Globally, a large proportion of donor livers are discarded due to concerns over inadequate organ quality. Normothermic machine perfusion (NMP) allows for hepatocellular and biliary viability assessment prior to transplantation and might therefore enable the safe use of these orphan donor livers. We describe here the first Australasian experience of NMP-preserved liver transplants using a 'backto-base' approach, where NMP was commenced at the recipient hospital following initial static cold storage. In the preclinical phase, 10 human donor livers declined for transplantation (7 from donation after circulatory death [DCD] and 3 from donation after brain death [DBD]) were perfused using a custom-made NMP setup. Subsequently, 10 orphan donor livers (5 from DCD and 5 from DBD) underwent NMP and viability assessment on the OrganOx metra device (OrganOx Limited, Oxford, United Kingdom). Both hepatocellular and biliary viability criteria were used. The median donor risk index was 1.53 (1.16-1.71), and the median recipient Model for End-Stage Liver Disease score was 17 (11-21). In the preclinical phase, 'back-to-base' NMP was deemed suitable and feasible. In the clinical phase, each graft met predefined criteria for implantation during NMP and was subsequently transplanted. Five (50%) recipients developed early allograft dysfunction based on peak aspartate aminotransferase. To date, all grafts function satisfactorily, and none of the 5 recipients who received a DCD liver have developed cholangiopathy. The OrganOx metra using a backto-base approach has enabled the safe use of 10 high-risk orphan donor livers with 100% 6-month patient and graft survival. NMP improved surgeon confidence to use orphan donor livers and has enabled a safe expansion of the donor pool.
The outcomes of right lobe split (RLS) liver transplantation are variable in adult recipients. This report is an analysis of outcomes of our initial 5-year experience with the right lobe trisegment split graft. A retrospective analysis was performed of the recipient and graft outcomes from July 2002 to March 2007 of all adult recipients of RLS grafts versus recipients of whole grafts (WGs). All data were analyzed with Stata version 8 (Stata Corp., Texas). There were 43 (19.1%) RLS recipients and 182 (80.9%) WG recipients. The median Model for End-Stage Liver Disease score was 13 (7-23) in the RLS group and 18 (6-50) in the WG group (P Ͻ 0.001). Hepatocellular carcinoma and primary sclerosing cholangitis were more common in the RLS group (P Ͻ 0.05), whereas alcoholic cirrhosis and chronic hepatitis C were more common in the WG group. The median donor age was lower in the RLS group at 39 (13-61) years versus the WG group at 47 (12-79) years (P Ͻ 0.001). Primary nonfunction occurred in 1.6% of the WG patients only. Biliary complications occurred in 28% of the RLS patients versus 28% of the WG patients. Vascular complications occurred in 18% of the RLS patients versus 14% of the WG patients. The retransplantation rate was similar at 2.3% in the RLS group versus 4.9% in the WG group (P ϭ not significant). Overall 3-year recipient survival was 92.7% in the RLS group versus 82.7% in the WG group (P ϭ 0.284). Graft survival was 88.4% in the RLS group at 3 years versus 78.5% in the WG group (P ϭ 0.304). In conclusion, good outcomes can be achieved with RLS liver transplantation in adult recipients without a detrimental effect on recipient or graft survival. Liver Transpl 15:1586Transpl 15: -1593Transpl 15: , 2009
Encapsulation of hepatocellular carcinoma reflects reduced invasiveness, rather than increased peritumoral collagen synthesis, which may instead enhance invasion. Increased intratumoral collagen I protein is also associated with increased tumor invasiveness. Pre-existing cirrhosis has little effect on tumor progression, possibly because the characteristics of cirrhosis are overwhelmed by tumor-induced changes in the adjacent parenchyma.
Carboplatin, a second-generation platinum-based antineoplastic drug, preferentially destroys inner hair cells (IHCs) in the chinchilla while sparing outer hair cells (OHCs). D-Methionine (D-Met), a sulfur-containing amino acid, has been shown to protect hair cells from cisplatin damage in rats, but its ability to protect IHCs from carboplatin damage has not yet been evaluated in the chinchilla. We tested whether D-Met would protect the hair cells in the chinchilla from carboplatin. Animals were divided into two groups: a control group that only received carboplatin (100 mg/kg, i.p.) and an experimental group that received 300 mg/kg D-Met (i.p.) 30 min before carboplatin treatment. Ototoxicity was assessed by measuring the amount of IHC and OHC loss. Average IHC loss in the group treated with D-Met was 62% compared with 84% in the untreated control group. Thus, D-Met causes a statistically significant reduction in IHC loss induced by carboplatin.
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