MELD-based allocation of deceased donor livers allows exceptions for patients whose score may not reflect their true mortality risk. We hypothesized that OPOs may differ in exception practices, use of exceptions may be increasing over time, and exception patients may be advantaged relative to other patients. We analyzed longitudinal MELD score, exception, and outcome in 88,981 adult liver candidates as reported to UNOS from2002–2010.Proportion of patients receiving an HCC exception was 0–21.4% at the OPO-level and 11.9–18.8% at the region-level; proportion receiving an exception for other conditions was 0.0%–13.1% (OPO-level) and 3.7%–9.5%% (region-level).HCC exceptions rose over time (10.5% in 2002 vs. 15.5% in 2008, HR=1.09 per year, p<0.001) as did other exceptions (7.0% in 2002 vs. 13.5% in 2008, HR=1.11, p<0.001).In the most recent era of HCC point assignment (since April 2005), both HCC and other exceptions were associated with decreased risk of waitlist mortality compared to non-exception patients with equivalent listing priority (multinomial logistic regression OR=0.47 for HCC, OR=0.43 for other, p<0.001) and increased odds of transplant (OR=1.65 for HCC, OR=1.33 for other, p<0.001).Policy advantages patients with MELD exceptions;differing rates of exceptions by OPO may create, or reflect, geographic inequity.

Severe geographic disparities exist in liver transplantation; for patients with comparable disease severity, 90-day transplant rates range from 18%–86% and death rates range from 14%–82% across donor service areas (DSAs). Broader sharing has been proposed to resolve geographic inequity; however, we hypothesized that the efficacy of broader sharing depends on the geographic partitions used. To determine the potential impact of redistricting on geographic disparity in disease severity at transplantation, we combined existing DSAs into novel regions using mathematical redistricting optimization. Optimized maps and current maps were evaluated using the Liver Simulated Allocation Model. Primary analysis was based on 6700 deceased donors, 28,063 liver transplant candidates, and 242,727 Model of End-Stage Liver Disease (MELD) changes in 2010. Fully regional sharing within the current regional map would paradoxically worsen geographic disparity (variance in MELD at transplantation increases from 11.2 to 13.5, p=0.021), although it would decrease waitlist deaths (from 1368 to 1329, p=0.002). In contrast, regional sharing within an optimized map would significantly reduce geographic disparity (to 7.0, p=0.002) while achieving a larger decrease in waitlist deaths (to 1307, p=0.002). Redistricting optimization, but not broader sharing alone, would reduce geographic disparity in allocation of livers for transplant across the United States.

Islet isolation is a time-consuming process. Islet yields vary, and previous in vitro studies suggest that Ficoll may be an islet toxin. Here, we describe an alternative, Ficoll-free method to purify murine islets by filtration through a cell strainer. Collagenase digestion of pancreata was carried out using standard procedures. The pancreatic digest was divided into aliquots and purified either by Ficoll or by filtration. Following filtration, islets were intact and separated from nondigested tissue. Purity was similar to that achieved using Ficoll. However, purification by filtration was faster, increased islet yield, and resulted in higher insulin secretion in vitro. Moreover, when syngeneic diabetic hosts were transplanted with a marginal islet mass, islets purified by filtration restored normoglycemia significantly faster than those isolated by Ficoll. This suggests that Ficoll exposure negatively impacts islet function. In conclusion, islet filtration is a simple and rapid procedure for purification of islets that demonstrate improved functional mass.

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Posttransplantation biliary strictures occur in 5-34% of the pediatric liver transplant patients and are conventionally managed by interventional radiological techniques. The aim of this manuscript is to assess the outcomes of patients with biliary strictures treated by percutaneous dilatation at our institution. Included in the study were 35 children with posttransplant biliary strictures that were treated with percutaneous dilatation and stenting. Initial dilation and biliary stent placement was accomplished in all patients without complications requiring surgical intervention. Recurrent strictures developed in 23 (66%) of 35 patients. The recurrence rate was 45% for anastomotic strictures, 90% for intrahepatic strictures, and 100% for those with both an anastomotic and intrahepatic component. Seven patients required revision of the choledochojejunostomy, 5 of them with a successful outcome and 2 requiring retransplant. Five patients were treated with retransplantation without surgical revision. Patients with an intrahepatic or a "combined" stricture were less likely to have a successful outcome after radiologic treatment.In conclusion, the radiological treatment of biliary strictures with balloon dilation and stenting can be performed successfully with minimal complications avoiding the need for surgical correction in many cases. Liver Transpl 12: 821-826, 2006.

Recipients of a SPK transplants from DCD and DBD donors had equivalent patient and graft survival rates at 1, 3 and 5 years. For recipients of SPK transplants, the wait for organs from DCD donors was significantly shorter than that for organs from DBD donors. SPK recipients of organs from DCD donors had longer hospital stays than did recipients of organs from DBD donors. With renal allografts, the incidence of delayed graft function was almost four times higher with organs from DCD donors than with organs from DBD donors.Selective use of organs from DCD donors is safe for pancreas transplantation.

Knockout and blocking studies have shown a critical role for CTLA-4 in peripheral tolerance, however, it is unknown whether augmenting CTLA-4 expression actually promotes tolerance. Here we demonstrate a specific and requisite role for CTLA-4 and its up-regulation in tolerance through anti-CD45RB. First, long-term murine islet allograft survival induced by anti-CD45RB is prevented by CTLA4-Ig, which interferes with B7:CTLA-4 interactions. Second, anti-CD45RB is ineffective in recipients lacking CTLA-4, B7-1, and B7-2. In contrast, CTLA4-Ig, which targets B7 on allogeneic cells, promotes long-term engraftment in these mice. Moreover, anti-CD45RB was effective in B7-deficient controls expressing CTLA-4. Finally, in wild-type mice, CTLA-4 expression returned to baseline 17 days after receiving anti-CD45RB, and was refractory to further increase. Transplantation and anti-CD45RB therapy at this time could neither augment CTLA-4 nor prolong engraftment. These data demonstrate a specific role for CTLA-4 in anti-CD45RB-mediated tolerance and indicate that CTLA-4 up-regulation can directly promote allograft survival.

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