Skip to main content

Advertisement

SpringerLink
Log in

Lebertransplantation bei primären Lebertumoren und Lebermetastasen

Liver transplantation for primary liver cancer and liver metastases

  • Schwerpunkt
  • Published:
Der Gastroenterologe Aims and scope

Zusammenfassung

Primäre Lebertumoren und Lebermetastasen sind häufige onkologische Erkrankungen mit – insbesondere im Bereich hepatobiliärer Malignome – auch in Deutschland stetig ansteigender Inzidenz. Primäre Lebertumoren setzten sich im Erwachsenenalter aus dem hepatozellulären Karzinom (HCC), dem cholangiozellulären Karzinom (CCC) sowie dem seltenen hepatozellulären Cholangiokarzinom (Mischtumor) zusammen. In Abhängigkeit der Entität und der oftmals zugrunde liegenden Lebererkrankung unterscheiden sich die Indikation und der Erfolg einer Lebertransplantation (LTx) deutlich. Auch bei metastatischen gastrointestinalen neuroendokrinen Tumoren (NET) sowie im Rahmen experimenteller Studien bei kolorektalen Lebermetastasen (CRLM) kann eine Lebertransplantation bei strenger Selektion eine Therapieoption darstellen. Aufgrund des insbesondere in Deutschland manifesten Spenderorganmangels muss eine Indikation zur Lebertransplantation immer vor dem Hintergrund der vom Transplantationsgesetz geforderten Prinzipien der Dringlichkeit, Erfolgsaussicht und Chancengleichheit gestellt werden. Ziel dieser Übersichtsarbeit ist es, aktuell gültige Transplantationsindikationen und Regeln zur Organvergabe für die einzelnen Entitäten darzustellen sowie einen Überblick über aktuelle internationale Entwicklungen im Hinblick auf neue Prognosemodelle und neue Indikationskriterien für Patienten mit anderweitig nicht kurativ zu behandelnden Lebermalignomen zu geben.

Abstract

In Germany, the incidence of primary liver cancer and liver metastases is steadily increasing—especially for hepatobiliary malignancies. Primary liver malignancies include hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC) and the rare hepatocellular–cholangiocarcinoma (mixed tumor). Depending on tumor entity and the underlying liver disease, indication and long-term results for liver transplantation differ significantly. In highly selected patients with hepatic metastases of gastrointestinal neuroendocrine tumors (NET) or nonresectable colorectal liver metastases (i-CRLM), liver transplantation can be a curative treatment option. Due to the very low number of organ donations especially in Germany, the indication and selection of patients for liver transplantation has to follow the principles of urgency, prospect of success, and equal opportunity. The aim of this review article is to provide an overview of transplant indications and organ allocation rules as well as give insight into recent international developments regarding new prognostic models and new indication criteria for liver transplantation in patients with hepatic malignancies or liver metastases who cannot be otherwise curatively treated.

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

Abb. 1
Abb. 2
Abb. 3

Literatur

  1. Starzl T, Iwatsuki S, van Thiel DH et al (1982) Evolution of liver transplantation. Hepatology 2(5):614–636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. White DJ, Calne RY (1982) The use of Cyclosporin A immunosuppression in organ grafting. Immunol Rev 65:115–131

    Article  CAS  PubMed  Google Scholar 

  3. Starzl T, Todo S, Fung J et al (1989) FK 506 for liver, kidney, and pancreas transplantation. Lancet 2(8670):1000–1004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bismuth H (1994) Consensus statement on indications for liver transplantation: Paris, June 22–23, 1993. Hepatology 20(1 Pt 2):63S–68S

    Article  Google Scholar 

  5. Mazzaferro V, Llovet JM, Miceli R et al (2009) Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 10(1):35–43

    Article  PubMed  Google Scholar 

  6. Bundesärztekammer (2017) Richtlinie gemäß § 16 Abs. 1 Nrn. 2 u. 5 TPG für die Wartelistenführung und Organvermittlung zur Lebertransplantation. Dtsch Arztebl 114(24):A1214

