Preclinical validation of a customized circuit for ex situ uninterrupted cold-to-warm prolonged perfusion of the liver.

CONTEXT: Clinical adoption of ex situ liver perfusion is growing. While hypothermic perfusion protects against ischemia-reperfusion injury in marginal grafts, normothermic perfusion enables organ viability assessment and therefore selection of borderline grafts. The combination of hypothermic and normothermic perfusion, known as "cold-to-warm," may be the optimal sequence for organ preservation, but is difficult to achieve with most commercial perfusion systems. We developed an adaptable customized circuit allowing uninterrupted "cold-to-warm" perfusion and conducted preclinical studies on healthy porcine livers and discarded human livers to demonstrate the circuit's efficacy. METHODS: In collaboration with bioengineers, we developed a customized circuit that adapts to extracorporeal circulation consoles used in cardiovascular surgery and includes a proprietary reservoir enabling easy perfusate change without interrupting perfusion. This preclinical study was conducted on porcine and human livers. Perfusion parameters (pressures, flows, oxygenation) and organ viability were monitored. RESULTS: The customized circuit was adapted to a LivaNova S5® console, and the perfusions were flow-driven with real-time pressure monitoring. Ten porcine liver and 12 discarded human liver perfusions were performed during 14 to 18 h and 7 to 25 h, respectively. No hyperpressure was observed (porcine and human portal pressure 2-6 and 2-8 mm Hg; arterial pressure 10-65 and 20-65 mm Hg, respectively). No severe histological tissue injury was observed (Suzuki score ≤ 3 at the end of perfusion). Seven (70%) porcine livers and five (42%) human livers met the UK viability criteria. CONCLUSION: The customized circuit and system design enables smooth uninterrupted "cold-to-warm" perfusion not present in current commercial perfusion systems.

Feasibility of Liver Transplantation after 90Y Radioembolization: Lessons from a Radiation Protection Incident.

ABSTRACT: Radioembolization using 90Y is a growing procedure in nuclear medicine for treating hepatocellular carcinoma. Current guidelines suggest postponing liver transplantation or surgical resection for a period of 14 to 30 d after radioembolization to minimize surgeons' exposure to ionizing radiation. In light of a radiation protection incident, we reevaluated the minimum delay required between radioembolization and subsequent liver transplantation. A patient with a hepatocellular carcinoma underwent a liver transplantation 44 h after undergoing radioembolization using 90Y (860 MBq SIR-Spheres). No specific radioprotection measures were followed during surgery and pathological analysis. We subsequently (1) evaluated the healthcare professionals' exposure to ionizing radiation by conducting dose rate measurements from removed liver tissue and (2) extrapolated the recommended interval to be observed between radioembolization and surgery/transplantation to ensure compliance with the radiation dose limits for worker safety. The surgeons involved in the transplantation procedure experienced the highest radiation exposure, with whole-body doses of 2.4 mSv and extremity doses of 24 mSv. The recommended delay between radioembolization and liver transplantation was 8 d when using SIR-Spheres and 15 d when injecting TheraSphere. This delay can be reduced further when considering the specific 90Y activity administered during radioembolization. This dosimetric study suggests the feasibility of shortening the delay for liver transplantation/surgery after radioembolization from the 8th or 15th day after using SIR-Spheres or TheraSphere, respectively. This delay can be decreased further when adjusted to the administrated activity while upholding radiation protection standards for healthcare professionals.

Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

BACKGROUND AND AIMS: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplantant (post-LT) outcomes in Europe. APPROACH AND RESULTS: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). CONCLUSIONS: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

Perceptions of surgical difficulty in liver transplantation: A European survey and development of the Pitié-Salpêtrière classification.

