Sonographic Image of Solitary Kidney in Wilms Tumour Survivors.

BACKGROUND/AIMS: This study presents an analysis of the sonographic and laboratory parameters of solitary kidney in Wilms tumour survivors (TWs) and compares these parameters with those of healthy individuals. METHODS: Fifty-three TWs who completed treatment for Wilms tumour and 44 healthy individuals were enrolled. The study protocol consisted of completing a medical history, sonographic examination of the solitary kidney, estimation of glomerular filtration rate (eGFR) by the Schwartz or MDRD formulas, albumin urine excretion and BP measurement. RESULTS: Sonographic signs of kidney damage were observed in 22 (41,5%) TWs. The most frequently detected abnormalities are hyperechoic rings around renal pyramids (28,3% TWs). Hypertrophy of the solitary kidney occurred in 71,7% of cases. The mean volume of the solitary kidney was 77% of the sum of the two kidney volumes in the control group. The median eGFR in the TWs group was 117 with 25Q-105,5, 75Q-130 ml/min/1,73 m2 vs 131,8 with 25Q-124, 75Q-140 ml/min/1,73 m2 in the control group (p=0,000). Six TWs (11,3%) had a value of eGFR below 90 ml/min/1,73 m2. Increased urine albumin excretion (> 30 mg/g) was observed in 7 TWs (13,2%) and in 3 (6,8%) individuals in the control group. CONCLUSION: Ultrasonographic abnormalities in solitary kidney of TWs are frequent. The most frequently detected abnormalities are hyperechoic rings around renal pyramids. Sonographic examination of TWs ought to be performed not only to detect tumour recurrence but also to assess the signs of kidney damage and their progression.

Coincidence of PTPN22 c.1858CC and FCRL3 -169CC genotypes as a biomarker of preserved residual ß-cell function in children with type 1 diabetes.

BACKGROUND: Genotype-phenotype studies in type 1 diabetes (T1DM) patients are needed for further development of therapy strategies. OBJECTIVE: Our aims were to investigate the distribution of selected PTPN22 and FCRL3 gene polymorphisms and their associations with clinical course of disease in children with newly diagnosed T1DM from the Pomeranian region of Poland. SUBJECTS/METHODS: The prospective, longitudinal study of 147 children with newly diagnosed T1DM-autoimmune subtype was conducted. The PTPN22 c.1858T>C (rs2476601) and FCRL3 -169C>T (rs7528684) polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and DNA sequencing. The frequencies of genotypes were compared between the study and population-matched control group (327 random anonymous samples from the Pomeranian region). Selected patients underwent a 24-monthly follow up [periodic re-evaluation of fasting C-peptide concentration (FCP) and hemoglobin A1c (HbA1c ) level]. RESULTS: A significantly lower coincidence of the PTPN22 c.1858CC and FCRL3 -169CC genotypes was found in the study group compared with controls (P = 0.04). The PTPN22 c.1858CC and FCRL3 -169CC genotype combination, restricted to female patients only, was associated with well-preserved residual ß-cell function throughout the entire follow up (prolonged FCP level increase up to the sixth month of disease, with further very stable dynamics-FCP median level ≥0.67 ng/mL without significant decrease up to the 24th month). HbA1c levels in this subgroup also remained the lowest during the observation period. CONCLUSIONS/INTERPRETATION: Ascertained phenomenon could be explained by an interacting mechanism of the two polymorphisms through estrogen-regulated nuclear factor kappa B signaling in regulatory T (Treg ) lymphocytes. This hypothesis, if confirmed, may lead to further development of Treg administration-based therapies.

When do paediatric patients with familial hypercholesterolemia need statin therapy?

