Article

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: 3.79). 08/2011; 17(8):934-42. DOI: 10.1002/lt.22307
Source: PubMed

ABSTRACT 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.

1 Follower
 · 
106 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: In 2002, the use of the MELD scoring system was adopted as the primary means of determining the priority of patients listed for liver transplantation. Implementation of the MELD system has changed the face of organ allocation for livers and as a result, overall waitlist times along with pre- and post-transplant mortality for patients with significant liver disease have declined. Although the MELD accurately predicts mortality in most patients with end stage liver disease, it may not adequately risk stratify some patients who have a high risk of morbidity and mortality not reflected in the score. Automatic exception points are granted for a subset of conditions if candidates meet agreed upon criteria. However, even within this framework, there are some at risk patients who will be missed. Herein we review conditions associated with increased mortality and morbidity that are not reflected in the MELD score and reflect on the issues which arise when considering allocation of organs to these patients.
    Current Hepatitis Reports 03/2014; 13(1):60-73. DOI:10.1007/s11901-014-0211-0
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Expression of liver progenitor cell (LPC) characteristics has been proposed as a negative prognostic marker in primary liver tumors. Hypoxia has been linked to activation of the Notch pathway which is responsible for activation and proliferation of LPCs and hypoxia-induced LPC activation has been shown in hepatocellular carcinoma. Our aim was to elucidate the time-dependent effects of hypoxia on the LPC niche in hepatocellular carcinoma which could aid in determining a safe time frame for use of hypoxia inducing therapies. We used dimethyloxaloylglycine to mimic a hypoxic reaction in mice by stabilizing hypoxia-inducible factor 1 alpha at three distinct time points in diethylnitrosamine induced hepatocarcinogenesis. LPC, metastasis and Notch pathway markers were determined by quantitative PCR and (immune)histochemistry (heamatoxillin-eosin, reticulin, Sirius red and cytokeratin 19 staining). Activating the hypoxia inducible pathway early in hepatocarcinogenesis resulted in an increased incidence of both cholangioma and hepatocellular lesions, associated with high expression of LPC, metastatic and Notch pathway markers. Adversely, activating the hypoxic response during tumor development resulted in decreased incidence of hepatocellular lesions and increased cholangioma incidence, with an unaltered gene expression profile of LPC-, Notch pathway- and metastatic markers. A hypoxic insult at advanced stages of hepatocarcinogenesis severely increased the expression of LPC characteristics, however without increased expression of actors of the Notch pathway and metastatic markers and minor changes in incidence of hepatocellular and cholangioma lesions. Our results indicate that increased hypoxia at the onset of tumor development has detrimental effects on tumor progression; patients with HCC developed in a background of fibrosis/cirrhosis might therefore represent a more difficult treatment group. In contrast, hypoxia during tumor development appears to favor tumor outcome, highlighting the importance of early detection. Finally, hypoxia in advanced stages resulted in increased expression of LPC characteristics indicating poor outcome.
    PLoS ONE 10(3):e0119555. DOI:10.1371/journal.pone.0119555 · 3.53 Impact Factor
  • Future Oncology 11/2014; 10(15s):89-92. DOI:10.2217/fon.14.232 · 2.61 Impact Factor

Preview

Download
0 Downloads