Increasing shortage of cadaveric grafts demands the utilization of living donor and split liver grafts. The purpose of this study was to 1) define the "small-for-size" graft in a pig liver transplant model 2) evaluate pathological changes associated with small-for-size liver transplantation. Pigs were divided into four groups based on the volume of transplanted liver: (a) control group (n‫,)4؍‬ 100% liver volume (LV) (b) group I (n‫,)8؍‬ 60% LV (c) group II (n‫,)8؍‬ 30% LV (d) group III (n‫,)51؍‬ 20% LV. Tacrolimus and methyl prednisone were administered as immunosuppression. Animals were followed for 5 days with daily serum biochemistry, liver biopsies on day 3 and 5 for light microscopy, and tissue levels of thymidine kinase (TK) and ornithine decarboxylase (ODC). Liver grafts were weighed pretransplant and at sacrifice. All the recipients of 100%, 60%, and 30% grafts survived. Transplantation of 20% grafts (group III) resulted in a 47% mortality rate. Group III animals showed significantly prolonged prothrombin times (p<0.05), elevated bilirubin levels (p<0.05), and ascites. The rate of regeneration, as indicated by TK activity and graft weight was inversely proportional to the size of the transplanted graft. The severity of the microvascular injury was inversely proportional to graft size and appeared to be the survival-limiting injury. Frank rupture of the sinusoidal lining, parenchymal hemorrhage, and portal vein injury were prominent in group III animals 1 hour following reperfusion. This study established a reproducible large animal model of partial liver grafting; it defined the small-for-size syndrome in this model and described the associated microvascular injury. (Liver Transpl 2004;10:253-263.) R ecent technical innovations in the field of liver transplantation have been driven by the critical shortage of cadaveric organs. [1][2][3] It is hoped that the increasing number of adult living donor liver transplants (LDLT) and split liver transplants being performed annually will significantly reduce the number of deaths on the liver transplant waiting list. However, split liver transplantation for adults is hindered by the logistics of dividing a perfect donor liver to provide grafts of sufficient size for two small adult recipients of the same blood group. The split technique has the additional problem of prolonged cold ischemia times unless the liver is split in-situ. Currently LDLT is the technique with the greatest potential to address the organ shortage crisis but its widespread application is limited by the volume of liver that can be safely resected from a living donor, while at the same time providing a graft of sufficient size for the recipient. The size of graft required for successful liver transplantation is 30 -40% of the expected liver volume for the recipient or 0.8 -1.0% of the body weight. 4 For most adult recipients of an LDLT graft, this will require a right lobe graft from another adult. Given the smaller volume of the left lobe graft it is most suitable for small adults or larger ped...

Donor hypernatremia was reported to cause postoperative graft dysfunction in human orthotopic liver transplantation (OLT). However, the effects of the correction of donor hypernatremia before organ procurement have not been confirmed. The aim of this study is to determine whether donor hypernatremia is associated with early graft dysfunction after OLT and to determine the effect of the correction of donor hypernatremia. One hundred eighty-one consecutive OLTs performed between May 1997 and July 1998 were entered onto this study. The cases were divided into three groups according to the donor serum sodium concentration: group A, serum sodium of 155 mEq/L or less before organ procurement (n ‫؍‬ 118); group B, peak sodium greater than 155 mEq/L and final sodium 155 mEq/L or less (n ‫؍‬ 36); and group C, final sodium greater than 155 mEq/L (n ‫؍‬ 27). Graft survival within 90 days after OLT and early postoperative graft function were analyzed. There were no significant differences in donor and recipient variables among the three groups. The frequencies of graft loss were 15 of 118 grafts (12.7%) in group A, 4 of 36 grafts (11.1%) in group B, and 9 of 27 grafts (33.3%; P F .05 v groups A and B) in group C. The liver enzyme values in groups B and C were significantly greater than those in group A postoperatively. The prothrombin times of group C were significantly longer than those of group A for the first 4 postoperative days. Recipients of hepatic allografts from donors with uncorrected hypernatremia had a significantly greater incidence of graft loss compared with recipients of hepatic allografts from normonatremic donors. However, the differences in graft survival were abrogated by the correction of donor hypernatremia before procurement. Copyright 1999 by the American Association for the Study of Liver DiseasesS everal retrospective analyses of donor and recipient variables have attempted to identify risk factors predictive of both patient and graft survival after orthotopic liver transplantation (OLT). To date, the following donor-associated risk factors have been shown to adversely affect patient or graft survival: donor age, 1,2 sex, 3,4 liver function test results, 5 cytotoxic cross-match, 6 length of intensive care unit (ICU) stay, 1 use of vasopressors, 7 and preservation time. 2,8,9 Previously, all these risk factors were considered static and not subject to manipulation by the procurement team, primarily because of time constraints. However, recent legislation requiring earlier notification of potential organ donors and earlier turnaround time for serum chemistries have provided additional time to manage brain-dead donors before organ procurement and correct such abnormalities as hypernatremia that may adversely impact on both graft and recipient survival.Uncorrected hypernatremia in organ donors has been associated with poor graft or patient survival in at least four studies. 7,9-11 These retrospective analyses suggested donor hypernatremia resulted in a greater incidence of early postoperative graft dys...