    Google Scholar 

  7. European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69(1):182–236

    Article  Google Scholar 

  8. Sia D, Villanueva A, Friedman SL et al (2017) Liver cancer cell of origin, molecular class, and effects on patient prognosis. Baillieres Clin Gastroenterol 152(4):745–761

    CAS  Google Scholar 

  9. United Nation Network for Organ Sharing. http://www.unos.org. Zugegriffen: 4. April 2019

  10. Otto G, Schuchmann M, Hoppe-Lotichius M, Heise M, Weinmann A, Hansen T, Pitton MP (2013) How to decide about liver transplantation in patients with hepatocellular carcinoma: size and number of lesions or response to TACE? J Hepatol 59(2):279–284

    Article  PubMed  Google Scholar 

  11. Vitale A, Lai Q, Farinati F et al (2018) Utility of tumor burden score to stratify prognosis of patients with hepatocellular cancer: results of 4759 cases from ITA.LI.CA study group. J Gastrointest Surg 22(5):859–871

    Article  PubMed  Google Scholar 

  12. Duvoux C, Thoraval FR, Decaens T et al (2012) Liver transplantation for hepatocellular carcinoma: a model including a‑fetoprotein improves the performance of Milan criteria. Baillieres Clin Gastroenterol 143:e3

    Google Scholar 

  13. Lai Q, Avolio AW, Graziadei I et al (2013) European Hepatocellular Cancer Liver Transplant Study Group. Alpha-fetoprotein and modified response evaluation criteria in solid tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation. Liver Transpl 19(10):1108–1118

    PubMed  Google Scholar 

  14. Amado V, Rodríguez-Perálvarez M, Ferrín G et al (2018) Selecting patients with hepatocellular carcinoma for liver transplantation: incorporating tumor biology criteria. J Hepatocell Carcinoma 6:1–10

    Article  PubMed  PubMed Central  Google Scholar 

  15. Stoot JH, Coelen RJ, De Jong MC et al (2010) Malignant transformation of hepatocellular adenomas into hepatocellular carcinomas: a systematic review including more than 1600 adenoma cases. HPB (Oxford) 12(8):509–522

    Article  Google Scholar 

  16. Lang H, Sotiropoulos GC, Brokalaki EI et al (2007) Survival and recurrence rates after resection for hepatocellular carcinoma in noncirrhotic livers. J Am Coll Surg 205(1):27–36

    Article  PubMed  Google Scholar 

  17. Mergental H, Adam R, Ericzon BG et al (2012) Liver transplantation for unresectable hepatocellular carcinoma in normal livers. J Hepatol 57(2):297–305

    Article  PubMed  Google Scholar 

  18. Sapisochin G, de Lope CR, Gastaca M et al (2014) Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort Multicenter study. Ann Surg 259(5):944–952

    Article  CAS  PubMed  Google Scholar 

  19. Lunsford KE, Court C, Seok Lee Y et al (2018) Propensity-matched analysis of patients with mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing liver transplantation. Liver Transpl 24(10):1384–1397

    Article  PubMed  Google Scholar 

  20. Banales JM, Cardinale V, Carpino G et al (2016) Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol 13(5):261–280

    Article  PubMed  Google Scholar 

  21. Walter D, Ferstl P, Waidmann O et al (2018) Cholangiocarcinoma in Germany: epidemiologic trends and impact of misclassification. Liver Int. https://doi.org/10.1111/liv.13954

    Article  PubMed  Google Scholar 

  22. Becker NS, Rodriguez JA, Barshes NR et al (2008) Outcomes analysis for 280 patients with cholangiocarcinoma treated with liver transplantation over an 18-year period. J Gastrointest Surg 12:117–122

