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Can the Limits of Liver Transplantation Be Expanded in Perihilar Cholangiocarcinoma?

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Abstract

The most common location of cholangiocarcinomas is the perihilar region with a frequency of 50–70%. Current standard treatment for perihilar cholangiocarcinomas (pCCA) is surgical resection. In cases where resection treatment is possible, the 5-year survival rate is 8–40%. However, using a very strict patient selection, neoadjuvant radiochemotherapy (NRCT), staging laparotomy, and liver transplantation (LT), called “the Mayo protocol,” 5-year survivals of up to 70% in pCCA were reported. This treatment protocol clearly requires an intensive workforce and a harmonious multidisciplinary approach. Reoperation and retransplantation rates are high, which is a reflection of the NRCT. Multicenter studies, systemic reviews, and meta-analysis results, comparing both resection and LT in pCCA treatment and evaluating only LT results, pointed to LT with strict patient selection and full compliance with the treatment. The results of centers experienced in LT are better in treating pCCA. According to Mayo clinical data, histopathological diagnosis could not be obtained in half of the patients with pCCA before NRCT was given. This situation can be explained by the necrosis of the tumor due to the effect of NRCT and the fact that the tumor cannot be detected in the explant liver. This situation raises the following questions: did all patients actually have pCCA? Were these good results due to some patients not having pCCA? The 5-year survival rate was worse in patients with a pathological diagnosis than those without a pathological diagnosis. However, interestingly, recurrence rates were statistically similar in both groups. There was no difference in survival between LT and resection in the R0N0 subgroup in de novo pCCA. There are still many issues that need to be addressed and corrected in pCCA, which is one of the most problematic indications for LT. Significant success has been achieved with NRCT, staging laparotomy, and LT in selected patients with pCCA developing on the basis of PSC or early-stage unresectable de novo pCCA. It can be expected that new NRCT modalities will provide better survival by expanding the indications for LT in pCCA.

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References

  1. Cameron JL, Pitt HA, Zinner MJ, Kaufman SL, Coleman J. Management of proximal cholangiocarcinomas by surgical resection and radiotherapy. Am J Surg. 1990;159:91–7. https://doi.org/10.1016/s0002-9610(05)80612-9.

    Article  CAS  PubMed  Google Scholar 

  2. Bismuth H, Nakache R, Diamond T. Management strategies in resection for hilar cholangiocarcinoma. Ann Surg. 1992;215:31–8. https://doi.org/10.1097/00000658-199201000-00005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Childs T, Hart M. Aggressive surgical therapy for Klatskin tumors. Am J Surg. 1993;165:554–7. https://doi.org/10.1016/s0002-9610(05)80433-7.

    Article  CAS  PubMed  Google Scholar 

  4. Pitt HA, Nakeeb A, Abrams RA, Coleman J, Piantadosi S, Yeo CJ, Lillemore KD, Cameron JL. Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival. Ann Surg. 1995;221:788–97. https://doi.org/10.1097/00000658-199506000-00017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Su CH, Tsay SH, Wu CC, Shyr YM, King KL, Lee CH, Lui WY, Liu TJ, P’eng FK. Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma. Ann Surg. 1996;223:384–94. https://doi.org/10.1097/00000658-199604000-00007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pichlmayr R, Weimann A, Klempnauer J, Oldhafer KJ, Maschek H, Tusch G, Ringe B. Surgical treatment in proximal bile duct cancer. A single-center experience. Ann Surg. 1996;224:628–38. https://doi.org/10.1097/00000658-199611000-00007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Klempnauer J, Ridder GJ, Werner M, Weimann A, Pichlmayr R. What constitutes long-term survival after surgery for hilar cholangiocarcinoma? Cancer. 1997;79:26–34. https://doi.org/10.1002/(SICI)1097-0142(19970101)79:1%3c26::AID-CNCR5%3e3.0.CO;2-K.

    Article  CAS  PubMed  Google Scholar 

  8. Ogura Y, Kawarada Y. Surgical strategies for carcinoma of the hepatic duct confluence. Br J Surg. 1998;85:20–4. https://doi.org/10.1046/j.1365-2168.1998.00532.x.

