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BackgroundLiver tumors are rare in children with histologic heterogeneity that makes diagnosis challenging. Systematic histopathological review, performed as part of collaborative therapeutic protocols, identified relevant histologic subtypes that are important to distinguish. The Children's Hepatic tumors International Collaboration (CHIC) was established to study pediatric liver tumors on a global scale and led to establishment of a provisional consensus classification for use in international clinical trials. The current study is the validation of this initial classification and first large-scale application by international expert reviewers.ProcedureThe CHIC initiative includes data from 1605 children treated on eight multicenter hepatoblastoma (HB) trials. Review of 605 available tumors was performed by seven expert pathologists from three consortia (US, EU, Japan). Cases with discordant diagnoses were collectively reviewed to reach a final consensus diagnosis.ResultsOf 599 cases with sufficient material for review, 570 (95.2%) were classified as HB by all consortia, and 29 (4.8%) as non-HB, which included "hepatocellular neoplasm, NOS" and malignant rhabdoid tumors. 453 of 570 HBs were classified as epithelial by final consensus. Some patterns (i.e., small cell undifferentiated, macrotrabecular, cholangioblastic) were selectively identified by reviewers from different consortia. All consortia identified a similar number of mixed epithelial-mesenchymal HB.ConclusionsThis study represents the first large-scale application and validation of the pediatric malignant hepatocellular tumors consensus classification. It is a valuable resource to train future generations of investigators on accurate diagnosis of these rare tumors and provides a framework for further international collaborative studies and refinement of the current classification of pediatric liver tumors.

Small cell undifferentiated (SCU) histology and alpha-fetoprotein (AFP) levels below 100 ng/mL have been reported as poor prognostic factors in hepatoblastoma (HB); subsequent studies reported SMARCB1 mutations in some SCU HBs confirming the diagnosis of rhabdoid tumor. The Children's Hepatic tumors International Collaboration (CHIC) database was queried for patients with HB who had AFP levels less than 100 ng/mL at diagnosis or were historically diagnosed as SCU HBs. Seventy-three of 1605 patients in the CHIC database were originally identified as SCU HB, HB with SCU component, or HB with low AFP levels. Upon retrospective review, they were re-classified as rhabdoid tumors (n = 11), HB with SCU component (n = 41), and HB with low AFP (n = 14). Seven were excluded for erroneously low AFP levels. Overall survival was 0% for patients with rhabdoid tumors, 76% for patients with HB with SCU component, and 64% for patients with HB with AFP less than 100 ng/mL. Patients with HB with SCU component or low AFP should be assessed for SMARCB1 mutations and, if confirmed, treated as rhabdoid tumors. When rhabdoid tumors are excluded, the presence of SCU component and low AFP at diagnosis were not associated with poor prognosis in patients diagnosed with HB.

BackgroundComparative assessment of treatment results in paediatric hepatoblastoma trials has been hampered by small patient numbers and the use of multiple disparate staging systems by the four major trial groups. To address this challenge, we formed a global coalition, the Children's Hepatic tumors International Collaboration (CHIC), with the aim of creating a common approach to staging and risk stratification in this rare cancer.MethodsThe CHIC steering committee-consisting of leadership from the four major cooperative trial groups (the International Childhood Liver Tumours Strategy Group, Children's Oncology Group, the German Society for Paediatric Oncology and Haematology, and the Japanese Study Group for Paediatric Liver Tumours)-created a shared international database that includes comprehensive data from 1605 children treated in eight multicentre hepatoblastoma trials over 25 years. Diagnostic factors found to be most prognostic on initial analysis were PRETreatment EXTent of disease (PRETEXT) group; age younger than 3 years, 3-7 years, and 8 years or older; α fetoprotein (AFP) concentration of 100 ng/mL or lower and 101-1000 ng/mL; and the PRETEXT annotation factors metastatic disease (M), macrovascular involvement of all hepatic veins (V) or portal bifurcation (P), contiguous extrahepatic tumour (E), multifocal tumour (F), and spontaneous rupture (R). We defined five clinically relevant backbone groups on the basis of established prognostic factors: PRETEXT I/II, PRETEXT III, PRETEXT IV, metastatic disease, and AFP concentration of 100 ng/mL or lower at diagnosis. We then carried the additional factors into a hierarchical backwards elimination multivariable analysis and used the results to create a new international staging system.ResultsWithin each backbone group, we identified constellations of factors that were most predictive of outcome in that group. The robustness of candidate models was then interrogated using the bootstrapping procedure. Using the clinically established PRETEXT groups I, II, III, and IV as our stems, we created risk stratification trees based on 5 year event-free survival and clinical applicability. We defined and adopted four risk groups: very low, low, intermediate, and high.InterpretationWe have created a unified global approach to risk stratification in children with hepatoblastoma on the basis of rigorous statistical interrogation of what is, to the best of our knowledge, the largest dataset ever assembled for this rare paediatric tumour. This achievement provides the structural framework for further collaboration and prospective international cooperative study, such as the Paediatric Hepatic International Tumour Trial (PHITT).FundingEuropean Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission (grant number 261474); Children's Oncology Group CureSearch grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Clinical Trials for Development of New Drugs and Medical Devices, Japan Agency for Medical Research; and Swiss Cancer Research grant.

