Utilization of livers donated after circulatory death for transplantation - An international comparison.

BACKGROUND & AIMS: Liver graft utilization rates are a hot topic due to the worldwide organ shortage and the increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially enable the assessment of livers before use. METHODS: Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht type III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, the UK, and the US. Initial type-III DCD liver offers were correlated with accepted, recovered and implanted livers. RESULTS: A total number of 34,269 DCD livers were offered, resulting in 9,780 liver transplants (28.5%). The discard rates were highest in the UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g. between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, we observed large differences in the use of various machine perfusion techniques, as well as in graft and donor risk factors. For example, the median donor age and functional donor warm ischemia time were highest in Italy, e.g. >40 min, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in 5-year graft survival rates, which ranged between 60-82% in this analysis. CONCLUSIONS: Overall, DCD liver discard rates across the eight countries were high, although this primarily reflects the situation in the Netherlands, the UK and the US. Countries where in situ and ex situ machine perfusion strategies were used routinely had better DCD utilization rates without compromised outcomes. IMPACT AND IMPLICATIONS: A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5% but varies significantly between 18.9% and 74.2%. For example, the median DCD-III liver utilization in five countries, e.g. Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, 1- and 5-year graft survival rates remain fairly similar among all participating countries. A highly varying experience with modern machine perfusion technology was observed. In situ and ex situ liver perfusion concepts, and application of assessment tools for type-III DCD livers before transplantation, may be a key explanation for the observed differences in DCD-III utilization.

A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation.

BACKGROUND & AIMS: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. METHODS: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. RESULTS: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). CONCLUSIONS: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. IMPACT AND IMPLICATIONS: This randomized controlled phase III trial is the first to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation. Compared to conventional cold storage, HOPE did not have a significant effect on the number of patients with at least one Clavien ≥III complication. However, we believe that HOPE may have a beneficial effect on the quantity of complications per patient, based on its application leading to fewer severe liver graft-related complications, and to a lower risk of liver-related graft loss. The HOPE approach can be applied easily after organ transport during recipient hepatectomy. This appears fundamental for wide acceptance since concurring perfusion technologies need either perfusion at donor sites or continuous perfusion during organ transport, which are much costlier and more laborious. We conclude therefore that the post hoc findings of this trial should be further validated in future studies.

Results from the european survey on preoperative management and optimization protocols for PeriHilar cholangiocarcinoma.

BACKGROUND: Major surgery, along with preoperative cholestasis-related complications, are responsible for the increased risk of morbidity and mortality in perihilar cholangiocarcinoma (pCCA). The aim of the present survey is to provide a snapshot of current preoperative management and optimization strategies in Europe. METHODS: 61 European centers, experienced in hepato-biliary surgery completed a 59-questions survey regarding pCCA preoperative management. Centers were stratified according to surgical caseload (<5 and ≥ 5 cases/year) and preoperative management protocols' application. RESULTS: The overall case volume consisted of 6333 patients. Multidisciplinary discussion was routinely performed in 91.8% of centers. Most respondents (96.7%) recognized the importance of a well-structured preoperative protocol. The preferred method for biliary drainage was percutaneous transhepatic biliary drainage (60.7%) while portal vein embolization was the preferred technique for liver hypertrophy (90.2%). Differences in preoperative pathologic confirmation of malignancy (35.8% vs 28.7%; p < 0.001), number of mismanaged referred patients (88.2% vs 50.8%; p < 0.001), biliary drainage (65.1% vs 55.6%; p = 0.015) and liver function evaluation (37.2% vs 5.6%; p = 0.001) were found between centers according to groups' stratification. CONCLUSION: The importance of a correct preoperative management is recognized. Nevertheless, the current lack of guidelines leads to wide heterogeneity of behaviors among centers. This survey can provide recommendations to improve pCCA perioperative outcomes.

Prolonged preservation by hypothermic machine perfusion facilitates logistics in liver transplantation: A European observational cohort study.