INTRODUCTION: Familial hypercholesterolemia (FH) is one of the most common autosomal dominant disorders. It is characterized by elevated LDL cholesterol levels occurring already by early childhood. Awareness of health risks in FH patients should incite health professionals to actively seek and treat children with lipid disorders to reduce their risk of myocardial infarction and stroke. OBJECTIVE: The aim of the study was to evaluate the suitability of taking into account the following parameters: ApoB/ApoA index, IMT and e-tracking examination, when initiating statin therapy in FH patients. Materials and methods The study included 57 male and female patients aged 9.57±3.2 years (ranging from 1 year to 17 years), diagnosed with familial hypercholesterolemia confirmed by molecular testing. All the participants had their lipid profile, ApoA and ApoB levels determined. Carotid intima-media thickness (IMT) was measured by carotid ultrasound and arterial stiffness was assessed by e-tracking. The dietary treatment efficacy was monitored in 40 patients and the 12-month combination treatment efficacy in 27 patients. The study was conducted prospectively and retrospectively. Statistical analysis was performed with the EPIINFO Ver. 7.1.1.14 statistical software package. RESULTS: Patients with familial hypercholesterolemia had high mean levels of total cholesterol and LDL cholesterol (287±67 mg/dL and 213±73 mg/dL respectively). 34.37% of the study subjects had a markedly increased ApoB/ApoA index. On IMT or e-tracking examination all the subjects (100%) had vascular abnormalities. After 6 months of a low-cholesterol diet, the mean total and LDL cholesterol levels in the serum had been reduced by 7.2% and 6.2%, respectively. Statins in an average dose of 10.42±2.49 mg daily were prescribed to 36 patients. After one year of the statin therapy, the average serum total and LDL cholesterol levels were 203.5±34.8 mg/dL and 139.1±32.1 mg/dL, respectively, and were still above the target values. Moreover, side effects of the statin therapy were monitored. An increase in AST levels seen in the study group was not statistically significant. The mean creatine kinase level was within the range of normal. Moreover, in our study material we estimated the risk of cardiovascular events in relation to the ApoB/ApoA index. Higher cardiovascular risk was found in 34.37% participants. CONCLUSIONS: Increased risk of cardiovascular events based on ApoB/ApoA index and carotid e-tracking or IMT examination in paediatric patients with FH is an indication for statin therapy initiation.

Deregulated systemic IL-10/IL-12 balance in advanced and poor prognosis paediatric soft tissue sarcomas.

CONTEXT: The roles of interleukin 10 (IL-10) and IL-12 in regulation of cancer growth and Th1/Th2 immune responses towards cancer are unclear. OBJECTIVE: To establish the prognostic significance of serum IL-10 and IL-12 in paediatric soft tissue sarcomas (STS). MATERIALS AND METHODS: ELISA determinations of cytokines were performed as pre-treatment in 59 children with STS and 30 healthy controls. RESULTS: Elevated IL-10 and decreased IL-12 serum levels correlated with advanced disease, poor response to chemotherapy and poor outcome. IL-10 ≥ 9.5 pg/ml, IL-12 ≤ 65 pg/ml and lymph nodes involvement independently predicted poor overall survival (OS) in multivariate Cox analysis. CONCLUSION: Serum IL-10/IL-12 balance determination may facilitate to assess risk groups and prognosis in childhood STS.

Serum IL-10 and IL-12 levels reflect the response to chemotherapy but are influenced by G-CSF therapy and sepsis in children with soft tissue sarcomas.

INTRODUCTION: Pre-treatment serum IL-10/IL-12 balance has been recently found deregulated in childhood soft tissue sarcomas (STS). Its role in STS monitoring and assessment of response to therapy is unknown. OBJECTIVE: To establish whether serum IL-10 and IL-12 levels and their reciprocal ratios reflect childhood STS course and actual activity and whether G-CSF therapy and central vein catheter (CVC)-related sepsis influence the interleukins levels. MATERIALS AND METHODS: ELISA determinations of serum interleukins were performed before treatment, in remission without complications (CR), at relapse and after treatment in 59 STS patients and during G-CSF administration and CVC-related sepsis (in 18) and also in 30 healthy controls. RESULTS: In CR IL-10 declined and IL-12 increased as compared to pretreatment levels; in relapse IL-10 rose and IL-12 decreased significantly as compared to levels in CR. Also rates of IL-10, IL-12, and IL-10/IL-12 ratios recently estimated by us as of prognostic significance reflected well the STS course. During G-CSF therapy and CVC-related sepsis, IL-10 increased and IL-12 decreased significantly from levels in CR without complications. IL-10 levels and rates of IL-10 ≥ 11 pg/ml in sepsis could falsely suggest relapse. However, IL-12 levels, rates of IL-12 ≤ 60 pg/ml and/or simultaneous determination of both interleukins differed significantly from levels at relapse. CONCLUSION: Serial determinations of serum IL-10 and IL-12 reflected well the course of STS in children and enabled remission and relapse phases to be distinguished. To avoid G-CSF and sepsis influence, IL-12 and IL-10/IL-12 ratio and not IL-10 alone should be analysed.

