Annals of Surgical Oncology

, Volume 20, Issue 1, pp 318–324

Surgical Resection after Downsizing Chemotherapy for Initially Unresectable Locally Advanced Biliary Tract Cancer: A Retrospective Single-center Study

  • Atsushi Kato
  • Hiroaki Shimizu
  • Masayuki Ohtsuka
  • Hiroyuki Yoshidome
  • Hideyuki Yoshitomi
  • Katsunori Furukawa
  • Dan Takeuchi
  • Tsukasa Takayashiki
  • Fumio Kimura
  • Masaru Miyazaki
Hepatobiliary Tumors



Surgical resection is the only method for curative treatment of biliary tract cancer (BTC). Recently, an improved efficacy has been revealed in patients with initially unresectable locally advanced BTC to improve the prognosis by the advent of useful cancer chemotherapy. The aim of this study was to evaluate the effect of downsizing chemotherapy in patients with initially unresectable locally advanced BTC.


Initially unresectable locally advanced cases were defined as those in which therapeutic resection could not be achieved even by proactive surgical resection. Gemcitabine was administered intravenously once a week for 3 weeks followed by 1 week’s respite. Patients whose disease responded to chemotherapy were reevaluated to determine whether their tumor was resectable.


Chemotherapy with gemcitabine was provided to 22 patients with initially unresectable locally advanced BTC. Tumor was significantly downsized in nine patients, and surgical resection was performed in 8 (36.4%) of 22 patients. Surgical resection resulted in R0 resection in four patients and R1 resection in four patients. Patients who underwent surgical resection had a significantly longer survival compared with those unable to undergo surgery.


Preoperative chemotherapy enables the downsizing of initially unresectable locally advanced BTC, with radical resection made possible in a certain proportion of patients. Downsizing chemotherapy should be proactively carried out as a multidisciplinary treatment strategy for patients with initially unresectable locally advanced BTC with the aim of expanding the surgical indication.


