Assessment of liver graft quality during hypothermic oxygenated perfusion: the first international validation study.

BACKGROUND AND AIM: While it is currently assumed that liver assessment is only possible during normothermic machine perfusion (NMP), there is uncertainty regarding a reliable and quick prediction of graft injury during ex situ hypothermic oxygenated perfusion (HOPE). We therefore intended to test, in an international liver transplant cohort, recently described mitochondrial injury biomarkers measured during HOPE before liver transplantation. STUDY DESIGN: Perfusate samples of human livers from 10 centers in 7 countries with HOPE-experience were analyzed for released mitochondrial compounds, i.e. flavin mononucleotide (FMN), NADH, purine derivates and inflammatory markers. Perfusate FMN was correlated with graft loss due to primary non-function or symptomatic non-anastomotic biliary strictures (NAS), and kidney failure, as well as liver injury after transplantation. Livers deemed unsuitable for transplantation served as negative control. RESULTS: We collected 473 perfusate samples of human DCD (n=315) and DBD livers (n=158). Fluorometric assessment of FMN in perfusate was validated by mass spectrometry (R=0.7011,p<0.0001). Graft loss due to primary non-function or cholangiopathy was predicted by perfusate FMN values (c-statistic mass spectrometry 0.8418 (95%CI 0.7466-0.9370,p<0.0001), c-statistic fluorometry 0.7733 (95%CI 0.7006-0.8461,p<0.0001). Perfusate FMN values were also significantly correlated with symptomatic NAS and kidney failure, and superior in prediction of graft loss when compared to conventional scores derived from donor and recipient parameters, such as the donor risk index and the balance of risk score. Mitochondrial FMN values in liver tissues of non-utilized livers were low, and inversely correlated to high perfusate FMN values and purine metabolite release. CONCLUSIONS: This first international study validates the predictive value of the mitochondrial co-factor FMN, released from complex I during HOPE, and may therefore contribute to a better risk stratification of injured livers before implantation. IMPACT AND IMPLICATIONS: Analysis of 473 perfusates, collected from 10 international centers during hypothermic oxygenated perfusion (HOPE), revealed that mitochondria derived flavin mononucleotide (FMN) values in perfusate is predictive for graft loss, cholangiopathy, and kidney failure after liver transplantation. This result is of high clinical relevance, as recognition of graft quality is urgently needed to improve the safe utilization of marginal livers. Ex-situ machine perfusion approaches, such as HOPE, are therefore likely to increase the number of useable liver grafts.

Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study).

BACKGROUND & AIMS: Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). RESULTS: We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p = 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p = 0.26, p = 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.

Porto-sinusoidal vascular disorder in surgical candidates for liver metastases: Prevalence, non-invasive diagnosis, and burden on surgical outcomes.

BACKGROUND & AIMS: Chemotherapy can cause vascular and metabolic liver injury in patients with liver metastases, but scarce data is available. We aimed to i) describe the prevalence of porto-sinusoidal vascular disorder (PSVD) among patients undergoing resection for liver metastases; ii) assess whether liver (LSM) and spleen stiffness measurements (SSM) could diagnose PSVD and predict post-operative complications. METHODS: This is a prospective single center study enrolling consecutive patients undergoing hepatic resection for metastases at a tertiary center. For each patient we evaluated previous exposure to chemotherapy, co-morbidities, elastography, type of surgery, histological features at the resection specimen, morbidity [post-hepatectomy liver failure (PHLF), major complications according to Clavien-Dindo], and 90-days survival. RESULTS: Sixty-eight patients were included, of whom 60 (88%) had received chemotherapy. Twenty-nine (44%) patients had PSVD. SSM <21 kPa (NPV 87%) and >40 kPa (PPV 100%) could accurately diagnose PSVD. PSVD significantly increased the risk of PHLF (22 vs 45%) and major complications (11 vs 31%). Pre-operative LSM was associated with post-operative morbidity. The cut-offs LSM <4.5 kPa and >8 kPa predicted the risk of clinically significant PHLF (0%, 11%, and 33% in LSM <4.5 kPa, 4.5-8 kPa,>8 kPa respectively) and major complications (0%, 25%, 44% in LSM <4.5 kPa, 4.5-8 kPa,>8 kPa, respectively). CONCLUSIONS: PSVD is very common among patients undergoing liver surgery for metastases and it is associated with increased morbidity. LSM and SSM can correctly identify patients with PSVD and those at risk of clinically relevant post-operative complications.

