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AIMS: Pediatric posterior fossa tumor (PFT) survivors experience long-term cognitive sequelae, including memory disorders, for which irradiation is one of the main risk factors. The aims of the present study were to (1) explore the profile of impairment in episodic, semantic, working and procedural memory systems in irradiated versus nonirradiated PFT survivors, and (2) test whether an autobiographical questionnaire and a two-phase ecological test (Epireal) assessing episodic memory are more sensitive to radiation-induced hippocampal damage than commonly used tests. MATERIALS AND METHODS: A total of 60 participants (22 irradiated PFT survivors, 17 nonirradiated PFT survivors, and 21 controls) were included in the prospective IMPALA study. They all underwent a broad battery of tests assessing the different memory systems in two 2-day sessions 3 weeks apart. We performed between-groups comparisons and analyzed impairment profiles, using -1.65 SDs as a cut-off. For irradiated patients, correlations were calculated between mean radiation doses to key brain structures involved in memory (hippocampus, cerebellum, and striatum) and corresponding memory scores. RESULTS: PBT survivors performed significantly more poorly than controls (p < 0.001) on conventional tests of episodic, semantic and working memory: 64% of irradiated patients and 35% of nonirradiated patients had a deficit in at least two memory systems, with episodic memory impairment being more specific to the irradiated group. Epireal had a larger effect size than the other episodic memory tests, allowing us to detect deficits in a further 18% of irradiated patients. These deficits were correlated with the mean radiation dose to the left hippocampus. CONCLUSION: Memory impairment is a frequent long-term cognitive sequela in PFT survivors, especially after radiation therapy. New ecological tests of episodic memory that are more sensitive to radiation-induced deficits than conventional tests could yield specific markers of the toxicity of medial temporal lobe irradiation.
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Hipocampo , Neoplasias Infratentoriais , Transtornos da Memória , Memória Episódica , Humanos , Masculino , Hipocampo/efeitos da radiação , Hipocampo/patologia , Feminino , Criança , Neoplasias Infratentoriais/radioterapia , Adolescente , Estudos Prospectivos , Transtornos da Memória/etiologia , Lesões por Radiação/etiologia , Estudos de Casos e Controles , Sobreviventes de Câncer/psicologia , Testes NeuropsicológicosRESUMO
Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.
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Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Anemia Aplástica/diagnóstico , Anemia Aplástica/etiologia , Humanos , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Itália , COVID-19/diagnóstico , Imunossupressores/uso terapêutico , SARS-CoV-2RESUMO
This study identifies a new chronic form of immune neutropenia in the young with or without detectable indirect anti-neutrophil antibodies, characterized by mild/moderate neutropenia low risk of severe infection (14%), tendency to develop autoimmune phenomena over the course of the disease (cumulative incidence of 58.6% after 20 years of disease duration), leukopenia, progressive reduction of absolute lymphocyte count and a T- and B-cell profile similar to autoimmune disorders like Sjogren syndrome, rheumatoid arthritis, and systemic lupus erythematosus (increased HLADR+ and CD3 + TCRγδ cells, reduced T regulatory cells, increased double-negative B and a tendency to reduced B memory cells). In a minority of patients, P/LP variants related to primary immuno-regulatory disorders were found. This new form may fit the group of "Likely acquired neutropenia," a provisional category included in the recent International Guidelines on Diagnosis and Management of Neutropenia of EHA and EUNET INNOCHRON ACTION 18233. The early recognition of this form of neutropenia would help clinicians to delineate better specific monitoring plans, genetic counseling, and potentially targeted therapies.
