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Background: There is ongoing debate regarding liver transplantation (LT) versus liver resection (LR) for locally advanced hepatoblastoma. However, comparative studies are lacking. Consequently, a significant evidence gap persists, hindering the establishment of consensus guidelines. This study aimed to compare LT and LR for locally advanced hepatoblastoma, using predefined inclusion criteria to ensure comparable intervention groups., Methods: According to current Children's Oncology Group (COG) and SIOPEL (European Childhood Liver Tumour Study Group) recommendations, hepatoblastoma that requires LT evaluation was defined as either PRETEXT (PRE-Treatment EXTent of tumor) IV F+, POST-TEXT (POST-Treatment EXTent of tumor) IV, POST-TEXT P+, and/or POST-TEXT V+. A systematic literature search (Medline/Web-of-Science/Embase) was performed. Only patients who met the aforementioned criteria were included. Patient data were extracted individually and pooled., Results: A total of 189 patients with locally advanced hepatoblastoma from 55 studies met the specified criteria, with 111 undergoing LT and 78 LR. There were no significant differences between the two groups in age, alpha-fetoprotein (AFP), and PRETEXT stages. Local recurrence was more common after LR (14% vs. 3% in LT, p = .008), while distant recurrence was more often observed after LT (16% vs. 5% in LR, p = .035). Overall survival (OS) and event-free survival (EFS) did not differ significantly between LT and LR (5-year OS: LT = 75.3% [95% confidence interval: 66.5-85.2], LR = 87.6% [80.4-95.6], p = .140; 5-year EFS: LT = 68.5% [59.3-79.1], LR = 71.1% [60.7-83.3], p = .700)., Conclusion: Real-life data revealed that a considerable number of patients with locally advanced hepatoblastoma underwent LR. This analysis suggests that outcomes are similar and favorable for both approaches. LR can therefore be considered an effective alternative to LT in selected cases even in locally advanced hepatoblastoma., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Objective: To assess the incidence of posthepatectomy liver failure (PHLF) and the role of the future liver remnant (FLR) in children undergoing major hepatectomy., Summary Background Data: Incidence and risk factors of PHLF in children are unclear, with no validated definition for this age group. Consequently, the role of the FLR in pediatric hepatectomy and evidence-based preoperative guidelines remain undefined., Methods: All pediatric patients undergoing major hepatectomy at a tertiary care center over a 10-year study period were analyzed. Preoperative imaging was used for volumetry. The incidence of PHLF was assessed applying predefined definitions, and the prognostic impact of the FLR on PHLF and complications was evaluated., Results: 125 children underwent major hepatectomy, including 35 trisectionectomies. There was a strong correlation between imaging-based measured total liver volume and calculated standard liver volume (r=0.728, P<0.001). The median total liver volume-to-body weight (BW) ratio was 3.4%, the median FLR/BW ratio was 1.5%. The median FLR-to-total liver volume ratio was 44% (range 18%-97%). No clinically relevant PHLF occurred. FLR/total liver volume and FLR/BW ratios had low predictive value for postoperative liver dysfunction and morbidity., Conclusion: This is the largest reported single-center series of pediatric major hepatectomies. PHLF is exceedingly rare in children. The liver volume-to-body weight ratio is higher in children compared to adults, and the FLR is sufficient even in extreme resections with less than 20% of liver remnant. These findings strongly question the use of ALPPS, portal vein embolization, or transplantation based on suspected insufficient liver remnant in children., Competing Interests: Conflict of Interest: All authors declare that there no conflicts of interest with regard to this work., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with metastatic hepatoblastoma are treated with severely toxic first-line chemotherapies in combination with surgery. Yet, inadequate response of lung metastases to neo-adjuvant chemotherapy still compromises patient outcomes making new treatment strategies, tailored to more efficient lung clearance, mandatory., Methods: We harnessed a comprehensive patient-derived xenograft platform and a variety of in vitro and in vivo assays to establish the preclinical and biological rationale for a new drug for patients with metastatic hepatoblastoma., Results: The testing of a library of established drugs on patient-derived xenografts identified histone deacetylase inhibitors, most notably panobinostat, to be highly efficacious on hepatoblastoma cells, as compared to non-cancerous cells. Molecularly, the anti-tumor effect of panobinostat is mediated by posttranslational obstruction of the MYC oncoprotein as a