    Article  CAS  PubMed  Google Scholar 

  9. Burke EC, Jarnagin WR, Hochwald SN, Pisters PW, Fong Y, Blumgart LH. 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. https://doi.org/10.1097/00000658-199809000-00011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Figueras J, Llado L, Valls C, Serrano T, Ramos E, Fabregat J, Rafecas A, Torras J, Jaurrieta E. Changing strategies in diagnosis and management of hilar cholangiocarcinoma. Liver Transpl. 2000;6:786–94. https://doi.org/10.1053/jlts.2000.18507.

    Article  CAS  PubMed  Google Scholar 

  11. Seyama Y, Kubota K, Sano K, Noie T, Takayama T, Kosuge T, Makuuchi M. Long-term outcome of extended hemihepatectomy for hilar bile duct cancer with no mortality and high survival rate. Ann Surg. 2003;238:73–83. https://doi.org/10.1097/01.SLA.0000074960.55004.72.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 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. https://doi.org/10.1097/01.SLA.0000074984.83031.029.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Witzigmann H, Berr F, Ringel U, Caca K, Uhlmann D, Schoppmeyer K, Tannapfel A, Wittekind C, Mossner J, Hauss J, Wiedmann M. 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;244:230–9. https://doi.org/10.1097/01.sla.0000217639.10331.47.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hidalgo E, Asthana S, Nishio H, Wyatt J, Toogood GJ, Prasad KR, Lodge JP. Surgery for hilar cholangiocarcinoma: the Leeds experience. Eur J Surg Oncol. 2008;34:787–94. https://doi.org/10.1016/j.ejso.2007.10.005.

    Article  CAS  PubMed  Google Scholar 

  15. Ercolani G, Zanello M, Grazi GL, Cescon M, Ravaioli M, Del Gaudio M, Vetrone G, Cucchetti A, Brandi G, Ramacciato G, Pinna AD. Changes in the surgical approach to hilar cholangiocarcinoma during an 18-year period in a Western single center. J Hepatobiliary Pancreat Sci. 2010;17:329–37. https://doi.org/10.1007/s00534-009-0249-5.

    Article  PubMed  Google Scholar 

  16. Nimura Y, Hayakawa N, Kamiya J, Kondo S, Shionoya S. Hepatic segmentectomy with caudate lobe resection for bile duct carcinoma of the hepatic hilus. World J Surg. 1990;14:535–43. https://doi.org/10.1007/BF01658686.

    Article  CAS  PubMed  Google Scholar 

  17. Tsao JI, Nimura Y, Kamiya J, Hayakawa N, Kondo S, Nagino M, Miyachi M, Kanai M, Uesaka K, Oda K, Rossi RL, Braasch JW, Dugan JM. Management of hilar cholangiocarcinoma: comparison of an American and a Japanese experience. Ann Surg. 2000;232:166–74. https://doi.org/10.1097/00000658-200008000-00003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kitagawa Y, Nagino M, Kamiya J, Uesaka K, Sano T, Yamamoto H, Hayakawa N, Nimura Y. Lymph node metastasis from hilar cholangiocarcinoma: audit of 110 patients who underwent regional and paraaortic node dissection. Ann Surg. 2001;233:385–92. https://doi.org/10.1097/00000658-200103000-00013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 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;238:720–7. https://doi.org/10.1097/01.sla.0000094437.68038.a3.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Nishio H, Nagino M, Nimura Y. Surgical management of hilar cholangiocarcinoma: the Nagoya experience. HPB (Oxford). 2005;7:259–62. https://doi.org/10.1080/13651820500373010.

    Article  Google Scholar 

  21. Nagino M, Kamiya J, Arai T, Nishio H, Ebata T, Nimura Y. “Anatomic” right hepatic trisectionectomy (extended right hepatectomy) with caudate lobectomy for hilar cholangiocarcinoma. Ann Surg. 2006;243:28–32. https://doi.org/10.1097/01.sla.0000193604.72436.63.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Igami T, Nishio H, Ebata T, Yokoyama Y, Sugawara G, Nimura Y, Nagino M. Surgical treatment of hilar cholangiocarcinoma in the “new era”: the Nagoya University experience. J Hepatobiliary Pancreat Sci. 2010;17:449–54. https://doi.org/10.1007/s00534-009-0209-0.

