Urinary and pancreatic juice neopterin excretion after combined pancreas-kidney transplantation.

The aim of this study was to investigate excretion of urinary and pancreatic juice neopterin in patients after combined pancreas-kidney transplantation and to relate it to the clinical course. The study design was a prospective observation study. Thirty consecutive patients with end-stage diabetic disease received a simultaneous pancreas-kidney transplant with pancreaticocystostomy and temporary exteriorization of pancreatic juice. In 30 patients urinary neopterin (UN) was measured daily from day +1 until hospital discharge by high-performance liquid chromatography; in ten of these 30 patients pancreatic juice neopterin (PJN) was additionally analyzed daily from day +1 for as long as pancreatic juice was diverted to the exterior. Elevated urinary neopterin levels were observed in acute cellular rejection (19/24 rejection episodes) and in bacterial infection (9/16 cases)--however, increments were more pronounced in acute cellular rejection. In contrast, pancreatic juice neopterin increased in all seven observed pancreatic graft rejection episodes. Pancreatic juice infection did not result in a rise in pancreatic juice neopterin excretion. Patients without postoperative complications exhibited stable and low urinary/pancreatic juice neopterin levels. The highest urinary neopterin levels were observed in CMV disease. Levels measured prior to discharge from hospital did not correlate with graft and patient survival. Evaluation of urinary and pancreatic juice neopterin, although nonspecific, helps identify patients with an uncomplicated or complicated clinical course. Pancreatic juice neopterin appears to be superior to urinary neopterin in early detection of pancreatic graft rejection. This may be of particular importance in monitoring nonuremic pancreas allograft recipients.

Histological features of acute pancreatic allograft rejection after pancreaticoduodenal transplantation in the rat.

For characterization of histopathological changes during pancreas graft rejection, pancreaticoduodenal transplants were performed in three groups: (1) Brown Norway into diabetic Lewis rats without immunosuppression, (2) Brown Norway into diabetic Lewis rats with cyclosporin A, and (3) Lewis into Lewis rats. Diffuse inflammatory infiltration of the acini by mononuclear cells indicated the onset of rejection (stage I). Shortly after acinar infiltration, damage to small and large interlobular excretion ducts occurred. This took the form of florid circumferential inflammation and vacuolar degeneration of epithelium similar to the bile duct damage seen in primary biliary cirrhosis, graft-versus-host disease, and liver allograft rejection (stage II). Thereafter, endothelialitis and destruction of islets were evident, consistent with a more advanced and irreversible stage of rejection (stage III). Acinar inflammation and moderate duct lesions were not prevented by immunosuppression but were delayed. Nonetheless, severe vascular changes and loss of islets were avoided. We conclude that duct lesions are a reliable criterion for pancreas allograft rejection. They are more sensitive than vascular changes and more specific than cellular infiltration of acinar tissue, which may also occur in infection.

Morphology of acute rejection and corresponding cytological findings in exocrine secretion after pancreas transplantation in the rat.

Reliable and timely rejection diagnosis still represents a major problem of pancreas allotransplantation. The aim of this study was to confirm the clinical findings of exocrine function impairment and pancreatic juice cytology during rejection, to refine the latter by means of flow cytometry, and to correlate these changes with graft histology. Heterotopic pancreatic transplants were performed in a modified technique in Lewis rats rendered diabetic by means of streptozotocin from LEW donors (group I, n = 10), Brown Norway rats without immunosuppression (group II, n = 16), and from BN rats where recipients were given cyclosporine 12 mg/kg/BW (group III, n = 10). Pancreatic juice was obtained by daily aspiration from a self-made fully implantable catheter reservoir system. In group II animals acute rejection diagnosed on histomorphological grounds was clearly associated with a decrease in the amount of exocrine secretion and its enzyme content from day 8 on. In contrast to groups I and III, a significant increase in lymphocytes in the pancreatic juice up to 13.5% occurred in group II between days 5 and 7. Activated lymphocytes increased from 7% to 13%, pan-T cells from 193 to 340 events. Histology revealed three distinct phases of acute rejection--phase I: diffuse infiltration of acinar structures; phase II: destruction of interlobular ducts; phase III: vasculitis associated with islet cell damage. The anatomy of the pancreas with the slackness of its highly vascularized interstitial connective tissue facilitates early infiltration of inflammatory cells and migration of these cells into the lumen of the pancreatic duct. Thus pancreatic juice cytology together with an impaired exocrine graft function is highly indicative of acute rejection.

A technique of pancreas transplantation in the rat securing pancreatic juice for monitoring.

In order to study exocrine pancreas graft function and cytological findings, a technique of vascularized pancreas transplantation with special reference to a pancreatic juice collecting system has been developed in the rat model. For this purpose, a catheter is introduced into the common bile duct, which is ligated close to the duodenum, thus covering all pancreatic ducts. This catheter is connected to a reservoir implanted subcutaneously, from which pancreatic juice can easily be aspirated. The amount of 0.7-1.2 cc of juice produced over a 24-h period has proven to be sufficient for various analyses and cytological examination.

[A technique for pancreatic juice collection in the rat]. / Technik der Pankreassaftgewinnung bei der Ratte.

Monitoring of exocrine graft function and pancreatic juice cytology have proved to be a reliable method of detection of pancreas allograft rejection. In order to confirm these clinical findings and to define further parameters, experimental work is still needed. The rat was chosen for these experiments and a technique of pancreatic juice procurement developed. In five animals a fully implantable closed reservoir-catheter system was used. For the prevention of bacterial contamination it was necessary to install a mixture of antibiotics and culture medium into the reservoir. Pancreatic juice was procured daily under general anaesthesia. During the observation time of 14 days no further complications were encountered with the exception of one catheter dislocation. The mean amount of juice of 1 cc per day has proved to be sufficient for various enzyme estimations as well as for juice cytology.