Are there any benefits of prolonged hypothermic oxygenated perfusion?: Results from a national retrospective study.

Dual hypothermic oxygenated perfusion (DHOPE) is increasingly being used to extend liver preservation to improve transplant logistics. However, little is known about its benefits in high-risk liver grafts. This study aimed to investigate whether prolonged DHOPE provides benefits other than improved logistics in all liver types. We performed a national retrospective cohort study of 177 liver transplants from 12 Italian centers preserved with DHOPE for ≥4 hours between 2015 and 2022. A control group of 177 DHOPEs of <4 hours during the same period was created using 1:1 propensity score matching. The impact of risk profiles and preservation times on the outcomes was assessed using univariable and multivariable regression models. No significant differences in posttransplant outcomes were found between prolonged and short DHOPEs. However, the prolonged group had a significantly lower incidence of posttransplant acute kidney injury (AKI) compared to the short group (30.5% vs. 44.6%, p = 0.008). Among prolonged DHOPEs, no differences in transplant outcomes were observed according to donor risk index, Eurotransplant definition for marginal grafts, and balance of risk score. DHOPE duration was associated with a lower risk of AKI in multivariable models adjusted for donor risk index, Eutrotransplant marginal grafts, and balance of risk score. Prolonged hypothermic oxygenated perfusion confirmed its protective effect against AKI in a multivariable model adjusted for donor and recipient risk factors [OR: 0.412, 95% CI: 0.200-0.850, p = 0.016]. Prolonged DHOPE is widely used to improve transplant logistics, provides good results with high-risk grafts, and appears to be associated with a lower risk of posttransplant AKI. These results provide further insight into the important role of DHOPE in preventing posttransplant complications.

Recipient hepatectomy technique may affect oncological outcomes of liver transplantation for hepatocellular carcinoma.

To date, caval sparing (CS) and total caval replacement (TCR) for recipient hepatectomy in liver transplantation (LT) have been compared only in terms of surgical morbidity. Nonetheless, the CS technique is inherently associated with an increased manipulation of the native liver and later exclusion of the venous outflow, which may increase the risk of intraoperative shedding of tumor cells when LT is performed for HCC. A multicenter, retrospective study was performed to assess the impact of recipient hepatectomy (CS vs. TCR) on the risk of posttransplant HCC recurrence among 16 European transplant centers that used either TCR or CS recipient hepatectomy as an elective protocol technique. Exclusion criteria comprised cases of non-center-protocol recipient hepatectomy technique, living-donor LT, HCC diagnosis suspected on preoperative imaging but not confirmed at the pathological examination of the explanted liver, HCC in close contact with the IVC, and previous liver resection for HCC. In 2420 patients, CS and TCR approaches were used in 1452 (60%) and 968 (40%) cases, respectively. Group adjustment with inverse probability weighting was performed for high-volume center, recipient age, alcohol abuse, viral hepatitis, Child-Pugh class C, Model for End-Stage Liver Disease score, cold ischemia time, clinical HCC stage within Milan criteria, pre-LT downstaging/bridging therapies, pre-LT alphafetoprotein serum levels, number and size of tumor nodules, microvascular invasion, and complete necrosis of all tumor nodules (matched cohort, TCR, n = 938; CS, n = 935). In a multivariate cause-specific hazard model, CS was associated with a higher risk of HCC recurrence (HR: 1.536, p = 0.007). In conclusion, TCR recipient hepatectomy, compared to the CS approach, may be associated with some protective effect against post-LT tumor recurrence.

Higher Postoperative Mortality and Inferior Survival After Right-Sided Liver Resection for Perihilar Cholangiocarcinoma: Left-Sided Resection is Preferred When Possible.

