University Childrens Hospital Wuerzburg

Würzburg, Germany

University Childrens Hospital Wuerzburg

Würzburg, Germany
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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.


PubMed | The Hospital for Sick Children, Baylor College of Medicine, St Jude Childrens Research Hospital, St. Anna Kinderspital and 20 more.
Type: Journal Article | Journal: British journal of haematology | Year: 2015

Patients with Langerhans cell histiocytosis (LCH) refractory to conventional chemotherapy have a poor outcome. There are currently two promising treatment strategies for high-risk patients: the first involves the combination of 2-chlorodeoxyadenosine and cytarabine; the other approach is allogeneic haematopoietic stem cell transplantation (HSCT). Here we evaluated 87 patients with high-risk LCH who were transplanted between 1990 and 2013. Prior to the year 2000, most patients underwent HSCT following myeloablative conditioning (MAC): only 5 of 20 patients (25%) survived with a high rate (55%) of transplant-related mortality (TRM). After the year 2000 an increasing number of patients underwent HSCT with reduced intensity conditioning (RIC): 49/67 (73%) patients survived, however, the improved survival was not overtly achieved by the introduction of RIC regimens with similar 3-year probability of survival after MAC (77%) and RIC transplantation (71%). There was no significant difference in TRM by conditioning regimen intensity but relapse rates were higher after RIC compared to MAC regimens (28% vs. 8%, P=002), although most patients relapsing after RIC transplantation could be salvaged with further chemotherapy. HSCT may be a curative approach in 3 out of 4 patients with high risk LCH refractory to chemotherapy: the optimal choice of HSCT conditioning remains uncertain.


Neuhaus W.,University of Würzburg | Neuhaus W.,University of Vienna | Samwer F.,University of Würzburg | Kunzmann S.,University Childrens Hospital Wuerzburg | And 5 more authors.
Differentiation | Year: 2012

The blood-air barrier in the lung consists of the alveolar epithelium, the underlying capillary endothelium, their basement membranes and the interstitial space between the cell layers. Little is known about the interactions between the alveolar and the blood compartment. The aim of the present study was to gain first insights into the possible interplay between these two neighbored cell layers. We established an. in vitro Transwell model of the alveolar epithelium based on human cell line H441 and investigated the influence of conditioned medium obtained from human lung endothelial cell line HPMEC-ST1.6R on the barrier properties of the H441 layers. As control for tissue specificity H441 layers were exposed to conditioned medium from human brain endothelial cell line hCMEC/D3. Addition of dexamethasone was necessary to obtain stable H441 cell layers. Moreover, dexamethasone increased expression of cell type I markers (caveolin-1, RAGE) and cell type II marker SP-B, whereas decreased the transepithelial electrical resistance (TEER) in a concentration dependent manner. Soluble factors obtained from the lung endothelial cell line increased the barrier significantly proven by TEER values and fluorescein permeability on the functional level and by the differential expression of tight junctional proteins on the molecular level. In contrast to this, soluble factors derived from brain endothelial cells weakened the barrier significantly. In conclusion, soluble factors from lung endothelial cells can strengthen the alveolar epithelium barrier. in vitro, which suggests communication between endothelial and epithelial cells regulating the integrity of the blood-air barrier. © 2012 International Society of Differentiation.


Braun M.,University Childrens Hospital Wuerzburg | Wolfl M.,University Childrens Hospital Wuerzburg | Wiegering V.,University Childrens Hospital Wuerzburg | Winkler B.,University Childrens Hospital Wuerzburg | And 6 more authors.
Pediatric Blood and Cancer | Year: 2014

Congenital dyserythropoietic anemias are rare hematological disorders leading to ineffective erythropoiesis with chronic anemia, complicated by iron overload. Here we present a remarkable clinical course of an infant with CDA type II who first presented as a severe fetal hydrops, requiring serial intrauterine red cell transfusions. While postnatal transfusion dependency persisted, the patient was successfully transplanted with a myeloablative conditioning regimen and peripheral blood stem cells of a matched donor. We believe that allogeneic HSCT is a reasonable therapeutic approach for patients with very severe CDA, even if only a matched unrelated donor is available. Pediatr Blood Cancer 2014;61:743-745. © 2013 Wiley Periodicals, Inc.


