Mixed Hepatocellular Cholangiocarcinoma and Intrahepatic Cholangiocarcinoma in Patients Undergoing Transplantation for Hepatocellular Carcinoma

Department of Surgery, University of California San Francisco, San Francisco, CA 94143-0538, USA.
Liver Transplantation (Impact Factor: 4.24). 08/2011; 17(8):934-42. DOI: 10.1002/lt.22307
Source: PubMed


Mixed hepatocellular cholangiocarcinoma (HCC-CC) and intrahepatic cholangiocarcinoma (I-CC) are increasingly being reported in patients with cirrhosis. The aims of this study were (1) to evaluate the incidence, imaging features, and posttransplant outcomes for patients who underwent transplantation for hepatocellular carcinoma (HCC) and were found to have HCC-CC or I-CC in the explant and (2) to compare the outcomes of these patients with those of controls with HCC who were matched (1:3) by the tumor size and the number of nodules in the explant. In the explant specimens of 10 of 302 patients (3.3%) who underwent liver transplantation (LT) for HCC, mixed HCC-CC or I-CC was identified. There were 4 additional incidental cases of HCC-CC. After a median follow-up period of 32 months, 8 of the 14 patients (57%) suffered from tumor recurrence, and the median disease-free survival time was 8 months. The cumulative risk of tumor recurrence was 40% and 70% at 1 and 5 years, respectively, for these 14 patients. When the 4 incidental cases were excluded, the study group with HCC-CC or I-CC (n = 10) had a significantly lower incidence of well-differentiated tumors (11.1% versus 43.3%, P < 0.02) and a higher rate of recurrence (60% versus 16.7%, P = 0.008) in comparison with the control group of patients with HCC (n = 30). The 1- and 5-year cumulative risks of tumor recurrence were 42% and 65%, respectively, in the study group and 10% and 17%, respectively, in the control group (P < 0.002). The actuarial 1- and 5-year patient survival rates without recurrence were also significantly lower in the study group (79% and 32% in the study group and 90% and 62% in the control group, P < 0.03). Dynamic contrast-enhanced computed tomography or magnetic resonance imaging showed progressive contrast enhancement throughout the arterial and portal venous phases without washout in 8 of the 10 patients. In conclusion, HCC-CC and I-CC are associated with a poor prognosis and a high rate of tumor recurrence after LT, and both tumors exhibit radiographic features that are distinct from those observed with HCC.

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    • "In mixed tumors, the presence of cholangiocarcinoma elements can be confirmed by a positive cytokeratin 19 (CK19) and cytokeratin 7 (CK7) staining by immunohistochemistry. With the recognition that patients can harbor mixed HCC-iCCA tumors [177] [178], a liver biopsy should be considered for atypical lesions (lesions not diagnostic for HCC by classical imaging criteria on cross-sectional studies) prior to LT. Mixed HCC-iCCA lesions have worse outcomes following LT than patients with HCC [177] [178] with a five-year recurrence rate of 65% [178]. Such patients should either not undergo transplantation or be enrolled in research protocols combining adjuvant or neoadjuvant therapy for iCCA in the transplant setting. "

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