Pancreas Transplantation: Lessons Learned From a Decade of Experience at Wake Forest Baptist Medical Center

Abstract

■ AbstractThis article reviews the outcome of pancreas transplantations in diabetic recipients according to risk factors, surgical techniques, and immunosuppression management that evolved over the course of a decade at Wake Forest Baptist Medical Center. A randomized trial of alemtuzumab versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT) at our institution demonstrated lower rates of acute rejection and infection in the alemtuzumab group. Consequently, alemtuzumab induction has been used exclusively in all pancreas transplantations since February 2009. Early steroid elimination has been feasible in the majority of patients. Extensive experience with surveillance pancreas biopsies in solitary pancreas transplantation (SPT) is described. Surveillance pancreas biopsy-directed immunosuppression has contributed to equivalent long-term pancreas graft survival rates in SKPT and SPT recipients at our center, in contrast to recent registry reports of persistently higher rates of immunologic pancreas graft loss in SPT. Furthermore, the impact of donor and recipient selection on outcomes is explored. Excellent results have been achieved with older (extended) donors and recipients, in recipients of organs from donation after cardiac death donors managed with extracorporeal support, and in African-American patients. Type 2 diabetics with detectable C-peptide levels have been transplanted successfully with outcomes comparable to those of insulinopenic diabetics. Our experiences are discussed in the light of findings reported in the literature.

Maturation of Stem Cell-Derived Beta-cells Guided by the Expression of Urocortin 3

“…These islets have already shown longevity potential in humans. Human pancreas [13] and islet transplantations [14] result in varying degrees of insulin independence, with 5-yr independence rates >50% [15,16]. Nevertheless, the application of human tissue transplantation approaches to a large majority of T1D patients is hampered by the limiting supply of donor tissue [17].…”

Pancreas Transplantation with Systemic-Enteric Drainage when Portal-Enteric Drainage is Contraindicated

“…Indications for PT were insulin-requiring diabetes with complications and the predicted ability to tolerate the operative procedure and manage the requisite immunosuppression and close follow-up irrespective of C-peptide production [9,10]. Selection criteria for SKPT in "type 2" diabetes included patients <55 years of age with a body mass index (BMI) <30 kg/m2, insulin-requiring for a minimum of 3 years with a total daily insulin requirement <1 u/kg/ day, a fasting C-peptide level <10 ng/ml, absence of severe vascular disease or tobacco abuse, adequate cardiac function, and presence of "complicated" or hyperlabile diabetes [9,10].…”

“…Selection criteria for SKPT in "type 2" diabetes included patients <55 years of age with a body mass index (BMI) <30 kg/m2, insulin-requiring for a minimum of 3 years with a total daily insulin requirement <1 u/kg/ day, a fasting C-peptide level <10 ng/ml, absence of severe vascular disease or tobacco abuse, adequate cardiac function, and presence of "complicated" or hyperlabile diabetes [9,10]. Selection criteria for solitary PT were similar to SKPT except for renal function, in which the calculatedglomerular filtration rate was >70 ml/min/1.73m2 in PTA (native renal function) and >40 ml/min/1.73m2in PAK (renal allograft function) recipients who were already receiving a calcineurin inhibitor.…”

“…Selection criteria for solitary PT were similar to SKPT except for renal function, in which the calculatedglomerular filtration rate was >70 ml/min/1.73m2 in PTA (native renal function) and >40 ml/min/1.73m2in PAK (renal allograft function) recipients who were already receiving a calcineurin inhibitor. Donor selection was more stringent for solitary PT, including younger donors and a minimum of a 2-3 human leukocyte antigen (HLA) match [9,11].…”

Emerging Trends for Radioimmunotherapy in Solid Tumors

“…In clinical settings, extracorporeal elimination is employed for the management of autoimmune diseases (removal of autoantibodies and immune complexes), cases of poisoning, sepsis, and organ transplantation. [76][77][78][79][80][81] In a series of studies, Tennvall et al have demonstrated the utility of extracorporeal affinity adsorption using avidin columns to deplete biotinylated radiolabeled antibodies from circulation. [82][83][84][85][86][87][88][89][90][91][92] In one of the earliest demonstrations of the approach using athymic rats bearing human melanoma and lung cancer xenografts, removal of biotinylated 125 I-labeled antimelanoma (MAb 96.5) and anticarcinoma (MAb L6) antibodies improved the tumor to normal tissue ratios by a factor of four or five.…”