[Plasmacytoma of the thyroid gland. Case report and review of over 32 cases in the literature].
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Humans↗
Biomedical subjects
M Bamberg
Publications and source records attributed to M Bamberg.
Preliminary experimental results with the nitrosourea derivative ACNU in the treatment of malignant gliomas.
Comparative studies were carried out to evaluate the cytotoxic effectiveness of the nitrosureas ACNU (Nimustine) and BCNU (Carmustine) at equitoxic dose levels in xenografts from two astrocytomas grades III/IV (Li, Re) and one oligodendroglioma grade III (Oe) on nude mice. Growth delay was measured as the endpoint. All tumours were characterized initially and at regular intervals in later passages as to their histomorphologic pattern, expression of glial fibrillary acid protein and DNA-content by means of flow cytometry. These characteristics were shown to be unchanged in our xenografts over more than 27 passages. Growth delays of 18.7 days (ACNU) and 2.4 days (BCNU) for the Li-xenograft (p less than 0.01) were observed at an LD10 for both drugs. For the Re- and Oe-xenografts, growth delays of 18.0 vs. 14.0 days (p less than 0.001) and greater than 27.0 vs. 14.2 days (p less than 0.02) were observed at an equitoxic dose of 33 mg/kg ACNU or BCNU i.p., respectively. These preclinical data suggest a therapeutic advantage with ACNU for these high grade gliomas and should encourage further experimental and clinical investigations.
Animals↗
[Heterotransplantation of a human glioma and brain metastases in the athymic nude mouse--a preclinical model for radiation oncology. 1. Basic principles and methodology].
In spite of the great efforts undertaken in the different disciplines, the prognosis of patients with highly malignant gliomas, i.e. astrocytomas of degrees III and IV remains unfavorable. Up to now, new findings about an improvement of radiooncologic therapy methods are obtained retrospectively from the results of complex and time-consuming clinical studies. The heterotransplantation of human tumor tissue in immune-deficient nu/nu mice gives the opportunity to check preclinically the efficiency of different fractionation schemes and cytostatic drugs already. The author's experiences and therapy results are presented in order to demonstrate the possibilities as well as the limits of this in-vivo model performed with a view to clinical conditions.
Animals↗
[Breast carcinoma in men: radiotherapy and treatment results].
The treatment of 34 men with stage T1 N0 M0 to T3/4 N1 M0 mammary carcinomas was followed by a five-year survival rate of 70%. Three patients suffering from initial remote metastases died after 2 to 3.5 years. The probability of a five-year survival decreases with increasing tumor growth and axillary involvement. The prognostic effect of receptor state and grading could not be investigated in our patients. Our own data as well as recent data from literature suggest that, with respect to TNM stages in mammary carcinoma, there is no prognostic difference between men and women. It is not very clear at present if postoperative irradiation exerts a favorable influence on the survival rate. However, it reduces the local recurrence risk for men and women. 45 Gy in five weeks should be considered as a minimum dose. The indications for postoperative irradiation are discussed.
Adenocarcinoma↗
[Thyroid cancers--current diagnostic and therapeutic strategies].
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Adenocarcinoma↗
Effect of route of administration on the selectivity of hematoporphyrin derivative for tumor tissue.
Hematoporphyrin derivative (HPD) has the ability to localize with moderate selectivity to tumor tissue, where it can be activated by visible light and produce singlet oxygen-mediated damage to cellular biomolecules. However, HPD is less than ideal as an agent for tumor photoradiation therapy because it produces a period of photosensitivity that can last 30 days or more, and it can be toxic to surrounding tissues such as skin when used in the treatment of subcutaneous metastases. The usefulness of intraarterial injection for refining the selectivity of HPD was investigated in this work. Intraarterial administration of HPD was not found to provide higher tumor levels of HPD, nor was it able to increase significantly the concentration of HPD relative to surrounding tissues, such as skin and muscle. However, fluorescence microscopy findings suggested that some fluorescent HPD component is rapidly accumulated in tumor macrophages following intraarterial injection.
Animals↗
Bone marrow transplantation in acute leukemia.
In Essen 142 bone marrow transplantations were carried out between December 1975 and February 1985. In 74 cases the indication was acute leukemia in relapse (n = 23) or in first or consecutive remission (n = 51). The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections, intravenous CMV-hyperimmune globulin and CMV-negative blood products have been applied routinely for 2 years. MTX was used as prophylaxis against GvHD. In the prognostically unfavorable group of acute leukemia in relapse, only one patient showed long-term survival. In this patient, leukemic relapse occurred 6 years after transplantation. The survival rate of AML patients grafted during the first remission is 55% (16/29) with a median observation time of 41 months. For patients grafted in first or consecutive remission of acute lymphoblastic leukemia, the survival rate is 50% (7/14) with a maximal observation time of 34 months. The overall incidence of GvHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL, and 63% in CML. In aplastic anemia, no patient developed an interstitial pneumonia. In leukemia, the risk of fatal interstitial pneumonia was 34%.
