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Purpose: The aim of this study was to investigate the biodistribution of (super-)selective trans-arterial radioembolization (TARE) with holmium-166 microspheres ( 166 Ho-MS), when administered as adjuvant therapy after RFA of HCC 2-5 cm. The objective was to establish a treatment volume absorbed dose that results in an absorbed dose of ≥ 120 Gy on the hyperemic zone around the ablation necrosis (i.e., target volume)., Methods: In this multicenter, prospective dose-escalation study in BCLC early stage HCC patients with lesions 2-5 cm, RFA was followed by (super-)selective infusion of 166 Ho-MS on day 5-10 after RFA. Dose distribution within the treatment volume was based on SPECT-CT. Cohorts of up to 10 patients were treated with an incremental dose (60 Gy, 90 Gy, 120 Gy) of 166 Ho-MS to the treatment volume. The primary endpoint was to obtain a target volume dose of ≥ 120 Gy in 9/10 patients within a cohort., Results: Twelve patients were treated (male 10; median age, 66.5 years (IQR, [64.3-71.7])) with a median tumor diameter of 2.7 cm (IQR, [2.1-4.0]). At a treatment volume absorbed dose of 90 Gy, the primary endpoint was met with a median absorbed target volume dose of 138 Gy (IQR, [127-145]). No local recurrences were found within 1-year follow-up., Conclusion: Adjuvant (super-)selective infusion of 166 Ho-MS after RFA for the treatment of HCC can be administered safely at a dose of 90 Gy to the treatment volume while reaching a dose of ≥ 120 Gy to the target volume and may be a favorable adjuvant therapy for HCC lesions 2-5 cm., Trial Registration: Clinicaltrials.gov NCT03437382 . (registered: 19-02-2018)., (© 2024. The Author(s).)

Background: The administration of contrast medium is associated with acute kidney injury; however, the effect of exposure of a deceased organ donor to contrast medium on kidney transplant outcomes has been poorly studied., Methods: A retrospective analysis of all deceased kidney donors between 2011 and 2021 and their corresponding recipients in the Netherlands was conducted. Multivariable analyses were performed to assess the associations between contrast medium exposure and delayed graft function (DGF)/graft survival. Linear mixed models were used to assess the differences in mean estimated glomerular filtration rate values in recipients 1 to 6 y after transplantation., Results: In total, 2177 donors and 3638 corresponding kidney graft recipients were included. Twenty-four percent of the donors (n = 520) were exposed to contrast medium, corresponding to 23% of recipients (n = 832). DGF was observed in 36% (n = 1321) and primary nonfunction in 3% (n = 122) of recipients. DGF rates for donation after brain death (DBD) and donation after circulatory death (DCD) donors showed no significant effect of contrast medium exposure ( P  = 0.15 and P  = 0.60 for DBD and DCD donors, respectively). In multivariable analyses, contrast medium administration was not significantly associated with a higher DGF risk (odds ratio 1.06; 95% confidence interval, 0.86-1.36; P  = 0.63) nor was a significant predictor for death-censored graft failure (hazard ratio 1.01; 95% confidence interval, 0.77-1.33; P  = 0.93). Linear mixed models showed no difference in mean estimated glomerular filtration rate values in recipients 1 to 6 y posttransplantation ( P  = 0.78)., Conclusions: This study indicates that contrast medium administration in DBD and DCD donors has no negative effect on early and long-term kidney graft function., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Currently, no practical definition of potentially resectable, borderline or unresectable perihilar cholangiocarcinoma (pCCA) is available. Aim of this study was to define criteria to categorize patients for use in a future neoadjuvant or induction therapy study., Method: Using the modified DELPHI method, hepatobiliary surgeons from all tertiary referral centers in the Netherlands were invited to participate in this study. During five online meetings, predefined factors determining resectability and additional factors regarding surgical resectability and operability were discussed., Results: The five online meetings resulted in 52 statements. After two surveys, consensus was reached in 63% of the questions. The main consensus included a definition regarding potential resectability. 1) Clearly resectable: no vascular involvement (≤90°) of the future liver remnant (FLR) and expected feasibility of radical biliary resection. 2) Clearly unresectable: non-reconstructable venous and/or arterial involvement of the FLR or no feasible radical biliary resection. 3) Borderline resectable: all patients between clearly resectable and clearly unresectable disease., Conclusion: This DELPHI study resulted in a practical and applicable resectability, or more accurate, an explorability classification, which can be used to categorize patients for use in future neoadjuvant therapy studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lynn Nooijen reports financial support was provided by Amsterdam Gastroenterology Endocrinology Metabolism., (© 2023 Published by Elsevier Ltd.)

Background & Aims: In the USA, inequal liver transplantation (LT) access exists between patients with and without hepatocellular carcinoma (HCC). Survival benefit considers survival without and with LT and could equalise LT access. We calculated bias-corrected LT survival benefit for patients with(out) HCC who underwent a transplant, based on longitudinal data in a recent United States cohort., Methods: Adult LT candidates with(out) HCC between 2010 and 2019 were included. Waitlist survival over time was contrasted to post-transplant survival, to estimate 5-year survival benefit from the moment of LT. Waitlist survival was modelled with a bias-corrected Cox regression, and post-transplant survival was estimated through Cox proportional hazards regression., Results: Mean HCC survival without LT was always lower than non-HCC waitlist survival. Below model for end-stage liver disease (sodium) (MELD(-Na)) 30, patients with HCC gained more life-years from LT than patients without HCC at the same MELD(-Na) score. Only patients without HCC below MELD(-Na) 9 had negative benefit. Most patients with HCC underwent a transplant below MELD(-Na) 14, and most patients without HCC underwent a transplant above MELD(-Na) 26. Liver function [MELD(-Na), albumin] was the main predictor of 5-year benefit. Therefore, during 5 years, most patients with HCC gained 0.12 to 1.96 years from LT, whereas most patients without HCC gained 2.48 to 3.45 years., Conclusions: On an individual level, performing a transplant in patients with HCC resulted in survival benefit. However, on a population level, benefit was indirectly decreased, as patients without HCC were likely to gain more survival owing to decreased liver function. For patients who underwent a transplant, a constructed online calculator estimates 5-year survival benefit given specific patient characteristics. Survival benefit scores could serve to equalise LT access., Impact and Implications: Benefit is a comparison of the survival with and without liver transplantation, and it is important when deciding who should undergo a transplant. Liver function is most important when predicting possible benefit from transplantation. Patients with liver cancer die sooner on the waiting list than similar patients without liver cancer. However, patients with liver cancer more often have better liver function. Most patients without liver cancer derive more benefit from transplantation than patients with liver cancer., Competing Interests: The authors of this manuscript have no conflict of interest to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Background: Disseminated disease (DD) is often found at (re-)exploration in gallbladder cancer (GBC) patients. We aimed to assess the yield of staging laparoscopy (SL) and identify predictors for DD., Methods: This retrospective study included patients from all Dutch academic centres with primary GBC (pGBC) and incidentally diagnosed GBC (iGBC) planned for (re-)resection. The yield of SL was determined. In iGBC, predictive factors for DD were assessed., Results: In total, 290 patients were included. Of 183 included pGBC patients, 143 underwent laparotomy without SL, and 42 (29%) showed DD perioperatively. SL, conducted in 40 patients, identified DD in eight. DD was found in nine of 32 patients who underwent laparotomy after SL. Of 107 included iGBC patients, 100 underwent laparotomy without SL, and 19 showed DD perioperatively. SL, conducted in seven patients, identified DD in one. Cholecystitis (OR = 4.25; 95% CI 1.51-11.91) and primary R1/R2 resection (OR = 3.94; 95% CI 1.39-11.19) were independent predictive factors for DD., Conclusions: In pGBC patients, SL may identify DD in up to 20% of patients and should be part of standard management. In iGBC patients, SL is indicated after primary resection for cholecystitis and after initial R1/R2 resection due to the association of these factors with DD., (© 2023. The Author(s).)

