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Sirolimus was introduced in de novo immunosuppression at Stanford University in view of its favorable effects on reduced rejection and cardiac allograft vasculopathy. After an apparent increase in the incidence of post-surgical wound complications as well as symptomatic pleural and pericardial effusions, we reverted to a mycophenolate mofetil (MMF)-based regimen. This retrospective study compared the outcome in heart transplant recipients on sirolimus (48 patients) with those on MMF (46 patients) in de novo immunosuppressive regimen. The incidence of any post-surgical wound complication (52% vs. 28%, p = 0.019) and deep surgical wound complication (35% vs. 13%, p = 0.012) was significantly higher in patients on sirolimus than on MMF. More patients on sirolimus also had symptomatic pleural (p = 0.035) and large pericardial effusions (p = 0.033) requiring intervention. Logistic regression analysis showed sirolimus (p = 0.027) and longer cardiac bypass time (OR = 1.011; p = 0.048) as risk factors for any wound complication. Sirolimus in de novo immunosuppression after cardiac transplantation was associated with a significant increase in the incidence of post-surgical wound healing complications as well as symptomatic pleural and pericardial effusions.

OBJECTIVE To evaluate our experience with surgical resection of renal cell carcinoma (RCC) with inferior vena cava (IVC) involvement and examine the relationship between prognosis and tumour extent. PATIENTS AND METHODS A retrospective review of nephrectomy performed between 1985 and 2005 identified 50 patients presenting with tumour thrombus extension into the IVC. Clinical characteristics and outcome were evaluated. RESULTS Of the 50 patients evaluated, 7, 26, 10 and 7 presented with level I, II, III and IV thrombus, respectively. Major postoperative complications occurred in 16% of patients. Local or distant failure occurred in 25 (64%) patients. The mean time to recurrence was 10 months. Only supra‐diaphragmatic extension of the tumour thrombus was predictive of disease recurrence. CONCLUSION Locally advanced RCC with IVC thrombus remains associated with significant local and distant failure rate. The level of thrombus extension is significantly associated with disease recurrence. Effective adjuvant therapy is needed to improve outcome in this patient population.

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Marrow stromal cells (MSCs) are postnatal progenitor cells that can be easily cultured ex vivo to large amounts. This feature is attractive for cell therapy applications where genetically engineered MSCs could serve as an autologous cellular vehicle for the delivery of therapeutic proteins. The usefulness of MSCs in transgenic cell therapy will rely upon their potential to engraft in nonmyeloablated, immunocompetent recipients. Further, the ability to deliver MSCs subcutaneously -as opposed to intravenous or intraperitoneal infusions -would enhance safety by providing an easily accessible, and retrievable, artificial subcutaneous implant in a clinical setting. To test this hypothesis, MSCs were retrovirally engineered to secrete mouse erythropoietin (Epo) and their effect was ascertained in nonmyeloablated syngeneic mice. Epo-secreting MSCs when administered as 'free' cells by subcutaneous or intraperitoneal injection, at the same cell dose, led to a significant -yet temporaryhematocrit increase to over 70% for 55713 days. In contrast, in mice implanted subcutaneously with Matrigeltembedded MSCs, the hematocrit persisted at levels 480% for over 110 days in four of six mice (Po0.05 logrank). Moreover, Epo-secreting MSCs mixed in Matrigel elicited and directly participated in blood vessel formation de novo reflecting their mesenchymal plasticity. MSCs embedded in human-compatible bovine collagen matrix also led to a hematocrit 470% for 7578.9 days. In conclusion, matrixembedded MSCs will spontaneously form a neovascularized organoid that supports the release of a soluble plasma protein directly into the bloodstream for a sustained pharmacological effect in nonmyeloablated recipients.

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