Antineoplastic Combined Chemotherapy Protocols↗
Allogeneic bone marrow transplantation for acute leukaemia or chronic myeloid leukaemia in the fifth decade of life.
To determine the influence of advanced age on long-term survival after allogeneic bone marrow transplantation (BMT), the probability of survival and the frequency of transplantation-associated complications were analysed retrospectively in 20 patients with acute leukaemia (AL) or chronic myeloid leukaemia (CML), who were 40-49 years of age (median 44.5 years) at the time of transplant. The results of this patient group were compared to those of 32 patients aged 30-39 years (median 33.5 years) with AL or CML, who also underwent BMT during the same period of time. The overall actuarial survival of the two age groups was comparable with 44% and 41% at 5.9 and 5.6 years, respectively. Patients with standard risk criteria (i.e. HLA-genotypically identical sibling donor, 1st chronic phase of CML or 1st remission of AL) showed a higher probability of survival in both groups (62% at 5.9 years in older patients and 59% at 5.5 years in younger patients, respectively). In contrast, actuarial survival in patients who underwent BMT at an advanced stage of their disease or with marrow from a partially HLA-compatible donor was significantly inferior (P = 0.04). The cumulative incidence of acute and chronic graft-versus-host disease was low in older patients (27%), who received marrow from an HLA-identical sibling donor. The most frequent cause of death was interstitial pneumonia, occurring in seven of the older patients (35%) and in seven of the younger patients (22%). This difference, however, was not statistically significant. Our results indicate that allogenic marrow transplantation in the fifth decade of life might be associated with a tolerable risk of transplantation-related complications. This treatment modality may therefore be regarded as first-line therapy for patients in 1st remission of AL or first chronic phase of CML, who show a normal performance status. The same applies to older patients in advanced stages of disease, since the results are comparable to those achieved in the younger patient group.
Acute Disease↗
[Primary radiotherapy of prostatic carcinoma--the results at Essen with 173 patients].
173 patients suffering from prostate carcinomas of stages A to C received percutaneous irradiations. The five-year survival is 100% in stage A (n = 6), 79% in stage B (n = 41), and 68% in stage C (n = 126). 116 patients received only percutaneous irradiation after needle biopsy, 30 patients were irradiated subsequently to surgical intervention, and 27 were treated by hormones during primary therapy. An analysis was made about survival, recurrence rate, metastasis-free interval, and incidence of metastases in dependence on stage, grading, and different forms of primary treatment. The importance of stage and grading as prognostic factors is confirmed by the results of this study. Extended primary therapy (surgery and/or hormones) seems to bring no benefit as compared to radiotherapy alone. Transurethral resection of the prostate as a surgical/diagnostic intervention has an unfavorable influence on the prognosis.
Actuarial Analysis↗
Diagnostic criteria in pituitary tumour recurrence--combined modality of surgery and radiotherapy.
The tumour recurrence rate of 210 patients with operated hypophysomas were investigated. Depending on the surgical approach, total or subtotal extirpation of the adenomas, the recurrence rates varied from 10,4 to 35%. 33 patients with pituitary tumour recurrences were followed up over a period of 20 years. Clinical symptoms CT-results at relapse are represented. Serum prolactin level (PRL) was determined before and after surgical and radiotherapy of PRL-producing adenomas. In these cases PRL can be accepted as a tumour marker. 13 patients with relapsed hypophysomas received local irradiation (5.7 MeV linear accelerator) after recurrence operation. An individual comparison in the same patient between surgical therapy alone and combined surgical and radiotherapy was possible. Based on the obtained experience with this combined treatment a therapy scheme using combined surgery and radiotherapy in pituitary tumours is suggested.
Adenoma↗
Cytotoxicity of human brain tumors by hematoporphyrin derivative.
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Astrocytoma↗
Serial xenotransplantation of a human embryonal carcinoma in experimental urology.
The rare incidence of testicular germ cell tumours makes it necessary for clinicians to look for a valid experimental model to investigate basic tumour properties and different therapeutic modalities preclinically in order to improve clinical cure rates. A human embryonal carcinoma with hCG-production was successfully established in nude mice for more than 40 passages. We were able to show striking maintenance of histological and ultrastructural features, tumour markers (Beta-hCG) and DNA indices of the original tumour during subsequent xenograft passages as well as stability of tumour growth. Dedifferentiation of the tumour with changing growth fractions or loss of hCG production was not evident.
Animals↗
Bone marrow transplantation in severe aplastic anemia and acute or chronic leukemia.
In Essen 121 bone marrow transplantations were carried out. The indications were severe aplastic anemia (n = 18), acute leukemia in relapse (n = 20), acute leukemia in remission (n = 46) or chronic myeloid leukemia (n = 37). The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections intravenous CMV-hyperimmunoglobulin and CMV-negative blood products have been applied routinely since two years. MTX was used as prophylaxis against GVH-disease. In case of severe aplastic anemia 13 patients (72%) are still alive with a median observation time of 24 months. In the prognostically unfavourable group of acute leukemia in relapse only one patient showed long term survival. In this patient leukemic relapse occurred six years after transplantation. The survival rate of AML patients grafted during the first remission is 55% (15/27) with a median observation time of 40 months. For patients grafted in first or consecutive remission of ALL the survival rate is 42% (5/12) with a maximal observation time of 29 months. Out of 37 patients grafted because of CML, eight were in an advanced stage of the disease. 13 patients are still alive, the maximal observation time is 37 months. The overall incidence of GVHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL and 63% in CML. In aplastic anemia no patient developed an interstitial pneumonia. In leukemia the risk of fatal interstitial pneumonia was 34%.
