Dantonello T.M.,Olgahospital Pediatrics 5 |
Leuschner I.,University of Kiel |
Vokuhl C.,University of Kiel |
Gfroerer S.,Goethe University Frankfurt |
And 12 more authors.
Pediatric Blood and Cancer | Year: 2013
Background: Malignant ectomesenchymoma (MEM) is a soft tissue tumor with heterologous rhabdomyoblastic components believed to arise from pluripotent migratory neural crest cells. To date merely 50 cases have been published and the knowledge about the course of disease and optimal treatment is limited. Methods: Six patients with MEM were registered 1996-2009. The diagnosis was confirmed according to current criteria. Their treatment and outcome was analyzed. Results: The median age of the three females and three males was 0.6 years (range, 0.2-13.5). The mesenchymal component in all tumors was rhabdomyosarcoma (RMS), the neural component ganglioneuroblastoma/neuroblastoma (n=5) and peripheral primitive neuroectodermal tumor in one case. Five patients presented with localized, one with metastatic disease. All but one patient received multiagent chemotherapy during their initial treatment. The tumors of 4/5 patients with localized MEM were at least grossly resected at best surgery; the patient without gross resection was additionally irradiated. Three of four evaluable tumors responded well to induction chemotherapy. All patients achieved a first complete remission (CR), but three recurrences (two local, one systemic) occurred. The individual with metastatic MEM did not survive, but all five patients with localized MEM are currently alive in CR with a median follow-up of 5 years (range: 2.1-13.7). Conclusions: Risk-factors and outcome of MEM appear to be comparable with other highly malignant pediatric soft tissue sarcoma when a multimodal treatment strategy including chemotherapy and adequate local treatment is pursued. We propose that treatment of patients with MEM be done according to pediatric protocols similar to other rhabdomyosarcoma-like soft tissue sarcoma. © 2012 Wiley Periodicals, Inc.
PubMed | University Hospital of Tuebingen, University Childrens Hospital Dresden, University of Ulm, Medical University of Graz and 10 more.
Type: Journal Article | Journal: Pediatric blood & cancer | Year: 2016
Colorectal carcinoma (CRC) is the second most common adult cancer in Germany, however, it is extremely rare in children and adolescents. In these patients, previous literature describes aggressive behavior and diagnosis at advanced stage.Thirty-one patients with CRC age 18 years and treated between 1990 and 2012 have been identified through the structures and registries of the German Society for Pediatric Oncology and Hematology.The age range was 9-18 years (median 13.5 years); the median follow-up time was 43.9 months (range 1-124 months). Twenty-six patients (84%) were tested for a genetic tumor syndrome (GTS); of these, 11 patients (35% of all patients) tested positive (eight cases of Lynch syndrome, one patient with familial adenomatous polyposis, two patients with constitutional mismatch repair deficiency). An unfavorable histology was reported in 55% of the records (n = 17), a poor differentiation (grade III) in 68% of carcinoma (n = 21). Overall survival (OS) and event-free survival at 5 years was 52.0% and 65.6%, respectively. Five-year survival according to stage was 100% in stage II (n = 2), 100% in stage III (n = 13), and 12.9% in stage IV (n = 15; P < 0.001). Five-year OS in patients with and without a defined GTS was 100% and 36.5% (P = 0.019), respectively.Children and adolescents with CRC are frequently diagnosed in advanced stages and have an unfavorable prognosis. In this study, a high percentage of pediatric CRC patients presented with a tumor predisposition syndrome and showed an especially favorable OS.
Brecht I.B.,Pediatric Oncology and Hematology Childrens University Hospital |
Bremensdorfer C.,University Hospital Freiburg |
Schneider D.T.,Clinic of Pediatrics |
Fruhwald M.C.,Childrens Hospital |
And 10 more authors.
