The first investigation of Wilms' tumour atomic structure-nitrogen and carbon isotopic composition as a novel biomarker for the most individual approach in cancer disease.

The paper describes a novel approach to investigating Wilms' tumour (nephroblastoma) biology at the atomic level. Isotope Ratio Mass Spectrometry (IRMS) was used to directly assess the isotope ratios of nitrogen and carbon in 84 Wilms' tumour tissue samples from 28 cases representing the histological spectrum of nephroblastoma. Marked differences in nitrogen and carbon isotope ratios were found between nephroblastoma histological types and along the course of cancer disease, with a breakout in isotope ratio of the examined elements in tumour tissue found between stages 2 and 3. Different isotopic compositions with regard to nitrogen and carbon content were observed in blastemal Wilms' tumour, with and without focal anaplasia, and in poorly- and well-differentiated epithelial nephroblastoma. This first assessment of nitrogen and carbon isotope ratio reveals the previously unknown part of Wilms' tumour biology and represents a potential novel biomarker, allowing for a highly individual approach to treating cancer. Furthermore, this method of estimating isotopic composition appears to be the most sensitive tool yet for cancer tissue evaluation, and a valuable complement to established cancer study methods with prospective clinical impact.

Hepatoblastoma Biology Using Isotope Ratio Mass Spectrometry: Utility of a Unique Technique for the Analysis of Oncological Specimens.

INTRODUCTION: Hepatoblastoma is the most common primary liver tumor in children. However, it occurs rarely, with an incidence of 0.5-1.5 cases per million children. There is no clear explanation of the relationship between clinicopathologic features, therapy, and outcome in hepatoblastoma cases, so far. One of the most widely accepted prognostic factors in hepatoblastoma is histology of the tumor. The aim of the study was to determine the potential differences in biology of hepatoblastoma histological subtypes at the atomic level using the unique method of isotope ratio mass spectrometry, which is especially valuable in examination of small groups of biological samples. MATERIAL/METHODS: Twenty-four measurements of nitrogen stable isotope ratio, carbon stable isotope ratio and total carbon to nitrogen mass ratio in fetal and embryonal hepatoblastoma tissue were performed using a Sercon 20-22 Continuous Flow Isotope Ratio Mass Spectrometer (CF-IRMS) coupled with a Sercon SL elemental analyzer for simultaneous carbon-nitrogen-sulfur (NCS) analysis. RESULTS: A difference of about 1.781‰ in stable nitrogen isotope 15N/14N ratio was found between examined hepatoblastoma histological subtypes. CONCLUSIONS: The prognosis in liver tumors cases in children may be challenging particularly because of the lack of versatile methods of its evaluation. Isotope ratio mass spectrometry allows one to determine the difference between hepatoblastoma histological subtypes and clearly indicates the cases with the best outcome.

Evaluation of potential prognostic value of Bmi-1 gene product and selected markers of proliferation (Ki-67) and apoptosis (p53) in the neuroblastoma group of tumors.

INTRODUCTION: Cancer in children is a very important issue in pediatrics. The least satisfactory treatment outcome occurs among patients with clinically advanced neuroblastomas. Despite much research, the biology of this tumor still remains unclear, and new prognostic factors are sought. The Bmi-1 gene product is a currently highly investigated protein which belongs to the Polycomb group (PcG) and has been identified as a regulator of primary neural crest cells. It is believed that Bmi­1 and N-myc act together and are both involved in the pathogenesis of neuroblastoma. The aim of the study was to assess the potential prognostic value of Bmi-1 protein and its relations with mechanisms of proliferation and apoptosis in the neuroblastoma group of tumors. MATERIAL/METHODS: 29 formalin-fixed and paraffin-embedded neuroblastoma tissue sections were examined using mouse monoclonal antibodies anti-Bmi-1, anti-p53 and anti-Ki-67 according to the manufacturer's instructions. RESULTS: There were found statistically significant correlations between Bmi-1 expression and tumor histology and age of patients. CONCLUSIONS: Bmi-1 seems to be a promising marker in the neuroblastoma group of tumors whose expression correlates with widely accepted prognostic parameters. The pattern of BMI-1 expression may indicate that the examined protein is also involved in maturation processes in tumor tissue.