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Artrite Reumatoide , Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Neutropenia , Trombocitopenia , Humanos , Neutropenia/etiologia , Neutropenia/terapia , Doenças Autoimunes/complicações , Lúpus Eritematoso Sistêmico/complicações , Trombocitopenia/complicaçõesRESUMO
BACKGROUND AND PURPOSE: A new brain tumor entity occurring in early childhood characterized by a somatic BCL6 corepressor gene internal tandem duplication was recently described. The aim of this study was to describe the radiologic pattern of these tumors and correlate this pattern with histopathologic findings. MATERIALS AND METHODS: This retrospective, noninterventional study included 10 children diagnosed with a CNS tumor, either by ribonucleic acid-sequencing analysis or deoxyribonucleic acid methylation analysis. Clinical, radiologic, and histopathologic data were collected. A neuropathologist reviewed 9 tumor samples. Preoperative images were analyzed in consensus by 7 pediatric radiologists. RESULTS: All tumors were relatively large (range, 4.7-9.2 cm) intra-axial peripheral masses with well-defined borders and no peritumoral edema. All tumors showed mild and heterogeneous enhancement and marked restriction on DWI of the solid portions. Perfusion imaging showed a relatively lower CBF in the tumor than in the adjacent normal parenchyma. Nine of 10 tumors showed areas of necrosis, with the presence of hemorrhage in 8/10 and calcifications in 4/7. Large intratumoral macroscopic veins were observed in 9/10 patients. No intracranial or spinal leptomeningeal dissemination was noted at diagnosis. CONCLUSIONS: CNS tumors with a BCL6 corepressor gene internal tandem duplication present as large intra-axial peripheral masses with well-defined borders, no edema, restricted diffusion, weak contrast enhancement, frequent central necrosis, hemorrhage and calcifications, intratumoral veins, and no leptomeningeal dissemination at the time of diagnosis. Knowledge of these imaging characteristics may aid in histologic, genomic, and molecular profiling of brain tumors in young children.
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Neoplasias Encefálicas , Neoplasias Neuroepiteliomatosas , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Humanos , Imageamento por Ressonância Magnética , Neoplasias Neuroepiteliomatosas/diagnóstico por imagem , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/patologia , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Estudos RetrospectivosRESUMO
BACKGROUND: Two definitions of a positive circumferential resection margin (CRM) in esophageal cancer coexist: one by the College of American Pathologists (CAP) (CRM = 0 mm) and another by the Royal College of Pathologists (RCP) (CRM ≤ 1 mm). This study aimed to evaluate the prognostic value of both definitions in esophageal cancer and to identify a new cutoff value for the CRM to predict survival. METHODS: Patients who underwent curative esophageal resection for locally advanced (≥ pT3) adenocarcinoma or squamous cell carcinoma were selected from 2007 to 2016. The CRM was reassessed using an ocular micrometer. Overall survival (OS) and disease-free survival were estimated with uni- and multivariate analyses. RESULTS: The study enrolled 283 patients: 48 with a positive CRM according to the CAP definition and 171 with a positive CRM according to the RCP definition. In the multivariate analysis, a positive CRM according to both definitions was significantly associated with a poor OS (CAP: hazard ratio [HR], 2.26, p < 0.001; RCP: HR, 1.42, p = 0.035). A CRM of 0 mm was predictive of a worse OS and DFS than a CRM of 1 mm or less (p < 0.0001), whereas no significant difference was found between a CRM greater than 1 mm and a CRM of 1 mm or less, indicating that the CAP definition was more accurate for predicting prognosis and recurrence. New cutoff CRM values of 100 µm in squamous cell carcinoma and 200 µm in adenocarcinoma were optimal for predicting OS. CONCLUSION: The CAP definition was more accurate for predicting prognosis and recurrence. The study identified a new cutoff value of CRM according to histologic type.
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Neoplasias Esofágicas , Neoplasias Retais , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Children who have been treated for a medulloblastoma often suffer long-term cognitive impairments that often negatively affect their academic performance and quality of life. In this article, we will review the neuropsychological consequences of childhood medulloblastoma and discuss the risk factors known to influence the presence and severity of these cognitive impairments and possible interventions to improve their quality of life. METHODS: This narrative review was based on electronic searches of PubMed to identify all relevant studies. RESULTS: Although many types of cognitive impairments often emerge during a child's subsequent development, the core cognitive domains that are most often affected in children treated for a medulloblastoma are processing speed, attention and working memory. The emergence and magnitude of these deficits varies greatly among patients. They are influenced by demographic (age at diagnosis, parental education), medical and treatment-related factors (perioperative complications, including posterior fossa syndrome, radiation therapy dose, etc.), and the quality of interventions such as school adaptations provided to the child or rehabilitation programs that focus on cognitive skills, behavior and psychosocial functioning. CONCLUSION: These patients require specialized and coordinated multidisciplinary rehabilitation follow-up that provides timely and adapted assessments and culminates in personalized intervention goals being set with the patient and the family. Follow-up should be continued until referral to adult services.
