The Impact of Ischemia/Reperfusion Injury on Liver Allografts from Deceased after Cardiac Death versus Deceased after Brain Death Donors

BACKGROUND AND AIMS:The shortage of organs for transplantation has led to increased use of organs procured from donors after cardiac death (DCD). The effects of cardiac death on the liver remain poorly understood, however. Using livers obtained from DCD versus donors after brain death (DBD), we aimed to understand how ischemia/reperfusion (I/R) injury alters expression of pro-inflammatory markers ceramides and influences graft leukocyte infiltration. METHODS:Hepatocyte inflammation, as assessed by ceramide expression, was evaluated in DCD (n = 13) and DBD (n = 10) livers. Allograft expression of inflammatory and cell death markers, and allograft leukocyte infiltration were evaluated from a contemporaneous independent cohort of DCD (n = 22) and DBD (n = 13) livers. RESULTS:When examining the differences between transplant stages in each group, C18, C20, C24 ceramides showed significant difference in DBD (p<0.05) and C22 ceramide (p<0.05) were more pronounced for DCD. C18 ceramide is correlated to bilirubin, INR, and creatinine after transplant in DCD. Prior to transplantation, DCD livers have reduced leukocyte infiltration compared to DBD allografts. Following reperfusion, the neutrophil infiltration and platelet deposition was less prevalent in DCD grafts while cell death and recipients levels of serum aspartate aminotransferase (AST) of DCD allografts had significantly increased. CONCLUSION:These data suggest that I/R injury generate necrosis in the absence of a strong inflammatory response in DCD livers with an appreciable effect on early graft function. The long-term consequences of increased inflammation in DBD and increased cell death in DCD allografts are unknown and warrant further investigation

Lipidomics comparing DCD and DBD liver allografts uncovers lysophospholipids elevated in recipients undergoing early allograft dysfunction

Finding specific biomarkers of liver damage in clinical evaluations could increase the pool of available organs for transplantation. Lipids are key regulators in cell necrosis and hence this study hypothesised that lipid levels could be altered in organs suffering severe ischemia. Matched pre- and post-transplant biopsies from donation after circulatory death (DCD, n = 36, mean warm ischemia time = 21min) and donation after brain death (DBD, n = 76, warm ischemia time = none) were collected. Lipidomic discovery and multivariate analysis (MVA) were applied. Afterwards, univariate analysis and clinical associations were conducted for selected lipids differentiating between these two groups. MVA grouped DCD vs. DBD (p = 6.20 × 10(−12)) and 12 phospholipids were selected for intact lipid measurements. Two lysophosphatidylcholines, LysoPC (16:0) and LysoPC (18:0), showed higher levels in DCD at pre-transplantation (q < 0.01). Lysophosphatidylcholines were associated with aspartate aminotransferase (AST) 14-day post-transplantation (q < 0.05) and were more abundant in recipients undergoing early allograft dysfunction (EAD) (p < 0.05). A receiver-operating characteristics (ROC) curve combining both lipid levels predicted EAD with 82% accuracy. These findings suggest that LysoPC (16:0) and LysoPC (18:0) might have a role in signalling liver tissue damage due to warm ischemia before transplantation

Breast cancer liver metastases in a UK tertiary centre: outcomes following referral to tumour board meeting

Introduction To assess the outcomes from multidisciplinary board meetings (MDM) for patients with breast cancer liver metastases (BCLM) and identify prognostic factors for survival. Materials and methods A retrospective review of MDM records for patients referred with BCLM to a tertiary centre between 2005 and 2016. Patient demographics, clinicopathological factors and intervention type were analysed to find predictive factors for overall survival. Results 61 patients with BCLM were referred to the MDM. Treatment pathways included surgical resection (n = 23), radiofrequency ablation (RFA, n = 11), or chemotherapy (n = 27). Surgical resection patients had an improved median overall survival compared to chemotherapy (49 v 20mo; p < 0.001). RFA showed comparable survival benefit (37 v 20mo; p = 0.011). Resection and RFA showed no significant difference in survival over one another (49 v 37mo; p = 0.854). Survival analysis identified that resection (p = 0.002) and RFA (p = 0.001) were associated with improved overall survival compared to chemotherapy. Multivariate analysis identified extrahepatic disease (HR = 14.21; p = 0.044) and R0 resection (HR = 0.068; p = 0.023) as prognostic factors. Conclusions Surgical resection of BCLM may improve the overall survival in selected patient groups. This study identifies a cohort of patients, without extrahepatic disease and responsive to chemotherapy, who may particularly benefit from surgery