The Snail transcription factor plays as a master regulator of epithelial mesenchymal transition (EMT), one of the steps of tumor metastasis. Snail enhances expressions of a lot of mesenchymal genes including the matrix degradation enzyme matrix metalloproteinases 9 (MMP9) and the EMT transcription factor zinc finger E-box binding homeobox 1 (ZEB1), however, the underlying mechanisms are not clarified. Herein, we investigated how Snail upregulated transcription of ZEB1 and MMP9 induced by the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate (TPA) in hepatoma cell HepG2. According to deletion mapping and site directed mutagenesis analysis, the TPA-responsive elements on both MMP9 and ZEB1 promoters locate on a putative EGR1 and SP1 overlapping region coupled with an upstream proposed Snail binding motif TCACA. Consistently, chromatin immunoprecipitation (ChIP) assay showed TPA triggered binding of Snail, EGR1 and SP1 on MMP9 and ZEB1 promoters. Double ChIP further indicated TPA induced association of Snail with EGR1 and SP1 on both promoters. Also, electrophoresis mobility shift assay revealed TPA enhanced binding of Snail with a MMP9 promoter fragment. According to shRNA techniques, Snail was essential for gene expression of both ZEB1 and MMP9. In conclusion, Snail transactivates genes involved in tumor progression via direct binding to a specific promoter region.

Wnt/β-catenin signaling pathway is thought to be implicated in the development of arterial stiffness and vascular calcification. As a Wnt signaling pathway inhibitor, it is interesting to investigate whether sclerostin or dickkopf-1 (DKK1) level is correlated with arterial stiffness in renal transplant (RT) recipients. Fasting blood samples were obtained for biochemical data, sclerostin, DKK1, and osteoprotegerin (OPG) determinations. In this study, we applied automatic pulse wave analyzer (VaSera VS-1000) to measure brachial-ankle pulse wave velocity and either sides of brachial-ankle pulse wave velocity value, which greater than 14.0 m/s was determined as high arterial stiffness. Among 68 RT recipients, 30 patients (44.1%) were in the high arterial stiffness group. Compared with patients in the low arterial stiffness group, patients in the high arterial stiffness group had higher prevalence of hypertension (P = 0.002), diabetes (P < 0.001), metabolic syndrome (P = 0.025), longer posttransplant duration (P = 0.005), higher systolic blood pressure (P < 0.001) and diastolic blood pressure (P = 0.018), and higher fasting glucose (P = 0.004), total cholesterol (P = 0.042), blood urea nitrogen (P = 0.020), phosphorus (P = 0.042), and sclerostin levels (P = 0.001). According to our multivariable forward stepwise linear regression analysis, age (β = 0.272, P = 0.014), phosphorus (β = 0.308, P = 0.007), and logarithmically-transformed OPG (log-OPG; β = 0.222, P = 0.046) were positively associated with sclerostin levels, and multivariate logistic regression analysis, sclerostin (odds ratio 1.052, 95% confidence interval 1.007–1.099, P = 0.024), and posttransplant duration (odds ratio 1.024, 95% confidence interval 1.004–1.045, P = 0.019) were the independent predictors of peripheral arterial stiffness in RT recipients. In this study, serum sclerostin level, but not DKK1, was proved to be involved in the pathogenetic process of peripheral arterial stiffness in RT recipients.