Increasing metformin concentrations and its excretion in both rat and porcine ex vivo normothermic kidney perfusion model.

Introduction: Metformin can accumulate and cause lactic acidosis in patients with renal insufficiency. Metformin is known to inhibit mitochondria, while renal secretion of the drug by proximal tubules indirectly requires energy. We investigated whether addition of metformin before or during ex vivo isolated normothermic machine perfusion (NMP) of porcine and rat kidneys affects its elimination.

Metformin Preconditioning and Postconditioning to Reduce Ischemia Reperfusion Injury in an Isolated Ex Vivo Rat and Porcine Kidney Normothermic Machine Perfusion Model.

Metformin may act renoprotective prior to kidney transplantation by reducing ischemia-reperfusion injury (IRI). This study examined whether metformin preconditioning and postconditioning during ex vivo normothermic machine perfusion (NMP) of rat and porcine kidneys affect IRI. In the rat study, saline or 300 mg/kg metformin was administered orally twice on the day before nephrectomy.

Metformin Preconditioning Improves Hepatobiliary Function and Reduces Injury in a Rat Model of Normothermic Machine Perfusion and Orthotopic Transplantation.

Background: Preconditioning of donor livers before organ retrieval may improve organ quality after transplantation. We investigated whether preconditioning with metformin reduces preservation injury and improves hepatobiliary function in rat donor livers during ex situ normothermic machine perfusion (NMP) and after orthotopic liver transplantation.

Methods: Lewis rats were administered metformin via oral gavage, after which a donor hepatectomy was performed followed by a standardized cold storage period of 4 hours.

Comparing peri-operative complications of paediatric and adult anaesthesia: A retrospective cohort study of 81 267 cases.

Background: Comparisons of peri-operative complications associated with paediatric (≤16 years) and adult anaesthesia are poorly available, especially in which cardiac surgery, organ transplantation and neurosurgery are involved.

Objective: The aim of this study was to evaluate the nature and incidence of peri-operative complications that might be due to anaesthesia and to identify independent risk factors for complications in children and adults, including those undergoing cardiac surgery, organ transplantation and neurosurgery.

Design: Retrospective cohort study.

Normothermic machine perfusion of donor livers without the need for human blood products.

Normothermic machine perfusion (NMP) enables viability assessment of donor livers prior to transplantation. NMP is frequently performed by using human blood products including red blood cells (RBCs) and fresh frozen plasma (FFP). Our aim was to examine the efficacy of a novel machine perfusion solution based on polymerized bovine hemoglobin-based oxygen carrier (HBOC)-201.

Oxygenated hypothermic machine perfusion after static cold storage improves endothelial function of extended criteria donor livers.

Background: Lack of oxygen and biomechanical stimulation during static cold storage (SCS) of donor livers compromises endothelial cell function. We investigated the effect of end-ischemic oxygenated hypothermic machine perfusion (HMP) on endothelial cell function of extended criteria donor (ECD) livers.

Methods: Eighteen livers, declined for transplantation, were transported to our center using static cold storage (SCS).

Activation of Fibrinolysis, But Not Coagulation, During End-Ischemic Ex Situ Normothermic Machine Perfusion of Human Donor Livers.

Background: Ex situ normothermic machine perfusion (NMP) can be performed after traditional static cold preservation to assess graft function and viability before transplantation. It is unknown whether this results in activation of coagulation and fibrinolysis, as may occur upon graft reperfusion in vivo.

Methods: Twelve donor livers declined for transplantation underwent 6 hours of end-ischemic NMP using a heparinized plasma-based perfusion fluid.

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.

Intraoperative frozen section analysis of the proximal bile ducts in hilar cholangiocarcinoma is of limited value.

Frozen section analysis (FS) during cancer surgery is widely used to assess resection margins. However, in hilar cholangiocarcinoma (HCCA), FS may be less reliable because of the specific growth characteristics of the tumor. The aim of this study was to determine the accuracy and consequences of intraoperative FS of the proximal bile duct margins in HCCA.

Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers.

Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts.

Oxygenated Hypothermic Machine Perfusion After Static Cold Storage Improves Hepatobiliary Function of Extended Criteria Donor Livers.

Background: The mechanism through which oxygenated hypothermic machine perfusion (HMP) improves viability of human extended criteria donor (ECD) livers is not well known. Aim of this study was to examine the benefits of oxygenated HMP after static cold storage (SCS).

Methods: Eighteen ECD livers that were declined for transplantation underwent ex situ viability testing using normothermic (37 °C) machine perfusion (NMP) after traditional SCS (0 °C-4 °C) for 7 to 9 hours.

Diffuse reflectance spectroscopy accurately quantifies various degrees of liver steatosis in murine models of fatty liver disease.

