DNA in human glioblastomas. A flow-fluorescence cytometrical examination of 96 tumors

The Flow-Fluorescence Cytometric Method (FCM) was applied to investigate the DNA content and the ploidy outlines of each of 96 glioblastomas. No specific DNA pattern was detected, possibly because of the tangle morphology of these variable tumors. Due to their capricious growth the DNA distribution proved to fluctuate greatly. Thus, the series, arranged according to increased PI (proliferation index) values, exhibited a wide spread within a total range from 7.1–97.15% (mean 39.3%) PI. A threefold subdivision of main types (I–III) appears to be of practical use for clinical prognostic assessment: diploid tumors with a PI range up to 10% (N=7) are followed by abnormal chiefly tretra- and hyper-tetraploid tumors up to PI values about 30% (N=21). The third category includes cases showing excessive aneuploidy combined more and more with polyploidy and valid stemlines, up to the PI maximum of about 97 rel.% (N=68). Thus, in 89 tumors clear pathological changes of DNA content can be decoded; of these 68 (76.4%) express a considerable aneuploidy and polyploidy respectively.Dedicated to Prof. Dr. HJ Bauer for his 75th birthday, March 31, 1989     

Metastasen

Ohne Zusammenfassung     

Recruitment barriers in a randomized controlled trial from the physicians' perspective – A postal survey

Background  

The feasibility of randomized trials often depends on successful patient recruitment. Although numerous recruitment barriers have been identified it is unclear which of them complicate recruitment most. Also, most surveys have focused on the patients' perspective of recruitment barriers whereas the perspective of recruiting physicians has received less attention. Therefore, our aim was to conduct a postal survey among recruiting physicians of a multi-center trial to weigh barriers according to their impact on recruitment.     

Über entzündliche Veränderungen mit Kerneinschlüssen in der Nebenniere (Adrenalitis inclusio-necroticans) beim akuten Landry-Guillain-Barré-Syndrom

Zusammenfassung 1. Bei einer 59jährigen Frau, die 29 Tage nach Beginn einer rasch aufsteigenden Tetraplegie verstarb, fand sich neben typischen Veränderungen in den Wurzelnerven eine nekrotisierende Adrenalitis mit Einschlußkörpern vom Typ A, wie sie bei herpetischen Infektionen vorkommen.2. Ein 35jähriger Mann hatte in den letzten beiden Lebensmonaten mindestens fünf schwere tetraplegische Anfälle und starb unter den Zeichen einer Nebenniereninsuffizienz. Der Liquorbefund entsprach einem Guillain-Barré-Syndrom. Die Nebennieren zeigten eine hochgradige Atrophie durch nekrotisierende Entzündung mit einschlußkörperverdächtigen Bildungen in einzelnen Zellkernen.3. In beiden Fällen hatte der Nebennierenprozeß maßgeblichen Anteil am Krankheitsverlauf und am tödlichen Ausgang, der im zweiten Fall vermutlich durch Hyperkaliämie bedingt war.4. Die genaue Überwachung der Nebennierenfunktion erscheint geeignet, die durch Elektrolytstörungen gefährdeten Krankheitsfälle aufzudecken (Schaltenbrand) und einer gezielten Behandlung zuzuführen.5. Ohne zur Ätiologie endgültig Stellung nehmen zu können, sehen wir in den Nebennierenveränderungen den Ausdruck einer Virusinfektion. Die histologischen Einzelheiten sprechen dafür, daß herpetische Infektionen eine wichtige Rolle beim akuten Landry-Guillain-Barré-Syndrom spielen können.

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Adrenalitis inclusio-necroticans in the Landry-Guillain-Barré-Syndrom

Summary 1. In a 59-year-old female patient who died 29 days after the onset of a rapidly ascending tetraplegia, a necrotizing adrenalitis was found, besides typical lesions in the nerves arising from the spinal roots, with type A inclusion bodies resembling those known from herpes infections.2. A 35-year-old man who experienced at least five severe tetraplegic attacks during the last two months of his life, died with symptoms of adrenal insufficiency. The cerebrospinal fluid findings were typical of a Guillain-Barré syndrome. The adrenal glands showed extreme atrophia caused by a necrotizing inflammation and several nuclei contained formations which were suggestive of inclusion bodies.3. In both cases the inflammatory process in the adrenal glands contributed to the fatal course of the disease, in the second case probable caused by hypercalemia.4. A consequent evaluation of the adrenal functions seems the best way, to find out cases endangered by electrolyte disturbances (Schaltenbrand) and to bring them to a adequate treatment.5. The histological findings in the adrenal glands are suggestive but not conclusive of a viral infection, especially of the herpes type.

