Neoadjuvant chemoradiotherapy followed by liver transplantation is a promising treatment for patients with unresectable hilar cholangiocarcinoma: A case report

Wang,Jun; Obulkasim,Halmurat; Zou,Xiaoping; Liu,Baorui; Wu,Yafu; Wu,Xingyu; Ding,Yitao

doi:10.3892/ol.2018.9878

Neoadjuvant chemoradiotherapy followed by liver transplantation is a promising treatment for patients with unresectable hilar cholangiocarcinoma: A case report

Authors:
- Jun Wang
- Halmurat Obulkasim
- Xiaoping Zou
- Baorui Liu
- Yafu Wu
- Xingyu Wu
- Yitao Ding
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Affiliations: Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China, Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China, Department of Oncology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China
Published online on: December 28, 2018 https://doi.org/10.3892/ol.2018.9878
Pages: 2069-2074
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hilar cholangiocarcinoma is a highly malignant tumor and is currently treated by surgical resection or liver transplantation; however, these treatments result in poor patient prognosis accompanied with high recurrence and low patient mortality rates. Neoadjuvant therapy with liver transplantation is a novel treatment that exhibits promising clinical application, with a reported 5‑year survival rate of 82%. However, transplantation centers conducting research into this treatment are limited due to its length and complexity. In the current study, the effects of brachytherapy and chemoradiotherapy followed by orthotopic liver transplantation (OLT) were investigated in a patient with unresectable hilar cholangiocarcinoma. Following treatment, the liver function of the patient normalized and physical status significantly improved. Furthermore, tomographic evaluation demonstrated no sign of recurrence 8 months later following continued adjunct chemotherapy. Therefore, neoadjuvant therapy followed by OLT may be an effective novel therapeutic strategy to treat patients with unresectable hilar cholangiocarcinoma.

