Strict selection alone of patients undergoing liver transplantation for hilar cholangiocarcinoma is associated with improved survival

Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five-year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience

Pre-and postconditioning effects of metformin in rat donor livers

Background: Pre- or reconditioning of donor livers can improve organ quality prior to transplantation. The aim of this study was to investigate whether metformin as pre- or reconditioning agent is able to reduce preservation injury in rat donor livers and improve hepatobiliary function during ex situ normothermic machine perfusion (NMP). Methods: To study the preconditioning effects of metformin, metformin was administered via oral gavage 12 and 2 hours before the hepatectomy. To assess the reconditioning effects of metformin, in 2 other groups, metformin was added to the NMP perfusion fluid in two different concentrations (30 and 300 mg/L). In the reference group, no pre- or reconditioning was carried out. In all groups, rat donor livers were preserved for 4 hours in preservation fluid on melting ice. Thereafter, NMP was performed for viability assessment. Results: Preconditioning improved ATP production and hepatobiliary function (assessed by total bile production, biliary bilirubin and bicarbonate) and significantly lowered levels of lactate and glucose during NMP. On the other hand, metformin preconditioning did not reduce markers for hepatobiliary injury such as AST, ALT, LDH, caspase-3 activity, TBARS or biliary gamma-GT and LDH. Reconditioning with metformin did not improve hepatobiliary function or reduce injury markers during NMP. Conclusion: Preconditioning of rat donor livers with metformin improves hepatobiliary function but does not reduce preservation injury as assessed during 3 hours of NMP. Reconditioning with metformin showed no beneficial effects