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Biomedical subjects

D Harms

Publications and source records attributed to D Harms.

At least 289 records · Page 16Linked to original sources
PubMedDate not supplied

[The German Society of Pediatric Oncology Cooperative Ewing Sarcoma Studies CESS 81/86: report after 6 1/2 years].

The GPO Cooperative Ewing's Sarcoma Study (CESS 81 with 10 months four-drug combination chemotherapy (vincristine, actinomycin D, cyclophosphamide, and adriamycin = VACA) and local control with surgery and/or radiation, following week 18, resulted in a Kaplan-Meier estimated disease-free survival of 51% after 6 1/2 years (51/93 patients disease-free). Tumor volume and histological response to primary chemotherapy were identified as most significant prognostic factors. As a consequence, the CESS 86 regimen was stratified according to risk of relapse. Standard risk patients (extremity tumors less than 100 ml tumor volume) were continued on VACA chemotherapy. In high risk patients (extremity tumors greater than 100 ml tumor volume, central tumors), cyclophosphamide in conventional dose (1200 mg/m2/course) was replaced by high doses of ifosfamide (6 g/m2/course) with mesna uroprotection (VAIA). Local control was obtained following week 9. Patients with radiation were randomised for conventional fractionation or accelerated split-course hyperfractionation. The study was piloted from February to December 1985: 27/37 patients were disease-free on October 1, 1987. The ongoing trial was started on January 1, 1986. On October 1, 1987. 63/66 patients were disease-free. In patients with large primaries, according to Kaplan-Meier life-table analysis, the disease-free survival was significantly better in patients receiving VAIA chemotherapy, compared to the previous VACA regimen. The toxicity of both combination chemotherapy regimens was comparable.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Pathology of soft tissue sarcomas: 238 cases of the childhood tumor registry].

Until April 1981 malignant soft tissue sarcomas were registered from 238 patients. Rhabdomyosarcoma was the most common tumor (115/238 = 48.3%). The embryonal subtype was predominantly seen among the rhabdomyosarcomas (83/115 = 72.2%). Rhabdomyosarcomas were localized most frequently in the head and neck area (40/115 = 34.8%), followed by genitourinary system (15/115), pelvis soft tissue (12), abdomen (10) and extremities (10). Non-rhabdomyosarcomatous soft tissue sarcomas (123/238 = 51.7%) were synovial sarcomas (20 = 8.4%), fibrosarcomas including spindle cell sarcoma (17 = 7.4%), leiomyosarcomas (12 = 5.0%), malignant tumors of the vascular system (11 = 4.6%) and neurofibrosarcomas (9 = 3.8%). Other types of sarcoma were extremely rare. 42 (17.6%) of all soft tissue sarcomas could not be classified histogenetically. Rhabdomyosarcomas could be diagnosed much more accurately (105/115 = 91.3%), compared to all other soft tissue sarcomas (99/121 = 81.8%). At present, the most difficult diagnostic problems remain with the tumors of connective tissue, in particular with fibrosarcomas and with the differential diagnosis of juvenile fibrosarcomas versus juvenile fibromatoses.

Adolescent↗
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[Sonographic detection of brain tumors in infancy].

Using the open fontanelle as an acoustic window brain tumours were diagnosed by gray scale ultrasonography in 3 infants aged 1 day to 5 months. The tumours were characterized by their echo dense structure and their good delimination from the surrounding brain. In 2 children the tumour was localized infratentorially (medulloblastoma and unclassified neuroectodermal tumour) and had caused an occlusive hydrocephalus. Both children died aged 3 and 5 months in central nervous dysregulation. One child suffered from plexus papilloma which had caused a hypersecretory hydrocephalus. After resection of the tumour the hydrocephalus decreased without any further treatment. Comparison with axial computed tomography and autopsy findings showed, that gray scale ultrasonography is equally efficient in diagnosing brain tumours and associated hydrocephalus.

Brain Neoplasms↗
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[Pathological anatomy of germ cell tumors (especially testicular tumors) in children].

