An undifferentiated sarcoma with BCOR-CCNB3 fusion transcript - pathological and clinical retrospective study.

The BCOR-CCNB3 positive sarcoma is a recently identified sarcoma morphologically and clinically similar to Ewing sarcoma in adolescents and young adults. The BCOR-CCNB3 fusion transcript originates from a paracentric inversion on the X chromosome with an in-frame fusion between the last codon of BCOR and the exon 5 of CCNB3 gene. We report morphological and molecular genetic analysis of 8 undifferentiated sarcomas positive for the BCOR-CCNB3 fusion. Six of the eight BCOR-CCNB3 positive sarcoma patients were male. Five of the eight patients were in their second decade of life (median of all patients 14 years at diagnosis). The bone marrow involvement was demonstrated in 2 of 4 patients tested. Detection of the fusion transcripts BCOR-CCNB3 in the bone marrow suggests that patients with positive findings are at high risk of the tumor progression.

The role of sibutramine in weight reduction.

BACKGROUND: The effectiveness of pharmacologic support with sibutramine along with the preservation of dietary and regimen measures is shown in a group of long-term treated patients at the Metabolic Clinic of the University Hospital in Hradec Králové. METHODS: In ambulatory patients, basic anthropometric parameters as body weight, BMI, waist circumference and the total amount of adipose tissue were compared before substitution with 10 mg sibutramine and after a four-month therapy. This group included 94 patients who were administered the same dose of sibutramine for the whole period of time. This group consisted of 37 men and 57 women. RESULTS: After a four-month therapy with sibutramine there was a mean reduction in weight by 7.9 ± 3.8 kg in the monitored group of patients. Their BMI was reduced by 2.3 ± 1.5 kg/height2 and the waist circumference by 4.4 ± 3.8 cm. The decrease in the percentage of the total body lipid was 2.9 %. CONCLUSION: Despite a surprising decision of the European Drug Agency to suspend the registration of sibutramine in the whole of Europe since January 2010 we can state that in our patients we have proven a positive effect of sibutramine substitution on their weight reduction (Tab. 1, Ref. 19).

Rhabdomyosarcoma: molecular analysis of Igf2, MyoD1 and Myogenin expression.

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. There are two major histopathological types of RMS ­ embryonal (eRMS) and alveolar (aRMS). A molecular study of Igf2, MyoD1 and Myogenin was performed to determine the expression profiles and to assess the possible utility of these genes as potential treatment targets. Patients with RMS showed up to 100-fold increase of Igf2 transcription in comparison with normal skeletal muscle. Our data suggest that overexpression of Igf2 occurs in RMS of both histological subtypes. No correlation between the results of Igf2 mRNA expression and LOH at the 11p15 region (p= 0.12) was observed, but there was a trend of a higher expression of Igf2 mRNA in RMS samples with LOH. We observed a high level of MyoD1 mRNA in both aRMS and eRMS, and we detected a similar level of MyoD1 mRNA in RMS and normal skeletal muscles. There was a correlation between the results of MyoD1 mRNA expression and LOH at the 11p15 region.We did not observe any statistical difference in the level of Myogenin mRNA in the subgroups of RMS. Analogous to MyoD1, we observed a similar level of Myogenin mRNA in RMS and normal skeletal muscles.

[Radical surgery and intensive chemotherapy are necessary for successful treatment of osteosarcoma]. / Radikální operacní výkon a intenzivní chemoterapie jsou podmínkou úspesné lécby osteosarkomu.