Renal function and solitary kidney disease: Wilms tumour survivors versus patients with unilateral renal agenesis.

AIMS: To test the hypothesis that Wilms tumour survivors (WTs) experience increased disturbance in renal function, even after prompt treatment, compared to patients with unilateral renal agenesis (URA). METHODS: To assess the renal function of 30 WTs and 17 individuals with URA, the estimated glomerular filtration rate (eGFR) was calculated using the Schwartz and Filler formulas as well as the new Schwartz equation for chronic kidney disease. To measure kidney damage, serum levels and urine excretion of ß(2)-microglobulin (B2M), cystatin C (Cys C), neutrophil gelatinase-associated lipocalin (NGAL) were tested, N-acetyl-ß-glucosaminidase (NAG), and albumin urine excretion and urine sediment were examined. Blood pressure was measured. RESULTS: No differences were found between the groups in terms of eGFR, serum Cys C, B2M and NGAL concentrations. The urine excretion of Cys C, NGAL and NAG was similar in both groups. URA patients had higher B2M excretion than WTs. Arterial hypertension was present in 7/30 (23%) WTs and 1/17 (6%) patients with URA. CONCLUSIONS: WTs have similar eGFR to individuals with URA and are more likely to have arterial hypertension. The patients with URA have signs of tubular damage. This study demonstrates the need for nephrological monitoring of individuals with a single kidney.

Renal function and low-molecular-weight proteins (cystatin C, ß2-microglobulin, neutrophil gelatinase-associated lipocalin) in child and young adult cancer survivors.

BACKGROUND: We sought to verify the hypothesis that children and young adults with cancer who have completed treatment differ according to the type and degree of renal damage. PROCEDURE: This study included 144 children and young adults (73 female) who had completed treatment for leukemias and lymphomas (group L, n=45), Wilms tumor (group W, n=52) and other solid tumors (group S, n=47). The following parameters were evaluated: serum concentrations of creatinine, cystatin C, ß2-microglobulin, neutrophil gelatinase-associated lipocalin and urine excretion of albumin, and urinalysis with sediment. Glomerular filtration rate (eGFR) was estimated using the classic Schwartz (eGFRSch), Schwartz redux (eGFRSchred), and Filler (eGFRFiller) formulas and with the new Schwartz equation for patients with chronic kidney disease (eGFRSchCKD). RESULTS: Group S had the lowest eGFRSchCKD and eGFRFiller, the highest serum cystatin C and the highest albumin excretion compared with groups L and W. Groups S and W had lower eGFRSch and eGFRSchred and higher serum ß2-microglobulin and neutrophil gelatinase-associated lipocalin compared with group L. Group W had lower eGFRSchCKD than group L. CONCLUSIONS: Children and young adults with cancer who have completed treatment differ in the type and degree of renal damage they sustain.

Methemoglobinemia in postchemotherapy stomatitis topical treatment: 2 pediatric cases.

Methemoglobinemia is a rare congenital or acquired disease of increased blood methemoglobin concentration. We documented 2 cases of children suffering from neuroblastoma whose postchemotherapy anemia, leucopenia, and stomatitis were complicated by methemoglobinemia after using a formulary oral gel (7.5% benzocaine, doxycycline, nystatin, glycerin). The complication resulted in hospital treatment. Percutaneous oxygen saturation remained at 85% and 87% despite administration of 100% oxygen through a nonrebreather mask. Arterial blood gas analysis showed an oxygen saturation of 98% and 97%, respectively. Spectroscopic measurement showed methemoglobin concentration of 42% and 35.5%, respectively. After red blood cell transfusion and oral ascorbic acid in case 1 and methylene blue in case 2, the patients' condition improved. Although the benzocaine gel is not in use in several medical systems, it should be considered as a possible reason for methemoglobinemia.

