Prostate cancer represents a major cause of cancer death in men worldwide. Novel non-invasive methods are still required for differentiation of non-aggressive from aggressive tumors. Recently, changes in prostate-specific antigen glycosylation pattern, such as core-fucosylation, have been described in prostate cancer. The objective of this study was to evaluate whether the core-fucosylation determinant of serum prostate-specific antigen may serve as refined marker for differentiation between benign prostate hyperplasia and prostate cancer or identification of aggressive prostate cancer. A previously developed liquid chromatography–mass spectrometry/mass spectrometry–based strategy was used for multiplex analysis of core-fucosylated prostate-specific antigen (fuc-PSA) and total prostate-specific antigen levels in sera from 50 benign prostate hyperplasia and 100 prostate cancer patients of different aggressiveness (Gleason scores, 5–10) covering the critical gray area (2–10 ng/mL). For identification of aggressive prostate cancer, the ratio of fuc-PSA to total prostate-specific antigen (%-fuc-PSA) yielded a 5%–8% increase in the area under the curve (0.60) compared to the currently used total prostate-specific antigen (area under the curve = 0.52) and %-free prostate-specific antigen (area under the curve = 0.55) tests. However, our data showed that aggressive prostate cancer (Gleason score > 6) and non-aggressive prostate cancer (Gleason score ≤ 6) could not significantly (p-value = 0.08) be differentiated by usage of %-fuc-PSA. In addition, both non-standardized fuc-PSA and standardized %-fuc-PSA had no diagnostic value for differentiation of benign prostate hyperplasia from prostate cancer. The %-fuc-PSA serum levels could not improve the differentiation of non-aggressive and aggressive prostate cancer compared to conventional diagnostic prostate cancer markers. Still, it is unclear whether these limitations come from the biomarker, the used patient cohort, or the imprecision of the applied method itself. Therefore, %-fuc-PSA should be further investigated, especially by more precise methods whether it could be clinically used in prostate cancer diagnosis.

Heart transplant recipients treated with long-term calcineurin inhibitors (CNIs) experience significant nephrotoxicity and transplant vasculopathy. Signal proliferation inhibitors might prevent the development of transplant vasculopathy. In an open, prospective pilot study, 33 primary heart transplant recipients received tacrolimus (Tac) and sirolimus (rapamycin, Rapa) with steroids. To reduce both nephrotoxicity and transplant vasculopathy at the same time, both Tac and Rapa exposure was kept low (6 to 8 ng/ml). Steroids were withdrawn successfully from all patients within 6 months. Just one acute rejection occurred at 54 days post-transplant, resulting in 0.03 acute rejection episode per patient at 1-year (primary end-point) and 2-year follow-up. Transplant vasculopathy assessed by angiogram was absent at 2 years. Graft and patient survival were 100% at 1 and 2 years. Accordingly, the survival estimate for freedom from first acute rejection, transplant vasculopathy, graft loss or death was 0.97 at 1 and 2 years. The regimen was well tolerated with only 3 patients requiring a change of study medication. Mean serum creatinine increased during the first year but returned to baseline at 2 years.

Objectives: Sirolimus and tacrolimus are immunosuppressants competing for the same binding-protein. This study evaluated the efficacy and safety of the immunosuppressive combination tacrolimus and sirolimus after heart transplantation using subtherapeutic trough levels for each compound.

This combination has hardly been considered for immunosuppression since both compounds compete for the same binding protein.

Background: In end-stage cardiomyopathy where concomitant chronic renal failure is a contraindication for cardiac transplantation (HTx), Simultaneous heart and kidney transplantation (HKTx) may be the only feasible therapeutic option. Due to the increased donor shortage, the clinical outcome of combined HKTx patients on tacrolimus-based immunosuppression was assessed and compared with a group of HTx patients.Methods: Three hundred forty-nine HTxs, including 13 (4%) combined HKTxs, were performed since 1995. Two hundred twenty-one HTx and all HKTx recipients received tacrolimus-based immunosuppression. Acute rejection episodes (AREs), infections, renal function and clinical outcome were evaluated. Pre-operative renal diagnoses for HKTx patients included cystic nephropathy (n = 4), glomerulonephritis (n = 4), cytostatica-induced nephropathy (n = 1), chronic rejection after renal transplant (n = 1), reflux nephropathy (n = 2) and chronic calcineurin-inhibitor -induced nephropathy after HTx (n = 1). Twelve patients (92%) were on hemodialysis pre-operatively, 1 underwent implantation of a left ventricular assist device (LVAD) before HKTx.Results: After 4.7 +/- 2 years, 92% of HKTx compared with 85% of HTx patients had survived (p = 0.42). Acute cardiac rejection episodes were more frequent in HTx than in HKTx patients (0.04 +/- 0.09 vs 0.02 +/- 0.04 ARE/100 patient-days; p = 0.07). Incidence of infection was comparable (0.3 +/- 0.2 vs 0.5 +/- 0.4 infection/100 patient-days). Freedom from transplant vasculopathy was 100% in the HKTx group compared with 71% in the HTx group after 4 years (p = 0.04).Conclusions: Tacrolimus-based immunosuppression yields promising long-term results in HKTx and HTx. The incidence of transplant vasculopathy seems to be lower after HKTx than after HTx. If these results are secondary to a protective effect of tacrolimus-induced tolerance or of tolerance-associated co-transplantation they will need to be investigated in prospective multicenter trials.

