Skip to main content

Advertisement

SpringerLink
Log in

Liver Transplantation for Peri-hilar Cholangiocarcinoma

  • Review Article
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Background

Liver transplantation for peri-hilar cholangiocarcinoma (pCCA) following neoadjuvant chemoradiation achieves excellent long-term survival in carefully selected patients with early-stage unresectable pCCA and patients with primary sclerosing cholangitis (PSC)–associated pCCA. Strict adherence to selection criteria, aggressive neoadjuvant therapy, operative staging prior to transplantation, and several technical accommodations during the transplant operation are necessary for success. In this review, we provide a contemporaneous overview of liver transplantation for pCCA, including selection criteria, neoadjuvant therapy, operative staging, and technical aspects of liver transplantation unique to patients with pCCA and an irradiated operative field. We also discuss several evolving trends intended to improve patient outcomes.

Results and Conclusion

Intention-to-treat and patient outcomes after liver transplantation for PSC-associated pCCA are superior to de novo pCCA. Outcomes between living donor liver transplantation (LDLT) and deceased donor liver transplantation are similar for patients with PSC-associated pCCA. However, LDLT for de novo pCCA shows a trend toward more disease recurrence and worse patient survival. A period of waiting time before transplant may be beneficial in selecting for patients with superior outcomes after transplant. Compared with liver transplantation for other indications, there is an increased risk of late arterial and portal vein complications, presumably due to the radiation. However, with close follow-up and prompt intervention for vascular complications, graft loss can be avoided. Neoadjuvant therapy and liver transplantation can achieve results comparable with resection for patients with early-stage unresectable pCCA and is the treatment of choice for patients with pCCA arising in the setting of PSC.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet (London, England). 2014;383(9935):2168-79. doi:https://doi.org/10.1016/s0140-6736(13)61903-0.

    Article  Google Scholar 

  2. Banales JM, Cardinale V, Carpino G, Marzioni M, Andersen JB, Invernizzi P et al. Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nature reviews Gastroenterology & hepatology. 2016;13(5):261-80. doi:https://doi.org/10.1038/nrgastro.2016.51.

    Article  Google Scholar 

  3. Sripa B, Kaewkes S, Sithithaworn P, Mairiang E, Laha T, Smout M et al. Liver fluke induces cholangiocarcinoma. PLoS medicine. 2007;4(7):e201. doi:https://doi.org/10.1371/journal.pmed.0040201.

    Article  Google Scholar 

  4. Vatanasapt V, Martin N, Sriplung H, Chindavijak K, Sontipong S, Sriamporn H et al. Cancer incidence in Thailand, 1988–1991. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 1995;4(5):475-83.

    CAS  Google Scholar 

  5. Saha SK, Zhu AX, Fuchs CS, Brooks GA. Forty-year trends in cholangiocarcinoma incidence in the U.S.: intrahepatic disease on the rise. The oncologist. 2016;21(5):594-9. doi:https://doi.org/10.1634/theoncologist.2015-0446.

    Article  Google Scholar 

  6. DeOliveira ML, Cunningham SC, Cameron JL, Kamangar F, Winter JM, Lillemoe KD et al. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Annals of surgery. 2007;245(5):755-62. doi:https://doi.org/10.1097/01.sla.0000251366.62632.d3.

    Article  Google Scholar 

  7. Suarez-Munoz MA, Fernandez-Aguilar JL, Sanchez-Perez B, Perez-Daga JA, Garcia-Albiach B, Pulido-Roa Y et al. Risk factors and classifications of hilar cholangiocarcinoma. World journal of gastrointestinal oncology. 2013;5(7):132-8. doi:https://doi.org/10.4251/wjgo.v5.i7.132.

    Article  Google Scholar 

  8. Zhang XF, Squires MH, 3rd, Bagante F, Ethun CG, Salem A, Weber SM et al. The impact of intraoperative re-resection of a positive bile duct margin on clinical outcomes for hilar cholangiocarcinoma. Annals of surgical oncology. 2018;25(5):1140-9. doi:https://doi.org/10.1245/s10434-018-6382-0.

    Article  Google Scholar 

  9. Groot Koerkamp B, Wiggers JK, Gonen M, Doussot A, Allen PJ, Besselink MG et al. Survival after resection of perihilar cholangiocarcinoma—development and external validation of a prognostic nomogram. Annals of oncology : official journal of the European Society for Medical Oncology. 2015;26(9):1930-5. doi:https://doi.org/10.1093/annonc/mdv279.