Prognostic significance of MCM 2 and Ki-67 in neuroblastic tumors in children.

INTRODUCTION: Neuroblastic tumors can be characterized by three features: spontaneous regression, maturation and aggressive proliferation. The most common and routinely used method of assessing tumor cell proliferation is to determine the Ki-67 index in the tumor tissue. Despite numerous studies, neuroblastoma biology is not fully understood, which makes treatment results unsatisfactory. MCM 2 is a potential prognostic factor in the neuroblastoma group. MATERIAL/METHODS: The study is based on retrospective analysis of 35 patients treated for neuroblastic tumors in the Department of Pediatric Surgery and Oncology of the Medical University of Lodz, during the period 2001-2011. The material comprised tissues of 16 tumors excised during the operation and 19 biopsy specimens. Immunohistochemical examinations were performed with immunoperoxidase using mouse monoclonal anti-MCM 2 and anti-Ki-67 antibodies. RESULTS: We observed that MCM 2 expression ranged from 2% to 98% and the Ki-67 index ranged from 0 to 95%. There was a statistically significant correlation between expression of MCM 2 and the value of the Ki-67 index and a correlation close to statistical significance between expression of MCM 2 and unfavorable histopathology. There was no statistical relationship between expression of MCM 2 and age over 1 year and N-myc amplification. DISCUSSION: The presented research shows that MCM 2 may have prognostic significance in neuroblastic pediatric tumors and as a potential prognostic factor could be the starting point of new individualized therapy.

The first protocol of stable isotope ratio assessment in tumor tissues based on original research.

Thanks to proteomics and metabolomics, for the past several years there has been a real explosion of information on the biology of cancer, which has been achieved by spectroscopic methods, including mass spectrometry. These modern techniques can provide answers to key questions about tissue structure and mechanisms of its pathological changes. However, despite the thousands of spectroscopic studies in medicine, there is no consensus on issues ranging from the choice of research tools, acquisition and preparation of test material to the interpretation and validation of the results, which greatly reduces the possibility of transforming the achieved knowledge to progress in the treatment of individual patients. The aim of this study was to verify the utility of isotope ratio mass spectrometry in the evaluation of tumor tissues. Based on experimentation on animal tissues and human neoplasms, the first protocol of stable isotope ratio assessment of carbon and nitrogen isotopes in tumor tissues was established.

Rhabdomyosarcoma in children in the light of isotope ratio mass spectrometry.

Rhabdomyosarcoma is the third most common solid tumor in children and the most common soft tissue sarcoma in this age group. However, 5-year survival is only observed in approximately 70% of cases, and the prognosis for patients with progressive disease is still poor. The authors hypothesize that the still unidentified differences in embryonal and alveolar tumor biology reflect the complex chemical reactions occurring during cell growth and metabolism and may be pursued in isotopic fractionation processes. Presented herein is the first evaluation of the nitrogen and carbon isotope ratio using isotope ratio mass spectrometry in the two major rhabdomyosarcoma histologic types. 15N enrichment was found in tumor tissues of embryonal histological type. The obtained result may indicate that individual patient considerations such as isotope ratio, in addition to widely accepted prognostic factors, may facilitate patient classification in terms of risk groups.

The correlation analysis of WWOX expression and cancer related genes in neuroblastoma- a real time RT-PCR study.