Parameters of antioxidant barrier in different histopathologic types of pediatric cancers.

AIM OF THE STUDY: The goal of this study was to evaluate the activities of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the levels of glutathione (GSH) and ischemia-modified albumin (IMA), as potential markers in different histopathologic types of pediatric neoplasms. No studies on this subject have been reported to date. MATERIAL AND METHODS: SOD, GSH-Px, GSH, and IMA were measured before oncologic treatment in 129 children with neuroblastoma (NB), soft tissue sarcomas (STS), brain tumors, Hodgkin's disease (HD), and acute leukemias, and in 30 healthy controls. RESULTS: The statistical significance of SOD was observed in patients with brain tumors (median 1840.2 U/g Hb, p = 0.0500). The level of GSH was significantly higher in patients with NB (median 6.38 U/g Hb, p = 0.0031) and leukemias (5.16 U/g Hb, p = 0.0200). IMA was statistically significant in cases of STS, NB, and leukemias compared to healthy children (p = 0.0244, p = 0.0069, and p = 0.0000, respectively). The activity of GSH-Px was not statistically significant. CONCLUSIONS: The antioxidant barrier in all types of pediatric cancers is disturbed. None of the measured parameters was specific enough to represent a reliable marker for any particular histopathologic type of children's neoplasm.

G-CSF therapy and catheter-related Gram-positive sepsis increase serum IL-2 receptor α level and may falsely suggest a relapse in children with soft tissue sarcomas unless serum beta2-microglobulin, lactate dehydrogenase and C-reactive protein levels are determined concomitantly.

Many components of oncologic treatment increase serum sIL-2Rα level, which may falsely suggest a relapse. We tried to establish whether granulocyte colony stimulating factor (G-CSF) and central vein catheter (CVC)-related sepsis increase serum sIL-2Rα level to values on relapse of childhood soft tissue sarcomas (STS) and how to distinguish real relapse from a "false" one. Serum sIL-2Rα, B2-M, LDH, CRP and ESR levels and rates of markers' elevated values were determined prospectively in 18 STS children: pre-treatmently (ST1), in complete remission (CR; ST2), in CR during G-CSF therapy (ST3), in CR during CVC-related sepsis (ST4), on relapse (ST5) and after treatment (ST6) and once in 50 healthy pediatric controls. It appeared that pre-treatment serum sIL-2Rα, LDH, CRP and ESR but not B2-M declined significantly with remission (ST2) achievement. At ST5 sIL-2Rα, B2-M, LDH and CRP increased from ST2 to ST1 values. SIL-2Rα levels at ST3 and ST4 rose significantly in all patients from ST2 to ST1 and ST5 values. At ST3 also serum LDH and B2-M increased to values at ST1 and ST5 and exceeded significantly those at ST2 and ST4. At ST4 CRP but not B2-M and LDH, rose significantly in most patients to values at ST1 and ST5. Thus, serum sIL-2Rα monitoring in pediatric STS reflects well response to chemotherapy unless samples are collected during G-CSF therapy or CVC-related sepsis. Determination of serum B2-M, LDH and CRP together with sIL-2Rα may help to distinguish between "real" relapse and "false" sIL-2Rα increase due to G-CSF administration or CVC-related sepsis.

Malignant germ cell tumors associated with Swyer syndrome.

Swyer syndrome is characterized by a higher risk of developing genital malignancies. In this disorder, the most common is gonadoblastoma and dysgerminoma but also, in rare cases, choriocarcinoma. The prognosis in choriocarcinoma is poor. The early diagnosis of dysgenetic gonads is necessary in view of the risk of malignancies. It can be difficult due to its different clinical masks. When the neoplasm precedes the diagnosis of gonadal dysgenesis, adequate oncological treatment should be introduced with parallel gonadectomy. We present a case of 14-year-old female with 46, XY karyotype with choriocarcinoma in one gonad and dysgerminoma in the second one.

