Association of CYP3A5 Expression and Vincristine Neurotoxicity in Pediatric Malignancies in Turkish Population.

Vincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolism and the neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish children with malignancies, relation between CYP3A5 genotype and neurotoxicity rates, as well as severity and duration of neuropathy and total vincristine doses were investigated. Patient group consisted of 115 patients (age, 1 to 17 y) with acute lymphoblastic leukemia and solid tumors, who were treated with vincristine consisting chemotherapy protocols. Control group consisted of 50 children without any neurological symptom or disorders. All patient files were reviewed for presence and severeness of neurotoxicity symptoms. Blood samples were obtained and CYP3A5 genotypes were analyzed. Neurotoxicity occurred in 20.8% of patients. Although it was found to occur more frequently after 4 doses of vincristine, and rates were higher in the low-dose vincristine group suggesting other contributing factors. Although neurotoxicity rate in the CYP3A5*1/*3 genotype was 17.6%, it was 21.6% in the CYP3A5*3/*3 genotype and the difference was not statistically significant (P<0.05). This study suggested that vincristine-related neurotoxicity is dose-independent and genotype is not the only causative factor in the occurrence of neurotoxicity in these patients.

Recurrent Sertoli-Leydig cell tumor of ovary in 8-year-old girl.

Sertoli-Leydig cell tumors are rare sex cord-stromal neoplasms that account for <0.2% of ovarian tumors. These tumors with a retiform pattern pose difficult diagnostic problems, with the majority of being misinterpreted as serous papillary cystadenocarcinoma and endodermal sinus tumor. We report an 8-year-old female patient presented to our institution with a huge mass and pain in the lower abdomen and recurrence in the 10th months following the first operation. Only four cases of Sertoli-Leydig cell tumors have been reported under age of the eight years in the literature so far. It is difficult to define the stage and the morphology of Sertoli-Leydig cell tumors with retiform pattern in children and chemotherapy or radiotherapy administration is contraversial. However, fertility sparing surgeries should be considered as a first treatment choice on the time of the diagnosis and the recurrence.

Assessment of brachial artery reactivity, carotid intima-media thickness, and adhesion molecules in pediatric solid tumor patients treated with anthracyclines.

The aim of this study was to determine subclinical atherosclerosis and endothelial functional disturbance with measurement of carotid intima-media thickness (IMT), brachial artery reactivity (BAR), and levels of serum adhesion molecules in children with solid tumors who were treated with anthracyclines and are actually in complete remission. Fifty patients who were in remission and 30 healthy children were included in the study. Mean ages of patient and control groups were 13.5 ± 4.7 years (range: 3-23 years) and 12.00 ± 4.3 years (range: 4-21 years), respectively. The patients were divided into 3 groups according to cumulative doxorubicin dose: Group 1, ≤100 mg/m(2); Group 2, 101-299 mg/m(2); Group 3, ≥300 mg/m(2). The BAR and carotid IMT were measured in order to determine the endothelial function. The serum adhesion molecule levels in our patients and controls were also measured. The BAR of the patients with cumulative anthracycline dose ≥300 mg/m(2) was significantly lower than the patients with cumulative anthracycline dose ≤100 mg/m(2) and healthy controls (P =.005 and P =.003, respectively). Also, there was a negative correlation between brachial artery reactivity and increasing cumulative anthracycline dose (r = -.287, P =.044). We also found significant difference between the mean carotid IMT of the patients and the healthy children (P =.041). No statistically significant difference was detected between the serum levels of sICAM-1 (soluble intercellular adhesion molecule-1), sVCAM-1 (soluble vascular cell adhesion molecule-1), sE-selectin of the patients and controls. The use of anthracyclines in pediatric patients with cancer could result in increase of the carotid IMT and endothelial dysfunction.

Multisystem langerhans cell histiocytosis with thymic involvement diagnosed with anterior mediastinal mass in a 2-month-old boy.

Thymus gland involvement in Langerhans cell histiocytosis (LCH) is usually part of multi-system disease and may be more common than previously recognized. However, thymic involvement causing an anterior mediastinal mass is an extremely rare presentation of multisystem LCH. Here we report a 2-month-old-boy admitted to hospital with a giant anterior mediastinal mass with multisystem LCH involving the thymus, lungs, liver and skin. The differential diagnosis of mediastinal mass in children should also include LCH, especially multisystem disease. LCH should also be kept in mind in the differential diagnosis of skin lesions in infants, even if spontaneous regression occurs.

Breastfeeding and Childhood Cancer: Is Breastfeeding Preventative to Childhood Cancer?