A short period (1-2 h) of hypothermic oxygenated machine perfusion (HOPE) after static cold storage is safe and reduces ischemia-reperfusion injury-related complications after liver transplantation. Machine perfusion time is occasionally prolonged for logistical reasons, but it is unknown if prolonged HOPE is safe and compromises outcomes. We conducted a multicenter, observational cohort study of patients transplanted with a liver preserved by prolonged (≥4 h) HOPE. Postoperative biochemistry, complications, and survival were evaluated. The cohort included 93 recipients from 12 European transplant centers between 2014-2021. The most common reason to prolong HOPE was the lack of an available operating room to start the transplant procedure. Grafts underwent HOPE for a median (range) of 4:42 h (4:00-8:35 h) with a total preservation time of 10:50 h (5:50-20:50 h). Postoperative peak ALT was 675 IU/L (interquartile range 419-1378 IU/L). The incidence of postoperative complications was low, and 1-year graft and patient survival were 94% and 88%, respectively. To conclude, good outcomes are achieved after transplantation of donor livers preserved with prolonged (median 4:42 h) HOPE, leading to a total preservation time of almost 21 h. These results suggest that simple, end-ischemic HOPE may be utilized for safe extension of the preservation time to ease transplantation logistics.

Introduction of the Concept of Diagnostic Sensitivity and Specificity of Normothermic Perfusion Protocols to Assess High-Risk Donor Livers.

Normothermic machine perfusion (NMP) allows objective assessment of donor liver transplantability. Several viability evaluation protocols have been established, consisting of parameters such as perfusate lactate clearance, pH, transaminase levels, and the production and composition of bile. The aims of this study were to assess 3 such protocols, namely, those introduced by the teams from Birmingham (BP), Cambridge (CP), and Groningen (GP), using a cohort of high-risk marginal livers that had initially been deemed unsuitable for transplantation and to introduce the concept of the viability assessment sensitivity and specificity. To demonstrate and quantify the diagnostic accuracy of these protocols, we used a composite outcome of organ use and 24-month graft survival as a surrogate endpoint. The effects of assessment modifications, including the removal of the most stringent components of the protocols, were also assessed. Of the 31 organs, 22 were transplanted after a period of NMP, of which 18 achieved the outcome of 24-month graft survival. The BP yielded 94% sensitivity and 50% specificity when predicting this outcome. The GP and CP both seemed overly conservative, with 1 and 0 organs, respectively, meeting these protocols. Modification of the GP and CP to exclude their most stringent components increased this to 11 and 8 organs, respectively, and resulted in moderate sensitivity (56% and 44%) but high specificity (92% and 100%, respectively) with respect to the composite outcome. This study shows that the normothermic assessment protocols can be useful in identifying potentially viable organs but that the balance of risk of underuse and overuse varies by protocol.

The role of T-tubes and abdominal drains on short-term outcomes in liver transplantation - A systematic review of the literature and expert panel recommendations.

BACKGROUND: This systematic review and expert panel recommendation aims to answer the question regarding the routine use of T-tubes or abdominal drains to better manage complications and thereby improve outcomes after liver transplantation. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel to assess the potential risks and benefits of T-tubes and intra-abdominal drainage in liver transplantation (CRD42021243036). RESULTS: Of the 2996 screened records, 33 studies were included in the systematic review, of which 29 (six RCTs) assessed the use of T-tubes and four regarding surgical drains. Although some studies reported less strictures when using a T-tube, there was a trend toward more biliary complications with T-tubes, mainly related to biliary leakage. Due to the small number of studies, there was a paucity of evidence on the effect of abdominal drains with no clear benefit for or against the use of drainage. However, one study investigating the open vs. closed circuit drains found a significantly higher incidence of intra-abdominal infections when open-circuit drains were used. CONCLUSIONS: Due to the potential risk of biliary leakage and infections, the routine intraoperative insertion of T-tubes is not recommended (Level of Evidence moderate - very low; grade of recommendation strong). However, a T-tube can be considered in cases at risk for biliary stenosis. Due to the scant evidence on abdominal drainage, no change in clinical practice in individual centers is recommended. (Level of Evidence very low; weak recommendation).

Long-term outcomes of pediatric liver transplantation using organ donation after circulatory death: Comparison between full and reduced grafts.