BACKGROUND: Significant variations exist regarding the definition of difficult liver transplantation. The study goals were to investigate how liver transplant surgeons evaluate the surgical difficulty of liver transplantation and to use the identified factors to classify liver transplantation difficulty. METHODS: A Web-based online European survey was presented to liver transplant surgeons. The survey was divided into 3 parts: (1) participant demographics and practices; (2) various situations based on recipient, liver disease, tumor treatment, and technical factors; and (3) 8 real-life clinical vignettes with different levels of complexity. In part 3 of the survey, respondents were asked whether they would perform liver transplantation but were not aware that these patients eventually underwent liver transplantation. RESULTS: A total of 143 invites were sent out, and 97 (67.8%) participants completed the survey. Most participants considered previous spontaneous bacterial peritonitis, previous supra-mesocolic surgery, hypertrophy of segment I, and obesity to be recipient factors for high-difficulty liver transplantation. Most participants considered liver transplantation to be challenging in patients with Budd-Chiari syndrome, Kasai surgery, polycystic liver disease, diffuse portal vein thrombosis, and a history of open hepatectomy. The proportion of participants indicating that liver transplantation was warranted varied across the 8 cases, from 69% to 100%. Our classification of the surgical difficulty of liver transplantation employed these recipient-related, surgical history-related, and liver disease-related variables and 3 difficulty groups were identified: low, intermediate, and high difficulty groups. CONCLUSION: This survey provides an overview of the surgical difficulty of various situations in liver transplantation that could be useful for further benchmark and textbook outcome studies.

Strategy for Oligometastatic Recurrence of Cardia Adenocarcinoma: Liver Radiofrequency Ablation Associated with PIPAC Inducing Response Permitting Cytoreductive Surgery and HIPEC.

Management of oligometastatic disease (OMD) in esophagogastric junction cancer is complex due to anatomical location and adenocarcinoma pathway. Specific curative strategy is mandatory to increase survival. A multimodal approach combining surgery, systemic and peritoneal chemotherapy, radiotherapy, and radiofrequency could be envisaged. We report a strategy proposed for a 61-year-old male with cardia adenocarcinoma, initially treated with chemotherapy and superior polar esogastrectomy. He developed at later stage an OMD with peritoneal metastasis, single liver metastasis, and single lung metastasis. Considering that peritoneal metastases were unresectable at first, he was given multiple Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with oxaliplatin, associated with intravenous docetaxel. Percutaneous radiofrequency ablation was performed during the first PIPAC procedure. Peritoneal response allowed a secondary Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

Binding and Kinetic Analysis of Human Protein Phosphatase PP2A Interactions with Caspase 9 Protein and the Interfering Peptide C9h.

The serine/threonine phosphatase PP2A and the cysteine protease Caspase 9 are two proteins involved in physiological and pathological processes, including cancer and apoptosis. We previously demonstrated the interaction between Caspase 9 and PP2A and identified the C9h peptide, corresponding to the binding site of Caspase 9 to PP2A. This interfering peptide can modulate Caspase 9/PP2A interaction leading to a strong therapeutic effect in vitro and in vivo in mouse models of tumor progression. In this manuscript, we investigate (I) the peptide binding to PP2A combining docking with molecular dynamics and (II) the secondary structure of the peptide using CD spectroscopy. Additionally, we compare the binding affinity, using biolayer interferometry, of the wild-type protein PP2A with Caspase 9 and vice versa to that observed between the PP2A protein and the interfering peptide C9h. This result strongly encourages the use of peptides as new therapeutics against cancer, as shown for the C9h peptide already in clinical trial.

In situ normothermic regional perfusion versus ex situ normothermic machine perfusion in liver transplantation from donation after circulatory death.

In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.

Restrictive intraoperative fluid intake in liver surgery and postoperative renal function: A propensity score matched study.