Purpose: To investigate the biodistribution of holmium-166 microspheres ( 166 Ho-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to establish a perfused liver administration dose that results in a tumoricidal dose of holmium-166 on the hyperaemic zone around the ablation necrosis (i.e. target volume)., Materials and Methods: This is a multicentre, prospective, dose-escalation study in HCC patients with a solitary lesion 2-5 cm, or a maximum of 3 lesions of ≤ 3 cm each. The day after RFA patients undergo angiography and cone-beam CT (CBCT) with (super)selective infusion of technetium-99 m labelled microalbumin aggregates ( 99m Tc-MAA). The perfused liver volume is segmented from the CBCT and 166 Ho-MS is administered to this treatment volume 5-10 days later. The dose of holmium-166 is escalated in a maximum of 3 patient cohorts (60 Gy, 90 Gy and 120 Gy) until the endpoint is reached. SPECT/CT is used to determine the biodistribution of holmium-166. The endpoint is met when a dose of ≥ 120 Gy has been reached on the target volume in 9/10 patients of a cohort. Secondary endpoints include toxicity, local recurrence, disease-free and overall survival., Discussion: This study aims to find the optimal administration dose of adjuvant radioembolization with 166 Ho-MS after RFA. Ultimately, the goal is to bring the efficacy of thermal ablation up to par with surgical resection for early-stage HCC patients., Trial Registration: Clinicaltrials.gov identifier: NCT03437382., (© 2022. The Author(s).)

Liver function is measured regularly in liver transplantation (LT) candidates. Currently, these previous disease development data are not used for survival prediction. By constructing and validating joint models (JMs), we aimed to predict the outcome based on all available data, using both disease severity and its rate of change over time. Adult LT candidates listed in Eurotransplant between 2007 and 2018 (n = 16 283) and UNOS between 2016 and 2019 (n = 30 533) were included. Patients with acute liver failure, exception points, or priority status were excluded. Longitudinal MELD(-Na) data were modeled using spline-based mixed effects. Waiting list survival was modeled with Cox proportional hazards models. The JMs combined the longitudinal and survival analysis. JM 90-day mortality prediction performance was compared to MELD(-Na) in the validation cohorts. MELD(-Na) score and its rate of change over time significantly influenced patient survival. The JMs significantly outperformed the MELD(-Na) score at baseline and during follow-up. At baseline, MELD-JM AUC and MELD AUC were 0.94 (0.92-0.95) and 0.87 (0.85-0.89), respectively. MELDNa-JM AUC was 0.91 (0.89-0.93) and MELD-Na AUC was 0.84 (0.81-0.87). The JMs were significantly (p < .001) more accurate than MELD(-Na). After 90 days, we ranked patients for LT based on their MELD-Na and MELDNa-JM survival rates, showing that MELDNa-JM-prioritized patients had three times higher waiting list mortality., (© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: The utilization of liver allografts could be optimized if nonacceptance is predicted. This study aimed to evaluate the prognostic ability of an updated Discard Risk Index in Eurotransplant., Materials and Methods: Potential deceased donors from January 2010 to December 2015 who had been reported to Eurotransplant were included in our analyses. Liver utilization was defined by transplant status as the primary outcome to evaluate the performance of the Eurotransplant-developed Discard Risk Index., Results: Of 11670 potential livers, 9565 (81%) were actually transplanted. Donor sex, age, history of diabetes, drug abuse, use of vasopressors, body mass index category, serum sodium, cause of death, donor type, and levels of C-reactive protein, bilirubin, aspartate and alanine aminotransferases, international normalized ratio, and gamma-glutamyltranspeptidase were associated with discard and combined in the Eurotransplant-developed Discard Risk Index. Correlation between the two Discard Risk Indexes was high (r = 0.86), and both achieved high C statistics of 0.72 and 0.75 (P < .001), respectively. Despite strong calibration, discard rates of 0.8% for overall donors and 6% of donors after circulatory death could be predicted with 80% accuracy., Conclusions: The Eurotransplant-developed Discard Risk Index showed a high prognostic ability to predict liver utilization in a European setting. The model could therefore be valuable for identifying livers at high risk of not being transplanted in an early stage. These organs might profit the most from modified allocation strategies or advanced preservation techniques.

Background & Aims: Hepatocellular adenomas (HCA) rarely occur in males, and if so, are frequently associated with malignant transformation. Guidelines are based on small numbers of patients and advise resection of HCA in male patients, irrespective of size or subtype. This nationwide retrospective cohort study is the largest series of HCA in men correlating (immuno)histopathological and molecular findings with the clinical course., Methods: Dutch male patients with available histological slides with a (differential) diagnosis of HCA between 2000 and 2017 were identified through the Dutch Pathology Registry (PALGA). Histopathology and immunohistochemistry according to international guidelines were revised by two expert hepatopathologists. Next generation sequencing (NGS) was performed to confirm hepatocellular carcinoma (HCC) and/or subtype HCA. Final pathological diagnosis was correlated with recurrence, metastasis and death., Results: A total of 66 patients from 26 centres fulfilling the inclusion criteria with a mean (±SD) age of 45.0 ± 21.6 years were included. The diagnosis was changed after expert revision and NGS in 33 of the 66 patients (50%). After a median follow-up of 9.6 years, tumour-related mortality of patients with accessible clinical data was 1/18 (5.6%) in HCA, 5/14 (35.7%) in uncertain HCA/HCC and 4/9 (44.4%) in the HCC groups (P = .031). Four B-catenin mutated HCA were identified using NGS, which were not yet identified by immunohistochemistry and expert revision., Conclusions: Expert revision with relevant immunohistochemistry may help the challenging but prognostically relevant distinction between HCA and well-differentiated HCC in male patients. NGS may be more important to subtype HCA than indicated in present guidelines., (© 2021 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background & Aims: Acute-on-chronic liver failure (ACLF) is usually associated with a precipitating event and results in the failure of other organ systems and high short-term mortality. Current prediction models fail to adequately estimate prognosis and need for liver transplantation (LT) in ACLF. This study develops and validates a dynamic prediction model for patients with ACLF that uses both longitudinal and survival data., Methods: Adult patients on the UNOS waitlist for LT between 11.01.2016-31.12.2019 were included. Repeated model for end-stage liver disease-sodium (MELD-Na) measurements were jointly modelled with Cox survival analysis to develop the ACLF joint model (ACLF-JM). Model validation was carried out using separate testing data with area under curve (AUC) and prediction errors. An online ACLF-JM tool was created for clinical application., Results: In total, 30,533 patients were included. ACLF grade 1 to 3 was present in 16.4%, 10.4% and 6.2% of patients, respectively. The ACLF-JM predicted survival significantly ( p <0.001) better than the MELD-Na score, both at baseline and during follow-up. For 28- and 90-day predictions, ACLF-JM AUCs ranged between 0.840-0.871 and 0.833-875, respectively. Compared to MELD-Na, AUCs and prediction errors were improved by 23.1%-62.0% and 5%-37.6% respectively. Also, the ACLF-JM could have prioritized patients with relatively low MELD-Na scores but with a 4-fold higher rate of waiting list mortality., Conclusions: The ACLF-JM dynamically predicts outcome based on current and past disease severity. Prediction performance is excellent over time, even in patients with ACLF-3. Therefore, the ACLF-JM could be used as a clinical tool in the evaluation of prognosis and treatment in patients with ACLF., Lay Summary: Acute-on-chronic liver failure (ACLF) progresses rapidly and often leads to death. Liver transplantation is used as a treatment and the sickest patients are treated first. In this study, we develop a model that predicts survival in ACLF and we show that the newly developed model performs better than the currently used model for ranking patients on the liver transplant waiting list., Competing Interests: The authors of this manuscript have no conflict of interest to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Author(s).)