Pediatric Blood and Cancer | Year: 2014
Background: The German Childhood Cancer Registry (GCCR) annually registers approximately 2,000 children diagnosed with a malignant disease (completeness of registration >95%). While most pediatric cancer patients are diagnosed and treated according to standardized cooperative protocols of the German Society for Pediatric Oncology and Hematology (GPOH), patients with rare tumors are at risk of not being integrated in the network including trials and reference centers. Procedure: A retrospective analysis of all rare extracranial solid tumors reported to the GCCR 2001-2010 (age <18 years) was undertaken using a combination of the International Classification of Childhood Cancer (ICCC-3) and the International Classification of Diseases-Oncology (ICD-O-3). Tumors accounting for <0.3% of all malignancies were defined as rare (approx. 6 cases/year and registered malignancy). Results: According to this definition 1,189 rare extracranial solid tumors (18.2% of all malignant extracranial solid tumors) were registered, among these 232 patients (19.5% of rare tumor cases), were not included in preexisting GPOH studies/registries. Within 10 years, the number of registered non-GPOH-trial patients with a rare tumor increased. Conclusions: Though most of the GCCR-registered patients with rare malignant tumors are treated within GPOH trials, there is a considerable number of patients that have been diagnosed and treated outside the structures of the GPOH. These patients should be reported to the recently founded German Pediatric Rare Tumor Registry (STEP). Active data accrual and the development of appropriate structures will allow for better registration and improvement of medical care in these patients. Pediatr Blood Cancer 2014;61:1202-1209. © 2014 Wiley Periodicals, Inc.
Winther J.F.,Danish Cancer Society |
Olsen J.H.,Danish Cancer Society |
Olsen J.H.,Vanderbilt University |
Wu H.,Vanderbilt University |
And 7 more authors.
Journal of Clinical Oncology | Year: 2012
Purpose: Preconception radiation and chemotherapy have the potential to produce germ cell mutations leading to genetic disease in the next generation. Dose-response relationships were evaluated between cancer treatments and untoward pregnancy outcomes. Patients and Methods: A case-cohort study was conducted involving 472 Danish survivors of childhood and adolescent cancer and their 1,037 pregnancies. Adverse outcomes included 159 congenital malformations, six chromosomal abnormalities, seven stillbirths, and nine neonatal deaths. Preconception radiation doses to the gonads, uterus, and pituitary gland and administered chemotherapy were quantified based on medical records and related to adverse outcomes using a generalized estimating equation model. Results: No statistically significant associations were found between genetic disease in children and parental treatment with alkylating drugs or preconception radiation doses to the testes in male and ovaries in female cancer survivors. Specifically, the risk of genetic disease was similar among the children of irradiated survivors when compared with nonirradiated survivors (relative risk [RR], 1.02; 95% CI, 0.59 to 1.44; P = .94). A statistically significant association between abdominopelvic irradiation and malformations, stillbirths, and neonatal deaths was not seen in the children of female survivors overall (P = .07) or in the children of mothers receiving high uterine doses (mean, 13.5 Gy; max, 100 Gy; RR, 2.3; 95% CI, 0.95 to 5.56). Conclusion: Mutagenic chemotherapy and radiotherapy doses to the gonads were not associated with genetic defects in children of cancer survivors. However, larger studies need to be conducted to further explore potential associations between high-dose pelvic irradiation and specific adverse pregnancy outcomes. © 2011 by American Society of Clinical Oncology.
Becerir T.,Pamukkale University |
Akcay A.,Clinic of Pediatrics |
Duksal F.,Cumhuriyet University |
Ergin A.,Pamukkale University |
And 2 more authors.
Allergologia et Immunopathologia | Year: 2014
Background: There is currently no standard tool for the measurement of asthma in epidemiological studies. The objectives of this study were to determine the prevalence of asthma, to describe the potential local risk factors, and to assess the agreement between written and video questionnaires in 13- to 14-year-old schoolchildren. Methods: We performed a cross-sectional study involving 5427 adolescents in 26 schools. Prevalence of asthma symptoms were evaluated using the International Study of Asthma and Allergies in Childhood (ISAAC) written and video questionnaire. The adolescents were asked additional questions for risk factors of asthma. Results: The prevalence of lifetime wheeze, wheeze in the last 12 months and doctor-diagnosed asthma with written questionnaire were found as 13.5%, 6.3% and 11.2% respectively. Prevalence of lifetime wheeze, wheeze in the last 12 months, wheeze after exercise in the last 12 months, with video questionnaire were found as 9.6%, 5.5%, 11.9% and 1.9% respectively. The proportion of total agreement between the two questionnaires was high (0.77-0.81) with poor kappa value (0.25-0.50). In multivariate analysis, family history of atopy, stuffed toys and accompaniment of children to their parents after school hours in textile industry were found as risk factors for asthma. In addition kind of bird, such as canary was found as a risk factor. Conclusion: Prevalence of asthma is moderate in Turkey. Agreement between the two questionnaires was high. Accompaniment of children to their parents in textile industry is a newly-described risk factor for asthma. © 2013 SEICAP.
