The quality of life in extracorporeal life support survivors: single-center experience of a long-term follow-up

Objective: To evaluate the health-related quality of life on a very long-term follow-up in patients treated with extracorporeal membrane oxygenation (ECMO) during neonatal and pediatric age. Design: Prospective follow-up study. Setting: Pediatric Intensive Care Unit of a tertiary-care University-Hospital. Patients: Out of 20 neonates and 21 children treated with ECMO in our center, 24 patients underwent short-term neurological follow-up. Twenty of them underwent long-term neurological follow-up. Intervention: Short-term follow-up was performed at 18 months and consisted in clinical evaluation, electroencephalography, and neuroimaging. Long-term follow-up was performed in 2017, at the mean period 19.72 years from ECMO (median 20.75, range 11.50-24.08) and consisted in a standardized questionnaires self-evaluation (PedsQL 4.0 Generic Core Scale) of health-related quality of life and an interviewed about the presence of organ morbidity, school level, or work position. Measurements and main results: Sixty-one percent (25/41) of the patients survived within 30 days after ECMO treatment. Short-term follow-up was performed in 24 patients (1 patient but died before the evaluation): 21 patients (87%) showed a normal neurological status, and 3 developed severe disability. Long-term follow-up was performed in 20 long-term survivors (3 patients were not possible to be contacted and considered lost to follow-up): mean age of patients at long-term follow-up was 21.23 (median 20.96, range 13.33-35.58) years; 90% (18/20) of them have no disability with a complete normal quality of life and 95% have no cognitive impairment. Conclusions: ECMO represents a life-saving treatment for infants and children with respiratory and/or heart failure; survivors show a good quality of life comparable to healthy peers

The SIOPE strategic plan: a European cancer plan for children and adolescents

Cancer in young people is rare, but it is still a major health issue in Europe. Each year, more than 6,000 young people in Europe die of cancer. There are more than 300,000 European childhood cancer survivors (in 2020, they will be nearly half a million): two-thirds of them have some late side effects of treatment, that are severe and impact on the daily life of half of those affected. Within the European Network for Cancer research in Children and Adolescents (ENCCA), SIOPE and the European paediatric haematology-oncology community have established a longterm sustainable Strategic Plan to increase the cure rate and the quality of survivorship for children and young people with cancer over the next ten years. The ultimate goal is to increase the disease- and late-effect- free survival after 10 years from the disease, and beyond. Seven medical and scientific objectives have been set up to achieve these goals: 1. Innovative treatments: to introduce safe and effective innovative treatments (i.e. new drugs, new technologies) into standard care; 2. Precision cancer medicine: to use improved risk classification as well as biological characteristics of both the tumour and patient (such as molecular and immunological factors) to help guide decisions on which therapies to use; 3. Tumour biology: to increase knowledge of tumour biology and speed up translation from basic research to clinical care to benefit patients; 4. Equal access: to bring about equal access across Europe to standard care (in both diagnosis and treatment), expertise and clinical research; 5. TYA: to address the specific needs of teenagers and young adults (TYA), in cooperation with adult oncology; 6. Quality of survivorship: to address the consequences of cancer treatment such as long-term side effects, to better understand the genetic background/risk of an individual, and to improve quality of life of childhood cancer survivors; 7. Causes of cancer: to understand the causes of paediatric cancers and to address prevention wherever possible

The SIOPE strategic plan: A European cancer plan for children and adolescents

[EN] Within the European Network for Cancer research in Children and Adolescents (ENCCA), SIOPE and the European paediatric haematology-oncology community have established a long-term sustainable Strategic Plan to increase the cure rate and the quality of survivorship for children and young people with cancer over the next ten years. The ultimate goal is to increase the diseaseand late-effect- free survival after 10 years from the diagnosis, and beyond. As a result of several initiatives to involve all stakeholders and ensure that all their points of view would be taken into account in the document, this long-term sustainable Strategic Plan has achieved a broad consensus, and will serve as the "European Cancer Plan for Children and Adolescents".This publication has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under the project ENCCA (European Network for Cancer research in Children and Adolescents), grant agreement nr. HEALTH-F2-2011-261474.Vassal, G.; Schrappe, M.; Pritchard-Jones, K.; Arnold, F.; Basset-Salom, L.; Biondi, A.; Bode, G.... (2016). The SIOPE strategic plan: A European cancer plan for children and adolescents. Journal of Cancer Policy. 8:17-32. https://doi.org/10.1016/j.jcpo.2016.03.007S1732

