Biomedical subjects

I Leuschner

Publications and source records attributed to I Leuschner.

41 records · Page 3Linked to original sources

PubMed1989

[New aspects of nephroblastoma (Wilms tumor) and other metanephrogenic neoplasms].

We differentiate (continuing the scheme of the National Wilms' Tumor Study) three groups of Wilms' tumors (WT), which for practical reasons also encompass WT variants: 1. a group of low-grade malignant tumors comprising 9.3% of cases (congenital mesoblasticnephroma; cystic, partially differentiated nephroblastoma); 2. the main group of tumors with histologically standard malignancy and constituting 77.7% of cases, against which a combined therapy is used depending upon age and stage of spread; and 3. a small group of tumors of high-grade malignancy (anaplastic WT, clear cell sarcoma of the kidney; malignant rhabdoid tumor of the kidney). This latter group constitutes only 13% of cases but is responsible for a high percentage of total deaths due to WT. To the tumor group with standard malignancy belong the classic triphasic WT (without anaplasia) as well as WT "with quantitative deviations", in which either the blastemic, the epithelial, or the stroma component dominates. In the differential diagnosis the relatively frequent blastemic WT must be differentiated from other so-called small, round, and blue cell tumors of childhood, especially the undifferentiated neuroblastomas. Pseudo-rosettes and cytokeratin expression are signs of an "early" epithelial differentiation. Anaplastic WT (comprising 6.1% of our cases) are diagnosed according to the criteria of BECKWITH and PALMER (1978). They are aneuploid tumors and occur predominantly in children over two years of age. By contrast, the histogenetic still undefined clear cell sarcomas and malignant rhabdoid tumors of the kidney occur chiefly in children under two. Both tumors are diploid, notwithstanding their high-grade malignancy. Clear cell sarcoma, which contains a high content of vessels and comprises 3.7% of our cases, consists of cells with weakly stained and partially vacuolized cytoplasm. In contrast to normal WT, clear cell sarcoma often progresses to bone metastases. Malignant rhabdoid tumor (2.7% of our cases) possesses cells with large, roundish nuclei, pale chromatin, very prominent nucleoli and characteristic spherical intermediate filament condensations. Cross striation and myoglobin are never present. Malignant rhabdoid tumor is not a genuine kidney tumor; it may also occur extrarenally. Low-grade congenital mesoblastic nephroma is a spindel cell tumor often exhibiting high cellularity and characterized by fingerlike projections extending into the adjacent kidney tissue. Nephroblastomatosis, with preferential perilobular localization, is a potential WT precursor found in 25% to 40% of all nephrectomy specimens containing WT and in all cases of bilateral and multifocal WT. Nevertheless, only a small proportion of the usually very small "nephrogenic remnants" lead by way of an adenomatous proliferation to manifestation of WT.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

PubMed1988

The association of hepatocellular carcinoma in childhood with hepatitis B virus infection.

Eleven cases of hepatocellular carcinoma (HCC) in childhood were investigated by immunohistochemistry for association with hepatitis B virus (HBV) infection. Seven of 11 cases (64%) demonstrated positivity for hepatitis B surface antigen (HBsAG), whereas all 11 were negative for hepatitis B core antigen (HBcAG). Cirrhosis was absent in all cases, and other causes for HCC in childhood were not found. All children with HBV-associated HCC died within 6 months of diagnosis. The median survival time of these children was 2 months. Only one child with HCC of trabecular subtype without HBV association is still living after 18 months. However, this child has metastases and a local recurrence. Three other children with HCC of fibrolamellar subtype are free of disease after 2, 5, and 6 years, respectively. The high number of cases of HBV-associated HCC shows the important role of HBV infection as an etiologic factor for the development of childhood HCC in middle Europe.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Results of the SIOP 93-01/GPOH trial and study for the treatment of patients with unilateral nonmetastatic Wilms Tumor.