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Herrn Professor Dr. Georges Schaltenbrand zu seinem 70. Geburtstag am 26. 11. 1967 gewidmet.

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Anatomische Untersuchungen mit Unterstützung durch die Stiftung Volkswagenwerk.     

Acute lymphoblastic leukemia in childhood: the COALL studies

In the cooperative study COALL-80 151 children with acute lymphoblastic leukemia were treated according to the modified protocol BFM 79/81. The probability of continuous complete remission (CCR) for the total group is 74% after 6 years. In the subsequent study COALL-82 high-risk patients (initial white blood count greater than or equal to 25/nl or T-cell leukemia and acute undifferentiated leukemia) received additional high-dose methotrexate as fifth drug in the intensive phase and the combination VM-26/arabinosyl-cytosine in the reinduction phase. In all others patients (low-risk group) intermediate-dose methotrexate was substituted for the myelosuppressive agent cyclophosphamide in the intensive phase. Reinduction was no longer given in the low-risk group. In both risk groups cranial irradiation was postponed until after the intensive phase therapy. Radiotherapy was withheld for a group with minimal risk (white blood count less than 3/nl, liver/spleen less than 3 cm). The probability of CCR for the total group of 129 patients is 64% after 3.5 years. The comparative analysis between the studies COALL-82 and COALL-80 shows that low-risk patients have an equally high probability of continuous hematologic remission (91% vs. 85%) despite reduction of therapy in COALL-82. High-risk patients, however, had a significantly higher rate of bone marrow relapses; in this group the probability of continuous hematologic remission is 52% in COALL-82 vs. 73% in COALL-80. Also relapses in the central nervous system in irradiated patients were significantly more frequent in COALL-82 than in COALL-80 (12% vs. 4%) whereas the group of patients without radiotherapy has remained free of relapse. The possible influence of the modifications in therapy in study COALL-82 on the higher relapse rate is discussed.     

Analysis of prognostic factors in rhabdomyosarcoma. Preliminary univariate and multivariate results of the Cooperative Soft Tissue Sarcoma Study (CWS-81)

The characteristics of 129 children with rhabdomyosarcoma entered into the CWS-81 study between 1981 and 1984 were examined for their relationship to prognosis. Prognosis was defined as relapse-free survival time. The trial was stratified to clinical groups depending on the surgical procedure at onset. So, each group had to be analysed separately. The patient characteristics of group I/IIA mostly related to prognosis were primary site (disease in extremities, unfavorable; paratesticular primary, favorable) and tumor infiltration into adjacent bone (bone infiltration, unfavorable). In group IIB/III the degree of tumor response within 7-9 weeks, chemotherapy exclusively given, was the only characteristic significantly related to prognosis (greater than 2/3 tumor reduction, favorable; less than 2/3 tumor reduction, unfavorable). Other prognostic factors as histological subtype, primary site, tumor diameter, lymph node involvement, bone infiltration, sex and age had no significant influence. The tumor diameter was the only characteristic with significant influence in group IV. The larger the tumor diameter, the poorer was prognosis. Furthermore, the alveolar subtype was seen predominantly in non-responding tumors of group IV. In group III, we fitted the patient characteristics in a multivariate regression model (Cox's model). The degree of tumor response within 7-9 weeks was analysed to be the main hazard function related to prognosis. In future, the degree of tumor response within a certain time can be used as the measurement of effectiveness of chemotherapy. So, in patients of group III and IV a risk adapted therapeutic procedure can be undertaken.     

