Biomedical subjects

F Berthold

Publications and source records attributed to F Berthold.

139 records · Page 8Linked to original sources

PubMedDate not supplied

Preradiation chemotherapy of children and young adults with malignant brain tumors: results of the German pilot trial HIT'88/'89.

BACKGROUND: Preradiation chemotherapy could be beneficial in malignant brain tumors, because the blood-brain tumor-barrier is disrupted after surgery, bone marrow recovery--essential for intense chemotherapy--is still intact, and CNS toxicity and ototoxicity of active drugs are lower before irradiation of a child's brain. PATIENTS AND METHODS: A neoadjuvant phase 2 and a single arm pilot trial were initiated to investigate the efficacy and toxicity of an intense multidrug regimen before radiotherapy in 147 patients aged between 3 and 29; 9 years with medulloblastoma (94), malignant glioma (22), ependymoma (21), and stPNET (10). They were treated with one or two cycles consisting of procarbazine, ifosfamide/mesna with etoposide, high dose methotrexate/CF, and cisplatin with cytarabine. RESULTS: Radiation therapy was delayed for 17-30 weeks (median 23 weeks) in 112 patients who received two cycles. Chemotherapy was well tolerated. Serious infections were observed in 20 patients, with one fatal fungal septicemia. In 69 high risk patients with a residual tumor and/or solid CNS metastases an objective response (CR plus PR) was achieved in 67% medulloblastoma, 57% stPNET, 55% anaplastic ependymoma and 25% malignant glioma. Progression-free survival (PFS) at 5 years was 57% in 14 high risk patients with medulloblastoma, who achieved a complete response (CR). After a less than CR the PFS was 20% (p = 0.01). Overall survival at 5 years was 57% in medulloblastoma, 62% in ependymoma, 36% in malignant glioma and 30% in stPNET. CONCLUSION: The HIT'88/'89 regimen was well tolerated and efficacious in regard to response rates and early PSF particularly in medulloblastoma and anaplastic ependymoma. Based on these results the prospectively randomized trial HIT'91 was designed to investigate the optimal timing of chemotherapy. Preradiation chemotherapy according to the HIT'88/'89 regimen was compared with the standard regimen using CCNU, cisplatin, and vincristine after radiation therapy. Additionally, strict quality control of the three treatment modalities was instituted to help improve the survival rates in both trial arms.

Adolescent↗

PubMedDate not supplied

Does megatherapy contribute to survival in metastatic neuroblastoma? A retrospective analysis. German Cooperative Neuroblastoma Study Group.

To evaluate the impact of megatherapy on the outcome of high risk neuroblastoma, 39 patients with stage IV neuroblastoma, who underwent megatherapy, were analyzed retrospectively and compared to 49 patients, who continued chemotherapy according to the German cooperative trial NB85. The groups were comparable concerning age, primary localisation, pattern of metastases, clinical risk groups and response to induction therapy. Overall survival of the megatherapy group was 0.23 +/- 0.07 compared to 0.14 +/- 0.05 of the chemotherapy group (p = 0.0149). In particular patients with partial response to induction chemotherapy appeared to gain from megatherapy, while patients in complete remission did not benefit. Subset analysis confirmed the superiority of megatherapy in patients with bone marrow infiltration at diagnosis, in patients with or without bone metastases at diagnosis and in patients older than 2 years. On the background of the poor prognosis of stage 4 neuroblastoma and lack of other effective treatment modalities these data support the utilization of megatherapy in treatment strategies for stage IV neuroblastoma.

Bone Marrow Transplantation↗

PubMedDate not supplied

Case control study of neuroblastoma in west-Germany after the Chernobyl accident.