Germ cell tumors are rare in childhood. They are localized - in decreasing frequency - in the sacrococcygeal area, in the ovary, in the mediastinum, in the testis and elsewhere. Seminoma, dysgerminoma, teratoma and yolk sac tumors are "real" germ cell tumors. As to classification of germ cell tumors of all localizations the (modified) schemes of Pugh and Cameron (1976) and of the WHO (Mostofi) and Sobin, 1977) are suitable. The tumors should be classified according to both systems. Morphology and biological behaviour including prognosis of the germ cell tumors depend heavily upon patient's age at diagnosis and tumor localization. 92 germ cell tumors were already examined and analyzed in the childhood tumor registry, comprising (due to selection) 55 malignant tumors (17 of the ovary, 16 of the testis). In the testes of children yolk sac tumors and differentiated teratomas are seen most frequently with maximum age peak in infancy and early childhood. Starting in or after puberty malignant teratomas of the testis do occur. Paratesticular tumors (especially rhabdomyosarcomas) are more common (in relative and absolute numbers) in childhood as compared to adults.

Adolescent↗
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[Malignant testicular tumors in children and adolescents: concept of the MAHO 82 cooperative therapeutic study of the Society for Pediatric Oncology].

The German Society of Pediatric Oncology (GPO) designed a cooperative study to improve the outlook of patients with malignant (testicular) germ cell tumors. According to stage and histology of the tumor different surgical approaches to retroperitoneal lymphadenectomy are suggested. Local radiotherapy is not recommended. Adjuvant chemotherapy with Vinblastine, Bleomycin and Cis-Platinum according to stage of disease, histologic classification and age of the patient is outlined. For non-responders or patients with only partial response an alternative aggressive chemotherapy with VP 16, Ifosfamide and Cis-Platinum is guidelined.

Adolescent↗
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[Treatment strategy in non-testicular malignant germ cell tumors in children and adolescents--concept of the MAKEI 83 cooperative therapeutic study of the Society for Pediatric Oncology].

In December 1982 the German Society of Pediatric Oncology (GPO) has initiated a cooperative study for non-testicular malignant germ cell tumors with initial vinblastine, bleomycin and cisplatinum chemotherapy depending on stage and histological grading, followed by ifosfamide, cisplatinum and VP 16 chemotherapy. Dysgerminoma patients with advanced disease are also treated with primary chemotherapy including vinblastine, bleomycin and cisplatinum; radiotherapy is limited to current disease. Patients with more differentiated teratomas receive combination chemotherapy with vinblastine, actinomycin D and cyclophosphamide.

Adolescent↗
PubMedDate not supplied

[Histology and prognosis of nephroblastoma--with special reference to special variants].

101 cases of Wilms' tumor (nephroblastoma) were investigated by light microscopy. In 80 cases a diagnosis of triphasic nephroblastoma was made. 21 cases were classified as special variants of Wilms' tumor. These included congenital mesoblastic nephroma (n = 5), fetal rhabdomyomatous nephroblastoma (n = 2), cystic partially differentiated nephroblastoma (n = 3), nephroblastoma with focal or diffuse anaplasia (n = 2), clear cell sarcoma or bone metastasizing renal tumor of childhood (n = 4), rhabdoid tumor (n = 2) and rhabdomyosarcomatous nephroblastoma (n = 3). Based on our own follow-up data and on information from the literature we propose to separate the group of nephroblastomas into three categories of different prognosis: 1. Nephroblastomas of low risk (congenital mesoblastic nephroma, fetal rhabdomyomatous nephroblastoma, cystic partially differentiated nephroblastoma) - in most of these cases simple nephrectomy sufficient as adequate therapy. 2. Nephroblastomas of standard risk (triphasic nephroblastomas) - therapy according to stage of disease. 3. Nephroblastomas of high risk (nephroblastomas with focal or diffuse anaplasia, clear cell sarcoma, rhabdoid tumor, rhabdomyosarcomatous nephroblastoma) - successful therapy has as yet to be developed.

Adolescent↗
PubMedDate not supplied

Testicular germ cell tumors, an update. Results of the German cooperative studies 1982-1997.