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Neoplasias Cerebelares/psicologia , Disfunção Cognitiva/psicologia , Meduloblastoma/psicologia , Testes Neuropsicológicos , Adulto , Atenção/fisiologia , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/terapia , Criança , Pré-Escolar , Cognição/fisiologia , Terapia Cognitivo-Comportamental/tendências , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Feminino , Humanos , Masculino , Meduloblastoma/complicações , Meduloblastoma/terapia , Qualidade de Vida/psicologiaRESUMO
Medulloblastoma is a frequent high-grade neoplasm among pediatric brain tumours. Its classical imaging features are a midline tumour growing into the fourth ventricle, hyperdense on CT-scan, displaying a hypersignal when using diffusion-weighted imaging, with a variable contrast enhancement. Nevertheless, atypical imaging features have been widely reported, varying according to the age of the patient, and histopathological subtype. In this study, we review the classical and atypical imaging features of medulloblastomas, with emphasis on advanced MRI techniques, histopathological and molecular subtypes and characteristics, and follow-up modalities.
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Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/metabolismo , Imagem de Difusão por Ressonância Magnética/métodos , Meduloblastoma/diagnóstico por imagem , Meduloblastoma/metabolismo , Imagem de Perfusão/métodos , Criança , Feminino , Humanos , Masculino , Análise Espectral/métodosRESUMO
INTRODUCTION: Medulloblastoma is the most common type of pediatric malignant brain tumor where the most important amount of clinical and radiological data has been accumulated in recent years. This has led to its sophistication in the management of these patients with a clear benefit for the patients. Long-term outcome and sequelae have been described and their causes well understood such as preventive measures which can now be implemented. MATERIAL AND METHODS: This review paper does not attempt to make a systematic review of the literature in the field of research regarding medulloblastoma. It rather reflects more the opinion of a pediatric oncological team involved for a long time in this type of research. Therefore, a relevant literature review was carried out and selected by the senior author. RESULTS: Medulloblastoma is no longer a single entity but a group of at least 4 different diseases with a specific oncogenesis. In addition, biomarkers for prognosis have emerged to complement the known clinico-radiological risk factors. If this biological classification has allowed to modulate the therapeutic strategies, it has not yet brought many new drugs (except for the Sonic Hedgehog inhibitors) in the armamentarium against medulloblastomas. Consequently, some high-risk tumors remain difficult to cure. Combining data on oncogenesis and prognostic biomarkers will allow to define risk groups more specifically. New targeted therapies that are more effective and less toxic are desperately needed. Alternatively, it is also justified to study preventive measures to decrease the sequelae of the tumor and its treatments. From the therapeutic point of view, we scarcely know the biological determinants of chemosensitivity and radiosensitivity, as well as those associated with metastases which are indeed invaluable for tailored therapeutic strategies. CONCLUSION: If some genetic causes of medulloblastoma are known, the occurrence of the disease is largely unexplained for the others, justifying more research in this area. If genomics (and to a lesser extent epigenomics) of these neoplasms has been well studied, little is known on their proteomics and on the regulatory networks involved in the biological behavior of these tumor cells. New models are developed to test these aspects.
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Pesquisa Biomédica/tendências , Neoplasias Cerebelares/genética , Meduloblastoma/genética , Biomarcadores , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/cirurgia , Criança , Epigênese Genética/genética , Feminino , Proteínas Hedgehog/genética , Humanos , Masculino , Meduloblastoma/diagnóstico , Meduloblastoma/cirurgia , PrognósticoRESUMO
BACKGROUND AND PURPOSE: Focal areas of high signal intensity are T2WI/T2-FLAIR hyperintensities frequently found on MR imaging of children diagnosed with neurofibromatosis type 1, often thought to regress spontaneously during adolescence or puberty. Due to the risk of tumor in this population, some focal areas of high signal intensity may pose diagnostic problems. The objective of this study was to assess the characteristics and temporal evolution of focal areas of high signal intensity in children with neurofibromatosis type 1 using long-term follow-up with MR imaging. MATERIALS AND METHODS: We retrospectively examined the MRIs of children diagnosed with neurofibromatosis type 1 using the National Institutes of Health Consensus Criteria (1987), with imaging follow-up of at least 4 years. We recorded the number, size, and surface area of focal areas of high signal intensity according to their anatomic distribution on T2WI/T2-FLAIR sequences. A generalized mixed model was used to analyze the evolution of focal areas of high signal intensity according to age, and separate analyses were performed for girls and boys. RESULTS: Thirty-nine patients (ie, 285 MR images) with a median follow-up of 7 years were analyzed. Focal areas of high signal intensity were found in 100% of patients, preferentially in the infratentorial white matter (35% cerebellum, 30% brain stem) and in the capsular lenticular region (22%). They measured 15 mm in 95% of cases. They appeared from the age of 1 year; increased in number, size, and surface area to a peak at the age of 7; and then spontaneously regressed by 17 years of age, similarly in girls and boys. CONCLUSIONS: Focal areas of high signal intensity are mostly small (<15 mm) abnormalities in the posterior fossa or capsular lenticular region. Our results suggest that the evolution of focal areas of high signal intensity is not related to puberty with a peak at the age of 7 years. Knowledge of the predictive evolution of focal areas of high signal intensity is essential in the follow-up of children with neurofibromatosis type 1.
