Individualization of immunosuppressive therapy. III. Sirolimus associated with a reduced incidence of malignancy.

OBJECTIVE: We examined the occurrence of neoplasms among 1008 renal transplant recipients treated with a sirolimus-cyclosporine (CsA) +/- prednisone (Pred) regimen. METHODS: A comprehensive database of demographic, laboratory, clinical, and histopathologic features of these patients all followed in our transplant center was analyzed using Student t test and Mann-Whitney U test for continuous and chi-square test for categorical variables. Comparisons were performed with information in the Israel Penn International Transplant Tumor Registry (IPITTR). RESULTS: During the mean patient follow-up of 62.3 +/- 26.1 months (range 27.1 to 131), 36 tumors occurred in 35 patients (3.6%) at 32.5 +/- 29.8 months. The most common neoplasms were skin tumors (2.4%), a value that was significantly lower than the 6% rate observed with CsA-azathioprine-Pred treatment. Also, the 0.4% incidence of posttransplant lymphoproliferative disorders and 0.2% incidence of renal cell carcinomas were less than half of those previously reported with a combination of tacrolimus and mycophenolate mofetil. The distribution of tumor types was similar to that reported to the IPITTR. The mean trough drug concentrations in affected recipients at the time of diagnosis were within the putative target ranges. CONCLUSION: Renal transplant recipients treated with the sirolimus-CsA +/- Pred combination showed a low incidence of tumors of similar types as those encountered with other regimens.

Simvastatin therapy in lymphocyte cross-match-positive kidney transplantation candidates.

OBJECTIVES: Recent identification of several mechanisms by which statins decrease recruitment of monocytes and T cells into the arterial wall and inhibit both T-cell and B-cell activation and proliferation in vitro prompted us to study the immunomodulatory effects of statins. In this study, we examined the effect of simvastatin therapy on lymphocyte cross-match positivity in kidney transplantation candidates. METHODS: Simvastatin therapy (20 mg/d) was administered to 25 patients (18 men, 7 women of mean age 34 +/- 11.7 years who displayed positive lymphocyte cross-matches between July 2002 and October 2004. The etiologies of end-stage renal disease were vesicoureteral reflux (n = 5), urinary stone disease (n = 4), glomerulonephritis (n = 6), amyloidosis secondary to familial Mediterranean fever (n = 1), and unknown (n = 9). RESULTS: The lymphocyte cross-match became negative in 10 patients 4-9 months, and successful kidney transplantation was performed in 6 of them. The serum creatinine levels of these patients ranged between 0.8 and 1.4 mg/dL. Two patients required higher doses, but none suffered from adverse effects. The remaining 4 patients are still undergoing pretransplantation evaluation. CONCLUSION: Simvastatin therapy seems to be a cost-effective and useful method for lymphocyte cross-match-positive kidney transplantation candidates compared with immunoadsorption or intravenous immunoglobulin use.

Sirolimus as primary immunosuppression agent in kidney transplant recipients: Akdeniz University experience.

OBJECTIVES: Recently usage of sirolimus as the primary immunosuppressant is widening among kidney transplant recipients. We reviewed the clinical follow-up of patients transplanted at our center using sirolimus protocols. METHODS: Sirolimus including primary immunosuppressive treatment protocols were begun in February 2002. Among the 21 patients (15 men, six women) who received sirolimus, six patients were prescribed sirolimus + prednisolone; seven, sirolimus + mycophenolate mofetil + prednisolone; and eight, sirolimus + cyclosporine + prednisolone. The mean age of the patients was 32.9 +/- 7.3 years and the mean posttransplantation follow-up, 13.2 +/- 4.5 months. RESULTS: Three patients experienced acute rejection episodes, which were treated successfully with steroids. None of the patients had either hematologic or wound healing problems. Lymphoceles developed in eight patients. Serum creatinine level was 1.4 +/- 0.5 mg/dL at 12 months. There was a serious increase in serum cholesterol and triglyceride levels starting from the first month posttransplant (total cholesterol levels pretransplant and at 1 month, respectively: 159.3 +/- 29.5 and 255.7 +/- 52.3 mg/dL, P = .0001; triglycerides pretransplant and at 1 month, respectively: 146.9 +/- 89.5 and 215.1 +/- 102.5 mg/dL, P = .001). Despite routine antihyperlipemic treatment those high levels were maintained for 12 months. CONCLUSIONS: We achieved 100% graft and patient survival rates for 1 year among patients who were using sirolimus. But the most important role in defining the morbidity and mortality in this group of patients is cardiovascular events; for this reason the abnormalities in the lipid profile must be taken seriously.

Kidney-pancreas transplantation: single-center experience at a university hospital in Turkey.

INTRODUCTION: One treatment option for patients with type 1 diabetes mellitus with end-stage nephropathy is combined pancreas-kidney transplantation, which can be performed either simultaneously (SPK) or following kidney transplantation (PAK). PATIENTS AND METHODS: Between February 2003 and November 2004, 14 patients, including 10 males and 4 females of overall mean age of 31.3 +/- 6.1 years (range, 23-44 years), presented with end-stage renal disease secondary to type 1 diabetes mellitus. Five patients (35.7%) received SPK; 7 patients (50%) received PAK; and 2 patients (14.3%) received simultaneous pancreas and living-related kidney (SPLK) transplantations. RESULTS: Two among 14 pancreas grafts were lost in the early postoperative period secondary to venous thrombosis despite anticoagulation including 1 with poor portal drainage. Insulin therapy was reinitiated in 1 patient after a second rejection episode in the seventh postoperative month. By the ninth median follow-up month (range, 1-21 months), all kidney grafts were functioning. CONCLUSION: Our single-center short-term experience with 14 consecutive kidney-pancreas transplantations suggests that while the pancreas transplant is effective and safe to reestablish normoglycemia, this transplant creates additional surgical and immunosuppressive stresses on the patient.

Epididymal metastasis from gastric signet ring cell adenocarcinoma.

We report a 55 year old man complaining of painless left testicular swelling that developed over 2 months. The imaging studies revealed an epididymal mass separate from the testicle. The patient underwent left radical orchiectomy. The histopathological examination of the orchiectomy specimen revealed poorly differentiated signet cell metastatic adenocarcinoma.

The use and efficacy of the American Urological Association Symptom Index in assessing the outcome of urethroplasty for post-traumatic complete posterior urethral strictures.

OBJECTIVE: To determine if the American Urological Association (AUA) Symptom Index is an accurate and reliable instrument for use in assessing the outcome after urethroplasty. PATIENTS AND METHODS: The AUA Symptom Index questionnaire was answered by 33 men (mean age 31.3 years) who underwent end-to-end urethral reconstruction after complete urethral disruption; the index was completed at a mean of 6 months after surgery. The scores were then correlated with maximum flow rates (Qmax) and presence of re-stenosis on retrograde urethrography. RESULTS: The initial mean (SD) AUA score was 10.42 (9.6) and the Qmax 22.12 (9.37) mL/s. Of the 33 patients, six (18%) had re-stenosis, with a mean score of 30 and Qmax of 6 mL/s. There was a significant inverse correlation between the AUA symptom score and Qmax (r = - 0.401, P < 0.05). CONCLUSION: The AUA Symptom Index is inversely correlated with Qmax and may indicate the presence of re-stenosis after urethroplasty. The AUA score can thus be used as a cost-effective and easy method in the first-line screening of the outcome of urethroplasty.