BACKGROUND: To explore possible causes of a 1988 incidence peak of infant neuroblastoma in west German regions which were contaminated with more than 6000 Bq/m2 Cs137 from the Chernobyl accident. The primary working hypothesis was that parents of the diseased children had been contaminated by an excessive intake of locally produced food, especially mushrooms or deer. DESIGN: Case control study with 1:2 (cases:controls) matching. Data were collected from the children's parents by questionnaires and telephone interviews. SETTING: Nation-wide study (former FRG) based on the German Childhood Cancer Registry. SUBJECTS: Cases born in 1988 and reported with a neuroblastoma to the registry until March 1992. Population-based healthy controls, matched for age, sex and residence at time of diagnosis. RESULTS: The working hypothesis could not be confirmed by the study, because the parents of cases tended to eat less locally grown food than the parents of controls (RR = 0.63, 95% CI:0.20-1.97). Possible influence factors which previously have been described to be associated with neuroblastoma incidence could not be confirmed by the study. Parental exposure to herbicides and pesticides was associated with the occurrence of neuroblastoma (RR = 4.2, 95% CI:1.4-12.9). Neuroblastoma stage distribution in the contaminated regions was shifted towards lower stages as compared to the less contaminated regions and previous age cohorts. CONCLUSIONS: The study does not show additional evidence that the observed increase in neuroblastoma incidence might have been caused by exposure to fallout from the Chernobyl accident. The observed shift towards lower clinical stages may rather indicate increased diagnostic awareness. The association between neuroblastoma and parental exposure with herbicides and pesticides resulted from an extensive exploratory data analysis and needs to be confirmed in further studies.

Child, Preschool↗

PubMedDate not supplied

[Hepatopathy in patients with stage 4S neuroblastoma].

The survival probability is 79% for patients with neuroblastoma stage 4S treated according to the German Society for Pediatric Oncology and Hematology (GPOH) treatment studies. Most of these patients (80%) have liver metastases. Patients are grouped according to their condition at diagnosis and tumour resectability to different risk groups (A, B, C). Chemotherapy is provided for patients who are initially diagnosed as critically ill, caused for example by excessive hepatomegaly due to liver metastases. The aim of this study is to clarify whether liver infiltration is associated with liver dysfunction and whether chemotherapy plays a role in this process. Hepatopathy was diagnosed when clinical signs were present and/or liver function tests revealed pathologic results. The charts of 48 patients (22 boys, 26 girls) diagnosed between 1990 and 1994 from the ongoing NB-90 treatment study were evaluated retrospectively. Median age at diagnosis was 52 days (range: 1-328). 41 patients (85%) had liver infiltration, 26 patients (54%) had bone marrow involvement and in nine patients (19%) skin metastases were found. 12 patients were in poor general condition at diagnosis (risk group C). 36 of 48 patients (75%) received chemotherapy, three children were treated with radiotherapy additionally, due to massive liver enlargement. 15 patients (31%) had signs of hepatic dysfunction at diagnosis or during their illness, 14 of these had liver metastases. All these 15 patients were treated with chemotherapy. 12 of 15 patients with hepatopathy were younger than two months at diagnosis. Five patients with liver dysfunction were not critically ill at diagnosis. Hepatomegaly > or = 6 cm was present in 10 of 15 patients with liver dysfunction. Hepatopathy was transient in eight patients, four patients died soon of multiorgan failure during progression of disease. Three children developed liver fibrosis with conversion to cirrhosis. Hepatopathy was correlated with distribution to risk groups (A and B (5/36) vs. C (10/12), p < 0.001). The appearance of hepatic dysfunction in patients with neuroblastoma stage 4S remains a serious problem especially for young children with excessive hepatic infiltration. Liver dysfunction was of short duration and reversible in most patients, however, even with age-adapted dosages of chemotherapy long-standing cases of hepatopathy were observed. A general recommendation for treatment strategy in this heterogeneous patient group is difficult. Attention should be given to for this complication.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

[Expression of CD44-standard in 182 primary neuroblastomas].

182 untreated neuroblastomas were examined for the expression of the adhesion molecule CD44s by immunohistochemistry; all tumors were also tested for amplification of the oncogene N-myc by conventional Southern blot analyses. Positive CD44s immunoreactivity correlated not with a more favorable prognosis in contrast to an absence of CD44s expression in stage dependent or independent evaluations. All patients with stage 4S disease (n = 16) expressed CD44s on a high level and had an event-free survival probability of 82%. In undifferentiated neuroblastoma subgroups could be defined, depending on the expression of CD44s (p < 0.01). In 93% of N-myc non-amplified tumors CD44s expression was detected, whereas only 62% of N-myc amplified tumors were positive for CD44s expression. These results point to CD44s expression as a new histological marker in neuroblastoma, having prognostic impact in tumors of undifferentiated morphology.

