Procurement and workbench procedures in preparation of pancreatic allografts. Factors essential for a successful pancreas transplant.

The rapidly developing field of pancreas allotransplantation can be regarded as an excellent school of surgery in which the topics of meticulous surgical technique and attention to detail by virtue of their significance strongly outweigh all other topics. The growing experience of the rather grave complications after pancreas transplantation points to the need for consistent use of meticulous techniques during organ procurement and application of workbench procedures just prior to transplantation. In addition, with the further development of the extra-renal transplant programs, the procurement of multiple organs from the same donor is becoming more common and the pancreatic team is more frequently faced with a less than optimal situation in regard to the vascular supply of the pancreatic graft. It, therefore, becomes imperative to carefully evaluate the vasculature and to make the necessary modifications prior to transplantation, since the best surgical techniques will not outweigh the consequences of a suboptimal blood supply, which will compromise the viability of any segment of the delicate pancreaticoduodenal graft.

Islet cell transplantation: important factors contributing to optimal pancreatic function.

This study investigates four factors which are of utmost importance in contributing to optimal function of pancreatic tissue fragment allotransplants. Those being: viability of donor tissue, optimal weight of pancreatic tissue fragments, method of allograft preparation, and site of implantation. Seven groups of unrelated mongrel dogs underwent total pancreatectomy before being randomly assigned to one of the following experimental groups. Group I (n = 10) animals were transplanted with greater than 0.75 g/kg of viable, pancreatic tissue fragments, whereas those in Group II (n = 6) received less than 0.75 g/kg of nonviable pancreatic pieces. In both groups, the donor pancreases were processed without collagenase, before being injected into the renal subcapsular space. Mean survival among Group I animals was 43 +/- 17 days (M +/- SD), while dogs in Group II survived a mean of 2.6 +/- 0.9 days (M +/- SD). Dogs in Group III (n = 5) were injected in the supracapsular peritoneum with greater than 0.75 g/kg of viable, collagenase-free pancreatic tissue fragments, and mean survival was noted to be 3.1 +/- 1.2 days (M +/- SD). Recipients in Group IV (n = 5) received greater than 0.75 g/kg of nonviable pancreatic tissue pieces prepared without collagenase in the renal subcapsular space, resulting in a mean survival of 2.8 +/- 0.9 days (M +/- SD). Group V (n = 6) animals survived a mean of 20 +/- 18 days (M +/- SD) when transplanted with greater than 0.75 g/kg of viable pancreatic tissue fragments prepared with collagenase, in the renal subcapsular space.(ABSTRACT TRUNCATED AT 250 WORDS)

Perinephric and subhepatic abscesses associated with renal subcapsular islet cell transplantation

Este manuscrito describe las complicaciones asociadas en uno de los casos de nuestra serie con transplante de islotes. Un paciente con diabetes insulino-dependiente recibió un transplante de islotes adentro de la cápsula renal. Después del transplante, abscesos perirenal y subhepático complicaron el cuadro clínico que requirieron drenaje y tratamiento con antibióticos. Después de seis semanas, las complicaciones se resolvieron y el paciente fue dado de alta. Después de varios meses, los requerimientos de insulina han descendido por 50%. En el futuro, el uso de técnicas estériles estrictas durante la preparación de los islotes y durante el transplante, posiblemente prevenga estas complicaciones en pacientes que reciban islotes del pancreas

Renal subcapsular islet cell transplantation.

This study was directed towards improving islet cell allotransplantation (ICTx) by testing the renal subcapsular region (RSC) as an alternative site for graft placement. In addition, a simplified, non-collagenase method was assessed for preparation of the allograft from the donor pancreas. Five groups of pancreatectomized mongrel dogs were followed. Group I (n = 10) were not transplanted and survived 5.0 +/- 2.92 days (M +/- SD). Five of six animals in Group II (n = 6) which received an ICTx prepared without collagenase in the RSC survived until allograft removal by nephrectomy at greater than 90 days (P less than .0005). No immunosuppression was given to this group. Recipients in Group III (n = 11) were transplanted as in Group II, but were given minimal immunosuppression with azathioprine. They also demonstrated excellent graft function until removal of the graft by nephrectomy at between 3 weeks and greater than 90 days. Animals in Group IV (n = 6) received an intrasplenic (IS) ICTx prepared without collagenase and survived only 4.16 +/- 1.16 days. In Group V (n = 6) poor survival was also noted (7.66 +/- 4.58 days) after IS-ICTx of a collagenase prepared allograft. All animals in Group IV and V received minimal immunosuppression as in Group III. These results indicate the potential for utilization of the RSC as an alternative site for ICTx. In addition, the collagenase-free method was satisfactory for ICTx preparation.