Kremer L.S.,TU Munich |
Kremer L.S.,Helmholtz Center Munich |
Danhauser K.,Heinrich Heine University Düsseldorf |
Herebian D.,Heinrich Heine University Düsseldorf |
And 26 more authors.
American Journal of Human Genetics | Year: 2016
To safeguard the cell from the accumulation of potentially harmful metabolic intermediates, specific repair mechanisms have evolved. APOA1BP, now renamed NAXE, encodes an epimerase essential in the cellular metabolite repair for NADHX and NADPHX. The enzyme catalyzes the epimerization of NAD(P)HX, thereby avoiding the accumulation of toxic metabolites. The clinical importance of the NAD(P)HX repair system has been unknown. Exome sequencing revealed pathogenic biallelic mutations in NAXE in children from four families with (sub-) acute-onset ataxia, cerebellar edema, spinal myelopathy, and skin lesions. Lactate was elevated in cerebrospinal fluid of all affected individuals. Disease onset was during the second year of life and clinical signs as well as episodes of deterioration were triggered by febrile infections. Disease course was rapidly progressive, leading to coma, global brain atrophy, and finally to death in all affected individuals. NAXE levels were undetectable in fibroblasts from affected individuals of two families. In these fibroblasts we measured highly elevated concentrations of the toxic metabolite cyclic-NADHX, confirming a deficiency of the mitochondrial NAD(P)HX repair system. Finally, NAD or nicotinic acid (vitamin B3) supplementation might have therapeutic implications for this fatal disorder. © 2016 American Society of Human Genetics
Tibussek D.,Heinrich Heine University Düsseldorf |
Schneider D.T.,Clinic of Pediatrics |
Vandemeulebroecke N.,Heinrich Heine University Düsseldorf |
Turowski B.,Heinrich Heine University Düsseldorf |
And 4 more authors.
Child's Nervous System | Year: 2010
Purpose: Our aim was to improve diagnosis and management of pseudotumor cerebri (PTC; also known as idiopathic intracranial hypertension) in children. Methods: We performed a comprehensive analysis of epidemiology, diagnostic work-up, therapy, and clinical follow-up in 53 consecutive patients. Results: We identified several important aspects to be considered in the management of these children. First, patients may present without obvious symptoms at diagnosis. Second, bilateral papilledema might not or not yet be present in symptomatic patients. Third, measurement of cerebrospinal fluid (CSF) opening pressure may not always be reliable due to drugs used for sedation, which may alter intracranial pressure. Fourth, normal CSF pressure values in childhood are not well established and diagnosis might even be justified if pressure is <20 cm H2O. Fifth, associated conditions are frequent (at least in our cohort); however, in most cases, a causative link cannot be proven. Finally, disease relapse is a serious problem (20% in our group), which stresses the importance of standardized follow-up programs. Conclusions: PTC constitutes an important and possibly underrecognized disorder in children and adolescents. Considering the high percentage of possibly associated conditions in our study, a detailed diagnostic work-up is crucial to identify treatable underlying conditions. © 2009 Springer-Verlag.
Gobel U.,Heinrich Heine University Düsseldorf |
Von Kries R.,Heinrich Heine University Düsseldorf |
Von Kries R.,Ludwig Maximilians University of Munich |
Teske C.,University of Munster |
And 4 more authors.
Pediatric Blood and Cancer | Year: 2013
Background: The overall risk for brain metastases among children and adolescents with extracranial malignant germ cell tumors (mGCT) is low but may vary between subgroups. Early identification of subgroups with an increased risk for brain metastasis is therefore important. Procedure: We analyzed 900/2,160 patients from the German MAHO/MAKEI registry on children and adolescents with malignant extracranial GCT (pure teratomas (grade 0-3) were not included). For follow-up evaluation, patients with brain metastases at diagnosis and those with a follow-up shorter than 32 months after diagnosis (longest interval to brain metastases in our cohort) were excluded. Patients were censored at detection of brain metastases or death due to other causes. A decision tree analysis considering age, gender, site of primary tumor, and presence of other metastases at diagnosis as risk factors for brain metastases was performed. Results: Among 838 eligible patients, 9 acquired brain metastases during follow-up, accounting for death in 5. There were no brain metastases in absence of extracranial metastases at diagnosis. If extracranial metastases were detected in absence of mediastinal mGCT the risk for brain metastases was 1.2% (95% CI: 0.2-3.5.%). In contrast, risk was increased to 37.5 (95% CI 15.2-64.6%) in patients with mediastinal GCTs and extracranial metastases. Conclusion: A high-risk subgroup is detected with a decision tree analysis approach. These patients may benefit from an intensified chemotherapy. Close surveillance for CNS-metastases is warranted in this high-risk group while less close monitoring in low-risk patients is justified. © 2012 Wiley Periodicals, Inc.
