Background: Thrombosis is an increasingly recognized complication of childhood malignancy and its treatment. The etiology of pediatric cancer-related thrombosis is multifactorial and not well understood at present. The aim of this study was to evaluate the prevalence of common prothrombotic genetic conditions in children with cancer, the frequency of thrombosis, and the role of inherited thrombophilia in the development of thrombosis in a pediatric oncology population. Methods: Forty-seven children (36 treated for hematological malignancies and 11 for solid tumors) with the median age of 8.8. years (range 0.4 – 19.3 years) were included in the study. Genetic polymorphisms of Factor V Leiden, prothrombin G20210A mutation, and methylenetetrahydrofolate reductase (MTHFR) C677T were determined by real-time polymerase chain reaction-based DNA analysis. Results: Four (8.5%) patients were heterozygous for Factor V Leiden, 3 (6.4%) were heterozygous for prothrombin G20210A mutation, and 3 (6.4%) were homozygous for MTHFR C677T mutation. All patients had inserted central venous lines. Four (8.5%) children had documented thrombosis, 3 of which were located in the upper venous system. Two of four patients with thrombosis had Factor V Leiden heterozygosity. Conclusions: Thrombosis is an important complication of childhood cancer. Our results suggest that congenital prothrombotic abnormalities could be implicated in increasing the risk of thrombosis and support a recommendation that children with cancer be evaluated for inherited thrombophilia.

Background: Late effects in childhood cancer survivors are a major cause of morbidity and mortality. The objective was to establish knowledge about the disease, late effects, self-care practices, application of health knowledge/education, sources of information, and biopsychosocial impact of cancer, and compare the results of Chile and Croatia. Procedure: one hundred and seventy-one, five-year survivors who were treated for leukemia or non-Hodgkins lymphoma responded to a questionnaire (119 in Chile and 52 in Croatia). The instrument was reviewed by BFM- ELTEC. Results: health knowledge about past diagnosis and general treatment had 96% Chilean and 85% Croatian survivors. Ninety percent of Chilean and 73% of Croatian survivors were unaware of possible late effects, and half did not know which specialist to visit for follow-up. Forty-six percent of Chilean and 35% of Croatian survivors knew about healthy lifestyles, but most did not practice them. Health education was received during the treatment in 74% Chilean and 87% Croatian survivors. About 50% survivors in both groups had experienced fear or anguish, but it was also considered an experience to grow for 60% of Chilean and 42% Croatian survivors. Eighty-seven percent Chilean and 77% Croatian survivors considered themselves physically independent, while 76% and 75% felt psychologically independent, respectively. Conclusion: It was detected a significant lack of knowledge about the specific treatment, late effects, and future health in both countries. They did not achieve significant learning with the education received. Psychological sequelae were found that are important to prevent.

TITLE PAGEManuscript title: Isolated neutropenia preceding acute lymphoblastic leukemia in children

Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm affecting typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological examination is required for diagnosis. The mainstay of treatment is a complete surgical resection. Inoperable and/or metastatic PBL may become amenable to complete, delayed surgery after neo-adjuvant chemotherapy. This manuscript presents the internationally consensus recommendations for the diagnosis and treatment of children with PBL, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER (Paediatric Rare Tumors Network – European Registry) project.

As part of the European Union-funded project designated PARTN-ER, the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) is continuously developing consensus recommendations in order to harmonize standard care for very rare solid tumors of children and adolescents. This paper presents the internationally recognized recommendations for the diagnosis and treatment of sex cord stromal tumors (SCST). The clinical approach to sex cord stromal tumors of the testis (TSCST) and ovary (OSCST) depends on histological differentiation and tumor stage. Virtually all TSCSTs present as localized non-metastatic tumors, with excellent prognosis after complete resection. In contrast, the prognosis of OSCSTs may be adversely affected by tumor spillage during surgery or presence of metastases. In these cases, cisplatin-based chemotherapy is recommended. Of note, some SCSTs may develop in the context of tumor predisposition syndromes e.g. DICER-1, so that specific follow-up is indicated. SCSTs should be diagnosed and treated according to standardized recommendations that include reference pathology, genetic testing for tumor predisposition syndromes in selected cases, and stratified adjuvant chemotherapy in patients with unfavorable risk profile. To ensure high quality of diagnosis and therapy, patients should be enrolled into prospective registries.