PubMed Health⌕ Search

Biomedical subjects

I Leuschner

Publications and source records attributed to I Leuschner.

At least 37 records · Page 2Linked to original sources
PubMed1998

Comparative activity of cisplatin, ifosfamide, doxorubicin, carboplatin, and etoposide in heterotransplanted hepatoblastoma.

BACKGROUND: Hepatoblastoma is the most common primary malignant liver tumor affecting infants and young children. Recent clinical experience with advanced hepatoblastoma shows that a reliable in vivo model to study the tumor's response to drugs is needed urgently. METHODS: Hepatoblastoma cell suspensions from three children were transplanted subcutaneously into NMRI nude mice (nu/nu). One of the primary tumors was a embryonal multifocal hepatoblastoma, whereas the other tumors were embryonal/fetal hepatoblastomas localized to one liver lobe. The xenograft tumors resembled their original tumors histologically and produced high levels of alpha-fetoprotein. The mice who received the tumors were given ifosfamide, cisplatin, doxorubicin, carboplatin, and etoposide as single agents. Thereafter, the tumor growth rate and alpha-fetoprotein levels in the animal sera were measured before and after chemotherapy and compared with the control group. After chemotherapy, the tumors were studied by conventional histology. RESULTS: The tumors in the nude mice derived from the multifocal hepatoblastoma reacted minimally against four of the five cytotoxic agents, whereas cisplatin reduced the tumor volume significantly. There was a marked reduction in tumor volume in the other tumors after application of cisplatin and doxorubicin, respectively. The tumors displayed a moderate reduction in size after treatment with ifosfamide, etoposide, and carboplatin. The responses to the different cytostatic agents also corresponded with serum alpha-fetoprotein levels and mitotic rates in the tumor cells. CONCLUSIONS: To the authors' knowledge, this is the first time an in vivo model for analyzing the effects of chemotherapy on hepatoblastoma has been established. The animal model may be suited for the evaluation of new drugs for the treatment of hepatoblastoma and for the investigation of multidrug resistance mechanisms in hepatoblastoma.

Animals↗
PubMed1998

[Rhabdomyosarcoma and extraosseous Ewing's sarcoma].

Rhabdomyosarcomas (RMS) and extraosseous Ewing's sarcomas (EOE) including malignant peripheral neuroectodermal tumors (MPNT) are the most frequent soft tissue malignancies of childhood. They account for 60.2% of 2.350 cases collected in the files of the Kiel Pediatric Tumor Registry. RMS: It is absolutely necessary to distinguish between embryonal (e) and alveolar (a) RMS, since these are two distinct tumor entities with significant differences in clinical presentation, morphology, molecular biology, cytogenetics and prognosis (Botryoid and spindle cell RMS are special variants of eRMS). The overall proportion of eRMS: aRMS is 2.4:1. Most cases of eRMS develop in the first 10 years of life (77.3%) while the age distribution of aRMS is almost constant in childhood and adolescence. Embryonal RMS exhibit a significantly higher proportion of male patients than aRMS (m:f = 1.72:1 vs. 1.06:1). A higher percentage of aRMS cases (25%) shows metastatic disease at the time of diagnosis than eRMS (8%), and the overall survival rates of aRMS are significantly lower even in localised disease (stage I-III) than in eRMS (59% vs. 76%; p < 0.002) (Data from the Cooperative Soft Tissue Sarcoma Study CWS). EOE: Despite proven histogenetic relationship (identical chromosomal rearrangements and fusion genes) the members of the Ewing's sarcoma (ES) family, classic ES and MPNT, whether osseous or extraosseous display significant differences in location, morphology and prognosis. Morphologically, MPNT and classic ES can be considered to be the extremes of a spectrum with overt neurodifferentiation in the former and lack of neural differentiation in the latter. Matched-pairs analysis of CWS EOE and MPNT cases show dramatically more unfavorable overall survival rates in MPNT than in EOE (45% vs. 67%).

Adolescent↗
PubMed1998

The fetal form of the acetylcholine receptor distinguishes rhabdomyosarcomas from other childhood tumors.

