Dactinomycin-induced veno-occlusive disease in rats. The hepatoprotective action of amifostine. Evaluation in a light and electron microscope

The purpose of the study was to draw upan experimental model of hepatic veno-occlusive disease (VOD) induced by dactinomycin (ACT) and to investigate the possible hepatoprotective effects of Ethyol (amifostine). Pathological changes corresponding to a VOD picture of varying intensification were found in the liver samples obtained from all the rats receiving ACT. Amifostine appears to act protectively to liver changes caused by dactinomycin

Dziecko z asplenią w praktyce lekarza pierwszego kontaktu

Przedstawiono rolę lekarza pierwszego kontaktu jako niezwykle istotnego ogniwa w realizacji programu kompleksowej opieki nad dzieckiem z asplenią. Opisano postępowanie, które obejmuje realizację profilaktyki przeciwinfekcyjnej w postaci szczepień ochronnych oraz długotrwałej antybiotykoterapii, postępowanie w nadpłytkowości po splenektomii oraz szeroko rozumianą edukację pacjenta i jego rodziny. W pracy zamieszczono przykłady pięciu sytuacji klinicznych, z jakimi może spotkać się lekarz pierwszego kontaktu mający pod swoją opieką dziecko bez śledziony: stosowanie profilaktyki antybiotykowej, leczenie posocznicy, postępowanie w przypadku pogryzienia przez psa i w przypadku nadpłytkowości po splenektomii

Guidelines from the Polish Surgical Society and Polish Society of Oncological Surgery Concerning Quality Assurance for Centres Performing Cytoreductive Procedures and HIPEC Procedures in the Treatment of Primary and Secondary Peritoneal Tumours

Surgical treatment of patients with peritoneal metastases in combination with Hyperthermic intraperitoneal Chemotherapy (HIPEC) and systemic treatments is applied with increasing frequency and, with correct patient qualification, allows for obtaining 5-year survival at a level of 32–52%. The conditions necessary for positive results of such treatment include the high experience of a given centre, its appropriate infrastructure, and appropriate patient qualification for the procedure. As a result of the debate connected with the need to evaluate treatment quality and results, at the request of the Peritoneal Cancer Section of the Polish Society of Oncological Surgery, the conditions for quality assurance were worked out and a Quality Assurance Commission was set up for the centres performing cytoreductive procedures and HIPEC procedures in the treatment of primary and secondary peritoneal tumours

2005 PRETEXT: a revised staging system for primary malignant liver tumours of childhood developed by the SIOPEL group

Over the last 15 years, various oncology groups throughout the world have used the PRETEXT system for staging malignant primary liver tumours of childhood. This paper, written by members of the radiology and surgery committees of the International Childhood Liver Tumor Strategy Group (SIOPEL), presents various clarifications and revisions to the original PRETEXT system

Computational drug prediction in hepatoblastoma by integrating pan-cancer transcriptomics with pharmacological response

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

Trudne, bo nietypowe przypadki guzów litych u dzieci

Nietypowy obraz kliniczny nowotworów wieku dziecięcego niejednokrotnie stwarza trudności diagnostyczne i staje się przyczyną opóźnień w ustaleniu rozpoznania. Poniżej przedstawiamy troje dzieci z rozpoznaniami guzów litych o nietypowym przebiegu klinicznym, leczonych w Klinice Pediatrii, Hematologii, Onkologii i Endokrynologii Akademii Medycznej w Gdańsku

Upfront or delayed surgery in resectable hepatoblastoma: analysis from the childrens hepatic tumors international collaboration database.

BACKGROUND: In the treatment of resectable hepatoblastoma (HB), it has not been established whether upfront surgery (UF) at diagnosis or neoadjuvant chemotherapy and delayed surgery (DL) is preferred. We compared patients with localized HB who underwent either UF, or DL after neoadjuvant chemotherapy in the Childrens Hepatic tumors International Collaboration (CHIC) database of 1605 cases enrolled in eight multicenter hepatoblastoma trials between 1988 and 2010. METHODS: Among the 512 resectable HB patients who had PRETEXT (PRETreament EXTent of disease) I or II unruptured tumors at diagnosis without extrahepatic invasion, distant metastases, or massive vascular invasion, 172 underwent UF and 340 underwent DL. The primary outcomes were event-free and overall survivals after start of treatment in these two groups. Survival analysis was performed using the Kaplan-Maier analysis with long-rank tests and multivariable Cox regression models. FINDINGS: Complete resection rates were comparable (93.6% in UF and 89.7% in DL). The total cycles of chemotherapy of DL (median:6) were significantly more than those of UF (median:4) (P < 0.01). The 5-year event-free survival (EFS) was 90.6% and 86.6% (P = 0.89) in the UF and DL cohorts, respectively. The surgical complications, recurrence rates, and late complications were not significantly different between the cohorts but the EFS rates of DL patients with a low alpha-fetoprotein (AFP) level (100-999 ng/mL) or older age at diagnosis (≥3 years old) were significantly worse than others. INTERPRETATION: The outcomes, surgical resectability, and complications were not significantly different between the UF and DL groups. Eligible patients with a low AFP level (<1000 ng/mL) or older age (≥3 years old) showed better outcomes in the UF group and might be considered for initial resection. FUNDING: European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission; Childrens Oncology Group Cure Search 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 Development; Japan Society for the Promotion of Science; and Swiss Cancer Research grant

Consensus classification of pediatric hepatocellular tumors: A report from the Children's Hepatic tumors International Collaboration (CHIC)

Background: Liver 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. Procedure: The 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. Results: Of 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. Conclusions: This 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

Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches

Introduction: The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. Methods: Extensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors. Results: Results revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. Discussion: The key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies.Peer Reviewe

COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.

Funder: Bundesministerium für Bildung und ForschungFunder: Bundesministerium für Bildung und Forschung (BMBF)We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective