Biomedical subjects

I Leuschner

Publications and source records attributed to I Leuschner.

At least 19 recordsLinked to original sources

PubMed2007

[Sarcomatoid renal cell carcinoma. A rare and aggressive variation of primary renal cell carcinoma].

Every year, renal cell carcinoma (RCC) is responsible for the highest proportion of cancer-associated deaths in relation to all other malignant urological diseases. Initially called carcinosarcoma, the sarcomatoid differentiation confers higher aggressiveness on any of the different subtypes of RCC, with a frequency of ca. 1%. The presence of a sarcomatoid component makes the disease locally aggressive, which typically presents an advanced grade that is associated with fast progression and fatal outcome in a vast proportion of cases, with median survival lower than 1 year. This is important for predicting the outcome for patients undergoing nephrectomy due to RCC, since chemotherapy in a certain group of patients with progressive disease can be a reasonable alternative to the failure of immunotherapy in sarcomatoid renal carcinoma. We report our experience with sarcomatoid RCC in four patients with extensive tumor progression in comparison to the literature.

Adult↗

PubMed2006

[Emergent treatment of a malignant peripheral epineurial tumour].

BACKGROUND: Malignant peripheral epineurial tumours are a group of tumours that derive histomorphologically from peripheral nerve sheaths. They occur sporadically, with an incidence of approximately 0.001%, and very rarely require emergency operation. PATIENT AND PROCEDURE: An athletic 19-year-old man presented to an orthopaedic outpatient clinic with lumboischialgia and weakness of the third and fourth left toes. A 12 x 10 x 8-cm paravertebral/retroperitoneal tumour was diagnosed by CT, and the patient was referred to our clinic. For classification, CT-assisted puncture of the tumour was carried out. A haemorrhage into the tumour resulted from the puncture, with consequently lower Hb level and progressive peripheral sensomotoric deficits demanding emergency surgery on a weekend. On this occasion, the tumour was resected together with the L5 and S1 nerve roots through cooperation between the general surgical and neurosurgical departments and was classified as a malignant peripheral epineurial tumour in the rapid stage. Due to the spinal R2 resection, after-loading probes were inserted and the tumour bed was clip-marked. Percutaneous radiotherapy and brachytherapy followed postoperatively. Shortly afterwards, relaparotomy had to be performed due to an adhesive ileus, from which the patient recovered quickly. Chemotherapy was carried out due to a G2 tumour classification. The patient is currently undergoing rehabilitation, during which the peripheral neurological deficits are improving gradually. CONCLUSION: This rare case of a malignant peripheral epineurial tumour with acute symptoms demonstrates the ability of hospitals with maximum care facilities to maintain services even in times of financial cuts in health care services.

Adult↗

PubMed2006

[Reference radiology in nephroblastoma: accuracy and relevance for preoperative chemotherapy].

PURPOSE: A reference radiologic diagnosis was carried out for the purpose of quality control and in order to achieve high diagnostic accuracy in the ongoing trial and study SIOP 2001/GPOH for renal tumors during childhood. The aim of the present study is to evaluate the value of diagnostic imaging and the benefit of reference evaluation at a pediatric radiology center. MATERIALS AND METHODS: In 2004 the imaging studies of 97 patients suspected of having a renal tumor were presented at the beginning of therapy. Diagnostic imaging was compared to the primary imaging results and the histological findings and was analyzed in regard to the therapeutic consequence (primary chemotherapy without prior histology). 77 MRI, 35 CT and 67 ultrasound examinations of 47 girls and 50 boys (mean age 4 years; one day to 15.87 years old) were analyzed. In addition to the histological findings, the reference pathological results were submitted in 86 cases. Results from the primary imaging corresponding to the histology and results from the reference radiology corresponding to the histology were statistically compared in a binomial test. RESULTS: In 76 of the reference-diagnosed Wilms' tumors, 67 were confirmed histologically. In 72 cases preoperative chemotherapy was initiated. In 5 cases neither a Wilms' tumor nor a nephroblastomatosis was found. 16 of 21 cases (76 %) with reference-diagnosed non-Wilms' tumors were selected correctly. The results of the primary imaging corresponded to the histology in 71 cases, and those of the reference radiology in 82 cases. The statistical evaluation showed that the results of the reference radiology were significantly better (p = 0.03971). CONCLUSION: Reference radiological evaluation improved the diagnostic accuracy with therapeutic relevance. The differentiation of different renal tumors is not completely possible using imaging methods. The rate of patients with false preoperative chemotherapy for all renal neoplasms is currently 5.2 % and 1 % for benign renal tumors.

Antineoplastic Agents↗

PubMed2005

[Childhood kidney tumors -- the relevance of imaging].

Kidney tumors represent 6.2% of malignant tumors in children. History, clinical course and radiological findings are necessary elements in the differential diagnosis of the different renal tumors. In the case of nephroblastoma, chemotherapy is based solely on the radiological diagnosis without prior histology. In therapy-optimizing studies of the Society of Pediatric Oncology and Hematology, preoperative chemotherapy is performed. Therapy monitoring is performed in the course of and after preoperative chemotherapy to verify tumor response. Radiological staging plays a significant role in deciding on further treatment and in operative planning. Three-dimensional visualization of the abdominal situs can assist preoperative planning. In summary, diagnostic imaging in renal tumors in children plays a role in differential diagnosis, staging, monitoring of therapy, and surgical planning.

Abnormalities, Multiple↗

PubMed2005

[Decreased number of R1-resections in radical retropubic prostatectomy. Use of a newly developed fast sectioning technique].

Therapeutic success and prognosis in RRP is determined by negative surgical margins. In order to minimize the proportion of positive surgical margins in the final histological evaluation, valid intraoperative control by means of frozen margin analysis is indispensable. We have developed and evaluated a new frozen margin procedure based on the Stanford method with transverse and sagittal cut directions. This technique facilitates comprehensive intraoperative evaluation of curved margin areas for the first time. Retrospective analysis of the results of the new frozen section technique revealed positive surgical margins in 2.7% of patients. The results obtained with this new technique were significantly superior to those obtained with two established techniques (10.3%, P < or =0.001; 17.2%, P < or =0.001). Our results demonstrate that the new frozen margin technique is clearly more sensitive for intraoperative detection of positive margins and thus leads to substantially higher rates of negative surgical margins.

Cryoultramicrotomy↗

PubMed2005

[MRI-morphology and staging of congenital mesoblastic nephroma: evaluation of a collection with 20 patients].

PURPOSE: To differentiate classic and cellular type of congenital mesoblastic nephroma (CMN) in MRI and to evaluate MRI for staging according to the Societe Internationale de Oncologie Pediatrique (SIOP). MATERIAL AND METHODS: MRI examinations of 20 children with CMN (age 1st to 16th months, classic type n = 11, cellular type n = 7, mixed type n = 2) were analyzed retrospectively. Cysts, necrosis, hemmorhage in the tumor, signal intensity, tumor structure, thrombosis and dilatation of renal vein, crossing of the body midline, peripheral contrast-enhancement, tumor volume and existence of a tumor pseudocapsule in contrast to the residual kidney were described. The radiologic stage was compared with the histopathologic stage (infiltration of perirenal fat and infiltration of the renal sinus). RESULTS: Tumors of the classic type (mean volume 67.9 ml) had necrosis in 1 case, crossed the midline in 1 case, had no cysts or bleeding, and had a peripheral contrast-enhancement in 1 case, and were heterogeneous in 9 cases. The cellular type (mean volume 302.8 ml) had tumor necrosis in 6 cases, bleeding in 3 cases, cysts in 3 cases, crossed the midline in 4 cases, and peripheral contrast enhancement in 2 cases, and was predominantly heterogeneous. Mixed tumor types (7 ml and 202 ml) had tumor necrosis in 1 case and crossed the midline in 1 case, a peripheral contrast enhancement in 2 cases and a homogenous structure in 1 case. The signal intensity in T1 w and T2 w images was not specific. The renal vein was inconspicuous in all children. The evaluation of the infiltration in perirenal fatty tissue was true positive in 1 case, true negative in 10 cases, false negative in 4 cases and false positive in 5 cases. The infiltration of the renal hilus was true positive in 10 children, false positive in 8 cases and true negative in 2 cases. CONCLUSION: A typical finding of CMN in MRI is a heterogeneous tumor without demarcation from the rest of the kidney parenchyma by a pseudocapsule. The cellular type of CMN tends to have a higher tumor volume and shows more necrosis, bleeding and cysts than the classic type in MRI. A peripheral contrast-enhancement in MRI is not characteristic for any type of CMN. Local tumor staging is not possible with MRI.