The antioxidant status and response to therapy in children with soft tissue sarcomas and neuroblastoma.

BACKGROUND: Antioxidant systems in cells maintain the proper homeostasis of reactive oxygen species, which at high concentrations can induce carcinogenesis. The aim of this study was to evaluate the serum levels of ischemia-modified albumin (IMA), erythrocyte superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) as markers for prognosis in children with neuroblastoma (NB) and soft tissue sarcomas (STS), two cancer types for which reliable prognostic factors are needed. PROCEDURE: SOD, GSH-Px, and IMA were measured before and during responses to therapy assessment in 99 children with NB and STS and in 30 healthy controls. RESULTS: There were no statistically significant differences in the erythrocyte SOD and GSH-Px activities between the patients with cancer and healthy controls. The levels of IMA in patients with STS and NB were found to be significantly higher than in the controls (P = 0.0013; P = 0.0066, and 0.0164, respectively). Decreased activities of SOD and GSH-Px were found in all patients with poor-responding (PRS) cancers and decreased SOD activity was found in patients with PRS NB. An increase in GSH-Px was observed in patients with good-responding (GR) NB. All patients with GR cancers demonstrated higher SOD and GSH-Px activities than patients with PRS cancers. CONCLUSIONS: While determining the levels of specific antioxidants as antioxidant-barrier parameters in children with cancer may be valuable in predicting therapeutic responses as well as outcomes, additional studies are required.

Glomerular filtration rate and prevalence of chronic kidney disease in Wilms' tumour survivors.

Glomerular filtration rate (GFR) was evaluated in 32 Wilms' tumour survivors (WTs) in a cross-sectional study using 99 Tc-diethylene triamine pentaacetic acid (99 Tc-DTPA) clearance, the Schwartz formula, the new Schwartz equation for chronic kidney disease (CKD), cystatin C serum concentration and the Filler formula. Kidney damage was established by beta-2-microglobulin (B-2-M) and albumin urine excretion, urine sediment and ultrasound examination. Blood pressure was measured. No differences were found between the mean GFR in 99 Tc-DTPA and the new Schwartz equation for CKD (91.8 ± 11.3 vs. 94.3 ± 10.2 ml/min/1.73 m(2) [p = 0.55] respectively). No differences were observed between estimated glomerular filtration rate (eGFR) using the Schwartz formula and the Filler formula either (122.3 ± 19.9 vs. 129.8 ± 23.9 ml/min/1.73 m(2) [p = 0.28] respectively). Increased urine albumin and B-2-M excretion, which are signs of kidney damage, were found in 7 (22%) and 3 (9.4%) WTs respectively. Ultrasound signs of kidney damage were found in 14 patients (43%). Five patients (15.6%) had more than one sign of kidney damage. Eighteen individuals (56.25%) had CKD stage I (10 with signs of kidney damage; 8 without). Fourteen individuals (43.75%) had CKD stage II (6 with signs of kidney damage; 8 without). The new Schwartz equation for CKD better estimated GFR in comparison to the Schwartz formula and the Filler formula. Furthermore, the WT survivors had signs of kidney damage despite the fact that GFR was not decreased below 90 ml/min/1.73 m(2) with 99 Tc- DTPA.

Ischemia-modified albumin as a biochemical marker in children with neuroblastoma and soft tissue sarcomas.

In this study, the levels of ischemia-modified albumin (IMA) in pediatric oncology patients with soft tissue sarcomas (STSs) and neuroblastoma (NB) were analyzed. To date, there have been no studies concerning IMA in these groups of patients. Ninety-nine children with STSs and NB were analyzed from 2006 to 2009, and 30 healthy children were also enrolled in the study. IMA levels were measured throughout treatment in all patients. The levels of IMA in all cancer patients (mean 116.8±39.3 U/ml), in patients with STSs (mean 119.8±27.5 U/ml), and in patients with NB (mean 114.6±36.6 U/ml) were significantly higher than in the control patients (mean 87.3±38.3 U/ml; P=0.0013, 0.0066, and 0.0164, respectively). IMA levels increased before and during the treatment compared with levels in the controls. The determination of IMA levels in pediatric oncology patients with poor prognoses from STSs and NB may play an important role in predicting response to therapy and overall outcome.

