European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (1) pre-transplant evaluation.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment in end-stage liver disease. Imaging is a key element for successful organ-transplantation to assist surgical planning. So far, only limited data regarding the best radiological approach to prepare children for liver transplantation is available. OBJECTIVES: In an attempt to harmonize imaging surrounding pediatric liver transplantation, the European Society of Pediatric Radiology (ESPR) Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra-, and postoperative phase. This paper reports the responses on preoperative imaging. MATERIAL AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted and 22 institutions from 11 countries returned the survey. From 2018 to 2020, the participating centers collectively conducted 1,524 transplantations, with a median of 20 transplantations per center per annum (range, 8-60). RESULTS: Most sites (64%) consider ultrasound their preferred modality to define anatomy and to plan surgery in children before liver transplantation, and additional cross-sectional imaging is only used to answer specific questions (computed tomography [CT], 90.9%; magnetic resonance imaging [MRI], 54.5%). One-third of centers (31.8%) rely primarily on CT for pre-transplant evaluation. Imaging protocols differed substantially regarding applied CT scan ranges, number of contrast phases (range 1-4 phases), and applied MRI techniques. CONCLUSION: Diagnostic imaging is generally used in the work-up of children before liver transplantation. Substantial differences were noted regarding choice of modalities and protocols. We have identified starting points for future optimization and harmonization of the imaging approach to multicenter studies.

Hepatoblastoma in children aged less than six months at diagnosis: A report from the SIOPEL group.

BACKGROUND: The purpose of this study was to evaluate clinical characteristics, treatment, and survival of children, who were diagnosed with hepatoblastoma (HB) in their first 6 months of age, enrolled in the SIOPEL 2 and 3 protocols. METHODS: Seventy-nine patients, treated between 1994 and 2006, were analyzed after stratification into three age groups: <1 month, between 1 and 3 months, and between 3 and 6 months. All received preoperative chemotherapy. RESULTS: Clinical characteristics were similar in both trials: 4 patients had pulmonary metastases at diagnosis, 4 had α-fetoprotein <100 ng/ml, 68 were operated by partial hepatectomy, and 7 received liver transplant. Chemotherapy courses were delayed in 8.5%, 8.4%, and 11.8% of cycles in the three groups. Doses were calculated according to weight for children <5 and 5-10 kg, and further reduced in 18.1%, 6.8%, and 5.9% of cycles. Acute toxicity was manageable. Long-term hearing loss was the major problem at follow-up occurring in two-thirds of children. Ten patients experienced progression or relapse, and 5 of 10 died. After a median follow-up of 5.6 years, the 5-year overall survival (OS) and event-free survival (EFS) were 91% (95% confidence interval [CI]: 84-96%) and 87% (95% CI: 78-92%), respectively. CONCLUSIONS: The 5-year OS and EFS of children <6 months of age affected by HB seem to be similar to those documented in the elder children. Dose reduction does not seem to jeopardize the long-term outcome and may explain the lower toxicity profile. Ototoxicity though appears as high as in the whole population of SIOPEL 2 and 3. The treatment for these children should be further explored in international studies, particularly focusing on prevention of hearing loss.

YouTube and pediatric surgery. What is the danger for parents?

Internet became one of the most important sources of public health informations especially for relatives and/or caregivers of sick children. Use of YouTube as a source of information in pediatric surgery has not been evaluated. In this study, we want to evaluate the use of YouTube as a source of information about one of the most frequent surgical urgency in pediatric patients, the acute appendicitis, to evaluate the risks for patients and parents.

Pediatric liver transplantation using left hepatic segments from living related donors: surgical experience in 100 recipients at Saint-Luc University Clinics.

Living-related liver transplantation was developed in the context of deceased donor organ shortage, which is particularly acute for pediatric recipients. This retrospective study analyzes the surgical technique and complications in the first 100 pediatric liver transplantation using left segmental liver grafts from living donors, performed at Saint-Luc University Clinics between July 1993 and April 2002. Pre-operative evaluation in donors and recipients, analysis of the surgical technique, and postoperative complications were reviewed. After a median follow-up period of 2526 days, no donor mortality was encountered, with a minimal morbidity and no long-term sequelae. At one and five yr post-transplantation, the actuarial patient survival rates were 94% and 92%, the corresponding figures being 92% and 89% for graft survival. The incidences of portal vein and hepatic artery thromboses, and of biliary complications were 14%, 1%, and 27%, respectively. Living-related liver transplantation in children constitutes an efficient therapy for liver failure to face the increased demand for liver grafts. Donor morbidity was kept to acceptable incidence, and surgical technique in the recipient needs to be tailored to minimize postoperative complications.