BACKGROUND: Oncologic treatment of childhood testicular germ cell tumors can be regarded as a model of curable neoplasm. Over 50% of the tumors are stage I A, produce alpha-fetoprotein and thus provide after semicastration a "wait and see" policy. PATIENTS: The MAHO 82, 88, 94 cooperative studies registered between 1982 and 1997 197 patients, 110 patients had yolk sac tumors (YST), 47 differentiated teratomas (TD), 38 malignant teratomas of either intermediate (MTI), undifferentiated (MTU), or trophoblastic type (MTT) and two seminomas. After semicastration only 65 patients received standard chemotherapy according to stage and histology consisting of four courses of vinblastine, bleomycin and cisplatin. If after two courses viable tumor was indicated, delayed laparotomy was performed (seven patients). Patients with incomplete tumor response after two courses received three courses of etoposide, ifosfamide and cisplatin (nine patients). RESULTS: 105 patients had YST stage I, five higher stages of disease. One of these died by tumor progression. Of 91 patients followed according to "wait and see" only 14 needed standard chemotherapy. The NED of 105 patients is 99%. 47 patients had TD stage I; the NED is 100%. 13 patients had malignant teratomas stage I. 13 patients had stage II and received chemotherapy; the NED for these 26 patients is 100%. 12 patients had stages III or IV, four died. CONCLUSION: In testicular germ cell tumors of childhood in alpha-fetoprotein producing tumors of stage I A a "wait and see" program is safe. X-irradiation or primary lymphadenectomy can be omitted since chemotherapy alone reveals excellent results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Analysis of treatment efficiency of carboplatin and etoposide in combination with radical surgery in advanced and recurrent childhood hepatoblastoma: a report of the German Cooperative Pediatric Liver Tumor Study HB 89 and HB 94.

BACKGROUND: Hepatoblastoma (HB) is the most common liver tumor of childhood, and comprises approximately 1% of all pediatric malignancies. Although recent data from multicenter trials of GPOH, SIOP, CCG and POG indicate a remarkable improvement of therapy results, the prognosis of advanced or recurrent HB is still not satisfying. PATIENTS AND METHODS: During 1989 and 1997, the German Cooperative Pediatric Liver Tumor Studies HB 89 and HB 94 registered 141 patients with HB, who were treated according to the study protocols. These patients received standard chemotherapy with ifosfamide, cisplatin and doxorubicin (IPA) pre-operatively and/or post-operatively. Fourteen children with recurrent or advanced HB were additionally treated with carboplatin and etoposide (CARBO/VP 16), the reason being observations of drug resistance in children with HB after four or more courses of IPA-therapy in the HB 89 study. The clinical data and course of these patients were evaluated to investigate the efficiency of CARBO/VP 16 chemotherapy and for analyzing the role of surgery. RESULTS: Mean follow-up for survivors was 4.3 years (range 13 months-8 years). Tumor resection was attempted in 13 children but, in only 3 cases, was a complete tumor resection achieved in one operation. There was no perioperative death, and 7 of the patients (50%) are in remission. Two patients underwent adjuvant chemotherapy with CARBO/VP 16 for advanced HB at first operation: all are alive and well. Five patients with local relapse and/or distant metastases responded partially to CARBO/VP 16 therapy, and a complete remission was achieved in one patient. In five patients, progressive disease was observed during therapy with CARBO/VP 16. One patient, stable while on chemotherapy, had a successful resection. Acute toxicity of chemotherapy was observed in 7 patients (50%). CONCLUSION: An aggressive approach using IPA and CARBO/VP 16 chemotherapy and highly developed surgical techniques may improve the prognosis of advanced or recurrent HBs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Organization of the Pediatric Tumor Cell Bank of the Society of Pediatric Oncology and Hematology (GPOH)].