Background: Data on surgical outcomes of laparoscopic liver resection (LLR) versus open liver resection (OLR) of benign liver tumour (BLT) are scarce. This study aimed to provide a nationwide overview of postoperative outcomes after LLR and OLR of BLT., Methods: This was a nationwide retrospective study including all patients who underwent liver resection for hepatocellular adenoma, haemangioma and focal nodular hyperplasia in the Netherlands from 2014 to 2019. Propensity score matching (PSM) was applied to compare 30-day overall and major morbidity and 30-day mortality after OLR and LLR., Results: In total, 415 patients underwent BLT resection of whom 230 (55.4%) underwent LLR. PSM for OLR and LLR resulted in 250 matched patients. Median (IQR) length of stay was shorter after LLR than OLR (4 versus 6 days, 5.0-8.0, p < 0.001). Postoperative 30-day overall morbidity was lower after LLR than OLR (12.0% vs. 22.4%, p = 0.043). LLR was associated with reduced 30-day overall morbidity in multivariable analysis (aOR:0.46, CI:0.22-0.95, p = 0.043). Both 30-day major morbidity and 30-day mortality were not different., Conclusions: LLR for BLT is associated with shorter hospital stay and reduced overall morbidity and is preferred if technically feasible., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: The United Network for Organ Sharing's Model for End-Stage Liver Disease (UNOS-MELD) score is the basis of liver allocation in the Eurotransplant region. It was constructed 20 years ago in a small US cohort and has remained unchanged ever since. The best boundaries and coefficients were never calculated for any region outside the United States. Therefore, this study refits the MELD (reMELD) for the Eurotransplant region., Approach and Results: All adult patients listed for a first liver transplantation between January 1, 2007, and December 31, 2018, were included. Data were randomly split in a training set (70%) and a validation set (30%). In the training data, generalized additive models with splines were plotted for each MELD parameter. The lower and upper bound combinations with the maximum log-likelihood were chosen for the final models. The refit models were tested in the validation data with C-indices and Brier scores. Through likelihood ratio tests the refit models were compared to UNOS-MELD. The correlation between scores and survival of prioritized patients was calculated. A total of 6,684 patients were included. Based on training data, refit parameters were capped at creatinine 0.7-2.5, bilirubin 0.3-27, international normalized ratio 0.1-2.6, and sodium 120-139. ReMELD and reMELD-Na showed C-indices of 0.866 and 0.869, respectively. ReMELD-Na prioritized patients with 1.6 times higher 90-day mortality probabilities compared to UNOS-MELD., Conclusions: Refitting MELD resulted in new lower and upper bounds for each parameter. The predictive power of reMELD-Na was significantly higher than UNOS-MELD. ReMELD prioritized patients with higher 90-day mortality rates. Thus, reMELD(-Na) should replace UNOS-MELD for liver graft allocation in the Eurotransplant region., (© 2020 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

The MELD score is used in the Eurotransplant (ET) region to allocate liver grafts. Hyponatremia in cirrhotic patients is an important predictor of death but is not incorporated in MELD. This study investigated the performance of the MELD-Na score for the ET region. All adult patients with chronic liver disease on the ET liver transplantation waiting list (WL) allocated through lab MELD scores were included. The MELD-corrected effect of serum sodium (Na) concentration at listing on the 90-day WL mortality was calculated using Cox regression. The MELD-Na performance was assessed with c-indices, calibration per decile and Brier scores. The reclassification from MELD to MELD-Na score was calculated to estimate the impact of MELD-Na-based allocation in the ET region. For the 5223 included patients, the risk of 90-day WL death was 2.9 times higher for hyponatremic patients. The MELD-Na had a significantly higher c-index of 0.847 (SE 0.007) and more accurate 90-day mortality prediction compared to MELD (Brier score of 0.059 vs 0.061). It was estimated that using MELD-Na would reduce WL mortality by 4.9%. The MELD-Na score yielded improved prediction of 90-day WL mortality in the ET region and using MELD-Na for liver allocation will very likely reduce WL mortality., (© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: It is controversial whether patients with gallbladder cancer (GBC) presenting with jaundice benefit from resection. This study re-evaluates the impact of jaundice on resectability and survival., Methods: Data was collected on surgically explored GBC patients in all Dutch academic hospitals from 2000 to 2018. Survival and prognostic factors were assessed., Results: In total 202 patients underwent exploration and 148 were resected; 124 non-jaundiced patients (104 resected) and 75 jaundiced patients (44 resected). Jaundiced patients had significantly (P < 0.05) more pT3/T4 tumors, extended (≥3 segments) liver- and organ resections, major post-operative complications and margin-positive resection. 90-day mortality was higher in jaundiced patients (14% vs. 0%, P < 0.001). Median overall survival (OS) was 7.7 months in jaundiced patients (2-year survival 17%) vs. 26.1 months in non-jaundiced patients (2-year survival 39%, P < 0.001). In multivariate analysis, jaundice (HR1.89) was a poor prognostic factor for OS in surgically explored but not in resected patients. Six jaundiced patients did not develop a recurrence; none had liver- or common bile duct (CBD) invasion on imaging., Conclusion: Jaundice is associated with poor survival. However, jaundice is not an independent adverse prognostic factor in resected patients. Surgery should be considered in patients with limited disease and no CBD invasion on imaging., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Predicting survival of recipients after liver transplantation is regarded as one of the most important challenges in contemporary medicine. Hence, improving on current prediction models is of great interest.Nowadays, there is a strong discussion in the medical field about machine learning (ML) and whether it has greater potential than traditional regression models when dealing with complex data. Criticism to ML is related to unsuitable performance measures and lack of interpretability which is important for clinicians., Methods: In this paper, ML techniques such as random forests and neural networks are applied to large data of 62294 patients from the United States with 97 predictors selected on clinical/statistical grounds, over more than 600, to predict survival from transplantation. Of particular interest is also the identification of potential risk factors. A comparison is performed between 3 different Cox models (with all variables, backward selection and LASSO) and 3 machine learning techniques: a random survival forest and 2 partial logistic artificial neural networks (PLANNs). For PLANNs, novel extensions to their original specification are tested. Emphasis is given on the advantages and pitfalls of each method and on the interpretability of the ML techniques., Results: Well-established predictive measures are employed from the survival field (C-index, Brier score and Integrated Brier Score) and the strongest prognostic factors are identified for each model. Clinical endpoint is overall graft-survival defined as the time between transplantation and the date of graft-failure or death. The random survival forest shows slightly better predictive performance than Cox models based on the C-index. Neural networks show better performance than both Cox models and random survival forest based on the Integrated Brier Score at 10 years., Conclusion: In this work, it is shown that machine learning techniques can be a useful tool for both prediction and interpretation in the survival context. From the ML techniques examined here, PLANN with 1 hidden layer predicts survival probabilities the most accurately, being as calibrated as the Cox model with all variables., Trial Registration: Retrospective data were provided by the Scientific Registry of Transplant Recipients under Data Use Agreement number 9477 for analysis of risk factors after liver transplantation.