    Article  PubMed  Google Scholar 

  23. Casavilla FA, Marsh JW, Iwatsuki S et al (1997) Hepatic resection and transplantation for peripheral cholangiocarcinoma. J Am Coll Surg 185:429–436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Meyer CG, Penn I, James L (2000) Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation 69:1633–1637

    Article  CAS  PubMed  Google Scholar 

  25. Shimoda M, Farmer DG, Colquhoun SD, Rosove M, Ghobrial RM, Yersiz H et al (2001) Liver transplantation for cholangiocellular carcinoma: analysis of a single-center experience and review of the literature. Liver Transpl 7:1023–1033

    Article  CAS  PubMed  Google Scholar 

  26. Hong JC, Petrowsky H, Kaldas FM, Farmer DG, Durazo FA, Finn RS et al (2011) Predictive index for tumor recurrence after liver transplantation for locally advanced intrahepatic and hilar cholangiocarcinoma. J Am Coll Surg 212:514–520

    Article  PubMed  Google Scholar 

  27. Lunsford KE, Javle M, Heyne K, Shroff RT, Abdel-Wahab R, Gupta N, Mobley CM, Saharia A, Victor DW, Nguyen DT, Graviss EA, Kaseb AO, McFadden RS, Aloia TA, Conrad C, Li XC, Monsour HP, Gaber AO, Vauthey JN, Ghobrial RM, Methodist–MD Anderson Joint Cholangiocarcinoma Collaborative Committee (MMAJCCC). (2018) Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series. Lancet Gastroenterol Hepatol 3(5):337–348

    Article  PubMed  Google Scholar 

  28. Sapisochin G, Rodriguez de Lope C, Gastaca M, Ortiz de Urbina J, Suarez MA, Santoyo J et al (2014) “Very early” intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients? Am J Transplant 14:660–667

    Article  CAS  PubMed  Google Scholar 

  29. Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T et al (2014) Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol 60:1268–1289

    Article  PubMed  Google Scholar 

  30. Iwatsuki S, Todo S, Marsh JW, Madariaga JR, Lee RG, Dvorchik I, Fung JJ, Starzl TE (1998) Treatment of hilar cholangiocarcinoma (Klatskin tumors) with hepatic resection or transplantation. J Am Coll Surg 187(4):358–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pichlmayr R, Weimann A, Klempnauer J, Oldhafer KJ, Maschek H, Tusch G, Ringe B (1996) Surgical treatment in proximal bile duct cancer. A single-center experience. Ann Surg 224(5):628–638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. De Vreede I, Steers JL, Burch PA, Rosen CB, Gunderson LL, Haddock MG et al (2000) Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma. Liver Transpl 6:309–316

    Article  PubMed  Google Scholar 

  33. Sudan D, DeRoover A, Chinnakotla S, Fox I, Shaw B Jr, McCashland T et al (2002) Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant 2:774–779

    Article  PubMed  Google Scholar 

  34. Heimbach JK, Gores GJ, Nagorney DM, Rosen CB (2006) Liver transplantation for perihilar cholangiocarcinoma after aggressive neoadjuvant therapy: a new paradigm for liver and biliary malignancies? Surgery 140(3):331–334

    Article  PubMed  Google Scholar 

  35. Heimbach JK, Gores GJ, Haddock MG, Alberts SR, Pedersen R, Kremers W, Nyberg SL, Ishitani MB, Rosen CB (2006) Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma. Transplantation 82(12):1703–1707

    Article  CAS  PubMed  Google Scholar 

  36. Darwish Murad S, Kim WR, Therneau T, Gores GJ, Rosen CB, Martenson JA et al (2012) Predictors of pretransplant dropout and posttransplant recurrence in patients with perihilar cholangiocarcinoma. Hepatology 56:972–981

    Article  PubMed  Google Scholar 

  37. Darwish Murad S, Kim WR, Harnois DM, Douglas DD, Burton J, Kulik LM et al (2012) Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers. Gastroenterology 143:88–98