Multiple primary cranio-spinal tumours in a 13-year-old female with neurofibromatosis type 2 management strategy.

INTRODUCTION: Neurofibromatosis type 2 (NF2) is an inherited, rare autosomal dominant syndrome characterised by the development of multiple benign cranial and spinal tumours, peripheral neuropathy, ophthalmological and cutaneous lesions. Herein, we report one case of NF2 treated with multivariate chemotherapy. MATERIAL AND METHODS: A 13-year-old female presented with multiple cranio-spinal tumours in MRI. First symptoms were progressive changes in vision, left-sided paresis, unilateral sensorineural hearing loss, and left hypoglossal nerve paresis. The patient underwent palliative, partial surgical resection of the tumour which was located in a posterior fossa. Histopathological examination showed a psammomatous meningioma located near the great foramen and schwannomas of VIII nerve in the cerebello-pontine angle. Clinical and radiological examination revealed a rapid progression of the disease. As such, multivariate chemotherapy was used. The patient died 4 years after diagnosis. CONCLUSION: NF2 patients with multiple tumours at diagnosis may not be treatable with surgery alone and, as a result, presentation with such a disease in childhood results in poor prognosis. The unification of management strategies in NF2 patients is highly desirable.

Prognostic significance of HER2 expression in neuroblastic tumors.

HER2 is essential for normal embryonic development and has a critical function in oncogenesis and progression of some types of cancer. Neuroblastic tumors create a heterogenous group of pediatric embryonal tumors of sympathoadrenal lineage. The biological and prognostic function of HER2 in these tumors is not well established. In this study, we evaluated the status of HER2, its prognostic significance, and clinicopathological correlations in series of 79 untreated neuroblastoma. The immunohistochemical assessment of HER2 and Ki-67 (proliferation index) as well as HER2 copy number status were performed on tissue microarrays. HER2 expression characterized 63 tumors, including 34 with low and 29 with high level, showing either membranous or mixed membranous-cytoplasmic pattern. Sixteen cases were HER2 immunonegative. The pattern of immunolabeling depended on the maturity of neuroblastic cells, being the most intense in differentiating neuroblasts. None of the tumors revealed HER2 amplification. In the examined group, 20% of patients died of disease from 4 to 107 months (median 18) from the diagnosis, and the survivors were followed up for 14-149 months (median 59). Patients' age, stage of disease, tumor location, mitosis/karyorrhexis index (MKI), and presence of HER2 expression were statistically significantly related to survival probability as detected by the Cox proportional hazard model. In the univariate analysis, Kaplan-Meier curves revealed significantly poorer outcome of HER2 negative than HER2-positive tumors (either low or high expression). The immunonegativity was associated with adverse clinicopathological parameters, including poor survival, metastatic stage of disease, un- or poorly differentiated histology, high MKI, and higher proliferation index. In conclusion, HER2 expression, not accompanied by gene amplification, is common in neuroblastic tumors. HER2 positivity seems to have a positive prognostic significance. HER2 expression with a variable pattern is a marker of the stage of neuroblastic cells differentiation.

Factors predicting survival in childhood malignant and intermediate vascular tumors : retrospective analysis of the Polish and German cooperative paediatric soft tissue sarcoma study groups and review of the literature.