Background: While most of the evidence on minimally invasive liver surgery (MILS) is derived from expert centers, nationwide outcomes remain underreported. This study aimed to evaluate the implementation and outcome of MILS on a nationwide scale., Methods: Electronic patient files were reviewed in all Dutch liver surgery centers and all patients undergoing MILS between 2011 and 2016 were selected. Operative outcomes were stratified based on extent of the resection and annual MILS volume., Results: Overall, 6951 liver resections were included, with a median annual volume of 50 resections per center. The overall use of MILS was 13% (n = 916), which varied from 3% to 36% (P < 0.001) between centers. The nationwide use of MILS increased from 6% in 2011 to 23% in 2016 (P < 0.001). Outcomes of minor MILS were comparable with international studies (conversion 0-13%, mortality <1%). In centers which performed ≥20 MILS annually, major MILS was associated with less conversions (14 (11%) versus 41 (30%), P < 0.001), shorter operating time (184 (117-239) versus 200 (139-308) minutes, P = 0.010), and less overall complications (37 (30%) versus 58 (42%), P = 0.040)., Conclusion: The nationwide use of MILS is increasing, although large variation remains between centers. Outcomes of major MILS are better in centers with higher volumes., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: In most western countries, the median donor age is increasing. The incidence of malignancies in older populations is increasing as well. To prevent donor-derived malignancies we evaluated radiologic donor screening in a retrospective donor cohort., Methods: This study analyzes the efficacy of a preoperative computed tomography (CT) scan on detecting malignancies. All deceased organ donors in the Netherlands between January 2013 and December 2017 were included. Donor reports were analyzed to identify malignancies detected before or during organ procurement. Findings between donor screening with or without CT-scan were compared., Results: Chest or abdominal CT-scans were performed in 17% and 18% of the 1644 reported donors respectively. Screening by chest CT-scan versus radiograph resulted in 1.5% and 0.0% detected thoracic malignancies respectively. During procurement no thoracic malignancies were found in patients screened by chest CT compared with 0.2% malignancies in the radiograph group. Screening by abdominal CT-scan resulted in 0.0% malignancies, compared with 0.2% in the abdominal ultrasound group. During procurement 1.0% and 1.3% malignancies were found in the abdominal CT-scan and ultrasound groups, respectively., Conclusions: Screening by CT-scan decreased the perioperative detection of tumors by 30%. A preoperative CT-scan may be helpful by providing additional information on (aberrant) anatomy to the procuring or transplanting surgeon. In conclusion, donor screening by CT-scan could decrease the risk of donor-derived malignancies and prevents unnecessary procurements per year in the Netherlands., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2019 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Simultaneous pancreas-kidney transplant is the ultimate therapy for patients who have uncontrolled and complicated type 1 diabetes mellitus with end-stage renal disease. The combined pancreas transplant provides a euglycemic milieu for the kidney and protects it from recurrence of diabetic complications. Our patient, a 41-year-old woman with end-stage diabetic nephropathy and history of multiple abdominal surgeries (ovarian cyst fenestration, adnexal extirpation, abdominal wall reconstruction), including urinary diversion (Bricker loop, above double J stent), underwent simultaneous pancreas-kidney transplant. After reperfusion, the kidney had immediate function and creatinine levels dropped to normal levels during the early postoperative period (creatinine of 102 μmol/L, estimated glomerular filtration rate of 52 mL/min/1.73 m2) and remained stable during follow-up. Serum glucose levels dropped to within normal ranges postoperatively and remained so during follow-up. The postoperative course was complicated by hydronephrosis due to transient edema of the anastomosis of the ureter to the Bricker loop, after early incidental removal of the double J catheter. This was successfully treated with a temporary percutaneous nephrostomy. Multiple previous surgeries, including a Bricker deviation, may not be a definitive contraindication for simultaneous pancreas-kidney transplant. In selected cases, special considerations may lead to a successful procedure providing better quality of life and life expectancy, even for patients with multiple comorbidities.

Introduction: The success of pancreas transplantation, in combination with a stable number of available allografts has resulted in an increasing waiting list. This study investigated donor potential by expanding age and Body Mass Index (BMI) criteria., Methods: All reported donors in the Netherlands between 2013 and 2017 were analysed. Risk assessment of extended criteria donors was done by in-depth analysis of donor reports and calculation of the Pancreas Donor Risk Index (PDRI). The PDRI of these extended criteria donors was compared to standard criteria donors to evaluate the increased risk on graft failure., Results: A total of 1273 donors were reported. Of these donors, 405 donors were reported as pancreas donor, of which 93 (23%) pancreata were transplanted. Extending age criterion with 5 years could result in additional 40 Donation after Brain Death donors and 37 Donation after Circulatory Death donors reported. In 24 (31%) extended age criteria donors the PDRI was below the upper limit of currently transplanted pancreata. Extending BMI criteria to 35 kg/m 2 could result in an additional 19 (6%) donors reported., Conclusions: Extending BMI criteria could result in a slight increase of reported donors. Extending age criteria increased significantly the number of reported donors. In 24 (31%) of the older donors the PDRI showed a reduced risk compared to currently transplanted pancreata. This study suggest that, if other risk factors are absent, pancreata of extended age and/or BMI criteria donors should be considered for transplantation., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: About 15% of liver transplantations (LTs) in Eurotransplant are currently performed in patients with a high-urgency (HU) status. Patients who have acute liver failure (ALF) or require an acute retransplantation can apply for this status. This study aims to evaluate the efficacy of this prioritization., Methods: Patients who were listed for LT with HU status from January 1, 2007, up to December 31, 2015, were included. Waiting list and posttransplantation outcomes were evaluated and compared with a reference group of patients with laboratory Model for End-Stage Liver Disease (MELD) score (labMELD) scores ≥40 (MELD 40+)., Results: In the study period, 2299 HU patients were listed for LT. Ten days after listing, 72% of all HU patients were transplanted and 14% of patients deceased. Patients with HU status for primary ALF showed better patient survival at 3 years (69%) when compared with patients in the MELD 40+ group (57%). HU patients with labMELD ≥45 and patients with HU status for acute retransplantation and labMELD ≥35 have significantly inferior survival at 3-year follow-up of 46% and 42%, respectively., Conclusions: Current prioritization for patients with ALF is highly effective in preventing mortality on the waiting list. Although patients with HU status for ALF have good outcomes, survival is significantly inferior for patients with a high MELD score or for retransplantations. With the current scarcity of livers in mind, we should discuss whether potential recipients for a second or even third retransplantation should still receive absolute priority, with HU status, over other recipients with an expected, substantially better prognosis after transplantation.