  1. 1.
    Welzel TM, McGlynn KA, Hsing AW, O’Brien TR, Pfeiffer RM. Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra and extrahepatic cholangiocarcinoma in the United States. J Natl Cancer Inst. 2006;98:873–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Blechac B, Gores GJ. Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment. Hepatology. 2008;48:308–21.CrossRefGoogle Scholar
  3. 3.
    Shimizu H, Kimura F, Yoshidome H, et al. Aggressive surgical resection for hilar cholangiocarcinoma of the left-side predominance: radicality and safety of left-sided hepatectomy. Ann Surg. 2010;251:281–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Miyazaki M, Kimura F, Shimizu H, et al. One hundred seven consecutive surgical resections for hilar cholangiocarcinoma of Bismuth types II, III, IV between 2001 and 2008. J Hepatobiliary Pancreat Sci. 2009;17:470–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Raderer M, Hejna MH, Valencak JB, et al. Two consecutive phase II studies of 5-fluorouracil/leucovorin/mitomycin C and of gemcitabine in patients with advanced biliary cancer. Oncology. 1999;56:177–80.PubMedCrossRefGoogle Scholar
  6. 6.
    Penz M, Kornek GV, Raderer M, et al. II trial of two-weekly gemcitabine in patients with advanced biliary tract cancer. Ann Oncol. 2001;12:183–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Lin MH, Chen JS, Chen HH, Su WC. A phase II trial of gemcitabine in the treatment of advanced bile duct and periamullary carcinomas. Chemotherapy. 2003;49:154–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Bismuth H, Adam R, Lévi F, et al. Resection of non-resectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg. 1996;224:509–22.PubMedCrossRefGoogle Scholar
  9. 9.
    Adam R, Delvart V, Pascal G, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a mode to predict long-term survival. Ann Surg. 2004;240:644–58.PubMedCrossRefGoogle Scholar
  10. 10.
    Turrini O, Viret F, Moureau-Zabotto L, et al. Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially locally advanced head pancreatic adenocarcinoma. Eur J Surg Oncol. 2009;35:1306–11.PubMedCrossRefGoogle Scholar
  11. 11.
    Suda K, Ohtsuka M, Ambiru S, et al. Risk factors of liver dysfunction after extended hepatic resection in biliary tract malignancies. Am J Surg. 2009;197:752–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Yoshitomi H, Togawa A, Kimura F, et al.; Pancreatic cancer chemotherapy program of the Chiba university Department of general surgery affiliated hospital group. A randomized phase II trial of adjuvant chemotherapy with uracil/tegafur and gemcitabine versus gemcitabine alone in patients with resected pancreatic cancer. Cancer. 2008;113:2448–56.PubMedCrossRefGoogle Scholar
  13. 13.
    Adam R, Wicherts DA, de Haas RJ, et al. Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol. 2009;27:1829–35.PubMedCrossRefGoogle Scholar
  14. 14.
    Falcone A, Ricci S, Brunetti I, et al. Gruppo oncologico nord ovest. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the gruppo oncologico nord ovest. J Clin Oncol. 2007;25:1670–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Skof E, Rebersek M, Hlebanja Z, Ocvirk J. Capecitabine plus irinotecan (XELIRI regimen) compared to 5-FU/LV plus irinotecan (FOLFIRI regimen) as neoadjuvant treatment for patients with unresectable liver-only metastases of metastatic colorectal cancer: a randomised prospective phase II trial. BMC Cancer. 2009;9:120.PubMedCrossRefGoogle Scholar
  16. 16.
    Coskun U, Buyukberber S, Yaman E, et al. Xelox (capecitabine plus oxaliplatin) as neoadjuvant chemotherapy of unresectable liver metastases in colorectal cancer patients. Neoplasma. 2008;55:65–70.PubMedGoogle Scholar
  17. 17.
    Van Cutsem E, Rivera F, Berry S, et al.; First BEAT investigators. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol. 2009;20:1842–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Min BS, Kim NK, Ahn JB, et al. Cetuximab in combination with 5-fluorouracil, leucovorin and irinotecan as a neoadjuvant chemotherapy in patients with initially unresectable colorectal liver metastases. Onkologie. 2007;30:637–43.PubMedCrossRefGoogle Scholar
  19. 19.
    Morganti AG, Massaccesi M, La Torre G, et al. A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer. Ann Surg Oncol. 2010;17:194–205.PubMedCrossRefGoogle Scholar
  20. 20.
    Callery MP, Chang KJ, Fishman EK, et al. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16:1727–33.PubMedCrossRefGoogle Scholar
  21. 21.
    Sohn TA, Lillemoe KD, Cameron JL, et al. Re-exploration for periampullary carcinoma: resectability, perioperative results, pathology, and long-term outcome. Ann Surg. 1999;229:393–400.PubMedCrossRefGoogle Scholar
  22. 22.
    Gouma DJ, van Geenen RC, van Gulik TM, et al. Rates of complications and death after pancreaticoduodenectomy: risk factors and the impact of hospital volume. Ann Surg. 2000;232:786–95.PubMedCrossRefGoogle Scholar
  23. 23.
    Miyazaki M, Kato A, Ito H, et al. Combined vascular resection in operative resection for hilar cholangiocarcinoma: does it work or not? Surgery. 2007;141:581–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Pawlik TM, Scoggins CR, Zorzi D, et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg. 2005;241:715–22.PubMedCrossRefGoogle Scholar
  25. 25.
    Thongprasert S, Napapan S, Charoentrum C, Moonprakan S. Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. Ann Oncol. 2005;16:279–81.PubMedCrossRefGoogle Scholar
  26. 26.
    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
  27. 27.
    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
  28. 28.
    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
  29. 29.
    Leonard GD, Brenner B, Kemeny NE. Neoadjuvant chemotherapy before liver resection for patients with unresectable liver metastases from colorectal carcinoma. J Clin Oncol. 2005;23:2038–48.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2012

Authors and Affiliations

  • Atsushi Kato
    • 1
  • Hiroaki Shimizu
    • 1
  • Masayuki Ohtsuka
    • 1
  • Hiroyuki Yoshidome
    • 1
  • Hideyuki Yoshitomi
    • 1
  • Katsunori Furukawa
    • 1
  • Dan Takeuchi
    • 1
  • Tsukasa Takayashiki
    • 1
  • Fumio Kimura
    • 1
  • Masaru Miyazaki
    • 1
  1. 1.Department of General SurgeryChiba University Graduate School of MedicineChibaJapan

Personalised recommendations