Schneider D.T.,Clinic of Pediatrics |
Orbach D.,University Pierre and Marie Curie |
Cecchetto G.,University of Padua |
Stachowicz-Stencel T.,Medical University of Gdańsk |
And 10 more authors.
European Journal of Cancer | Year: 2015
Objective To analyse ovarian Sertoli-Leydig cell tumours (SLCTs) for potential prognostic markers and their use for treatment stratification. Patients Forty-four patients were included. Patients were prospectively reported to the German MAKEI (Maligne Keimzelltumoren) studies (n = 23), French TGM protocols (n = 10), Italian Rare Tumour Project (TREP) registry (n = 6), and the Polish Pediatric Rare Tumour Study group (n = 5). Tumours were classified according to World Health Organisation (WHO) and staged according to International Federation of Gynecological Oncology (FIGO). Results Median age was 13.9 (0.5-17.4) years. All patients underwent resection by tumour enucleation (n = 8), ovariectomy (n = 17), adenectomy isolated (n = 18) or with hysterectomy (n = 1). FIGO-stage: Ia 24 pts., Ic 17 pts., II/III 3 pts. One patient had bilateral tumours. Four patients (stage Ia: 3, stage Ic: 1) developed a metachronous contralateral tumour. Otherwise, all stage Ia patients remained in complete remission. Among 20 patients with incomplete resection or tumour spread (stage Ic-III), eight relapsed, and five patients died. Eleven patients were initially treated with two to six cycles of cisplatin-based chemotherapy. Of these, seven patients are in continuous remission. Poor histological differentiation was associated with higher relapse rate (5/13) compared to intermediate (3/18) and high differentiation (0/4). Tumours with retiform pattern or heterologous elements showed a high relapse rate, too (5/11). After a median follow-up of 62 months, event-free survival is 0.70 ± 0.07, relapse-free survival 0.81 ± 0.06 and overall survival 0.87 ± 0.05. Conclusions Prognosis of SLCTs is determined by stage and histopathologic differentiation. Complete resection with careful avoidance of spillage is a prerequisite of cure. The impact of chemotherapy in incompletely resected and advanced stage tumours remains to be evaluated. © 2014 Elsevier Ltd.All rights reserved.
PubMed | University of Padua, University of Angers, Heinrich Heine University Düsseldorf, Clinic of Pediatrics and 7 more.
Type: Journal Article | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2015
To analyse ovarian Sertoli-Leydig cell tumours (SLCTs) for potential prognostic markers and their use for treatment stratification.Forty-four patients were included. Patients were prospectively reported to the German MAKEI (Maligne Keimzelltumoren) studies (n=23), French TGM protocols (n=10), Italian Rare Tumour Project (TREP) registry (n=6), and the Polish Pediatric Rare Tumour Study group (n=5). Tumours were classified according to World Health Organisation (WHO) and staged according to International Federation of Gynecological Oncology (FIGO).Median age was 13.9 (0.5-17.4) years. All patients underwent resection by tumour enucleation (n=8), ovariectomy (n=17), adenectomy isolated (n=18) or with hysterectomy (n=1). FIGO-stage: Ia 24pts., Ic 17pts., II/III 3pts. One patient had bilateral tumours. Four patients (stage Ia: 3, stage Ic: 1) developed a metachronous contralateral tumour. Otherwise, all stage Ia patients remained in complete remission. Among 20 patients with incomplete resection or tumour spread (stage Ic-III), eight relapsed, and five patients died. Eleven patients were initially treated with two to sixcycles of cisplatin-based chemotherapy. Of these, seven patients are in continuous remission. Poor histological differentiation was associated with higher relapse rate (5/13) compared to intermediate (3/18) and high differentiation (0/4). Tumours with retiform pattern or heterologous elements showed a high relapse rate, too (5/11). After a median follow-up of 62 months, event-free survival is 0.700.07, relapse-free survival 0.810.06 and overall survival 0.870.05.Prognosis of SLCTs is determined by stage and histopathologic differentiation. Complete resection with careful avoidance of spillage is a prerequisite of cure. The impact of chemotherapy in incompletely resected and advanced stage tumours remains to be evaluated.