This result is largely attributed to cases in previous studies of the GCCR especially in the inner zone as there is clearly some overlap between those studies. The result was not to be expected under current radiation-epidemiological knowledge. Considering that there is no evidence of relevant accidents and that possible confounders could not be identified, the observed positive distance trend remains unexplained.
The question whether leukemia rates are increased near nuclear power plants is controversial. The German Childhood Cancer Registry has published an epidemiological case-control study on childhood cancer and nuclear power plants. METHOD: The study was based on the distance of children's residences from nuclear power plants and addressed the question whether children under age 5 with cancer live closer, on average, to nuclear power plants than randomly selected controls.
RESULTS: An association was found between the nearness of residence to nuclear power plants and the risk of leukemia cases, controls. Within the 5-km zone, the OR for the development of leukemia in children under 5 years of age was 2. Many factors may conceivably cause leukemia, possibly operating in combination, and these factors may be present to a greater extent in the vicinity of German nuclear power plants.
In the adjusted overall analysis, the odds ratio OR for SMN following any radiotherapy or chemotherapy is 2. The observed risks are in many instances lower than the ones published in previous studies relating to earlier treatment eras of the primary diseases. These differences may be attributed to less toxic but still effective treatment regimes but also to differences in the length of follow-up. A total of 2, controls were randomly drawn from population registries, matched by age, gender, and region.
Although recall bias is a concern, it is unlikely that this fully explains the observed effect. Further, the observed associations might be related to the underlying infections. Kaatsch P, Spix C Jahresbericht The incidence rate has increased in some populations or subgroups. However, only a few recent publications on epidemiologic data showing the trends in incidence of pediatric GCTs are available.
Demographic, diagnostic, tumor, treatment-related variables, response, and survival data were analyzed. RESULTS:: Of the 28 preschoolers, 27 presented with high-grade central osteosarcoma of an extremity, and 1 had a secondary osteosarcoma of the orbit. This analysis focused on the 27 patients with extremity tumors. Primary metastases were detected in 4 of 27 children. Limb-sparing surgery was performed in 9 cases, ablative procedures were performed in 15, and, in 3 cases, no local surgery was performed. With a median follow-up of 4 years 6. Four patients never achieved a complete remission, and 11 developed recurrences; 14 of these 15 patients died.
Better survival was correlated with good response to chemotherapy and later time period of diagnosis. These patients often have large tumors that may require mutilating resections. Prognosis is in the range of that reported for older patients. Cancer The disease, however, is very rare with less than 2, expected patients at all age groups per year within the European Union and the United States of America. Mifamurtide, a modulator of innate immunity, which activates macrophages and monocytes, which in turn release chemicals with potential tumoricidal effects, may help to control microscopic metastatic disease and has been safely given together with standard adjuvant chemotherapy to patients with high-grade osteosarcoma.
Results of the recently published intergroup study trial from the Children's Cancer and Pediatric Oncology Groups suggest that mifamurtide is a medicine that deserves further investigation in this orphan disease. RESULTS: Of the 28 preschoolers, 27 presented with high-grade central osteosarcoma of an extremity, and 1 had a secondary osteosarcoma of the orbit.
Kager L, Bielack S [Chemotherapeutic concepts for bone sarcomas]. Georg-Thieme-Verlag 6. Greten, K et al. Even long-term common remediation therapies such as conventional physical therapy and occupational therapy do not warrant full recovery.
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Innovative complementary therapy strategies offer a new option that needs evaluation. This holistic approach aims to promote self-regulation and self-healing powers e. This pilot study is a first attempt to assess the feasibility, treatment adherence and impact of eurythmy therapy EYT in pediatric neurooncology. Kappler R, von Schweinitz D A better way forward: targeting hedgehog signaling in liver cancer.
However, abnormal activation of this pathway in postnatal tissues has been linked to a large number of human cancers. With respect to the liver, it is known that Hh signaling not only influences bipotential precursor cells capable of pancreas and liver development, but is also implicated in the pathogenesis of liver tumors such as hepatoblastoma, hepatocellular and cholangiocellular carcinoma, if aberrantly activated.
Blockade of Hh signaling by several specific inhibitors has been proven to successfully inhibit tumor growth of various Hh-associated cancers in vitro and in preclinical mouse models, and recent clinical data suggest that the implementation of novel anticancer therapeutics based on Hh interference into commonly accepted regimens are within reach. Thus, it is highly probable that Hh targeted therapies could be used for the treatment of Hh-dependent liver cancers in the future.
To establish a protocol feasible under conditions there, ALL-MB 91 was designed to avoid prolonged bone marrow aplasia, thereby reducing needs for extensive supportive care, blood transfusions, long-lasting hospitalization and costs. This was randomized against a modified BFM protocol. From to , patients of age up to 18 years were registered in 10 centres and received after central randomization the allocated risk-stratified treatment. Clinical and epidemiological data were compared with those of pediatric patients with centrally reviewed glioblastoma multiforme GBM from the same database.
In this unique series, median age, male preference, and median clinical history did not differ significantly between pediatric GCG and GBM patients. GCG showed a stronger predilection for cerebral hemispheres than did GBM, which may only partly explain the higher percentage of gross total tumor resections in GCG patients. Most surprising, the widely distributed hypothesis that GCG may imply a better prognosis than GBM could not be substantiated for our pediatric series. Future studies with larger patient numbers and molecular pathological analyses are still needed to corroborate the present findings and further elucidate the biology of GCG in children.