Neuroblastoma is one of the most common paediatric cancers, described as unpredictable due to diverse patterns of behaviour. WWOX is a tumour suppressor gene whose expression is reduced in many tumour types. Loss of its expression was shown to correlate with more aggressive disease stage and mortality rate. The aim of this study was to investigate the role of the WWOX tumour suppressor gene in neuroblastoma formation. We performed real-time RT-PCR to analyse levels of WWOX expression in 22 neuroblastic tumour samples in correlation with genes involved in cell cycle regulation (CCNE1, CCND1), proliferation (MKI67), apoptosis (BCL2, BIRC5, BAX) and signal transduction (EGFR, ERBB4). We also evaluated two potential mechanisms - promoter methylation (MethylScreen method) and loss of heterozygosity (LOH) status, which could be connected with regulation of WWOX gene expression. We found a positive correlation between WWOX gene and BCL2 and HER4 JM-a and negative with cyclin D1 and E1. Our observations are consistent with previous findings and emphasise the role of WWOX in cell cycle and apoptosis regulation. Moreover, strong positive association with HER4 JM-a in this tumour type may indicate a role for WWOX in neuroblastoma cell differentiation. The presented results indicate that LOH in locus D16S3096 (located in intron 8) may be involved in the regulation of WWOX mRNAexpression. However, no association between methylation status of WWOX promoter and its expression was observed.

Is the SIOP-2001 Classification of Renal Tumors of Childhood accurate with regard to prognosis? A problem revisited.

INTRODUCTION: The goal of this study was to analyze morbidity and mortality of Wilms' tumor based on the revised SIOP-2001 classification. MATERIAL AND METHODS: Sixty-four patients with unilateral Wilms' tumor, 33 girls (51.5%) and 31 boys (48.5%), aged 1 to 144 months (mean: 42.8 months) were treated between 1993 and 2009. All patients underwent multimodal therapy according to the SIOP protocols. The follow-up period ranged from 2 to 18 years (mean: 11.6 years). RESULTS: Thirty-three patients (51.6%) had intermediate-risk, 6 (9.4%) low-risk and 25 (39%) high-risk tumors. Stage I disease was diagnosed in 28 (43.7%), stage II in 19 (29.7%), stage III in 8 (12.5%) and stage IV in 9 patients (14.1%). Event-free survival (EFS) in the entire group was 78.1% and OS was 92.2%. The EFS in stage IV (44.4%) was significantly lower than in stage I (82.1%, p = 0.04), stage II (89.5%, p = 0.02) and in the entire group (78.1%, p = 0.04). Sixteen complications were observed in 14 children (21.9%); metastases in 7 cases (10.9%), 8 relapses (12.5%) and 5 deaths (7.8%). Blastemal (20/24 - 83.3%) and anaplastic (3/24 - 12.5%) subtypes were responsible for mortality in high-risk tumors (OS - 87.5%), while poorly differentiated epithelial (7/34 - 20.6%) and regressive (8/34 - 23.5%) subtypes decreased OS (94.1%) in the intermediate-risk tumors. CONCLUSIONS: The results of our study show that epithelial and regressive subtypes were responsible for mortality in the intermediate-risk Wilms' tumors.

Genetic alterations of WWOX in Wilms' tumor are involved in its carcinogenesis.

Loss of heterozygosity (LOH) in 16q appears in ~20-30% cases of Wilms' tumor. Within this region, known as common fragile site FRA16D, the WWOX tumor suppressor gene is located. Abnormalities of WWOX gene expression levels were observed in many tumor types and were associated with worse prognosis. The purpose of this study was to investigate the role of the WWOX tumor suppressor gene in Wilms' tumor samples. We evaluated the correlation between expression of WWOX and genes involved in proliferation (Ki67), apoptosis (BCL2, BAX), signal transduction (ERBB4, ERBB2, EGFR), cell cycle (CCNE1, CCND1), cell adhesion (CDH1) and transcription (TP73) using real-time RT-PCR in 23 tumor samples. We also analyzed the potential causes of WWOX gene expression reduction i.e., promoter methylation status (MethylScreen method) and loss of heterozygosity (LOH) status. We revealed a positive correlation between WWOX expression and BCL2, BCL2/BAX ratio, EGFR, ERBB4 isoform JM-a, TP73 and negative correlation with both cyclins. Loss of heterozygosity of the WWOX gene was observed only at intron 8, however, it had no influence on the reduction of its expression levels. Contrary to LOH, methylation of the region covering the 3' end of the promoter and part of exon 1 was associated with statistically significant reduction of WWOX gene expression levels. In the present study we reveal that in Wilms' tumors the WWOX expression levels are positively associated with the process of apoptosis, signal transduction through the ErbB4 pathway and EGFR and negatively with the regulation of the cell cycle (by cyclin E1 and D1). Moreover, our analysis indicates that in this type of tumor the expression of the WWOX gene can be regulated by an epigenetic mechanism--its promoter methylation.