BACKGROUND: The rarity of malignant and intermediate vascular tumors in children means that little is known about their clinical course, optimal treatment, and variables predicting survival. METHODS: A total of 32 children with malignant vascular tumors (14 angiosarcomas [AS], 5 epithelioid hemangioendotheliomas, and 13 intermediate vascular tumors, including other hemangioendotheliomas plus adult-type hemangiopericytomas), registered in the German and Polish Paediatric Soft Tissue Sarcomas Study Groups, were treated following the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, -86, -91, and -96 protocols. RESULTS: Male sex, AS histology, tumor size >5 cm, and T2 invasiveness were independent predictors of inferior 5-year overall survival, while AS histology and T2 invasiveness were predictors of inferior 5-year event-free survival. AS histology was the most important negative prognostic factor for overall survival and event-free survival. Completeness of primary tumor excision was a good prognostic factor for survival in univariate, but not multivariate, analysis. Local therapy (radiotherapy and delayed surgery) were provided to the minority of patients (28% and 38%, respectively) late in the course of disease (after a mean of 9 and 6 months, respectively) and did not prevent local relapses. Response to systemic treatment was poor (44%) and did not prevent local and distant relapses. CONCLUSIONS: The clinical course and outcome in childhood epithelioid HE seems to be similar to intravascular tumors and less aggressive than AS. RTX and delayed surgery should be performed more frequently and earlier in the disease course. An urgent need for modification of systemic therapy is needed because of the development of many metastatic and/or combined relapses and poor response to classic chemotherapy. The problem of effective therapy for childhood AS is the most appaling: 13 of 14 patients died of progression despite multimodal treatment.

Thymic carcinoma in children: a report from the Polish Pediatric Rare Tumors Study.

BACKGROUND: Invasive thymomas and thymic carcinomas are rare tumors jointly accounting between 0.2% and 1.5% of malignancies in adults. They are usually at an advanced stage when diagnosed and have both high recurrence and poor survival rates. In this report, the aim is to explore our experience in the treatment of thymic carcinomas in Polish children. PROCEDURE: The clinical data of nine children with thymic carcinomas, treated between 1992 and 2008 in the Polish oncological and surgical centers was retrospectively analyzed. RESULTS: In five cases, presenting symptoms resulted from the compression of the respiratory ways by the mediastinal tumor. In two children paraneoplastic autoimmune syndromes were associated with thymic carcinoma. In accordance with the Masaoka classification, two patients had stage II, five had stage III, and two had stage IV of the disease. Diagnostic biopsy of mediastinal tumor was performed on eight patients and one underwent complete primary resection and subsequently received radiotherapy; he has passed 11 years since the conclusion of therapy. Six patients received multi-drug chemotherapy with or without steroids. Delayed surgery was performed in four children (R0-2, R1-1, and R2-1). After complete resection, one child received chemotherapy. In three patients, chemotherapy and radiotherapy was administered. Seven patients died, including six due to progression of the disease with the other as a result of complications following chemotherapy; only two patients classed at stage II remain alive. CONCLUSIONS: Most thymic tumors in pediatric patients are inoperable at diagnosis, which results in poor prognosis. Improved chemotherapy approaches are needed.

Analysis of PI3K/AKT/mTOR signalling pathway in high risk neuroblastic tumours.

Neuroblastoma (NB) represents one of the most common paediatric tumours. Despite advance in NB research and treatment, the outcome of the patients from the high-risk group remains poor. PI3K/AKT/mTOR signalling pathway which is involved in oncogenesis and cancer progression of many tumours, in parallel constitutes the target for the biologically based oncological therapy. In this study we analyzed the status of PI3K/AKT/mTOR signalling route in the primary tumour tissue samples from a group of 39 high-risk NB. The pathway activation state was assessed immunohistochemically using antibodies with specificity towards PI3Kp85, PI3Kp110, phospho-AKT, phospho-mTOR, phospho-p70S6K and phospho-4EBP1. Moreover, expression of PTEN, bcl2 and cyclin D1 was examined. We found that most of tumours were positive for PI3Kp85 and PI3Kp110, as well as for p-AKT, p-mTOR and its downstream effectors p-p70S6K and p-4EBPI. PTEN was expressed in all cases, bcl2 and cyclin D1 staining was found in more than 90% of examined NB. Statistical analysis revealed that p-AKT expression was correlated with p-mTOR and strong cyclin D1 labelling. Furthermore, high expression of p-4EBP1 was significantly associated with p-p70S6K expression, high cyclin D1 and lower differentiation of the tumour. PI3K/AKT/mTOR signalling pathway activation is a common event in high-risk NB and it seems that this group of patients may benefit from targeted therapy with kinase inhibitors.