Karow A, Baumann I, Niemeyer CM Morphologic differential diagnosis of juvenile myelomonocytic leukemia--pitfalls apart from viral infection. Inclusion criteria were diagnosis of AGG proven by a central neuropathological review and patient age 0 to 17 years. Eight patients five male and three female were identified. The median history of disease was 9 months range, 1.
Initial symptoms included signs of raised intracranial pressure, seizures, and, in the case of spinal cord tumor, bladder dysfunction. In five cases, AGGs were localized supratentorially with three patients having multiple lobes involved. Gross total tumor resection was achieved in six patients. While gender and tumor location did not affect survival rates, gross total tumor resection provided a better overall survival than non-total resection. We studied the clinical relevance of this histological glioblastoma subentity within the pediatric population.
We obtained patient data from the German HIT-GBM database, which contains clinical data for more than pediatric patients with centrally reviewed high-grade gliomas. By applying defined inclusion criteria diagnosis of GS proven by central neuropathological review; patient age 0 to 21 years , four patients were identified. In addition, after a review of the English medical scientific literature, 19 additional cases were found. In the whole series of 23 pediatric GS patients, including previously reported cases, the male-to-female-ratio was 1.
Since little is known about these tumours, the present study aimed at their further characterisation. Clinical and epidemiological data were compared with those of paediatric patients with cortical HGG. Results:Patients with cerebellar tumours were younger median age of 7. Except for an increased incidence of anaplastic pilocytic astrocytoma APA in the cerebellar subset Given considerable differences between primary and relapsed acute lymphoblastic leukemia treatment regimens, flow cytometric assessment of minimal residual disease in relapsed leukemia requires an independent comprehensive investigation.
In the present study we addressed evaluation of minimal residual disease by flow cytometry in the clinical trial for childhood relapsed acute lymphoblastic leukemia using eight-color flow cytometry. The major challenge of the study was to reliably identify low amounts of residual leukemic cells against the complex background of regeneration, characteristic of follow-up samples during relapse treatment. In a prospective study of follow-up bone marrow samples from patients with B-cell precursor acute lymphoblastic leukemia, we tested various B-cell markers, adapted the antibody panel to the treatment protocol, and evaluated its performance by a blinded parallel comparison with the polymerase chain reaction data.
Limited evidence is available to guide acute and chronic management of individuals with SCD and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology.
The primary end point was status of the bone marrow BM sampled shortly before the second course of chemotherapy the day 28 BM. Data are presented according to intention-to-treat for all randomly assigned patients median follow-up, 4. Grade 3 to 4 toxicity was essentially similar in both groups. International collaboration proved feasible and resulted in the best outcome for pediatric relapsed AML reported thus far.
The aim of this multicenter study was to analyze the relationships between the identified fusion transcripts and survival including some selected clinical parameters.
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The extent of disease was graded according to clinical staging system with following distribution: 3 children with stage I, 4 with stage II, 23 with stage III, and 18 with stage IV spread disease having distant metastases. In addition, fusion gene analysis is a helpful tool in differential diagnosis of poorly differentiated soft tissue tumors. Both areas of paediatric oncology research focus on cancers with a broad range of sensitivity to chemotherapy and radiation therapy, together with concerns about the neurodevelopmental, neuroendocrine and growth outcomes of survivors.
These considerations have influenced the design of curative- intent treatments, strategies for successfully eradicating leptomeningeal disease, and the importance of anatomic and functional identification of residual disease. Unlike the situation with childhood leukaemia, the emotional barriers of pessimism or even nihilism previously evident towards infants with brain tumours have only begun to crumble during the past decade.
The challenge to improve both the quality and overall survival of infants with CNS tumours described in this chapter is ours to meet as we move into the new millennium. This paper examines the development of 'infant' approaches to the treatment of CNS tumours, including a discussion of epidemiology, the reasons for avoiding or delaying radiation therapy, and traces the chemotherapy hypotheses tested over the past two decades in the process of developing potentially curative therapy.
The reasons for the disappointing rate of progress compared with that in childhood leukaemia, despite similar clinical research paradigms, are discussed, and potential opportunities are identified. There were patients with metastases, 44 with local recurrences, and 31 with both. Five-year OS was 0. Pre- and postoperative neurologic status and serial heights and weights were also recorded.
Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower ie, better z-scores for executive function in all participants mean intergroup difference 0. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores mean intergroup difference 0. In 12 out of the 13 patients with acute bronchitis, the acute clinical symptoms disappeared and in 11 out of the 13 patients the initial sputum organisms were two days after stopping cefaclor treatment.
With the introduction of anti-EGFR-targeted therapies in clinical practice, these findings regain increased attention. Experience with anti-EGFR-targeted therapies in other cancers has made clear that besides the expression status of EGFR, a detailed knowledge about gene mutations is of major predictive power. We therefore aimed to explore the EGFR expression and gene mutation status in high-grade osteosarcomas.
Sixty-three patients were treated according to the Cooperative Osteosarcoma Study Group protocols and complete clinical follow-up was available in these cases. EGFR expression showed a dose-response relation with improved event-free and overall survival. This was independent of the degree of tumor regression due to neoadjuvant chemotherapy.
All these cases expressed EGFR. This implies that low EGFR expression possibly predicts lack of response to conventional treatment in high-grade osteosarcomas and may warrant a more intensive therapeutic approach, although not based on EGFR targeting. Kehrel BE Platelets: biochemistry and physiology. Besides the basic processes in primary haemostasis, platelet adhesion, platelet secretion, platelet aggregation, clot retraction, the new model of thrombin formation on the platelet surface is presented.
