C. L. Marsh

Histologic diagnosis of rejection by using cystoscopically directed needle biopsy specimens from dysfunctional pancreatoduodenal allografts with exocrine drainage into the bladder

To determine the histologic features of rejection and to identify nonrejection causes of human pancreatic allograft dysfunction, we analyzed 31 needle biopsy specimens (17 pancreatic, 14 duodenal) obtained under cystoscopic direction from 15 dysfunctional pancreatoduodenal allografts with exocrine drainage into the bladder. Eight allografts undergoing rejection showed the most common histologic features of rejection to be diffuse mixed inflammatory infiltrates of pancreatic acinar tissue and duodenum wall. Diffuse infiltration of pancreatic acinar tissue by neutrophils was the earliest histologic change in rejection. Seven dysfunctional allografts not undergoing rejection (“nonrejection”) showed a normal pancreas or various changes including acinar dilation with inspissation of secretions, fibrosis, cytomegalovirus inclusions, and enzymatic necrosis. The histologic changes in the duodenum paralleled those in the pancreas in both rejection and nonrejection allografts. We conclude that the histologic features of rejection in pancreatoduodenal allografts are distinctive. The changes seen in biopsy specimens accurately reflect the state of the graft and can be used to diagnose rejection and to identify other causes of graft dysfunction. Biopsy samples from the duodenum as well as the pancreas are diagnostically useful. The biopsy findings can be used to guide the clinical management of rejection and in the development of other noninvasive tests for rejection.

Sequential histopathologic changes in pancreaticoduodenal allograft rejection in dogs

To determine the nature and sequence of the histologic changes in the early rejection of pancreaticoduodenal allografts and to assess the correlation between pancreaticoduodenal biopsy findings and the pathologic changes in the graft, we performed serial cystoscopically directed needle biopsies of pancreaticoduodenal allografts in 18 dogs and compared the findings with the histologic changes in 16 autografts as controls. Tissue adequate for evaluation was obtained by the biopsy technique in 70% of instances. The earliest and most characteristic manifestation of rejection was diffuse mixed inflammatory infiltrates involving the pancreatic acinar tissue and duodenum. The biopsy findings correlated well with the changes in the resected pancreatic specimens. Cellular rejection in the duodenum correlated with rejection in the pancreatic graft. There were no changes in the autografts that resembled cellular rejection. We conclude that, in the canine model, cystoscopically directed needle biopsy of pancreaticoduodenal allografts consistently provides adequate tissue for the diagnosis of rejection; the status of the graft can be monitored by serial biopsies of pancreatic acinar tissue and, possibly, by serial biopsies of the duodenal wall alone.

Diversion of the gastroduodenal vein: an in situ model of systemic insulin drainage

A technique of diversion of the gastroduodenal vein in a canine model is described to compare long-term metabolic effects of systemic versus portal pancreatic endocrine drainage. The vein was transected at its entrance into the portal vein and either diverted to the inferior vena cava (systemic group) or reanastomosed to the portal vein (portal group). All remaining venous drainage of the pancreas was interrupted. An additional group of animals underwent laparotomy without manipulation of pancreatic vasculature (sham group). Fasting peripheral insulin and glucose values were determined 3 months postoperatively. Fasting insulin values were significantly higher in the systemic group (mean 10.7 +/- 1.06 U/ml) than in the portal (5.8 +/- 0.70, P = 0.002) and sham (6.4 +/- 0.68, P = 0.01) groups. Fasting glucose values were not significantly different in the three groups. At sacrifice, venous thrombosis was noted in one systemically diverted dog (6.7%). All other anastomoses were patent. No significant collateralization was apparent in any group. No significant complications were noted. This procedure simulates the hormonal milieu created by heterotopic pancreatic transplantation while preserving pancreatic innervation and exocrine function, and serves as an excellent model for investigating the effects of systemic hyperinsulinemia on protein, carbohydrate, and lipid metabolism.

Canine Pancreaticoduodenal Allotransplantation: A Preparation for Human Pancreatic Transplantation

This canine pancreaticodunodenal autotransplantation model includes virtually the entire pancreas attached to a duodenal cuff (second portion). The blood supply is based on the superior pancreaticoduodenal artery and the venous outflow on the gastroduodenal vein. The vascular anastomoses are end-to-side to the external iliac artery and vein. Exocrine drainage is channeled through the bladder from the transplanted duodenum. This technique closely resembles whole-organ pancreas transplant in humans with a cystoduodenostomy. The bowel reconstruction consists of a Billroth I gastroduodenostomy and a cholecystoduodenostomy. The entire procedure is relatively free of major complications and may be performed in less than 4 hours.

Canine Pancreaticoduodenal Allotransplantation with Cystoduodenostomy: An Animal Model with Clinical Application

Most techniques described in animal models of pancreatic transplantation use either segmental or autotransplants. We employ a technique of pancreaticoduodenal allotransplantation in the dog that closely resembles the operation used in humans. The arterial supply of the entire pancreatic graft is preserved by procuring a Carrel patch of aorta encompassing the origin of the celiac and the superior mesenteric arteries. Splenic, inferior pancreaticoduodenal, and superior pancreaticoduodenal arteries remain intact with the graft. Venous drainage is through a short segment of portal vein. A 6-cm cuff of duodenum is taken with the head of the pancreas. Engraftment proceeds by placing the allograft within the peritoneal cavity of the recipient. End-to-side vascular anastomoses are constructed to distal aorta and inferior vena cava. The duodenal cuff is anastomosed to the dome of the bladder for drainage and analysis of exocrine secretions and to provide a port of entry for cystoscopically directed needle biopsy. A total pancreatectomy is performed to induce a state of diabetes. The average operating time is 5 h. Twenty-two dogs have undergone allotransplantation using this technique. Six dogs had no complications and were sacrificed after meeting criteria of their study protocol. There were three technical failures, two arterial thromboses and one exsanguination, yielding an 86% rate of successful engraftment. Three other dogs died of intussusception and three dogs died of sepsis, one secondary to wound dehiscence and one due to inadvertent common bile duct ligation during pancreatectomy. Wound problems, four dehiscences and two superficial infections, occurred only in immunosuppressed dogs.