The fetal nicotinic acetylcholine receptor (AChR) of muscle is an oligomeric membrane protein with subunit composition alpha2betadeltagamma. After birth, the adult form, in which an epsilon-subunit replaces the gamma-subunit, predominates, and expression of the fetal form is limited to thymic myoid cells, extraocular muscles, and denervated striated muscle. We looked for expression of AChR in rhabdomyosarcomas and other childhood tumors by reverse transcription polymerase chain reaction and immunohistochemistry. mRNA for the AChR gamma-subunit was detected in all embryonal and alveolar rhabdomyosarcomas tested (n = 16) and in some tumors with a rhabdomyomatous component (n = 2) but not in other nonrhabdomyomatous tumors of childhood and adults (n = 45). The fetal form of the AChR was detected immunohistochemically in five of eight embryonal and four of eight alveolar rhabdomyosarcomas and in two Wilms' tumors with a rhabdomyomatous component but not in other tumors or in normal muscle. We conclude that reverse transcription polymerase chain reaction for AChR gamma-subunit could be useful for the diagnosis of rhabdomyosarcoma of childhood and for the detection of micrometastases and minimal residual disease. In addition, the fetal AChR protein is the first extracellular tumor marker that can distinguish rhabdomyosarcomas from nonrhabdomyomatous tumors and from normal muscle. Our findings, therefore, imply that the fetal AChR may be a target for in vivo imaging and, as AChR internalization and degradation is increased by antibody-induced cross-linking, may also provide a sensitive and specific target for immunotherapeutic strategies.

Adolescent↗
PubMed1996

Expression of cell adhesion molecules and common acute lymphoblastic leukaemia antigen in hepatoblastoma.

Hepatoblastoma is an embryonal tumour of the liver, which often contains tissue components with multidirectional differentiation. The occurrence of cell surface antigens in this tumour has not been studied systematically, and we therefore investigated 20 hepatoblastomas for the expression of common acute lymphoblastic leukaemia antigen (CALLA) and cell adhesion molecules (CAMs) in their different tissue components. Epithelial tumour cells of fetal differentiation contained E-cadherin. This protein did not occur in tumour areas with embryonal or mesenchymal differentiation. In contrast, immature embryonal and anaplastic cells expressed CALLA and the hyaluronate receptor (HCAM, CD44). Both fetal and embryonal areas stained irregularly positive for ICAM-1, which, in contrast, was not present on anaplastic cells. Immature fibrous tissue did not contain any of these molecules except for ICAM-1. However, some cells adjacent to, or enclosed in, osteoid were positive for HCAM and NCAM. Like small undifferentiated hepatoblastoma cells, primitive mesenchymal spindle-shaped cells also expressed CALLA, HCAM, and the polysialylated embryonic form of NCAM strongly. This last is not present on other epithelial or mesenchymal tumour cells. Hepatoblastoma cells of varying differentiation express distinct patterns of CAMs and CALLA. Our results give further insight into their histogenesis and cellular interactions and may explain their variable ability for invasive growth and formation of metastases.

Antibodies, Monoclonal↗
PubMed1996

Desmoplastic small round cell tumor.

Desmoplastic small round cell tumor is an undifferentiated tumor associated with serosal surfaces, especially the peritoneum. It is found predominantly in adolescents and young adults and is much more common in males than in females. The tumor has a characteristic histology, with extensive stromal tissue around islands of small and undifferentiated cells revealing the desmoplastic appearance. The coexpression of epithelial and mesenchymal antigens distinguishes this entity from other small round and blue cell tumors of this age group. Cytogenetic studies showed a t(11;22) translocation that differs from the Ewing's tumor translocation and seems to be specific to this entity. The involvement of the WT1 and EWS genes in the translocation makes this tumor an interesting subject for research on histogenesis and differentiation in small round and blue cell tumors.

Abdominal Neoplasms↗
PubMed1994

Clinico-pathological criteria with prognostic relevance in hepatoblastoma.

We investigated clinical data and histological specimens of 46 patients with a hepatoblastoma (HB) for prognostic criteria. Disease-free survival (DFS) of 23 patients treated in the German Cooperative Study HB-89 (1988-1990) was 83%, in contrast to 40% in 10 children with other chemotherapy regimes (1977-1987) and 38% in 13 with only a tumour resection (P = 0.005). Tumour residence after resection (R category) correlated significantly with probability of DFS (P = 0.0001). This was also the case for pT status, according to the pTNM classification for liver carcinoma (P = 0.0007), involvement of one or both liver lobes (P = 0.004), multiplicity of tumour nodes (P = 0.001), vascular invasion (P = 0.0006) and expression of nucleolar organiser regions as an indicator for proliferation activity of tumour cells (P = 0.05). Patients' age and histopathological subtypes could only indicate outcome, while tumour size and serum alpha-fetoprotein values were not significantly related to prognosis. In multivariate analysis, pT status and R categories remained significant. These should be applied in all cooperative trials on HB.

Child↗
PubMed1993

DNA analysis in hepatoblastoma by flow and image cytometry.

