D Nasralla

A randomized trial of normothermic preservation in liver transplantation

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.Normothermic machine perfusion of the liver improved early graft function, demonstrated by reduced peak serum aspartate transaminase levels and early allograft dysfunction rates, and improved organ utilization and preservation times, although no differences were seen in graft or patient survival.

Past, Present, and Future of Dynamic Kidney and Liver Preservation and Resuscitation

The increased demand for organs has led to the increased usage of “higher risk” kidney and liver grafts. These grafts from donation after circulatory death or expanded criteria donors are more susceptible to preservation injury and have a higher risk of unfavorable outcomes. Dynamic, instead of static, preservation could allow for organ optimization, offering a platform for viability assessment, active organ repair and resuscitation. Ex situ machine perfusion and in situ regional perfusion in the donor are emerging as potential tools to preserve and resuscitate vulnerable grafts. Preclinical findings have ignited clinical organ preservation research that investigates dynamic preservation, its various modes (continuous, preimplantation) and temperatures (hypo‐, sub, or normothermic). This review outlines the current status of dynamic preservation of kidney and liver grafts and describes ongoing research and emerging clinical trials.

The case for normothermic machine perfusion in liver transplantation.

In recent years, there has been growing interest in normothermic machine perfusion (NMP) as a preservation method in liver transplantation. In most countries, because of a donor organ shortage, an unacceptable number of patients die while awaiting transplantation. In an attempt to increase the number of donor organs available, transplant teams are implanting a greater number of high‐risk livers, including those from donation after circulatory death, older donors, and donors with steatosis. NMP maintains the liver ex vivo on a circuit by providing oxygen and nutrition at 37°C. This permits extended preservation times, the ability to perform liver viability assessment, and the potential for liver‐directed therapeutic interventions during preservation. It is hoped that this technology may facilitate the enhanced preservation of marginal livers with improved posttransplant outcomes by reducing ischemia/reperfusion injury. Clinical trials have demonstrated its short‐term superiority over cold storage in terms of early biochemical liver function, and it is anticipated that it may result in increased organ utilization, helping to reduce the number of wait‐list deaths. However, further studies are required to demonstrate longer‐term efficacy and the impact on biliary complications as well as further knowledge to exploit and maximize the potential of this exciting new technology. Liver Transplantation 24 269–275 2018 AASLD.

Cold storage or normothermic perfusion for liver transplantation: probable application and indications.

Purpose of review Preservation of the liver via normothermic machine perfusion (NMP) is rapidly becoming an area of great academic and clinical interest. This review focuses on the benefits and limitations of NMP and where the role for static cold storage may lie. Recent findings Clinical studies have recently been published reporting the use of NMP in liver preservation for transplantation. They have described the technology to be well tolerated and feasible with potentially improved posttransplant outcomes. NMP facilitates extended preservation times as well as the potential to increase organ utilization through viability assessment and regeneration. However, this technology is considerably more costly than cold storage and carries significant logistical challenges. Cold storage remains the gold standard preservation for standard criteria livers with good long-term patient and graft survival. Summary NMP is an exciting new technological advancement in liver preservation, which is likely to have a positive impact in liver transplantation. However, randomized controlled trials are required to justify its inclusion into standard practice and provide evidence to support its efficacy.

The organ preservation and enhancement of donation success ratio effect of Extracorporeal Membrane Oxygenation in circulatory unstable brain death donor

Between 2010 and 2013, we recorded 66 cases of failed organ donation after brain death (DBD) due to the excessive use of the vasoactive drugs resulting in impaired hepatic and/or renal function. To investigate the effect of extracorporeal membrane oxygenation (ECMO) in donor management, ECMO was used to provide support for DBD donors with circulatory and/or respiratory failure from 2013 to 2015. A retrospective cohort study between circulatory non‐stable DBD with vasoactive drugs (DBD‐drug) and circulatory non‐stable DBD with ECMO (DBD‐ECMO) was designed to compare the transplant outcomes. A total of 19 brain death donors were supported by ECMO. The incidence rate of post‐transplant liver primary non‐function (PNF) was 10% (two of 20) in DBD‐drug group and zero in DBD‐ECMO group. Kidney function indicators, including creatinine clearance and urine production, were significantly better in DBD‐ECMO group, as well as the kidney delayed graft function (DGF) rate was found to be decreased by the use of ECMO in our study. Donation success rate increased steadily from 47.8% in 2011 to 84.6% in 2014 after the ECMO intervention. The use of ECMO in assisting circulatory and respiratory function of DBD can reduce liver and kidney injury from vasoactive drugs, thereby improving organ quality and reducing the organ discard rates.