    Article  CAS  Google Scholar 

  10. Komaya K, Ebata T, Yokoyama Y, Igami T, Sugawara G, Mizuno T et al. Recurrence after curative-intent resection of perihilar cholangiocarcinoma: analysis of a large cohort with a close postoperative follow-up approach. Surgery. 2018;163(4):732-8. doi:https://doi.org/10.1016/j.surg.2017.08.011.

    Article  Google Scholar 

  11. Meyer CG, Penn I, James L. Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation. 2000;69(8):1633-7.

    Article  CAS  Google Scholar 

  12. Shimoda M, Farmer DG, Colquhoun SD, Rosove M, Ghobrial RM, Yersiz H et al. Liver transplantation for cholangiocellular carcinoma: analysis of a single-center experience and review of the literature. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001;7(12):1023-33. doi:https://doi.org/10.1053/jlts.2001.29419.

    Article  CAS  Google Scholar 

  13. Salgia RJ, Singal AG, Fu S, Pelletier S, Marrero JA. Improved post-transplant survival in the United States for patients with cholangiocarcinoma after 2000. Digestive diseases and sciences. 2014;59(5):1048-54. doi:https://doi.org/10.1007/s10620-013-2626-9.

    Article  Google Scholar 

  14. Marchan EM, Landry JC. Neoadjuvant chemoradiation followed by orthotopic liver transplantation in cholangiocarcinomas: the Emory experience. Journal of gastrointestinal oncology. 2016;7(2):248-54. doi:https://doi.org/10.3978/j.issn.2078-6891.2015.117.

    Article  Google Scholar 

  15. Duignan S, Maguire D, Ravichand CS, Geoghegan J, Hoti E, Fennelly D et al. Neoadjuvant chemoradiotherapy followed by liver transplantation for unresectable cholangiocarcinoma: a single-centre national experience. HPB : the official journal of the International Hepato Pancreato Biliary Association. 2014;16(1):91-8. doi:https://doi.org/10.1111/hpb.12082.

    Article  Google Scholar 

  16. Loveday BPT, Knox JJ, Dawson LA, Metser U, Brade A, Horgan AM et al. Neoadjuvant hyperfractionated chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma in Canada. Journal of surgical oncology. 2018;117(2):213-9. doi:https://doi.org/10.1002/jso.24833.

    Article  CAS  Google Scholar 

  17. Mantel HT, Westerkamp AC, Adam R, Bennet WF, Seehofer D, Settmacher U et al. Strict selection alone of patients undergoing liver transplantation for hilar cholangiocarcinoma is associated with improved survival. PloS one. 2016;11(6):e0156127. doi:https://doi.org/10.1371/journal.pone.0156127.

    Article  CAS  Google Scholar 

  18. Welling TH, Feng M, Wan S, Hwang SY, Volk ML, Lawrence TS et al. Neoadjuvant stereotactic body radiation therapy, capecitabine, and liver transplantation for unresectable hilar cholangiocarcinoma. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2014;20(1):81-8. doi:https://doi.org/10.1002/lt.23757.

    Article  Google Scholar 

  19. Ethun CG, Lopez-Aguiar AG, Anderson DJ, Adams AB, Fields RC, Doyle MB et al. Transplantation versus resection for hilar cholangiocarcinoma: an argument for shifting treatment paradigms for resectable disease. Annals of surgery. 2018;267(5):797-805. doi:https://doi.org/10.1097/sla.0000000000002574.

    Article  Google Scholar 

  20. Rea DJ, Heimbach JK, Rosen CB, Haddock MG, Alberts SR, Kremers WK et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Annals of surgery. 2005;242(3):451-8; discussion 8-61.

    Google Scholar 

  21. Heimbach JK, Sanchez W, Rosen CB, Gores GJ. Trans-peritoneal fine needle aspiration biopsy of hilar cholangiocarcinoma is associated with disease dissemination. HPB : the official journal of the International Hepato Pancreato Biliary Association. 2011;13(5):356-60. doi:https://doi.org/10.1111/j.1477-2574.2011.00298.x.

    Article  Google Scholar 

  22. Bhat M, Hathcock M, Kremers WK, Darwish Murad S, Schmit G, Martenson J et al. Portal vein encasement predicts neoadjuvant therapy response in liver transplantation for perihilar cholangiocarcinoma protocol. Transplant international : official journal of the European Society for Organ Transplantation. 2015;28(12):1383-91. doi:https://doi.org/10.1111/tri.12640.

    Article  CAS  Google Scholar 

  23. Heimbach JK, Haddock MG, Alberts SR, Nyberg SL, Ishitani MB, Rosen CB et al. Transplantation for hilar cholangiocarcinoma. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2004;10(10 Suppl 2):S65-8. doi:https://doi.org/10.1002/lt.20266.