    Article  PubMed  Google Scholar 

  23. Nagino M, Nimura Y, Nishio H, Ebata T, Igami T, Matsushita M, Nishikimi N, Kamei Y. Hepatectomy with simultaneous resection of the portal vein and hepatic artery for advanced perihilar cholangiocarcinoma: an audit of 50 consecutive cases. Ann Surg. 2010;252:115–23. https://doi.org/10.1097/SLA.0b013e3181e463a7.

    Article  PubMed  Google Scholar 

  24. Nagino M, Ebata T, Yokoyama Y, Igami T, Sugawara G, Takahashi Y, Nimura Y. Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections. Ann Surg. 2013;258:129–40. https://doi.org/10.1097/SLA.0b013e3182708b57.

    Article  PubMed  Google Scholar 

  25. Ebata T, Mizuno T, Yokoyama Y, Igami T, Sugawara G, Nagino M. Surgical resection for Bismuth type IV perihilar cholangiocarcinoma. Br J Surg. 2018;105:829–38. https://doi.org/10.1002/bjs.10556.

    Article  CAS  PubMed  Google Scholar 

  26. Mizuno T, Ebata T, Yokoyama Y, Igami T, Yamaguchi J, Onoe S, Watanabe N, Kamei Y, Nagino M. Combined Vascular Resection for Locally Advanced Perihilar Cholangiocarcinoma. Ann Surg. 2020. https://doi.org/10.1097/SLA.0000000000004322.

    Article  PubMed  Google Scholar 

  27. Shimata K, Yamamoto H, Sugawara Y, Hibi T. Liver Transplantation for Perihilar Cholangiocarcinoma in the Era of Transplant Oncology: Urgent Need for a Common Definition of Resectability, Transplantability, and Curability. Surg Gastroenterol Oncol. 2018;23(4):225–9. https://doi.org/10.21614/sgo-23-4-225.

    Article  Google Scholar 

  28. Pichlmayr R, Weimann A, Klempnauer J, Oldhafer KJ, Maschek H, Tusch G, Ringe B. Surgical treatment in proximal bile duct cancer. A single-center experience Ann Surg. 1996;224:628–38. https://doi.org/10.1097/00000658-199611000-00007.

    Article  CAS  PubMed  Google Scholar 

  29. Iwatsuki S, Todo S, Marsh JW, Madariaga JR, Lee RG, Dvorchik I, Fung JJ, Starzl TE. Treatment of hilar cholangiocarcinoma (Klatskin tumors) with hepatic resection or transplantation. J Am Coll Surg. 1998;187:358–64. https://doi.org/10.1016/s1072-7515(98)00207-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Meyer CG, Penn I, James L. Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation. 2000;69:1633–7. https://doi.org/10.1097/00007890-200004270-00019.

    Article  CAS  PubMed  Google Scholar 

  31. Robles R, Figueras J, Turrión VS, Margarit C, Moya A, Varo E, Calleja J, Valdivieso A, Valdecasas JC, López P, Gómez M, de Vicente E, Loinaz C, Santoyo J, Fleitas M, Bernardos A, Lladó L, Ramírez P, Bueno FS, Jaurrieta E, Parrilla P. Spanish experience in liver transplantation for hilar and peripheral cholangiocarcinoma. Ann Surg. 2004;239:265–71. https://doi.org/10.1097/01.sla.0000108702.45715.81.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Starzl TE, Todo S, Tzakis A, Podesta L, Mieles L, Demetris A, Teperman L, Selby R, Stevenson W, Stieber A. Abdominal organ cluster transplantation for the treatment of upper abdominal malignancies. Ann Surg. 1989;210:374–85. https://doi.org/10.1097/00000658-198909000-00013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Neuhaus P, Blumhardt G. Extended bile duct resection–a new oncological approach to the treatment of central bile duct carcinomas? Description of method and early results. Langenbecks Arch Chir. 1994;379:123–8. https://doi.org/10.1007/BF00195875.

