Divergent WNT signaling and drug sensitivity profiles within hepatoblastoma tumors and organoids.

Hepatoblastoma, the most prevalent pediatric liver cancer, almost always carries a WNT-activating CTNNB1 mutation, yet exhibits notable molecular heterogeneity. To characterize this heterogeneity and identify novel targeted therapies, we perform comprehensive analysis of hepatoblastomas and tumor-derived organoids using single-cell RNA-seq/ATAC-seq, spatial transcriptomics, and high-throughput drug profiling. We identify two distinct tumor epithelial signatures: hepatic 'fetal' and WNT-high 'embryonal', displaying divergent WNT signaling patterns.

Prolonged hypothermic machine perfusion enables daytime liver transplantation - an IDEAL stage 2 prospective clinical trial.

Background: Liver transplantation is traditionally performed around the clock to minimize organ ischemic time. However, the prospect of prolonging preservation times holds the potential to streamline logistics and transform liver transplantation into a semi-elective procedure, reducing the need for nighttime surgeries. Dual hypothermic oxygenated machine perfusion (DHOPE) of donor livers for 1-2 h mitigates ischemia-reperfusion injury and improves transplant outcomes.

Neurodevelopment in patients with biliary atresia up to toddler age: Outcomes and predictability.

Aim: To assess neurodevelopment in young patients with biliary atresia (BA) and to determine the predictive value of General Movement Assessment (GMA) at infant age for neurodevelopmental impairments at toddler age.

Method: Infants diagnosed with BA were prospectively included in a longitudinal study. Neurodevelopmental status was previously assessed before Kasai porto-enterostomy (KPE) and one month after KPE using Prechtl's GMA, including motor optimality scores.

Doppler-ultrasound reference values after pediatric liver transplantation: a consecutive cohort study.

Objectives: Doppler ultrasound (DUS) is the main imaging modality to evaluate vascular complications of pediatric liver transplants (LT). The current study aimed to determine reference values and their change over time.

Methods: A consecutive cohort of pediatric patients undergoing an LT were retrospectively included between 2015 and 2020.

Incidence of Isolated Biliary Atresia during the COVID Lockdown in Europe: Results from a Collaborative Project by RARE-Liver.

Background: Biliary atresia (BA) is a rare cholangiopathy where one of the proposed aetiological mechanisms is an infectious viral trigger. Coronavirus disease-19 (COVID) lockdown restrictions were implemented to reduce the transmission of infections. Strictness of lockdown varied across European countries.

Indeterminate pediatric acute liver failure: Clinical characteristics of a temporal cluster of five children in the Netherlands in the spring of 2022.

There is increasing global concern of severe acute hepatitis of unknown etiology in young children. In early 2022, our center for liver transplantation in the Netherlands treated five children who presented in short succession with indeterminate acute liver failure. Four children underwent liver transplantation, one spontaneously recovered.

Severe acute hepatitis and acute liver failure of unknown origin in children: a questionnaire-based study within 34 paediatric liver centres in 22 European countries and Israel, April 2022.

To detect potential concern about severe acute hepatitis in children, we conducted a survey among 50 ERN RARE-LIVER centres. By 26 April 2022, 34 centres, including 25 transplant centres, reported an estimated median of 3-5, 0-2 and 3-5 cases in 2021, 2020 and 2019 and a mean of 2 (range: 0-8) cases between January and April 2022 (mean in 10 large liver transplant centres: 3). Twelve centres reported suspicion of an increase, but no rise.

Surgical Outcome of Children with a Malignant Liver Tumour in The Netherlands: A Retrospective Consecutive Cohort Study.

Introduction: Six to eight children are diagnosed with a malignant liver tumour yearly in the Netherlands. The majority of these tumours are hepatoblastoma (HB) and hepatocellular carcinoma (HCC), for which radical resection, often in combination with chemotherapy, is the only curative treatment option. We investigated the surgical outcome of children with a malignant liver tumour in a consecutive cohort in the Netherlands.

Incidence and impact of postoperative pancreatic fistula after minimally invasive and open distal pancreatectomy.

Background: Previous studies reported a higher rate of postoperative pancreatic fistula after minimally invasive distal pancreatectomy compared to open distal pancreatectomy. It is unknown whether the clinical impact of postoperative pancreatic fistula after minimally invasive distal pancreatectomy is comparable with that after open distal pancreatectomy. We aimed to compare not only the incidence of postoperative pancreatic fistula, but more importantly, also its clinical impact.

European Liver Transplant Registry: Donor and transplant surgery aspects of 16,641 liver transplantations in children.

Background And Aims: The European Liver Transplant Registry (ELTR) has collected data on liver transplant procedures performed in Europe since 1968.

Approach And Results: Over a 50-year period (1968-2017), clinical and laboratory data were collected from 133 transplant centers and analyzed retrospectively (16,641 liver transplants in 14,515 children). Data were analyzed according to three successive periods (A, before 2000; B, 2000-2009; and C, since 2010), studying donor and graft characteristics and graft outcome.

Parental wellbeing after diagnosing a child with biliary atresia: A prospective cohort study.

Purpose: To determine anxiety, stress, and quality of life (QoL) in parents of children who are diagnosed with biliary atresia (BA).

Methods: Parents of BA patients (0-3 years) completed validated questionnaires at three time points: at first hospitalization (T0); 1-2 months post diagnosis (T1); and 2-3 years post diagnosis (T2). Results are presented in medians (min-max).

Utility of Preoperative Computed Tomography-Based Body Metrics in Relation to Postoperative Complications in Pediatric Liver Transplantation Recipients.