Wiegering V.,University Childrens Hospital Wuerzburg | Schick J.,University Childrens Hospital Wuerzburg | Beer M.,University of Würzburg | Weissbrich B.,University of Würzburg | And 5 more authors.
BMC Pediatrics | Year: 2011

Background: Infection with varicella-zoster virus (VZV) contemporaneously with malignant disease or immunosuppression represents a particular challenge and requires individualized decisions and treatment. Although the increasing use of varicella-vaccines in the general population and rapid initiation of VZV-immunoglobulins and acyclovir in case of exposure has been beneficial for some patients, immunocompromised individuals are still at risk for unfavourable courses.Methods: In this single center, 6-year analysis we review incidence, hospitalization and complication rates of VZV-infections in our center and compare them to published data. Furthermore, we report three instructive cases.Results: Hospitalization rate of referred children with VZV-infections was 45%, among these 17% with malignancies and 9% under immunosuppressive therapy. Rate of complications was not elevated in these two high-risk cohorts, but one ALL-patient died due to VZV-related complications. We report one 4-year old boy with initial diagnosis of acute lymphoblastic leukemia who showed a rapidly fatal outcome of his simultaneous varicella-infection, one 1.8-year old boy with an identical situation but a mild course of his disease, and an 8.5-year old boy with a steroid-dependent nephrotic syndrome. This boy developed severe hepatic involvement during his varicella-infection but responded to immediate withdrawl of steroids and administration of acyclovir plus single-dose cidofovir after nonresponse to acyclovir after 48 h.Conclusion: Our data show that patients with malignant diseases or immunosuppressive therapy should be hospitalized and treated immediately with antiviral agents. Despite these measures the course of VZV-infections can be highly variable in these patients. We discuss aids to individual decision-making for these difficult situations. © 2011 Wiegering et al; licensee BioMed Central Ltd.


Wiegering V.,University Childrens Hospital Wuerzburg | Schlegel P.-G.,University Childrens Hospital Wuerzburg | Winkler B.,University Childrens Hospital Wuerzburg
Journal of Pediatric Hematology/Oncology | Year: 2012

BACKGROUND: Tumor genesis of many pediatric malignancies remains unclear. Data of immune function are lacking at diagnosis. We prospectively analyzed 109 pediatric patients with malignancy at diagnosis. METHODS: Lymphocyte subpopulations were characterized by FACS, TREC-assay, and Immunoscope, cytokines by FACS and ELISA. OBSERVATIONS: We detected higher values of CD4 T cells and consecutively shifted CD4/CD8 ratio in all patients compared with the control group. In patients with lymphoma, interleukin-2 was upregulated in all subpopulations. CONCLUSIONS: On the basis of these findings an altered immune function could be found in children with different malignancies at diagnosis. Further investigations are necessary to identify tumor-related immune deficiency for novel therapeutic approaches. Copyright © 2012 by Lippincott Williams &Wilkins.


PubMed | University Childrens Hospital Wuerzburg
Type: | Journal: BMC pediatrics | Year: 2011