BACKGROUND: A right- or left-sided liver resection can be considered in about half of patients with perihilar cholangiocarcinoma (pCCA), depending on tumor location and vascular involvement. This study compared postoperative mortality and long-term survival of right- versus left-sided liver resections for pCCA. METHODS: Patients who underwent major liver resection for pCCA at 25 Western centers were stratified according to the type of hepatectomy-left, extended left, right, and extended right. The primary outcomes were 90-day mortality and overall survival (OS). RESULTS: Between 2000 and 2022, 1701 patients underwent major liver resection for pCCA. The 90-day mortality was 9% after left-sided and 18% after right-sided liver resection (p < 0.001). The 90-day mortality rates were 8% (44/540) after left, 11% (29/276) after extended left, 17% (51/309) after right, and 19% (108/576) after extended right hepatectomy (p < 0.001). Median OS was 30 months (95% confidence interval [CI] 27-34) after left and 23 months (95% CI 20-25) after right liver resection (p < 0.001), and 33 months (95% CI 28-38), 27 months (95% CI 23-32), 25 months (95% CI 21-30), and 21 months (95% CI 18-24) after left, extended left, right, and extended right hepatectomy, respectively (p < 0.001). A left-sided resection was an independent favorable prognostic factor for both 90-day mortality and OS compared with right-sided resection, with similar results after excluding 90-day fatalities. CONCLUSIONS: A left or extended left hepatectomy is associated with a lower 90-day mortality and superior OS compared with an (extended) right hepatectomy for pCCA. When both a left and right liver resection are feasible, a left-sided liver resection is preferred.

The Importance of Multiorgan Procurement in the Improvement of Residents' Open Surgical Skills.

INTRODUCTION: The multiorgan procurement (MOP) represents a chance for the general surgery resident to learn the fundamental steps of open abdominal surgery. The objective of this study was to evaluate the impact of MOP on the residents' open surgical skills. METHODS: Residents' surgical skills were assessed during a 6-month transplant rotation (October 2020-March 2021) using a modified Objective Structured Assessment of Technical Skills with the global rating scale. The surgeries were self-assessed by residents and tutors based on 9 specific steps (SS) and 4 general skills (GS). Each item was rated from 1 (poor) to 5 (excellent) with a maximum score of 45 points for SS and 20 for GS. A crossed-effects linear regression analysis was performed both to evaluate any associations between GS/SS scores and some prespecified covariates, and to study differences in the assessments performed by residents and tutors. RESULTS: Residents actively participated in a total of 59 procurements. In general, there were no significant differences in SS/GS mean scorings between residents (n = 15) and tutors (n = 5). There was a significantly positive association between mean GS/SS scorings and the number of donor surgeries performed (at least 5). Comparing the evaluations of the tutors with the residents, this significance was retained only when scorings were assigned by the tutors. CONCLUSIONS: MOP was shown to improve basic open surgical skills among residents. Awareness of the utility of a clinical rotation in transplant surgery should be raised also on an institutional level.

Achievement of textbook outcome after hepatectomy combined with thermal ablation for colorectal liver metastases.

BACKGROUND: Hepatic resection combined with intraoperative ablation has been described as a technical solution potentially widening the resectability rate of patients with colorectal liver metastases (CRLM). Nevertheless, the perioperative and oncological benefit provided by this combined approach remains unclear. We hypothesized that textbook outcome (TO), which is a composite measure achieved for patients for whom some desired health indicators are met, may help to refine the indications of this approach. METHODS: Patients submitted to hepatectomy with curative intent in combination with radiofrequency ablation or microwave ablation for CRLM ≤ 3 cm in two tertiary referral centers were included. TO was defined according to a recent definition for liver surgery based on a Delphi process including also the achievement of complete radiological response of the ablated lesion/s at 4 weeks. RESULTS: Between 2015 and 2022, 112 patients were enrolled. Among them, 63 (56.2%) achieved a TO. According to multivariate analysis, minimally invasive (MI) approach (OR 2.72, 95% CI 0.99-7.48, p = 0.050), simultaneous CR resection (OR 0.28, 95% CI 0.11-0.70, p = 0.007), tumor burden score (OR 0.89, 95% CI 0.82-0.96, p = 0.004), and major hepatectomy (OR 0.12, 95% CI 0.03-0.52, p = 0.004) were significantly associated with the achievement of TO. Median overall survival was longer in those patients who were able to achieve a TO compared to those who did not. CONCLUSIONS: The combination of hepatectomy and ablation constitutes a valuable solution in patients affected by multiple CRLM and it may provide, also using a MI approach, adequate perioperative and oncological outcomes, allowing to achieve TO, however, in a selected number of patients and depending on several factors including the burden of disease.