BACKGROUND: Postoperative acute kidney injury (AKI) is a common complication in hepatic surgery. In hepatic surgery, relative hypovolemia may help to limit blood loss, but the consequences of restrictive fluid intake are unknown. The goal of this study was to determine the influence of intraoperative fluid intake on the incidence of AKI and its consequences. METHODS: Data from 397 consecutive patients who underwent liver resection were prospectively recorded and retrospectively analyszed. We compared the incidence of postoperative acute kidney failure in patients given restrictive (≤ 5 mL/kg/h) versus liberal (> 5 mL/kg/h) fluid therapy. We calculated a 1:1 match propensity score using logistic regression to estimate the likelihood of patients receiving restrictive or liberal intraoperative fluid intakes. The association between the intraoperative fluid intake strategy and occurrence of postoperative AKI were tested using a Cox frailty model on the database of matched patients. RESULTS: Postoperative AKI was diagnosed in 133 of the 397 patients. Fluid intake strategy was restrictive for 121 patients and liberal for 276 patients. After propensity score matching to balance confounding factors, the liberal strategy was associated with a significantly lower risk for postoperative AKI compared to the restrictive strategy (Hazard Ratio 0.40 [0.29; 0.56], P<0.001). Patients with postoperative AKI had longer hospital stays and higher mortality. There were no cases of further blood loss in the liberal fluid intake group. CONCLUSIONS: A restrictive fluid intake strategy is a risk factor for developing postoperative AKI, with serious consequences, without reducing blood loss in liver surgery.

Backtable preparation after liver harvesting with "en bloc" technique with video.

The aim of this didactical video is to show an easy and standardized technique of liver preparation after "en bloc" extraction and access a young surgeon to perform liver procurement. The technique entails five steps: beginning with the dissection of the vena cava, the superior mesenteric artery, and the coeliac trunk, followed by the common hepatic artery, the bile duct and finally the portal vein. This technique of liver graft preparation has high reproducibility while maintaining the safety of the procedure for young surgeons. The "en bloc" extraction with a standardized liver graft preparation is an easy and a reproducible technique.

Preclinical Validation of Tumor-Penetrating and Interfering Peptides against Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults. The disease is characterized by the accumulation of tumoral B cells resulting from a defect of apoptosis. We have in vitro and in vivo preclinically validated a tumor-penetrating peptide (named TT1) coupled to an interfering peptide (IP) that dissociates the interaction between the serine/threonine protein phosphatase 2A (PP2A) from its physiological inhibitor, the oncoprotein SET. This TT1-IP peptide has an antitumoral effect on CLL, as shown by the increased survival of mice bearing xenograft models of CLL, compared to control mice. The peptide did not show toxicity, as indicated by the mouse body weight and the biochemical parameters, such as renal and hepatic enzymes. In addition, the peptide-induced apoptosis in vitro of primary tumoral B cells isolated from CLL patients but not of those isolated from healthy patients. Finally, the peptide had approximately 5 h half-life in human serum and showed pharmacokinetic parameters compatible with clinical development as a therapeutic peptide against CLL.

Pulmonary infection after hepatic resection: Associated factors and impact on outcomes.

BACKGROUND AND AIMS: Postoperative pulmonary complications are frequent after hepatectomy. The aim of this retrospective study was to use preoperative and intraoperative data to establish specific factors associated with post-hepatectomy pneumonia (PHPN). METHODS: Patients underwent minor or major hepatectomy for cancer or non-cancer treatment. Surgical procedure was performed by laparoscopy or laparotomy. PHPN was defined as a new radiologic finding associated with fever, leucocytosis and purulent bronchial secretions. The incidence, associated factors and prognosis of PHPN were investigated. RESULTS: In 399 patients undergoing planned hepatectomy, 49 (12.3%) developed pneumonia. Of 81 patients (20.3%) with cirrhosis, 77 were Child-Pugh A and 4 were Child-Pugh B. Hepatectomy indication was cancer in 331 patients (of which metastasis in 213). Laparoscopy rate was 31.3%. In multivariate analysis, the main factors statistically associated with PHPN were: chronic obstructive pulmonary disease (COPD) (odds ratio [OR] = 4.17; 95% confidence interval [CI], 1.60-10.84; P = 0.003), intraoperative blood transfusion (OR = 2.46; 95% CI 1.01-5.70; P = 0.001), laparotomy (OR = 3.01; 95% CI 1.09-8.27; P = 0.03), and nasogastric tube maintained at day 1 (OR = 2.09; 95% CI 1.03-4.22; P = 0.04). Length of stay was significantly different between groups without PHPN (10.2 days) versus with PHPN (26.4 days; P < 0.001). Intra-hospital and one-year mortality were greater in the PHPN group than the pneumonia-free group (8.16 vs 0% and 18.4 vs 3.4%, respectively; P < 0.001). CONCLUSIONS: COPD, transfusion and laparotomy (versus laparoscopy) are factors associated with PHPN and impaired survival.