Characterized cell lines are absolutely necessary in applied research of cell biology and medicine. For the completion of diagnosis and therapy especially in pediatric oncology we are establishing a Cell Bank for Pediatric Tumors. The Cell Bank for Pediatric Tumors collects tissue samples of different types of solid malignant tumors from children and young adults. The specimens are transferred to in vitro culture (guidelines of the American Type Culture Collection-ATCC), the resulting cells are characterized to assure accordance with the histogenesis of the original tumor and stored in liquid nitrogen. The cell cultures are characterized morphologically (phase contrast microscopy) and immunocytochemically (ABC-method). To prove the malignancy of cells in primary culture the amount of hypertetraploid cells was determined (DNA-Scanning-Cytophotometry). Cell lines are checked to find out whether they develop tumors in nude mice followed by an analysis of the karyotype. Additional investigations (e.g. in vitro test of cytostatic drug resistance) are carried out on request by the sender. Part of the tumor tissue which is used to start the cell culture is in parallel diagnosed histopathologically at the Children's Tumor Register, Kiel and/or at the Charité. By the end of the year 1995 the Cell Bank for Pediatric Tumors had received 183 different specimens including 123 solid tumors (e.g. 24 neuroblastomas, 18 osteosarcomas, 12 Wilms' tumors, 13 rhabdomyosarcomas), 44 tissue specimens without any malignant cells, 8 probes without vital cells and 8 leukemias and lymphomas. We were able to establish primary cell cultures of 50% of the sterile tumor tissue probes, to cultivate them for a minimum of 5-10 passages, to characterize and freeze them. Six out of these tumor cell lines were already cultivated for one year and are available to the scientific community.

Adolescent↗
PubMedDate not supplied

Extracranial non-testicular teratoma in childhood and adolescence: introduction of a risk score for stratification of therapy.

PATIENTS AND METHODS: According to previous literature incomplete tumor resection, coccygeal or ovarian primary site and immaturity are known risk factors for relapse in teratoma. To establish a risk score points are allocated for resection, primary site and histology in the following manner and added: incomplete resection 4 points, primary site coccyx 3 points, ovary 2 points, other site 1 point, histological grading 0-3 points. This score system is evaluated on 270 extracranial non-testicular teratoma cases collected between 1982 and 1995 in the MAKEI cooperative treatment protocols of the German Society of Pediatric Oncology and Hematology. Treatment was resection alone (230 patients) or resection followed by postoperative adjuvant chemotherapy (40 patients). RESULTS: Patients treated with surgery alone: 28/230 (12%) patients relapsed, 14/230 (6%) patients showed highly malignant histology (mostly yolk sac tumor) in relapse. Mortality in case of relapse was 6/28 (21%). Patients scoring > or = 6 points (n = 45) had a relapse rate of 21/45 (47%) resulting in a 23%-mortality (5/21). Patients scoring < 6 points (n = 185) had a 4%-relapse risk (8/185) resulting in 13%-mortality (1/8) (p < 0.01). Patients treated with surgery and adjuvant chemotherapy: 7/40 patients (18%) suffered a relapse, none of them showing malignant histology. Mortality rate in case of relapse was 3/7 (43%). Patients scoring > or = 6 points initially treated with adjuvant chemotherapy (n = 18) had a relapse rate of 7/18 (39%), compared to patients scoring < 6 points (n = 22), in whom no relapses occurred (p < 0.01). There were no highly malignant relapses in the group treated with adjuvant chemotherapy. Regardless of the scored points the difference in highly malignant relapse histology comparing the group treated with surgery and adjuvant chemotherapy to the group treated with surgery was statistically significant (p = 0.02). CONCLUSION: The risk score system marks a high risk group including 63/270 (23%) of all evaluated extracranial non-testicular teratoma cases (scoring > or = 6 points). In this group 28/35 (80%) of relapses and 8/9 (89%) of tumor deaths occurred. For this high risk group a randomized trial will be suggested to evaluate the effect of adjuvant chemotherapy on the rate of malignant relapses. It should also be investigated, if adjuvant chemotherapy will influence relapse rate and mortality.

Child↗
PubMedDate not supplied

Treatment results in children and adolescents with loco-regional recurrences of abdominal germ cell tumors (GCTs): a pilot-study with PEI chemotherapy and regional deep hyperthermia (RHT) in comparison to a matched cohort.