Normothermic Machine Preservation of the Liver: State of the Art.

Purpose of ReviewThis review aims to introduce the concept of normothermic machine perfusion (NMP) and its role in liver transplantation. By discussing results from recent clinical studies and highlighting the potential opportunities provided by this technology, we aim to provide a greater insight into NMP and the role it can play to enhance liver transplantation.Recent FindingsNMP has recently been shown to be both safe and feasible in liver transplantation and has also demonstrated its superiority to traditional cold storage in terms of early biochemical liver function. Through the ability to perform a viability assessment during preservation and extend preservation times, it is likely that an increase in organ utilisation will follow. NMP may facilitate the enhanced preservation with improved outcomes from donors after cardiac death and steatotic livers. Furthermore, it provides the exciting potential for liver-directed therapeutic interventions.SummaryEvidence to date suggests that NMP facilitates the enhanced preservation of liver grafts with improved early post-transplant outcomes. The key role for this technology is to increase the number and quality of liver grafts available for transplantation and to reduce waiting list deaths.

Successful Outflow Reconstruction to Salvage Traumatic Hepatic Vein-Caval Avulsion of a Normothermic Machine Ex-Situ Perfused Liver Graft: Case Report and Management of Organ Pool Challenges

AbstractDonor organ shortage continues to limit the availability of liver transplantation, a successful and established therapy of end-stage liver diseases. Strategies to mitigate graft shortage include the utilization of marginal livers and recently ex-situ normothermic machine perfusion devices.A 59-year-old woman with cirrhosis due to primary sclerosing cholangitis was offered an ex-situ machine perfused graft with unnoticed severe injury of the suprahepatic vasculature due to road traffic accident.Following a complex avulsion, repair and reconstruction of all donor hepatic veins as well as the suprahepatic inferior vena cava, the patient underwent a face-to-face piggy-back orthotopic liver transplantation and was discharged on the 11th postoperative day after an uncomplicated recovery.This report illustrates the operative technique to utilize an otherwise unusable organ, in the current environment of donor shortage and declining graft quality. Normothermic machine perfusion can definitely play a role in increasing the graft pool, without compromising the quality of livers who had vascular or other damage before being ex-situ perfused. Furthermore, it emphasizes the importance of promptly and thoroughly communicating organ injuries, as well as considering all reconstructive options within the level of expertise at the recipient center.

Exophytic cystic liver lesion: an unusual presentation of a hepatocellular carcinoma in a young female

Hepatocellular carcinoma (HCC) is one of the most common malignant primary liver tumours. However, primary hepatic carcinomas are rare in young adults, accounting for approximately 1% of tumours in people below the age of 20. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the two most important aetiological agents of HCC. The average age at onset of HBV-related HCC (~50 years old) is 10 years younger than that of HCV-related HCC (61–64 years). Evidence for an association between the oral contraceptive pill (OCP) and development of HCC remains inconclusive. Here, we describe a case of a 28-year-old woman with normal background liver, who presented with a large palpable abdominal mass due to a bilobar, exophytic, cystic lesion arising from the right lobe of the liver, later diagnosed as HCC on histological analysis. We highlight the need for considering HCC even in the unusual setting of a cystic, exophytic lesion.

Surgical Endoscopy Training in England

Surgical training is going through a time of transition. With the introduction of the European Working Time Regulations (EWTR) and Modernising Medical Careers (MMC) the working week has been limited to 48 hours, while the time it takes to achieve the Certificate of Completion of Training has also been streamlined. This combination of factors poses problems for trainees with regards to exposure to procedures and obtaining adequate experience in their chosen specialty.