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1	Khan SA, Toledano MB and Taylor-Robinson SD: Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma. HPB (Oxford). 10:77–82. 2008. View Article : Google Scholar : PubMed/NCBI
2	Skipworth JR, Keane MG and Pereira SP: Update on the management of cholangiocarcinoma. Dig Dis. 32:570–578. 2014. View Article : Google Scholar : PubMed/NCBI
3	Hemming AW, Reed AI, Fujita S, Foley DP and Howard RJ: Surgical management of hilar cholangiocarcinoma. Ann Sur. 241:693–702. 2005. View Article : Google Scholar
4	Guthrie CM, Banting SW, Garden OJ and Carter DC: Segment III cholangiojejunostomy for palliation of malignant hilar obstruction. Br J Surg. 81:1639–1641. 1994. View Article : Google Scholar : PubMed/NCBI
5	Hassoun Z, Gores GJ and Rosen CB: Preliminary experience with liver transplantation in selected patients with unresectable hilar cholangiocarcinoma. Surg Oncol Clin N Am. 11:909–921. 2002. View Article : Google Scholar : PubMed/NCBI
6	Petrowsky H and Hong JC: Current surgical management of hilar and intrahepatic cholangiocarcinoma: The role of resection and orthotopic liver transplantation. Transplant Proc. 41:4023–4035. 2009. View Article : Google Scholar : PubMed/NCBI
7	Ghali P, Marotta PJ, Yoshida EM, Bain VG, Marleau D, Peltekian K, Metrakos P and Deschênes M: Liver transplantation for incidental cholangiocarcinoma: Analysis of the Canadian experience. Liver Transpl. 11:1412–1416. 2005. View Article : Google Scholar : PubMed/NCBI
8	Robles R, Figueras J, Turrion VS, Margarit C, Moya A, Varo E, Calleja J, Valdivieso A, Valdecasas JC, López P, et al: Spanish experience in liver transplantation for hilar and peripheral cholangiocarcinoma. Ann Surg. 239:265–271. 2004. View Article : Google Scholar : PubMed/NCBI
9	Meyer CG, Penn I and James L: Liver transplantation for cholangiocarcinoma: Results in 207 patients. Transplantation. 69:1633–1637. 2000. View Article : Google Scholar : PubMed/NCBI
10	Rea DJ, Heimbach JK, Rosen CB, Haddock MG, Alberts SR, Kremers WK, Gores GJ and Nagorney DM: Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 242:451–461. 2005.PubMed/NCBI
11	Gores GJ, Gish RG, Sudan D and Rosen CB: MELD Exception Study Group: Model for end-stage liver disease (MELD) exception for cholangiocarcinoma or biliary dysplasia. Liver Transpl (١٢ Suppl ٣). S95–S97. 2006. View Article : Google Scholar
12	Darwish Murad S, Kim WR, Harnois DM, Douglas DD, Burton J, Kulik LM, Botha JF, Mezrich JD, Chapman WC, Schwartz JJ, et al: Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers. Gastroenterology. 143:88–98, e3; quiz e14. 2012. View Article : Google Scholar : PubMed/NCBI
13	Paul A, Kaiser GM, Molmenti EP, Schroeder T, Vernadakis S, Oezcelik A, Baba HA, Cicinnati VR and Sotiropoulos GC: Klatskin tumors and the accuracy of the Bismuth-Corlette classification. Am Surg. 77:1695–1699. 2011.PubMed/NCBI
14	Razumilava N and Gores GJ: Classification, diagnosis, and management of cholangiocarcinoma. Clin Gastroenterol Hepatol. 11:13–21.e1; quiz e3-e4. 2013. View Article : Google Scholar : PubMed/NCBI
15	Todoroki T, Kawamoto T, Koike N, Takahashi H, Yoshida S, Kashiwagi H, Takada Y, Otsuka M and Fukao K: Radical resection of hilar bile duct carcinoma and predictors of survival. Br J Surg. 87:306–313. 2000. View Article : Google Scholar : PubMed/NCBI
16	Klempnauer J, Ridder GJ, von Wasielewski R, Werner M, Weimann A and Pichlmayr R: Resectional surgery of hilar cholangiocarcinoma: A multivariate analysis of prognostic factors. J Clin Oncol. 15:947–954. 1997. View Article : Google Scholar : PubMed/NCBI
17	Nakeeb A, Pitt HA, Sohn TA, Coleman J, Abrams RA, Piantadosi S, Hruban RH, Lillemoe KD, Yeo CJ and Cameron JL: Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg. 224:463–465. 1996. View Article : Google Scholar : PubMed/NCBI
18	Wu Y, Johlin FC, Rayhill SC, Jensen CS, Xie J, Cohen MB and Mitros FA: Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma. Liver Transpl. 14:279–286. 2008. View Article : Google Scholar : PubMed/NCBI
19	Neuhaus P, Jonas S, Bechstein WO, Lohmann R, Radke C, Kling N, Wex C, Lobeck H and Hintze R: Extended resections for hilar cholangiocarcinoma. Ann Surg. 230:808–819. 1999. View Article : Google Scholar : PubMed/NCBI
