Consensus Paper—ICIS Expert Meeting Basel 2009 treatment milestones in immune thrombocytopenia

The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients—the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life

Immature Sacrococcygeal Teratoma with Microfoci of Yolk Sac Tumor in a Preterm Female NewbornIs the Surgical Resection Enough?

Sacrococcygeal teratoma (SCT) is the most common neoplasm in neonates and the most common germ cell tumor in children. SCT with malignant elements is very rare in infants. Prenatal diagnosis is of exceptional importance for the adequate fetal intervention, evaluation of perinatal complications and the selection of the optimal treatment. The treatment of choice is complete surgical resection. Postsurgical approach for immature teratoma with malignant elements is not well established. Considering the risk for tumor recurrence, long term follow-up is mandatory. We report clinical, laboratory, radiological and histological findings, surgical procedure, and follow-up in the preterm female neonate with immature SCT with malignant elements

Attenuated Vasodilator Effectiveness of Protease-Activated Receptor 2 Agonist in Heterozygous par2 Knockout Mice

Studies of homozygous PAR2 gene knockout mice have described a mix of phenotypic effects in vitro and in vivo. However, there have been few studies of PAR2 heterozygous (wild-type/knockout; PAR2-HET) mice. The phenotypes of many hemi and heterozygous transgenic mice have been described as intermediates between those of wild-type and knockout animals. In our study we aimed to determine the effects of intermediary par2 gene zygosity on vascular tissue responses to PAR2 activation. Specifically, we compared the vasodilator effectiveness of the PAR2 activating peptide 2-furoyl-LIGRLO-amide in aortas of wild-type PAR2 homozygous (PAR2-WT) and PAR2-HET mice. In myographs under isometric tension conditions, isolated aortic rings were contracted by alpha 1-adrenoeceptor agonist (phenylephrine), and thromboxane receptor agonist (U46619) and then relaxation responses by the additions of 2-furoyl-LIGRLO-amide, acetylcholine, and nitroprusside were recorded. A Schild regression analysis of the inhibition by a PAR2 antagonist (GB-83) of PAR2 agonist-induced aortic ring relaxations was used to compare receptor expression in PAR2-WT to PAR2-HET. PAR2 mRNA in aortas was measured by quantitative real-time PCR. In aortas contracted by either phenylephrine or U46619, the maximum relaxations induced by 2-furoyl-LIGRLO-amide were less in PAR2-HET than in the gender-matched PAR2-WT. GB-83 was 3- to 4-fold more potent for inhibition of 2fly in PAR2-HET than in PAR2-WT. PAR2 mRNA content of aortas from PAR2-HET was not significantly different than in PAR2-WT. Acetylcholine- and nitroprusside-induced relaxations of aortas from PAR2-HET were not significantly different than in PAR2-WT and PAR2 knockout. An interesting secondary finding was that relaxations induced by agonists of PAR2 and muscarinic receptors were larger in females than in males. We conclude that the lower PAR2-mediated responses in PAR2-HET aortas are consistent with evidence of a lower quantity of functional receptor expression, despite the apparently normal PAR2 mRNA content in PAR2-HET aortas

The European Paediatric Rare Tumours Network - European Registry (PARTNER) project for very rare tumors in children

The PARTNER project (Paediatric Rare Tumours Network - European Registry) was launched in 2016. PARTNER aims to create a European Registry dedicated to children and adolescents with very rare tumors (VRT). It links existing national registries and provides a registry for those countries in which a VRT registry has not yet been created. This consortium is composed of the various national cooperative groups and their respective member institutions. The strategic value of this project is based on the Europe-wide data collection concerning the treatment of VRTs. These data are provided to experts and constitute the basis for new clinical practice guidelines for use by ERN (European Reference Network) and non-ERN institutions. The proposed tasks and milestones will increase collaboration in the field of pediatric oncology among member states and will also facilitate the inclusion of low health expenditure average rate (LHEAR) countries in this process. In addition, this project creates a platform for VRTs that may represent a model on how to elaborate a comprehensive approach (case registration, international case consultation and treatment recommendations, and website to provide information for parents/patients) for rare diseases

Pleuropulmonary blastoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations

Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the macroscopic appearance into three interrelated clinico-pathologic entities on a developmental continuum. Complete tumor resection is a main prognostic factor and can be performed at diagnosis or after neoadjuvant treatment that includes chemotherapy and in some cases radiotherapy. Optimal modalities of neo- or adjuvant treatments can be challenging taking into account potential long-term toxicities in this young population. This paper presents the recommendations for diagnosis and treatment of children and adolescents with PPB elaborated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the European Union-funded project PARTNER (Paediatric Rare Tumours Network - European Registry)