The purpose of the present study was to evaluate the significance of immunogenetic factors on the survival of pancreatic allografts in beagle dogs. Donors and recipients were leukocyte antigen (DLA)-typed and mixed lymphocyte culture (MLC)-tested. Recipients were made diabetic by total pancreatectomy and immediately implanted intraperitoneally with a vascularized, free-draining (duct unligated) pancreatic segmental (FDPS) allograft. Two groups of dogs were studied. In group I consisting of donor-recipient littermates, recipients were immunosuppressed with prednisone and azathioprine (n = 16 dogs), or not immunosuppressed (n = 4). In group II, recipients were made specifically unresponsive by total body radiation, autologous marrow implantation, and kidney transplantation from DLA-MLC identical donors, 1 yr before FDPS transplantation from the corresponding original kidney donors. Survival of the FDPS grafts in group I was inversely related to pretransplant MLC reactivity, irrespective of DLA genotyped match between donor and recipient. Thus, immunosuppressed high MLC reactors (n = 8) rejected FDPS grafts between 7 and 14 d, whereas immunosuppressed low MLC reactors (n = 8) accepted grafts for 25 to 260+ days, and nonimmunosuppressed low MLC reactors (n = 4) accepted grafts for 9-55 d. Rejection (hyperglycemia) of FDPS grafts was sudden, permanent, and unpredictable despite weekly intravenous glucose tolerance tests with measurements of glucose disappearance rates and serum insulin responses. Nevertheless, serial in vitro cell-mediated lymphocytotoxicity (CML) assays revealed increases in CML before graft rejection in low MLC reactors, and decreases in both CML and MLC responses before graft rejection in high MLC reactors. FDPS graft survival was indefinite (>6 mo) in group II dogs, despite low-grade MLC reactivity (2:4 dogs) and CML responses (4:4 dogs). Biopsies of FDPS grafts at 6 mo in normoglycemic dogs showed disappearance of exocrine tissue and coalescence of islets in both groups I and II, but with less fibrosis in group I (immunosuppressed). These results indicate that (a) pancreatic islets in vascularized grafts (FDPS) may survive indefinitely in the presence of a good tissue match best predicted by MLC testing, (b) tissue specific histocompatibility factors appear to be common enough between kidney and pancreas to allow for long-term survival of both organs transplanted from the same donor, at least in appropriate recipients (group II), and (c) immunosuppression is associated with less fibrosis in FDPS allografts.

/pdf/long-term-study-of-vascularized-free-draining-5f0ne9w9hp.pdf

Long-Term Study of Vascularized Free-Draining Intraperitoneal Pancreatic Segmental Allografts in Beagle Dogs

textThe relevance of pancreas transplantation is discussed in the Introduction to
this thesis. Chapter I gives the historical background, the specific problems in
relation to previous research, the surgical techniques applied, and a review of
the clinical pancreas transplantation performed so far. The conflicting results
published by various investigators concern the long-term quality of the endocrine
function of the organ when the exocrine function is abolished by ligation
of the pancreatic ducts. As a result, in extensive series of experimental pancreas
transplantations and a number performed in patients the endocrine function
was maintained intact, which can only be achieved by including the duodenum,
applying the Roux technique for anatomosis with the pancreas, or establishing
an anastomosis between the pancreatic duct and the ureter. The disadvantages
of these methods are discussed and the advantages of transplanting the pancreas
with ligated ducts are indicated. The latter method requires only a vascular
anastomosis and is in fact even less complicated than a kidney transplantation.
On the basis of these considerations we thought it worthwhile to investigate
the effects of transplantation of the pancreas with ligated ducts. This study was
performed in dogs, and the effect of tissue typing for SO determinants of the
DL-A complex on allograft survival was included in the investigation.

https://repub.eur.nl/pub/31362/750625_Gruyl, Johannes de.pdf

Pier L. Castelfranchi

Papers

Pancreas allotransplantation without duodenum