In this study treatment results in children and adolescents (n = 32) suffering from loco-regional abdominal relapses of germ cell tumors (GCT) (7 embryonal carcinoma, 17 Yolk sac tumors, 8 immature teratomas) aged from 1;0 to 23;3 years (mean = 10;11 years) were evaluated. In this pilot study 9 patients were treated with cisplatinum (40 mg/m2 on days 1 and 4), etoposide (100 mg/m2 on days 1 to 4), and ifosfamide (2000 mg/m2 on days 1 to 4) (PEI) +/- radiation in combination with regional deep hyperthermia (RHI). In sedation RHT was induced by non-invasive heat applicators (Sigma-40 and Sigma 60, BSD Medical Corporation, Utah, USA). In 7 out of these 9 patients with recurrent GCT a tumor response (5 CR, 2 PR, 1 SD, 1 PD) was found. In addition, in 2 patients a complete tumor resection could be achieved inspite of 2 previous incomplete tumor resections each. Five out of 9 patients are living event-free after an observation period ranging from 8 to 40 months (median = 15 months). Treatment results of this RHT study population were compared with treatment results in patients with recurrent GCT, who received conventional relapse therapy (chemotherapy/ surgery +/- radiation) alone. In this matched cohort 5 out of 23 patients are living event-free after an observation time ranging from 1 to 120 months (median = 8 months). According to Kaplan-Maier life table analysis, patients with relapse therapy combined with RHT have an event-free survival (EFS) of 0.41 +/- 0.33 whereas the matched cohort without RHT have an EFS of 0.16 +/- 0.25. The difference in treatment results of both groups is significant (Wilcoxon/p = 0.03). From the data presented in this study we conclude that children with loco-regional recurrences of extracranial non-testicular GCT have an unfavorable prognosis, unless local tumor control can be achieved. The additional application of RHT in combination with conventional therapy (PEI chemotherapy +/- radiation) can improve local tumor control and EFS in GCT patients with loco-regional recurrences. Therefore, based upon these results in the future MAKEI trial RHT will be applied to GCT patients with poor response to neoadjuvant chemotherapy alone as first line treatment.

Abdominal Neoplasms↗
PubMedDate not supplied

[Changes in the activation markers of blood coagulation and fibrinolysis in the neonatal period].

BACKGROUND: Activation markers of the clotting and fibrinolytic systems are elevated immediately after birth and decline to near adult levels during the first 24 hours of life. The aims of this study were to investigate, whether the activation of both clotting and fibrinolysis is dependent on the mode of delivery, and to measure activation markers in newborns with infection beyond the first days of life. PATIENTS: We have studied activation markers thrombin-antithrombin III complex, prothrombin fragment 1 + 2, D-dimer and plasmin-antiplasmin complex by use of commercially available ELISA techniques in 20 newborns after elective Cesarean sections because of previous sections, in 20 newborns after Cesarean sections and a trial of labor with uterine contractions over a period of > 20 hours and in 20 newborns (34.-41. gestational week) aged 10-25 days with infection. 20 healthy adults served as controls. RESULTS: A significant elevation of all activation markers was observed both in the newborns after Cesarean sections and in the 10-25 days old children with infection. There were no differences among newborns after elective sections compared to newborns after section and a trial of labor with uterine contractions over a period of > 20 hours. CONCLUSIONS: The clotting and fibrinolytic systems reveal increased activation immediately after delivery, but uterine contractions over a period of > 20 hours seem not to make a difference. During infection, the activation markers of the hemostatic system in newborns aged 10-25 days behaves similarly to the mature adult system.

Adult↗
PubMedDate not supplied

[Successful therapy of local recurrence of congenital mesoblastic nephroma].

A 3 1/2 month old girl was found to have a large abdominal tumor originating in the upper pole of the right kidney. At laparotomy the tumor had infiltrated the perirenal fat, the right lobe of the liver and the diaphragm. Partial nephrectomy was performed and the tumor was completely resected. However, an adequate safety margin could not be achieved. Histology showed a congenital mesoblastic nephroma of the cellular subtype. Postoperatively no chemotherapy was considered necessary. 11 months after diagnosis the patient had an extensive local recurrence with infiltration of the perirenal fat, mesenterium and colon. Complete resection could not be achieved and the tumor was classified as stage III. There was a striking morphological change from spindle cells in the initial tumor to malignant round cells in the relapse specimen. The patient was treated with Vincristine, Actinomycin-D and Adriblastin. Radiotherapy was not given. 38 months after relapse the patient is free of disease and developing normally. Our patient obviously had an aggressive variant of CMN. The significance of the potentially aggressive variant of CMN, atypical mesoblastic nephroma, is discussed and possibilities are suggested for management.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Testicular germ cell tumors. Results of the GPO MAHO studies -82, -88, -92.