The different signal transduction pathways in platelets are a main focus of this review. Rhabdoid tumors have only recently been registered and treated according to specifically designed treatment recommendations and in the framework of clinical trials. This review summarizes past and current clinical approaches and presents an overview of the rationales for targeted therapy with potential for future clinical treatment trials for rhabdoid tumors.
MLPA and Sanger sequencing of the SMARCB1 gene in the germ line may be useful for the initial diagnosis in a defined subgroup of infants with rhabdoid tumors, in which biopsies cannot be performed. Therefore, the standard thiopurine drug regimen is associated with increased hematopoetic toxicity in patients with low or absent TPMT activity, whereas patients with high activity may be insufficiently treated. However, presently available methods are labour intensive and time consuming and tend towards too high or too low enzyme activity due to their methodological approach.
The use of instable substrate solutions 6-MP or 6-TG , organic solvents like dimethyl sulfoxide and too high substrate and co-substrate saturation concentrations contribute to this phenomenon. Unspecific non-enzymatic methylation was not detectable. The assay dispenses with a time consuming extraction procedure with organic solvents, a heating step, and a gradient elution and is therefore, favourable for clinical routine application.
This study aimed at correlating these polymorphisms to lethal infections during childhood acute lymphoblastic leukemia ALL. A matched case-control study of 34 patients who died due to infections during ALL treatment and 68 ALL patients without lethal infections was performed.
Genomic DNA was isolated from blood smears and specific fragments including the polymorphic site of each gene were amplified. The variant genotypes were equally distributed between cases and controls [relative risk RR 1. With regard to infective organisms, no statistically significant differences could be detected between the groups for bacterial infections [RR 1. Patients with a LT-alpha These results support a role of specific genetic polymorphisms on lethal infections during induction chemotherapy of ALL treatment.
However, their value in predicting GvHD and survival is still limited.
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The median observation period at the time of this writing was 4. Kirton A, deVeber G Advances in perinatal ischemic stroke. These gene products constitute a common ubiquitin-phosphorylation network called the Kivela T Trilateral retinoblastoma: a meta-analysis of hereditary retinoblastoma associated with primary ectopic intracranial retinoblastoma. Data from children were used in a meta-analysis including frequency distributions and Kaplan-Meier survival curves. The mean study duration from the start of pharmacovigilance was The most common treatment at the last visit was prophylaxis One clinically relevant inhibitor in a previously untreated patient was documented during the study course.
Patients ranged in age from six months to 48 years, with a mean of 13 years; two thirds of the patients were male. Systemic metastases occurred on an average of two years after the diagnosis of the primary tumor in patients without shunts, but only 1. Fifty-nine percent of the patients were known to have experienced recurrence or spread of medulloblastoma within the central nervous system by the time systemic metastases appeared. Bones most frequently involved were pelvis, femur and vertebrae; pain was the most common initial symptom. The average survival was seven months after the appearance of systemic metastases for patients both with and without shunts.
This development is associated with increased morbidity and a shortened life expectancy. In addition, a number of complex clinical syndromes associating congenital neutropenia have been recognized and elucidated on a genetic level, e. The clinical and genetic findings of various neutropenia syndromes are being discussed. Springer Verlag Heidelberg 4.
Eligibility criteria were: diagnosis confirmed by reference pathology, primary stage IV, below 22 years of age, and having completed the study therapy. The main risk parameters were equally distributed in both arms. After a median follow-up of Kaplan-Meier analysis demonstrated an overall survival for the whole group of 0. Transplant centers initiating programs on haploHSCT for children may collaborate with more experienced centers.
Geburtstag von Herrn Prof. Notably, microarray analyses revealed severe defects in signaling cascades regulating the cell cycle, including c-Myc-downstream signaling, in myeloid cells transduced with SLPI shRNA. Taken together, these results indicate that SLPI controls the proliferation, differentiation, and cell cycle of myeloid cells.
Though TL resolves spontaneously in the majority of cases, early death and development of myeloid leukemia ML-DS may occur. Prognostic factors as well as treatment indication are currently uncertain. To resolve that issue, we prospectively collected clinical, biological and treatment data of patients with TL. Multivariate analysis revealed a correlation between high white blood cell WBC count, ascites, preterm delivery, bleeding diatheses, failure of spontaneous remission and the occurrence of early death.
Treatment with cytarabine 0. Multivariate analysis demonstrated its favorable prognostic impact. This study was registered at www. The factors on human chromosome 21 Hsa21 that confer this predisposing effect, especially in synergy with consistently mutated transcription factor GATA1 GATA1s , remain poorly understood. Integrative transcriptome analysis of hematopoietic cells upon modulation of miRb expression levels uncovered a set of miRb target genes, including DICER1 and ST18 as direct targets.
Thus, we propose miRb-2 as a positive regulator of megakaryopoiesis and an oncomiR involved in the pathogenesis of trisomy associated megakaryoblastic leukemia. The role of allogeneic stem cell transplantation in post-remission management of pediatric high-risk acute myeloid leukemia remains controversial. In the multi-center AML-BFM 98 study we prospectively evaluated the impact of allogeneic stem cell transplantation in children with high-risk acute myeloid leukemia in first complete remission.