    Article  CAS  PubMed  Google Scholar 

  34. Cameron JL, Pitt HA, Zinner MJ, Kaufman SL, Coleman J. Management of proximal cholangiocarcinomas by surgical resection and radiotherapy. Am J Surg. 1990;159:91–7. https://doi.org/10.1016/s0002-9610(05)80612-9.

    Article  CAS  PubMed  Google Scholar 

  35. Verbeek PC, Van Leeuwen DJ, Van Der Heyde MN, Gonzalez Gonzalez D. Does additive radiotherapy after hilar resection improve survival of cholangiocarcinoma? An analysis in sixty-four patients. Ann Chir. 1991;45:350–4.

    CAS  PubMed  Google Scholar 

  36. Foo ML, Gunderson LL, Bender CE, Buskirk SJ. External radiation therapy and transcatheter iridium in the treatment of extrahepatic bile duct carcinoma. Int J Radiat Oncol Biol Phys. 1997;39:929–35. https://doi.org/10.1016/s0360-3016(97)00299-x.

    Article  CAS  PubMed  Google Scholar 

  37. Sudan D, DeRoover A, Chinnakotla S, Fox I, Shaw B Jr, McCashland T, Sorrell M, Tempero M, Langnas A. Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant. 2002;2:774–9. https://doi.org/10.1034/j.1600-6143.2002.20812.x.

    Article  PubMed  Google Scholar 

  38. De Vreede I, Steers JL, Burch PA, Rosen CB, Gunderson LL, Haddock MG, Burgart L, Gores GJ. Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma. Liver Transpl. 2000;6:309–16. https://doi.org/10.1053/lv.2000.6143.

    Article  PubMed  Google Scholar 

  39. Heimbach JK, Gores GJ, Haddock MG, Alberts SR, Nyberg SL, Ishitani MB, Rosen CB. Liver transplantation for unresectable perihilar cholangiocarcinoma. Semin Liver Dis. 2004;24:201–17. https://doi.org/10.1055/s-2004-828896.

    Article  PubMed  Google Scholar 

  40. Rea DJ, Heimbach JK, Rosen CB, Haddock MG, Alberts SR, Kremers WK, Gores GJ, Nagorney DM. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005;242:451–8. https://doi.org/10.1097/01.sla.0000179678.13285.fa.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Rosen CB, Heimbach JK, Gores GJ. Current status of liver transplantation for hilar cholangiocarcinoma. Curr Opin Organ Transplant. 2007;12:215–9. https://doi.org/10.1097/MOT.0b013e32814e6b7d.

    Article  PubMed  Google Scholar 

  42. Rosen CB, Heimbach JK, Gores GJ. Surgery for cholangiocarcinoma: the role of liver transplantation. HPB (Oxford). 2008;10:186–9. https://doi.org/10.1080/13651820801992542.

    Article  CAS  Google Scholar 

  43. Heimbach JK. Successful liver transplantation for hilar cholangiocarcinoma. Curr Opin Gastroenterol. 2008;24:384–8. https://doi.org/10.1097/MOG.0b013e3282f706ce.

    Article  PubMed  Google Scholar 

  44. Rosen CB, Darwish Murad S, Heimbach JK, Nyberg SL, Nagorney DM, Gores GJ. Neoadjuvant therapy and liver transplantation for hilar cholangiocarcinoma: is pretreatment pathological confirmation of diagnosis necessary? J Am Coll Surg. 2012;215:31–8. https://doi.org/10.1016/j.jamcollsurg.2012.03.014.

    Article  PubMed  Google Scholar 

  45. Gores GJ, Darwish Murad S, Heimbach JK, Rosen CB. Liver transplantation for perihilar cholangiocarcinoma. Dig Dis. 2013;31:126–9. https://doi.org/10.1159/000347207.

    Article  PubMed  Google Scholar 

  46. Croome KP, Rosen CB, Heimbach JK, Nagorney DM. Is liver transplantation appropriate for patients with potentially resectable de novo hilar cholangiocarcinoma? J Am Coll Surg. 2015;221:130–9. https://doi.org/10.1016/j.jamcollsurg.2015.01.064.