Isolation of Primary Hepatocytes for Testing Tumor Penetrating Peptides.

Methods for isolation of human primary cells is an important tool to be able to test the effect of several drugs for the treatment of diseases. Protocols have been described for the isolation of healthy and tumoral hepatocytes; however, the quality and the amount of the isolated cells is not satisfactory. We describe here protocols for the isolation of healthy and tumoral hepatocytes as well as the use of tumor penetrating and interfering peptides as new therapeutics. Peptides are showed to be safe drugs and taking into account recent improvements in peptide administration, biodelivery, and bioavailability. Tumor penetrating peptides fused to an interfering peptide have a great potential to become therapeutic agents.

Auxiliary Liver Transplantation for Cirrhosis: From APOLT to RAPID: A Scoping Review.

OBJECTIVE: To survey the available literature regarding the use of auxiliary liver transplantation (ALT) in the setting of cirrhosis. SUMMARY OF BACKGROUND: ALT is a type of liver transplantation (LT) procedure in which part of the cirrhotic liver is resected and part of the liver graft is transplanted. The cirrhotic liver left in situ acts as an auxiliary liver until the graft has reached sufficient volume. Recently, a 2-stage concept named RAPID (Resection and Partial Liver segment 2/3 transplantation with Delayed total hepatectomy) was developed, which combines hypertrophy of the small graft followed by delayed removal of the native liver. METHODS: A scoping review of the literature on ALT for cirrhosis was performed, focusing on the historical background of RAPID and the status of RAPID for this indication. The new comprehensive nomenclature for hepatectomy ("New World" terminology) was used in this review. RESULTS: A total of 72 cirrhotic patients underwent ALT [heterotopic (n = 34), orthotopic (Auxiliary partial orthotopic liver transplantation, n = 34 including 5 followed by resection of the native liver at the second stage) and RAPID (n = 4)]. Among the 9 2-stage LTs (APOLT, n = 5; RAPID, n = 4), portal blood flow modulation was performed in 6 patients by deportalization of the native liver (n = 4), portosystemic shunt creation (n = 1), splenic artery ligation (n = 3) or splenectomy (n = 1). The delay between the first and second stages ranged from 18 to 90 days. This procedure led to an increase in the graft-to-recipient weight ratio between 33% and 156%. Eight patients were alive at the last follow-up. CONCLUSIONS: Two-stage LT and, more recently, the RAPID procedure are viable options for increasing the number of transplantations for cirrhotic patients by using small grafts.

Influence of the ABO Blood Group System on Hepatocellular Carcinoma Recurrence After Liver Transplantation.

