Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Here we sought to increase knowledge of HB pathobiology in an effort to move towards precision medicine. To this end, we used high-throughput technologies to identify new biomarkers and therapeutic targets for HB patients with poor prognosis METHODS: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically-annotated samples from 113 HB patients RESULTS: We discovered an unprecedented widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified two epigenomic clusters (Epi-CA, Epi-CB) with distinct degree of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first Molecular Risk Stratification of HB (MRS-HB), which encompasses three main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs since its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth CONCLUSIONS: Our findings expand our knowledge about the molecular features of HB and may contribute to improve current clinical stratification approaches and treatments to increase the survival of patients with HB.

BACKGROUND AND OBJECTIVE: Parapneumonic empyema (PPE) is a frequent complication of acute bacterial pneumonia in children. There is limited evidence regarding the optimal treatment of this condition. The aim of this study was to compare the efficacy of drainage plus urokinase versus video-assisted thoracoscopic surgery in the treatment of PPE in childhood. METHODS: This prospective, randomized, multicenter clinical trial enrolled patients aged <15 years and hospitalized with septated PPE. Study patients were randomized to receive urokinase or thoracoscopy. The main outcome variable was the length of hospital stay after treatment. The secondary outcomes were total length of hospital stay, number of days with the chest drain, number of days with fever, and treatment failures. The trial was approved by the ethics committees of all the participating hospitals. RESULTS: A total of 103 patients were randomized to treatment and analyzed; 53 were treated with thoracoscopy and 50 with urokinase. There were no differences in demographic characteristics or in the main baseline characteristics between the 2 groups. No statistically significant differences were found between thoracoscopy and urokinase in the median postoperative stay (10 vs 9 days), median hospital stay (14 vs 13 days), or days febrile after treatment (4 vs 6 days). A second intervention was required in 15% of children in the thoracoscopy group versus 10% in the urokinase group (P = .47). CONCLUSIONS: Drainage plus urokinase instillation is as effective as video-assisted thoracoscopic surgery as first-line treatment of septated PPE in children.