Introduction In pediatric Crohn's disease ileocecal resection is performed reluctantly as postoperative recurrence is frequent. Anti-tumor necrosis factor (TNF) therapy reduces postoperative recurrence rates but increases the risk for infections. Materials and Methods We retrospectively reviewed pediatric Crohn's disease patients who underwent ileocecal resection in our center. We compared disease activity and z -scores for height, weight, and body mass index of patients, who continuously received perioperative anti-TNF therapy (TNF +), with those who did not (TNF–). Results Of 29 patients (48% females), 13 and 16 were grouped to TNF+ and TNF–, respectively. Patients' characteristics did not differ between groups, except a longer follow-up time in TNF–. We saw significant postoperative improvement but no normalization in z -scores for weight (1.78 vs. 0.77, p < 0.001), body mass index (1.08 vs. 0.22, p < 0.001), and height (0.88 vs. 0.66, p < 0.001). Disease activity improved significantly more in patients receiving anti-TNF therapy (moderate improvement in 83% vs. 31%, p = 0.02). Endoscopic recurrence was more frequent in patients without anti-TNF therapy (80% vs. 20%; p = 0.023), but endoscopic follow-up was incomplete. There was no increase of infections under perioperative anti-TNF therapy (1 patient each; p = 1.000). Conclusion In patients with localized Crohn's disease an ileocecal resection leads to short-term postoperative improvement of disease activity, body mass index, weight, and growth. For relevant catch-up growth an earlier intervention is necessary. Continuous perioperative anti-TNF therapy had no increased risk of perioperative infections. [ABSTRACT FROM AUTHOR]

Background: Congenital diaphragmatic hernia (CDH) repair can be challenging, particularly when a larger defect is present. Barbed sutures prevent the suture from slipping back after approximation of the tissues. Although introduced almost 2 decades ago, barbed sutures have not been widely used for CDH repair. We report our initial experience and pitfalls. Methods: All patients presenting with CDH from 2021 onward underwent repair using barbed sutures. Demographics, operative parameters, complications, and outcomes were prospectively recorded. Results: A total of 13 patients underwent CDH repair during the study interval (median age 6 days, range 3 days to 5.75 years). Median operative time was 89 min (range 46 to 288 min). Five thoracoscopic and eight open procedures were performed. Severe pulmonary hypertension and ECMO (extracorporeal membrane oxygenation) were considered contraindications for thoracoscopic repair. The included patients were compared to a historic controlled group performed without barbed sutures. The barbed suture facilitated easy and quick closure of the defects in most cases and obviated the need for knot tying. One patient in the thoracoscopic group had a patch placed due to high tension after the barbed sutures tore the diaphragm. At a median follow-up time of 15 months (range 2 to 34 months), one patient had died, and one patient with complete diaphragmatic agenesis was home-ventilated. There were no recurrences. Median operative time trended lower (89 min) than in the historic control group repaired without barbed sutures (119 min, p < 0.06) after eliminating outliers with large, complex patch repairs. Conclusions: Barbed sutures simplify congenital diaphragmatic hernia repair regardless of whether a minimal-invasive or open approach is performed. Patch repair is not a contraindication for using barbed sutures. The resulting potential time savings make them particularly useful in patients with cardiac or other severe co-morbidities in which shorter operative times are essential. In cases with high tension, though, the barbs may tear through and produce a "saw" effect on the tissue with subsequent damage. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatoblastoma (HB) is an embryonal liver neoplasm of early childhood with a poor prognosis for patients with distant metastases and vascular invasion. We and others have previously shown that the overexpression of insulin-like growth factor 2 (IGF2), loss of imprinting at the IGF2/H19 locus, and amplification of pleomorphic adenoma gene 1 (PLAG1) are common features in HB, suggesting a critical role of the IGF axis in hepatoblastomagenesis. In this study, we investigated the role of the insulin-like growth factor binding protein 3 (IGFBP3), a known competitor of the IGF axis, in pediatric liver cancers. Results The IGFBP3 gene was highly expressed in normal pediatric livers but was heavily downregulated in four HB cell lines and the majority of HB primary tumors (26/36). Detailed methylation analysis of CpG sites in the IGFBP3 promoter region by bisulfite sequencing revealed a high degree of DNA methylation, which is causatively associated with the suppression of IGFBP3 in HB cell lines. Consequently, the treatment of HB cell lines with 5-aza-2'-deoxycytidine resulted in DNA demethylation and reactivation of the epigenetically silenced IGFBP3 expression. Interestingly, IGFBP3 promoter methylation predominantly occurred in metastatic HB with vascular invasion. Restoring IGFBP3 expression in HB cells resulted in reduced colony formation, migration, and invasion. Conclusion This study provides the first direct evidence that the reactivation of IGFBP3 decreases aggressive properties of pediatric liver cancer cells and that IGFBP3 promoter methylation might be used as an indicator for vessel-invasive tumor growth in HB patients.