Diagnosis, Differential↗

PubMed2004

Survival in nephroblastoma treated according to the trial and study SIOP-9/GPOH with respect to relapse and morbidity.

BACKGROUND: Recent Wilms' tumor (WT) trials and studies have tried to determine the minimal therapy needed for cure. The goal was survival without morbidity. PATIENTS AND METHODS: From January 1989 to March 1994 the German Society of Pediatric Oncology and Hematology registered 440 patients (median age 2.9 years; 231 male, 209 female) with WTs (preoperative chemotherapy 362) for therapy according to the International Society of Pediatric Oncology Trial and Study 9. Therapy for relapse depended on site of relapse and therapy already received. Follow-up included inquiries for morbidity. Prognostic factors for relapse and death were evaluated. RESULTS: Five-year survival of WTs was 89.5%; 98.2% (385 of 392) of survivors had a follow-up of 5 years (range 0.8-12.6; median 8). In non-anaplastic WTs, young age (<2 years) was of significance (P = 0.026) for a better survival. Non-anaplastic WTs (407 patients) had a 5-year survival of 92.3%, versus 48.5% in anaplastic WTs (33 patients), and a 5-year relapse-free survival of 87.6% versus 42.4%. Survival after relapse was significantly worse for anaplastic than for non-anaplastic WTs (residual 3-year survival 11.8% versus 54.3%; P <0.0001). In preoperatively treated WTs, anaplasia was a strong prognostic factor for death [relative risk (RR) 4.7], followed by poor response to preoperative therapy (RR 3.6), stage IV (RR 3.2) and abdominal stage III (RR 2.2). Low abdominal stages (<III) dominated (280 versus 82). In the 334 unilateral stage I-IV WTs (median age 3.2 years), diffuse anaplasia (21 patients) had a 5-year relapse-free survival of 38.1%, versus 58.4% in blastemal WTs (25 patients); survival was 42.9% in diffuse anaplasia versus 84% in blastemal WTs. None of 46 patients (median age 1.9 years; 91.3% stages I or II) with differentiated WTs (nine epithelial, 37 stromal) relapsed despite their non-response; two died (one therapy related, one due to bilaterization). In the 25 non-anaplastic bilateral WTs, differentiated cases (one epithelial, eight stromal, 33.3% abdominal stage III) were more frequent (P = 0.048) than in unilateral WTs (one stromal, abdominal stage III relapsed). In all, 52.9% of the 5-year survivors had received adriamycin (250-400 mg/m(2)), 25.7% radiation, 6.4% ifosfamide (24-30 g/m(2)) and 6.7% carboplatin plus etoposide. Abnormal parameters according to the National Cancer Institute score were seen in 18.9% during follow-up, but only 6.4% were treated for morbidity at the end of follow-up. Three WTs developed renal failure due to Drash syndrome, but none due to tumor therapy. After adriamycin 1.9% of WTs (9% of those receiving 400 mg/m(2)) required therapy for cardiac toxicity. CONCLUSIONS: Initial therapy should be more individualized, taking the above risk groups (age in non-anaplastic WTs, poor response, anaplasia, etc.) into account, as morbidity even after relapse therapy with ifosfamide, carboplatin and etoposide was not high. Milder therapy in low stages of differentiated and of well responding WTs should be tested.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Overexpression of phosphatidylinositol 3-kinase in human lung cancer.

BACKGROUND: This study was conducted to investigate the expression of phosphatidylinositol 3-kinase (PI3K) and AKT2, a downstream effector, in primary human lung carcinomas of different histological type. METHODS: Specimens from 105 human lung carcinomas and their corresponding lymph nodes and liver metastases were examined using immunohistochemistry and Northern-blot assays to study the PI3K p85 and p110 subunits and the AKT2-expression patterns. RESULTS: The p85 and p110 subunits of PI3K were overexpressed at the protein level in 77% and 59% of 80 primary lung carcinomas, respectively, irrespective of the histological type. PI3K overexpression was correlated with tumor grading. In contrast, no overexpression of PI3K subunits was observed in normal lung tissue and benign lung tumors. Consistent with these findings, upregulation of p110 mRNA transcripts was restricted to primary lung carcinomas. Overexpression of AKT2 was observed in 10% of the investigated lung tumor specimens, but in none of the healthy lung sections. A profound increase of PI3K expression was uniformly observed in lung tissue specimens and in corresponding extra-pulmonary lymph-node and liver metastases with low-differentiation grades. CONCLUSION: PI3K appears to be associated with the process of tumor-cell transformation and proliferation. One of its major downstream effector molecules, AKT2, which contributes to apoptotic cell death, was not upregulated by PI3K overexpression in primary lung carcinomas.