Design and Methods. All patients received double induction and consolidation. The main analysis was done on an intention-to-treat basis according to this allocation. In addition to the early interim PET after 2 cycles of chemotherapy, all patients undergo an initial PET investigation which is part of the staging processs and plays an essential role for the interpretation of the interim PET. Therefore, in the forthcoming EuroNet-PHL-C2 study bone marrow biopsy and bone scintigraphy will no longer be part of the staging algorithm.
Inter-reader reliability of the whole scale is not well characterised. Knowles DM Inmunodeficiency-associated lymphoproliferative disorders. Data from paediatric patients with hereditary thrombocytopathies HT treated in Germany, Austria, and Switzerland were obtained between May and August By evaluation of results of platelet function tests criteria were determined to assess the diagnosis in each patient into most likely, likely or unlikely.
A total of patients treated in 31 centers were identified. The low prevalence of these diseases and the high percentage of patients with unclassified HT stresses the necessity for the establishment of a competence network for comprehensive care of these patients in the three German-speaking countries.
Typical bleeding symptoms are easy bruising, epistaxis, menorrhagia as well as mucocutaneous and perioperative bleeding. The performance of platelet function diagnostics in children is hampered by age-dependent restriction of blood sample size, poor venous access, and the lack of reproducible test reference ranges for children of different age groups. Platelet function testing is limited to specialised centres, because platelet function test procedures are complicated and time-consuming, which most likely results in a relevant number of undiagnosed and incorrectly classified children with clinically relevant platelet function defects.
Evaluation of bleeding history and bleeding symptoms is essential for a rational step-by-step approach to diagnosis. Platelet function diagnostics should be preceded by the exclusion of thrombocytopenia, von Willebrand disease, and secondary haemostasis defects. Light transmission aggregometry is still considered the standard for the assessment of platelet function. Every effort should be made to classify the specific platelet function defect in the patient, because this is essential for accurate treatment and counselling. In clinical settings only a few methods have proven to be useful for identification and classification of inherited platelet disorders.
For a rational diagnostic approach, a stepwise algorithm is recommended. Patient history and clinical investigation are mandatory. Von Willebrand disease and other coagulation disorders should always be ruled out prior to specific platelet testing. Platelet count, size, volume MPV and morphology may guide further investigations. Platelet aggregometry allows assessment of multiple aspects of platelet function.
Flow cytometry enables diagnosis of thrombasthenia Glanzmann, Bernard-Soulier syndrome and storage pool defects. Molecular genetics may confirm a putative diagnosis or pave the way for identifying new defects. We present an unabridged version of the interdisciplinary guideline. The chosen diagnostic tests should be able to detect the presence of relatively common coagulation defects such as von Willebrand syndrome or hemophilia, but also rare diseases such as inherited thrombocytopathies.
For this purpose, specific platelet function testing is needed. However, the methods are only available in some coagulation laboratories. Also, other limitations need to be taken into consideration such as pre-analytical problems and difficulties in the interpretation of test results especially in infants. We present two cases that were diagnosed with an aspirin-like defect as an inherited thrombocytopathy, even though their PFA closure times were within the normal range. Based on pathological findings in the platelet aggregometry test, this diagnosis could be made.
Most HBs develop sporadically but their incidence is highly elevated in patients with familial adenomatous polyposis coli FAP. These patients carry germline mutations in the adenomatous polyposis coli APC tumour suppressor gene. APC forms a multi-protein complex involved in the WNT signalling pathway that controls the stability of beta-catenin, the central effector in this cascade.
Whereas APC mutations are rare in sporadic HBs, a high frequency of beta-catenin mutations leading to overactivation of WNT signalling was previously found in these tumours. This pathway is negatively controlled by conductin axin2 , representing a further partner in this signalling complex. To investigate whether alterations in conductin may also be involved in the pathogenesis of sporadic HBs, 37 HBs and five HB cell lines were screened for mutations using single-strand conformation polymorphism SSCP analysis, reverse transcription-polymerase chain reaction RT-PCR , and direct sequencing.
In two cases, larger deletions 52 and bp leading to frameshifts were found. In addition, one HB carried a somatic point mutation. This mRNA overexpression resulted in increased conductin protein levels demonstrated by western blot analysis. Tumours with activating beta-catenin mutations revealed higher levels of conductin mRNA transcripts.
This finding indicates that conductin is a direct target gene of WNT signalling in HBs, as has been demonstrated in other tissues. In summary, conductin mutations may represent an alternative mechanism leading to activation of WNT signalling in HBs. A high frequency of activating beta-catenin mutations in hepatoblastomas indicates that the Wnt signaling pathway plays an important role in the development of this embryonic neoplasm. Stabilization of beta-catenin leads to an increased formation of nuclear beta-catenin-T-cell factor complexes and altered expression of Wnt-inducible target genes.
We analyzed 23 hepatoblastoma biopsies for which matching liver tissue was available, 6 hepatoblastoma cell lines, and 3 human fetal liver samples. In human liver tumor cells without beta-catenin mutations, Nkd-1 inhibited the Wnt-3a-activated Tcf-responsive-luciferase reporter activity, whereas Nkd-1 in hepatoblastomas with beta-catenin mutations had no antagonistic effect.
Our data emphasize the inhibitory effect of beta-TrCP and Nkd-1 on the Wnt signaling pathway in a manner analogous to Conductin AXIN2 and Dkk-1, inhibitors shown previously to be up-regulated in hepatoblastomas. Our findings indicate that overexpression of the Wnt antagonists Nkd-1 and beta-TrCP reveals an activation of the Wnt signaling pathway as a common event in hepatoblastomas. We propose that Nkd-1 and beta-TrCP may be used as possible diagnostic markers for the activated Wnt signaling pathway in hepatoblastomas.
