Skip to main content
SpringerLink
Log in

Gemcitabine-Based Adjuvant Chemotherapy Improves Survival After Aggressive Surgery for Hilar Cholangiocarcinoma

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

The prognosis of hilar cholangiocarcinoma is dismal although aggressive surgery including major hepatectomy has been performed. The aim of this study was to clarify useful prognostic factors and the usefulness of gemcitabine-based adjuvant chemotherapy for patients with hilar cholangiocarcinoma who had undergone aggressive surgical resection.

Methods

Medical records of 42 patients with hilar cholangiocarcinoma who underwent surgical resection were reviewed retrospectively. Univariate and multivariate models were used to analyze the effect of various clinicopathological factors on long-term survival.

Results

Overall 1-, 3-, and 5-year survival rates of the 42 patients with hilar cholangiocarcinoma were 81%, 42%, and 30%, respectively (median survival time, 21.5 months). Univariate analysis revealed that adjuvant gemcitabine-based chemotherapy, tumor differentiation, lymph node metastasis, and surgical margin status were associated significantly with long-term survival (P < 0.05). Furthermore, use of a Cox proportional hazards regression model indicated that only adjuvant gemcitabine-based chemotherapy was a significant independent predictor of a favorable prognosis (P = 0.035). The toxicity of adjuvant gemcitabine-based chemotherapy was mild. Five-year actuarial survival rates of patients who did or did not receive adjuvant gemcitabine-based chemotherapy were 57% and 23%, respectively (P = 0.026).

Conclusions

Postoperative adjuvant gemcitabine-based chemotherapy may be a promising strategy to improve survival after surgical resection for hilar cholangiocarcinoma. A prospective randomized study should be done to confirm the results of this study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58:71–96. doi:10.3322/CA.2007.0010.

    Article  PubMed  Google Scholar 

  2. Nakeeb A, Pitt HA, Sohn TA, Coleman J, Abrams RA, Piantadosi S et al. Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg 1996;224:463–473. doi:10.1097/00000658-199610000-00005.

    Article  CAS  PubMed  Google Scholar 

  3. Murakami Y, Uemura K, Hayashidani Y, Sudo T, Hashimoto Y, Ohge H et al. Prognostic significance of lymph node metastasis and surgical margin status for distal cholangiocarcinoma. J Surg Oncol 2007;95:207–212. doi:10.1002/jso.20668.

    Article  PubMed  Google Scholar 

  4. Reding R, Buard JL, Lebeau G, Launois B. Surgical management of 552 carcinomas of the extrahepatic bile ducts (gallbladder and periampullary tumors excluded). Results of the French Surgical Association Survey. Ann Surg 1991;213:236–241. doi:10.1097/00000658-199103000-00010.

    Article  CAS  PubMed  Google Scholar 

  5. Washburn WK, Lewis WD, Jenkins RL. Aggressive surgical resection for cholangiocarcinoma. Arch Surg 1995;130:270–276.

    CAS  PubMed  Google Scholar 

  6. Schoenthaler R, Phillips TL, Castro J, Efird JT, Better A, Way LW. Carcinoma of the extrahepatic bile ducts. The University of California at San Francisco experience. Ann Surg 1994;219:267–274. doi:10.1097/00000658-199403000-00006.

    Article  CAS  PubMed  Google Scholar 

  7. Guthrie CM, Haddock G, De Beaux AC, Garden OJ, Carter DC. Changing trends in the management of extrahepatic cholangiocarcinoma. Br J Surg 1993;80:1434–1439. doi:10.1002/bjs.1800801128.

    Article  CAS  PubMed  Google Scholar 

  8. Kosuge T, Yamamoto J, Shimada K, Yamasaki S, Makuuchi M. Improved surgical results for hilar cholangiocarcinoma with procedures including major hepatic resection. Ann Surg 1999;230:663–671. doi:10.1097/00000658-199911000-00008.

    Article  CAS  PubMed  Google Scholar 

  9. Kondo S, Hirano S, Ambo Y, Tanaka E, Okushiba S, Morikawa T et al. Forty consecutive resections of hilar cholangiocarcinoma with no postoperative mortality and no positive ductal margins: results of a prospective study. Ann Surg 2004;240:95–101. doi:10.1097/01.sla.0000129491.43855.6b.

    Article  PubMed  Google Scholar 

  10. Ebata T, Nagino M, Kamiya J, Uesaka K, Nagasaka T, Nimura Y. Hepatectomy with portal vein resection for hilar cholangiocarcinoma: audit of 52 consecutive cases. Ann Surg 2003;238:720–727. doi:10.1097/01.sla.0000094437.68038.a3.

    Article  PubMed  Google Scholar 

  11. Zervos EE, Osborne D, Goldin SB, Villadolid DV, Thometz DP, Durkin A et al. Stage does not predict survival after resection of hilar cholangiocarcinomas promoting an aggressive operative approach. Am J Surg 2005;190:810–815. doi:10.1016/j.amjsurg.2005.07.025.

    Article  PubMed  Google Scholar 

  12. Su CH, Tsay SH, Wu CC, Shyr YM, King KL, Lee CH et al. Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma. Ann Surg 1996;223:384–394. doi:10.1097/00000658-199604000-00007.