    Article  PubMed  Google Scholar 

  47. Gulamhusein AF, Sanchez W. Liver transplantation in the management of perihilar cholangiocarcinoma. Hepat Oncol. 2015;2:409–21. https://doi.org/10.2217/hep.15.30.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Rosen CB. Transplantation versus resection for hilar cholangiocarcinoma: an argument for shifting paradigms for resectable disease in annals of surgery. Ann Surg. 2018;267:808–9. https://doi.org/10.1097/SLA.0000000000002716.

    Article  PubMed  Google Scholar 

  49. Tan EK, Taner T, Heimbach JK, Gores GJ, Rosen CB. Liver transplantation for peri-hilar cholangiocarcinoma. J Gastrointest Surg. 2020;24:2679–85. https://doi.org/10.1007/s11605-020-04721-4.

    Article  PubMed  Google Scholar 

  50. Tan EK, Rosen CB, Heimbach JK, Gores GJ, Zamora-Valdes D, Taner T. Living donor liver transplantation for perihilar cholangiocarcinoma: outcomes and complications. J Am Coll Surg. 2020;231:98–110. https://doi.org/10.1016/j.jamcollsurg.2019.12.037.

    Article  PubMed  Google Scholar 

  51. Kitajima T, Nagai S. ASO Author reflections: it is not a low-hanging fruit: center experience plays an important role in improving outcomes in liver transplantation for hilar cholangiocarcinoma. Ann Surg Oncol. 2020;27:5222–3. https://doi.org/10.1245/s10434-020-08686-1.

    Article  PubMed  Google Scholar 

  52. 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). Strict selection alone of patients undergoing liver transplantation for hilar cholangiocarcinoma is associated with improved survival. PLoS One. 2016. https://doi.org/10.1371/journal.pone.0156127.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kaiser GM, Sotiropoulos GC, Jauch KW, Löhe F, Hirner A, Kalff JC, Königsrainer A, Steurer W, Senninger N, Brockmann JG, Schlitt HJ, Zülke C, Büchler MW, Schemmer P, Settmacher U, Hauss J, Lippert H, Hopt UT, Otto G, Heiss MM, Bechstein WO, Timm S, Klar E, Hölscher AH, Rogiers X, Stangl M, Hohenberger W, Müller V, Molmenti EP, Fouzas I, Erhard J, Malagó M, Paul A, Broelsch CE, Lang H. Liver transplantation for hilar cholangiocarcinoma: a German survey. Transplant Proc. 2008;40:3191–3. https://doi.org/10.1016/j.transproceed.2008.08.039.

    Article  CAS  PubMed  Google Scholar 

  54. Welling TH, Feng M, Wan S, Hwang SY, Volk ML, Lawrence TS, Zalupski MM, Sonnenday CJ. Neoadjuvant stereotactic body radiation therapy, capecitabine, and liver transplantation for unresectable hilar cholangiocarcinoma. Liver Transpl. 2014;20:81–8. https://doi.org/10.1002/lt.23757.

    Article  PubMed  Google Scholar 

  55. Marchan EM, Landry JC. Neoadjuvant chemoradiation followed by orthotopic liver transplantation in cholangiocarcinomas: the emory experience. J Gastrointest Oncol. 2016;7:248–54. https://doi.org/10.3978/j.issn.2078-6891.2015.117].

    Article  PubMed  PubMed Central  Google Scholar 

  56. Zaborowski A, Heneghan HM, Fiore B, Stafford A, Gallagher T, Geoghegan J, Maguire D, Hoti E. Neoadjuvant chemoradiotherapy and liver transplantation for unresectable hilar cholangiocarcinoma: The Irish Experience of the Mayo Protocol. Transplantation. 2020;104:2097–104. https://doi.org/10.1097/TP.0000000000003114.