result of dual specificity phosphatase 1 upregulation, thereby leading to growth inhibition and programmed cell death. Of clinical importance, upregulation of the MYC target gene nucleophosmin 1 is indicative of response to panobinostat and associated with metastatic disease in patients with hepatoblastoma. The combination of panobinostat with the current SIOPEL 4 induction protocol, consisting of cisplatin and doxorubicin, revealed high synergies already at low nanomolar levels. The simulation of a clinical trial, with this combination therapy, in patient-derived xenograft models, and ultimately heterotypic lung metastasis mimics clearly underscored the potency of this approach., Conclusion: Integrated studies define MYC inhibition by panobinostat as a novel treatment element to be introduced into the therapeutic strategy for patients with metastatic hepatoblastoma., Competing Interests: Declarations Ethics approval and consent to participate In vivo testing in mice was carried out according to the Italian Decree (08/2023-UT). Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background/objectives: In paediatric liver transplantation, donor-recipient compatibility depends on graft size. We explored whether the graft weight can be predicted using the donor's biometric parameters., Methods: We used seven easily available biometric variables in 142 anonymised paediatric and adult donors, with data collected between 2016 and 2022. The whole or partial liver was transplanted in our hospital from these donors. We identified the variables that had the strongest correlation to our response variable: whole liver graft weight., Results: In child donors, we determined two linear models: using donor weight and height on the one hand and using donor weight and right liver span on the other hand. Both models had a coefficient of determination R 2 = 0.86 and p -value < 10 -5 . We also determined two models in adult donors using donor weight and height (R 2 = 0.33, p < 10 -4 ) and donor weight and sternal height (R 2 = 0.38, p < 10 -4 ). The models proved valid based on our external dataset of 245 patients from two institutions., Conclusions: In clinical practise, our models could provide rapidly accessible estimates to determine whole graft dimension compatibility in liver transplantation in children and adults. Determining similar models predicting the left lobe and lateral segment weight could prove invaluable in paediatric transplantation.

Background: Twenty percent of children with hepatoblastoma (HB) have lung metastasis at diagnosis. Treatment protocols recommend surgical removal of chemotherapy-refractory lung nodules, however no chronological order is established. As hepatectomy is followed by release of growth factors, it has been proposed that partial hepatectomy (PH) could boost local or distant residual tumor growth., Methods: To evaluate the impact of PH on distant tumor growth, PH was performed in mice subcutaneously implanted with a HB patient-derived xenograft (PDX). The influence of PH on tumor growth at primary site was assessed by performing PH concomitantly to HB PDXs orthotopic implantation., Results: Subcutaneously implanted HB PDX failed to show any influence of hepatectomy on tumor growth. Instead, intrahepatic tumor growth of one of the 4 HB PDXs implanted orthotopically was clearly enhanced. Cells derived from the hepatectomy-sensitive HB PDX exposed to hepatic growth factor (HGF) showed increased proliferation rate compared to cells derived from a hepatectomy-insensitive model, suggesting that the HGF/MET pathway could be one of the effectors of the crosstalk between liver regeneration and HB growth., Conclusion: These results suggest that hepatectomy can contribute to HB growth in some patients, further studies will be necessary to identify biomarkers predictive of patient risk of PH-induced HB recurrence., Impact: Key message: Cytokines and growth factors secreted following partial hepatectomy can contribute to intrahepatic tumor growth in some hepatoblastoma models. What does it add to the existing literature: It is the first article about the impact of liver regeneration induced by partial hepatectomy on hepatoblastoma local or distant tumoral growth in nude mice. What is the impact: It is important to identify the secreted factors that enhance tumor growth and to define biomarkers predictive of patient risk of partial hepatectomy-induced hepatoblastoma recurrence., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: About 5% of Wilms tumors present with vascular extension, which sometimes extends to the right atrium. Vascular extension does not affect the prognosis, but impacts the surgical strategy, which is complex and not fully standardized. Our goal is to identify elements of successful surgical management of Wilms tumors with vascular extensions., Patients and Methods: A retrospective study of pediatric Wilms