In contrary, granulocyte-monocyte colony-stimulating factor GM-CSF fails to increase neutrophil numbers in CN patients in vitro and in vivo, suggesting specific defects in signaling pathways downstream of GM-CSF receptor. However, many patients will show secondary malignancies years after the initial diagnosis, which appears to be connected with the intensity of treatment during primary disease.
In the GPOH-HD 95 trial, the indication for radiotherapy was limited to patients who did not show a complete remission after chemotherapy, as determined radiographically. In the future protocol, the indication for radiotherapy in patients with early-stage Hodgkin's lymphoma should be further refined by using FDG-PET for evaluating the response to chemotherapy. Furthermore, in patients at an advanced stage of the disease, it should be determined if sequential FDG-PET research during chemotherapy can separate patients into subgroups with an excellent or a poor prognosis.
This article gives a review of the current literature on FDG-PET in patients with Hodgkin's lymphoma and outlines the consequences for future protocols. Springer-Verlag GmbH Deutschland, 2. Two Ewing tumor cell lines were characterized in vitro before and 24 and 72 h after radiation with 5 Gy by multiparametric flow cytometry.
Based on these markers radiation induced apoptosis was quantified, multiple apoptotic subpopulations were identified and a characteristic individual apoptotic profile was characterized. The observed heterogeneity and the identification of multiple apoptotic subpopulations reflect the complexity and diversity of biology of radiation induced cell death. This might be an indication for co-existing apoptotic pathways or it might represent sequential steps of the apoptotic cascade.
Recently, the long pulsed dye laser LPDL with cryogen spray cooling CSC has been found relatively more effective and safer than the PDL in the treatment of port-wine stains and telangiectasia. This study reports the disease characteristics, treatment and outcome of all patients with the diagnosis of mature TCL registered in the Berlin-Frankfurt-Munster non-Hodgkin lymphoma database between and All diagnoses were centrally reviewed and revised by clinico-pathological correlation according to the criteria of the current World Health Organization classification.
Of the 69 patients originally registered as having PTCL, the diagnosis was confirmed in 38 of them. Most patients were treated with an anaplastic large cell lymphoma ALCL -like therapy regimen. Our results suggest that the outcomes of children with mature TCL other than ALCL depend on the subtype and are worse than in all other paediatric lymphomas.
The clinical experience presented in this largest study on paediatric mature TCL may serve as basis for future collaborative international prospective clinical trials. Its incidence is highest in Southeast Asia. Age distribution of NPC is bimodal, with one peak in young adolescents and another in patients years of age. EBV appears to be the primary etiologic agent in the pathogenesis, environmental factors such as nitrosamines and genetic factors are contributory. Response to therapy can be assessed by PET-imaging and in patients with complete remission after neoadjuvant chemotherapy, the radiation dose to the primary tumor can be safely reduced from Since the majority of long term sequalae such as xerostomia, skin and tissue fibrosis are caused by high radiation dosages, radiotherapy modalities such as intensity-modulated radiotherapy should be used to efficiently spare non-tumorous tissue.
For patients with metastatic disease and relapse, survival chances are low. New treatment strategies, such as the application of EBV-specific T-lymphocytes should be considered for these patients. Kook H Fanconi anemia: current management. The gold-standard screening test for FA is based on the characteristic hypersensitivity of FA cells to the crosslinking agents, such as mitomicin C or diepoxybutane. Recent progress has been made in identifying the genes bearing pathogenetically relevant mutations, but slower progress has been made in defining the precise functions of the proteins in normal cells, in part because that the proteins are multifunctional.
Stem cell transplantation SCT is the only option for establishing normal hematopoiesis. To reduce undue toxicities due to inherent hypersensitivity, nonmyeloablative conditioning for transplants has been advocated. This review summarizes the general clinical and hematologic features and the current management of FA. Fanconi anemia FA is the commonest type of inherited bone marrow failure syndrome with the birth incidence of around three per million.
The inheritance pattern is autosomal recessive with the estimated heterozygote frequency being one in in Europe and the US. Part II. Beuthien-Baumann, et al. Differentiation between recurrent tumor and radiation necrosis in a child with anaplastic ependymoma after chemotherapy and radiation therapy. Strahlenther Onkol ; Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft We aimed at the identification of recurrent genetic aberrations in ependymoma and evaluated their prognostic significance to develop a molecular staging system that could complement current classification criteria.
We investigated health-related QOL in 51 patients treated with iodine I brachytherapy for childhood low-grade gliomas. The time lapsed since I-brachytherapy was months median, range: months. The patients and their caregivers rated their QOL as not different from that of the normal population. However, many QOL dimensions correlated to the severity of disability. Comparison of QOL outcomes between different treatment measures would require a prospective study controlling for the most important factors of influence.
It is a rare but distinct post-operative complication of craniopharyngioma that is different from leptomeningeal progression of other low grade pediatric brain tumors such as pilocytic astrocytoma. We present clinical pathological data from a young boy who suffered a metastasis of his craniopharyngioma along the surgical route shortly after irradiation for progressive disease at the primary site. Diagnostik und Therapie. The present study evaluated questionnaire-based fertility characteristics in cancer survivors treated with irradiation to the hypo-thalamic-pituitary-axis.