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Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neurofibromatose 1/diagnóstico por imagem , Neurofibromatose 1/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Lactente , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Estudos RetrospectivosRESUMO
LUCS (Light-Up Cell System) is a new live cell test that allows assessment of a cell's homeostasis and its alteration by a toxic agent. To evaluate the effectiveness of LUCS as an alternative test method for acute oral toxicity, we compared EC50s determined in HepG2 cells treated with 53 chemicals selected from the ACuteTox EU database with corresponding human blood LC50s derived from human acute poisoning cases. Linear regression analysis showed that LUCS results predict human data to 69 %. Rodent oral LD50s and LUCS EC50s were then correlated to human LC50s using shared data sets. Linear regression analyses comparing LUCS and animal data clearly showed that LUCS always predicts human toxicity better than animal data do. These successful prediction values prompted us to simplify the LUCS test, adapting it to regulatory and high throughput applications, resulting in a new protocol with consistent dose-response profiles and EC50s. This study demonstrates that the LUCS test method could be relevant for assessing human acute oral toxicity with a simplified protocol adapted to commercially available fluorescence readers. We suggest that this new alternative method can be used for acute systemic toxicity testing in combination with other tests under European REACH and other regulations, wherever pertinent alternative methods are still lacking.
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Apoptose/genética , Caspase 10/genética , Caspase 8/genética , Mutação , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/etiologia , Proteína ADAMTS13/genética , Proteína ADAMTS13/metabolismo , Adolescente , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Biomarcadores , Caspase 10/metabolismo , Caspase 8/metabolismo , Suscetibilidade a Doenças , Feminino , Humanos , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Proteólise , Púrpura Trombocitopênica Trombótica/tratamento farmacológicoRESUMO
BACKGROUND AND PURPOSE: Embryonal tumors with multilayered rosettes, C19MC-altered, are brain tumors occurring in young children, which were clearly defined in the 2016 World Health Organization classification of central nervous system neoplasms. Our objective was to describe the multimodal imaging characteristics of this new entity. MATERIALS AND METHODS: We performed a retrospective monocentric review of embryonal brain tumors and looked for embryonal tumors with multilayered rosettes with confirmed C19MC alteration. We gathered morphologic imaging data, as well as DWI and PWI data (using arterial spin-labeling and DSC). RESULTS: We included 16 patients with a median age of 2 years 8 months. Tumors were both supratentorial (56%, 9/16) and infratentorial (44%, 7/16). Tumors were large (median diameter, 59 mm; interquartile range, 48-71 mm), with absent (75%, 12/16) or minimal (25%, 4/16) peritumoral edema. Enhancement was absent (20%, 3/15) or weak (73%, 11/15), whereas intratumoral macrovessels were frequently seen (94%, 15/16) and calcifications were present in 67% (10/15). Diffusion was always restricted, with a minimal ADC of 520 mm2/s (interquartile range, 495-540 mm2/s). Cerebral blood flow using arterial spin-labeling was low, with a maximal CBF of 43 mL/min/100 g (interquartile range, 33-55 mL/min/100 g 5). When available (3 patients), relative cerebral blood volume using DSC was high (range, 3.5-5.8). CONCLUSIONS: Embryonal tumors with multilayered rosettes, C19MC-altered, have characteristic imaging features that could help in the diagnosis of this rare tumor in young children.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/patologia , Neuroimagem/métodos , Pré-Escolar , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino , Imagem Multimodal/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