BACKGROUND: We evaluated the therapeutic results in 44 patients (17 girls and 27 boys) with osteosarcoma from 1997 to 2006.Their average age was 12.8 years (2.5-20.2). 41 patients had localised disease and 3 had primary metastases. PATIENTS AND METHODS: We treated our 44 patients using CCG 7921 POG 9351 INT 0133, the therapeutic protocol of the North American cooperative Children's Oncology Group.The median of the follow up was 5.5 years (2-11 years). RESULTS: 40 patients went into complete remission. 19 patients suffered relapses. Of these, 17 patients died - 15 progressed, 1 died due to treatment-related toxicity, 1 died due to secondary acute myeloid leukaemia. As a whole, the patients had a 5-year overall survival rate (OS) of 58.4% and a 5-year event free survival rate (EFS) of 46.7%. The patients with localised extremity osteosarcoma (n = 40) had a 5-year EFS rate of 51%. The patients with good histological response (n = 22) had a 5-year EFS rate of 63.6%, while patients with poor histological response (n = 18) achieved a 5-year EFS rate of 30.5% (p = 0.009). CONCLUSION: The results of treatment of patients with localised extremity osteosarcoma and patients with good histological response to preoperative treatment were very good. The prognosis of patients with axial localisation and metastatic involvement was poor.

Significance of P-glycoprotein expression in childhood malignant tumors.

Resistance to chemotherapy significantly affects the treatment results in various cancers. Multidrug resistance caused by P-glycoprotein expression is now widely studied in human malignancies. We present the results of P-glycoprotein expression examination in 91 tumor tissue samples obtained from children treated for different malignant tumors in the Dept. of Pediatric Oncology, Prague. The correlation between the level of P-glycoprotein expression and tumor histology, clinical outcome, use of therapy, relapse rate and metastatic disease was made. P-glycoprotein expression was found significantly more frequent in soft tissue sarcomas, neuroblastomas, and hepatoblastomas, and generally in disseminated disease. On the contrary, a high expression of P-glycoprotein was not found in malignant brain tumors and nephroblastomas. The data strongly support the possibility that the percentage of P-glycoprotein expressing cells in selected tumors (soft tissue sarcomas, neuroblastomas), may have a clinical importance.

[Mediastinal teratomas in children]. / Mediastinální teratomy u detí.

The objective of the work is a clinical and histopathological retrospective study of rare mediastinal teratomas in children. The authors present their experience with the treatment of eight children within the range from neonates to the age of 15 years with a histologically confirmed diagnosis of mediastinal teratoma. In two neonates the first symptom was postnatal dypnoea, teratomas in older children were diagnosed along with symptoms of acute respiratory infection. Complete resection of the tumor was performed in all patients, in neonates emergency operations were involved. Four tumors were histologically classified as mature teratomas, three as differentiated teratomas with an immature component and one as a malignant teratoma. The malignant teratoma contained mature tissues as well as tissues of embryonic carcinoma and a yolk sac tumor. Seven children with a mature or differentiated teratoma are without signs of disease 5-15 years after surgery. During the follow-up of the 15-year-old boy with the malignant teratoma the elevated alpha-fetoprotein serum level was evidence of a relapse of the disease after termination of comprehensive treatment. From the results ensues that radical extirpation is sufficient treatment for mature and differentiated teratomas. Malignant teratomas are indicated for primary resection and postoperative chemotherapy. Long-term follow up of alpha-fetoprotein and human beta-choriogonadotropin levels, clinical controls and controls by imaging methods are indicated in children with an immature or malignant component of the tumor.

Langerhans cell histiocytosis of vulva in adolescent.

Langerhans cell histiocytosis (LCH) affecting child vulva alone is a very rare disease. Only 13 cases of primary vulvar LCH have been previously reported in the medical literature. We describe an additional case in which the LCH was confined to the vulva, with review of the literature. A 16.5-year-old girl presented with papulous and ulcerative lesions on her labia majora and minora. The biopsy revealed a typical histopathologic finding consistent with LCH. A metastatic work-up did not reveal any evidence of the disease except on the vulva. Treatment was carried out according to LCH II protocol. The patient was diagnosed with a recurrent disorder in the vulva 8 months after the completion of primary chemotherapy. For this reason, she underwent second line treatment with 2-chlorodeoxyadenosine. Eighteen months after the second line chemotherapy, the patient has no signs of a local or systemic recurrence. Primary LCH of vulva is very unusual, but we have to keep in mind this possibility when an adolescent girl presents with an atypical chronic lesion on the vulva. This patient appears to be the first case of adolescent 16.5 year old having a solely cutaneous lesion of the vulva.