Correlation of rejection of the duodenum with rejection of the pancreas in a pig model of pancreaticoduodenal transplantation

To assess the correlation of rejection in the duodenum and the pancreas, we examined pancreatic and duodenal tissue from pancreaticoduodenal transplants in 32 outbred Yorkshire Landrace pigs. After streptozotocin-induced hyperglycemia, they were transplanted and treated with prednisone, AZA, and CsA. Immuno-suppression was reduced by 50% weekly and discontinued at 3 weeks. The tissues were harvested at necropsy at various time points. Each organ was graded for interstitial rejection and vascular rejection separately as no, mild, moderate, and severe. All but 1 animal rejected their organs. Complete concordance of rejection between duodenum and pancreas considering both interstitial and vascular findings was found in 15/32 (47%) animals. In 11/17 (65%) of the remaining allografts, the pancreas had a higher rejection grade (3 interstitial, 5 vascular, 3 both) and in 6/17 (35%) the duodenum had higher rejection grades (2 interstitial, 4 vascular). Considering interstitial and vascular rejection separately, 23/32 (72%) and 20/32 (63%) showed concordance, respectively. Most cases (7/9, 78%) of discordant interstitial rejection showed higher interstitial rejection grades in the pancreas. Five cases (4 pancreas, 1 duodenum) showed interstitial discordance of 2 grades or more. Discordant cases with higher vascular rejection were 7 pancreas (58%) and 5 duodenum. Five cases (3 pancreas, 2 duodenum) showed vascular discordance of 2 grades or more. Interstitial rejection was seen alone (11 cases) and with vascular rejection (20 cases), but vascular rejection was never seen alone. We made the following conclusions. (1) Concordance of duodenal and pancreas rejection occurs in 47% of cases. (2) Discordant cases usually show higher grades of rejection in the pancreas (65%), but the opposite can also occur. (3) Therefore, if duodenal biopsies are positive, they are likely to be representative of pancreatic pathology, but when negative, they do not rule out rejection of the pancreas. (4) Interstitial rejection appears to precede vascular rejection, suggesting that factors released during interstitial rejection play a role in endothelial cell activation and vascular rejection.