Minichromosome maintenance 2 (MCM2) is a new prognostic proliferative marker in Wilms tumour.

OBJECTIVE: We examined expression of minichromosome maintenance 2 (MCM2) by immunohistochemistry in nephrectomy specimens of children with nephroblastoma treated according to the Society International d'Oncologie Pediatrique (SIOP) scheme to determine its potential prognostic significance. MATERIAL AND METHODS: 18 children with nephroblastoma, 9 females and 9 males, 2 months to 7 years of age, treated in the Department of Oncology and Paediatric Surgery, Medical University of Lodz, during the period 1994-2006 were analysed. Children were treated by neoadjuvant chemotherapy and subsequent nephrectomy according to SIOP protocols -93 and 2001 and followed up from 2 to 11 years. The tumour stage and classification in nephrectomy specimens were established according to the revised 2001 SIOP working classification of renal tumours of childhood. RESULTS: In low risk nephroblastoma MCM2 expression was low, ranging from 0% in two cases of completely necrotic nephroblastoma to 5% in one child with cystic partially differentiated nephroblastoma. In mesoblastic nephroma, which is a distinct type of neoplasm with a low malignant potential and the most common congenital renal neoplasm, MCM2 expression was variable ranging from 2-5% in 2 children with stage I disease to 70% in one child with stage III disease In intermediate risk nephroblastoma MCM2 expression was low (10%) in one case of regressive type nephroblastoma and stage II disease and intermediate to high in children with epithelial type nephroblastoma, ranging from 40-50% in one case with stage I disease to 70% and 70-100% in 2 children with stage I and stage IV disease, respectively. In high risk nephroblastoma (7 children with nephroblastoma blastemal type) MCM2 expression was intermediate to high, ranging from 40 to 90%. MCM2 expression tends to be lower in children with less advanced stage of disease (stage II) and higher in more advanced disease (stage III and IV). Two children with blastemal type and high (> 60% MCM2) died of disease within 2-4 years from diagnosis and one child was lost to follow-up. Both children who died were older 8.5 yo M and 7 yo M and presented with advanced disease stage IV or III with anaplasia. CONCLUSION: MCM2 is a promising prognostic factor in WT treated according to the SIOP scheme.

[Rare case of congenital cystic adenomatoid malformation associated with polycystic kidney disease]. / Rzadki przypadek wspolwystepowania wrodzonej torbielowatosci gruczolakowatej pluca z wielotorbielowatoscia nerek.

Congenital cystic adenomatoid malformation (CCAM) is a rare pulmonary abnormality that results from aberrant fetal lung development. It about 4-26% of cases it can be associated with other congenital abnormalities. We describe a case of congenital cystic adenomatoid malformation 2 associated with polycystic kidney disease. The association of these two congenital malformations is exceptional. Only four similar cases have been reported in the literature. A 2-year-old girl was referred to the Department of Paediatric Surgery and Oncology Medical University of Lodz with pneumonia and left pneumothorax. For three weeks prior to referral the patient was treated with antibiotics. Chest x-ray revealed hyperinflation of left upper lobe with mediastinal shift to right. Computer tomographic scan of the lung revealed multiple cyst in the left upper lobe, left-site pneumothorax and mediastinal shift to the right. The patient underwent thoracotomy. Intraoperatively, multiple cysts in the left upper lobe were found and left upper lobectomy was performed. Histologic study was compatible with type 2 congenital cystic adenomatoid malformation. Ultrasound examination showed multilocular cysts in both kidneys. The dimensions of the cysts were: MWR4. 54x45x45 mm and 25x21x24 mm on the left and right sides, respectively. Significant increase in cyst size on the left side was observed. Ten months after first hospitalization resection of the cystic lower pole of the left kidney was performed. The presence of even a single renal cyst in a child with CCAM is an indication for further follow up examinations.