PURPOSE: The delineation of volumes of interest can be a source of significant interobserver variability. The purpose of this study was to improve the homogeneity of delineation between oncologist-radiotherapists in the territorial departments of Nord and Pas-de-Calais (France) through discussions of clinical cases and the adoption of common published reference documents. MATERIALS AND METHODS: All eleven radiotherapy centres in the Nord and Pas-de-Calais departments of France participated. The localizations assessed to date included prostate, head and neck, breast and brain cancers. For each localization, the junior or senior physician(s) in charge of pathology delineated the volumes of interest according to their usual practices. Validated indices, including the Dice similarity coefficient, were used to quantify the delineation differences. The anonymized results were presented at two to three annual meetings. A second delineation of the clinical cases was then carried out to quantify homogenization. An evaluation of dosimetry practices was also conducted for prostate cancer. Wilcoxon assay matched data were used. RESULTS: Our work showed either satisfactory delineation concordance after the initial assessment or improved delineation concordance. For prostate cancer, the Dice similarity coefficient values were greater than 0.6 initially in two of the three clinical cases. For head and neck cancers, a statistically significant improvement was observed for only one of the clinical target volumes. More than half of the Dice similarity coefficient values were greater than 0.6 in the first comparison. The study of clinical cases of breast cancer allowed a homogenization of the delineation of five of the six lymph node clinical target volumes. The dosimetry study of prostate cancer allowed for a homogenization of practices. CONCLUSION: This work makes it possible to harmonize the delineation practices around validated standards. An extension to the entire Hauts-de-France region is planned.
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Neoplasias/radioterapia , Dosagem Radioterapêutica/normas , Planejamento da Radioterapia Assistida por Computador/normas , Institutos de Câncer , Feminino , França , Humanos , Masculino , Neoplasias/patologia , Variações Dependentes do ObservadorRESUMO
Ce-Doped SiOxNy films are deposited by magnetron reactive sputtering from a CeO2 target under a nitrogen reactive gas atmosphere. Visible photoluminescence measurements regarding the nitrogen gas flow reveal a large emission band centered at 450 nm for a sample deposited under a 2 sccm flow. Special attention is paid to the origin of such an emission at high nitrogen concentration. Different emitting centers are suggested in Ce doped SiOxNy films (e.g. band tails, CeO2, Ce clusters, Ce3+ ions), with different activation scenarios to explain the luminescence. X-ray photoelectron spectroscopy (XPS) reveals the exclusive presence of Ce3+ ions whatever the nitrogen or Ce concentrations, while transmission electron microscopy (TEM) shows no clusters or silicates upon high temperature annealing. With the help of photoluminescence excitation spectroscopy (PLE), a wide excitation range from 250 nm up to 400 nm is revealed and various excitations of Ce3+ ions are proposed involving direct or indirect mechanisms. Nitrogen concentration plays an important role in Ce3+ emission by modifying Ce surroundings, reducing the Si phase volume in SiOxNy and causing a nephelauxetic effect. Taking into account the optimized nitrogen growth parameters, the Ce concentration is analyzed as a new parameter. Under UV excitation, a strong emission is visible to the naked eye with high Ce3+ concentration (6 at%). No saturation of the photoluminescence intensity is observed, confirming again the lack of Ce cluster or silicate phase formation due to the nitrogen presence.
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We studied the kinetics of peptide release during the gastric digestion of meat proteins in vivo, in view to predicting the release of bioactive peptides further on in the digestive tract. Six mini pigs fitted with gastric cannulas received a meal with cooked beef as protein source. Digesta was collected at regular time intervals up to 5½â¯h. The peptides generated by the gastric digestion of meat were identified and quantified using label-free LC MS, thereafter subjected to in silico digestion mimicking the action of intestinal enzymes. Three clusters of proteins presenting similar evolutions according to their dynamic hydrolysis were obtained. This study clearly improves the in silico prediction of the intestinal release of bioactive peptides by mapping meat protein degradation in the stomach in an in vivo model. Knowledge of the conformation of the peptides released in the stomach further improves this prediction.