Adult↗

PubMed2001

Clinical impact of histologic subtypes in localized non-anaplastic nephroblastoma treated according to the trial and study SIOP-9/GPOH.

BACKGROUND: Histologic subtypes of standard histology Wilms' tumor (WT) and the effect of preoperative therapy on their clinical and histologic features, deserve to be analysed in respect to outcome to find an adequate baseline for therapy. PATIENTS AND METHODS: The German Society of Paediatric Oncology & Haematology enrolled patients from January 1989 to March 1994 for therapy according the International Society of Paediatric Oncology trial & study 9. Standardised preoperative therapy with dactinomycin and vincristine for 4-8 weeks was generally applied in patients between 0.5 and 16 years with localized renal tumors and imaging typical for WT. In 99.5% of cases representative material was sent for review to the Kiel Paediatric Tumour Registry. For prospective subtyping of 329 WT (258 after preoperative therapy, 71 with immediate surgery) modified Beckwith & Palmer criteria were used. Reduction in volume measured by imaging prior to chemotherapy and surgery was used to assess response (poor response: reduction < 40%; good response: reduction > or = 40%). RESULTS: There were 39% of patients treated with immediate surgery and 12.4% of patients with preoperative therapy in the age group up to 12 months. The difference in age (P = 0.022) was linked with different amounts of epithelial WT (15.5% vs. 3.1%), median age: 0.58 and 0.93 years. Due to the effect of chemotherapy the amount of other WT changed: stromal 0% to 14%, mixed 45.1% to 29.4%, blastemal 39.4% to 9.3%). After preoperative therapy 37.6% of WT were predominantly regressive, 6.6% completely necrotic. Poor response was frequent in differentiated WT (86% of stromal, 75% of epithelial WT) but none relapsed. In the other WT with viable tumor left after preoperative therapy > 70% had good response, poor response was a risk factor (P = 0.0057). CONCLUSIONS: Subtyping according modified Beckwith & Palmer can be used in WT after preoperative therapy to stratify postoperative therapy in future. A milder therapy could be tested in differentiated WT at low stages and an intensified in the others with viable tumor left and poor response, i.e., mainly blastemal WT.

Adolescent↗

PubMed2001

Rhabdomyosarcoma of the urinary bladder and vagina: a clinicopathologic study with emphasis on recurrent disease: a report from the Kiel Pediatric Tumor Registry and the German CWS Study.

Rhabdomyosarcomas (RMS) of the urinary bladder and vagina vary in their biologic and clinical behavior and require different types of treatment. Anatomically the two organs are close, and the reason for these differences in behavior is unknown. We investigated tumor specimens of 51 urinary bladder RMS and 14 vaginal RMS with regard to histologic subtype, growth pattern, differentiation, and proliferation morphologically and immunohistochemically. Recurrences and/or "second look" specimens from 15 patients after chemotherapy were compared with the primary tumors. Within the 65 specimens we found 31 "classical" embryonal RMS, 26 embryonal RMS of botryoid subtype (BRMS), 3 embryonal RMS of spindle cell subtype, and 5 alveolar RMS. BRMS is more common in the vagina (11 BRMS of 14 cases) than in the urinary bladder RMS (15 BRMS of 54 cases). Classical embryonal RMS with a polypoid (exophytic) growth pattern is associated with a more favorable prognosis (92% 10-year survival) than the same type with a diffuse intramural (endophytic) growth pattern (68% 10-year survival, p = 0.02). The proliferation rate was associated with the degree of differentiation, but neither showed a correlation with prognosis. A marked maturation after chemotherapy was seen in the majority of recurrences and SL specimens, associated with lowered proliferation activity. Two of 12 patients with recurrences showing chemotherapy-induced maturation died of the disease. In conclusion, we determined that polypoid embryonal RMS of both the urinary bladder and the vagina have a comparably good prognosis. This includes all botryoid RMS. The poorer prognosis of the group of urinary bladder RMS as a whole was caused by a high incidence of diffusely growing RMS, which have a less favorable prognosis than polypoid RMS. Maturation after chemotherapy occurs frequently in RMS. In contrast to the excellent prognosis reported in other studies, we had two patients with fatal outcome despite chemotherapy-induced maturation in the recurrences.