The MAHO studies 82, 88 and 92 were cooperative studies for the treatment of testicular germ cell tumors in childhood. Between 1992 and 1993 137 Patients were registered: 76 suffered from yolk sac tumors (YST), 30 from differentiated teratomas (TD), 29 from malignant teratomas of either intermediate (MTI), undifferentiated (MTU) or trophoblastic type (MTT) and 2 from seminoma. All patients received semicastratio. Chemotherapy was administered to 53 patients based on stage and histology. Standard therapy consisted of four courses of vinblastine, bleomycin and cisplatinum. However, if viable tumor was suspected after two courses delayed laparotomy was performed (7 patients). If there was then complete tumor regression, standard therapy was continued (4 pts). If there was incomplete tumor response, the patients received a salvage therapy with 3 courses of VP 16, ifosfamide and cisplatinum (3 pts). Results YST: 73 patients had stage I, 3 patients higher stages. 56 were followed according to "watch and wait" policy. 9 of these needed a delayed standard chemotherapy, one died. The disease free survival of all 76 patients is 98%. TD: 30 patients had stage I. The disease free survival is 100%. Malignant teratomas (MTI, MTU, MTT): 13 patients had stage I. 8 received adjuvant chemotherapy and 5 lymphadenectomy without chemotherapy. All patients survived disease free. 10 patients had stage II and received chemotherapy. All patients survived disease free. 6 patients had stage III. 3 died. Altogether 26 of 29 patients survived disease free. In summary, the probability of disease free survival of all 137 patients suffering from testicular germ cell tumors is 97% after a median observation time of 60 months.

Adolescent↗
PubMedDate not supplied

[Multiple cerebral infarcts with resulting multicystic encephalomalacia in a premature infant with Enterobacter sakazakii meningitis].

Enterobacter sakazakii is an uncommon cause of neonatal meningitis. The prognosis of newborns with meningitis due to Enterobacter sakazakii is poor, the fatality rate is reported as high as 50%. Survivors usually have severe neurologic complications. Most computed tomography (CT) findings were low density lesions of white matter and cortex suggesting infarctions which underwent cystic degeneration. We present one premature baby with meningitis due to Enterobacter sakazakii and large bilateral regions of hypo- and hyperdensity suggesting massive hemorrhagic and nonhemorrhagic intracerebral infarctions leading to multiple cystic encephalomalacia.

Cerebral Infarction↗
PubMedDate not supplied

Successful systemic low-dose lysis of a caval thrombus by rt-PA in a neonate with congenital nephrotic syndrome.

PURPOSE: Thrombotic complications in nephrotic syndrome due to renal loss of antithrombin III (AT III) are well known. With this case report, we want to demonstrate the possibility of achieving the lysis of such a thrombosis in the neonatal period with low-dose rt-PA. PATIENTS AND METHODS: We treated a 10-day-old newborn who had congenital nephrotic syndrome, who developed a caval thrombosis during the first days of his life. After a trial of heparin (up to 20 IU/kg/hour) over a period of 24 hours and treatment with AT III (2 x 250 IU/day) proved to be ineffective, we started systemic thrombolytic therapy with rt-PA. An initial bolus of 0.4 mg/kg during 1 hour was followed by an infusion of 0.5 mg/kg/d rt-PA over a period of 36 hours. Low-dose heparin (5 IU/kg/hour) was given simultaneously. Complete clot dissolution could be achieved this way. No adverse effects were observed, including no clinical signs of bleeding. CONCLUSION: It seems that low-dose rt-PA treatment is safe and effective in dissoluting large caval thromboses in neonates.

Dose-Response Relationship, Drug↗