Subcutaneous tumor seeding after biopsy in gliomatosis cerebri

We observed a patient with subcutaneous seeding from gliomatosis cerebri with a low-grade histopathology. A 33-year-old woman with neurofibromatosis type 1 presented with progressive headache, diplopia, dysphagia, and a rightward instability. On neurological examination dysarthria, gait ataxia, and left-sided central facial and hypoglossal palsies were determined. MRI of the brain demonstrated diffuse, infiltrative non-enhancing lesions in the pons, both cerebellar hemispheres, the parahippocampal gyrus, and the thalamus. A stereotactic biopsy demonstrated an astrocytoma WHO grade 2. These characteristics confirmed gliomatosis cerebri. Three months later, the patient presented with hydrocephalus and a subcutaneous swelling directly underneath the surgical scar. The subcutaneous swelling was removed and the hydrocephalus was treated by ventriculoperitoneal shunting. Histopathological examination confirmed a subcutaneous manifestation of low-grade oligoastrocytoma. Gliomatosis cerebri with low-grade histology can seed subcutaneously

Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma

IGF2, a maternally imprinted foetal growth factor gene, is implicated in many childhood tumours including hepatoblastoma (HB); however, the genetic and epigenetic alterations have not comprehensively been studied. We analysed the methylation status of the H19 differentially methylated region (DMR), loss of heterozygosity (LOH) and allelic expression of IGF2 in 54 HB tumours, and found that 12 tumours (22%) with LOH, 9 (17%) with loss of imprinting (LOI) and 33 (61%) with retention of imprinting (ROI). Biallelic and monoallelic IGF2 expressions correlated with hypermethylation and normal methylation of H19 DMR, respectively, in two tumours with LOI and seven tumours with ROI. Quantitative RT–PCR analysis showed minimal expression of H19 mRNA and substantial expression of IGF2 mRNA in tumours with LOH or LOI, and substantial expression of both H19 and IGF2 mRNAs in tumours with ROI. Increased IGF2 expression with predominant embryonic P3 transcript was found in the majority of HBs with ROI and foetal livers. In contrast to the earlier reports, our findings suggest that the disruption of the enhancer competition model reported in Wilms' tumour may also occur in HB. Both frequencies of LOH and LOI seem to be lower in HB than in Wilms' tumour, reflecting the different tissue origins

The BH3 mimetic ABT-737 increases treatment efficiency of paclitaxel against hepatoblastoma

<p>Abstract</p> <p>Background</p> <p>The primary goal of current chemotherapy in hepatoblastoma (HB) is reduction of tumour volume and vitality to enable complete surgical resection and reduce risk of recurrence or metastatic disease. Drug resistance remains a major challenge for HB treatment. In some malignancies inhibition of anti-apoptotic pathways using small BH3 mimetic molecules like ABT-737 shows synergistic effects in combination with cystotoxic agents in vitro. Now we analysed toxicology and synergistic effects of this approach in HB cells and HB xenografts.</p> <p>Methods</p> <p>Viability was monitored in HB cells (HUH6 and HepT1) and fibroblasts treated with paclitaxel, ABT-737 and a combination of both in a MTT assay. HUH6 xenotransplants in NOD/LtSz-scid IL2Rγnull mice (NSG) were treated accordingly. Tumour volume and body weight were monitored. Xenografted tumours were analysed by histology and immunohistochemistry (Ki-67 and TUNEL assay).</p> <p>Results</p> <p>ABT-737 reduced viability in HUH6 and HepT1 cells cultures at concentrations above 1 μM and also enhanced the cytotoxic effect of paclitaxel when used in combination. Thereby paclitaxel could be reduced tenfold to achieve similar reduction of viability of tumour cells. In contrast no toxicity in fibroblasts was observed at the same regiments. Subcutaneous HB (HUH6) treated with paclitaxel (12 mg/kg body weight, n = 7) led to delayed tumour growth in the beginning of the experiment. However, tumour volume was similar to controls (n = 5) at day 25. Combination treatment with paclitaxel and ABT-737 (100 mg/kg, n = 8) revealed significantly 10 fold lower relative tumour volumes compared to control and paclitaxel groups. Paclitaxel dependent toxicity was observed in this mice strain.</p> <p>Conclusions</p> <p>Our results demonstrate enhancement of chemotherapy by using modulators of apoptosis. Further analyses should include improved pharmacological formulations of paclitaxel and BH3 mimetics in order to reduce toxicological effects. Sensitising HB to apoptosis may also render resistant HB susceptible to established chemotherapy regimens.</p