BACKGROUND: The treatment of Wilms Tumor is integrated into clinical trials since the 1970's. In contrast to the National Wilms Tumor Study Group (NWTSG) the SIOP trials and studies largely focus on the issue of preoperative therapy to facilitate surgery of a shrunken tumor and to treat metastasis as early as possible. PATIENTS AND METHODS: In the SIOP 93-01/GPOH trial and study 1 020 patients with a newly diagnosed renal tumor were registered. 847 of them had a histological proven Wilms Tumor, of whom 637 were unilateral localized, and 173 tumors had an other histology [40 congenital mesoblastic nephroma (CMN), 51 clear cell sarcoma (CCSK), 24 rhabdoid tumor (RTK) and 58 other tumors]. Preoperative chemotherapy in benign tumors was given to 1.3 % of the patients. The main objective of the trial was the randomized question, if the postoperative two drug chemotherapy for stage I in intermediate risk or anaplasia can be reduced from conventional 3 courses to an experimental 1 course without loss of efficacy. RESULTS: 519 patients with unilateral nonmetastatic Wilms did receive preoperative chemotherapy. The histology in this group of patients was of intermediate risk in 469 (90 %) patients, 14 (3 %) tumors were low risk and 36 (7 %) high risk. The stage distribution of the tumors was stage I in 315 (61 %), stage II N- in 126 (24 %), stage II N+ in 25 (5 %) and stage III in 36 (7 %) patients. In 17 (3 %) patients the tumor stage remained unclear. Tumor volume was measured in 487 patients before and in 402 after preoperative chemotherapy. The median tumor volume did shrink from 353 to 126 ml. The amount of volume reduction depends on the histological subtype. The event free survival (EFS) after 5 years was 91 % for all patients with unilateral Wilms tumor without distant metastasis. Randomisation was done in 43.7 % for stage I patients and there was no difference in EFS for both treatment arms (90 versus 91 %). The EFS is identical for patients with stage I and II N- (0.92), as well as for stage II N+ and III (0.82). The tumor volume after chemotherapy is a prognostic factor for intermediate risk tumors with the exception of epithelial and stromal predominant tumors. These two subtypes often present as large tumors, they do not shrink during preoperative chemotherapy but they still have an excellent prognosis. On the other hand the prognosis of patients with blastemal predominant subtype after preoperative chemotherapy is worse than in any other patient group of intermediate risk tumors. There are less blastemal predominant tumors compared to primary surgery, but they are chemotherapeutic resistant selected by the preoperative chemotherapy. CONCLUSION: Patients with unilateral Wilms tumor without metastasis have an excellent prognosis. The post-operative chemotherapy in stage I can be reduced to 4 weeks without worsening treatment outcome. The reduction of the tumor volume could be identified as a helpful marker for stratification of post-operative treatment. Post-chemotherapy blastemal predominant subtype of Wilms tumor has to be classified as high risk tumor. Focal anaplasia has a better prognosis than diffuse anaplasia and will be classified as intermediate risk tumor.

Adolescent↗

PubMedDate not supplied

Identification of various exon combinations of the ews/fli1 translocation: an optimized RT-PCR method for paraffin embedded tissue -- a report by the CWS-study group.