    Article  CAS  PubMed  Google Scholar 

  57. Darwish Murad S, Kim WR, Harnois DM, Douglas DD, Burton J, Kulik LM, Botha JF, Mezrich JD, Chapman WC, Schwartz JJ, Hong JC, Emond JC, Jeon H, Rosen CB, Gores GJ, Heimbach JK. Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers. Gastroenterology. 2012;143:88-98.e3. https://doi.org/10.1053/j.gastro.2012.04.008.

    Article  PubMed  Google Scholar 

  58. Salgia RJ, Singal AG, Fu S, Pelletier S, Marrero JA. Improved post-transplant survival in the United States for patients with cholangiocarcinoma after 2000. Dig Dis Sci. 2014;59:1048–54. https://doi.org/10.1007/s10620-013-2626-9.

    Article  PubMed  Google Scholar 

  59. Yu X, Tang J, Gong X, Zhang Y, Li Y, Yang H. Effectiveness and safety of liver transplantation for surgically unresectable hilar cholangiocarcinoma: a meta-analysis. Int J Clin Exp Med. 2016;9:9965–73.

    Google Scholar 

  60. Goldaracena N, Gorgen A, Sapisochin G. Current status of liver transplantation for cholangiocarcinoma. Liver Transpl. 2018;24:294–303. https://doi.org/10.1002/lt.24955.

    Article  PubMed  Google Scholar 

  61. Resch T, Esser H, Cardini B, Schaefer B, Zoller H, Schneeberger S. Liver transplantation for hilar cholangiocarcinoma (h-CCA): is it the right time? Transl Gastroenterol Hepatol. 2018. https://doi.org/10.21037/tgh.2018.06.06.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Ethun CG, Lopez-Aguiar AG, Anderson DJ, Adams AB, Fields RC, Doyle MB, Chapman WC, Krasnick BA, Weber SM, Mezrich JD, Salem A, Pawlik TM, Poultsides G, Tran TB, Idrees K, Isom CA, Martin RCG, Scoggins CR, Shen P, Mogal HD, Schmidt C, Beal E, Hatzaras I, Shenoy R, Cardona K, Maithel SK. Transplantation versus resection for hilar cholangiocarcinoma: an argument for shifting treatment paradigms for resectable disease. Ann Surg. 2018;267:797–805. https://doi.org/10.1097/SLA.0000000000002574.

    Article  PubMed  Google Scholar 

  63. Machairas N, Kostakis ID, Tsilimigras DI, Prodromidou A, Moris D. Liver transplantation for hilar cholangiocarcinoma: a systematic review. Transplant Rev (Orlando). 2020. https://doi.org/10.1016/j.trre.2019.100516.

    Article  Google Scholar 

  64. Moris D, Kostakis ID, Machairas N, Prodromidou A, Tsilimigras DI, Ravindra KV, Sudan DL, Knechtle SJ, Barbas AS. Comparison between liver transplantation and resection for hilar cholangiocarcinoma: a systematic review and meta-analysis. PLoS One. 2019. https://doi.org/10.1371/journal.pone.0220527.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Thelen A, Neuhaus P. Liver transplantation for hilar cholangiocarcinoma. J Hepatobiliary Pancreat Surg. 2007;14:469–75. https://doi.org/10.1007/s00534-006-1196-z.

    Article  PubMed  Google Scholar 

  66. Kitajima T, Hibi T, Moonka D, Sapisochin G, Abouljoud MS, Nagai S. Center experience affects liver transplant outcomes in patients with hilar cholangiocarcinoma. Ann Surg Oncol. 2020;27:5209–21. https://doi.org/10.1245/s10434-020-08682-5.

    Article  PubMed  Google Scholar 

  67. Cambridge WA, Fairfield C, Powell JJ, Harrison EM, Søreide K, Wigmore SJ, Guest RV. Meta-analysis and meta-regression of survival after liver transplantation for unresectable perihilar cholangiocarcinoma. Ann Surg. 2021;273:240–50. https://doi.org/10.1097/SLA.0000000000003801.

    Article  PubMed  Google Scholar 

  68. Iwasaki Y, Okamura T, Ozaki A, Todoroki T, Takase Y, Ohara K, Nishimura A, Otsu H. Surgical treatment for carcinoma at the confluence of the major hepatic ducts. Surg Gynecol Obstet. 1986;162:457–64.

