Abdominal Normothermic Regional Perfusion in Donation After Circulatory Death: A Systematic Review and Critical Appraisal

Background: Abdominal normothermic regional perfusion (aNRP) for donation after circulatory death is an emerging organ preservation technique that might lead to increased organ utilization per donor by facilitating viability testing, improving transplant outcome by early reversal of ischemia, and decreasing the risk of unintentional surgical damage. The aim of the current review is to evaluate the recent literature on the added value of aNRP when compared to local standard perfusion technique.Methods: The Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline for systematic reviews was used, and relevant literature databases were searched. Primary outcomes were organ utilization rate and patient and graft survival after 1 year. Secondary outcomes included delayed graft function, primary nonfunction, serum creatinine, and biliary complications.Results: A total of 24 articles were included in this review. The technique is unanimously reported to be feasible and safe, but the available studies are characterized by considerable heterogeneity and bias.Conclusions: Uniform reported outcome measures are needed to draw more definitive conclusions on transplant outcomes and organ utilization. A randomized controlled trial comparing aNRP with standard procurement technique in donation after circulatory death donors would be needed to show the added value of the procedure and determine its place among modern preservation techniques.Transplant surger

Fast, robust and effective decellularization of whole human livers using mild detergents and pressure controlled perfusion

Human whole-liver perfusion-decellularization is an emerging technique for producing bio-scaffolds for tissue engineering purposes. The native liver extracellular matrix (ECM) provides a superior microenvironment for hepatic cells in terms of adhesion, survival and function. However, current decellularization protocols show a high degree of variation in duration. More robust and effective protocols are required, before human decellularized liver ECM can be considered for tissue engineering applications. The aim of this study is to apply pressure-controlled perfusion and test the efficacy of two different detergents in porcine and human livers. To test this, porcine livers were decellularized using two different protocols; a triton-x-100 (Tx100)-only protocol (N = 3) and a protocol in which Tx100 was combined with SDS (N = 3) while maintaining constant pressure of 120 mm Hg. Human livers (N = 3) with different characteristics (age, weight and fat content) discarded for transplantation were decellularized using an adapted version of the Tx-100-only protocol. Decellularization efficacy was determined by histology and analysis of DNA and RNA content. Furthermore, the preservation of ECM components was assessed. After completing the perfusion cycles with detergents the porcine li

Hypothermic machine perfusion in liver transplantation: a randomized trial

BACKGROUNDTransplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited.METHODSIn this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications.RESULTSA total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P=0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups.CONCLUSIONSHypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Current practice in the management of acromioclavicular joint dislocations; a national survey in the Netherlands

Purpose: The aim of this study was to investigate current practice in the management of acromioclavicular joint dislocations in the Netherlands. Methods: A 36-item literature-based and expert consensus survey was developed. If available, one orthopaedic and one trauma surgeon for every hospital (n = 82) in the Netherlands was asked to complete the online questionnaire. Only complete data sets were included in the analysis. Descriptive analysis was performed using SPSS. Results: Of 149 invited surge

Scaffolds obtained from decellularized human extrahepatic bile ducts support organoids to establish functional biliary tissue in a dish

Biliary disorders can lead to life-threatening disease and are also a challenging complication of liver transplantation. As there are limited treatment options, tissue engineered bile ducts could be employed to replace or repair damaged bile ducts. We explored how these constructs can be created by seeding hepatobiliary LGR5+ organoids onto tissue-specific scaffold. For this, we decellularized discarded human extrahepatic bile ducts (EBD) that we recellularized with organoids of different origin, that is, liver biopsies, extrahepatic bile duct biopsies, and bile samples. Here, we demonstrate efficient decellularization of EBD tissue. Recellularization of the EBD extracellular matrix (ECM) with the organoids of extrahepatic origin (EBD tissue and bile derived organoids) showed more profound repopulation of the ductal ECM when compared with liver tissue (intrahepatic bile duct) derived organoids. The bile duct constructs that were repopulated with extrahepatic organoids expressed mature cholangiocyte-markers and had increased electrical resistance, indicating restoration of the barrier function. Therefore, the organoids of extrahepatic sources are identified to be the optimal candidate for the development of personalized tissue engineered EBD constructs

Donor eligibility criteria and liver graft acceptance criteria during normothermic regional perfusion: A systematic review

Acceptance of liver grafts from donations after circulatory death (DCD) largely remains a "black box," particularly due to the unpredictability of the agonal phase. Abdominal normothermic regional perfusion (aNRP) can reverse ischemic injury early during the procurement procedure, and it simultaneously enables graft viability testing to unravel this black box. This review evaluates current protocols for liver viability assessment to decide upon acceptance or decline during aNRP. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was used, and relevant literature databases were searched. The primary outcome consisted of criteria for liver graft viability assessment. Secondary outcomes included survival, primary nonfunction (PNF), early dysfunction, and biliary complications. A total of 14 articles were included in the analysis. In all protocols, a combination of criteria was used to assess suitability of the liver for transplantation. As many as 12 studies (86%) used macroscopic assessment, 12 studies (86%) used alanine transaminase (ALT) levels in perfusate, 9 studies (64%) used microscopic assessment, and 7 studies (50%) used lactate levels as assessment criteria. The organ utilization rate (OUR) was 16% for uncontrolled donation after circulatory death (uDCD) and 64% for controlled donation after circulatory death (cDCD). The most used acceptation criterion in uDCD is ALT level (31%), while in cDCD macroscopic aspect (48%) is most used. Regarding postoperative complications, PNF occurred in 13% (6%-25%) of uDCD livers and 3% (2%-4%) of cDCD livers. In uDCD, the 1-year graft and patient survival rates were 75% (66%-82%) and 82% (75%-88%). In cDCD, the 1-year graft and patient survival rates were 91% (89%-93%) and 93% (91%-94%), respectively. In conclusion, the currently used assessment criteria consist of macroscopic aspect and transaminase levels. The acceptance criteria should be tailored according to donor type to prevent an unacceptable PNF rate in uDCD and to increase the relatively modest OUR in cDCD

Salvage of Declined Extended-criteria DCD Livers Using In Situ Normothermic Regional Perfusion

Objective: This study investigates whether liver grafts donated after circulatory death (DCD) that are declined by the entire Eurotransplant region can be salvaged with abdominal normothermic regional perfusion (aNRP). Background: aNRP is increasingly used for DCD liver grafts because it prevents typical complications. However, it is unclear whether aNRP is capable to rescue pretransplant declined liver grafts by providing the opportunity to test function during donation. Methods: Donor livers from DCD donors, declined by all centers in the Eurotransplant region, were included for this study. The comparator cohort included standard DCD livers and livers donated after brain death, transplanted in the same time period. Results: After the withdrawal of life-sustaining treatment, 28 from the 43 donors had a circulatory death within 2 hours, in which case aNRP was initiated. Of these 28 cases, in 3 cases perfusion problems occurred, 5 grafts were declined based on liver assessment, and 20 liver grafts were transplanted. The main differences during aNRP between the transplanted grafts and the assessed nontransplanted grafts were alanine transaminase levels of 53 U/L (34-68 U/L) versus 367 U/L (318-488 U/L) (P=0.001) and bile production in 100% versus 50% of the grafts (P=0.024). The 12-month graft and patient survival were both 95%, similar to the comparator cohort. The incidence of ischemic cholangiopathy was 11%, which was lower than in the standard DCD cohort (18%). Conclusion: aNRP can safely select and thus is able to rescue DCD liver grafts that were deemed unsuitable for transplantation, while preventing primary nonfunction and minimizing ischemic cholangiopathy