BACKGROUND: The shortage of donors' livers for pediatric recipients inspired the search for alternatives including donation after cardiac death (DCD). METHODS: Retrospective review of pediatric liver transplant (PLT) using DCD grafts. Patients were divided into either FLG or RLG recipients. Pre-transplant recipient parameters, donor parameters, operative parameters, post-transplant recipient parameters, and outcomes were compared. RESULTS: Overall, 14 PLTs from DCD donors between 2005 and 2018 were identified; 9 FLG and 5 RLG. All donors were Maastricht category III. Cold ischemia time was significantly longer in RLG (8.2 h vs. 6.2 h; p = .038). Recipients of FLG were significantly older (180 months vs. 7 months; p = .012) and waited significantly longer (168 days vs. 22 days; p = .012). Recipients of RLG tended to be sicker in the immediate pre-transplant period and this was reflected by the need for respiratory or renal support. There was no significant difference between groups regarding long-term complications. Three patients in each group survived more than 5 year post-transplant. One child was re-transplanted in the RLG due to portal vein thrombosis but failed to survive after re-transplant. One child from FLG also died from a non-graft-related cause. CONCLUSIONS: Selected DCD grafts are an untapped source to widen the donor pool, especially for sick recipients. In absence of agreed criteria, graft and recipient selection for DCD grafts should be undertaken with caution.

Liver perfusion strategies: what is best and do ischemia times still matter?

PURPOSE OF REVIEW: This review describes recent developments in the field of liver perfusion techniques. RECENT FINDINGS: Dynamic preservation techniques are increasingly tested due to the urgent need to improve the overall poor donor utilization. With their exposure to warm ischemia, livers from donors after circulatory death (DCD) transmit additional risk for severe complications after transplantation. Although the superiority of dynamic approaches compared to static-cold-storage is widely accepted, the number of good quality studies remains limited. Most risk factors, particularly donor warm ischemia, and accepted thresholds are inconsistently reported, leading to difficulties to assess the impact of new preservation technologies. Normothermic regional perfusion (NRP) leads to good outcomes after DCD liver transplantation, with however short ischemia times. While randomized controlled trials (RCT) with NRP are lacking, results from the first RCTs with ex-situ perfusion were reported. Hypothermic oxygenated perfusion was shown to protect DCD liver recipients from ischemic cholangiopathy. In contrast, endischemic normothermic perfusion seems to not impact on the development of biliary complications, although this evidence is only available from retrospective studies. SUMMARY: Dynamic perfusion strategies impact posttransplant outcomes and are increasingly commissioned in various countries along with more evidence from RCTs. Transparent reporting of risk and utilization with uniform definitions is required to compare the role of different preservation strategies in DCD livers with prolonged ischemia times.

Marginal parental donors for pediatric living donor liver transplantation.

PURPOSE OF REVIEW: Living donor liver transplantation (LT) has been increasingly recognized as an effective treatment modality with excellent patient survival. Indications for LT have evolved not only for cholestatic liver disease, but also metabolic liver diseases. Living donor selection, particularly for pediatric inherited disease, is essential to prevent morbidity, both in the donor and recipient. RECENT FINDINGS: Based on 30 years of experience in pediatric living donor LT in Japan, we could identify marginal parental living donors who have potential risks following LT, including heterozygous mothers with ornithine transcarbamylase deficiency, heterozygous protein C deficiency, heterozygous hypercholesterolemia, heterozygous protoporphyria, asymptomatic parental donors with paucity of intrahepatic bile duct, and human leukocyte antigen-homozygous parental donors. SUMMARY: Although these situations seem rare due to infrequency of the condition, careful living donor evaluation is required to optimize the outcomes for pediatric recipients. In the setting of an appropriate selection of a living donor, we should avoid any additional hazards, given that the procedure itself has risks for a healthy individual.

How to Handle Arterial Conduits in Liver Transplantation? Evidence From the First Multicenter Risk Analysis.

OBJECTIVE: The aims of the present study were to identify independent risk factors for conduit occlusion, compare outcomes of different AC placement sites, and investigate whether postoperative platelet antiaggregation is protective. BACKGROUND: Arterial conduits (AC) in liver transplantation (LT) offer an effective rescue option when regular arterial graft revascularization is not feasible. However, the role of the conduit placement site and postoperative antiaggregation is insufficiently answered in the literature. STUDY DESIGN: This is an international, multicenter cohort study of adult deceased donor LT requiring AC. The study included 14 LT centers and covered the period from January 2007 to December 2016. Primary endpoint was arterial occlusion/patency. Secondary endpoints included intra- and perioperative outcomes and graft and patient survival. RESULTS: The cohort was composed of 565 LT. Infrarenal aortic placement was performed in 77% of ACs whereas supraceliac placement in 20%. Early occlusion (≤30 days) occurred in 8% of cases. Primary patency was equivalent for supraceliac, infrarenal, and iliac conduits. Multivariate analysis identified donor age >40 years, coronary artery bypass, and no aspirin after LT as independent risk factors for early occlusion. Postoperative antiaggregation regimen differed among centers and was given in 49% of cases. Graft survival was significantly superior for patients receiving aggregation inhibitors after LT. CONCLUSION: When AC is required for rescue graft revascularization, the conduit placement site seems to be negligible and should follow the surgeon's preference. In this high-risk group, the study supports the concept of postoperative antiaggregation in LT requiring AC.

