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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 11 (2000), S. 263-271 
    ISSN: 1569-8041
    Keywords: children ; diagnosis ; germ-cell tumor ; prognosis ; review ; therapy ; tutorial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In mature and immature teratoma the treatment is surgical. The risk ofrecurrence can be estimated from the parameters primary site (with thecoccygeal tumors being most at risk), histological grade of immaturity andcompleteness of the primary resection including the adjacent organ of origin(coccyx, ovary, testis etc.). In case of a microscopically complete tumorresection there is no role for adjuvant chemo- or radiotherapy irrespectiveof the histological grade of immaturity. Malignant germ-cell tumors (GCT) account for 2.9% of all malignanttumors of children younger than 15 years of age. More than half of the tumorsoccur at extragonadal sites such as the ovaries (26%), the coccygealregion (24%), the testes (18%) and the brain (18%)represent then primary sites. In patients with extensive tumor growth, metastatic disease or secretingintracranial tumors a delayed tumor resection after preoperative chemotherapyis preferable. In these patients malignant non-seminomatous GCT may bediagnosed clinically due to the increased serum or cerebrospinal fluid levelsof the tumor markers AFP and/or β-HCG. Current risk adapted treatmentprotocols containing cisplatinum allow long-term remissions in about80% including patients with bulky or metastatic tumors. In thecisplatinum era the prognostic factors like histology, primary site of thetumor and initial tumor stage have partly lost their former impressivesignificance in infants and children. On the other hand the completeness ofthe primary tumor resection according to oncological standards has beenestablished as the most powerful prognostic parameter superior to tumor markerlevels or primary site of the tumor.
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  • 2
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Keimzelltumoren (KZT) bei Kindern sind selten und gleichzeitig heterogen hinsichtlich der primären Lokalisation, der histologischen Diagnose, des biologischen Verhaltens und des therapeutischen Ansprechens. Durch kooperative Studien unter Einbindung unterschiedlicher Fachgruppen sind bei KZT des Kindes- und Jugendalters erhebliche Fortschritte zum klinischen Verständnis und therapeutischen Erfolg gemacht worden. Wesentliche Voraussetzung für den Behandlungserfolg war die Entwicklung effektiver Kombinationschemotherapien, die zuerst bei jungen Männern mit malignen Hodentumoren in sehr erfolgreicher Weise eingesetzt worden sind. Die Übertragung dieser Therapiemaßnahmen, die mit gravierenden und z. T. tödlichen Komplikationen verbunden waren [9, 14], bildete die Grundlage für den Behandlungserfolg auch bei bösartigen KZT des Kindesalters [1]. Vor diesem Hintergrund ist es nicht verwunderlich, dass weltweit nur zögerlich die effektiven Cisplatin-orientierten Zytostatikakombinationen in die kooperativen Therapieoptimierungsprotokolle für Kinder mit bösartigen KZT integriert worden sind [3, 13]. Das therapeutische Ansprechen der KZT bei Kindern auf effektive Chemotherapien hat die Wertigkeit allgemein anerkannter Risikofaktoren wie Tumorgröße, Ausbreitungsstadium und Knochenbeteiligung relativiert [21, 26]. Zudem lassen neuere zytogenetische bzw. molekularbiologische Untersuchungen deutliche Unterschiede zwischen Kindern und Erwachsenen erkennen [6, 25]. Deshalb sind im Rahmen der interdisziplinären Zusammenarbeit die besonderen Aspekte der KZT im Kindesalter zu beachten, um die Behandlungserfolge weiter zu verbessern, die Therapie noch risikoadaptierter zu gestalten und die Spätfolgen für die Patienten nach Möglichkeit weiter zu reduzieren.