20	Alessiani M, Tzakis A, Todo S, Demetris AJ, Fung JJ and Starzl TE: Assessment of five-year experience with abdominal organ cluster transplantation. J Am Coll Surg. 180:1–9. 1995.PubMed/NCBI
21	Zardavas D and Piccart M: Neoadjuvant therapy for breast cancer. Ann Rev Med. 66:31–48. 2015. View Article : Google Scholar : PubMed/NCBI
22	Kelsen D: Neoadjuvant therapy for gastrointestinal cancers. Oncol (Williston Park). 7:25-32-411993.
23	Sudan D, DeRoover A, Chinnakotla S, Fox I, Shaw B Jr, McCashland T, Sorrell M, Tempero M and Langnas A: Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant. 2:774–779. 2002. View Article : Google Scholar : PubMed/NCBI
24	Darwish Murad S, Kim WR, Therneau T, Gores GJ, Rosen CB, Martenson JA, Alberts SR and Heimbach JK: Predictors of pretransplant dropout and posttransplant recurrence in patients with perihilar cholangiocarcinoma. Hepatology. 56:972–981. 2012. View Article : Google Scholar : PubMed/NCBI
25	Hong JC, Jones CM, Duffy JP, Petrowsky H, Farmer DG, French S, Finn R, Durazo FA, Saab S, Tong MJ, et al: Comparative analysis of resection and liver transplantation for intrahepatic and hilar cholangiocarcinoma: A 24-year experience in a single center. Arch Surg. 146:683–689. 2011. View Article : Google Scholar : PubMed/NCBI
26	Gringeri E, Bassi D, D'Amico FE, Boetto R, Polacco M, Lodo E, D'Amico F, Vitale A, Boccagni P, Zanus G and Cillo U: Neoadjuvant therapy protocol and liver transplantation in combination with pancreatoduodenectomy for the treatment of hilar cholangiocarcinoma occurring in a case of primary sclerosing cholangitis: Case report with a more than 8-year disease-free survival. Transplant Proc. 43:1187–1189. 2011. View Article : Google Scholar : PubMed/NCBI
27	Schule S, Altendorf-Hofmann A, Utess F, Uteß F, Rauchfuß F, Freesmeyer M, Knösel T, Dittmar Y and Settmacher U: Liver transplantation for hilar cholangiocarcinoma--a single-centre experience. Langenbecks Arch Surg. 398:71–77. 2013. View Article : Google Scholar : PubMed/NCBI
28	Gu J, Bai J, Shi X, Zhou J, Qiu Y, Wu Y, Jiang C, Sun X, Xu F, Zhang Y and Ding Y: Efficacy and safety of liver transplantation in patients with cholangiocarcinoma: A systematic review and meta-analysis. Int J Cancer. 130:2155–2163. 2012. View Article : Google Scholar : PubMed/NCBI
29	Heimbach JK, Gores GJ, Haddock MG, Alberts SR, Pedersen R, Kremers W, Nyberg SL, Ishitani MB and Rosen CB: Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma. Transplantation. 82:1703–1707. 2006. View Article : Google Scholar : PubMed/NCBI
30	Kelley RK, Hirose R and Venook AP: Can we cure cholangiocarcinoma with neoadjuvant chemoradiation and liver transplantation? Time for a multicenter trial. Liver Transpl. 18:509–513. 2012. View Article : Google Scholar : PubMed/NCBI
31	Liu Y, Liu JL, Cai ZZ, Lu Z, Gong YF, Wu HY, Man XH, Jin ZD and Li ZS: A novel approach for treatment of unresectable extrahepatic bile duct carcinoma: design of radioactive stents and an experimental trial in healthy pigs. Gastrointest Endosc. 69:517–524. 2009. View Article : Google Scholar : PubMed/NCBI
32	Liu Y, Lu Z, Zou DW, Jin ZD, Liu F, Li SD, Zhan XB, Zhang WJ, Wu RP, Yao YZ, et al: Intraluminal implantation of radioactive stents for treatment of primary carcinomas of the peripancreatic-head region: a pilot study. Gastrointest Endosc. 69:1067–1073. 2009. View Article : Google Scholar : PubMed/NCBI
33	Sgourakis G, Radtke A, Fouzas I, Mylona S, Goumas K, Gockel I, Lang H and Karaliotas C: Corticosteroid-free immunosuppression in liver transplantation: a meta-analysis and meta-regression of outcomes. Transpl Int. 22:892–905. 2009. View Article : Google Scholar : PubMed/NCBI
34	Guba M, von Breitenbuch P, Steinbauer M, Koehl G, Flegel S, Hornung M, Bruns CJ, Zuelke C, Farkas S, Anthuber M, et al: Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med. 8:128–135. 2002. View Article : Google Scholar : PubMed/NCBI
35	Bruix J and Sherman M: Practice Guidelines Committee, American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma. Hepatology. 42:1208–1236. 2005. View Article : Google Scholar : PubMed/NCBI
36	Klintmalm G and O'Farrelly C: Taking the rap: Multiple effects of blocking mammalian target of rapamycin. Hepatology. 57:1–3. 2013. View Article : Google Scholar : PubMed/NCBI