    Article  PubMed  Google Scholar 

  38. Mantel HT, Westerkamp AC, Adam R, Bennet WF, Seehofer D, Settmacher U, Sánchez-Bueno F, Fabregat Prous J, Boleslawski E, Friman S, Porte RJ, European Liver and Intestine Transplant Association (ELITA) (2016) Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma Is Associated with Improved Survival. PLoS ONE 11(6):e156127

    Article  PubMed  PubMed Central  Google Scholar 

  39. Nagino M, Ebata T, Yokoyama Y, Igami T, Sugawara G, Takahashi Y et al (2013) Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections. Ann Surg 258:129–140

    Article  PubMed  Google Scholar 

  40. Sato Y, Sasaki M, Harada K, Aishima S, Fukusato T, Ojima H, Kanai Y, Kage M, Nakanuma Y, Tsubouchi H, Hepatolithiasis Subdivision of Intractable Hepatobiliary Diseases Study Group of Japan (Chairman, Hirohito Tsubouchi) (2014) Pathological diagnosis of flat epithelial lesions of the biliary tract with emphasis on biliary intraepithelial neoplasia. J Gastroenterol 49:64–72

    Article  PubMed  Google Scholar 

  41. Ettel M, Eze O, Xu R (2015) Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma. World J Hepatol 7:2563–2570

    Article  PubMed  PubMed Central  Google Scholar 

  42. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB (2008) One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 26(18):3063–3072

    Article  PubMed  Google Scholar 

  43. Pape UF, Perren A, Niederle B, Gross D, Gress T, Costa F, Arnold R, Denecke T, Plöckinger U, Salazar R, Grossman A, Barcelona Consensus Conference participants (2012) ENETS Consensus Guidelines for the management of patients with neuroendocrine neoplasms from the jejuno-ileum and the appendix including goblet cell carcinomas. Neuroendocrinology 95(2):135–156

    Article  CAS  PubMed  Google Scholar 

  44. Harring TR, Nguyen NT, Goss JA, O’Mahony CA (2011) Treatment of liver metastases in patients with neuroendocrine tumors: a comprehensive review. Int J Hepatol. https://doi.org/10.4061/2011/154541

    Article  PubMed  PubMed Central  Google Scholar 

  45. Rindi G, D’Adda T, Froio E, Fellegara G, Bordi C (2007) Prognostic factors in gastrointestinal endocrine tumors. Endocr Pathol 18(03):145–149

    Article  PubMed  Google Scholar 

  46. Working Group on Neuroendocrine Liver Metastases, Frilling A, Modlin IM, Kidd M, Working Group (2014) Recommendations for management of patients with neuroendocrine liver metastases. Lancet Oncol 15(01):e8–e21

    Article  Google Scholar 

  47. Le Treut YP, Grégoire E, Belghiti J et al (2008) Predictors of long-term survival after liver transplantation for metastatic endocrine tumors: an 85-case French multicentric report. Am J Transplant 8(06):1205–1213

    Article  PubMed  Google Scholar 

  48. For ELITA, Le Treut YP, Grégoire E, Klempnauer J et al (2013) Liver transplantation for neuroendocrine tumors in Europe-results and trends in patient selection: a 213-case European liver transplant registry study. Ann Surg 257(05):807–815

    Article  Google Scholar 

  49. Nguyen NT, Harring TR, Goss JA, O’Mahony CA (2011) Neuroendocrine liver metastases and orthotopic liver transplantation: the US experience. Int J Hepatol. https://doi.org/10.4061/2011/742890

    Article  PubMed  PubMed Central  Google Scholar 

  50. Gedaly R, Daily MF, Davenport D et al (2011) Liver transplantation for the treatment of liver metastases from neuroendocrine tumors: an analysis of the UNOS database. Arch Surg 146(08):953–958

    Article  PubMed  Google Scholar 

  51. Sher LS, Levi DM, Wecsler JS et al (2015) Liver transplantation for metastatic neuroendocrine tumors: outcomes and prognostic variables. J Surg Oncol 112(02):125–132