BACKGROUND: The ABO blood group system may influence tumorigenesis, but its prognostic value in liver transplantation (LT) for hepatocellular carcinoma (HCC) has never been assessed. METHODS: All consecutive patients who underwent LT for HCC between 2013 and 2017 at 9 centers were analyzed. Predictors of tumor recurrence were identified using multivariable analysis, while comparison between group A and non-A recipients was performed after propensity score matching. RESULTS: Among 925 LT recipients, 406 were blood group A, 94 group B, 380 group O, and 45 group AB. On multivariable analysis, group A was associated with tumor recurrence (hazard ratio [HR] = 1.574 [95% confidence interval; 95% CI = 1.034-2.394] P = 0.034). After propensity score matching, 1- and 5-y recurrence rates were 7.4% and 20.1% in group A recipients versus 3.3% and 13.2% in non-A recipients (HR = 1.66 [95% CI = 1.12-2.45], P = 0.011). One and 5-y recurrence-free survivals were 85.2% and 66.8% in group A recipients versus 88.5% and 71.3% in non-A recipients (HR = 1.38 [95% CI = 1.01-1.90], P = 0.045). Among recipients within Milan criteria (n = 604), 1- and 5-y recurrence rates were 5.8% and 12.7% in group A recipients versus 3.1% and 12.2% in non-A recipients (HR = 1.197 [95% CI = 0.721-1.987], P = 0.485). Among recipients outside Milan criteria (n = 182), 1- and 5-y recurrence rates were 12.1% and 43.8% in group A recipients versus 3.9% and 15.6% in non-A recipients (HR = 3.175 [95% CI = 1.526-6.608], P = 0.002). CONCLUSIONS: ABO blood system influences the oncological outcome of recipients undergoing LT for HCC. Its incorporation in the prognostication model of LT for HCC may allow improving the management of LT candidates.

Bi-Functional Peptides as a New Therapeutic Tool for Hepatocellular Carcinoma.

BACKGROUND: The interfering peptides that block protein-protein interactions have been receiving increasing attention as potential therapeutic tools. METHODS: We measured the internalization and biological effect of four bi-functional tumor-penetrating and interfering peptides into primary hepatocytes isolated from three non-malignant and 11 hepatocellular carcinomas. RESULTS: These peptides are internalized in malignant hepatocytes but not in non-malignant cells. Furthermore, the degree of peptide internalization correlated with receptor expression level and tumor aggressiveness levels. Importantly, penetration of the peptides iRGD-IP, LinTT1-IP, TT1-IP, and RPARPAR-IP induced apoptosis of the malignant hepatocytes without effect on non-malignant cells. CONCLUSION: Receptor expression levels correlated with the level of peptide internalization and aggressiveness of the tumor. This study highlights the potential to exploit the expression of tumor-penetrating peptide receptors as a predictive marker of liver tumor aggressiveness. These bi-functional peptides could be developed for personalized tumor treatment.

Pepscan Approach for the Identification of Protein-Protein Interfaces: Lessons from Experiment.

PEPscan is an old approach that has recently gained renewed interest for the identification of interfering peptides (IPs), i.e., peptides able to interfere with protein-protein interactions (PPIs). Its principle is to slice a protein sequence as a series of short overlapping peptides that are synthesized on a peptide array and tested for their ability to bind a partner, with positive spots corresponding to candidate IPs. PEPscan has been applied with a rather large success in various contexts, but the structural determinants underlying this success remain obscure. Here, we analyze the results of 14 PEPscan experiments, and confront the in vitro results with the available structural information. PEPscan identifies candidate IPs in limited numbers that in all cases correspond to solvent-accessible regions of the structures, their location at the protein-protein interface remaining to be further demonstrated. A strong point of PEPscan seems to be its ability to identify specific IPs. IPs identified from the same protein differ depending on the target PPI, and correspond to patches not frequently involved in the interactions seen in the 3D structures available. Overall, PEPscan seems to provide a cheap and rapid manner to identify candidate IPs, that also comes with room for improvement.

Association of shear-wave elastography with clinical outcomes post-liver transplantation.