Results of treatment of rhabdomyosarcomas (RMS) in children. A report of the Cooperative Soft Tissue Sarcoma Study (CWS-81) of the Society of Pediatric Oncology

This analysis refers to 129 children with RMS who were treated between 1981 and 1985 according to the protocol guidelines of the CWS-81 study. The duration of chemotherapy depended on the initial post-operative stage. Patients with stage I and IIA were not to receive any radiotherapy, and patients with primary stage III were treated according to the results of a 16-week chemotherapy treatment: either without radiation (stage Ipc), or with radiotherapy using 40 Gy (stage (IIpc) or 50 Gy (stage IIIpc). The median time of observation was 27 months (Juni 1985). The essential results of the study are as follow: RMS of the extremities in stages I and IIA need radiotherapy, contrary to all other localisations with the same stages. Patients with RMS stage III who are tumor-free after initial chemotherapy (histologically checked) do not need radiotherapy. Patients with microscopic residue (IIpc) or macroscopic residue (IIIpc) after pretreatment showed no difference in their local relapse rate, whereas metastases were found only in the group having macroscopic tumor residue up to week 16. An additional examination of this study observed tumor response during initial chemotherapy and its relationship to prognosis. This analysis showed that the degree of tumor regression per unit of time permits the most favorable prognostic statement. Patients with clinical complete remission after 7/9 weeks showed a 100% relapse-free chance of survival, independent of localisation, tumor size or histological subtype. Those with a tumor reduction of greater than 2/3 but no complete remission showed 67% chance of survival, and those with greater than 1/3-2/3 tumor reduction had 25%. Tumor response kinetics under initial chemotherapy allows better individual therapy in the future. The overall result of the study concerning localisation and stage corresponds to that of the IRS I and II studies. Patients with undifferentiated sarcomas, extraossary Ewing's sarcoma and synovial sarcomas can be treated according to the same principles as RMS, since no significant differences in prognosis could be found.     

BFM study 1981/83 of the treatment of highly malignant non-Hodgkin's lymphoma in children: results of therapy stratified according to histologic immunological type and clinical stage

99 children with non-Hodgkin's lymphoma entered the prospective, multicenter BFM study 81/83. They were treated with a four-fold stratified therapy according to clinical stage and origin of the lymphoma from B- or non-B-lymphocytes. In the BFM study 75/81, these criteria had been proven to be most relevant for prognosis. Therapy of non-B-NHL was very similar to the therapeutic concept as applied in acute lymphoblastic leukemias by the BFM group. For the NHL of B-type, a new therapeutic regimen was developed. Cytostatic drugs applied in this group were: medium dose methotrexate, cyclophosphamide in a fractionated manner of application, adriamycin, cytarabine, VM 26 and prednisone. The probability of disease-free survival was 80% after nearly 3 years for all patients. In non-B-NHL it was 89% in localized, and 79% in disseminated disease. All patients with localized B-NHL are surviving without relapse, while the probability of disease-free survival in patients with disseminated B-NHL was 67%. Thus, the therapy result in the latter group was doubled as compared to the result of the BFM study 75/81.     

Erhöhtes Serum-Myoglobin bei Niereninsuffizienz

Zusammenfassung Bei 44 Patienten mit chronischer Niereninsuffizienz unterschiedlicher Äthiologie wurde das immunreaktive Serum-Myoglobin bestimmt und mit den Werten von Probanden mit normaler Nierenfunktion verglichen. Es fand sich — unabhängig von der Grunderkrankung — eine hoch signifikante lineare Korrelation zwischen dem Serum-Myoglobin und der Serum-Kreatinin-Konzentration. Bei Patienten mit Serum-Kreatinin-Werten über 550 µMol/1 (6,2 mg-%) lagen die Serum-Myoglobin Konzentrationen fast regelmäßig im pathologischen Bereich. Dies gilt auch für chronische Dialysepatienten. Die Befunde zeigen, daß bei Patienten mit höhergradiger, chronischer Niereninsuffizienz das Serum-Myoglobin nur mit Einschränkung zur Infarktdiagnostik geeignet ist.Mit Unterstützung des SFB-89 Kardiologie der Deutschen Forschungsgemeinschaft