This study reports the comparative short-term results of pancreas transplantation from donors after circulatory death (DCD) (Maastricht III & IV), and pancreases from brainstem deceased donors (DBD). Between January 2006 and December 2010, 1009 pancreas transplants were performed in the United Kingdom, with 134 grafts from DCD and 875 from DBD. DCD grafts had no premortem pharmacological interventions performed. One-year pancreas and patient survival was similar between DCD and DBD, with pancreas graft survival significantly better in the DCD cohort if performed as an SPK. Early graft loss due to thrombosis (8% vs. 4%) was mainly responsible for early graft loss in the DCD cohort. These results from donors with broader acceptance criteria in age, body mass index, premortem interventions, etc. suggest that DCD pancreas grafts may have a larger application potential than previously recognized. This study reports the comparative short-term results of pancreas transplantation from donors after circulatory death (DCD) (Maastricht III & IV), and pancreases from brainstem deceased donors (DBD). Between January 2006 and December 2010, 1009 pancreas transplants were performed in the United Kingdom, with 134 grafts from DCD and 875 from DBD. DCD grafts had no premortem pharmacological interventions performed. One-year pancreas and patient survival was similar between DCD and DBD, with pancreas graft survival significantly better in the DCD cohort if performed as an SPK. Early graft loss due to thrombosis (8% vs. 4%) was mainly responsible for early graft loss in the DCD cohort. These results from donors with broader acceptance criteria in age, body mass index, premortem interventions, etc. suggest that DCD pancreas grafts may have a larger application potential than previously recognized.
Kosmoliaptsis, V.; Sharples, L.; Chaudhry, A. N.; Johnson, R. J.; Fuggle, S. V.; Dafforn, T. R.; Halsall, D. J.; Bradley, J. A.; Taylor, C. J. Author Information
HLA-DR3- and HLA-DRw52-associated functional polymorphism was investigated with selected tetanus toxoid (TT)-specific T cell clones. We have shown earlier that HLA-DR antigens are encoded by two distinct loci, DR beta I and DR beta III. The alloantigenic determinant(s) defined by the serological HLA-DR3 specificity map to the former, while the supratypic HLA-DRw52 determinants map to DR beta III. Furthermore, we have recently recognized by DNA sequencing three alleles of HLA-DRw52 at locus DR beta III, referred to as 52 a, b, and c. Our objective was to correlate the pattern of T cell restriction with the gene products of individual DR beta chain loci and with the three newly described alleles of locus DR beta III. Among the selected T cell clones, 5 reacted exclusively when TT was presented by HLA-DR3+ APCs (TT-DR3-APC). In contrast, two T cell clones were stimulated by TT-DRw52-APC. More specifically, these two T cell clones (Clones 10 and 16) were stimulated by different subsets of TT-DRw52-APC. Clone 16 responded to some DR3 and TT-DRw6-APC, while clone 10 was stimulated by other TT-DR3 and TT-DRw6, and all TT-DR5-APC. This same pattern of DRw52 restriction was found in panel, as well as in family studies. Because this suggested a correlation with the pattern of DRw52 polymorphism observed earlier by DNA sequencing and oligonucleotide hybridization, the APC used in these experiments were typed for the 52 a, b, and c alleles of locus DR beta III by allele-specific oligonucleotide probes. This distribution overlapped exactly with the stimulation pattern defined by the T cell clones. Clone 16 responded to TT-52a-APC, clone 10 to TT-52b-APC, and both clones to a TT-52c-APC. The response of the T cell clones was inhibited differentially by mAbs to DR. Raising TT concentration, or increasing HLA-class II expression with INF-gamma both affected the magnitude of response of the TT-specific clones but did not modify their specificities. These results demonstrate that a restriction specificity can be attributed to the DR beta III locus and illustrate the functional relevance of the polymorphism observed at this locus. This is of special interest in view of the striking difference in the pattern of structural diversity among alleles of DR beta I and DR beta III.
1Statistics And Clinical Audit, NHS Blood and Transplant (UK), Bristol/UNITED KINGDOM, 2NHS Blood and Transplant, Bristol/UNITED KINGDOM, 3Scientific Advisor, NHS Blood and Transplant (UK), Bristol/UNITED KINGDOM, 4Department Of Surgery, University of Cambridge, Cambridge/UNITED KINGDOM
P119 Aims: The shortage of organs for transplantation has lead to an expansion in the criteria for acceptance of donors for transplantation and to use of livers from non heart-beating donors (NHBDs). NHBD allografts have been shown to be affected less by the inflammatory events surrounding brain death in the donor. However little is known about the changes that occur in these organs following cold ischaemia and reperfusion. The aim of this study is to evaluate the inflammatory response in NHBD livers immediately following reperfusion and to compare the findings with conventional cadaver allografts. Methods: Tru-cut biopsies were obtained from controlled NHBD (CNHBD; n=13) and conventional cadaveric (n=13) liver transplants prior to, and 2 hours following reperfusion. Cryostat tissue sections were stained with antibodies against P-selectin, CD41 and neutrophil elastase. The percentage area of P-selectin, CD41 and neutrophil staining was quantitated by morphometric point counting and the results were correlated with clinical and post-transplant parameters. Results: CNHBD liver allografts showed minimal changes post-reperfusion compared to the cadaver allografts. Significantly increased levels of neutrophil infiltration (6/13, 46%) and CD41 (5/13, 38%) were detected in the cadaveric allografts after reperfusion. In contrast, none of the CNHB allografts showed changes in the levels of neutrophil infiltration following transplantation, and only one liver had a significant rise in CD41 deposition following reperfusion. Increased expression of P-selectin after reperfusion was only detected in one conventional cadaver liver, whereas none of the CNHBD livers showed changes in P-selectin expression. Post transplantation CNHBD liver allografts had significantly higher levels of aspartate aminotransferase (720 ± 598 vs. 362 ± 164; p>0.02). However, The rate of allograft rejection was significantly lower in CNHBD allografts (3/13, 23%) compared to the conventional cadaver group (7/13, 53%). Conclusions: In summary, CHNBD livers suffer from periods of warm ischemia during retrieval, resulting in elevation of aspartate aminotransferase following transplantation. However they appear to be more resistant to reperfusion injury as measured by platelet deposition and neutrophil infiltration. This may be attributable to pre-existing inflammatory changes in conventional cadaver donor livers, associated with brain death.
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