    Article  CAS  PubMed  Google Scholar 

  13. Klempnauer J, Ridder GJ, von Wasielewski R, Werner M, Weimann A, Pichlmayr R. Resectional surgery of hilar cholangiocarcinoma: a multivariate analysis of prognostic factors. J Clin Oncol 1997;15:947–954.

    CAS  PubMed  Google Scholar 

  14. Neuhaus P, Jonas S, Bechstein WO, Lohmann R, Radke C, Kling N et al. Extended resections for hilar cholangiocarcinoma. Ann Surg 1999;230:808–819. doi:10.1097/00000658-199912000-00010.

    Article  CAS  PubMed  Google Scholar 

  15. Todoroki T, Kawamoto T, Koike N, Takahashi H, Yoshida S, Kashiwagi H et al. Radical resection of hilar bile duct carcinoma and predictors of survival. Br J Surg 2000;87:306–313. doi:10.1046/j.1365-2168.2000.01343.x.

    Article  CAS  PubMed  Google Scholar 

  16. Jarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz BSJ et al. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg 2001;234:507–517. doi:10.1097/00000658-200110000-00010.

    Article  CAS  PubMed  Google Scholar 

  17. Ramesh H, Kuruvilla K, Venugopal A, Lekha V, Jacob G. Surgery for hilar cholangiocarcinoma: feasibility and results of parenchyma-conserving liver resection. Dig Surg 2004;21:114–122. doi:10.1159/000077335.

    Article  PubMed  Google Scholar 

  18. Rea DJ, Munoz-Juarez M, Farnell MB, Donohue JH, Que FG, Crownhart B et al. Major hepatic resection for hilar cholangiocarcinoma: analysis of 46 patients. Arch Surg 2004;139:514–525. doi:10.1001/archsurg.139.5.514.

    Article  PubMed  Google Scholar 

  19. Hemming AW, Reed AI, Fujita S, Foley DP, Howard RJ. Surgical management of hilar cholangiocarcinoma. Ann Surg 2005;241:693–702. doi:10.1097/01.sla.0000160701.38945.82.

    Article  PubMed  Google Scholar 

  20. Dinant S, Gerhards MF, Busch OR, Obertop H, Gouma DJ, Van Gulik TM. The importance of complete excision of the caudate lobe in resection of hilar cholangiocarcinoma. HPB Oxf 2005;7:263–267.

    Google Scholar 

  21. Witzigmann H, Berr F, Ringel U, Caca K, Uhlmann D, Schoppmeyer K 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;244:230–239. doi:10.1097/01.sla.0000217639.10331.47.

    Article  PubMed  Google Scholar 

  22. Hasegawa S, Ikai I, Fujii H, Hatano E, Shimahara Y. Surgical resection of hilar cholangiocarcinoma: analysis of survival and postoperative complications. World J Surg 2007;31:1256–1263. doi:10.1007/s00268-007-9001-y.

    Article  PubMed  Google Scholar 

  23. Miyazaki M, Kato A, Ito H, Kimura F, Shimizu H, Ohtsuka M et al. Combined vascular resection in operative resection for hilar cholangiocarcinoma: does it work or not? Surgery 2007;141:581–588. doi:10.1016/j.surg.2006.09.016.

    Article  PubMed  Google Scholar 

  24. Seyama Y, Kubota K, Sano K, Noie T, Takayama T, Kosuge T et al. Long-term outcome of extended hemihepatectomy for hilar bile duct cancer with no mortality and high survival rate. Ann Surg 2003;238:73–83. doi:10.1097/00000658-200307000-00010.

    Article  PubMed  Google Scholar 

  25. Penz M, Kornek GV, Raderer M, Ulrich-Pur H, Fiebiger W, Lenauer A et al. Phase II trial of two-weekly gemcitabine in patients with advanced biliary tract cancer. Ann Oncol 2001;12:183–186. doi:10.1023/A:1008352123009.

    Article  CAS  PubMed  Google Scholar 

  26. Nehls O, Klump B, Arkenau HT, Hass HG, Greschniok A, Gregor M et al. Oxaliplatin, fluorouracil and leucovorin for advanced biliary system adenocarcinomas: a prospective phase II trial. Br J Cancer 2002;87:702–724. doi:10.1038/sj.bjc.6600543.

    Article  CAS  PubMed  Google Scholar 

  27. Knox JJ, Hedley D, Oza A, Feld R, Siu LL, Chen E et al. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol 2005;23:2332–2338. doi:10.1200/JCO.2005.51.008.

    Article  CAS  PubMed  Google Scholar 

  28. Ueno H, Okusaka T, Ikeda M, Takezako Y, Morizane C. Phase II study of S-1 in patients with advanced biliary tract cancer. Br J Cancer 2004;91:1769–1774. doi:10.1038/sj.bjc.6602208.

    Article  CAS  PubMed  Google Scholar 

  29. Murakami Y, Uemura K, Hayasidani Y, Sudo T, Hashimoto Y, Ohge H, et al. Indication for postoperative adjuvant therapy in biliary carcinoma based on analysis of recurrence and survival after surgical resection. Dig Dis Sci 2008; in press (Oct 31).