The role of cold ischemia time and hypothermic perfusion in predicting early hepatocellular carcinoma recurrences after liver transplantation.

AIM: The aim of the study was to identify predictors of early tumor recurrence in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). METHODS: Retrospective cohort study in 237 consecutive liver recipients with HCC between 2016 and 2021. Multivariate logistic analysis was performed to identify predictors of early HCC recurrences. The impact of hypothermic-oxygenated perfusion (HOPE) on outcome was analyzed after propensity score weighting. RESULTS: Early recurrences were observed in 15 cases. Microvascular invasion (OR 3.737, 95% CI 1.246-11.206, p = 0.019) and cold ischemia time (OR 1.155, 95% CI 1.001-1.333, p = 0.049) were independently associated with a lower risk of HCC recurrences. After balancing for relevant variables, patients in the HOPE group had lower rates of tumor recurrence (weighted OR 0.126, 95% CI 0.016-0.989, p = 0.049) and higher recurrence free survival (weighted HR 0.132, 95% CI 0.017-0.999, p = 0.050). CONCLUSION: Reducing cold ischemia time and graft perfusion with HOPE can lead to lower rates of early HCC recurrences and higher recurrence-free survival.

Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers.

OBJECTIVE: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. BACKGROUND: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. METHODS: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. RESULTS: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. CONCLUSION: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.

The Effect of a Liver Transplant Program on the Outcomes of Resectable Hepatocellular Carcinoma: A Nationwide Multicenter Analysis.

OBJECTIVE: To evaluate the effect of a liver transplantation (LT) program on the outcomes of resectable hepatocellular carcinoma (HCC). BACKGROUND: Surgical treatment of HCC includes both hepatic resection (HR) and LT. However, the presence of cirrhosis and the possibility of recurrence make the management of this disease complex and probably different according to the presence of a LT program. METHODS: Patients undergoing HR for HCC between January 2005 and December 2019 were identified from a national database of HCC. The main study outcomes were major surgical complications according to the Comprehensive Complication Index, posthepatectomy liver failure (PHLF), 90-day mortality, overall survival, and disease-free survival. Secondary outcomes were salvage liver transplantation (SLT) and postrecurrence survival. RESULTS: A total of 3202 patients were included from 25 hospitals over the study period. Three of 25 (12%) had an LT program. The presence of an LT program within a center was associated with a reduced probability of PHLF (odds ratio=0.38) but not with overall survival and disease-free survival. There was an increased probability of SLT when HR was performed in a transplant hospital (odds ratio=12.05). Among transplant-eligible patients, those who underwent LT had a significantly longer postrecurrence survival. CONCLUSIONS: This study showed that the presence of a LT program was associated with decreased PHLF rates and an increased probability to receive SLT in case of recurrence.

Beyond the Concepts of Elder and Marginal in DCD Liver Transplantation: A Prospective Observational Matched-Cohort Study in the Italian Clinical Setting.

Donation after circulatory determination of death (DCD) is a valuable strategy to increase the availability of grafts for liver transplantation (LT). As the average age of populations rises, the donor pool is likely to be affected by a potential increase in DCD donor age in the near future. We conducted a prospective cohort study to evaluate post-transplantation outcomes in recipients of grafts from elderly DCD donors compared with younger DCD donors, and elderly donors after brainstem determination of death (DBD). From August 2020 to May 2022, consecutive recipients of deceased donor liver-only transplants were enrolled in the study. DCD recipients were propensity score matched 1:3 to DBD recipients. One-hundred fifty-seven patients were included, 26 of whom (16.6%) were transplanted with a DCD liver graft. After propensity score matching and stratification, three groups were obtained: 15 recipients of DCD donors ≥75 years, 11 recipients of DCD donors <75 years, and 28 recipients of DBD donors ≥75 years. Short-term outcomes, as well as 12 months graft survival rates (93.3%, 100%, and 89.3% respectively), were comparable among the groups. LT involving grafts retrieved from very elderly DCD donors was feasible and safe in an experienced high-volume center, with outcomes comparable to LTs from younger DCD donors and age-matched DBD donors.

Renal Vessel Extension With Cryopreserved Vascular Grafts: Overcoming Surgical Pitfalls in Living Donor Kidney Transplant.