Objectives: This study evaluates the impact of immunosupressive combinations with Cyclosporine A (CSA), Azathioprine (Aza), Tacrolimus (Tac) and Mycophenolate Mofetil (MMF) on the time of onset, extent and progression of graft vessel disease (GVD).

The impact of sirolimus on hormone levels involved in the hypothalamus-pituitary-gonad axis in male heart transplant recipients was investigated.A pair-matched analysis with 132 male heart transplant recipients on either sirolimus based- or calcineurin inhibitor-based immunosuppression was performed. Matching criteria were age, years after transplantation and creatinine levels. Measured parameters were testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), sexual hormone-binding globulin (SHBG) and free androgen index (FAI).Mean testosterone was 3.86 +/- 1.41 ng/mL in the sirolimus group and 4.55 +/- 1.94 ng/mL in the controls (p = 0.025). Serum LH was 12.82 +/- 11.19 mlU/mL in the sirolimus patients and 6.2 +/- 5.25 mlU/mL in the controls (p = 0.015). Follicle stimulating hormone levels were 13.31 +/- 18.4 mlU/mL vs. 7.32 +/- 5.53 mlU/mL, respectively (p = 0.015). The analysis revealed a significant decrease in testosterone and a significant increase in FSH and LH in the sirolimus group. The duration of sirolimus treatment correlated positively with SHBG (p < 0.01), LH (p < 0.05) and FSH (p < 0.05) and negative with the FAI (p < 0.05). Sirolimus trough levels correlated with LH and FSH levels (p < 0.01).Heart transplant recipients treated with sirolimus revealed significantly lower testosterone levels and a significant increase in gonadotropic hormones. These effects were trough-level dependent. All candidates awaiting organ transplantation should be informed about these adverse effects.

Background: Calcineurin-inhibitor-(CNI)-induced renal failure is a common complication after cardiac transplantation (HTx). In this prospective study the impact of immunosuppressive conversion to a CNI-free immunosuppressive regimen (MMF+Sir) on efficacy, safety and renal function was evaluated.

Introduction: Although Amphotericin is the gold standard in the treatment of invasive Aspergillosis (IA) in transplant recipients, toxicity and lack of efficacy often limit its use. Itraconazole is better tolerated but less efficacious and influences immunosuppressants (IS)- trough levels significantly. We report our first clinical experience with the use of Caspofungin (CSF) in patients (pts.) after heart and lung transplantation suffering from invasive aspergillosis.

Background: CMV-infection and CMV-disease is a common adverse event after heart transplantation (HTx). Todate oral formulations of virostatics had a limited bioavailability. Therefore state of the art therapy of CMV-infections used to be intravenous application of ganciclovir. Patients had to be hosptalized and intravenous application was associated with the risk of catheter-related complications.

O411 Aims: Calcineurin-inhibitor (CNI) related nephrotoxicity is a common problem after cardiac transplantation. We studied the impact of CNI-free immunosuppressive regimen (mycophenolate mofetil (MMF) and sirolimus (Sir)) on renal function in heart transplant recipients with posttransplant renal impairment (serum creatinine level >2mg/dl). Methods: Thirty heart transplant recipients (27men, 7 woman; 0.1 to 14.2 years after transplantation) with CNI-based immunosuppression (plus MMF) and a serum creatinine level >2.0 mg/dl were included in the study. Serum creatinine level and cystatine were monitored to detect renal function. Mean patient age was 52±14 years (range 19-68years). Sir was started with 6mg, continued with 2mg and adjusted according fasting target trough levels. Target trough levels for Sir were of 10-14 ng/mL. Subsequently, the CNIs were tapered down and finally stopped. Clinical follow up (1 month after conversion and every three month thereafter) included endomyocardial biopsies, echocardiography, EKG and laboratory studies. Results: No acute rejection episode occurred during the study period. Renal function improved significantly after a mean follow up of 22.5±8months after conversion: Creatinine pre vs post conversion: 3.10±0.88mg/dl vs 2.12±0.71mg/dl, p=0.001. Cystatin pre vs post conversion: 2.9±0.6mg/dl vs 2.2±0.6mg/dl, p=0.04. Three patients were on hemodialysis prior conversion and recovered after conversion from CI treatment so that hemodialysis therapy could be stopped completely. Graft function remained stabile: Fractional shortening pre vs post conversion: 36.8±6% vs 35.9±8%. Serious adverse events did not occur. One patient had to be excluded due to noncompliance. Conclusions: Conversion from CI based immunosuppression to MMF and Sir in heart transplant recipients with chronic renal failure is safe, preserves graft function and improves renal function.