tumors treated at three sites (January 1999-June 2019) was conducted. The inclusion criterion was the presence of a renal vein and vena cava thrombus at diagnosis. Tumor stage, pre and postoperative treatment, preoperative imaging, operative report, pathology, operative complications, and follow-up data were reviewed., Results: Of the 696 pediatric patients with Wilms tumors, 69 (9.9%) met the inclusion criterion. In total, 24 patients (37.5%) had a right atrial extension and two presented with Budd-Chiari syndrome at diagnosis. Two died at diagnosis owing to pulmonary embolism. All patients received neoadjuvant chemotherapy and thrombus regressed in 35.6% of cases. Overall, 14 patients had persistent intra-atrial thrombus extension (58%) and underwent cardiopulmonary bypass. Most thrombi (72%) were removed intact with nephrectomy. Massive intraoperative bleeding occurred during three procedures. Postoperative renal insufficiency was identified as a risk factor for patient survival (p = 0.01). With a median follow-up of 9 years (range: 0.5-20 years), overall survival was 89% and event-free survival was 78%., Conclusions: Neoadjuvant chemotherapy with proper surgical strategy resulted in a survival rate comparable to that of children with Wilms tumors without intravascular extension. Clinicians should be aware that postoperative renal insufficiency is associated with worse survival outcomes., (© 2024. Society of Surgical Oncology.)

Background and Aims: Hepatoblastoma (HB) is the predominant form of pediatric liver cancer, though it remains exceptionally rare. While treatment outcomes for children with HB have improved, patients with advanced tumors face limited therapeutic choices. Additionally, survivors often suffer from long-term adverse effects due to treatment, including ototoxicity, cardiotoxicity, delayed growth, and secondary tumors. Consequently, there is a pressing need to identify new and effective therapeutic strategies for patients with HB. Computational methods to predict drug sensitivity from a tumor's transcriptome have been successfully applied for some common adult malignancies, but specific efforts in pediatric cancers are lacking because of the paucity of data., Approach and Results: In this study, we used DrugSense to assess drug efficacy in patients with HB, particularly those with the aggressive C2 subtype associated with poor clinical outcomes. Our method relied on publicly available collections of pan-cancer transcriptional profiles and drug responses across 36 tumor types and 495 compounds. The drugs predicted to be most effective were experimentally validated using patient-derived xenograft models of HB grown in vitro and in vivo. We thus identified 2 cyclin-dependent kinase 9 inhibitors, alvocidib and dinaciclib as potent HB growth inhibitors for the high-risk C2 molecular subtype. We also found that in a cohort of 46 patients with HB, high cyclin-dependent kinase 9 tumor expression was significantly associated with poor prognosis., Conclusions: Our work proves the usefulness of computational methods trained on pan-cancer data sets to reposition drugs in rare pediatric cancers such as HB, and to help clinicians in choosing the best treatment options for their patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Hepatoblastomas (HB) display heterogeneous cellular phenotypes that influence the clinical outcome, but the underlying mechanisms are poorly understood. Here, we use a single-cell multiomic strategy to unravel the molecular determinants of this plasticity. We identify a continuum of HB cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activations underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation states. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy., (© 2024. The Author(s).)

Objectives: We aimed to analyze the risk factors for management failure of BC after pediatric liver transplantation (pLT) by retrospectively analyzing primary pLT performed between 1997 and 2018 (n = 620 patients)., Results: In all, 117/620 patients (19%) developed BC. The median (range) follow-up was 9 (1.4-21) years. Patient survival at 1, 5 and 10 years was 88.9%, 85.7%, 84.4% and liver graft survival was 82.4%, 77.4%, and 74.3% respectively. Graft not patient survival was impaired by BC (p = 0.01). Multivariate analysis identified the number of dilatation courses > 2 (p = 0.008), prolonged cold ischemia time (p = 0.004), anastomosed multiple biliary ducts (p = 0.019) and hepatic artery thrombosis (p = 0.01) as factors associated with impaired graft survival. The number of dilatation courses > 2 (p < 0.001) and intrahepatic vs anastomotic stricture (p = 0.014) were associated with management failure. Thus, repeated (> 2) radiologic dilatation courses are associated with impaired graft survival and management failure. Overall, graft but not patient survival was impaired by BC., (© 2024. The Author(s).)

