A regimen of daclizumab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction. (ClinicalTrials.gov number, NCT00231764 [ClinicalTrials.gov].).

Belatacept, an investigational selective costimulation blocker, did not appear to be inferior to cyclosporine as a means of preventing acute rejection after renal transplantation. Belatacept may preserve the glomerular filtration rate and reduce the rate of chronic allograft nephropathy.

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Cardiac and cerebral vascular diseases are leading causes of morbidity and death in solid organ transplant recipients. Immunosuppressant drugs are associated with dyslipidemia, hypertension, and hyperglycemia, which along with obesity are the main features of metabolic syndrome. In the nontransplant population, metabolic syndrome is associated with increased risk for major vascular complications. We postulated that metabolic syndrome is common post-liver transplantation and plays a significant role leading to cardiac and cerebrovascular events. Our Multi-Organ Transplant Program database was reviewed for all liver transplant recipients between January 1998 and June 2004 with follow-up until December 2005. We adapted the 2001 National Cholesterol Education Program-Adult Treatment Panel III Guidelines to define posttransplantation metabolic syndrome (PTMS) as the presence at least 3 of the following: 1) obesity (body mass index Ͼ30 kg/m 2 ); 2) serum triglyceride level Ն1.7 mmol/L; 3) high density lipoprotein level Ͻ1 mmol/L in men and Ͻ1.3 mmol/L in women; 4) hypertension; and 5) fasting plasma glucose Ն5.6 mmol/L. A total of 118 patients were included. Among them, 69 patients (58%) had PTMS. The mean (Ϯ standard deviation) time from transplant was 59 Ϯ 21 months (no significant difference in patients with or without metabolic syndrome). Overall, patients with metabolic syndrome had a significantly higher average age, posttransplantation body mass index, fasting glucose, high-density lipoprotein levels, and serum triglycerides. There was no difference in creatinine, hemoglobin, or prednisone average dose between the 2 groups. There were 25 major vascular events affecting 21% of patients. There were significantly more vascular events in patients with metabolic syndrome posttransplantation than in those without (30% vs. 8%; P ϭ 0.003) during the study period. In conclusion, the prevalence of metabolic syndrome post-liver transplant is significantly higher than that estimated in the general population. Metabolic syndrome appears to be associated with an increased risk of major vascular events in our liver transplant population.

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Current imaging technologies do not sufficiently detect micrometastasis and therefore do not allow adequate stratification of patients with hepatocellular carcinoma (HCC) for curative or systemic therapy. In HCC, presence of stem cell-like, epithelial cell adhesion molecule (EpCAM)-positive cells correlates with tumor aggressiveness and formation of metastasis. Therefore, we investigated the prognostic relevance of EpCAM-positive circulating tumor cells (CTCs) in patients with HCC. Blood from 78 patients (19 patients in the control cohort and 59 patients with HCC) was tested for CTCs with the CellSearch TM system. Correlation analysis to overall survival (OS), the Barcelona Clinic Liver Cancer (BCLC) staging system, macroscopic and microscopic vascular invasion and alpha-fetoprotein (AFP) levels were performed. We detected 1 CTC in 18=59 HCC patients and in 1=19 patients with cirrhosis or benign hepatic tumor (p 5 0.026). OS was significantly shorter (460 vs. 746 days) in the CTC-positive cohort (p 5 0.017). Comparing BCLC stages, significant differences in CTC detection rates were also observed: BCLC stages A 1=9, B 6=31 and C 11=19 (p 5 0.006). Ten of 18 patients with macroscopic and 10=16 patients with microscopic vascular invasion exhibited positive findings in CTC testing (p 5 0.004 and p 5 0.006). Furthermore, CTC results correlated to AFP (cutoff > 400 ng=mL) levels (p 5 0.050). Our study demonstrates frequent presence of EpCAM-positive CTC in patients with intermediate or advanced HCC and its prognostic value for OS with possible implications for future treatment stratification.Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, has a rising incidence in Western countries, and is ranked third in global cancer-related mortality. 1-7 Most cases result from cirrhosis of the liver or chronic viral hepatitis. It is believed that alcoholic liver disease and nonalcoholic steatohepatitis (NASH) will play a dominant role as underlying etiology in Western countries in the near future. 4 Treatment of patients with confirmed HCC is based on the Barcelona Clinic Liver Cancer (BCLC) staging system. Patients with early-stage HCC (BCLC stage A) are selected for curative resection, local ablative therapy or orthotopic liver transplantation. Unfortunately, most patients in Western countries are diagnosed in an advanced stage (BCLC stage C), characterized by vascular invasion, metastases and an impaired performance status (PS 1-2). 8,9 The key problem in curative treatment in HCC (BCLC stage A) is recurrence after curative therapy. This might be owing to undetectable micrometastasis at initial staging. Therefore, it would be pivotal to rule out a possible metastatic dissemination at the time of diagnosis, including micrometastasis or potential "metastasis-initiating" circulating tumor cells (CTCs) in order to evaluate the true benefit of curative treatment. Furthermore, it is important to determine to what extent BCLC stage B patients (HCC limited to the liver) without CTC might benefit from curative th...

Administration of daclizumab in addition to dual immunosuppression therapy significantly reduced biopsy-proven acute rejection after renal transplantation, improved patient survival, and did not add to the toxicity of the immunosuppressive regimen.

Although the calcineurin inhibitors (CNI) cyclosporine (CsA) and tacrolimus are highly effective immunosuppressants, they are associated with serious side effects. There is great interest in immunosuppressive regimens that permit reduction or elimination of CNIs, while maintaining adequate immunosuppression and acceptable acute rejection rates. Patients (n = 536) receiving their first renal allograft were randomized to one of three immunosuppressant regimens: daclizumab, mycophenolate mofetil (MMF), corticosteroids (CS) and low-dose CsA (target trough levels of 50-100 ng/mL), weaned from month 4 and withdrawn by month 6; daclizumab, MMF, CS and low-dose CsA; or MMF, CS and standard-dose CsA. Mean GFR 12 months after transplantation (primary end point) was not statistically different in the CsA withdrawal and low-dose CsA groups (both 50.9 mL/min/1.73 m 2 ) vs. the standard-dose CsA group (48.6 mL/min/1.73 m 2 ). At 12 months, the incidence of biopsy-proven acute rejection was significantly higher in the CsA withdrawal group (38%) vs. the low-or standard-dose CsA groups (25.4% and 27.5%, respectively; p < 0.05). In summary, a regimen of continuous low-dose CsA with MMF, CS and daclizumab induction is a clinically safe and effective immunosuppressive regimen in renal transplant recipients.