COVID-19, liver transplant, and immunosuppression: Allies or foes?

Liver transplant (LT) recipients are considered at a particularly high risk for developing critical COVID-19 infection. To date, available data are heterogeneous and scarce and mortality in LT recipients seems to be higher compared to normal population, but whether this is caused by altered immunological status, immunosuppression (IS), or underlying comorbidities has not yet been fully clarified. Some evidences show that IS might play a role in the pathophysiology of this new disease. We searched all available data regarding LT recipients infected by COVID-19, focusing on the role of IS. To date, 244 LT recipients have been reported as COVID-19-positive. Trends among transplant physicians are to reduce overall IS, especially antimetabolite drugs, but the current available observations are still not enough to build strong evidences for recommendation and IS should be meticulously tailored case by case.

The effects of resection margin and KRAS status on outcomes after resection of colorectal liver metastases.

BACKGROUND: The aim of this study was to investigate the influence of resection margin status in patients with KRAS mutations (mt-KRAS) when compared to those with wild-type KRAS (wt-KRAS) on long-term outcomes in patients with resected CRLM. METHODS: All patients who underwent resection of CRLM with curative intent between January 2011 and December 2016 and had a KRAS type recorded were included in the study. Overall survival (OS), as well as death-censored overall (RFS) and liver-specific (LS-RFS) recurrence-free survival between KRAS types and the margin status within KRAS subgroups were compared using Cox regression models. RESULTS: Data were available for N = 500 patients (30.4% mt-KRAS). mt-KRAS status was independently associated with significantly shorter OS. Within the wt-KRAS subgroup, smaller margins were found to be associated with significantly shorter death-censored LS-RFS (p < 0.001), with HRs of 1.93 (p = 0.005) for 1-4 mm margins and 2.83 (p < 0.001) for <1 mm margins, relative to those with clear margins. No such association was observed in the mt-KRAS subgroup (p = 0.721). CONCLUSION: The resection margin status is of greater importance in patients with wt-KRAS. Such information could be useful in the operative planning, especially for those with multiple metastatic deposits, and also in the post-operative counselling and surveillance based on the margin and KRAS status.

Liver Resection and role of Extended Histology (LiREcH study) in patients with multifocal colorectal cancer liver metastases.

BACKGROUND: The aim of this study is to assess the correlation between the margin status on the specimen side (Rs) and that from the patient side (base of resection) (Rp) and the influence of positive margins (R1s and R1p) on cancer related outcomes in patients with colorectal liver metastases (CRLM). METHODS: In this prospective study, patients undergoing non-anatomical resection (NAR) of multifocal CRLM, with suspected close resection margins were included. The primary outcome evaluated was the correlation of Rs and Rp. RESULTS: Twenty-three patients had 89 NARs, and CUSA samples from the base of 36 specimens were analysed. Among 36 specimens where extended histology (EH) was performed, margin status on the specimen side (Rs) was positive in 69.4% (25/36), whereas on the patient side, the margin (Rp) was positive in only 8.3% (3/36) of specimens. On univariate analysis, there was no significant difference in the site-specific recurrence at previous resection with regards to Rs positivity (P = 0.56) and Rp positivity (P = 0.48). CONCLUSION: There is a poor correlation between Rs and Rp and the local recurrence rates in the liver. These results might further support that tumour biology is more relevant than the margin status in patients with multifocal CRLM.

Variations between the anatomical and functional distribution, based on 99m technetium -mebrofinate SPECT-CT scan, in patients at risk of post hepatectomy liver failure.