PURPOSE: Two-dimensional shear-wave elastography (2D-SWE) assessment of liver stiffness has the advantage of being obtained during conventional ultrasound. Liver-stiffness values on 2D-SWE for grafted livers are unknown, as are their potential link to post-transplantation morbidity. This study was undertaken to determine liver-stiffness values on 2D-SWE for grafted livers without complications, and examine relationships between liver-stiffness values on 2D-SWE and early post-operative arterial or biliary complications. METHODS: In our facility, all liver-transplant recipients are entered in a comprehensive surgical database, where donor, procedure and recipient characteristics are described. All patients underwent systematic 2D-SWE assessment. Potential relationships were analyzed between liver-stiffness findings and donor, procedure and recipient characteristics, and follow-up events, including death, arterial or biliary complications, graft removal and allograft-dysfunction scores. RESULTS: Liver-stiffness values on 2D-SWE of 337 ultrasound examinations from 165 liver-transplant recipients were collected retrospectively. Median time from transplantation to 2D-SWE examination was 149 days, with median follow-up at 36 months. The mean±SD stiffness value for grafts without complications was 7.3±2.3kPa; it was significantly higher during the first 90 days (8.2±2.5kPa) post-transplant than after 1year (7.0±2.4kPa) (P=0.01). Patients with biliary complications during the first-year post-transplantation had significantly higher mean liver-stiffness values on 2D-SWE than those without, respectively: 9.8±7.0 vs 7.5±1.8kPa (P=0.01). CONCLUSIONS: Post-transplantation patients without complications had stiffer livers than the general population, with higher values during the first 90 days after surgery. Liver-stiffness values on 2D-SWE were significantly higher for patients with biliary, but not arterial, complications.

Hypothermic Oxygenated Perfusion Versus Normothermic Regional Perfusion in Liver Transplantation From Controlled Donation After Circulatory Death: First International Comparative Study.

OBJECTIVE: To compare HOPE and NRP in liver transplantation from cDCD. SUMMARY OF BACKGROUND DATA: Liver transplantation after cDCD is associated with higher rates of graft loss. Dynamic preservation strategies such as NRP and HOPE may offer safer use of cDCD grafts. METHODS: Retrospective comparative cohort study assessing outcomes after cDCD liver transplantation in 1 Swiss (HOPE) and 6 French (NRP) centers. The primary endpoint was 1-year tumor-death censored graft and patient survival. RESULTS: A total of 132 and 93 liver grafts were transplanted after NRP and HOPE, respectively. NRP grafts were procured from younger donors (50 vs 61 years, P < 0.001), with shorter functional donor warm ischemia (22 vs 31 minutes, P < 0.001) and a lower overall predicted risk for graft loss (UK-DCD-risk score 6 vs 9 points, P < 0.001). One-year tumor-death censored graft and patient survival was 93% versus 86% (P = 0.125) and 95% versus 93% (P = 0.482) after NRP and HOPE, respectively. No differences in non-anastomotic biliary strictures, primary nonfunction and hepatic artery thrombosis were observed in the total cohort and in 32 vs. 32 propensity score-matched recipients CONCLUSION:: NRP and HOPE in cDCD achieved similar post-transplant recipient and graft survival rates exceeding 85% and comparable to the benchmark values observed in standard DBD liver transplantation. Grafts in the HOPE cohort were procured from older donors and had longer warm ischemia times, and consequently achieved higher utilization rates. Therefore, randomized controlled trials with intention-to-treat analysis are needed to further compare both preservation strategies, especially for high-risk donor-recipient combinations.

Endoscopic Ultrasound-Guided Enteroenterostomy for Afferent Limb Syndrome.

Afferent limb syndrome (ALS) is a rare complication of duodenopancreatectomy, resulting from the mechanical obstruction of the afferent limb usually after local malignancy recurrence. Management of ALS (ie, surgery and palliative therapy) is often unsatisfactory. We present 5 cases of endoscopic ultrasound-guided internal drainage of the afferent limb using lumen-apposing metal stents. All procedures were successful, with no related complications; 2 patients had a complete regression of their symptoms, one experienced cholangitis recurrence, and 2 patients died after some weeks because of their malignancies. Endoscopic ultrasound-guided enteroenterostomy offers a convenient and safe palliative solution for patients presenting ALS.