Background: A real-time objective evaluation for the extent of liver steatosis during liver transplantation is currently not available. Diffuse reflectance spectroscopy (DRS) rapidly and accurately assesses the extent of steatosis in human livers with mild steatosis. However, it is yet unknown whether DRS accurately quantifies moderate/severe steatosis and is able to distinguish between micro- and macrovesicular steatosis.

End-ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature.

A short period of oxygenated machine perfusion (MP) after static cold storage (SCS) may reduce biliary injury in donation after cardiac death (DCD) donor livers. However, the ideal perfusion temperature for protection of the bile ducts is unknown. In this study, the optimal perfusion temperature for protection of the bile ducts was assessed.

Ex Situ Normothermic Machine Perfusion of Donor Livers.

In contrast to conventional static cold preservation (0-4 °C), ex situ machine perfusion may provide better preservation of donor livers. Continuous perfusion of organs provides the opportunity to improve organ quality and allows ex situ viability assessment of donor livers prior to transplantation. This video article provides a step by step protocol for ex situ normothermic machine perfusion (37 °C) of human donor livers using a device that provides a pressure and temperature controlled pulsatile perfusion of the hepatic artery and continuous perfusion of the portal vein.

Elderly donor liver grafts are not associated with a higher incidence of biliary complications after liver transplantation: results of a national multicenter study.

Background: Liver transplantation with livers grafts from elderly donors has been associated with a higher risk of biliary complications. The aim of this study was to examine whether our national protocol could contribute to a lower incidence of biliary complications.

Methods: All adult recipients in the Netherlands transplanted with a liver from an elderly donor (≥ 65 yrs; n = 68) in the period January 2000-July 2011 were matched with recipients of a liver from a donor <65 yr (n = 136).

Diffuse reflectance spectroscopy: toward real-time quantification of steatosis in liver.

Assessment of fatty liver grafts during orthotopic liver transplantation is a challenge due to the lack of real-time analysis options during surgery. Diffuse reflectance spectroscopy (DRS) could be a new diagnostic tool to quickly assess steatosis. Eight hundred and seventy-eight optical measurements were performed in vivo in 17 patients in liver tissue during surgery and ex vivo on liver resection specimens from 41 patients.

Similar outcome after transplantation of moderate macrovesicular steatotic and nonsteatotic livers when the cold ischemia time is kept very short.

Background: Livers with moderate (30-60%) macrovesicular steatosis have been associated with poor outcome after transplantation. Aim of this study was to examine the outcome after transplantation of livers with moderate macrovesicular steatosis when the cold ischemia time (CIT) is kept very short.

Methods: Postoperative outcome of 19 recipients of a moderate steatotic liver were compared with a matched control group of 95 recipients of a nonsteatotic liver graft (1:5 ratio).

Biliary complications after orthotopic liver transplantation.

Purpose Of Review: The incidence, pathogenesis and management of the most common biliary complications are summarized, with an emphasis on nonanastomotic biliary strictures (NAS) and potential strategies to prevent NAS after liver transplantation.

Recent Findings: NAS have variable presentations in time and localization, suggesting various underlying pathogeneses. Early-onset NAS (presentation within 1 year) have shown to be largely related to ischemia-induced bile duct injury, whereas late-onset NAS [>1 year after orthotopic liver transplantation (OLT)] have more immune-mediated causes.

Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures.

Background & Aims: The peribiliary glands of large bile ducts have been identified as a niche of progenitor cells that contribute to regeneration of biliary epithelium after injury. We aimed to determine whether injury to the peribiliary glands of donor livers is a risk factor for development of non-anastomotic biliary strictures (NAS) after liver transplantation.

Methods: In 128 liver transplant procedures, biopsies were taken from the donor bile duct and injury was assessed using an established histological grading system.

Open-book tests: search behaviour, time used and test scores.

Background: Because of the increasing medical knowledge and the focus of medical education on acquiring competencies, the use of open-book tests seems inevitable. Dealing with a large body of information, indicating which kind of information is needed to solve a problem, and finding and understanding that knowledge at the right moment are behaviours that cannot be assessed during closed-book tests.

Aims: To examine whether there is a relationship between students' search behaviour - using references or not when answering a question - during open-book tests and their test scores.

How to minimize blood loss during liver surgery in patients with cirrhosis.

Patients with liver disease frequently have substantial changes in their haemostatic system. This is reflected in abnormal test results on routine coagulation screening assays such as the prothrombin time (PT), activated thromboplastin time (APTT) and platelet count. Traditionally, attempts were made to correct abnormalities in the haemostatic system as measured by routine coagulation assays prior to invasive procedures by infusion of platelets or fresh frozen plasma (FFP).