Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy with mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) histological features. It is almost impossible to obtain an accurate, preoperative noninvasive diagnosis of cHCC-CC with tumor markers or crosssectional abdominal imaging due to the mixed histological features. Despite these difficulties, accurate cHCC-CC diagnosis remains an important goal with prognostic significance. In our study, we retrospectively reviewed the tumor markers: AFP and CA 19-9, and cross-sectional liver imaging, in light of liver explant findings, to identify and characterize cHCC-CC features followed by liver transplantation (LT) outcome analysis. The results from this 12 patient cohort failed to identify characteristic features for cHCC-CC. None of the imaging features helped to identify the cHCC-CC tumor and they mimicked either HCC or CC, depending on the degree of glandular differentiation expressed histologically. In our cHCC-CC LT recipients, the 1-, 3-and 5-year cumulative survival probabilities were 79%, 66% and 16%, respectively with a 5-year survival comparable to or better than LT for intrahepatic CC but poorer than LT for HCC following the Milan criteria. Conceivably explained by its cholangiocarcinoma component the LT outcome for this rare and hard to diagnose tumor appears poor.

The very early experience with liver transplantation (LT) for cholangiocarcinoma (CC) was dismal because of the poor survival outcomes and the high recurrence rates. However, LT for CC in conjunction with neoadjuvant chemoradiation recently has shown encouraging results, although the data are extremely limited. At our institution between 2001 and 2008, 22 CC patients underwent protocol orthotopic LT at a median age of 45 years (range ¼ 24-63 years). At a median follow-up of 601.5 days (range ¼ 111-1388 days), the median survival time of the cohort was 3.3 years. The 1-, 2-, and 3-year KaplanMeier survival probabilities were 90%, 70%, and 63%, respectively, whereas the historical 5-year survival rates were 0% to 18% for intrahepatic CC and 23% to 26% for extrahepatic CC when patients underwent transplantation without neoadjuvant therapy. These encouraging survival rates for patients with this type of tumor, which is difficult to diagnose and treat, are no less significant when they are compared to the national 1-and 3-year survival rates (86% and 68%, respectively) of patients undergoing deceased donor LT for malignant neoplasms of the liver (as reported by the United Network for Organ Sharing). In our series, disease recurrence was significantly associated with a larger residual tumor [6.3 versus 2.0 cm (mean values), P ¼ 0.008] and with a shorter waiting time for LT after the chemoradiation protocol [18 versus 56 days (mean values), P ¼ 0.04]. Our LT protocol for CC was found to be promising for patients with truly extrahepatic CC and for patients within stages I to IIB of the American Joint Committee on Cancer Staging system (100% survival at a median follow-up of 2.2 years), but the results were notably poor for patients with stage III extrahepatic CC (median survival ¼ 1.2 years). These observations highlight the need for accurate preoperative staging of CC for ideal LT recipient selection and the importance of a low tumor burden and a longer wait after neoadjuvant therapy. More effective chemoradiation regimens for reducing the tumor burden and the appropriate timing of LT after neoadjuvant chemoradiation require further research. Liver Transpl 18:594-601, 2012. V C 2012 AASLD.Received April 8, 2011; accepted October 19, 2011. See Editorial on Page 509Cholangiocarcinoma (CC), a devastating bile duct cancer, is often diagnosed late in the disease process and accounts for 10% to 20% of deaths from hepatobiliary malignancies. 1 Currently available chemotherapeutic regimens neither are curative nor have a survival benefit. Surgical resection for CC patients without lymph node metastases and vascular invasion, when it is anatomically practical, is the current treatment of choice. However, the 5-year survival rates are 22% to 40% for intrahepatic CC, 11% to 41% for hilar CC, and 27% to 37% for distal extrahepatic CC. [2][3][4][5][6][7][8][9][10][11] This bleak outcome is attributable in part to the difficulty in diagnosing CC early.

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Independent prognostic factors in patients with HCC undergoing DEB chemoembolization have been identified. Increased bilirubin level was not an independent risk factor. These data can be used in HCC patient selection and counseling for DEB chemoembolization.