BACKGROUND: In several types of tumors, including hepatocellular carcinoma, prognosis could be correlated with DNA ploidy. Few studies have been performed on hepatoblastoma with contradictory results. METHODS: Twenty-nine cases of nonpretreated hepatoblastoma were studied with flow cytometry and image cytometry for DNA index and proliferation index using paraffin-embedded tissue. RESULTS: Twenty-three (79.9%) tumors were diploid, and 6 (20.7%) were aneuploid (hyperdiploid). Patients with diploid tumors were younger than those with aneuploid tumors. With regard to stage, diploid tumors were almost equally distributed among stages (tumor, lymph node metastases, distant metastases), whereas aneuploid tumors tended to occur in higher stages (tumor, lymph node metastases, distant metastases). Diploid tumors had clearly a better prognosis than aneuploid tumors, although the difference was not statistically significant (flow cytometry, P = 0.06; image cytometry, P = 0.16). A more favorable prognosis was also noted for hepatoblastomas with low-proliferation index (< or = 7%), but the difference from tumors with high-proliferation index (> 7%) again was not statistically significant (P = 0.16). CONCLUSIONS: Although no statistically significant differences in prognosis between hepatoblastomas with diploid and aneuploid DNA content, respectively, were found, there is a clear tendency that diploid hepatoblastomas behave more favorably. The same is true for hepatoblastomas with low-proliferation index.

Aneuploidy↗
PubMed1993

Spindle cell variants of embryonal rhabdomyosarcoma in the paratesticular region. A report of the Intergroup Rhabdomyosarcoma Study.

We reviewed 173 cases of paratesticular rhabdomyosarcoma (RMS) of Intergroup Rhabdomyosarcoma Studies (IRS)-I, -II, and -III for evaluation of possible histological factors that might account for the good prognosis of these patients. Almost all cases (161 of 173 cases, 93.1%) occurring in this site were of embryonal histology. A spindle-cell subtype of embryonal RMS was identified that presented a storiform growth pattern with abundant collagen between the tumor cells in most cases. Other tumors of this subtype showed an arrangement of tumor cells in bundles with a low to moderate amount of collagen, resembling a leiomyosarcoma. The other embryonal RMS in this site had the classical embryonal cytology. The spindle-cell subtype was highly differentiated by immunohistochemistry and electron microscopy. Lymph node metastasis was found in seven of 43 patients (16.3%) with a RMS of spindle-cell subtype, compared with 40 of 112 patients (35.7%) with RMS of non-spindle-cell type. Clinical data from patients with spindle-cell subtypes of the paratesticular lesions revealed that they almost always had an association with clinical groups of limited disease (32 patients, 74.4%, with Group I; 10 patients, 23.3%, with Group II disease) and a significantly better prognosis (95.5% survival at 5 years) when compared with patients with the classic embryonal variant of RMS (80% survival at 5 years, p < 0.035). The incidence and anatomic distribution of this spindle cell subtype of embryonal RMS was estimated on 800 randomly selected patients from IRS-II. It was found in the head and neck, extremities, orbit, and some other sites, but 30.6% were located in the paratesticular area. Patients with spindle cell RMS of nonparatesticular sites usually had more extensive disease compared with patients having paratesticular lesions; two thirds of the cases had gross residual tumor after surgery or metastatic tumor at diagnosis. We conclude that spindle-cell RMS is a subtype of embryonal RMS with a very favorable prognosis. The site factor of the paratesticular localization may allow earlier diagnosis of the spindle-cell lesions compared with other sites. Other unknown factors may also play a role.

Child↗
PubMed1992

[Type-2B multiple endocrine neoplasms with diffuse liver metastases as the cause of chronic diarrhea].

During examination before surgical correction of pes valgus a 20-year-old man reported having 3-5 pasty, foul smelling diarrhoeic motions per day for the past 3 years. He was noted to have rather thick lips and Marfan-like body build. Erythrocyte sedimentation rate was 18/34 mm, serum activity of GOT 22.5 U/l, GPT 35.7 U/l. Faecal weight was increased to 640 g/d, fat content to 12 g/d. Serum levels of the carcinoembryonic antigen (2494 ng/ml; normal: < 2.5) and of calcitonin (1,619,760 pg/ml; normal < 100) were elevated. Gastroscopy, partial coloscopy, colon-contrast imaging, ultrasonography and computed tomography of the neck and abdomen, as well as magnetic nuclear imaging of the neck were all normal. But laparoscopy revealed the liver to be infiltrated by small whitish nodules which immunohistologically proved to be metastases of a C-cell carcinoma. Total thyroidectomy was performed and the diagnosis of a C-cell carcinoma of the thyroid confirmed intra-operatively. After the operation the diarrhoea was stopped with codeine (9 mg/d). In case of tumour progression, therapy with octreotide, a somatostatin analogue, will be carried out. The concomitant occurrence of C-cell carcinoma, Marfan-like body build, thick lips and skeletal changes is typical of multiple endocrine neoplasia type 2B, which is caused by a chromosomal defect.