Adolescent↗

PubMed2000

Combretastatin A-4 prodrug: a potent inhibitor of malignant hemangioendothelioma cell proliferation.

Anti-vascular treatment by targeting proliferating endothelial cells has become a promising option in anti-neoplastic therapy. Combretastatin A-4 prodrug (CA-4PD) has been identified as a selective inhibitor of endothelial cell proliferation, acting by the interruption of microtubule assembly. In this study, the effect of CA-4PD on proliferating endothelial cells derived from a primary tumor of the vascular endothelium was investigated in vitro and in vivo. In vitro, CA-4PD was an effective inhibitor of endothelial cell proliferation in a time- and dose-dependent manner, displaying a certain selectivity toward endothelial cells in comparison to proliferating fibroblasts. Analysis of DNA profiles by FACS revealed an increasing proportion of cells arrested in the G(2) cell-cycle phase with correlation to the duration of drug exposure. A decrease in cell viability correlated with duration of drug exposure, whereas FACS analysis, DNA fragmentation assay, and DNA gel electrophoresis failed to demonstrate that DNA fragmentation was indicative of apoptosis up to 48 hr of continued drug exposure. In vivo, CA-4PD induced excessive regressive alterations in experimentally allotransplanted hemangioendotheliomas within 24 hr after singular i. p. injection of 100 mg CA-4PD/kg body weight. This represented less than one-tenth of the maximum tolerated dose. In conclusion, our findings characterize CA-4PD as a potent inhibitor of malignant endothelial cell proliferation in vitro, effecting arrest of proliferating cells in the G(2) cell-cycle phase with subsequent cell death on a pathway different from apoptosis. in vivo, CA-4PD induces extensive intratumoral cell loss within 24 hr following systemic administration, suggesting a synergistic effect of direct cell killing and the induction of vascular shutdown.

Animals↗

PubMed2000

[Improvement of transrectal ultrasound. Artificial neural network analysis (ANNA) in detection and staging of prostatic carcinoma].

As a result of the enhanced clinical application of prostate specific antigen (PSA), an increasing number of men are becoming candidates for prostate cancer work-up. A high PSA value over 20 ng/ml is a good indicator of the presence of prostate cancer, but within the range of 4-10 ng/ml, it is rather unreliable. Even more alarming is the fact that prostate cancer has been found in 12-37% of patients with a "normal" PSA value of under 4 ng/ml (Hybritech). While PSA is capable of indicating a statistical risk of prostate cancer in a defined patient population, it is not able to localize cancer within the prostate gland or guide a biopsy needle to a suspicious area. This necessitates an additional effective diagnostic technique that is able to localize or rule out a malignant growth within the prostate. The methods available for the detection of these prostate cancers are digital rectal examination (DRE) and Transrectal ultrasound (TRUS). DRE is not suitable for early detection, as about 70% of the palpable malignancies have already spread beyond the prostate. The classic problem of visual interpretation of TRUS images is that hypoechoic areas suspicious for cancer may be either normal or cancerous histologically. Moreover, about 25% of all cancers have been found to be isoechoic and therefore not distinguishable from normal-appearing areas. None of the current biopsy or imaging techniques are able to cope with this dilemma. Artificial neural networks (ANN) are complex nonlinear computational models, designed much like the neuronal organization of a brain. These networks are able to model complicated biologic relationships without making assumptions based on conventional statistical distributions. Applications in Medicine and Urology have been promising. One example of such an application will be discussed in detail: A new method of Artificial Neural Network Analysis (ANNA) was employed in an attempt to obtain existing subvisual information, other than the gray scale, from conventional TRUS and to improve the accuracy of prostate cancer identification.

Adult↗

PubMed2000

An improved orthotopic xenotransplant procedure for human lung cancer in SCID bg mice.