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Carne/análise , Peptídeos/metabolismo , Suínos/metabolismo , Ração Animal/análise , Animais , Bovinos , Cromatografia Líquida , Simulação por Computador , Proteínas Alimentares/química , Proteínas Alimentares/metabolismo , Digestão , Mucosa Gástrica/metabolismo , Cinética , Mapeamento de Peptídeos , Peptídeos/química , Proteólise , Suínos/crescimento & desenvolvimento , Espectrometria de Massas em TandemRESUMO
Children with diffuse intrinsic pontine glioma (DIPG) need new and more efficient treatments. They can be developed at relapse or at diagnosis, but therefore they must be combined with radiotherapy. Survival of children after recurrence and its predictors were studied to inform the possibility to design early phase clinical trials for DIPG at this stage. Among 142 DIPG patients treated between 1998 and 2014, 114 had biopsy-proven DIPG with histone H3 status available for 83. We defined as long survivors' patients who survived more than 3 months after relapse which corresponds to the minimal life expectancy requested for phase I/II trials. Factors influencing post-relapse survival were accordingly compared between short and long-term survivors after relapse. Fifty-seven percent of patients were considered long survivors and 70% of them had a Lansky Play Scale (LPS) above 50% at relapse. Patients who became steroids-independent after initial treatment for at least 2 months had better survival after relapse (3.7 versus 2.6 months, p = 0.001). LPS above 50% at relapse was correlated with better survival after relapse (3.8 versus 1.8 months, p < 0.001). Patients with H3.1 mutation survived longer after relapse (4.9 versus 2.7 months, p = 0.007). Patients who received a second radiotherapy at the time of relapse had an improved survival (7.5 versus 4 months, p = 0.001). In the two-way ANOVA analysis, steroid-independence and LPS predicted survival best and the type of histone H3 (H3.1 or H3.3) mutated did not improve prediction. Survival of many DIPG patients after relapse over 3 months would make possible to propose specific trials for this condition. Steroid-independence, H3 mutation status and LPS should be considered to predict eligibility.
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Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/terapia , Glioma/diagnóstico , Glioma/terapia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Adolescente , Adulto , Neoplasias do Tronco Encefálico/mortalidade , Criança , Pré-Escolar , Feminino , Glioma/mortalidade , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Recidiva Local de Neoplasia/mortalidade , Resultado do Tratamento , Adulto JovemRESUMO
The aim of this study was to review and describe therapeutic approaches in children with choroid plexus tumor (CPT) based on a nationwide series. The World Health Organization classification subdivides these rare tumors into three histological subtypes corresponding to three grades of malignancy: low grade (grade I) choroid plexus papilloma (CPP), intermediate grade (grade II) atypical choroid plexus papilloma (aCPP) and high grade (grade III) choroid plexus carcinoma (CPC). This retrospective study included 102 French children younger than 18 years, treated from 2000 to 2012: 54 CPP, 26 aCPP and 22 CPC. The 5 year overall survival was 100% in CPP, 96.2% in aCPP and 64.7% in CPC. In patients with localized disease, complete surgical resection was achieved in 48/52 CPP, 20/26 aCPP and 7/14 CPC. In this group, patients with complete surgical resection had better event free survival than patients with partial resection (88.9 vs. 41.6%). 28 patients (1 CPP, 6 aCPP and 22 CPC) had adjuvant chemotherapy. 2 aCPP and 9 CPC had radiotherapy. We underlined the need for a central histological review to accurately analyze clinical data; we reported a much higher overall survival for CPC than in most previous CPT series probably including atypical teratoid rhabdoid tumors. In our series, the 5 years overall survival in CPC (64.7%) was higher than event free survival (25.2%) and could be interpreted as a clue for the efficiency of adjuvant/salvage therapy even if the heterogeneity of applied treatments in this retrospective series does not allow for meaningful statistical comparisons.