Background: Hepatoblastoma is the most frequent pediatric liver cancer. The current treatments lead to 80% of survival rate at 5 years. In this study, we evaluated the clinical relevance of molecular features to identify patients at risk of chemoresistance, relapse and death of disease., Methods: All the clinical data of 86 children with hepatoblastoma were retrospectively collected. Pathological slides were reviewed, tumor DNA sequencing (by whole exome, whole genome or target) and transcriptomic profiling with RNAseq or 300-genes panel were performed. Associations between the clinical, pathological, mutational and transcriptomic data were investigated., Results: High-risk patients represented 44% of our series and the median age at diagnosis was 21.9 months (range: 0-208). Alterations of the WNT/ß-catenin pathway and of the 11p15.5 imprinted locus were identified in 98% and 74% of the tumors, respectively. Other cancer driver genes mutations were only found in less than 11% of tumors. After neoadjuvant chemotherapy, disease-specific survival and poor response to neoadjuvant chemotherapy were associated with 'Liver Progenitor' (p = 0.00049, p < 0.0001) and 'Immune Cold' (p = 0.0011, p < 0.0001) transcriptomic tumor subtypes, SBS35 cisplatin mutational signature (p = 0.018, p = 0.001), mutations in rare cancer driver genes (p = 0.0039, p = 0.0017) and embryonal predominant histological type (p = 0.0013, p = 0.0077), respectively. Integration of the clinical and molecular features revealed a cluster of molecular markers associated with resistance to chemotherapy and survival, enlightening transcriptomic 'Immune Cold' and Liver Progenitor' as a predictor of survival independent of the clinical features., Conclusions: Response to neoadjuvant chemotherapy and survival in children treated for hepatoblastoma are associated with genomic and pathological features independently of the clinical features., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Liver tumors account for approximately 2% of all pediatric malignancies. Children with advanced stages of hepatoblastoma (HB) are cured only 50-70% of the time while children with advanced hepatocellular carcinoma (HCC) have a <20% 5-year overall survival. This scoping review was performed to highlight the paucity of rigorous, reliable data guiding the management of relapsed pediatric HB or HCC. When these patients are enrolled on prospective trials, the trials are often histology-agnostic, exclude patients less than a year of age, lack a liquid formulary of the drug under study, exclude recipients of a solid organ transplant, and enroll only 1-2 patients limiting the ability to deduce efficacious regimens for current use or future study. We highlight the creation of a global pediatric consortium intended to source retrospective relapse data from over 100 institutions spanning 4 continents. The data collected from this effort will inform future relapse trials., Competing Interests: Howard Katzenstein is employed by Merck, Rayway NJ but has no conflicts with this manuscript. Marc Ansari’s institute receives financial support from CANSEARCH and Jazz Pharmaceuticals, but this does not constitute a personal conflict. All other authors report no conflicts of interest., (Crown Copyright © 2024 Published by Elsevier Ltd.)