Adult↗
PubMed1992

Malignant renal tumors of childhood.

The prognosis in nephroblastoma (Wilms' tumor) has been improved considerably by treatment protocols combining surgery, chemotherapy, radiation therapy, and, in some clinical trials, pre-operative chemotherapy. Cure is now achieved in most patients. All clinical trials have employed treatment strategies tailored to the individual risk of the patient, including the histological subtype of the tumor. In the National Wilms' Tumor Study (NWTS) of the United States these subtypes have been divided into two groups of tumors according to their "favorable" or "unfavorable" histology. At the Kiel Pediatric Tumor Registry we have devised a system which distinguishes three groups of tumors classified according to prognosis. The first group includes tumors with a favorable prognosis, even if only surgery is performed. These comprise congenital mesoblastic nephroma (CMN) and cystic, partially differentiated nephroblastoma (CPDN). The second group consists of tumors posing an intermediate risk, such as typical nephroblastoma and its histological variants characterized by variations in the relative proportions of the histological components. Fetal rhabdomyomatous nephroblastoma (FRN) is also included in this group. The third group comprises tumors of high risk such as anaplastic nephroblastoma, clear cell sarcoma of the kidney (CCSK), and malignant rhabdoid tumor of the kidney (MRTK). Since histological diagnosis plays a crucial role in the assignment of a patient to a particular type of treatment protocol, knowledge of the histological appearance of the various tumor types both with and without preoperative treatment is of utmost importance.

Antineoplastic Agents↗
PubMed1991

Renal cell carcinoma in children: histology, immunohistochemistry, and follow-up of 10 cases.

Ten renal cell carcinomas in children under 15 years were investigated. The average age was 122.5 months and the girls predominated in our cases (7 girls, 3 boys). By using the classification of Thoenes et al., Pathol Res Pract 181: 125-143, 1986 a predominance of clear cell-eosinophilic tumor cell type and of the tubulopapillary growth pattern was found. Immunohistochemistry revealed a heterogeneity of cytokeratin expression. By using the monoclonal antibodies Cam 5.2 and KL 1, cytokeratins were found in 7 cases each. The other 4 cytokeratin antibodies used were less sensitive. The expression of cytokeratin 13 in 3 cases suggested a more complex histogenesis than assumed. Vimentin was found in 3 tumors, but an association to a higher grade (G) of malignancy was not found in these cases. One tumor expressed the Tamm-Horsfall-protein, which is predominantly found in the distal tubule of the normal kidney. In summary the results of immunohistochemistry characterized the great heterogeneity of these tumors. Follow-up information was available in 9 cases. All patients with G I- and G II-tumors were free of disease after an average time of 39.6 months (mean 27 months). Two of the 3 cases with G III-tumors died after 9 and 15 months, despite additional chemo- or radiotherapy. Therefore tumors of grade I and II of the Thoenes classification seem to have a good prognosis.

Adenocarcinoma↗
PubMed1991

Infantile desmoid-type fibromatosis. Morphological features correlate with biological behaviour.

It is generally agreed that the biological behaviour of infantile desmoid-type fibromatosis is unpredictable in terms of the likelihood of local recurrence. We evaluated the prognostic importance of the number of slit-like blood vessels with a mean diameter of less than 20 microns and of the quantity of undifferentiated mesenchymal cells. In addition, we studied the immunophenotypic characteristics of the proliferating cells and their nucleolar organizer region (AgNOR) numbers and distribution. Statistical analysis showed that the tendency to recur locally was correlated with larger numbers of slit-like blood vessels and undifferentiated mesenchymal cells. The proliferating cells were identified by immunohistochemistry as myofibroblasts. No correlation was found between AgNOR numbers and clinical course of the disease. We conclude that histological features easily evaluated by conventional light microscopy provide useful information on the possible course of infantile desmoid-type fibromatosis.

Actins↗
PubMed1990

Undifferentiated sarcoma of the liver in childhood: morphology, flow cytometry, and literature review.

