Long Term Studies of Pancreas Transplantation in Experimental Diabetes Mellitus

Orloff, Marshall J.; Lee, Sun; Charters, A C; Grambort, David E.; Storck, Lena J.; Knox, Dale G.

doi:10.1097/00000658-197509000-00003

Cited by 71 publications

(25 citation statements)

References 7 publications

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“…The unique value of the composite graft technique is that the duodenal component of the organ complex can be used to drain the exocrine pancreatic excretions into the recipient gastrointestinal tract without jeopardizing the pancreatic duct system [8]. Unfortunately, it has not been possible to exploit this advantage using conventional immunosuppression with azathioprine and prednisone because of the inability to consistently control rejection of the duodenum.…”

Section: Commentsmentioning

confidence: 99%

Total pancreaticoduodenal homotransplantation in dogs immunosuppressed with cyclosporine and steroids

Diliz-Pérez¹,

Hong²,

Santibañés³

et al. 1984

The American Journal of Surgery

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Improved survival of segmental pancreatic homografts has been obtained in animals using cyclosporine alone for immunosuppression [1,2]. Despite this, the results in clinical trials of pancreas transplantation have remained poor, in part because effective ways of draining or eliminating the exocrine drainage of the segmental grafts have not been developed [3]. Herein we report our experience in dogs with the alternative procedure of total pancreaticoduodenal homotransplantation using cyclosporine combined with small doses of steroids. Material and MethodsTwenty mongrel dogs of both sexes weighing between 15 and 25 kg were used as donors or recipients in 10 experiments. The homografts were removed from the donor through a midline incision. The transplant specimen was prepared, preserving the splenic vessels out to their entry into the spleen at the site of splenectomy and retaining the hepatic artery throughout its course, including its termination as the gastroduodenal artery (Figure 1, top). The splenic, superior mesenteric, and portal veins were retained with the specimen which included both lobes of the pancreas as well as the duodenum. The composite organ graft was flushed through the celiac axis with chilled, modified Collin's solution (Travenol) and preserved for 2 to 3 hours.The organ complex was revascularized in the left iliac fossa with end-to-side anastomoses of the donor celiac axis and portal vein, to the recipient iliac vessels (Figure 1, above). The proximal duodenum of the graft was closed, and the distal end was anastomosed end-to-side to the proximal recipient jejunum. Either then or a few days later, the recipient dog underwent total pancreaticoduodenectomy. Gastrointestinal reconstruction was performed with cholecystojejunostomy and gastrojejunostomy (Figure 1, right).All dogs were given intravenous fluids, penicillin, and gentamicin for 5 days postoperatively. The animals were allowed to drink water ad libitum after the second postoperative day and to eat solid food after the fifth postoperative day. Immunosuppression consisted of cyclosporine at an oral dose of 17 mg/kg per day beginning on the day after operation, and prednisone, 0.5 mg/kg per day. Fasting glucose concentrations in the venous plasma were measured daily during the first postoperative week and 3 times a week thereafter. Intravenous glucose tolerance tests were performed in two dogs who survived more than 60 days. The homografts were sampled at the time of sacrifice or at autopsy. TheRequests for reprints should be addressed to Thomas E. Starzl, MD,

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Section: Commentsmentioning

confidence: 99%

Total pancreaticoduodenal homotransplantation in dogs immunosuppressed with cyclosporine and steroids

Diliz-Pérez¹,

Hong²,

Santibañés³

et al. 1984

The American Journal of Surgery

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show abstract

“…Heterotophic pancreaticoduodenal transplantation can ameliorate diabetes in rats [25], but the operative mortality is high, particularly if combined with en bloc transplantation of other organs [26]. Nevertheless, the rat is a useful model because inbred strains can be used and the results of experiments can be interpreted with the immunological factors controlled.…”

Section: A Transplantation Of the Pancreas With Exocrine Drainage Esmentioning

confidence: 99%

“…In rats, duct ligated pancreatic isografts undergo acute inflammatory reactions followed by progressive fibrosis [25,41]. Orloff et al [25] could not detect any differences in the islet function of ligated and nonligated pancreatic grafts tested up to two years after transplantation, although Fairbrother et al [41] detected deterioration in function in the long term by glucose tolerance testing and serum insulin assay.…”

Section: B Transplantation Of the Pancreas Without Provision For Exomentioning

confidence: 99%

“…The factors responsible for the different results are difficult to sort out because of the variations in the models studied. However, several investigators have reported survival of recipients of autografts for months or years with normal blood glucose levels and without deterioration of graft function [9,23,25,28].…”

Section: Metabolic Efficiency Of Whole or Segmental Pancreatic Tramentioning

confidence: 99%

“…There are a few reports on the effect of islet transplantation on the nerve [25] and eye [288,293,294] lesions that develop in diabetic rats. Gray and Watkins [288] found that new vessel formation and retinal capillary dilation did not develop in rats transplanted within a month of induction of diabetes.…”

Section: Effect Of Pancreas and Islet Transplantation On Long Termentioning

confidence: 99%

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