[Own experience in the treatment of infantile haemangiomas with propranolol - preliminary results].

BACKGROUND: Infantile haemangiomas are the most common vascular tumours in children. Since 2008 the application of propranolol has been a promising therapy in the management of haemangiomas. AIM OF THE STUDY: Analysis of the patients with infantile haemangiomas treated with propranolol. MATERIAL AND METHODS: Between June 2009 and December 2010 in Department of Pediatric Surgery and Oncology Medical University of Lodz, 35 children with infantile haemangiomas (29 females and 6 males) were treated with propranolol. Therapy was initiated in age of 2-15 months (mean 4.5). All infantile haemangiomas were in a proliferative phase. In 27 children lesions were located in the head and neck, 2 of them were located in the orbital region and 3 penetrated into the orbit. In 5 children haemangiomas were located in the trunk, with 3 in the perineum and 3 in limbs. In 2 children the PHACE Syndrome was diagnosed. In one of these cases exploratory laparatomy revealed jejunal haemangiomatosis. The indication for propranolol application was impairment of physiological functions in 23 cases, cosmetic defect in 8 and ulceration in 4. The duration of treatment was 4 to 12 months (mean 7.5-months). The change of haemangioma volume, density and colour were evaluated. Reduction of ˝ haemangioma volume was assessed as very good response, 1/3 as good response, and 1/4 as poor. RESULTS: In 7 patients therapy has been finished. In all cases decrease in density, volume and fading was observed. Very good result was achieved in 27 patients, good in 5, poor in 3. Recurrence of haemangioma appeared in two patients after termination of treatment. A spectacularly good result was achieved in the child with PHACE syndrome and in one with jejunal haemangiomatosis. CONCLUSIONS: Propranolol therapy is safe and effective in children with infantile proliferating haemangiomas. It can be the treatment of choice in cases with impairment of physiological functions or severe cosmetic defect. Election and therapy of the children should be carried out in highly reference centres.

Soluble receptors for vascular endothelial growth factor (sVEGFR1/sVEGFR2) in infantile hemangioma.

UNLABELLED: Vascular endothelial growth factor (VEGF) and its receptors were postulated to be involved in pathogenesis of infantile hemangioma. The aim of this study was to determine the serum levels of VEGF and soluble VEGF receptors (sVEGFR1/sVEGFR2) in children with hemangiomas. MATERIALS AND METHODS: Thirty-eight children with infantile hemangiomas (25 proliferating, 13 involuting) and 34 healthy children were included in the study. sVEGFR1 and sVEGFR2 serum levels in peripheral blood and in vascular tumors were determined with ELISA test. RESULTS: sVEGFR1 serum levels were slightly lower in hemangioma patients (p = 0.049). No significant differences in sVEGFR2 levels were observed in any study group. VEGF levels did differ significantly, with median level being 364.05 pg/ml in hemangioma patients and 107.40 pg/ml in the control group (p < 0.0001). CONCLUSIONS: The obtained results suggest that VEGF is involved in hemangioma angiogenesis but that soluble VEGFRs marginally influence this process. Lower serum levels of sVEGFR1 in hemangioma patients indicate the possible dysregulation between VEGFR1 and VEGFR2 receptors.

