Recurrent hepatocellular carcinoma in liver transplant recipients with hepatitis C.
ABSTRACT Hepatitis C (HCV) is the most common liver disease in patients transplanted with hepatocellular carcinoma (HCC) in the West. We examined predictors of HCC recurrence in liver transplant recipients with HCV.
From 1997 to 2006, 53 patients with HCC and HCV underwent liver transplantation. Pre-and post-operative data (including liver biopsies 4 months post-transplant) were collected. Differences between HCC recurrence and non-recurrence groups were detected by Student's t test or chi-square test. Data were analyzed as predictors of HCC recurrence by logistic regression multivariate analysis. Cumulative survival was analyzed by Kaplan-Meier curves and compared by the log-rank test.
Eleven of 53 patients (20.8%) developed HCC recurrence at a median interval of 15 months (2 to 55 months). Median Histology Activity Index (HAI) of liver biopsies, AST, and ALT at 4 months were significantly greater in patients with HCC recurrence. Independent predictors of HCC recurrence were HAI ≥ 4 at 4 months, ALT ≥ 100 at 4 months, and vascular invasion. Patients with HCC recurrence had significantly decreased survival.
In this preliminary study, Histology Activity Index and ALT at 4 months, as well as vascular invasion, predicted HCC recurrence in liver transplant recipients with HCV.
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ABSTRACT: Posttransplant malignancies, which occur either de novo or as cancer recurrences, are due to chronic exposure to immunosuppressive agents and are often more aggressive than those that develop in the nontransplant setting. Mammalian target of rapamycin (mTOR) inhibitors have antitumor and immunosuppressive effects. The dual effects of this class of agents may provide adequate immunosuppression to prevent organ rejection while simultaneously reducing the risk of posttransplant malignancy. mTOR inhibitors have become established approved agents for treating renal cell carcinoma and other cancers and, as reviewed herein, accumulating experience among organ transplant recipients collectively points toward a potential to prevent the development of de novo malignancies of various types in the posttransplant period. To date, most research efforts surrounding mTOR inhibitors and cancer control in the transplant population have been in the area of skin-cancer prevention, but there have also been interesting observations regarding regression of posttransplant Kaposi's sarcoma and posttransplantation lymphoproliferative disorder that warrant further study. This article is protected by copyright. All rights reserved.Clinical Transplantation 03/2014; · 1.49 Impact Factor
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ABSTRACT: BACKGROUND: Hepatitis C infection (HCV) and hepatocellular carcinoma (HCC), the two main causes of liver transplantation (LT), have reduced survival post-LT. The impact of HCV, HCC and their coexistence on post-LT survival were assessed. METHODOLOGY: All 601 LT patients from 1992 to 2011 were reviewed. Those deceased within 30 days (n = 69) and re-transplants (n = 49) were excluded. Recipients were divided into four groups: (a) HCC-/HCV-(n = 252) (b) HCC+/HCV- (n = 58), (c) HCC-/HCV+ (n = 106) and (d) HCC+/HCV+ (n = 67). Demographics, the donor risk index (DRI), Model for End-Stage Liver Disease (MELD) score, survival, complications and tumour characteristics were collected. Statistical analysis included anova, chi-square, Fisher's exact tests and Cox and Kaplan-Meier for overall survival. RESULTS: Groups were comparable with regards to baseline characteristics, but HCC patients were older. After adjusting for age, MELD, gender and the donor risk index (DRI), survival was lower in the HCC+/HCV+ group (59.5% at 5 yrs) and the hazard ratio (HR) was 1.90 [95% confidence interval (CI),1.24-2.95, P = 0.003] and 1.45 (95% CI, 0.99-2.12, P = 0.054) for HCC-/HCV+. HCC survival was similar to controls (HR 1.18, 95% CI, 0.71-1.93, P = 0.508). HCC+/HCV- patients exceeded the Milan criteria (50% versus 31%, P < 0.04) and had more micro-vascular invasion (37.5% versus 20.6%, P = 0.042). HCC+/HCV+ versus HCC+/HCV- survival remained lower (HR 1.94, 95% CI, 1.06-3.81, P = 0.041) after correcting for tumour characteristics and treatment. CONCLUSION: HCV patients had lower survival post-LT. HCC alone had no impact on survival. Patient survival decreased in the HCC+/HCV+ group and this appears to be as a consequence of HCV recurrence.HPB 03/2013; · 2.05 Impact Factor
Conference Paper: Loop Optimization in Register-Transfer Scheduling for DSP-Systems.[Show abstract] [Hide abstract]
ABSTRACT: In this paper, we discuss a control-flow transformation called loop folding, during the scheduling of register-transfer code for DSP-systems. Loop folding is functionally equivalent to data-path pipelining. An iterative loop-folding procedure, implemented in the CATHEDRAL II compiler, is presented. This technique may significantly improve the utilization of parallel hardware, available in a data path.Design Automation, 1989. 26th Conference on; 01/1989