A nationwide survey was conducted in collaboration with the German Childhood Cancer Registry. Patterns of dissemination and recurrence in childhood ependymoma: Preliminary results of Pediatric Oncology Group Protocol The patients were staged according to the International Neuroblastoma Staging System, and histologic grading of the tumors was performed according to the criteria of Hughes and those of the International Neuroblastoma Pathology Classification. The MYCN gene copy number was determined by Southern blot analysis or fluorescence in situ-hybridization, and repp86 expression was assessed immunohistochemically by means of monoclonal antibody Ki-S2 on paraffin sections from archival tumor samples.
The critical gene for ERMS development in this region is unknown. The association of CS and ERMS as well as previous reports illustrating that somatic HRAS mutations are found in a proportion of these tumors prompted us to clarify the significance and a possible correlation of HRAS mutations and genomic rearrangements at 11p We screened for somatic HRAS mutations and 11p Therefore, they must have succeeded the emergence of UPD. Subsequent development of UPD at 11p Sixty-six patients mean age at diagnosis 7.
Although there was a statistically significant decline of intellectual function after reinduction therapy for younger patients and girls IQ scores still within normative data range , there were no differences in visual-motor performance and concentration over the time of induction therapy. Thus, neurocognitive examination should focus on younger ALL patients and girls.
Because very little is known about these tumors, we aimed to further characterize them. In our series of 99 pediatric thalamic HGGs, there were no significant differences in survival between patients with tumors affecting the thalamus alone including bithalamic lesions and patients with tumors affecting the thalamus plus adjacent structures.
The varying extent of tumor resection in the different tumor localizations may play some role in the observed clinical differences, as shown by multivariate Cox regression analyses, but the tumor site itself was also identified as an independent prognostic parameter. Therefore, future investigations should try to further characterize the obviously site-specific heterogeneity of pediatric HGG on a molecular genetic basis. Eighty-four boys 48 prepubertal and 36 pubertal were evaluated, including 50 with acute lymphoblastic leukemia ALL or non-Hodgkin lymphoma NHL , 10 with Hodgkin lymphoma HL , and 24 with solid tumors.
The control group consisted of 24 healthy prepubertal and 24 pubertal boys. The levels of follicle-stimulating hormone FSH , luteinizing hormone LH , inhibin B, and testosterone were determined, and testicular volumes were measured. We used high-dose chemotherapy HDC with peripheral hematopoietic stem cell transplantation in such patients in an attempt to improve their survival.
Four patients with bone marrow metastases and one child with extraorbital disease were treated with HDC after achieving complete remission by enucleation and conventional chemotherapy. The child with extraorbital tumor was the only one to receive local irradiation. Hematologic recovery occurred without delay in all patients. The main toxicities were diarrhea, mucositis and infectious complications.
No toxic deaths or any major late toxicities were observed. The child treated with the BCNU regimen developed a meningeal relapse 10 months after HDC, which was partially resected and treated with conventional chemotherapy, but not with radiotherapy. He is in complete remission CR months off treatment. HDC with thiotepa, etoposide and carboplatin may represent a curative option for children with extrabulbar or disseminated retinoblastoma responsive to chemotherapy. It may control occult CNS disease. The necessity to irradiate these children and the curative potential of this strategy for patients with bulky CNS disease remain to be determined.
MVD was correlated with demographic and tumor-related variables, response, and survival. At a median follow-up period of 3. However, a pilot study to assess the harm and benefit of the questionnaire was approved. Although the numerical data cannot be directly translated to ethical conclusions, they can provide guidance for future ethical decisions. Median expression levels were 1. Marked proteinuria may already be present before a child has any clinical signs of nephrotic syndrome edema, oliguria. Urinary dipstick tests mainly disclose the presence of albumin, in semiquantitative fashion, and thus cannot reveal tubular proteinuria.
In contrast, the Biuret reaction gives a quantitative measure of all urinary proteins. To quantify further proteins in the urine, other methods are needed, e. Asymptomatic proteinuria is present as an isolated finding in 0. In a cohort of children, significant proteinuria was found in a single sample in Clearly, urinalysis should always be repeated if proteinuria is found before any further testing is done for renal or systemic disease.
Proteinuria can be transient or functional. In general, proteinuria is not indicative of renal disease in the following situations 32 , e8 :. Orthostatic proteinuria is characterized by moderate, nonselective proteinuria of up to 1. It is diagnosed by separate analysis of daytime and nighttime urine samples. Its overall prognosis is favorable, as it does not seem to be associated with renal disease of any kind 11 , e A finding of proteinuria combined with hematuria necessitates consultation with a pediatric nephrologist, particularly if there are signs of nephritic syndrome or of a systemic disease.
Proteinuria can also be the sole manifestation of a malformation of the urinary tract. The incidence of nephrotic syndrome has been estimated at 1. In infants and toddlers, marked proteinuria often reflects a congenital nephrotic syndrome traceable to a genetic abnormality of podocyte function; in older children, the main elements of the differential diagnosis are focal-segmental glomerulosclerosis, membranoproliferative glomerulonephritis, immune disorders, and connective-tissue diseases e6. Serial studies reveal hematuria in 1. Macrohematuria arises in 1. The evaluation of hematuria should not end with a positive dipstick test.
Urine microscopy is obligatory in all cases. Hematuria is the abnormal excretion of blood or erythrocytes in the urine It is subcategorized as erythrocyturia red blood cells in the urine or hemoglobinuria hemoglobin in the urine. Even 1 mL of blood in a liter of urine produces macrohematuria ca. Microhematuria is usually an incidental finding, while macrohematuria often leads patients to consult a physician.
