Hilar Cholangiocarcinoma: No Longer Hopeless

Abstract

Cholangiocarcinoma affecting the bifurcation of the common hepatic duct is a devastating disease. Surgical resection is standard therapy, but tumor involvement of vascular and biliary structures in the hilus of the liver often preclude a margin-free resection with preservation of viable liver. During the 1980s, it was thought that liver transplantation would overcome the aforementioned barriers to resection and achieve success in the treatment of unresectable hilar cholangiocarcinoma. The entire tumor can be removed with the liver, including involved vascular and biliary structures, which are simply replaced by implantation of a donor liver. Unfortunately, liver transplantation did not achieve results good enough to justify use of scarce donor livers [1], and hilar cholangiocarcinoma became recognized as a contraindication for liver transplantation. The University of Nebraska attempted to overcome the limitations of transplantation by treating patients with high dose brachytherapy prior to transplantation [2]. Complications from the brachytherapy were prohibitive, but there was an excellent tumor response. Our team at Mayo Clinic Rochester refined this approach and cautiously moved forward with a neoadjuvant therapy protocol that included high-dose external beam therapy, lower dose brachytherapy, and chemosensitization with 5-FU. We proposed that liver transplantation—after careful selection of patients with early stage disease, neoadjuvant therapy, and operative staging—could achieve reasonable survival. We reported our initial results with treatment of 19 patients between 1993 and 2000 [3]. Twelve underwent transplantation with 100 % survival at a median follow-up of 44 months. Since that time, other centers have implemented identical or similar protocols and achieved comparable success. The United Network for Organ Sharing (UNOS) adopted the Mayo Clinic approach, including diagnostic and selection criteria, for MELD (Model for End-stage Liver Disease) exception guidelines [4] and policies. Most commercial insurance plans will cover this treatment, and the CMS (Center for Medicare Services) recently agreed to provide reimbursement as well. In this issue of Digestive Diseases and Sciences, Salgia et al. [5] from the University of Michigan report their findings from a study of the US experience with liver transplantation for cholangiocarcinoma using the US Scientific Registry of Transplant Recipients (SRTR) database. They associate an improvement in patient survival after transplantation with publication of the initial results from Mayo Clinic Rochester in 2000. Their key findings are: (1) national results with liver transplantation for cholangiocarcinoma showed significant improvement after 2000; (2) there were no differences in survival between UNOS regions; (3) the number of transplants for cholangiocarcinoma increased after 2000. They also report that survival was favorably associated with acute cellular rejection. These findings validate the Mayo Clinic protocol, highlight the value of a national registry study, and also demonstrate the limitations of a registry study. Does this report validate the Mayo Clinic protocol? The authors report a significant improvement in survival after 2000 (Figure 4), the time of publication of our initial results. Their study included 595 patients registered for transplantation and 359 transplanted with a diagnosis of cholangiocarcinoma between October 1987 and May 2008. During that time, Mayo Clinic Rochester registered 163 C. B. Rosen (&) Division of Transplantation Surgery, Mayo Clinic, Rochester, MN, USA e-mail: Rosen.Charles@mayo.edu