Fatal leucoencephalopathy is a rare calcineurin inhibitor-related complication, especially in kidney and liver transplant recipients. The only means of clinical management reported so far is the discontinuation or reduction in the calcineurin inhibitor. We herein report a case of a 37-yr-old male who developed leucoencephalopathy 12 wk after heart transplantation and recovered after stabilization of metabolism and arterial blood pressure. The findings in this case support the hypothesis that tacrolimus-associated neurotoxicity is severely increased by an impairment of the blood-brain barrier. Withdrawal of tacrolimus was not necessary while other causes of endothelial injury were treated successfully.

Objective: Calcineurin-inhibitor related nephrotoxicity is a common problem after cardiac transplantation. We studied the impact of calcineurin-inhibitor(CI)-free immunosuppression (mycophenolate mofetil (MMF) and sirolimus (Sir)) treatment on renal function in heart transplant recipients with posttransplant renal impairment (serum creatinine level >2mg/dl).

Objective: CMV-infection is a common risk factor for the postoperative course after heart transplantation (HTx). The prophylactic use of Ganciclovir (in order to avoid CMV-infection) is costly and the efficacy is discussed controversly. In a randomised, prospective, clinical trial, CMV-prophylaxis on incidence of CMV-infection, transplant vasculopathy (TVP) and clinical outcome was compared to a untreated control group.

Objective: Advanced recipient age is generally considered a relative contraindication for heart transplantation since it might be associated with increased morbidity and decreased long-term survival. Aim of the study was to evaluate the impact of immunosuppression on morbidity and mortality in elderly heart transplant recipients.

BACKGROUND:Graft vessel disease, the major limitation for long-term success after heart transplantation, is triggered by injury to the graft vessel endothelium, resulting in the expression of adhesion molecules, the migration of leukocytes into the graft, and the release of growth factors. Angiopeptin, a stable analog of somatostatin, is a growth-hormone inhibitor with additional anti-proliferative effects. We evaluated angiopeptin for prevention of graft vasculopathy after cardiac transplantation in the first prospective, randomized, double-blind, clinical trial.METHODS:Thirty-one patients received treatment with either angiopeptin (n = 13) or placebo (n = 18). Patients were randomized according to the presence of hypercholesterolemia, recipient cytomegalovirus-antibody status, and donor age. All patients received standard triple-drug immunosuppression. Angiopeptin 1.5 mg or placebo was given subcutaneously immediately before surgery and twice a day after transplantation from Day 1 to Day 14. Furthermore, 1.5 mg was added to each liter of cardioplegic solution, 1.5 mg was given intravenously during surgery, and another 3 mg was given during the first 6 post-operative hours. During the first post-operative year, angiopeptin 1.5 mg or placebo was added to each treatment for acute rejection (twice a day subcutaneously). Baseline angiography was performed within the first 4 post-operative weeks and annually thereafter. Twenty-three patients each underwent an additional intracoronary ultrasound.RESULTS:One- and 4-year survival rates were comparable: 85% and 85% for the group receiving angiopeptin, and 89% and 78% for the placebo group, respectively. One patient in the control group died of myocardial infarction caused by graft vessel disease. Although the mean number of rejection and infection episodes was similar, the overall incidence of newly occurring graft vessel disease after 2 and 4 years was greater in the control cohort: 9% vs 38% after 2 years and 27% vs 44% after 4 years (p = 0.183, 0.448). Comparison of the results of intracoronary ultrasound performed in a sub-group of patients confirmed that trend: the modified Stanford score, the mean intimal thickness, and the mean intimal index were lower in the angiopeptin group. Again, because of the relatively small number of patients available for evaluation, the difference did not reach statistical significance.CONCLUSIONS:Short-term peri-operative angiopeptin treatment along with additional injections during rejection episodes within the first year resulted in a marked decrease in graft vessel disease 2 and 4 years after heart transplantation. Based on our results, continuous, long-term application of slow-release angiopeptin could significantly decrease or even prevent graft vessel disease.