    Article  PubMed  Google Scholar 

  52. Mazzaferro V, Sposito C, Coppa J, Miceli R, Bhoori S, Bongini M, Camerini T, Milione M, Regalia E, Spreafico C, Gangeri L, Buzzoni R, de Braud FG, De Feo T, Mariani L (2016) The long-term benefit of liver transplantation for hepatic metastases fromneuroendocrine tumors. Am J Transplant 16(10):2892–2902

    Article  CAS  PubMed  Google Scholar 

  53. Nobel YR, Goldberg DS (2015) Variable use of model for end-stage liver disease exception points in patients with neuroendocrine tumors metastatic to the liver and its impact on patient outcomes. Transplantation 99(11):2341–2346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Öberg K et al (2012) Ann Oncol 23(Supplement 7):vii124–vii130

    PubMed  Google Scholar 

  55. https://optn.transplant.hrsa.gov/resources/by-organ/liver-intestine/guidance-onmeld-peld-exception-review/#NET. Zugegriffen: 1. März 2019

  56. Deutsches Register Neuroendokrine Tumoren (NET-Register). https://www.net-register.org/. Zugegriffen: 4. April 2019

  57. Foss A, Adam R, Dueland S (2010) Liver transplantation for colorectal liver metastases: revisiting the concept. Transpl Int 23:679–685

    Article  PubMed  Google Scholar 

  58. Hagness M, Foss A, Line PD et al (2013) Liver transplantation for nonresectable liver metastases from colorectal cancer. Ann Surg 257:800–806

    Article  PubMed  Google Scholar 

  59. Königsrainer A, Templin S, Capobianco I, Königsrainer I, Bitzer M, Zender L, Sipos B, Kanz L, Wagner S, Nadalin S (2018) Paradigm shift in the management of Irresectable colorectal liver metastases: living donor auxiliary partial orthotopic liver transplantation in combination with two-stage Hepatectomy (LD-RAPID). Ann Surg. https://doi.org/10.1097/SLA.0000000000002861

    Article  PubMed  Google Scholar 

  60. Rauchfuß F, Nadalin S, Königsrainer A, Settmacher U (2019) Living donor liver transplantation with two-stage hepatectomy for patients with isolated, irresectable colorectal liver-the LIVER-T(W)O-HEAL study. World J Surg Oncol 17(1):11

    Article  PubMed  PubMed Central  Google Scholar 

  61. Yao FY, Ferrell L, Bass NM et al (2001) Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 33(6):1394–1403

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sektion für Klinische Transplantation, Klinik für Allgemeine, Viszeral‑, Thorax‑, Transplantations- und Kinderchirurgie, Universitätsklinikum Schleswig-Holstein (UKSH), Campus Kiel, Arnold-Heller-Str. 3, Haus 18, 24105, Kiel, Deutschland

    A. Bernsmeier &  F. Braun MBA, FEBS

Authors
  1. A. Bernsmeier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Braun MBA, FEBS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. Braun MBA, FEBS.

Ethics declarations

Interessenkonflikt

A. Bernsmeier gibt an, dass kein Interessenkonflikt besteht. F. Braun gibt keine finanziellen Interessenskonflikte an. F. Braun ist als Gutachter für das Institut für Qualität im Gesundheitswesen (IQTiG), als stellvertrender Vorsitzender der AG Leber der Deutschen Transplantationsgesellschaft sowie als Mitglied des Eurotransplant Liver Intestinal Advisory Comitee (ELIAC) tätig.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

Redaktion

G. Gerken, Essen

S. Zeuzem, Frankfurt am Main

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bernsmeier, A., Braun, F. Lebertransplantation bei primären Lebertumoren und Lebermetastasen. Gastroenterologe 14, 269–281 (2019). https://doi.org/10.1007/s11377-019-0352-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11377-019-0352-3

Schlüsselwörter

Keywords

Search

Navigation