Microhematuria should always be confirmed by multiple urinalyses. Hematuria combined with proteinuria indicates renal disease and calls for further diagnostic evaluation. Reddish discoloration of the urine is not, however, synonymous with macrohematuria, as it may also be due to hemoglobinuria, myoglobinuria dipstick test positive, microscopy negative , or medications or foods dipstick test and microscopy both negative Table 4 , [e5]. The basic diagnostic evaluation of macrohematuria for its further differentiation always includes microscopic analysis of the urine.
Phase-contrast microscopy of the urine sediment is suitable for distinguishing glomerular from non-glomerular causes of hematuria. Erythrocyturia can be of either glomerular or post-glomerular non-glomerular origin. Postrenal sources of bleeding may be located anywhere in the urinary pathway, from the calyces to the urethral opening. Macrohematuria of postrenal origin causes bright red discoloration of the urine, while macrohematuria of glomerular origin is rusty brown. Centrifugation of fresh blood-tinged urine yields a clear fluid if hematuria is postrenal, a brownish fluid if hematuria is renal, and an unchanged reddish fluid in case of hemoglobinuria or myo-globinuria.
The demonstration of erythrocyte cylinders proves that the source of the erythrocytes is glomerular, as the cylinders arise by compaction of glomerular-derived erythrocytes in the renal tubules and collecting ducts e Blood clots are not found in glomerular hematuria Table 5. Transient hematuria is often not of any pathological significance. In girls, the urine sample may contain blood from vaginal secretions menstruation or after sexual intercourse. Rare but serious causes of glomerular hematuria include hereditary defects of the glomerular basal membrane, as in Alport syndrome e20 , e21 and the thin basement membrane disease benign familial microhematuria e These diseases are due to defects in the synthesis of type 4 collagen; they have different inheritance patterns and overlapping clinical manifestations.
They are often associated with sensorineural hearing impairment and ocular changes. Isolated asymptomatic microhematuria requires long-term follow-up, as it may indicate the presymptomatic stage of a renal disease e Glomerular micro- hematuria needs further evaluation if other family members also have this finding, or if there is a family history of chronic renal disease or hearing impairment.
As these diseases do not involve the glomerulus, the erythrocytes in the urine are eumorphic. The same holds for hematuria of vascular origin, e. In children and adolescents with hematuria, an underlying nephrologic disease should be ruled out. The erythrocyte morphology should be evaluated early to localize the source of erythrocyturia.
Postrenal causes of hematuria include trauma, urinary tract infections, urolithiasis, hypercalciuria, and anatomical lesions obstruction, hydronephrosis, tumor. A tumor causing postrenal hematuria in childhood is almost always a nephroblastoma Wilms tumor ; such tumors can be visualized by ultrasonography e27 , e In this article, which focuses on basic nephrologic testing, we cannot provide a complete diagnostic algorithm and instead give only a rough guide to the relevant clinical situations. Alhough isolated erythrocyturia may be a clinically irrelevant finding, it nonetheless requires comprehensive nephrologic evaluation and follow-up.
The basic prerequisites for the interpretation of urinalysis findings are the correct acquisition of the sample and the correct performance of the tests in question. Dipstick tests can be used to detect leukocyturia, nitrituria, proteinuria, and hematuria; their findings are best interpreted together with the findings of urine microscopy and in view of the clinical situation, sometimes with targeted further testing. Leukocyturia should be evaluated in connection with the presence or absence of any clinical signs of a urinary tract infection, a systemic inflammatory reaction, and a clearly identified pathogen.
Proteinuria should be quantified and subcategorized by type. Orthostatic proteinuria is of no pathological significance. The detection of erythrocyturia should be followed by urine microscopy to determine whether its origin is glomerular or non-glomerular. The further diagnostic evaluation depends on which of these is the case. Microhematuria, if it is an isolated finding, may be of no pathological significance.
Hematuria accompanied by other abnormal urinary findings or clinical manifestations may be a sign of nephritis or of a systemic disease with renal involvement. Even a small amount of blood can cause macrohematuria. The finding of red discoloration of the urine provides no information about its cause glomerular or non-glomerular hematuria, other.
See the following website: cme. The EFN must be entered in the appropriate field in the cme. What method of obtaining a urine sample is most suitable for reliable biochemical testing? Which of the following statements about the interpretation of findings of urinary dipstick tests is true? What symptoms and signs are characteristic of pyelonephritis in school-aged children? Which of the following is the most likely underlying cause of a bacterial urinary tract infection in an infant?
Which of the following testing methods in urinalysis in childhood has the highest specificity? What is the reference range for an abnormal leukocyte count in midstream urine from a girl under 3 years of age? Which of the following is a tubulo-interstitial cause of erythrocyturia? What type of malignant tumor is the cause of nearly all cases of postrenal hematuria in childhood?
What conditions are often associated with type 4 collagen mutations?
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The snippet could not be located in the article text. This may be because the snippet appears in a figure legend, contains special characters or spans different sections of the article. Dtsch Arztebl Int. Published online Sep PMID: Boris Utsch , PD Dr. Received Aug 27; Accepted Jul 8. Copyright notice. This article has been cited by other articles in PMC. Abstract Background Urinalysis is the most commonly performed biochemical test in infancy and early childhood.