Background: Several risk models to predict outcome after liver transplantation (LT) have been developed in the last decade. This study compares the predictive performance of 7 risk models., Methods: Data on 62 294 deceased donor LTs performed in recipients ≥18 years old between January 2005 and December 2015 in the United Network for Organ Sharing region were used for this study. The balance of risk, donor risk index (DRI), Eurotransplant-DRI, donor-to-recipient model (DRM), simplified recipient risk index, Survival Outcomes Following Liver Transplantation (SOFT), and donor Model for End-stage Liver Disease scores were calculated, and calibration and discrimination were evaluated for patient, overall graft, and death-censored graft survival. Calibration was evaluated by outcome of high-risk transplantations (>80th percentile of the respective risk score) and discrimination by concordance index (c-index)., Results: Patient survival at 3 months was best predicted by the SOFT (c-index: 0.68) and Balance of Risk score (c-index: 0.64), while the DRM and SOFT score had the highest predictive capacity at 60 months (c-index: 0.59). Overall, graft survival was best predicted by the SOFT score at 3-month follow-up (c-index: 0.65) and by the SOFT and DRM at 60-month follow-up (c-index: 0.58). Death-censored graft survival at 60-month follow-up is best predicted by the DRI (c-index: 0.59) and Eurotransplant-DRI (c-index: 0.58). For patient and overall graft survival, high-risk transplantations were best defined by the DRM. For death-censored graft survival, this was best defined by the DRI., Conclusions: This study shows that models dominated by recipient factors have the best performance for short-term patient survival. Models that also include sufficient donor factors have better performance for long-term graft survival. Death-censored graft survival is best predicted by models that predominantly included donor factors.

Complete graft thrombosis is the leading cause of early graft loss following pancreas transplantation. Partial thrombosis is usually subclinical and discovered on routine imaging. Treatment options may vary in such cases. We describe the incidence and relevance of partial graft thrombosis in a large transplant center. All consecutive pancreas transplantation at our center (2004-2015) were included in this study. Radiological follow-up, type and quantity of thrombosis prophylaxis, complications and, graft and patient survival were collected. Partial thrombosis and follow-up were also studied. All 230 pancreas transplantations were included in the analysis. Computed tomography was performed in most cases (89.1%). Early graft failure occurred in 23 patients (13/23 due to graft thrombosis, 3/23 bleeding, 1/23 anastomotic leakage, 6/23 secondary to antibody mediated rejection). There was evidence of partial thrombosis in 59 cases (26%), of which the majority was treated with heparin and a vitamin K antagonist with graft preservation in 57/59 patients (97%). Thrombosis is the leading cause of early graft loss following pancreas transplantation. Computed tomography allows for early detection of partial thrombosis, which is usually subclinical. Partial graft thrombosis occurs in about 25% of all cases. In this series, treatment with anticoagulant therapy (heparin and vitamin K antagonist) resulted in graft preservation in almost all cases., (© 2018 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Acceptance criteria for liver allografts are ever more expanding because of a persisting wait-list mortality. Older livers are therefore offered and used more frequently for transplantation. This study aims to analyze the use and longterm outcome of these transplantations. Data were included on 17,811 first liver transplantations (LTs) and information on livers that were reported for allocation but not transplanted from 2000 to 2015 in the Eurotransplant (ET) region. Graft survival was defined as the period between transplantation and date of retransplantation or date of recipient death. In the study period, 2394 (13%) transplantations were performed with livers ≥70 years old. Graft survival was 74%, 57%, and 41% at 1-, 5-, and 10-year follow-up, respectively. A history of diabetes mellitus in the donor (hazard ratio [HR], 1.3; P = 0.01) and positive hepatitis C virus antibody in the recipient (HR, 1.5; P < 0.001) are specific risk factors for transplantations with livers ≥70 years old. Although donor age is associated with a linearly increasing risk of graft loss between 25 and 80 years old, no difference in graft survival could be observed when "preferred" recipients were transplanted with a liver <70 or ≥70 years old (HR 1.1; CI 0.92-1.23, P = 0.40) or with a donor <40 or ≥70 years old (HR 1.2; CI 0.96-1.37, P = 0.13). Utilization of reported livers ≥70 years old increased from 42% in 2000-2003 to 76% in 2013-2015 without a decrease in graft survival (P = 0.45). In conclusion, an important proportion of LTs in the ET region are performed with livers ≥70 years old. The risk of donor age on graft loss increases linearly between 25 and 80 years old. Livers ≥70 years old can, however, be transplanted safely in preferred patients and are to be used more frequently to further reduce wait-list mortality., (Copyright © 2018 The Authors. Liver Transplantation published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.)

Background: Outcome after liver transplantation (LT) is determined by donor, transplant and recipient risk factors. These factors may have different impact on either patient or graft survival (outcome type). In the literature, there is wide variation in the use of outcome types and points in time (short term or long term). Objective of this study is to analyze the predictive capacity of risk factors and risk models in LT and how they vary over time and per outcome type., Methods: All LTs performed in the Netherlands from January 1, 2002, to December 31, 2011, were analyzed with multivariate analyses at 3-month, 1-year, and 5-year for patient and (non-)death-censored graft survival. The predictive capacity of the investigated risk models was compared with concordance indices., Results: Recipient age, model for end-stage liver disease sodium, ventilatory support, diabetes mellitus, hepatocellular carcinoma, previous malignancy, hepatitis C virus antibody, hepatitis B virus antibody, perfusion fluid, and Eurotransplant donor risk index (ET-DRI) had significant impact on outcome (graft or patient survival) at 1 or multiple points in time. Significant factors at 3-month patient survival (recipient age, model for end-stage liver disease sodium, ventilatory support) were used to compose a concept model. This model, had a higher c-index than the balance-of-risk score, DRI, ET-DRI, donor-recipient model and simplified recipient risk index for long-term patient and non-death-censored graft survival., Conclusions: In this study, the effects of recipient risk factors and models on different outcome types and time points were shown. Short-term patient survival mainly depends on recipient risk factors, long-term graft survival on donor risk factors and is more difficult to predict. Next to the concept model, the donor-recipient model has a higher predictive capacity to other risk models for (long-term) patient and non-death-censored graft survival. The DRI and ET-DRI best predicted death-censored graft survival. Knowledge about risk factors and models is critical when using these for waitlist management and/or help in organ allocation and decision-making., Competing Interests: The authors declare no funding or conflicts of interest.