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  • 3
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: In den letzten Jahrzehnten hat sich der Stellenwert der Strahlentherapie bei der Behandlung pädiatrischer Tumoren gewandelt. Fortschritte auf dem Gebiet strahlentherapeutischer Techniken und Kenntnisse über notwendige Dosierungen für eine maximale Tumorkontrolle bei minimaler Nebenwirkungsrate (Dosis-Wirkungs-Beziehungen) erlauben eine effiziente und schonende Bestrahlung mit Anhebung der Überlebenszeiten bei gleichzeitiger Reduktion von Therapiefolgen, ohne jedoch die Metastasierungstendenz wesentlich zu beeinflussen. Die Einführung von Chemotherapien erreichte eine zusätzliche systemische Tumorkontrolle, sodass heute bei der überwiegenden Mehrheit der Erkrankungen Heilungsraten erzielt werden, die 70% übersteigen (Tabelle 1). Während im Erwachsenenalter vorwiegend Tumoren epithelialen Ursprungs im Vordergrund stehen, werden Tumoren im Kindesalter vorwiegend durch Neoplasien embryonaler Genese gebildet. Diese zeigen eine erhöhte Empfindlichkeit gegenüber ionisierender Strahlung und chemotherapeutischen Substanzen. Hierdurch werden die im Vergleich zum Erwachsenenalter deutlich erhöhten Heilungsraten erklärt. Gleichzeitig reagiert aber der wachsende Organismus sensibler auf zytotoxische Agenzien. Einige chemotherapeutische Substanzen können zwar durch einen strahlensensibilisierenden Effekt die Tumorkontrolle verbessern, erhöhen jedoch gleichzeitig das Risiko für akute, maximale Nebenwirkungen und Spätfolgen (Tabelle 2). Hierdurch können nicht nur einzelne Organfunktionen beeinträchtigt werden, sondern auch die gesamte Entwicklung des betroffenen Kindes. Die Dosisschwelle für die Toleranz des kindlichen Gewebes v. a. der sich entwickelnden Organe liegt häufig unter den Dosierungen, die für die lokale Tumorkontrolle notwendig sind, und ändern sich durch eine zusätzliche Chemotherapie. Daher werden spezielle Anforderungen an die Strahlentherapie gestellt, um Normalgewebe und v. a. Risikoorgane zu schonen.
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  • 4
    ISSN: 1432-1076
    Keywords: Key words Renal venous thrombosis ; Neonate ; Incidence ; Therapy ; Outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Renal venous thrombosis (RVT) occurs mainly in the neonatal period and bears a dismal prognosis for individual kidney function. There is no generally accepted therapeutic regimen as controlled clinical trials are lacking. Over the last few years, thrombolytic therapy has been successfully employed by single centres. The present study set out to gather up-to-date information on the incidence, therapy and outcome of neonatal RVT as part of a prospective nation wide survey on neonatal thrombosis in Germany to serve as a basis for therapeutic trials in the future. Between 1992 and 1994 the minimum incidence of symptomatic neonatal RVT in Germany was 2.2 per 100,000 live births (95% confidence interval 1.4–3.3). Out of 35 cases, RVT occurred in 15 premature babies (incidence 13 per 100,000 live births (95% confidence interval 5.9–24.8). Ten babies had associated caval occlusion. Therapy was supportive in 8, low dose heparin was used in 14, full heparinization in 9 and thrombolytic therapy in 4 children. On follow-up after a median time of 11.5 months, renal atrophy was present in 26 out of 39 affected kidneys. Conclusion Neonatal renal venous thrombosis still leads to irreversible kidney damage in the majority of cases. Because of the low incidence a multi-national multi-centre therapeutic trial over a long period has to be considered in order to determine the optimal therapeutic approach.
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  • 5
    ISSN: 1433-0350
    Keywords: Keywords Pediatric brain tumor ; Malignant CNS tumors ; Multimodality treatment ; Chemotherapy ; Radiation therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Despite sophisticated surgical methods only a few pediatric CNS tumors can be controlled by operation alone. Therefore multimodality treatment regimens are needed to improve quality of life and survival, which is most important in malignant neoplasms. Since 1998 we have treated 16 children with malignant CNS tumors. All 16 patients have been treated on an interdisciplinary basis and are therefore accompanied by a pediatric neuro-oncology group consisting of a neurosurgeon, pediatric oncologist, and radiotherapist. Depending on tumor histology, child"s age, and extent of surgery, further adjuvant therapy is planned by this group. Newly diagnosed tumors are typically treated by a specific chemotherapy protocol according to a multi-institutional study. In recurrent tumors more individual treatment regimens are considered. Data concerning surgery, adjunctive treatment, complications, and outcome of all patients and four case reports are presented.