Serum levels of basic fibroblastic growth factor (bFGF) in children with vascular anomalies: Another insight into endothelial growth.

OBJECTIVES: Dysregulation of angiogenesis has been proposed to play a central role in hemangioma pathogenesis. The aim of the study was to determine the peripheral and local serum levels of bFGF in patients with hemangiomas and vascular malformations (VM). DESIGN AND METHODS: The study group consisted of 52 children with infantile hemangioma, 14 with VM and 36 healthy patients. bFGF serum levels were analyzed by an ELISA assay. Urinary bFGF was determined in 11 individuals with hemangioma. RESULTS: The serum peripheral bFGF concentrations in children with proliferating hemangiomas were lower than in healthy controls (p=0,03). There was no correlation between the measured cytokine level and hemangioma size, as well as patients' age. The serum local bFGF levels in 29 children with hemangiomas were higher than in the peripheral blood (p=0.022). Urinary bFGF in hemangioma patients did not differ statistically from healthy controls. CONCLUSIONS: (1) Determination of bFGF serum levels is not helpful in differentiating the phases of hemangioma growth and distinguishing hemangiomas from VM; (2) serum levels of bFGF cannot distinguish between extrinsic and intrinsic theories of endothelial cell proliferation in hemangiomas.

Histoclinical study of nephroblastoma in relation to current and previous SIOP Classification of Renal Tumors of Childhood.

Histological classifications are essential for prognosis in children malignancies. Currently, the histological type of tumor is one of the main prognostic factors in this group. We investigated histoclinical features of nephroblastoma in relation to SIOP 93-01 and SIOP 2001 Classifications of Renal Tumors of Childhood. We examined all the routinely available histological features and histological nephroblastoma types and investigated their influence on patients' survival with the use of log-rank test and Kaplan-Meier method. The results of statistical analysis indicated that SIOP 93-01 more precisely separated nephroblastoma types according to their biology and malignant potential. We also observed that epithelial type of nephroblastoma showed a mixture of results typical for both intermediate and high risk tumors. What is more, we noticed statistically important correlations between developmental defects found in patients with nephroblastoma and tumor volume and the course of disease.

Local serum levels of vascular endothelial growth factor in infantile hemangioma: intriguing mechanism of endothelial growth.

UNLABELLED: The pathogenesis of hemangiomas still remains poorly understood. Dysregulation of angiogenesis has been proposed to play a central role in hemangioma pathogenesis. The aim of our study was to determine the peripheral and local serum levels of VEGF in patients with hemangiomas and vascular malformations. MATERIAL AND METHODS: The study group consisted of 52 children with infantile hemangioma (33 with proliferative lesions, 19 with involuting lesions), 14 children with vascular malformations and 36 healthy children. VEGF serum levels were analyzed by an ELISA assay and the values between the groups were compared. RESULTS: The serum peripheral VEGF concentrations in children with proliferative hemangiomas were significantly higher than in patients with involuting hemangiomas, vascular malformations and controls. There was no correlation between the measured cytokine level, hemangioma size, and the age of the patients. The local serum VEGF levels in 29 children with hemangiomas were distinctly lower than in the peripheral blood, both in 20 proliferating hemangiomas (p<0.0001) and 9 involuting ones (p=0.007); and the difference between females and males was non-significant (NS p=0.06). CONCLUSIONS: (1) VEGF serum levels vary in the different phases of hemangioma growth and may help to distinguish hemangiomas from vascular malformations; (2) obtained local results may support the intrinsic theory of endothelial cell proliferation in hemangiomas.

Serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in children with hemangiomas and vascular malformations--preliminary report.