BACKGROUND: The aim of the current study is to investigate the variations of anatomical (LVRem%) and functional remnant volumes (fLVRem%) and the dynamic uptake of Technetium-Mebrofinate (FRLF) measured from 99m Technetium-Mebrofinate SPECT-CT scan (TMSCT) in patients at high risk of post-hepatectomy liver failure (PHLF). METHODS: Variations in the measures of LVRem% and fLVRem% were assessed. The predictive accuracies of LVRem%, fLVRem% and FRLF with respect to PHLF were reported. RESULTS: From the N = 92 scans performed, LVRem% and fLVRem% returned identical results in 15% of cases, and ±10 percentage points in 79% of cases. Some patients had larger discrepancies, with difference of >10 percentage points in 21% of cases. The difference was significant in those with primary liver cancers (-4.4 ± 9.2, p = 0.002). For the N = 29 patients that underwent surgery as planned on TMSCT, FRLF was a strong predictor of PHLF, with an AUROC of 0.83 (p = 0.005). CONCLUSION: TMSCT is emerging as a useful modality in pre-operative assessment of patients undergoing major liver resection. For those with primary liver cancer, there is a significant variation in the anatomical and functional distributions that needs considered in surgical planning. Reduced FRLF, measured as the dynamic uptake in the future liver remnant, is a strong predictor of PHLF.

An international multicenter study of protocols for liver transplantation during a pandemic: A case for quadripartite equipoise.

BACKGROUND & AIMS: The outbreak of COVID-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern. There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources. METHODS: We performed an international multicenter study of transplant centers to understand the evolution of policies for transplant prioritization in response to the pandemic in March 2020. To describe the ethical tension arising in this setting, we propose a novel ethical framework, the quadripartite equipoise (QE) score, that is applicable to liver transplantation in the context of limited national resources. RESULTS: Seventeen large- and medium-sized liver transplant centers from 12 countries across 4 continents participated. Ten centers opted to limit transplant activity in response to the pandemic, favoring a "sickest-first" approach. Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors - recipient outcome, donor/graft safety, waiting list mortality and healthcare resources - for 7 countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. CONCLUSIONS: This four-dimensional model of quadripartite equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems. LAY SUMMARY: There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources during the COVID-19 pandemic. We describe a four-dimensional model of quadripartite equipoise that models these ethical tensions and can guide the regulation of transplant activity in response to the increasing burden on healthcare systems.

Hypothermic Oxygenated Liver Perfusion (HOPE) Prevents Tumor Recurrence in Liver Transplantation From Donation After Circulatory Death.

OBJECTIVE: The aim of this study was to investigate tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC), with and without hypothermic oxygenated liver perfusion (HOPE) before transplantation. PATIENTS AND METHODS: We analyzed all liver recipients with HCC, transplanted between January 2012 and September 2019 with donation after circulatory death (DCD) livers after previous end-ischemic HOPE-treatment (n = 70, Center A). Tumor parameters and key confounders were compared to consecutive recipients with HCC, transplanted during the same observation period with an unperfused DBD liver (n = 70). In a next step, we analyzed unperfused DCD (n = 70) and DBD liver recipients (n = 70), transplanted for HCC at an external center (Center B). RESULTS: Tumor parameters were not significantly different between HOPE-treated DCD and unperfused DBD liver recipients at Center A. One-third of patients were outside established tumor thresholds, for example, Milan criteria, in both groups. Despite no difference in tumor load, we found a 4-fold higher tumor recurrence rate in unperfused DBD livers (25.7%, 18/70), compared to only 5.7% (n = 4/70) recipients with tumor recurrence in the HOPE-treated DCD cohort (P = 0.002) in Center A. The tumor recurrence rate was also twice higher in unperfused DCD and DBD recipients at the external Center B, despite significant less cases outside Milan. HOPE-treatment of DCD livers resulted therefore in a 5-year tumor-free survival of 92% in HCC recipients, compared to 73%, 82.7%, and 81.2% in patients receiving unperfused DBD or DCD livers, from both centers. CONCLUSION: We suggest that a simple machine liver perfusion approach appears advantageous to protect from HCC recurrence after liver transplantation, despite extended tumor criteria.

Defining Benchmark Outcomes for Pancreatoduodenectomy With Portomesenteric Venous Resection.