Apart from donor and recipient risk factors, the effect of center-related factors has significant impact on graft survival after liver transplantation (LT). To investigate this effect in Eurotransplant, a retrospective database analysis was performed, including all LT's in adult recipients (≥18 years) in the Eurotransplant region from 1.1.2007 until 31.12.2013. Additionally, a survey was sent out to all transplant centers requesting information on surgeons' experience and exposure. In total, 10 265 LT's were included (median follow-up 3.3 years), performed in 39 transplant centers. Funnel plots showed significant differences in graft survival between the transplant centers. After correction for donor and recipient risk, with the Eurotransplant donor risk index (ET-DRI) and the simplified recipient risk index (sRRI) and random effects, these differences diminished. Mean historical volume (in the preceding 5 years) was a significant (P < 0.001), nonlinear marker for graft survival in the multivariate analysis. This study demonstrates that funnel plots can be used for benchmarking purposes in LT. Case-mix correction can be performed with the use of the ET-DRI and sRRI. The center effect encompasses the entire complex process of preoperative workup, operation to follow-up., (© 2018 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Background: Postoperative recovery after live donor nephrectomy is largely determined by the consequences of postoperative pain and analgesia consumptions. The use of deep neuromuscular blockade has been shown to reduce postoperative pain scores after laparoscopic surgery. In this study, we will investigate whether deep neuromuscular blockade also improves the early quality of recovery after live donor nephrectomy., Methods: The RELAX-study is a phase IV, multicenter, double-blinded, randomized controlled trial, in which 96 patients, scheduled for living donor nephrectomy, will be randomized into two groups: one with deep and one with moderate neuromuscular blockade. Deep neuromuscular blockade is defined as a post-tetanic count of 1-2. Our primary outcome measurement will be the Quality of Recovery-40 questionnaire (overall score) at 24 h after extubation., Discussion: This study is, to our knowledge, the first randomized study to assess the effectiveness of deep neuromuscular blockade during laparoscopic donor nephrectomy in enhancing postoperative recovery. The study findings may also be applicable for other laparoscopic procedures., Trial Registration: clinicaltrials.gov, NCT02838134 . Registered on 29 June 2016.

Between March 2012 and August 2013, 591 quality forms were filled out for abdominal organs in the Netherlands. In 133 cases (23%), there was a discrepancy between the evaluation from the procuring and transplanting surgeons. Injuries were seen in 148 (25%) organs of which 12 (2%) led to discarding of the organ: one of 133 (0.8%) livers, five of 38 (13%) pancreata and six of 420 (1.4%) kidneys (P < 0.001). Higher donor BMI was a risk factor for procurement-related injury in all organs (OR: 1.06, P = 0.011) and donor after cardiac death (DCD) donation in liver procurement (OR: 2.31, P = 0.034). DCD donation is also associated with more pancreata being discarded due to injury (OR: 10.333, P = 0.046). A higher procurement volume in a centre was associated with less injury in pancreata (OR = -0.95, P = 0.013) and kidneys (OR = -0.91, P = 0.012). The quality form system efficiently monitors the quality of organ procurement. Although there is a relatively high rate of organ injury, the discard rate is low and it does not significantly affect 1-year graft survival for any organ. We identified higher BMI as a risk factor for injury in abdominal organs and DCD as a risk factor in livers. A higher procurement volume is associated with fewer injuries., (© 2016 Steunstichting ESOT.)

Professional abdominal organ recovery with certification has been mandatory in the Netherlands since 2010. This study analyses the effects of certification (January 2010-September 2015) on pancreas transplantation and compares it to an era before certification (February 2002-May 2008) for surgical injuries and the number of pancreases transplanted. A total of 264 cases were analysed. Eighty-four recovered pancreases (31.8%) with surgically injuries were encountered. Forty-six of those were surgically salvaged for transplantation, resulting in a total of 226 (85.6%) being transplanted. It was found that certified surgeons recovered grafts from older donors (36.8 vs. 33.3; P = 0.021), more often from donation after circulatory death (DCD) donors (18% vs. 0%; P < 0.001) and had less surgical injuries (21.6% vs. 41.0%; P < 0.001). Certification (OR: 0.285; P < 0.001) and surgeons from a pancreas transplant centre (OR: 0.420; P = 0.002) were independent risk factors for surgical organ injury. Predictors for proceeding to the actual pancreas transplantation were a recovering surgeon from a pancreas transplantation centre (OR: 3.230; P = 0.003), certification (OR: 3.750; P = 0.004), donation after brain death (DBD) (OR: 8.313; P = 0.002) and donor body mass index (BMI) (OR: 0.851; P = 0.023). It is concluded that certification in abdominal organ recovery will limit the number of surgical injuries in pancreas grafts which will translate in more pancreases available for transplantation., (© 2016 Steunstichting ESOT.)

Background: Tumor recurrence after radical resection of hepatic tumors is not uncommon, suggesting that malignant lesions are missed during surgery. Intraoperative navigation using fluorescence guidance is an innovative technique enabling real-time identification of (sub)capsular liver tumors. The objective of the current study was to compare fluorescence imaging (FI) and conventional imaging modalities for laparoscopic detection of both primary and metastatic tumors in the liver., Methods: Patients undergoing laparoscopic resection of a malignant hepatic tumor were eligible for inclusion. Patients received standard of care, including preoperative CT and/or MRI. In addition, 10 mg indocyanine green was intravenously administered 1 day prior to surgery. After introduction of the laparoscope, inspection, FI, and laparoscopic ultrasonography (LUS) were performed. Histopathological examination of resected suspect tissue was considered the gold standard., Results: Twenty-two patients suspected of having hepatocellular carcinoma (n = 4), cholangiocarcinoma (n = 2) or liver metastases from colorectal carcinoma (n = 12), uveal melanoma (n = 2), and breast cancer (n = 2) were included. Two patients were excluded because their surgery was unexpectedly postponed several days. Twenty-six malignancies were resected in the remaining 20 patients. Sensitivity for various modalities was 80 % (CT), 84 % (MRI), 62 % (inspection), 86 % (LUS), and 92 % (FI), respectively. Three metastases (12 %) were identified solely by FI. All 26 malignancies could be detected by combining LUS and FI (100 % sensitivity)., Conclusion: This study demonstrates added value of FI during laparoscopic resections of several hepatic tumors. Although larger series will be needed to confirm long-term patient outcome, the technology already aids the surgeon by providing real-time fluorescence guidance., Competing Interests: Compliance with ethical standardsDisclosuresDr. Frangioni is CEO of Curadel, LLC, a for-profit company that has licensed FLARE® technology from the Beth Israel Deaconess Medical Center. Drs. Boogerd, Drs. Handgraaf, Drs. Lam, Dr. Huurman, Dr. Farina-Sarasqueta, Dr. van de Velde, Dr. Braat, and Dr. Vahrmeijer have no conflicts of interest or financial ties to disclose.