Breastfeeding is well-known to have a protective effect against infection in infants. It has been suggested that breast milk may play a role in the prevention of certain childhood cancer. We investigated this issue in a case-control study comprising 300 patients with childhood cancer. There was 73 patients (24.3%) with leukemia, 82 patients (27.3%) with lymphoma, and 146 patients (48.4%) with solid tumors (brain tumors, neuroblastoma, soft tissue sarcomas, germ cell tumors, renal tumor, bone tumor, retinoblastoma, hepatoblastoma, and others) and 316 controls matched for age and sex. Breastfeeding duration of the control group was found to be significantly longer than the patient group (X(2) = 57.774; P < .001). In conclusion, breastfeeding was found to be inversely associated with pediatric cancer in our study.

Risk factors for cisplatin-induced long-term nephrotoxicity in pediatric cancer survivors.

BACKGROUND: The aim of this study was to compare the nephrotoxicity risk of cisplatin (CPL) and ifosfamide (IFO) combination treatment (CT) with that of CPL alone and to evaluate the prevalence of CPL-induced long-term nephrotoxicity in pediatric cancer survivors (CS). METHODS: A total of 33 patients with pediatric solid tumors who have been cured of their disease were included in the study. They were divided into two groups based on the type of chemotherapeutics, either CPL (n = 21) or CT (n = 12), given during cancer treatment and were evaluated for glomerular and tubular function using the Skinner grading system. RESULTS: Nephrotoxicity was found in 15 CS (45.4%): seven (21.3%) of those had moderate, six (18.2%) had mild, and two (6.1%) had severe nephrotoxicity. Neither the rates of overall nephrotoxicity, glomerular toxicity and tubular toxicity, nor the mean overall, glomerular and tubular toxicity scores differed significantly among the CPL and CT groups (P > 0.05 for all parameters). Cumulative IFO dose and age at treatment were found to be independent risk factors for both development and severity of CPL-induced nephrotoxicity (P = 0.025 and P = 0.036 for development of nephrotoxicity; P = 0.004 and P = 0.050 for severity of nephrotoxicity, respectively). CONCLUSIONS: Although CPL-induced long-term nephrotoxicity was found in half of the pediatric CS of solid tumors, clinically significant nephrotoxicity was detected only in a minority of them. Both higher cumulative IFO dose and younger age at treatment were found to be independent risk factors for both development and severity of CPL-induced nephrotoxicity.

Thyroid abnormalities in survivors of childhood cancer.

OBJECTIVE: To investigate the late side effects of childhood cancer therapy on the thyroid gland and to determine the risk factors for development of thyroid disorder among childhood cancer survivors. METHODS: One hundred and twenty relapse-free survivors of childhood cancer (aged 6-30 years) were included in this study. The diagnoses of patients were lymphoma, leukemia, brain tumor, rhabdomyosarcoma and nasopharyngeal carcinoma (NPC). The patients were divided into two groups depending on the treatment: group 1-chemotherapy (ChT) only (n=52) and group 2-combination therapy of ChT + radiotherapy (RT) (head/neck/thorax) (n=68). Thyroid function tests, urinary iodine levels, and thyroid gland ultrasound examinations were evaluated in both groups. RESULTS: Incidence of thyroid disease was 66% (n=79) in the survivors. The thyroid abnormalities were: hypothyroidism (HT) (n=32, 27%), thyroid nodules (n=27, 22%), thyroid parenchymal heterogeneity (n=40, 33%), autoimmune thyroiditis (n=36, 30%), and thyroid malignancy (n=3, 2%). While the incidence of HT and thyroid nodules in group 2 was significantly higher than in group 1, the incidence of thyroid parenchymal heterogeneity and autoimmune thyroiditis was similar in the two patient groups. HT and thyroid malignancy were seen only in group 2. In multivariate logistic regression analysis, a history of Hodgkin lymphoma (HL), brain tumor and NPC, as well as cervical irradiation and 5000-5999 cGy doses of radiation were found to constitute risk factors for HT. History of HL and 4000-5999 cGy doses of radiation were risk factors for thyroid nodules. Head/neck irradiation and treatment with platinum derivatives were risk factors for autoimmune thyroiditis. In univariate analysis, a history of NPC, cervical + nasopharyngeal irradiation, and treatment with platinum derivatives were risk factors for thyroid parenchymal heterogeneity. CONCLUSION: Our results indicate that there is especially an increased risk of HT and thyroid nodules in patients treated with combination therapy of ChT with head/neck/thorax RT. Although chemotherapeutic agents per se do not seem to cause HT, longer follow-up is needed to assess whether or not there is an increased risk for autoimmune thyroiditis and thyroid parenchymal heterogeneity after antineoplastic therapy.

