oncol Biol Phys. 1996;34:963–4.CrossRefGoogle Scholar
  93. 93.
    Pitt HA, Nakeeb A, Abrams RA, et al. Perihilar cholangiocarcinoma. Post-operative radiotherapy does not improve survival. Ann Surg. 1995;221:788–97.PubMedCrossRefGoogle Scholar
  94. 94.
    Kobayashi S, Nagano H, Marubashi S, et al. Impact of postoperative irradiation after non-curative resection of hilar biliary cancer. J Surg Oncol. 2009;100:657–62.PubMedCrossRefGoogle Scholar
  95. 95.
    Morak MJ, van der Gaast A, Incrocci L, et al. Adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer: a prospective randomized controlled trial. Ann Surg. 2008;248:1031–41.PubMedCrossRefGoogle Scholar
  96. 96.
    Krishnan S, Rana V, Evans DB, et al. Role of adjuvant chemoradiation therapy in adenocarcinomas of the ampulla of Vater. Int J Radiat Oncol Biol Phys. 2008;70:735–43.PubMedCrossRefGoogle Scholar
  97. 97.
    Kim K, Chie EK, Jang JY, et al. Role of adjuvant chemoradiotherapy for ampulla of Vater cancer. Int J Radiat Oncol Biol Phys. 2009;75:436–41.PubMedCrossRefGoogle Scholar
  98. 98.
    Smeenk HG, van Eijck CH, Hop WC, et al. Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891. Ann Surg. 2007;246:734–40.PubMedCrossRefGoogle Scholar
  99. 99.
    Lim KH, Oh DY, Chie EK, et al. Adjuvant concurrent chemoradiation therapy (CCRT) alone versus CCRT followed by adjuvant chemotherapy: which is better in patients with radically resected extrahepatic biliary tract cancer? A non-randomized, single center study. BMC Cancer. 2009;9:345.PubMedCrossRefGoogle Scholar
  100. 100.
    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;95:1685–95.PubMedCrossRefGoogle Scholar
  101. 101.
    Murakami Y, Uemura K, Sudot, et al. Gemcitabine-based adjuvant chemotherapy improves survival after aggressive surgery for hilar cholangiocarcinoma. J Gastrointest Surg. 2009;13:1470–9.PubMedCrossRefGoogle Scholar
  102. 102.

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Adriana Romiti
    • 1
  • Chiara D’Antonio
    • 1
  • Angelo Zullo
    • 2
  • Ida Sarcina
    • 1
  • Roberta Di Rocco
    • 1
  • Viola Barucca
    • 1
  • Valeria Durante
    • 1
  • Paolo Marchetti
    • 1
  1. 1.Department of Oncology, Sant’Andrea Hospital“La Sapienza” UniversityRomeItaly
  2. 2.Department of Gastroenterology and Digestive Endoscopy“Nuovo Regina Margherita” HospitalRomeItaly

Personalised recommendations