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Prolonged cold ischemia time (CIT) during graft preservation and warm ischemia time (WIT)during rewarming time have been reported to cause postoperative graft dysfunction afterorthotopic liver transplantation (OLT). However, the effects of both CIT and WIT in combination onpatient and graft survivals are not yet defined. The aim of this study was to determinewhether simultaneously prolonged CIT and WIT were associated with early graft outcomes afterclinical OLT. For analysis of liver graft survival within 90 days of OLT and postoperative graftfunction, 186 consecutive OLT cases weredivided into four groups as follows: group A, CIT < 12 hours and WIT < 45 minutes; group B, CIT > 12hours and WIT < 45 minutes; group C, CIT < 12 hours and WIT > 45 minutes; and group D, CIT > 12 hoursand WIT > 45 minutes.The graft loss rates were 5.4% in group A, 9.8% in group B, 11.1% ingroup C, and 42.9% in group D. The mean highest aspartate aminotransferase (AST) valueafter OLT in group D (3352.3 ± 569.4 U/L) was significantly greater than those in groups A(1411.7 ± 169.2 U/L) and B (1931.3 ± 362.6 U/L). The simultaneously prolonged cold andwarm ischemia times significantly caused hepatic allograft injury and failure, suggesting somecumulative effects of CIT and WIT on postoperative graft function. [Copyright &y& Elsevier]

Abstract: The inherent tolerogenicity of liver allografts may be due to tolerogenic dendritic cells (DC) therein. It is not clear whether the unique antigen-presenting function of liver DC is intrinsic or whether it is altered by microenvironmental factors in the liver. In the present study, we investigated the effect of hepatic stellate cells (HSC) on the development and function of DC propagated from bone marrow. DC exposed to HSC or HSC supernates expressed low CD11c, CD86, and major histocompatibility complex class II and elicited inferior allostimulatory function compared with conventional DC. These results suggested that soluble factor(s) secreted from HSC influence DC development. [Copyright &y& Elsevier]

Background The aim of this study was to assess the effect of low-dose adenosine on hepatic artery flow (HAF) when administered intraoperatively by continuous infusion. Materials and Methods Between January 2009 and August 2009, 74 patients underwent orthotopic liver transplantation (OLT). Ten patients were enrolled for adenosine treatment, and 64 non-study patients served as controls. After arterial reperfusion, a 16-G central venous catheter was placed in the gastroduodenal artery, and adenosine was continuously infused at doses ranging from 0.7 to 2.8 μg/kg/min for 30 min. HAF and portal vein flow were measured using a transit time flow meter before adenosine infusion, during infusion, and 10 min after infusion. Liver function tests were monitored routinely, duplex ultrasonography was performed on postoperative day 1, and the hepatic artery resistive index measured. The patients were followed for 1 year. Results Adenosine significantly increased HAF at doses from 0.7 to 2.8 μg/kg/min. The smallest increase in HAF was 24% above the baseline; in 80% of patients, the increase in HAF was >50% of the baseline values. In 2 patients, HAF was increased by >300%. The dosing started at 0.7 μg/kg/min, and 6 of 10 patients responded. Three patients required an increase to 1.4 μg/kg/min. Doses >2.8 μg/kg/min did not further increase HAF. One patient showed a minimal response regardless of the dose. There were no differences between the adenosine group and control group with respect to liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and International Normalized Ratio), platelet count on POD2, hepatic artery resistive index, and post-transplant length of stay, intensive care days, or 1-year patient survival rates. Conclusions This pilot study established that adenosine administered directly into the hepatic artery produces a similar effect on HAF in cadaveric liver transplant recipients to that found in the laboratory without producing systemic side effects. [ABSTRACT FROM AUTHOR]

Abstract: Between September 2002 and February 2004, 40 kidney transplant (27 from deceased and 13 from living donors) recipients (25 male and 15 female, aged 50.3 ± 15.1 years) were treated with Campath 1H (C 1H; 30 mg/dose IV) for biopsy-proven steroid-resistant rejection (SRR) or rejections equal to or worse than Banff 1B. All transplantations occurred between August 2001 and May 2003. All patients had received antibody preconditioning (RATG 5 mg/kg, n = 34; C 1H 60 mg, n = 4; C 1H 30 mg, n = 2) preoperatively and were treated with Tacrolimus monotherapy (target level 10 ng/ml) postoperatively and subsequent spaced weaning. Elevated creatinine levels at follow-up were evaluated by renal transplant biopsy. Rejection was treated with steroids, reversal of weaning, addition of sirolimus, and/or antibody treatment, depending on grade of rejection. The mean duration of follow-up was 453 ± 163 days after C 1H administration. Twenty-nine patients received C 1H for SRR and 11 patients for Banff 1B or worse rejections; 26 patients received more than 1 dose of C 1H. Graft survival was 62.5% (25 patients); 6 of the 15 allografts (40%) that failed had presented with rejections because of noncompliance. Graft survival in compliant patients with SRR or rejections equal to or worse than Banff 1B was 73.5% (25 of 34). Fourteen patients (35%) had infectious complications, of whom 2 patients (5%) died. C 1H is an effective agent for SRR and Banff 1B or worse rejections, with 95% patient survival and 73.5% graft survival (in compliant patients). The number of doses of 30 mg C 1H should be restricted to two, as there is a high incidence of potentially fatal infectious complications. [Copyright &y& Elsevier]