Permanent access to the portal system for cellular transplantation using an implantable port device.

A novel application of the implantable Port-a-Cath (PAC) system is described in the context of cellular transplantation. A silicone catheter was inserted in a collateral branch of the portal vein and connected to a port device positioned subcutaneously on the left thoracic cage. This permanent vascular access allowed iterative intraportal infusions of allogenic hepatocytes without the need of repeated transhepatic catheterization of the portal vein. Using this technique, repeated infusions of cryopreserved and / or fresh hepatocytes were successfully carried out in 3 children with inborn errors of liver metabolism, with the aim of progressively providing a sufficient mass of transplanted liver cells to stabilize the metabolic condition of the patients. We suggest that this technique might also be valuable in pancreatic islet cell transplantation.

The role of Notch receptor expression in bile duct development and disease.

Mutations in the Jagged1 gene, a ligand for the Notch signalling pathway, have been implicated in the pathogenesis of Alagille syndrome (AGS), resulting in bile duct paucity. Recently, a mouse model for AGS suggested that abnormalities of the Notch2 receptor, as well as of Jagged1, may be present. Expression patterns of Notch receptors have not been described in the developing human liver or in paediatric liver. The expression of Notch receptors and ligands was examined in fetal, paediatric normal, and diseased human liver by RT-PCR and immunohistochemistry. RT-PCR showed Notch1-4 mRNA expression to be present. In fetal liver, Notch3 protein was expressed on mesenchymal cells, closely adjacent to ductal plate cells that expressed Jagged1. In paediatric normal liver, Notch1 and Notch2 were present on mature bile duct cells. Notch expression was altered in disease, with distinct differences in AGS from extrahepatic biliary atresia (EHBA) and alpha1-anti-trypsin deficiency (alpha1AT). In AGS, where extensive ductular reaction was present, Jagged1 was expressed on ductular reactive cells (DRCs), along with marked Notch2 and Notch3 staining. Where there was ductular paucity, Notch2 and Notch3 were not expressed on remaining biliary epithelial cells. In EHBA and alpha1AT, Notch receptor expression was not seen on DRCs. Instead, Notch2 and Notch3 were expressed by stromal cells. In all diseases, Notch3 was expressed on neovessels in portal tracts and cirrhotic fibrous septa. In conclusion, Notch3 is expressed in close proximity to Jagged1 at the time of ductal plate formation, suggesting that Notch3 is important for bile duct development. The expression of both Notch2 and Notch3 in AGS on DRCs confirms that these receptors may be important in the pathogenesis of this disease. Further studies are required to investigate the presence of Notch2 and Notch3 at other periods in liver development and to clarify the role of Notch signalling in paediatric cholestases.

Congenital, solitary, large, intrahepatic arterioportal fistula in a child: management and review of the literature.

Congenital intrahepatic arterioportal fistula (APF) is a rare condition. In most cases, the symptoms and complications develop during infancy. We report here the incidental finding of a large and solitary congenital APF in a 13-year-old boy, with subsequent related clinical complications. At angiography, an APF connecting the left hepatic artery and the left branch of the portal vein (PV) was demonstrated with reversed flow in the left and main PV. The fistula was successfully occluded, in a single embolisation session, using an Amplatzer occlusion device. This was associated with immediate restoration of normal hepatopetal flow in the PV and followed by resolution of the clinical signs of portal hypertension. This patient is the oldest child with congenital intrahepatic APF to be reported. We emphasise the interest of using a large device (Amplatzer) to occlude a solitary large APF in a single session and, more importantly, to avoid other possible complications related to embolisation.

Progenitor cells of the biliary epithelial cell lineage.

Stem-like cells have been identified in liver that are able to differentiate in vivo and in culture to biliary epithelial cells (BEC), hepatocytes and oval cells. The growth factors/cytokines and signal pathways required for the differentiation processes are beginning to be evaluated. There is increasing evidence to suggest that these stem-like cells may originate from both the bone marrow population or from a precursor remnant from liver embryogenesis, as they share many of the same markers (CD34, c-kit, CD45). Most recently, it has been shown that a population of progenitor cells can copurify with mesenchymal bone marrow cells and differentiate under specific culture conditions to form both hepatic epithelial and also endothelial cells. The interaction of haemopoietic and mesenchymal stem cells needs further evaluation. The close association of ductular reactive cells and neovessels in end-stage cholestatic liver diseases and the relation to Jagged/Notch signalling pathway may be important in the regulation of stem cells to form both biliary epithelial and endothelial cells.