BACKGROUND: Overall prognosis in human lung cancer is still poor. A highly reproducible, easy to perform in vivo model, which closely resembles the clinical features of advanced human lung cancer, is required for the evaluation of novel therapies. METHODS: Tumor cells, originated from a human adenocarcinoma, a squamous cell carcinoma, and an undifferentiated large cell carcinoma, were xenotransplanted heterotopically by subcutaneous and intravenous injection and compared with orthotopic intrapleural and intrapulmonary xenotransplantation by a facilitated engraftment procedure into SCID bg mice. RESULTS: Subcutaneous injection of tumor cells resulted in a 100% engraftment rate with establishment of solid tumors without clinically relevant metastases. Intravenous injection had poor engraftment rates by hematogenous spread. Depending on the cell line, a 80% to 100% engraftment rate in orthotopic xenotransplantation was achieved, resulting in a consistent pattern of mediastinal and bilateral pulmonary metastases. CONCLUSIONS: The facilitated orthotopic xenotransplantation of human lung cancer is easy to perform and results in a reproducible in vivo model that closely resembles the clinical features of advanced human lung cancer. Consequently, this model appears suitable for in vivo evaluation of novel cancer therapies in preclinical tests.

Adenocarcinoma↗

PubMed1999

Artificial neural network analysis (ANNA) of prostatic transrectal ultrasound.

BACKGROUND: Our purpose was to determine the diagnostic potential of a new, computerized method of interpreting transrectal ultrasound (TRUS) information by artificial neural network analysis (ANNA). This method was developed to resolve the current dilemma of visual differentiation between benign and malignant tissue on TRUS. To train and objectively evaluate ANNA, a new precise method of computerized virtual correlation of preoperative ultrasound findings and radical prostatectomy histopathology was devised. After training with this pathologically confirmed digitized TRUS information, ANNA was tested in a blinded study. METHODS: Following radical prostatectomy, 289 pathology whole-mount sections of 61 patients were correlated digitally with the corresponding TRUS slices. Specific selection of TRUS areas unequivocally identified on the correlated digitized pathohistology resulted in 553 pathology-confirmed representations (samples). Of these, 53 were used for training and 500 were subjected to blind analysis by ANNA. RESULTS: ANNA classified 378 (99%) of the 381 benign pathology-confirmed samples correctly as benign. The false-positive rate was 1% (n = 3). Of the 119 pathology-confirmed malignant samples, 94 (79%) were classified correctly; 25 (21%) were falsely classified as normal. Out of all 119 cancers, ANNA classified 60 (71%) of the hypoechoic cancers as malignant and 24 (29%) as benign. Surprisingly, 34 (97%) of the isoechoic cancers were correctly classified by ANNA, missing only one sample. CONCLUSIONS: The introduction of ANNA enhanced the accuracy of TRUS prostate cancer identification. Although not all malignant areas were detected, cancer was detected in each patient. The ability to detect isoechoic cancerous lesions appears to be the essential innovation over conventional TRUS interpretation.

Aged↗

PubMed1999

Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the beta-catenin gene.

Hepatoblastomas (HBs) are embryonal tumors affecting young children and representing the most frequent malignant liver tumors in childhood. The molecular pathogenesis of HB is poorly understood. Although most cases are sporadic, the incidence is highly elevated in patients with familial adenomatous polyposis coli. These patients carry germline mutations of the APC tumor suppressor gene. APC controls the degradation of the oncogene product beta-catenin after its NH2-terminal phosphorylation on serine/threonine residues. APC, as well as beta-catenin, has been found to be a central effector of the growth promoting wingless signaling pathway in development. To find out if this pathway is involved in the pathogenesis of sporadic HBs, we examined 52 biopsies and three cell lines from sporadic HBs for mutations in the APC and beta-catenin genes. Using single-strand conformational polymorphism analysis, deletion screening by PCR, and direct sequencing, we found a high frequency of beta-catenin mutations in sporadic HBs (48%). The mutations affected exon 3 encoding the degradation targeting box of beta-catenin leading to accumulation of intracytoplasmic and nuclear beta-catenin protein. The high frequency of activating mutations in the beta-catenin gene indicates an important role in the pathogenesis of HB.

Adolescent↗

PubMed1999

Paclitaxel: an effective antineoplastic agent in the treatment of xenotransplanted hepatoblastoma.