Background: The optimal immunosuppressive regimen in simultaneous pancreas-kidney transplant (SPKT) recipients that prevents acute rejection episodes (AREs) and allows optimal outcome remains elusive., Methods: This cohort study assessed incidence and time to AREs in 73 consecutive SPKT recipients receiving alemtuzumab induction and steroid-free maintenance with tacrolimus and mycophenolate mofetil. A cohort with single high-dose antithymocyte globulin (ATG; n = 85) and triple therapy served as controls. In addition, we provided mechanistic insights in AREs after alemtuzumab depletion, including composition and alloreactivity of lymphocytes (flow cytometry and mixed lymphocyte reaction) plasma alemtuzumab levels (enzyme-linked immunosorbent assay), and maintenance drug exposure., Results: Overall number of AREs at 3 years was significantly lower with alemtuzumab versus ATG induction (26.0% vs 43.5%; adjusted hazard ratio, 0.38; P = 0.029). Most AREs (94.6%) with ATG occurred within the first month, whereas 84.2% of AREs with alemtuzumab occurred beyond 3 months. Patients with and without an ARE in the steroid-free alemtuzumab group showed no differences in composition of lymphocytes, or in alemtuzumab levels. Of note, more than two thirds of these AREs were preceded by empiric tacrolimus and/or mycophenolate mofetil dose adjustments due to viral infections, leukopenia, or gastrointestinal symptoms., Conclusions: Alemtuzumab induction resulted in a significant lower incidence of AREs. Empiric dose adjustments beyond 3 months in the absence of steroids carry a significant risk for subsequent rejection in SPKT recipients., Competing Interests: The authors declare no conflicts of interest.

Aim: Organ procurement errors account for almost 20% of discarded pancreatic allografts. For this reason, the anatomical significance of the dorsal pancreatic artery (DPA) was reviewed., Methods: A strategy on dealing with an often overlooked DPA is evaluated., Results: The DPA provides together with the splenic artery the main blood supply to the pancreatic tail. Three different arterial variations have been described. In the rare instances when the DPA arises from the common hepatic artery or the celiac trunk, instead of the splenic origin, the DPA can easily be overlooked by surgeons not familiar with this artery. This may result in an unintentional damage to the pancreatic tail blood supply. If unrecognized during the back-table inspection, it could potentially jeopardize the pancreatic graft after reperfusion. When a cut DPA is encountered during inspection, efforts should be attempted to revascularize the graft, especially if there is no backflow from the splenic artery as sign of absent collateral circulation., Conclusion: The DPA may play a more prominent role in the vascularization of pancreas transplants than currently assumed. Better understanding of the vascular anatomy may lead to improved results in pancreas transplantation., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pancreas donor selection and recognition are important to cope with increasing organ shortage. We aim to show that the PDRI is more useful than the P-PASS to predict acceptance and should thus be preferred over P-PASS. Eurotransplant donors from 2004 until 2014 were included in this study. PDRI logistical factors were set to reference to purely reflect donor quality (PDRI donor ). PDRI and P-PASS association with allocation outcome was studied using area under the receiver operating characteristic curve (AUROC). Regional differences in donor quality were also investigated. Of the 10 444 pancreata that were reported, 6090 (58.3%) were accepted and 2947 (28.2%) were transplanted. We found that P-PASS was inferior to PDRIdonor in its ability to predict organ reporting, acceptance, and transplantation: AUC 0.63, 0.67 and 0.73 for P-PASS vs. 0.78, 0.79 and 0.84 for PDRIdonor , respectively. Furthermore, there were significant differences in donor quality among different Eurotransplant countries, both in reported donors and in transplanted organs. PDRI is a powerful predictor of allocation outcome and should be preferred over P-PASS. Proper donor selection and recognition, and possibly a more liberal approach toward inferior quality donors, may increase donation and transplant rates., (© 2016 Steunstichting ESOT.)

Donation after circulatory death (DCD) liver transplantation (LT) may imply a risk for decreased graft survival, caused by posttransplantation complications such as primary nonfunction or ischemic-type biliary lesions. However, similar survival rates for DCD and donation after brain death (DBD) LT have been reported. The objective of this study is to determine the longterm outcome of DCD LT in the Eurotransplant region corrected for the Eurotransplant donor risk index (ET-DRI). Transplants performed in Belgium and the Netherlands (January 1, 2003 to December 31, 2007) in adult recipients were included. Graft failure was defined as either the date of recipient death or retransplantation whichever occurred first (death-uncensored graft survival). Mean follow-up was 7.2 years. In total, 126 DCD and 1264 DBD LTs were performed. Kaplan-Meier survival analyses showed different graft survival for DBD and DCD at 1 year (77.7% versus 74.8%, respectively; P = 0.71), 5 years (65.6% versus 54.4%, respectively; P = 0.02), and 10 years (47.3% versus 44.2%, respectively; P = 0.55; log-rank P = 0.038). Although there was an overall significant difference, the survival curves almost reach each other after 10 years, which is most likely caused by other risk factors being less in DCD livers. Patient survival was not significantly different (P = 0.59). Multivariate Cox regression analysis showed a hazard ratio of 1.7 (P < 0.001) for DCD (corrected for ET-DRI and recipient factors). First warm ischemia time (WIT), which is the time from the end of circulation until aortic cold perfusion, over 25 minutes was associated with a lower graft survival in univariate analysis of all DCD transplants (P = 0.002). In conclusion, DCD LT has an increased risk for diminished graft survival compared to DBD. There was no significant difference in patient survival. DCD allografts with a first WIT > 25 minutes have an increased risk for a decrease in graft survival. Liver Transplantation 22 1107-1114 2016 AASLD., (© 2016 American Association for the Study of Liver Diseases.)

The aim of the present study was to assess whether flushing the donor liver with urokinase immediately before implantation reduces the incidence of nonanastomotic biliary strictures (NASs) after liver transplantation, without causing increased blood loss, analyzed as a historical cohort study. Between January 2005 and October 2012, all liver (re-)transplantations were included. Of the 185 liver transplant recipients included, 63 donor livers between January 2010 and October 2012 received urokinase (study group), whereas the donor liver of 122 consecutive recipients, who served as a historical control group, between January 2005 and January 2010 did not receive urokinase. Basic donor (Eurotransplant donor risk index) and recipient (age, body mass index, laboratory Model for End-Stage Liver Disease score) characteristics did not significantly differ in both groups. Thirty-three recipients developed NASs: 22 in the control group (18%) and 11 (17.5%) in the study group (P = 0.68). Analyzed separately for donation after circulatory death (P = 0.42) or donation after brain death (P = 0.89), there was no difference between the groups in incidence of NAS. Of all the recipients developing NAS, 7 (21%) needed retransplantation and all others were treated conservatively. Autologous blood transfusion requirements did not differ significantly between both groups (P = 0.91), whereas interestingly, more heterologous blood transfusions were needed in the control group (P < 0.001). This study has its limitations by its retrospective character. A multi-institutional prospective study could clarify this issue. In conclusion, arterial flushing of the liver with urokinase immediately before implantation did not lead to a lower incidence of NAS in this study, nor did it lead to increased blood loss., (© 2015 American Association for the Study of Liver Diseases.)