    CAS  PubMed  Google Scholar 

  69. Bengmark S, Ekberg H, Evander A, Klofver-Stahl B, Tranberg KG. Major liver resection for hilar cholangiocarcinoma. Ann Surg. 1988;207:120–5. https://doi.org/10.1097/00000658-198802000-00002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ogura Y, Mizumoto R, Tabata M, Matsuda S, Kusuda T. Surgical treatment of carcinoma of the hepatic duct confluence: analysis of 55 resected carcinomas. World J Surg. 1993;17:85–92. https://doi.org/10.1007/BF01655714.

    Article  CAS  PubMed  Google Scholar 

  71. Kurosaki I, Tsukada K, Hatakeyama K, Muto T. The mode of lymphatic spread in carcinoma of the bile duct. Am J Surg. 1996;172:239–43. https://doi.org/10.1016/S0002-9610(96)00156-0.

    Article  CAS  PubMed  Google Scholar 

  72. Feng JW, Yang XH, Wu BQ, Jiang Y, Qu Z. Progress in diagnosis and surgical treatment of perihilar cholangiocarcinoma. Gastroenterol Hepatol. 2019;42:271–9. https://doi.org/10.1016/j.gastrohep.2018.11.003.

    Article  PubMed  Google Scholar 

  73. Bagante F, Tran T, Spolverato G, Ruzzenente A, Buttner S, Ethun CG, Groot Koerkamp B, Conci S, Idrees K, Isom CA, Fields RC, Krasnick B, Weber SM, Salem A, Martin RC, Scoggins C, Shen P, Mogal HD, Schmidt C, Beal E, Hatzaras I, Vitiello G, IJzermans JN, Maithel SK, Poultsides G, Guglielmi A, Pawlik TM. Perihilar cholangiocarcinoma: number of nodes examined and optimal lymph node prognostic scheme. J Am Coll Surg. 2016;222:750–9. https://doi.org/10.1016/j.jamcollsurg.2016.02.012.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Mao K, Liu J, Sun J, Zhang J, Chen J, Pawlik TM, Jacobs LK, Xiao Z, Wang J. Patterns and prognostic value of lymph node dissection for resected perihilar cholangiocarcinoma. J Gastroenterol Hepatol. 2016;31:417–26. https://doi.org/10.1111/jgh.13072.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Sotiropoulos GC, Lang H, Niebel W, Malago M, Broelsch CE. 10-year tumor-free survival after intraoperative radiation therapy and secondary liver transplantation for hilar cholangiocarcinoma. Transplantation. 2004;77:1625. https://doi.org/10.1097/01.tp.0000116391.25570.94.

    Article  PubMed  Google Scholar 

  76. Juntermanns B, Grabellus F, Zhang H, Radunz S, Bernheim J, Fingas CD, Sauerwein W, Paul A, Kaiser GM. Vascular and nerval damage after intraoperative radiation therapy of the liver hilum in a large animal model. J Invest Surg. 2014;27:163–8. https://doi.org/10.3109/08941939.2013.868961.

    Article  PubMed  Google Scholar 

  77. Lupascu C, Lerut J. Allograft inflow - concern in liver transplantation after intraoperative radiotherapy for cholangiocarcinoma. Chirurgia (Bucur). 2014;109:837–42.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Liver Transplant Institute, Faculty of Medicine, Inonu University, Malatya, 44280, Turkey

    Sezai Yilmaz, Brian I. Carr & Sami Akbulut

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  1. Sezai Yilmaz
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  2. Brian I. Carr
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  3. Sami Akbulut
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Yilmaz S, Carr BI, and Akbulut S wrote manuscript. Yilmaz S and Akbulut S projected development and reviewed the final version.

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Correspondence to Sami Akbulut.

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Yilmaz, S., Carr, B.I. & Akbulut, S. Can the Limits of Liver Transplantation Be Expanded in Perihilar Cholangiocarcinoma?. J Gastrointest Canc 53, 1104–1112 (2022). https://doi.org/10.1007/s12029-021-00735-6

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