In LDKT, right kidneys and kidneys with anomalous vascularization are often deferred because of concerns on complications and vascular reconstructions. To date, only few reports have examined renal vessel extension with cryopreserved vascular grafts in LDKT. The aim of this study is to investigate the effect of renal vessel extension on short-term outcomes and ischemia times in LDKT. From 2012 to 2020, recipients of LDKT with renal vessels extension were compared with standard LDKT recipients. Subset analysis of rights grafts and grafts with anomalous vascularization, with or without renal vessel extension, was performed. Recipients of LDKT with (n = 54) and without (n = 91) vascular extension experienced similar hospital stays, surgical complications and DGF rates. For grafts with multiple vessels, renal vessel extension granted a faster implantation time (44±5 vs. 72±14 min), which resulted comparable to that of standard anatomy grafts. Right kidney grafts with vascular extension had a faster implantation time compared to right kidney grafts without vascular lengthening (43±5 vs. 58±9 min), and a comparable implantation time to left kidney grafts. Renal vessel extension with cryopreserved vascular grafts allows faster implantation time in right kidney grafts or grafts with anomalous vascularization, maintaining similar surgical and functional outcomes.

Can repeated surgical resection offer a chance of cure for recurrent cholangiocarcinoma?

INTRODUCTION: The incidence of cholangiocarinoma (CCA), as well as the related mortality rate, has progressively increased over the last decades. Nevertheless improvement in patient management, diagnosis and therapies, recurrence rate remains high (50-70%) with a low 5-year survival (7-20%). Palliative chemotherapy and best supportive care are the treatment of choice in case of recurrence. In recent years, some reports have been published on repeated resection suggesting a survival benefit. The aim of this study was to evaluate the long-term outcome of all repeated resections for recurrent CCA in our institution. MATERIALS AND METHODS: We performed a retrospective analysis of all data recorded in our prospective maintained database of all patients who underwent repeated resection for recurrence of any type of CCA (intrahepatic, perihilar, distal, and gallbladder) with curative intent in our institution. RESULTS: Between 1997 and 2017, twenty-six patients underwent repeated surgical resection for recurrent CCA. Median time to first recurrence was 20 months. Site of recurrence was liver in 18 patients (70%), lymph nodes in 6 (23%), and lungs in 2 (7%). Twenty-five patients (96%) underwent upfront surgical resection of the recurrence, while one received preoperative chemotherapy. Median overall and disease-free survival from repeated surgical resection was 21 and 18 months with a 1-, 3-, and 5-year survival of 87, 41, 29% and 75%, 27%, and 17% respectively. Five patients (21%) did not experience recurrence after repeated surgical resection after a median follow-up of 73 months. CONCLUSIONS: Repeated surgical resection of recurrent CCAs is feasible with good postoperative results and can lead to an increase in survival.

Hypothermic oxygenated perfusion in extended criteria donor liver transplantation-A randomized clinical trial.

Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p = .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p = .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p = .03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at six months, in particular cardio-vascular adverse events (p = .04 and p = .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.

Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

BACKGROUND & AIMS: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy. METHODS: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p <0.001) and a higher probability of being transplanted (HR 2.27; 95% CI 1.78-2.90; p = 0.001) in ERA-2 compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio 0.56; 95% CI 0.46-0.68; p = 0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high-volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high-volume center and ERA-2, while MELD ≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD ≥30 priority allocation was associated with improved patient outcomes, although MELD ≥30 was associated with a higher risk of graft loss. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes.

A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation.

BACKGROUND & AIMS: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values. METHODS: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. RESULTS: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups and to provide a valid comparator cohort for future clinical trials. LAY SUMMARY: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2,219 liver transplantations following controlled DCD donation in 17 centres worldwide. Donor and recipient combinations with higher risk had significantly worse outcomes. However, the use of novel organ perfusion technology helped high-risk patients achieve similar outcomes as the benchmark cohort.

Anastomotic Pseudoaneurysm in Kidney Transplant: A Challenging Management for a Rare Entity.