  30. Bismuth H, Corlette MB. Intrahepatic cholangioenteric anastomosis in carcinoma of the hilus of the liver. Surg Gynecol Obstet 1975;140:170–178.

    CAS  PubMed  Google Scholar 

  31. International Union Against Cancer (UICC). TNM classification of malignant tumors. 6th ed. New York: Wiley-Liss, 2002.

    Google Scholar 

  32. Kawasaki S, Imamura H, Kobayashi A, Noike T, Miwa S, Miyagawa S. Results of surgical resection for patients with hilar bile duct cancer: application of extended hepatectomy after biliary drainage and hemihepatic portal vein embolization. Ann Surg 2003;238:84–92. doi:10.1097/00000658-200307000-00011.

    Article  PubMed  Google Scholar 

  33. Todoroki T, Ohara K, Kawamoto T, Koike N, Yoshida S, Kashiwagi H et al. Benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma. Int J Radiat Oncol Biol Phys 2000;46:581–587. doi:10.1016/S0360-3016(99)00472-1.

    CAS  PubMed  Google Scholar 

  34. Gerhards MF, van Gulik TM, González González D, Rauws EA, Gouma DJ. Results of postoperative radiotherapy for resectable hilar cholangiocarcinoma. World J Surg 2003;27:173–179.

    PubMed  Google Scholar 

  35. Cheng Q, Luo X, Zhang B, Jiang X, Yi B, Wu M. Predictive factors for prognosis of hilar cholangiocarcinoma: postresection radiotherapy improves survival. Eur J Surg Oncol 2007;33:202–207. doi:10.1016/j.ejso.2006.09.033.

    Article  CAS  PubMed  Google Scholar 

  36. Pitt HA, Nakeeb A, Abrams RA, Coleman J, Piantadosi S, Yeo CJ et al. Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival. Ann Surg 1995;221:788–798. doi:10.1097/00000658-199506000-00017.

    Article  CAS  PubMed  Google Scholar 

  37. Sagawa N, Kondo S, Morikawa T, Okushiba S, Katoh H. Effectiveness of radiation therapy after surgery for hilar cholangiocarcinoma. Surg Today 2005;35:548–552. doi:10.1007/s00595-005-2989-4.

    Article  PubMed  Google Scholar 

  38. Kim S, Kim SW, Bang YJ, Heo DS, Ha SW. Role of postoperative radiotherapy in the management of extrahepatic bile duct cancer. Int J Radiat Oncol Biol Phys 2002;54:414–419. doi:10.1016/S0360-3016(02)02952-8.

    PubMed  Google Scholar 

  39. Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H et al. Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 2002;95:1685–1695. doi:10.1002/cncr.10831.

    Article  PubMed  Google Scholar 

  40. Matsumoto K, Nagahara T, Okano J, Murawaki Y. The growth inhibition of hepatocellular and cholangiocellular carcinoma cells by gemcitabine and the roles of extracellular signal-regulated and checkpoint kinases. Oncol Rep 2008;20:863–872.

    CAS  PubMed  Google Scholar 

  41. Gallardo JO, Rubio B, Fodor M, Orlandi L, Yáñez M, Gamargo C et al. A phase II study of gemcitabine in gallbladder carcinoma. Ann Oncol 2001;12:1403–1406. doi:10.1023/A:1012543223020.

    Article  CAS  PubMed  Google Scholar 

  42. Nakamura K, Yamaguchi T, Ishihara T, Sudo K, Kato H, Saisho H. Phase II trial of oral S-1 combined with gemcitabine in metastatic pancreatic cancer. Br J Cancer 2006;94:1575–1579.

    CAS  PubMed  Google Scholar 

  43. Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Nakagawa N et al. Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma. Am J Surg 2008;195:757–762. doi:10.1016/j.amjsurg.2007.04.018.

    Article  CAS  PubMed  Google Scholar 

  44. Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007;297:267–277. doi:10.1001/jama.297.3.267.

    Article  CAS  PubMed  Google Scholar 

  45. Jarnagin WR, Ruo L, Little SA, Klimstra D, D’Angelica M, DeMatteo RP et al. Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies. Cancer 2003;98:1689–1700. doi:10.1002/cncr.11699.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Yoshiaki Murakami, Kenichiro Uemura, Takeshi Sudo, Yasuo Hayashidani, Yasushi Hashimoto, Hiroaki Nakamura, Akira Nakashima & Taijiro Sueda

Authors
  1. Yoshiaki Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenichiro Uemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takeshi Sudo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasuo Hayashidani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasushi Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroaki Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Akira Nakashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Taijiro Sueda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshiaki Murakami.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Murakami, Y., Uemura, K., Sudo, T. et al. Gemcitabine-Based Adjuvant Chemotherapy Improves Survival After Aggressive Surgery for Hilar Cholangiocarcinoma. J Gastrointest Surg 13, 1470–1479 (2009). https://doi.org/10.1007/s11605-009-0900-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-009-0900-0

Keywords

Search

Navigation