Infection with varicella-zoster virus (VZV) contemporaneously with malignant disease or immunosuppression represents a particular challenge and requires individualized decisions and treatment. Although the increasing use of varicella-vaccines in the general population and rapid initiation of VZV-immunoglobulins and acyclovir in case of exposure has been beneficial for some patients, immunocompromised individuals are still at risk for unfavourable courses.In this single center, 6-year analysis we review incidence, hospitalization and complication rates of VZV-infections in our center and compare them to published data. Furthermore, we report three instructive cases.Hospitalization rate of referred children with VZV-infections was 45%, among these 17% with malignancies and 9% under immunosuppressive therapy. Rate of complications was not elevated in these two high-risk cohorts, but one ALL-patient died due to VZV-related complications. We report one 4-year old boy with initial diagnosis of acute lymphoblastic leukemia who showed a rapidly fatal outcome of his simultaneous varicella-infection, one 1.8-year old boy with an identical situation but a mild course of his disease, and an 8.5-year old boy with a steroid-dependent nephrotic syndrome. This boy developed severe hepatic involvement during his varicella-infection but responded to immediate withdrawl of steroids and administration of acyclovir plus single-dose cidofovir after nonresponse to acyclovir after 48 h.Our data show that patients with malignant diseases or immunosuppressive therapy should be hospitalized and treated immediately with antiviral agents. Despite these measures the course of VZV-infections can be highly variable in these patients. We discuss aids to individual decision-making for these difficult situations.


PubMed | University of Würzburg, Goethe University Frankfurt, University Childrens Hospital Wuerzburg and Medical University of Vienna
Type: Journal Article | Journal: PloS one | Year: 2015

Antenatal steroid treatment decreases morbidity and mortality in premature infants through the maturation of lung tissue, which enables sufficient breathing performance. However, clinical and animal studies have shown that repeated doses of glucocorticoids such as dexamethasone and betamethasone lead to long-term adverse effects on brain development. Therefore, we established a mouse model for antenatal dexamethasone treatment to investigate the effects of dexamethasone on brain vessel differentiation towards the blood-brain barrier (BBB) phenotype, focusing on molecular marker analysis. The major findings were that in total brains on postnatal day (PN) 4 triple antenatal dexamethasone treatment significantly downregulated the tight junction protein claudin-5, the endothelial marker Pecam-1/CD31, the glucocorticoid receptor, the NR1 subunit of the N-methyl-D-aspartate receptor, and Abc transporters (Abcb1a, Abcg2 Abcc4). Less pronounced effects were found after single antenatal dexamethasone treatment and in PN10 samples. Comparisons of total brain samples with isolated brain endothelial cells together with the stainings for Pecam-1/CD31 and claudin-5 led to the assumption that the morphology of brain vessels is affected by antenatal dexamethasone treatment at PN4. On the mRNA level markers for angiogenesis, the sonic hedgehog and the Wnt pathway were downregulated in PN4 samples, suggesting fundamental changes in brain vascularization and/or differentiation. In conclusion, we provided a first comprehensive molecular basis for the adverse effects of multiple antenatal dexamethasone treatment on brain vessel differentiation.


PubMed | University Childrens Hospital Wuerzburg
Type: Journal Article | Journal: Journal of pediatric hematology/oncology | Year: 2012

Tumor genesis of many pediatric malignancies remains unclear. Data of immune function are lacking at diagnosis. We prospectively analyzed 109 pediatric patients with malignancy at diagnosis.Lymphocyte subpopulations were characterized by FACS, TREC-assay, and Immunoscope, cytokines by FACS and ELISA.We detected higher values of CD4(+) T cells and consecutively shifted CD4(+)/CD8(+) ratio in all patients compared with the control group. In patients with lymphoma, interleukin-2 was upregulated in all subpopulations.On the basis of these findings an altered immune function could be found in children with different malignancies at diagnosis. Further investigations are necessary to identify tumor-related immune deficiency for novel therapeutic approaches.


PubMed | University Childrens Hospital Wuerzburg
Type: Case Reports | Journal: Pediatric blood & cancer | Year: 2014

Congenital dyserythropoietic anemias are rare hematological disorders leading to ineffective erythropoiesis with chronic anemia, complicated by iron overload. Here we present a remarkable clinical course of an infant with CDA type II who first presented as a severe fetal hydrops, requiring serial intrauterine red cell transfusions. While postnatal transfusion dependency persisted, the patient was successfully transplanted with a myeloablative conditioning regimen and peripheral blood stem cells of a matched donor. We believe that allogeneic HSCT is a reasonable therapeutic approach for patients with very severe CDA, even if only a matched unrelated donor is available.

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