Biomarkers, Tumor↗

PubMedDate not supplied

Artificial abdominal hernia for the treatment of hepatomegaly in a neonate with stage 4S neuroblastoma.

Surgical widening of the abdomen by a silastic pouch has been used very rarely in the management of critically ill infants with hepatomegaly due to neuroblastoma stage 4S. A female newborn baby was referred on the second day of life because of local compressive effects of a massive hepatomegaly, which lead to multiorgan failure. An artificial abdominal hernia was created on the third day of life using a silastic pouch. During the operation oxygenation and ventilation improved and urinary output returned. After chemotherapeutic reduction of hepatic metastases and primary tumor the pouch was successfully removed on day 57 without local complications. The child has survived for more than 1 year and is in complete remission. An artificial abdominal hernia should be considered more often in the critically ill neonate with stage 4S neuroblastoma and massive hepatomegaly.

Decompression↗

PubMedDate not supplied

Plasma neurotensin: lack of a differentiation and tumor marker in children with neuroblastoma.

Neurotensin is a tridecapeptide with changing receptor expression in central and peripheral neural cells during ontogeny suggesting its potential use as a differentiation and tumor marker in neuroectodermal malignancies. We investigated the neurotensin levels in plasma samples of 58 patients with neuroblastoma using a sensitive radioimmunoassay. Elevated levels were found only in one stage III and in one stage IVs patient, while the neurotensin concentrations of 56 patients were in the range of control children. We conclude that plasma neurotensin reflects neither the differentiation nor the tumor status in children with neuroblastoma.

Biomarkers, Tumor↗

PubMedDate not supplied

Expression and clinical relevance of NY-ESO-1, MAGE-1 and MAGE-3 in neuroblastoma.

Human genes NY-ESO-1, MAGE-1 and MAGE-3 code for antigens which are expressed in malignancies of various histological types but not in normal tissues except testis. These antigens might therefore represent potential targets for specific immunotherapy. We studied the expression of genes NY-ESO-1, MAGE-1 and MAGE-3 in 98 neuroblastoma tumors by reverse transcription-polymerase chain reaction (RT-PCR). MAGE-1 was expressed in 66%, NY-ESO-1 in 36% and MAGE-3 in 33% of the tumors. NY-ESO-1 gene expression was associated with age older than one year (p = 0.017), more differentiated tumor histology (p = 0.044), elevated urinary vanillylmandelic acid (VMA, p = 0.018) and normal serum ferritin levels (p = 0.023). MAGE-1 expression correlated significantly with normal serum ferritin levels (p = 0.009) and absence of MycN amplification (p = 0.007) while MAGE-3 expression was associated with absence of metastasis (p = 0.027). We conclude that approximately 70% of the neuroblastoma tumors express at least one of the genes coding for NY-ESO-1, MAGE-1 or -3, respectively.

Adult↗

PubMedDate not supplied

Abnormalities in serum osteocalcin values in children receiving chemotherapy including ifosfamide.

In patients undergoing high-dose ifosfamide treatment tubular nephrotoxicity with hypophosphatemia has been described. Long-lasting hypophosphatemia may be associated with bone disease including rickets. Serum osteocalcin is considered a sensitive marker for reduced osteoblast activity and bone formation. In our study we determined osteocalcin serum levels in 11 children with cancer and chemotherapy, comparing them with fractional reabsorption of phosphate, aminoaciduria and a1-microglobulin excretion. A decrease of serum levels of osteocalcin and serum phosphate during chemotherapy was found. Progressive hyperaminoaciduria, a1-microglobulin loss and a low fractional reabsorption of phosphate were also detected during chemotherapy. All parameters tended to become normal after treatment. We conclude that serum osteocalcin levels may decrease soon after the initiation of chemotherapy, indicating low osteoblast activity, probably as a result of phosphate loss. Patients with decreased osteocalcin levels may therefore be at risk for osteoporosis.

Adolescent↗

PubMedDate not supplied

Primary myeloblastoma of the pineal region.