BACKGROUND: Chromosomal translocations t(11;22) (q24;q12) are characteristic of about 80-90 % of Ewing's sarcoma family of tumors [bone and soft tissue Ewing's sarcoma and peripheral neuroectodermal tumors (PNET)]. They generate ews/fli1 rearrangements showing great diversity in breakpoint exon combination. In about 5 % of Ewing's tumors, ews is fused to the erg gene at 21q22. The various chimeric proteins encoded may function as aberrant oncogenic transcription factors. These specific translocations can be used for exact molecular diagnosis in these poorly differentiated small round-cell tumors. Moreover, the prognostic relevance of different translocational variants has been previously suggested. Furthermore, the sensitive molecular detection of minimal metastatic and residual disease and its clinical significance can be evaluated. To address these questions more definitively in the large number of patients registered in multicenter studies, it is often necessary to access archival paraffin-embedded tumor tissue if no fresh or frozen tumor material is available for analysis by RT (reverse transcription)-PCR. Specific problems arise from formalin-fixed and paraffin-embedded tissue due to the degradation of RNA and insufficient extraction efficiency. Therefore, primer distance and product size are limited for successful PCR amplification. This conflicts with the requirement for identification of various possible exon combinations by PCR simultaneously using one single primer pair with larger distance. PATIENTS: We examined paraffin embedded soft part tumor tissue samples from 47 Ewing's tumor patients. Patients were treated according to either CWS (Cooperative Weichteilsarkomstudie, CWS-91 or CWS-96) or Euro-E.W.I.N.G. 99 therapy protocols. METHOD: We established a novel RT-PCR method, using 3 different exon specific sets of PCR primer pairs, selected according to the coding ews and fli1 nucleotide sequences (NCBI database), suitable for RT-PCR identification of variant ews/fli1 fusion transcripts in RNA isolated from formalin-fixed, paraffin-embedded tissue. For use in combination with ews -primer, an erg specific primer was selected to alternatively test for ews/erg fusion transcripts. As positive control for the integrity of isolated mRNA, we used the ubiquitously expressed gapdh transcript for RT-PCR amplification in each sample. RESULTS: In 31 cases (= 66 %) of 47 paraffin samples of Ewing's tumors analysed, gapdh control indicated adequate quality of RNA. In 16 cases no gapdh control fragment was amplifiable, nevertheless in 2 of these 16 samples distinct ews fusion products could be detected. In 23 cases we identified ews fusion transcripts. Thereof in 65 % ews exon 7 being fused to fli1 exon 6 (fusion type I), in 22 % to fli1 exon 5 (fusion type II). In 4 % each ews exon 10 being juxtaposed to fli1 either exon 6 or exon 5, respectively. An ews/erg fusion was detected in 4 % ( ews exon 7 fused to erg exon 6). In 10 samples, a gapdh fragment was amplified, but no ews/fli1 or - erg fusion transcript could be identified. The reference pathological review (I. L., Kiel, Germany) disproved the primary histopathology in 5 cases. CONCLUSIONS: Using our different sets of exon specific primer pairs, it was possible to detect 4 different breakpoints of ews/fli1 fusion transcripts and the ews/erg fusion by RT-PCR in RNA isolates from formalin-fixed, paraffin-embedded Ewing's tumor tissue. This method can be a very useful alternative in clinical situations (to ensure diagnosis and perform minimal metastatic and residual disease investigations) and in order to assess prognostic significance of translocation subtypes when no fresh tumor tissue is available.

Electrophoresis, Agar Gel↗

PubMedDate not supplied

Teratoma with malignant transformation: experiences of the cooperative GPOH protocols MAKEI 83/86/89/96.

BACKGROUND: The designation of a teratoma with malignant transformation (TMT) refers to the occurrence of somatic non-germ cell malignancies within a teratoma. While TMT is a rare but well recognised phenomenon in adult germ cell tumors (GCT), data on TMT in pediatric GCTs are lacking. PATIENTS AND METHODS: Between 1982 and 2003, 641 patients with extracranial nontesticular pure teratoma (256 coccygeal, 246 ovarian, 139 other sites) were reported to the MAKEI protocols 83/86/89/96 by various, mainly German centres. Patients with teratoma and somatic malignancy were identified by database queries. Patients with malignant germ cell tumor components were excluded from this analysis. The clinical files were reviewed and re-evaluated centrally. Information was actualized by requisition to the participating hospitals. RESULTS: We identified nine patients (all female, age 0-39 years) meeting the histological criteria of TMT. Two patients had coccygeal teratomas and seven ovarian tumors. Carcinoma was the dominating malignancy (five of nine cases). Tumors with glial differentiation and embryonal tumors occurred in two cases each. Resection was performed in seven patients (including both coccygeal tumors) and adjuvant chemotherapy was administered in one of them. Two patients relapsed after resection, but both were cured with chemotherapy. Two patients suffered from advanced tumors and both were treated with primary chemotherapy. One patient was cured from the malignant component (astrocytoma), but the teratomatous components persisted. The other patient died as a result of progression of her malignant medulloepithelioma. CONCLUSIONS: Malignant transformation of pure teratomas constitutes a very rare entity in children and adolescents that is most commonly observed in postpubertal girls with ovarian teratoma. Compared to adult patients, similar malignant entities can be observed in association with teratoma. However, in our series, no sarcoma was diagnosed. In localised tumors, complete resection appears to be adequate, whereas chemotherapy should be considered in patients with R1- or R2-resection. Cisplatinum-based chemotherapy was effective as two of four relapsed patients survived tumor free. However, the ideal regimen has not yet been established and the known sensitivity of the histologic components to cytostatic drugs has to be considered in the choice of treatment. Further molecular biologic studies are necessary to understand the origin of these tumors.

Adolescent↗