The influence of donor major histocompatibility complex (MHC) class I- or class II-deficiency on the initiation of first- and second-set rejection of mouse heart and liver allografts was examined. C3H (H-2k) mice received heterotopic cardiac or orthotopic liver grafts from unmodified B10 (H2b), B6 (H-2b), b2m (H-2b; class I deficient) or AB0 (H-2b; class II deficient) donors. Organ survival was also investigated in C3H recipients that had been presensitized by a normal B10 skin graft 2-3 weeks before heart or liver transplantation. The absence of cell surface MHC class I or class II resulted in significant prolongation of primary cardiac allograft survival. Three of seven (43%) MHC class I-deficient, and two of five (40%) class II-deficient heart grafts were accepted indefinitely (survival time > 100 days). Thus both MHC class I and class II molecules appear to be important for the elicitation of first-set rejection in the heart allograft model. All liver allografts survived > 100 days in normal recipients. In C3H recipients that had been presensitized by a B10 skin graft, however, both heart and liver grafts from AB0 (class II deficient) donors underwent accelerated rejection (median survival time [MST] 3 and 4 days, respectively). In contrast, liver grafts from class I-deficient mice (b2m) were still accepted indefinitely by B10 skin-presensitized C3H recipients, whereas class I-deficient hearts survived significantly longer than those from class II-deficient or normal donors. These data demonstrate that the expression of donor MHC class I, and not class II is crucial in initiating second-set organ allograft rejection. In vitro monitoring revealed that at the time of organ transplant, both splenocytes and serum of the skin-presensitized animals displayed high cytotoxicity against AB0 (class II-deficient) but not against b2m (class I-deficient) targets. [ABSTRACT FROM AUTHOR]

Administration of donor-derived immature dendritic cells (DC) treated with NF-κB oligodeoxyribonucleotides (ODN) prevents allograft rejection. We attempted to explore the use of recipient-derived DC pulsed with donor antigens, in which the donor antigens were presented to host T cells via an indirect pathway (cross-priming). Expression of CD40, CD80, and CD86 on DC was significantly inhibited by treatment with NF-κB ODN, whereas MHC class I and II were minimally affected. Normal C3H DC pulsed with B10 antigens stimulated proliferative responses and donor-specific CTL activity in C3H T cells, both of which were, however, markedly inhibited when DC were treated with NF-κB ODN. This manipulation was associated with reduced IFN-γ and increased IL-10 production in the supernate, suggesting a Th2 bias. More frequent apoptotic T cells were observed in cultures with NF-κB ODN DC. In contrast to administration of normal DC pulsed with donor antigens that accelerated rejection of B10 cardiac allografts (median survival time [MST] 7 days versus 10 days in no-DC treatment control, P < .05), a single injection of 2 × 106 NF-κB ODN DC significantly prolonged allograft survival (MST 50 days, P < .05 compared with no-DC treatment control). The anti-donor CTL activity in infiltrating T cells isolated from cardiac grafts in recipients that received NF-κB ODN DC was significantly suppressed. These data indicate that vaccination with immature DC, propagated from recipient BM is an attractive approach to induce T-cell hyporesponsiveness. [Copyright &y& Elsevier]

Abstract: Administration of donor-derived immature dendritic cells (DC) treated with transforming growth factor-beta (TGF-β) to prevent allograft rejection is not applicable for clinical use. We therefore attempted to explore the use of recipient-derived DC pulsed with donor antigens via the indirect pathway (cross-priming). DC were propagated from C3H (H2k) bone marrow (BM) using granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). TGF-β (0.2 ng/mL) was added at the initiation of culture. The resultant TGF-β DC were pulsed with B10 (H2b) splenocyte lysate. Expression of major histocompatibility complex (MHC) class I and II was not affected, while CD40, CD80, and CD86 costimulatory molecules on DC were significantly inhibited by treatment with TGF-β. C3H DC pulsed with B10 antigens stimulated a proliferative response in C3H T cells which was inhibited when DC were treated with TGF-β, and the cytotoxic T-lymphocyte (CTL) activity was also inhibited. This observation correlated with reduced interferon-gamma (IFN-γ) and increased IL-10 production. A single injection of TGF-β DC prolonged allograft survival (median survival time [MST] 18 days vs 10 days in no-DC treatment control; P < .05). These data indicated that an approach utilizing recipient DC as a “vaccine” strategy is possible. [Copyright &y& Elsevier]

Abstract: Percutaneous ultrasound-guided pancreas allograft biopsy is the preferred technique for evaluating pancreas allograft rejection. Experience from large centers has shown it to be safe and effective. We report our experience with 120 percutaneous allograft biopsies performed at a single center. Biopsy tissue was obtained in 54 patients. Thirty-three patients received simultaneous pancreas and kidney transplants, 14 received isolated pancreas transplants, and 7 received a pancreas transplant after kidney transplantation. Biopsies were performed by pancreas transplantation surgeons with the assistance of radiologists under ultrasound guidance using an Acuson XP 128/10 ultrasound machine. One hundred twenty allograft biopsies were performed in 54 patients. Twenty-seven (50%) patients underwent multiple biopsies. In 102 (85%) biopsies the specimens were adequate for examination. Eighteen (15%) biopsy samples had no pancreatic tissue and showed surrounding fat and small bowel. 1 (1.8%) patient bleeding developed that required transfusion of 3 units of packed red blood cells, but no surgical intervention was necessary. One (1.8%) patient had a pancreatic fistula, which healed with nonoperative management. Biochemical evidence of pancreatitis was noted in 5 (9.2%) patients, but none of these patients had clinical signs of pancreatitis. Percutaneous ultrasound-guided pancreas allograft biopsy is a safe procedure with a low complication rate and a high tissue yield for histopathologic examination. [Copyright &y& Elsevier]