The risk of cholangiocarcinoma in PSC patients ranges from 7 to 13%. Due to this risk, the majority of PSC patients undergo routine surveillance cholangiography [13]. In contrast, patients with cholangiocarcinoma arising de novo are frequently diagnosed when they develop jaundice later after the onset of nonspecific symptoms. De novo cholangiocarcinoma is often diagnosed at a more advanced stage of disease than cholangiocarcinoma arising in PSC. Indeed, in the Mayo Clinic experience, de novo patients are more likely to have a mass visible on cross-sectional imaging. Thus, it is not surprising that the results with neoadjuvant therapy and liver transplantation are better for patients with cholangiocarcinoma arising in PSC than those with de novo disease. Current 2-year-survival rates at Mayo Clinic are 60% for PSC patients and 30% for de novo patients after the start of neoadjuvant therapy, and 77 and 56% after liver transplantation. The differences in survival are likely due to earlier detection in PSC patients, since there were no significant differences in survival for de novo cholangiocarcinoma patients following adjustment for patient age, lymph node metastases, and tumor size [14]. Due to limited donor resources and equivocal results compared to resection, neoadjuvant therapy and liver transplantation is not the preferred treatment for de novo patients with resectable disease (Table 20.2) [15]. In contrast, patients with underlying PSC have a predisposition to multifocal cancer; they often have underlying parenchymal disease and/or cholangiopathy such that they are best treated by neoadjuvant therapy and liver transplantation regardless of tumor resectability.

In preparation for liver transplantation, all patients should undergo operative staging following completion of neoadjuvant therapy. Operative staging is best performed the day prior to living donor liver transplantation, such that it has minimal impact on technical difficulty and patient recovery. Patients awaiting deceased donor liver transplantation should undergo operative staging as the time nears for donor organ availability. Timing of the operation depends on ABO-specific MELD scores for patients undergoing deceased donor transplantation and will vary between transplant center willingness to accept extended criteria donors, donor service areas, and UNOS regions in the United States. MELD exception scores are granted by UNOS regional review boards for patients with cholangiocarcinoma which fulfill UNOS diagnosis guidelines and are enrolled in a neoadjuvant therapy protocol. MELD scores for cholangiocarcinoma begin at 22 and increase to a score representing a 10% increase in risk every 3 months, a score increase identical to that for hepatocellular carcinoma (22, 25, 27, 29, 31, 33, etc.).

Operative staging was done in an open fashion at our institution between 1993 and 2005. Since 2005, we have been able to accomplish most staging operations using hand-assisted laparoscopy. The hand port is placed through a right subcostal incision, which is later incorporated in the bilateral subcostal incision required for liver transplantation. Operative staging involves thorough intraperitoneal examination with biopsy of any suspicious peritoneal nodules or intrahepatic nodules, excision of the hepatic artery lymph node overlying the takeoff of the gastroduodenal artery, excision of a pericholedochal lymph node usually found posterior to the bile duct, and excision of any suspicious lymph nodes within the hepatoduodenal pedicle. If patients were to have had a cholecystectomy shortly before diagnosis of cholangiocarcinoma (which is not infrequent), the cystic duct stump should be excised for pathological examination. Clinical factors associated with a high likelihood of positive staging and/or patient dropout prior to transplantation include a CA 19-9 ≥ 500 U/L, mass ≥3 cm in radial diameter, and a biologic MELD ≥20 [16].

Although initially controversial, the use of deceased donors for treatment of cholangiocarcinoma has gained acceptance and is necessary for patients who do not have a suitable living donor. Despite being granted MELD exception points, cholangiocarcinoma patients remain disadvantaged and at risk for dropout while awaiting a deceased donor organ. As a result, marginal, high risk, and other extended criteria donor livers are often accepted for these patients to enable transplantation sooner than would otherwise be possible.

In the past, we used donor livers procured after circulatory arrest (donation after cardiac death, DCD). DCD livers have a high risk for cholangiopathy, which can lead to recurrent and severe cholangitis and require retransplantation in up to 30% of patients [17, 18]. We have been able to achieve a 5.9% risk of cholangiopathy by using experienced staff surgeons for DCD procurement and minimizing preservation time, but only for patients amenable to duct-to-duct or choledochoduodenostomy biliary reconstruction. Despite our efforts, we still have a 30% incidence of cholangiopathy with cholangiocarcinoma patients that require Roux-en-Y choledochojejunostomy (due to resection of the recipient duct and irradiation of the duodenum). We now avoid use of DCD donor livers for cholangiocarcinoma patients and reserve their use for patients much less likely to develop cholangiopathy. Older donor livers, however, are excellent grafts for cholangiocarcinoma patients. These donors often have significant iliac artery arteriosclerosis, so a graft from a younger donor should be available for use if necessary.

Technical modifications necessary during liver transplantation for cholangiocarcinoma are outlined below. In order to perform the best possible cancer operation, dissection in the liver hilus is avoided to prevent tumor seeding. Similarly, the hepatoduodenal ligament is dissected close to the duodenum and pancreas with proximal division of the proper hepatic artery and portal vein. Intraoperatively, it can be difficult to differentiate tumor from radiation-induced fibrosis and a generalized desmoplastic response. It can also be very difficult to separate the common bile duct from the portal vein. The portal vein wall can be very friable. Examination of explanted livers has shown that, in most instances, these findings are the result of radiation injury and not tumor infiltration of the soft tissues surrounding the duct (Fig. 20.4).