Method This review is based on a selective literature search in electronic databases, textbooks, and guidelines from Germany and abroad on the acquisition of urine samples and the performance of urinalysis in infancy and early childhood. Results The timing and mode of acquisition of the urine sample affect the assessment of hematuria, proteinuria, leukocyturia, nitrituria, and the uropathogenic bacterial colony count in the urine culture.
Conclusion Urinalysis in infancy and early childhood is a simple and informative diagnostic test as long as the urine sample has been obtained properly and the results are interpreted appropriately for this age group. Learning objectives After reading this article, the reader should be able to list the main principles of urine sample acquisition in infancy and childhood and critically assess dipstick test findings. Urine sample acquisition Single urine samples Midstream urine — Midstream urine can be obtained from any child that has achieved urinary continence.
Acquisition of urine samples from infants and toddlers — There are four ways to obtain urine samples from small children who cannot yet control their voiding: Urine acquisition for reliable biochemical testing. Bag urine: The genitals are inspected, thoroughly cleaned, and dried, and a self-adhesive urine collection bag is securely attached. Ideally, the child should void after being given fluids, and the urine sample should be processed immediately. Bag urine is unsuitable for culture, because contamination frequently causes false-positive findings 5 — 7. Catheter urine: A suitable urine sample for culture can be obtained from a female infant or toddler by one-time catheterization i.
In boys, suprapubic bladder puncture should be performed instead of transurethral catheterization 9. Suprapubic bladder puncture: This is a simple though rarely performed , relatively noninvasive means of acquiring a urine sample if pyelonephritis is suspected, particularly when the patient is an infant. Vesical puncture is indicated whenever bag urine can be expected to be contaminated, e. Urine acquisition for reliable microbiological testing. Collected urine Common indications for urine collection include the determination of endogenous creatinine clearance, the quantification and differentiation of proteinuria Table 1 , and the measurement of fluid and electrolyte excretion.
Open in a separate window. Table 2 Sensitivity and specificity or urine tests 14 , 20 , 22 , 23 , 38 , e2 , e Isolated leukocyturia or bacteriuria. Nitrite test Most urinary pathogens with the important exception of enterococci can reduce nitrate to nitrite; thus, nitrite in the urine indicates bacteriuria. The diagnosis of urinary tract infection. Complicated urinary tract infections.
Proteinuria Proteinuria—excessive elimination of protein in the urine—is a feature of tubular or glomerular dysfunction. Utility of dipstick tests for proteinuria. Orthostatic proteinuria. Marked proteinura. Proteinuria combined with hematuria. Hematuria Serial studies reveal hematuria in 1. Determining the cause of hematuria. Table 4 Causes of dark urine e5.
Endogenous erythrocytes hemoglobin myoglobin metabolic products homogentisic acid alcaptonuria , porphyrins amorphous urates brick-dust sediment Exogenous foods red beets betanidine , rhubarb anthrone derivatives , blackberries, food coloring e. Glomerular vs.
Table 5 Charakteristic findings in erythrocyturia of glomerular and non-glomerular origin 29 , 40 , e Transient hematuria Transient hematuria is often not of any pathological significance. Persistent hematuria Rare but serious causes of glomerular hematuria include hereditary defects of the glomerular basal membrane, as in Alport syndrome e20 , e21 and the thin basement membrane disease benign familial microhematuria e Tubulointerstitial causes of erythrocyturia include the following: cystic renal diseases.
Localizing the source of erythrocyturia. Isolated erythrocyturia. Overview The basic prerequisites for the interpretation of urinalysis findings are the correct acquisition of the sample and the correct performance of the tests in question. Red discoloration of the urine. Please answer the following questions to participate in our certified Continuing Medical Education program. Only one answer is possible per question. Please select the answer that is most appropriate. The time the urine spent in the bladder does not affect the result of the nitrite dipstick test. The nitrite dipstick test can be falsely negative if the voided urine has been in the bladder for too short a time less than 4 hours.
Footnotes Conflict of interest statement Prof. References 1. Screening dipstick urinalysis: a time to change. Role of routine urinalysis in asymptomatic pediatric patients. Clin Pediatr. Urinary tract infection: a search for evidence. J Pediatr Rio J ; 79 — To clean or not to clean: effect on contamination rates in midstream urine collections in toilet-trained children. Comparison of sterile bag, clean catch and suprapubic aspiration in the diagnosis of urinary infection in early childhood.
Br J Urol. Urine culture from bag specimens in young children: are the risks too high? J Pediatr. Contamination rates of different urine collection methods for the diagnosis of urinary tract infections in young children: an observational cohort study. J Paediatr Child Health. Accuracy of clean-catch urine collection in infancy.
Subcommittee on Urinary Tract Infection. Technical report—Diagnosis and management of an initial UTI in febrile infants and young children. Use of protein:creatinine ratio measurements on random urine samples for prediction of significant proteinuria: a systematic review.
Clin Chem. Orthostatic proteinuria and the spectrum of diurnal variability of urinary protein excretion in healthy children. Pediatr Nephrol. Comparison of albumin excretion rate obtained with different times of collection. Diabetes Care. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months.
Downs SM. Technical report: urinary tract infections in febrile infants and young children. Kass EH. Bacteriuria and the diagnosis of infections of the urinary tract. Arch Int Med.
Redefining urinary tract infections by bacterial colony counts. Clinical and demographic factors associated with urinary tract infection in young febrile infants. Should we abandon standard microscopy when screening for urinary tract infections in young children? Pediatr Infect Dis J.