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Carcinoma/terapia , Neoplasias do Plexo Corióideo/terapia , Papiloma do Plexo Corióideo/terapia , Tumor Rabdoide/terapia , Teratoma/terapia , Adolescente , Carcinoma/genética , Carcinoma/patologia , Criança , Pré-Escolar , Neoplasias do Plexo Corióideo/genética , Neoplasias do Plexo Corióideo/patologia , Feminino , Seguimentos , França , Humanos , Lactente , Masculino , Gradação de Tumores , Papiloma do Plexo Corióideo/genética , Papiloma do Plexo Corióideo/patologia , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Tumor Rabdoide/genética , Tumor Rabdoide/patologia , Análise de Sobrevida , Teratoma/genética , Teratoma/patologia , Resultado do TratamentoRESUMO
The purpose of this study is to analyze the effectiveness of surgery and follow-up of children operated on for burn sequelae. For many years, we have organized two missions per year to Benin and Togo, one for surgery and one for follow-up. We analyzed the files of children born in Africa and victims of burns from the years 2002 to 2011. Children were referred through a non-governmental organization (NGO) and assessed in Africa by local paediatricians before and after surgery. Treatment consisted in operating on burn sequelae such as contractures, hypertrophic scars and hard cords. Impaired mobility was our only indication for the operation. We kept a database on all patients. Sixty files were reviewed, of which fifty were deemed suitable for analysis. The most common methods of surgery were skin grafting and Z-plasty. There were no complications, such as infection or graft/flap necrosis after immediate surgery. Long-term follow-up revealed a recurrence of hypertrophic scarring (47%), retractions (24%) and hard cords (2%) due to a lack of occupational therapy and physiotherapy treatment. Partnership with an NGO and a local team allows us to treat children with burn injury sequelae in Western Africa. A continued and often long-lasting follow-up by occupational therapists and physiotherapists is highly mandatory in order to guarantee good long-term results. In 2010, we initiated local rehabilitation therapy.
Le but de cette étude est d'analyser l'efficacité de la chirurgie et le suivi d'enfants opérés pour des séquelles de brûlures. Nous avons analysé les dossiers d'enfants africains, victimes de brûlures depuis l'année 2002 jusqu'en 2011. Pendant de nombreuses années, nous avons organisé deux missions par an au Bénin et au Togo, une pour la chirurgie et une pour le suivi. Les enfants nous étaient confiés par une O.N.G. et examinés en Afrique par des pédiatres locaux avant et après la chirurgie. Le traitement chirurgical s'adressait aux séquelles de brûlures telles que rétractions, cicatrices hypertrophiques et brides. La perte de mobilité fut notre unique indication. Nous avons une base de données sur tous les patients. 60 dossiers furent revus mais 50 retenus pour l'analyse. Les traitements les plus fréquents furent la greffe de peau et les plasties en Z. Il n'y a pas eu de complications, ni infection ou nécrose de la greffe ou du lambeau après chirurgie immédiate. Le suivi à long terme a montré une récidive des cicatrices hypertrophiques (47%), des rétractions (24%) et des brides (2%), et ceci dû à une absence d'ergothérapie et de physiothérapie. La coopération avec une O.N.G. et une équipe locale a permis de traiter ces enfants présentant des séquelles de brûlures en Afrique de l'Ouest. Un suivi continu et souvent long par les ergothérapeutes et les physiothérapeutes est indispensable, si l'on veut garantir de bons résultats à long terme. En 2010 nous avons initié localement un traitement par rééducation fonctionnelle.
RESUMO
Hematopoietic stem cell transplantation (HSCT) is an established procedure for many acquired and congenital disorders of the hematopoietic system. A record number of 42 171 HSCT in 37 626 patients (16 030 allogeneic (43%), 21 596 autologous (57%)) were reported by 655 centers in 48 countries in 2015. Trends include continued growth in transplant activity over the last decade, with the highest percentage increase seen in middle-income countries but the highest absolute growth in the very-high-income countries in Europe. Main indications for HSCT were myeloid malignancies 9413 (25%; 96% allogeneic), lymphoid malignancies 24 304 (67%; 20% allogeneic), solid tumors 1516 (4%; 3% allogeneic) and non-malignant disorders 2208 (6%; 90% allogeneic). Remarkable is the decreasing use of allogeneic HSCT for CLL from 504 patients in 2011 to 255 in 2015, most likely to be due to new drugs. Use of haploidentical donors for allogeneic HSCT continues to grow: 2012 in 2015, a 291% increase since 2005. Growth is seen for all diseases. In AML, haploidentical HSCT increases similarly for patients with advanced disease and for those in CR1. Both marrow and peripheral blood are used as the stem cell source for haploidentical HSCT with higher numbers reported for the latter.