BACKGROUND: Before embarking on a clinical human pancreas transplantation program we sought a canine animal model with enteric drainage to refine our technical skills, to evaluate the surgical risks and to study the rejection pictures under modern triple immunosuppression therapy. METHODS: Twenty donor-recipient pairs of unrelated mongrel dogs underwent pancreaticoduodenal allotransplantation with enteric drainage. All dogs were immunosuppressed by triple therapy with prednisolone, cyclosporine (Neoral) and mycophenolate mofetil (MMF). Rejection grade and surgical risk were evaluated. RESULTS: Group 1 included 10 (50%) dogs surviving at least 14 days. In group 2 surviving less than 14 days, the median survival was 5.5 days, ranging from 1 day to 13 days. The most common complications were duodenal stump leakage and wound infection. Duodenal stump leakage eventually led to mortality in 3 dogs of group 2. Two (in group 2) of the 3 wound infections became too severe to control and caused death. There were 2 dogs complicated with graft necrosis and 2 with graft vascular thrombosis individually, which all resulted in death. Other fatal complications included 1 chyle leakage, 1 intraabdominal abscess and 1 pneumonia individually. Ninety percent in each group developed rejection. Severe rejection developed in 5 (50%) dogs in group 2 (grade 4 and 5), p = 0.033, as compared with none in group 1. The rejection in most cases (90%) of group 1 was mild to moderate, with 4 grade 3, 3 grade 2 and 2 grade 1. CONCLUSIONS: Canine pancreas allotransplantation with enteric drainage is a feasible animal model to achieve survival longer than 14 days in 50% cases studied. Duodenal stump leakage was the most common fatal complication in this model. Severity of rejection was closely associated with posttransplant fatal complications and played a crucial role in determining the dog survival.
BACKGROUND: Before embarking on a clinical human pancreas transplantation program we sought a canine animal model with enteric drainage to refine our technical skills, to evaluate the surgical risks and to study the rejection pictures under modern triple immunosuppression therapy. METHODS: Twenty donor-recipient pairs of unrelated mongrel dogs underwent pancreaticoduodenal allotransplantation with enteric drainage. All dogs were immunosuppressed by triple therapy with prednisolone, cyclosporine (Neoral) and mycophenolate mofetil (MMF). Rejection grade and surgical risk were evaluated. RESULTS: Group 1 included 10 (50%) dogs surviving at least 14 days. In group 2 surviving less than 14 days, the median survival was 5.5 days, ranging from 1 day to 13 days. The most common complications were duodenal stump leakage and wound infection. Duodenal stump leakage eventually led to mortality in 3 dogs of group 2. Two (in group 2) of the 3 wound infections became too severe to control and caused death. There were 2 dogs complicated with graft necrosis and 2 with graft vascular thrombosis individually, which all resulted in death. Other fatal complications included 1 chyle leakage, 1 intraabdominal abscess and 1 pneumonia individually. Ninety percent in each group developed rejection. Severe rejection developed in 5 (50%) dogs in group 2 (grade 4 and 5), p = 0.033, as compared with none in group 1. The rejection in most cases (90%) of group 1 was mild to moderate, with 4 grade 3, 3 grade 2 and 2 grade 1. CONCLUSIONS:Caninepancreas allotransplantation with enteric drainage is a feasible animal model to achieve survival longer than 14 days in 50% cases studied. Duodenal stump leakage was the most common fatal complication in this model. Severity of rejection was closely associated with posttransplant fatal complications and played a crucial role in determining the dog survival.