The first case of a pinealis region tumor of the hematopoietic system without known leukemia (so-called primary myeloblastoma, primary granulocytic sarcoma) is reported. Two weeks after resection, the 3.5-year-old patient suffered from a local recurrence. At this time, a bone marrow infiltration by leukemic blasts was diagnosed for the first time. An aggressive chemotherapy and radiation induced a complete remission, over a 26-month follow-up period. We examined the removed tumor tissue by routine histology methods, immuno- and enzyme histochemistry and electron microscopy. The CSF was studied by conventional microscopy and enzyme cytochemistry. We discuss the epidemiological data of nine previously published cases of primary intracranial myeloblastoma.

Brain Neoplasms↗

PubMedDate not supplied

Age dependence and prognostic impact of neuron specific enolase (NSE) in children with neuroblastoma.

Serum neuron specific enolase (NSE) was determined in 159 patients with neuroblastoma at diagnosis and in 183 children of various age groups. We found an age dependence of reference intervals for NSE and defined the 95th percentiles as upper normal limits. The specificity was 91.3% and the sensitivity 73.0%. The incidence of abnormal NSE levels increased with stage. The NSE serum levels were not influenced by histologic differentiation. Neuron specific enolase proved to be a reliable tumor-marker for monitoring the disease. Moreover, abnormal NSE values at diagnosis were of prognostic significance for patients with localized neuroblastoma (stages I-III) and for children with metastatic disease (stage IV), but not for infants with stage IV S. In comparison to catecholamine metabolite determination neuron specific enolase appeared to be a slightly less specific, equally sensitive tumor marker but with prognostic information for children with neuroblastoma.

Age Factors↗

PubMedDate not supplied

Persistent active herpes virus infection associated with atypical polyclonal lymphoproliferation (APL) and malignant lymphoma.

This study focuses on lymphoproliferative diseases associated with persistent infection by Epstein-Barr virus (EBV) and human herpes virus 6 (HHV-6). A suggestive premalignant lymphoproliferative state is distinguished from malignant lymphoma and identified as "atypical polyclonal lymphoproliferation" (APL). Sixteen cases of herpes virus (HHV)-associated APL are compared with 21 cases of HHV-associated malignant lymphomas (ML), with 108 cases of EBV or HHV-6 related acute infections mononucleosis, with 14 cases of seronegative non-specific lymphoid hyperplasia and with 304 cases of HHV-unrelated ML. Six cases of APL and two ML occurred in AIDS patients, two cases in Sjogren's syndrome, one in a kidney allograft recipient, and the remaining cases had no identified underlying disease. APL was histologically reminiscient of excessive infectious mononucleosis, while other cases of Castleman's disease or even of malignant lymphoma. Seropositive APL and ML contained significantly more virus genome than is found in latent background infection. There was no histologic difference between HHV-6 or EBV-positive APL or ML, although both viruses infect different lymphocyte populations. From histology alone, seropositive ML cases were not distinguished from seronegative ones, yet persistent active EBV and HHV-6 appear to predominate in follicular center cell- and immunoblastic lymphoma and in HOdgkin's disease. Although no a direct oncogenic activity of these viruses could be observed in our cases, they may contribute to lymphomagenesis by inducing progressive lymphoproliferation.

Adolescent↗

PubMedDate not supplied

Monoclonal B cell proliferation in lymphoproliferative disease associated with herpes virus type 6 infection.

Clonal gene rearrangements and aneuploidy are commonly recognized as characteristics of malignancy. We challenge this by an observation of a 3 1/2 year old boy with chronic benign lymphadenopathy, connatal splenomegaly and peripheral lymphocytosis. His brother and mother suffered from similar disease without progression. Cervical lymph node biopsy from our patient revealed a benign histology corresponding to the clinical course; however, clonal rearrangements of the JH and TCR gamma gene were demonstrated in lymph node cells and DNA aneuploidy in 11% of bone marrow cells. Immunohistology showed an inverse T-helper/T-suppressor cell ratio with polyclonal B cell increase and extensive lymphocyte activation. In situ hybridization demonstrated foci of lymphoid cells in the paracortical zone with expression of herpes virus type 6 genome. In addition, the patient, his brother and his mother showed serological evidence of active infection with the human herpes virus-6 (HHV-6). The association of HHV-6 infection, monoclonality and benign lymphoproliferation is discussed.

Antibody Formation↗