Background: As the variable clinical outcome of patients with hepatoblastoma (HB) cannot be explained by genetics alone, the identification of drugs with the potential to effectively reverse epigenetic alterations is a promising approach to overcome poor therapy response. The gene ubiquitin like with PHD and ring finger domains 1 (UHRF1) represents an encouraging epigenetic target due to its regulatory function in both DNA methylation and histone modifications and its clinical relevance in HB., Methods: Patient-derived xenograft in vitro and in vivo models were used to study drug response. The mechanistic basis of CM-272 treatment was elucidated using RNA sequencing and western blot experiments., Results: We validated in comprehensive data sets that UHRF1 is highly expressed in HB and associated with poor outcomes. The simultaneous pharmacological targeting of UHRF1-dependent DNA methylation and histone H3 methylation by the dual inhibitor CM-272 identified a selective impact on HB patient-derived xenograft cell viability while leaving healthy fibroblasts unaffected. RNA sequencing revealed downregulation of the IGF2-activated survival pathway as the main mode of action of CM-272 treatment, subsequently leading to loss of proliferation, hindered colony formation capability, reduced spheroid growth, decreased migration potential, and ultimately, induction of apoptosis in HB cells. Importantly, drug response depended on the level of IGF2 expression, and combination assays showed a strong synergistic effect of CM-272 with cisplatin. Preclinical testing of CM-272 in a transplanted patient-derived xenograft model proved its efficacy but also uncovered side effects presumably caused by its strong antitumor effect in IGF2-driven tumors., Conclusions: The inhibition of UHRF1-associated epigenetic traces, such as IGF2-mediated survival, is an attractive approach to treat high-risk HB, especially when combined with the standard-of-care therapeutic cisplatin., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Pediatric liver tumors are very rare tumors with the most common diagnosis being hepatoblastoma. While hepatoblastomas are predominantly sporadic, around 15% of cases develop as part of predisposition syndromes such as Beckwith-Wiedemann (11p15.5 locus altered). Here, we identify mosaic genetic alterations of 11p15.5 locus in the liver of hepatoblastoma patients without a clinical diagnosis of Beckwith-Wiedemann syndrome. We do not retrieve these alterations in children with other types of pediatric liver tumors. We show that mosaic 11p15.5 alterations in liver FFPE sections of hepatoblastoma patients display IGF2 overexpression and H19 downregulation together with an alteration of the liver zonation. Moreover, mosaic livers' microenvironment is enriched in extracellular matrix and angiogenesis. Spatial transcriptomics and single-nucleus RNAseq analyses identify a 60-gene signature in 11p15.5 altered hepatocytes. These data provide insights for 11p15.5 mosaicism detection and its functional consequences during the early steps of carcinogenesis., (© 2023. The Author(s).)

Background Data: EA is the most frequent congenital esophageal malformation. Long gap EA remains a therapeutic challenge for pediatric surgeons. A case case-control prospective study from a multi-institutional national French data base was performed to assess the outcome, at age of 1 and 6 years, of long gap esophageal atresia (EA) compared with non-long gap EA/tracheo-esophageal fistula (TEF). The secondary aim was to assess whether initial treatment (delayed primary anastomosis of native esophagus vs. esophageal replacement) influenced mortality and morbidity at ages 1 and 6 years., Methods: A multicentric population-based prospective study was performed and included all patients who underwent EA surgery in France from January 1, 2008 to December 31, 2010. A comparative study was performed with non-long gap EA/TEF patients. Morbidity at birth, 1 year, and 6 years was assessed., Results: Thirty-one patients with long gap EA were compared with 62 non-long gap EA/TEF patients. At age 1 year, the long gap EA group had longer parenteral nutrition support and longer hospital stay and were significantly more likely to have complications both early post-operatively and before age 1 year compared with the non-long gap EA/TEF group. At 6 years, digestive complications were more frequent in long gap compared to non-long gap EA/TEF patients. Tracheomalacia was the only respiratory complication that differed between the groups. Spine deformation was less frequent in the long gap group. There were no differences between conservative and replacement groups at ages 1 and 6 years except feeding difficulties that were more common in the native esophagus group., Conclusions: Long gap strongly influenced digestive morbidity at age 6 years., Competing Interests: Conflict of interest All the authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Early biliary drainage surgery (BDS; Kasai) is associated with longer transplant-free survival in biliary atresia. However, evidence is lacking on whether an age limit can be established at which liver transplantation should be performed as first-line treatment for children with a delayed diagnosis of biliary atresia. The aim of the current study was to compare the outcome of a large cohort of children with biliary atresia who underwent BDS after 90 days of life with those who underwent early BDS (before 90 days) and those who did not receive BDS and were directly referred for primary liver transplantation., Methods: All patients with biliary atresia treated at Bicêtre, Paris-Saclay University Hospital between 1995 and 2017 were analysed in this STROBE-compliant study. Three groups were defined: BDS before 90 days of life (early BDS); BDS after 90 days of life (late BDS); and patients without BDS who were referred for primary liver transplantation (no BDS). Patient characteristics, overall survival, and native liver survival were compared., Results: Of 424 children with biliary atresia, 69 patients (16 per cent) were older than 90 days when they underwent BDS. Twenty-five patients had no BDS and were referred for primary liver transplantation (6 per cent). The main reason for not performing BDS was manifest portal hypertension (18/25). Two- and 5-year transplant-free survival were significantly higher in patients with late BDS compared with no BDS (53.5 versus 12.0 per cent respectively for 2-year data and 30.4 versus 4.0 per cent respectively for 5-year data, P < 0.001). Five- and 10-year overall survival did not differ between early BDS (92 and 91 per cent respectively), late BDS (88 and 83 per cent respectively) and no BDS (80 and 80 per cent respectively, P = 0.061)., Conclusion: Age alone should not routinely be considered a contraindication to BDS in patients older than 90 days. Liver transplantation in infancy (less than 12 months) could be avoided in 88 per cent of cases with late diagnosis of biliary atresia and is delayed significantly even when BDS is performed after 3 months. Overall survival is at least equal to patients who are referred for primary liver transplantation., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Aim of the study: The cavitron ultrasonic surgical aspirator (CUSA) has gained popularity in adult surgical oncology, but its application in children is limited to liver surgery and neurosurgical procedures. The complete resection of neuroblastoma with image-defined risk factors (IDRFs) is still considered one of the most difficult procedures to achieve in pediatric surgical oncology, with a high morbidity rate and potential risk of intraoperative mortality. The aim of our study is to describe the application of ultrasonic dissection in neuroblastoma with IDRFs. Methods: A retrospective study was performed, analyzing patients operated on from 2000 to 2018. Patient characteristics, resection completeness, and postoperative surgical and oncology outcomes were analyzed. Main results: Twenty-six patients with high-risk neuroblastoma and IDRFs were operated on in the study period with a CUSA. A complete macroscopic resection was performed in 50% of patients, while the other half was operated on with minimal residual (<5 mL). Six post-operative complications occurred without the need for surgery (Clavien−Dindo < 3). The overall survival was 50%, with a median follow-up of 69.6 months (5.6−140.4). Conclusions: The application of the CUSA in neuroblastoma with IDRFs can be considered an effective and safe alternative technique to achieve a radical resection.

Background: Focal nodular hyperplasia (FNH) in children is a rare but benign tumour, which must be differentiated from malignant entities to avoid unnecessary treatment, leading to potential morbidity., Objectives: To provide data on imaging findings of these lesions with a suggested algorithm for diagnosis, sampling and follow-up., Materials and Methods: This retrospective review evaluated imaging of all patients diagnosed with FNH in two tertiary referral centres in Europe between 1975 and 2018., Results: One hundred and four patients with 137 tumours were reviewed. The mean age at presentation was 8.2 years. The median tumour size was 5 cm (range: 0.3-29 cm). Multiple lesions were seen in 16.3% of patients. The male-to-female ratio was 1:2., Conclusion: FNH with typical features on imaging can be safely followed up once the diagnosis has been established. The use of contrast-enhanced ultrasound and magnetic resonance imaging allows accurate characterisation in most cases. Histological sampling is only advised when there is diagnostic doubt. Atypical arterial enhancement of FNH should prompt the search for a congenital portosystemic shunt., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The present study aimed to assess