Acute Disease↗
The incidence of interstitial pneumonitis: comparison of total body irradiation schedules for allogenic bone marrow transplantation.
Interstitial pneumonitis (IP) is one of the major causes of death following bone marrow transplantation (BMT). This report deals with a comparison between data compiled from six centers concerning the essential factors responsible for the development of IP. Special concern has been paid to the idiopathic form of disease where TBI is thought to be the most important factor in its pathogenesis. Our own experience using different TBI modalities shows that the instantaneous dose rate seems to be an important factor in the development of IIP. Comparing the data from various centers it is not possible at the present time to recommend one optimal modality.
Bone Marrow Transplantation↗
Total body irradiation: the lung as critical organ.
The pathogenesis of interstitial pneumonitis (IP) after chemoradiotherapy and subsequent bone marrow transplantation is not completely understood. Total body irradiation (TBI) with a dose of about 10 Gy significantly contributes to this very serious complication. The radiation induced morphological alterations especially of the crucial targets, namely the pneumocytes type II and capillaries are described. Investigations in animals and in humans reveal that pneumonitis occurs over a very short range of doses. In humans a single dose of 9.3 Gy given at a high dose rate leads to an incidence of 50%. Reduction of the dose by shielding the lungs, fractionation of irradiation and decreasing the dose rate are considered to be the main possibilities which diminish the risk of pneumonitis after TBI. The role of further factors involved in the development of IP such as cytomegalovirus, age, reduced lung volume, immunological mechanisms and others is discussed. Especially chemotherapeutic agents may increase lung morbidity by interacting with TBI.
Animals↗
[Esophageal carcinoma: the final results of a multicenter and controlled German study with misonidazole and radiation].
A prospective, randomized clinical study on 91 patients with squamous cell carcinoma of the oesophagus was undertaken in order to investigate the radiosensitizing effect of misonidazole. After histologic verification and extensive diagnosis, the greater tumor region was at first irradiated during 2.5 weeks with ten fractions of 3 Gy each up to a target volume dose of 30 Gy. Prior to each fraction, patients received randomly misonidazole or a placebo in a dose of 1 g/m2 body surface. Then they were presented to the oncologic surgeon in order to decide whether a surgical resection should be performed or not. Following to this operation no further radiotherapy was performed. However, if a surgical intervention did not take place, radiotherapy was continued without administration of misonidazole or placebo up to a target volume dose of 60 to 70 Gy. There was no evidence of neurotoxic side effects or modifications of the blood count and some laboratory parameters caused by misonidazole. As to recurrence-free interval and survival time, no significant differences were found between the different therapy groups, so that a radiosensitizing effect of misonidazole was not demonstrated in this study. Regarding several positive phase II studies with misonidazole, some hopes had been placed in this study because at present the therapeutic situation in oesophagus carcinoma is extremely unsatisfactory. Even the combination of a most sophisticated operation technique prior or following to irradiation could not essentially improve the poor healing rates.
Adolescent↗
The value of neutron- and neutron-boost irradiation for the local control of advanced soft tissue sarcomas.
An analysis of neutron- and neutron-boost irradiation of 191 patients with soft tissue sarcomas is given. 101 patients had T3 (IVA) tumours. The actuarial disease free survival rate of all stages at 6.5 years is 59.8%. Patients with T1 and T2 tumours fared significantly better (73.5%) than patients with T3 tumours (31.3%, p = 0.016). Similar difference are seen according to grade, i.e. 75.1% for G1, 48.3% for G2 (p = 0.035) and 30.9% for G3 tumours (p = 0.024). Patients without microscopic tumour residue fared best (84%), followed by patients with microscopic tumour (72.3%) and patients with gross tumour (29.8%) left behind (p = 0.0003). A functional limb was preserved in 80.5% of patients with extremity lesions (95/118), 50 of them had T3-lesions. The highest local control rate of 76.5% was seen after neutron therapy of differentiated gross tumours. This finding underlines the biological advantage of densely ionizing radiation qualities in these tumours.
Combined Modality Therapy↗
Tumors of the pineal region in children and adolescents.
The treatment of tumors in the pineal area remains controversial. There are two main approaches: Conservative treatment, consisting in CSF shunting and radiotherapy, and direct surgical removal. We report on 25 children (22 boys and 3 girls) aged between 4 and 20 years who underwent conservative treatment. The follow-up period ranges from 1 to 11 years (mean, 4.8 years). 19 patients are still alive at a mean survival time of 5.8 years. 17 children are free of disease, two have severe neurological deficits. Our diagnostic and therapeutical concepts are presented.
Adolescent↗