Nine cases of undifferentiated sarcoma of the liver in childhood were investigated by conventional light microscopy, immunohistochemistry, and DNA flow cytometry. Different histologic patterns were discernible. In some cases, areas resembling poorly differentiated rhabdomyosarcoma were present. This histologic diversity was supported by the immunohistologic detection of desmin and cytokeratins in five cases. When evaluated by flow cytometry, four of five cases investigated were diploid; only one was aneuploid, and this patient had the most aggressive course. Follow-up investigations of our patients and those described in the literature revealed that the prognosis of this type of tumor is not as bad as is generally assumed. Of the patients reported in the literature with detailed follow-up information, 37.5% survived without evidence of disease for an average of 37.5 months, death occurred in 47.5% after an average of 11.9 months, and 15.0% were alive with disease.

Adolescent↗
PubMed1990

Cytokeratin expression in malignant Triton tumor.

A malignant Triton tumor in a 9-year-old boy is described. The first biopsy which was taken from the thenar prominence was diagnosed as a monophasic fibrous synovial sarcoma based on the finding of a spindle cell neoplasm with plump nuclei and cytokeratin expression. The true nature of the tumor became apparent when a second biopsy was investigated. In this specimen a rhabdomyosarcomatous component was found in association with a spindle cell sarcoma fulfilling the criteria of a malignant schwannoma. Immunohistochemical staining using antibodies against vimentin, desmin, muscle-specific actin, cytokeratin, glial fibrillary acidic protein, protein S-100, Leu 7 and myoglobin served to distinguish the two tumor components and documented the possible reactivity of malignant Triton tumor for cytokeratins.

Biopsy↗
PubMed1989

Abdominal, retroperitoneal and sacrococcygeal tumours of the newborn and the very young infant. Report from the Kiel Paediatric Tumour Registry.

We examined 226 abdominal, retroperitoneal and sacrococcygeal tumours in newborns and infants aged 6 months or less. Most frequent were neuroblastomas (n = 83) followed by germ cell tumours (n = 76), 37 of which were immature and 32 were mature teratomas. Fully malignant germ cell tumours and malignant germ cell tumour components were much rarer in this age group (9.2%) than in older children (58.1%). The majority of germ cell tumours were localized in the sacrococcygeal region (72.4%). Next in frequency were tumours of the kidney (n = 54), including 28 congenital mesoblastic nephromas. In contrast to children over 6 months of age, kidney tumours were frequently low grade malignant with a favourable prognosis. Among liver tumours there were 19 infantile haemangioendotheliomas and 9 hepatoblastomas. By contrast, at ages 7-24 months hepatoblastomas (n = 28) were much more frequent than haemangioendotheliomas (n = 2). Tumours in the newborn and very young infant differ from those in older children in many respects: (1) the relative frequency; (2) localization; (3) distribution of histological types; (4) degree of differentiation, often associated with a tendency toward maturation but occasionally also with increasing malignancy; and (5) prognosis, which is comparatively favourable.

Abdominal Neoplasms↗
PubMed1989

Malignant rhabdoid tumor. A morphological and flow cytometric study.

Sixteen cases of malignant rhabdoid tumor (MRT) were studied by conventional light microscopy, immunohistochemistry, electron microscopy and flow cytometry. The age of the 16 patients varied from two months to 25.9 years. There were 11 males and five females. Eleven tumors were located in the kidney. The remaining five were found in the chest wall (n = 2) and the head and neck (n = 3). Particular histopathological findings included myxoid, pseudoalveolar and hyalinized areas. By immunohistochemistry, 15/15 cases stained positively for vimentin, 9/14 for cytokeratin, 6/15 for desmin, 9/14 for epithelial membrane antigen (EMA), 10/14 for neuron specific enolase (NSE) and 10/15 for protein S-100. Stains for neurofilaments, myoglobin and Ulex europaeus aggl. I (UEA I) were negative. The characteristic finding by electron microscopy in three cases were large numbers of intermediate filaments arranged either randomly or in concentric whorls. None of the 11 cases studied revealed aneuploid DNA stem lines as determined by flow cytometry. Of the 16 patients 12 died, one is living with disease and three are living without evidence of disease. Postoperative treatment consisted of chemotherapy, in some cases combined with radiotherapy. Two patients developed a medulloblastoma in addition to a renal and extrarenal MRT, respectively. Our findings demonstrate that MRT may present more histopathological patterns than hitherto recognized. In addition, they show that MRT may express a wide range of antigenic "markers", similar to epithelioid sarcoma with which it may be confused on cytological grounds. Despite aggressive postoperative chemotherapy prognosis is still poor.

Adolescent↗