    Article  Google Scholar 

  24. Lehrke HD, Heimbach JK, Wu TT, Jenkins SM, Gores GJ, Rosen CB et al. Prognostic significance of the histologic response of perihilar cholangiocarcinoma to preoperative neoadjuvant chemoradiation in liver explants. The American journal of surgical pathology. 2016;40(4):510-8. doi:https://doi.org/10.1097/pas.0000000000000588.

    Article  Google Scholar 

  25. Sio TT, Martenson JA, Jr., Haddock MG, Novotny PJ, Gores GJ, Alberts SR et al. Outcome of transplant-fallout patients with unresectable cholangiocarcinoma. American journal of clinical oncology. 2016;39(3):271-5. doi:https://doi.org/10.1097/coc.0000000000000056.

    Article  Google Scholar 

  26. Al-Nowaylati AR, Al-Haddad BJ, Dorman RB, Alsaied OA, Lake JR, Chinnakotla S et al. Gastric bypass after liver transplantation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2013;19(12):1324-9. doi:https://doi.org/10.1002/lt.23734.

    Article  Google Scholar 

  27. Mantel HT, Rosen CB, Heimbach JK, Nyberg SL, Ishitani MB, Andrews JC et al. Vascular complications after orthotopic liver transplantation after neoadjuvant therapy for hilar cholangiocarcinoma. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2007;13(10):1372-81. doi:https://doi.org/10.1002/lt.21107.

    Article  Google Scholar 

  28. Tan EK, Rosen CB, Heimbach JK, Gores GJ, Zamora-Valdes D, Taner T. Living donor liver transplantation for perihilar cholangiocarcinoma: outcomes and complications. Journal of the American College of Surgeons. 2020;231(1):98-110. doi:https://doi.org/10.1016/j.jamcollsurg.2019.12.037.

    Article  Google Scholar 

  29. Darwish Murad S, Kim WR, Therneau T, Gores GJ, Rosen CB, Martenson JA et al. Predictors of pretransplant dropout and posttransplant recurrence in patients with perihilar cholangiocarcinoma. Hepatology (Baltimore, Md). 2012;56(3):972-81. doi:https://doi.org/10.1002/hep.25629.

    Article  Google Scholar 

  30. Schaefer B, Zoller H, Schneeberger S. Con: Liver transplantation for expanded criteria malignant diseases. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2018;24(1):104-11. doi:https://doi.org/10.1002/lt.24975.

    Article  Google Scholar 

  31. Heimbach JK, Gores GJ, Haddock MG, Alberts SR, Pedersen R, Kremers W et al. Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma. Transplantation. 2006;82(12):1703-7. doi:https://doi.org/10.1097/01.tp.0000253551.43583.d1.

    Article  CAS  Google Scholar 

  32. Croome KP, Rosen CB, Heimbach JK, Nagorney DM. Is liver transplantation appropriate for patients with potentially resectable de novo hilar cholangiocarcinoma? Journal of the American College of Surgeons. 2015;221(1):130-9. doi:https://doi.org/10.1016/j.jamcollsurg.2015.01.064.

    Article  Google Scholar 

  33. Mansour JC, Aloia TA, Crane CH, Heimbach JK, Nagino M, Vauthey JN. Hilar cholangiocarcinoma: expert consensus statement. HPB : the official journal of the International Hepato Pancreato Biliary Association. 2015;17(8):691-9. doi:https://doi.org/10.1111/hpb.12450.

    Article  Google Scholar 

  34. Rosen CB. Transplantation versus resection for hilar cholangiocarcinoma: an argument for shifting paradigms for resectable disease. Annals of Surgery. 2018;267(5):808-9. doi:https://doi.org/10.1097/sla.0000000000002716.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Division of Transplantation Surgery, Mayo Clinic, Rochester, MN, USA

    Ek Khoon Tan, Timucin Taner, Julie K. Heimbach & Charles B. Rosen

  2. Department of Immunology, Mayo Clinic, Rochester, MN, USA

    Timucin Taner

  3. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

    Gregory J. Gores

Authors
  1. Ek Khoon Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timucin Taner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julie K. Heimbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gregory J. Gores
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Charles B. Rosen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charles B. Rosen.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tan, E.K., Taner, T., Heimbach, J.K. et al. Liver Transplantation for Peri-hilar Cholangiocarcinoma. J Gastrointest Surg 24, 2679–2685 (2020). https://doi.org/10.1007/s11605-020-04721-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-020-04721-4

Keywords

Search

Navigation