BACKGROUND: Hepatoblastoma is an uncommon liver tumor of infancy and early childhood. Though most patients with nonmetastatic hepatoblastomas can be cured by defining surgical strategies and chemotherapy regimes, new drugs are needed for children with advanced hepatoblastomas. The activity of paclitaxel as a new antineoplastic agent with limited experience in pediatric oncology was studied in a xenograft model. PROCEDURE: Hepatoblastoma cell suspensions from three children were transplanted subcutaneously into nude mice NMRI (nu/nu). One of the primary tumors was an embryonal multifocal hepatoblastoma, whereas the other tumors were embryonal/fetal hepatoblastomas localized on a liver lobe. After 4 weeks, xenografted tumor sizes reached 50-100 mm3. The xenografted tumors resembled their originals histologically and produced high levels of alpha-fetoprotein. The efficiency of paclitaxel at equitoxic doses was analyzed. RESULTS: Paclitaxel produced an effect in all three hepatoblastomas. There was a significant reduction of tumor volume (P < 0.001) and alpha-fetoprotein levels after chemotherapy (P < 0.0001). The proliferation activity of the tumor cells corresponded with these results. Histologically, after treatment with paclitaxel the tumor regression was 35%-49%. The mechanism of paclitaxel action could be demonstrated by light microscopy immunohistochemistry and electron microscopy. CONCLUSIONS: The preliminary results in phase I trials of solid tumors in children and the results of this study suggest that paclitaxel in phase II studies can now be entertained for patients with hepatoblastoma.

Animals↗

PubMed1999

[Pathology of childhood and adolescent rhabdomyosarcoma].

Rhabdomyosarcoma (RMS) is the most important and a very heterogeneous group of malignant soft tissue tumors of childhood and adolescence. The two major subtypes (embryonal and alveolar) share a common myogenic differentiation, but seem to be histogenetically not related. The so-called 'International Classification of Rhabdomyosarcoma' includes, besides the two major subtypes, the botryoid and leiomyomatous subtypes of embryonal RMS which are associated with a better prognosis and are treated less aggressively according to current protocols. In addition, the solid variant of alveolar RMS is included in the alveolar group of RMS. The identification of the various subtypes is necessary and important because the treatment with the current protocols is also related to histology. Using conventional stains and immunohistochemistry, these subtypes are distinguishable. Genetic analysis can be helpful in the demonstration of t(2;13) or t(1;13) translocations in alveolar RMS. The identification of alveolar RMS with t(1;13) translocation might become important in the future, because this type of translocation seems to be related to a better prognosis as compared to tumors with a t(2;13) translocation.

Adolescent↗

PubMed1999

A comparison of MyoD1 and fetal acetylcholine receptor expression in childhood tumors and normal tissues: implications for the molecular diagnosis of minimal disease in rhabdomyosarcomas.

Detection of minimal residual disease or micrometastases in rhabdomyosarcoma (RMS) has been an unresolved problem in 70 to 80% of RMS patients. In patients with alveolar type RMS, which harbors chromosomal translocations and produces tumor-specific fusion products, polymerase chain reaction (PCR)-based diagnosis is clear-cut. In the more frequent embryonal RMS, however, no such PCR-based marker has been described. Recently it has been suggested that the PCR-based detection of MyoD1 may be a valuable adjunct in the diagnosis of minimal disease in embryonal RMS. We report here that MyoD1 mRNA is not specific for RMS, but can be amplified from ex vivo samples of many other childhood tumors and some normal tissues. By contrast, simultaneous amplification of alpha and gamma subunit message of the fetal type acetylcholine receptor (AChR), by a novel duplex PCR, and the quantification of both transcripts resulting in a alpha/gammaAChR ratio <1 was 100% sensitive in alveolar (n = 8) and embryonal (n = 10) RMS. Moreover, gammaAChR was not detected in other childhood (n = 27) or adult tumors (n = 12), or normal tissues, except thymus. The high sensitivity and specificity of the method were confirmed by the successful detection of five cases of cytologically or molecularly verified RMS bone marrow micrometastases among 47 bone marrow samples from childhood tumor patients. By contrast, MyoD1 showed no amplification because of its low level of transcription. We conclude that mRNA of the fetal type AChR is a more specific and (about 100 times) more sensitive marker for the molecular detection of RMS than MyoD1, and thus appears to be a promising candidate for the detection of minimal disease in RMS lacking tumor-specific translocations.

Base Sequence↗