long-term functional outcomes of children with anorectal malformations (ARMs) across a network of expert centers in France., Methods: Retrospective cross-sectional study of patients ages 6-30 years that had been surgically treated for ARM. Patient and ARM characteristics (eg, level, surgical approach) and functional outcomes were assessed in the different age groups., Results: Among 367 patients, there were 155 females (42.2%) and 212 males (57.8%), 188 (51.2%) cases with, and 179 (48.8%) higher forms without, perineal fistula. Univariate and multivariate statistical analyses with logistic regression showed correlation between the level of the rectal blind pouch and voluntary bowel movements (odds ratio [OR] = 1.84 [1.31-2.57], P < 0.001), or soiling (OR = 1.72 [1.31-2.25], P < 0.001), which was also associated with the inability to discriminate between stool and gas (OR = 2.45 [1.28-4.67], P = 0.007) and the presence of constipation (OR = 2.97 [1.74-5.08], P < 0.001). Risk factors for constipation were sacral abnormalities [OR = 2.26 [1.23-4.25], P = 0.01) and surgical procedures without an abdominal approach (OR = 2.98 [1.29-6.87], P = 0.01). Only the holding of voluntary bowel movements and soiling rates improved with age., Conclusion: This cross-sectional study confirms a strong association between anatomical status and functional outcomes in patients surgically treated for ARM. It specifically highlights the need for long-term follow-up of all patients to help them with supportive care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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. The use of living donors steadily increased from A to C (A, n = 296 [7%]; B, n = 1131 [23%]; and C, n = 1985 [39%]; p = 0.0001). Overall, the 5-year graft survival rate has improved from 65% in group A to 75% in group B (p < 0.0001) and to 79% in group C (B versus C, p < 0.0001). Graft half-life was 31 years, overall; it was 41 years for children who survived the first year after transplant. The late annual graft loss rate in teenagers is higher than that in children aged <12 years and similar to that of young adults. No evidence for accelerated graft loss after age 18 years was found., Conclusions: Pediatric liver transplantation has reached a high efficacy as a cure or treatment for severe liver disease in infants and children. Grafts that survived the first year had a half-life similar to standard human half-life. Transplantation before or after puberty may be the pivot-point for lower long-term outcome in children. Further studies are necessary to revisit some old concepts regarding transplant benefit (survival time) for small children, the role of recipient pathophysiology versus graft aging, and risk at transition to adult age., (© 2021 American Association for the Study of Liver Diseases.)

Background and Aims: Prognosis of hepatoblastoma patients has increased with cisplatin-based chemotherapy and high-quality resection including liver transplant. Consequently current risk-adapted therapeutic strategy aims to reduce long-term side effects in patients with standard risk disease., Methods: We report long-term mortality and morbidity data concerning 151 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies (sex-ratio M/F = 1.6, median age at diagnosis = 2.6 years [range 0-17.7], median year at diagnosis = 2008 [1994-2017]). Fifty-three patients had loco-regional risk factors VPEFR, 12 were PRETEXT-IV and 30 were metastatic. All received cisplatin and 84 anthracyclines. Twelve had liver transplant. To assess hearing, renal and cardiac functions, audiograms were performed in 116/151 patients (76.8%), glomerular filtration rate in 113/151 (74.8%) and cardiac ultrasound in 65/84 (77.4%) anthracycline-exposed patients., Results: With a median follow-up of 9.4 years (range 2.1-25.8), four late relapses, one second malignancy (Acute Myeloid Leukemia AML-M5) and two deaths (one from hepatoblastoma, one from AML) occurred. The 10-years event free survival and overall survival probabilities were 95.5% (95% CI 91.9-99.1) and 98.7% (95% CI 96.8-100), respectively. Sixty-eight non-oncologic health-events included 57 cases of hearing loss (including 25 Brock 3-4), three liver cirrhosis, three pre-operative portal cavernoma, two focal nodular hyperplasia, two grade-1 chronic kidney diseases and one asymptomatic cardiac dysfunction were reported. Ototoxicity was significantly associated with cisplatin cumulative dose (OR = 2.07, 95% CI 1.32-3.24, p = 0.001) and carboplatin exposure (OR = 3.14, 95% CI 1.30-7.58, p = 0.01) in multivariable analysis adjusted for sex and age at diagnosis., Conclusions: With current risk-adapted strategies, hepatoblastoma is a highly curable disease, with very rare relapses, and few late effects except hearing loss which remains a serious condition in these very young patients., (© 2021. Asian Pacific Association for the Study of the Liver.)