Impaired balance between proangiogenic and antiangiogenic factors has been implicated in the development of hemangiomas. Elevated vascular endothelial growth factor serum levels and basic fibroblastic growth factor urine levels in patients with proliferating hemangiomas were reported. However, whether these growth factors can be used for the differential diagnosis of vascular anomalies or assessment of the clinical course of hemangiomas has yet to be determined. We report here our preliminary results of serum vascular endothelial growth factor and basic fibroblastic growth factor levels as an aid in the diagnosis of hemangiomas and in the follow up of patients with this lesion. Twenty two children with infantile hemangioma (13 with proliferating hemangiomas, nine with involuting lesions), five children with vascular malformations, and 25 healthy children study group. Vascular endothelial growth factor and basic fibroblastic growth factor serum levels were analyzed by an ELISA assay. The serum vascular endothelial growth factor concentrations in children with proliferating hemangiomas were significantly higher than in patients with involuting hemangiomas, vascular malformations and healthy patients. The serum basic fibroblastic growth factor concentrations were low and similar in all patients with no statistical correlation between study groups. We concluded that (i) ELISA can easily determine vascular endothelial growth factor concentrations in different phases of hemangioma growth and help distinguishing them from vascular malformations. (ii) A potential role for vascular endothelial growth factor in the pathophysiology of hemangiomas is probable.

Estimation of prognostic value of CD44 expression in neuroblastic tumours in children.

Adversities observed in treatment of children with neoplastic disease based on new diagnostic markers and new prognostic factors. Both of them allow prognosis to be established for a single patient. The aim of our study was to examine the expression of CD44 adhesion molecule in different histologic types in a neuroblastoma group of tumours (35 cases of neuroblastoma from current files and archives) and to estimate the possible prognostic value of CD44 expression by comparison with widely accepted prognostic markers and chosen histoclinical parameters (9 cases of neuroblastoma with follow-up data). We did not find a statistically significant correlation between CD44 expression and histologic type of the tumour. However, we found that all relapses appeared among patients with tumours with the strongest CD44 expression, and that in none of the investigated tumours without relapses was strong CD44 expression ever observed. We noticed CD44 expression in 88.88% of examined tissue samples which underwent statistical analysis and we found the strongest CD44 expression in tumours situated in the retroperitoneal space. Results of log-rank test and Kaplan-Meier estimation showed that a correlation between CD44 expression and survival time was close to a statistically significant value (p=0.065). We conclude that lack of a clear statistically significant correlation between CD44 expression and histoclinical parameters and currently known prognostic factors in our study is due to the presence of many CD44 isoforms, which cannot be distinguished with commercially used antibodies, but they may play a different role in pathogenesis and spread of neuroblastoma.

[Severe bilateral hydronephrosis in a 12 years old boy with neurofibromatosis type-1]. / Skrajne obustronne wodonercze u 12-letniego chlopca z nerwiako-wlókniakowatoscia typu 1.

The large neurofibromatic tumours developing in head, neck and abdominal cavity in children with neurofibromatosis type 1 make a serious clinical problem. In this report the case of 12 years old boy with benign abdominal tumor leading from nerve roots (S1-S2) is presented. He has been treated for 6 years. The other malignant neoplasms, additional congenital defects or neurological dysfunctions were not confirmed. The primary resection was not radical and adjuvant therapy (chemotherapy, hormonotherapy) was ineffective. Due to the progression and not coming to hospital in next 2 years severe obstructive uropathy developed leading to complete destruction of the left kidney. Bilateral ureterocutaneostomies were performed. Despite of slow tumor grow the patient is stable now. However he needs regular calibrations of the right ureterocutaneostomy due to the progressive contraction. Further treatment of this case remains open question.

[Yolk sac tumor--case report and literature review]. / Guz pecherzyka zóltkowego--opis przypadku i przeglad pismiennictwa.

Yolk sac tumor is the rare neoplasm, detected mostly in girls and young women above 30 yr. It is characterized by the high malignancy and short survival rate. We described the case of yolk sac tumor detected in 12-yrs old girl treated by combined method (nonradical tumor resection, chemotherapy, hysterectomy, bilateral adnexectomy and chemotherapy according to SFOP) and with the complete remission more than 1 year after the treatment was completed.