Computed tomography (CT)-derived body metrics such as skeletal muscle index (SMI), psoas muscle index (PMI), and subcutaneous fat area index (ScFI) are measurable components of sarcopenia, frailty, and nutrition. While these body metrics are advocated in adults for predicting postoperative outcomes after liver transplantation (LT), little is known about their value in pediatric populations. This study assessed the relation between preoperative CT-based body metrics and postoperative short-term outcomes in pediatric LT recipients.

Portal vein obstruction after pediatric liver transplantation: A systematic review of current treatment strategies.

Introduction: Portal vein obstruction (PVO) is a significant vascular complication after liver transplantation (LT) in pediatric patients. Current treatment strategies include percutaneous transluminal angioplasty (PTA), with or without stent placement, mesorex bypass (MRB), splenorenal shunt, mesocaval shunt, endovascular recanalization (EVR), splenic artery embolization and splenectomy. However, specific characteristics of patients undergoing intervention and selection of individual treatment and its efficacy have remained unclear.

Assessment of hepatic artery anatomy in pediatric liver transplant recipients: MR angiography versus CT angiography.

During LT screening, children undergo CTA to determine hepatic artery anatomy. However, CTA imparts radiation, unlike MRA. The aim was to compare MRA to CTA in assessing hepatic artery anatomy in pediatric LT recipients.

Controlled DCD Liver Transplantation Is Not Associated With Increased Hyperfibrinolysis and Blood Loss After Graft Reperfusion.

Background: The specific effect of donation after circulatory death (DCD) liver grafts on fibrinolysis, blood loss, and transfusion requirements after graft reperfusion is not well known. The aim of this study was to determine whether transplantation of controlled DCD livers is associated with an elevated risk of hyperfibrinolysis, increased blood loss, and higher transfusion requirements upon graft reperfusion, compared with livers donated after brain death (DBD).

Methods: A retrospective single-center analysis of all adult recipients of primary liver transplantation between 2000 and 2019 was performed (total cohort n = 628).

Early Motor Repertoire in Infants With Biliary Atresia: A Nationwide Prospective Cohort Study.

Objectives: The aim of the study was to assess the neurological status in infants with biliary atresia (BA) at time of diagnosis, using Prechtl's validated General Movement Assessment.

Methods: Infants diagnosed with BA were prospectively included in a nationwide cohort study. From birth to approximately 46 weeks of postmenstrual age (PMA), general movements (GMs) are defined as "writhing movements.

Quality of Life in Parents of Children With Biliary Atresia.

Objectives: The aim of the study was to determine quality of life (QoL), stress, and anxiety levels in parents of children with biliary atresia (BA), and to assess factors associated with parental QoL.

Methods: Parents of children (6-16 years) with BA were included in this cross-sectional study. We used validated questionnaires to assess parental QoL, stress, and anxiety levels.

A Higher Incidence of Isolated Biliary Atresia in Rural Areas: Results From an Epidemiological Study in The Netherlands.

Objectives: Environmental factors may be involved in the pathogenesis of biliary atresia (BA). This epidemiological study aimed to analyze the relationships between the incidence of BA, the incidence of confirmed viral or bacterial infections and population density, and geographical and temporal clustering of BA in the Netherlands.

Study Design: Correlations between the monthly incidence of BA and the number of confirmed infections were assessed.

Health-Related Quality of Life in Biliary Atresia Patients with Native Liver or Transplantation.

Introduction:  We aimed to assess health-related quality of life (HrQoL) in biliary atresia (BA) patients, based on original data and a literature review, and to determine factors associated with their HrQoL.

Materials And Methods:  We reviewed available studies describing HrQoL in BA patients. We assessed HrQoL in Dutch BA patients (6-16 years) using the validated Child Health Questionnaire.

Choledochal malformations in adults in the Netherlands: Results from a nationwide retrospective cohort study.

Background And Aims: Patients with a choledochal malformation, formerly described as cysts, are at increased risk of developing a cholangiocarcinoma and resection is recommended. Given the low incidence of choledochal malformation (CM) in Western countries, the incidence in these countries is unclear. Our aim was to assess the incidence of malignancy in CM patients and to assess postoperative outcome.

Variceal Bleeds in Patients with Biliary Atresia.

Introduction:  Portal hypertension often occurs in biliary atresia (BA). The subsequent development of esophageal varices and bleeding from these varices are a well-known complication. We aim to describe the incidence and severity of variceal bleeding in patients with BA.

Minimally invasive versus open distal pancreatectomy (LEOPARD): study protocol for a randomized controlled trial.

Background: Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking.

The timing of surgery of antenatally diagnosed choledochal malformations: A descriptive analysis of a 26-year nationwide cohort.

Introduction: Choledochal malformations (CMs) are increasingly diagnosed antenatally. There is a dilemma between early surgery to prevent CM-related symptoms and postponing surgery to reduce complications. We aimed to identify the optimal timing of surgery in asymptomatic neonates with antenatally diagnosed CM and to identify predictors for development of symptoms.

Impact of a Nationwide Training Program in Minimally Invasive Distal Pancreatectomy (LAELAPS).

Objective: To study the feasibility and impact of a nationwide training program in minimally invasive distal pancreatectomy (MIDP).

Summary Of Background Data: Superior outcomes of MIDP compared with open distal pancreatectomy have been reported. In the Netherlands (2005 to 2013) only 10% of distal pancreatectomies were in a minimally invasive fashion and 85% of surgeons welcomed MIDP training.