Objective: In 2008, the preprocurement pancreas suitability score (P-PASS) was introduced within Eurotransplant to predict suitability of pancreas donors. A P-PASS of 17 or higher would have lower graft survival compared with pancreatic grafts from donors with a P-PASS lower than 17. In 2010, a continuous model, the pancreas donor risk index (PDRI), was designed. Before using this model in the European donor population, it has to be validated in the European setting., Methods: In this study, P-PASS and PDRI were validated using the results of all pancreas transplants performed at our center. The P-PASS and PDRI were compared as both continuous and dichotomous values. The original cutoff point of 17 divided P-PASS groups. Median PDRI (1.24) divided PDRI groups., Results: In total, 349 pancreas transplantations were performed. The P-PASS of 17 or higher was not associated with graft survival (P = 0.448). The PDRI of 1.24 or higher was associated with reduced graft survival in univariate analysis (P = 0.007) and multivariate analysis (P = 0.002). The PDRI concordance index was 0.69., Conclusions: The P-PASS has no predictive value for pancreas graft survival and should not be used in clinical decision making. The PDRI is a significant predictor of pancreas graft survival but should be used carefully, because good results can be achieved with grafts from high-PDRI donors.

Recently the Eurotransplant donor risk index (ET-DRI) was published, a model based on data from the Eurotransplant database that can be used for risk indication of liver donors within the Eurotransplant region. Because outcome after liver transplantation (LT) depends both on donor and recipient risk factors, a combined donor-recipient model (DRM) would give a more complete picture of the overall risk involved. All liver transplants in adult recipients from January 1, 2008 to December 31, 2010 in the Eurotransplant region were included. Risk factors in donors and recipients for failure-free (retransplant free) survival were analyzed in univariate and multivariate analyses. A simplified recipient risk index (sRRI) was constructed using all available recipient factors. A total of 4466 liver transplants were analyzed. Median donor risk index and ET-DRI were 1.78 and 1.91, respectively. The ET-DRI was validated in this new cohort (P < 0.001; concordance index [c-index], 0.59). After construction of a simplified recipient risk index of significant recipient factors, Cox regression analysis showed that the combination ET-DRI and sRRI into a new DRM gave the highest predictive value (P < 0.001; c-index, 0.62). The combined model of ET-DRI and sRRI gave a significant prediction of outcome after orthotopic LT in the Eurotransplant region, better than the ET-DRI alone. This DRM has potential in comparing data in the literature and correcting for sickness/physical condition of transplant recipients. It is a first step toward benchmarking of graft survival in the Eurotransplant region., (© 2015 American Association for the Study of Liver Diseases.)

Background: An overview of 30 years of pancreas transplantation at a high volume center. Analysis of patient survival- and graft survival-associated risk factors., Methods: All pancreas transplantations performed in our center from January 1, 1984, till December 31, 2012, were evaluated. Covariates influencing pancreas graft survival were analyzed using both univariate and multivariate analysis and Kaplan-Meier analysis., Results: In the study period, 349 pancreas transplantations were performed. With the introduction of modern induction therapy in 1999, 5-year patient survival improved to 92.0% (P = 0.003). Five-year pancreas graft survival improved to 80.3% (P = 0.026). Pancreas graft survival was influenced by left or right donor kidney, transplant type, local origin of procurement team, pancreas cold ischemia time, recipient cerebrovascular disease. Pancreas donor risk index increased to 1.39 over the years and pancreas donor risk index 1.24 or higher is a risk factor for graft survival (P = 0.007)., Conclusions: This study has shown excellent results in patient and pancreas graft survivals after 30 years of pancreas transplantation in a high volume center. Different donor, transplant, and recipient related risk factors influence pancreas graft survival. Even with higher risk pancreas donors, good results can be achieved.

Orthotopic liver transplantation (OLT) with donation after circulatory death (DCD) often leads to a higher first week peak alanine aminotransferase (ALT) and a higher rate of biliary nonanastomotic strictures (NAS) as compared to donation after brain death (DBD). This retrospective study was to evaluate whether an association exists between peak ALT and the development of NAS in OLT with livers from DBD (n = 399) or DCD (n = 97) from two transplantation centers. Optimal cutoff value of peak ALT for risk of development of NAS post-DCD-OLT was 1300 IU/l. The 4-year cumulative incidence of NAS after DCD-OLT was 49.5% in patients with a high ALT peak post-OLT, compared with 11.3% in patients with a low ALT peak. (P < 0.001). No relation between peak ALT and NAS was observed after DBD-OLT. Multivariate analysis revealed peak ALT ≥1300 IU/l [adjusted hazard ratio (aHR) = 3.71, confidence interval (CI) (1.26-10.91)] and donor age [aHR = 1.04, CI 1.00-1.07] to be independently associated with development of NAS post-DCD-OLT. A peak ALT of <1300 IU/l carries a risk for NAS similar to DBD-OLT. Thus, in DCD-OLT, but not in DBD-OLT, peak ALT discriminates patients at high or low risk for NAS., (© 2015 Steunstichting ESOT.)

Background: Uveal melanoma is the most common primary intraocular tumor in adults, and up to 50% of patients will develop liver metastases. Complete surgical resection of these metastases can improve 5-year survival, but only a few patients are eligible for radical surgical treatment. The aim of this study was to introduce a near-infrared (NIR) fluorescence laparoscope during minimally invasive surgery for intraoperative identification of uveal melanoma hepatic metastases and to use it to provide guidance during resection., Methods: Three patients diagnosed with one solitary liver metastasis from uveal melanoma are presented. Patients received 10 mg indocyanine green (ICG) intravenously 24 hours before surgery. A NIR fluorescence laparoscope was used to detect malignant liver lesions., Results: In all 3 patients, laparoscopic NIR fluorescence imaging using ICG successfully identified uveal melanoma metastases. In 2 patients, multiple additional lesions were identified by inspection and NIR fluorescence imaging, which were not identified by preoperative conventional imaging. In one patient, one additional lesion, not identified by computed tomography, magnetic resonance imaging, laparoscopic ultrasonography, and inspection, was observed with NIR fluorescence imaging only. Importantly, NIR fluorescence imaging provided guidance during resection of these metastases., Conclusions: We describe the successful use of laparoscopic identification and resection of uveal melanoma liver metastases using NIR fluorescence imaging and ICG. This procedure is minimally invasive and should be used as complementary to conventional techniques for the detection and resection of liver metastases., (© The Author(s) 2014.)