OBJECTIVE: The aim of this study was to establish clinically relevant outcome benchmark values using criteria for pancreatoduodenectomy (PD) with portomesenteric venous resection (PVR) from a low-risk cohort managed in high-volume centers. SUMMARY BACKGROUND DATA: PD with PVR is regarded as the standard of care in patients with cancer involvement of the portomesenteric venous axis. There are, however, no benchmark outcome indicators for this population which hampers comparisons of patients undergoing PD with and without PVR resection. METHODS: This multicenter study analyzed patients undergoing PD with any type of PVR in 23 high-volume centers from 2009 to 2018. Nineteen outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of the centers (NCT04053998). RESULTS: Out of 1462 patients with PD and PVR, 840 (58%) formed the benchmark cohort, with a mean age was 64 (SD11) years, 413 (49%) were females. Benchmark cutoffs, among others, were calculated as follows: Clinically relevant pancreatic fistula rate (International Study Group of Pancreatic Surgery): ≤14%; in-hospital mortality rate: ≤4%; major complication rate Grade≥3 and the CCI up to 6 months postoperatively: ≤36% and ≤26, respectively; portal vein thrombosis rate: ≤14% and 5-year survival for patients with pancreatic ductal adenocarcinoma: ≥9%. CONCLUSION: These novel benchmark cutoffs targeting surgical performance, morbidity, mortality, and oncological parameters show relatively inferior results in patients undergoing vascular resection because of involvement of the portomesenteric venous axis. These benchmark values however can be used to conclusively assess the results of different centers or surgeons operating on this high-risk group.

Machine Perfusions in Liver Transplantation: The Evidence-Based Position Paper of the Italian Society of Organ and Tissue Transplantation.

The use of machine perfusion (MP) in liver transplantation (LT) is spreading worldwide. However, its efficacy has not been demonstrated, and its proper clinical use has far to go to be widely implemented. The Società Italiana Trapianti d'Organo (SITO) promoted the development of an evidence-based position paper. A 3-step approach has been adopted to develop this position paper. First, SITO appointed a chair and a cochair who then assembled a working group with specific experience of MP in LT. The Guideline Development Group framed the clinical questions into a patient, intervention, control, and outcome (PICO) format, extracted and analyzed the available literature, ranked the quality of the evidence, and prepared and graded the recommendations. Recommendations were then discussed by all the members of the SITO and were voted on via the Delphi method by an institutional review board. Finally, they were evaluated and scored by a panel of external reviewers. All available literature was analyzed, and its quality was ranked. A total of 18 recommendations regarding the use and the efficacy of ex situ hypothermic and normothermic machine perfusion and sequential normothermic regional perfusion and ex situ MP were prepared and graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. A critical and scientific approach is required for the safe implementation of this new technology.

Outcome after ex situ or ante situm liver resection with hypothermic perfusion and auto-transplantation: A single-centre experience in adult and paediatric patients.

BACKGROUND: Evolving surgical technology and medical treatment have led to an expansion of indications to enable resection of large hepatic tumours with involvement of other abdominal structures. METHODS: Twelve extended liver and abdominal resections, either ex situ with auto-transplantation of the liver remnant or ante situm with veno-venous bypass (VVBP) were performed between 2016 and 2018. We describe our preoperative assessment, compare surgical strategies and assess outcomes. RESULTS: The median age of the 10 adult patients was 50.5 years with a majority suffering from sarcoma-like tumours. The two paediatric patients were 3 and 8 years of age, both with hepatoblastoma. Two patients underwent ex situ resections with auto-transplantation of the liver remnant, and nine patients had ante situm tumour removal with the use of VVBP in four. All patients achieved a good immediate liver function. Local infection and acute kidney injury were found in two patients. One patient underwent biliary reconstruction for bile leak. Tumour recurrence was seen in seven patients (58.3%), with four lung metastases. Five patients died from tumour recurrence (41.7%) during the follow-up. CONCLUSION: Extreme liver resections should be performed in experienced centres, where surgical subspecialties are available with access to cardiovascular support. Additionally, experience in split and living-donor liver transplantation is beneficial.

Preventing Tumour Recurrence after Liver Transplantation: The Role of Machine Perfusion.

Tumour recurrence is currently a hot topic in liver transplantation. The basic mechanisms are increasingly discussed, and, for example, recurrence of hepatocellular carcinoma is often described in pre-injured donor livers, which frequently suffer from significant ischemia/reperfusion injury. This review article highlights the underlying mechanisms and describes the specific tissue milieu required to promote tumour recurrence after liver transplantation. We summarise the current literature in this field and show risk factors that contribute to a pro-tumour-recurrent environment. Finally, the potential role of new machine perfusion technology is discussed, including the most recent data, which demonstrate a protective effect of hypothermic oxygenated perfusion before liver transplantation.