PURPOSE: Anastomotic pseudoaneurysms of transplanted kidneys are a very rare complication encountered in less than 1% of cases. They may be devastating, leading to functional impairment, kidney transplantectomy, or death. Treatment has not been standardized, with open surgical repair considered the safest procedure even if it is often complicated by bleeding and graft loss. The purpose of this case report is to describe an endovascular treatment of this condition, consisting of the combination of coil embolization and arterial stenting. CASE REPORT: A 61-year-old woman developed an anastomotic pseudoaneurysm 2 months after kidney transplantation, causing acute kidney injury related to ab-extrinsic stenosis of the transplant renal artery (TRA) and external iliac artery. The pseudoaneurysm was successfully treated by coil embolization, and the arterial patency was restored by the stenting of TRA and external iliac artery. The patient completely recovered kidney function, and after a 6-month-follow-up, creatinine values were stable with normal renal perfusion. CONCLUSION: Endovascular repair through coil embolization and TRA stenting can be a safe and effective option to treat anastomotic pseudoaneurysm in kidney transplant.

The impact of preservation fluid culture on graft site arteritis: A systematic review and meta-analysis.

BACKGROUND: The role of culturing the graft preservation fluid (PF) is controversial and its impact on graft arteritis development remains unclear. METHODS: Systematic literature search retrieving observational studies comparing solid organ transplant (SOT) recipients with culture-positive PF versus culture-negative PF. The quality of included studies was independently assessed according to the ROBINS-I tool for observational studies. Meta-analysis was performed using Mantel-Haenszel random-effect models. Graft site arteritis within 180 days from transplant was selected as the primary outcome. RESULTS: Twenty-one observational studies (N = 2208 positive PF vs. 4458 negative) were included. Among positive PF, 857 (38.8%) were classified as high-risk group pathogens and 1351 (61.2%) as low-risk pathogens. Low-risk and negative PF showed similar odds ratios. A significant higher risk of graft arteritis was found in SOT recipients with a PF yielding a high-risk pathogen (odds ratio [OR] 18.43, 95% confidence interval [CI] 7.83-43.40) compared to low-risk and negative PF, with low heterogeneity (I2 = 2.24%). Similar results were found considering separately high-risk bacteria (OR 12.02, 95%CI 4.88-29.60) and fungi (OR 71.00, 95%CI 28.07-179.56), with no heterogeneity (I2 = 0%), and in the subgroup analyses of the liver (OR 16.78, 95%CI 2.95-95.47) and kidney (OR 19.90, 95%CI 4.78-82.79) recipients. However, data about diagnostic features of graft arteritis were very limited, indeed for only 11 of the 93 events histological or microbiological results were reported. CONCLUSIONS: Our results may support the performance of PF culturing and a preemptive diagnostic or therapeutic management upon isolation of high-risk pathogens. Further studies based on a reliable diagnosis of graft arteritis are needed.

Assessment and Management of Transplant Renal Artery Stenosis. A Literature Review.

BACKGROUND: Transplant renal artery stenosis (TRAS) following kidney transplantation is a possible cause of graft failure. This review aimed to summarize the evidence about physiopathology, diagnosis and early and late effectiveness of the endovascular treatment (EVT), including angioplasty and stenting procedures. METHODS: A literature research was performed using Pubmed, Scopus and the Cochrane Library databases (January 2000-September 2020) according to PRISMA guidelines. Studies were included if they describe EVT, percutaneous transluminal angioplasty or stent placement of TRAS, published in English and with a minimum of ten patients. RESULTS: Fifty-six studies were included. TRAS incidence ranges from 1% up to 12% in transplanted kidneys. The TRAS risk factors were: elderly donor and recipient, cytomegalovirus match status, Class II Donor Specific Antibodies (DSA), expanded donor criteria, delayed graft functioning and other anatomical and technical factors. The highest frequency of TRAS presentation is after 3-6 months after kidney transplantation. The most frequent localization of stenosis was para-anastomotic (ranging from 25% to 78%). In 9 studies, all patients were treated by percutaneous transluminal angioplasty (PTA), in 16 studies all patients received percutaneous transluminal stenting (PTS) and in 21 series patients received either PTA or PTS. The twelve months patency rates after EVT ranged from 72% to 94%. The overall complication rate was 9%, with pseudoaneurysms and hematomas as most frequent complications. CONCLUSIONS: TRAS can be successfully and safely treated through an endovascular approach. Stent delivery seems to guarantee a higher patency rate compared to simple angioplasty, however further studies are needed to confirm these results.