Renal subcapsular islet cell transplantation.

Islet cell transplantation has been associated with ultimate graft rejection. This preliminary study investigates the use of the renal subcapsular region as a site for placement of canine islet cell allografts. A new noncollagenase mechanical technique was used for preparation of the allografts. Animals in group I (N = 6) died of hyperglycemia in 4.0 +/- 1.89 days (X +/- SD) after pancreatectomy without subsequent islet cell transplant. Normoglycemia and excellent survival (greater than 60 days) was obtained in pancreatectomized animals in group II (N = 6) and in group III (N = 6), who received an islet cell allograft to the renal subcapsular site. Group II recipients were given no immunosuppression, and animals in group III received minimal immunosuppression with azathioprine. Dependence on the islet cell allograft for maintenance of normoglycemia was confirmed in the majority of the recipients by nephrectomy, to remove the graft, with resulting hyperglycemia and death. One normoglycemic animal in group II died on day 6 from peritonitis. One recipient in group II was normoglycemic at greater than 1 mo after removal of the first graft by nephrectomy, followed by retransplantation of islet cells from a third-party donor. Two other recipients are being studied on a long-term basis, and have been normoglycemic for greater than 6 mo and greater than 4 mo after transplantation. These studies encourage further investigation in this area for application of islet cell transplantation in man, and elucidation of the possible mechanisms for prolongation of islet cell allograft survival at the renal subcapsular site.

Orthotopic liver transplantation. Various immunosuppressive regimens to improve survival.

New approaches to immunosuppression, including cyclosporin A (Cy A), are being utilized to improve liver transplantation survival results. Donor livers from unrelated dogs were orthotopically transplanted to recipient animals, and only recipients that survived 2 or more days were included in this study. Animals were divided into the following groups: Group 1 (n = 6) received minimal immunosuppression (azathioprine) after orthotopic liver transplantation, Group 2 (n = 7) liver allografts were pretreated with Cy A (50 mg/L) prior to transplantation, and recipients were given minimal immunosuppression as in Group 1, Group 3 (n = 6) animals received azathioprine and methylprednisolone after transplantation, and Group 4 (n = 6) liver allograft recipients were given Cy A and methylprednisolone for 30 days followed by azathioprine. The improved survival seen in Groups 2, 3, and 4 in comparison with Group 1 (minimally immunosuppressed controls) indicates that graft pretreatment with Cy A or prophylactic Cy A administration (30 days), in conjunction with minimal immunosuppression, can prolong canine liver allograft survival as well as more standard regimens (Group 3). Therefore, it is possible that the use of steroids could be reduced or eliminated in hepatic transplantation with the application Cy A.

Immunosuppression with cyclosporine. A new approach to improve patency of venous allografts.

In cases in which an autogenous vein is not available, the venous allograft still represents an interesting alternative; however, early occlusion of the allograft is the rule. Forty-five mongrel dogs received jugular allografts transplanted into the carotid artery. Group 1 (n = 6) received no immunosuppression; group 2 (n = 5) received systemic azathioprine (2.5 mg/kg/day). In group 3 (n = 10) the grafts were pretreated with cyclosporine at 4 degrees C, and in group 4 (n = 9) the grafts were cryopreserved in a solution of 15% dimethyl sulfoxide and cyclosporine (50 mg/L) at -196 degrees C prior to implantation. Groups 3 and 4 received azathioprine as in group 2. Group 5 received cyclosporine systemically (15 to 20 mg/kg/day). Patency rates at one month (groups 1 and 2, 0%; group 3, 57.1%; groups 4 and 5, 100%) indicate that cyclosporine improves venous allograft survival both when used systemically and as a graft pretreatment modality.