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  • 6
    ISSN: 1569-8041
    Keywords: advanced Ewing tumors ; allogeneic stem-cell transplantation ; autologous stem-cell transplantation ; IL-2 therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:An update of results from the High Risk Protocol ofthe Meta-EICESS Study, conducted at the Pediatric Stem-Cell Transplant Centersof Düsseldorf and Vienna. In order to evaluate a possible therapeuticbenefit after allogeneic SCT in patients with advanced Ewing tumors (AET), wecompared outcome after autologous and allogeneic stem-cell transplantation(SCT). Patients and methods:We analyzed 36 patients treated with themyeloablative Hyper-ME protocol (hyperfractionated total body irradiation,melphalan, etoposide ± carboplatin) between November 1986 and December1994. Minimal follow-up for all patients was five years. All patientsunderwent remission induction chemotherapy and local treatment beforemyeloablative therapy. Seventeen of thirty-six patients had multifocal primaryEwing's tumor, eighteen of thirty-six had early, multiple or multifocalrelapse, one of thirty-six patients had unifocal late relapse. Twenty-six ofthirty-six were treated with autologous and ten of thirty-six with allogeneichematopoetic stem cells. We analyzed the following risk factors, that couldpossibly influence the event-free survival (EFS): number of involved bones,degree of remission at time of SCT, type of graft, indication for SCT, bonemarrow infiltration, bone with concomitant lung disease, age at time ofdiagnosis, pelvic involvement, involved compartment radiation,histopathological diagnosis. Results:EFS for the 36 patients was 0.24 (0.21) ± 0.07.Eighteen of thirty-six patients suffered relapse or died of disease, nine ofthirty-six died of treatment related toxicity (DOC). Nine of thirty-sixpatients are alive in CR. Age ≥ 17 years at initial diagnosis (P〈 0.005) significantly deteriorated outcome. According to the type ofgraft, EFS was 0.25 ± 0.08 after autologous and 0.20 ± 0.13after allogeneic SCT. Incidence of DOC was more than twice as high afterallogeneic (40%) compared to autologous (19%) SCT, even thoughthe difference did not reach significance (P = 0.08, Fisher's exacttest). Conclusions:Because of the rather short observation period,secondary malignant neoplasm (SMN) may complicate the future clinical courseof some of our patients who are currently viewed as event-free survivors. EFSin AET is not improved by allogeneic SCT due to a higher complication rate.The patient group was to small to analyze for a possiblegraft-versus-tumor effect.
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  • 7
    ISSN: 1617-4623
    Keywords: Legionella pneumophila LysR family Transcription factor Flagellum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract. Flagellin gene regulation in Legionella pneumophila is modulated by various environmental factors. The expression of the virulent phenotype seems to be linked genetically to flagellum expression. To better understand the mechanisms of flagellin gene expression in L. pneumophila (Lp), we screened a pool of plasmids from a L. pneumophila Corby genomic library for the ability to prevent or reduce luciferase activity in the Escherichia coli strain YK410, which harbours a Lp-pflaA-luxAB fusion. We cloned a DNA fragment encoding the N-terminal part of a protein with significant similarity to members of the LysR family of transcriptional regulators (LTTRs). The entire gene, cloned by inverse PCR, was named flaR. It encodes a protein of 302 amino acids, and computer-assisted analysis of the amino acid sequence revealed a helix-turn-helix motif located near the N-terminus of the protein. The FlaR protein exhibits 21–31% identity to various LTTRs. Furthermore, gel retardation experiments indicate that the FlaR protein is able to bind to its own promoter region and, to a lesser extent, to the flaA promoter of L. pneumophila. The flaR promoter region contains putative LysR binding motifs and two putative Fur boxes. Taken together, these results indicate that FlaR is a DNA-binding protein which belongs to the LTTR family. Southern analysis with a L. pneumophila Corby-specific flaR probe revealed homologous genes in various L. pneumophila strains, but not in the 12 non-pneumophila strains tested so far.
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