Early pancreas transplant outcomes with histidine-tryptophan-ketoglutarate preservation: a multicenter study.
ABSTRACT Little is known about the use of histidine-tryptophan-ketoglutarate (HTK) preservation solution for pancreas preservation. We compared early pancreas graft outcomes at four pancreas transplant programs within the state of Michigan in 2002 and 2003 (University of Wisconsin [UW] era) with those in 2004 (HTK era). The primary endpoint was early graft loss. The UW group (n=41) and the HTK group (n=36) had similar outcomes with respect to: technical graft loss (9.8% vs. 8.3%, P=NS), 90-day graft function (90.2% vs. 86.1%, P=NS), and rate of pancreatic leak/abscess (12.2% vs. 11.1%, P=NS). There were also no significant differences in postoperative amylase and lipase levels between the two groups. The HTK group did have significantly more acute rejection within the first 180 days (25.0% vs. 9.8%, P<0.05). HTK is a suitable substitute for UW in the preservation of pancreas allografts.
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ABSTRACT: We previously reported a small-scale study on the efficacy of Histidine-Tryptophan-Ketoglutarate solution (HTK) versus University of Wisconsin solution (UW) on pancreas preservation for islet isolation. In this large-scale, retrospective analysis (n = 252), we extend our initial description of the impact of HTK on islet isolation outcomes and include pancreatic digestion efficacy, purification outcomes, and islet size distribution. Multi-variable linear regression analysis, adjusted for donor age, sex, BMI, cold ischemia time, and enzyme, demonstrated similar results for the HTK group (n = 95) and the UW group (n = 157), including post-purification islet yields (HTK: 289,702 IEq vs. UW: 283,036 IEq; p = 0.76), percentage of digested pancreatic tissue (HTK: 66.9% vs. UW: 64.1%; p = 0.18), and islet loss from post-digestion to post-purification (HTK: 24,972 IEq vs. UW: 39,551 IEq; p = 0.38). Changes in islet size between the post-digestion and post-purification stages were comparable within each islet size category for HTK and UW (p = 0.14 - 0.99). Tissue volume distribution across purification fractions and islet purity in the top fractions were similar between the groups; however, the HTK group had significantly higher islet purity in the middle fractions (p = 0.003 - 0.008). Islet viability and stimulation indices were also similar between the HTK and the UW groups. In addition, we analyzed a small sample of patients transplanted either with HTK (n = 7) or UW (n = 8) preserved islets and found no significant differences in post-transplant HbA(1c), beta-score, and frequency of insulin independence.This study demonstrates that HTK and UW solutions offer comparable pancreas preservation for islet transplantation. More in vivo islet outcome data are needed for a complete analysis of the effects of HTK on islet transplantation.Cell Transplantation 10/2012; · 4.42 Impact Factor
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ABSTRACT: PURPOSE OF REVIEW: Systematic and detailed analysis of risk factors, pathophysiology, clinical manifestation, diagnosis and management of graft pancreatitis in its different forms, that is acute and chronic graft pancreatitis (A-GP and C-GP), and A-GP being further distinguished into: physiological (P-AGP), early (E-AGP) and late AP (L-AGP). RECENT FINDINGS: Graft pancreatitis is the second most-frequent complication following pancreas transplantation. P-AGP is an unavoidable entity related to ischemic reperfusion injury. It is usually clinically silent. It is a timely and prognostically self-limited process. E-AGP occurs within 3 months after pancreas transplantation (PTx) in 35% of cases and is associated with high rates of graft loss (78-91%). Clinical signs are pain, systemic inflammatory response (SIRS) and haematuria. Therapy can be medical, interventional and surgical. L-AGP occurs 3 months following PTx in 14-25% of cases and represents an uncommon cause of graft loss. Typical clinical signs are pain, abdominal tenderness and fever. Typical laboratory signs are hyperamylasaemia, hyperglycaemia and hypercreatininaemia. Therapy is usually conservative. C-GP is difficult to be distinguished from chronic rejection and is associated to graft loss in 4-10% of cases. Recurrent A-GPs and infections are the main risk factors. Specific symptoms are chronic abdominal malaise, constipation and recurrence of DM. Isolated hyperglycaemia is typical of C-GP. The therapy is usually conservative. SUMMARY: This systematic analysis of different manifestations of graft pancreatitis provides the basis for a clinical approach to tackling this complex entity.Current opinion in organ transplantation 12/2012; · 3.27 Impact Factor
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ABSTRACT: One of the main factors limiting potential uptake of pancreas transplantation, particularly in the United Kingdom, is the shortage of grafts. There has therefore been a recent expansion, particularly in the United Kingdom, in the utilization of grafts from donation after cardiac death (DCD) donors. These grafts are subjected to a greater ischemic insult and are arguably at higher risk of poor functional outcome. Although conventional preservation techniques may be adequate for donation after brain death (DBD) and low-risk DCD pancreases, as the number of DCD pancreas transplants increase and the threshold for rejecting organs decreases, the importance of optimal preservation techniques is going to increase. Over recent years, there have been significant advances in preservation techniques for DCD kidneys, improving the outcome of these marginal grafts. However, the use of such techniques for pancreas preservation is extremely limited and mainly historical. This overview describes the background and results of the established method of pancreas preservation for DBD, namely, cold static storage, and describes the use of the two-layer method. It also reviews pulsatile machine perfusion and normothermic perfusion for pancreas preservation techniques, which have shown promise in the preservation of DCD kidney grafts. The use of these techniques in pancreas preservation is predominantly historical but warrants reevaluation as to the feasibility of applying these techniques to DCD pancreas grafts not only for preservation but also for viability assessment. Further areas for development of pancreas preservation are discussed.Transplantation 02/2013; · 3.78 Impact Factor