A complication to be aware of: hyperkalaemia following propranolol therapy for an infant with intestinal haemangiomatozis.

Infantile haemangiomas, benign vascular tumours seen in 4-10% of infants are characterised by their spontaneous remission following a 3-9 month period of dynamic growth. Propranolol has been reported to be used as a successful treatment of severe symptomatic infantile haemangiomas. Hyperkalaemia has not been recognised as a serious effect of propranolol since recently. Here, we would like to portray a 2-year-old male patient with intestinal haemangiomatosis who presented with severe hyperkalaemia and was successfully managed with hydration, loop diuretics, potassium binding granules, inhaler ß-2 agonists and insulin. To date, this is the first case of intestinal haemangiomatosis complicated with severe hyperkalaemia. Our case suggested the idea of close monitorisation of potassium levels as well as haemodynamic status at the initialisation of the propranolol treatment.

Successful multimodal treatment for aggressive metastatic and recurrent fibrolamellar hepatocellular carcinoma in a child.

Fibrolamellar variant of hepatocellular carcinoma (FLHCC) does not have a favorable prognosis than conventional HCC, and there is no difference regarding the response to chemotherapy and the degree of surgical resectability. FLHCC commonly recurs after complete surgical resection, and there is a high rate of lymph node metastases. Herein, we report a 12-year-old girl with metastatic FLHCC with multiple recurrences aggressively treated with surgery, chemotherapy, and antiangiogenic agents. She is in complete remission after 4 years and 2 months after the diagnosis of metastatic FLHCC. The standard treatment of FLHCC is excision of the primary tumor and its metastases. Chemotherapy for FLHCC is controversial, and it has been suggested that cytoreductive chemotherapy was ineffective and adjuvant chemotherapy did not improve survival. Our patient with multiple recurrences was successfully treated with surgery, first-line chemotherapy with cisplatin and doxorubicin, second-line chemotherapy with 5-fluorouracil/interferon-α combination, and adjuvant antiangiogenic agents like cyclophosphamide and thalidomide. As FLHCC patients have no underlying liver disease, they can tolerate higher doses of chemotherapy compared with conventional HCC patients. We support the use of repeated aggressive surgery with adjuvant chemotherapy and antiangiogenic therapy, which provided complete remission in our patient with metastatic and recurrent FLHCC.

Resveratrol and adipose-derived mesenchymal stem cells are effective in the prevention and treatment of doxorubicin cardiotoxicity in rats.

Anthracyclines can cause severe cardiac toxicity leading to heart failure. The aim of this study was to determine the effects of cardioprotective polyphenolic compound resveratrol (RES) and adipose-derived mesenchymal stem cells (ADMSCs) on cardiac tissue of rats treated with doxorubicin (DOX). Forty-two female and three male Wistar-Albino rats were included in the study. The study groups and the control groups were as follows: Group I: DOX; Group II: DOX + RES; Group III: DOX + ADMSCs; Group IV: DOX + RES + ADMSCs; Group V: Sham operation; and Group VI: normal saline. ADMSCs obtained from male rats were defined with stem cell markers [CD11b/c(-), CD45(-), CD90(+), CD44(+), and CD49(+)]. DOX 12 mg/kg intraperitoneally (i.p.) was injected as a single dose in female rats. Resveratrol 100 mg/kg was injected three times i.p. in Groups II and IV. ADMSCs 2 × 10(6) cells/kg/dose were labeled with bromodeoxyuridine (BrdU) and injected i.p. for a total of three times in Groups III and IV. When the study was terminated after 4 weeks, the beating hearts were connected to a Langendorff setup and records were obtained for 30 minutes. Histopathological, immunhistochemical, and immunofluorescent examination with H&E, Troponin I, and BrdU stains were also performed. Also, ADMSCs were demonstrated in the myocardium of transplanted rats. Left ventricle functions and myocardial histology demonstrated significant impairment in DOX only group compared to groups with ADMSCs (P < .05). We suggest that RES and ADMSCs were successful in the prevention and treatment of the doxorubicin cardiomyopathy in rats. The hypothetical mechanisms of regeneration are multiple, including cell differentiation and autocrine/paracrine effects of ADMSCs.

High-risk ALK negative anaplastic large-cell lymphoma presenting with hypereosinophilic syndrome in a 2.5-year-old child.

The hypereosinophilic syndromes (HES) are characterized by prolonged nonreactive peripheral blood hypereosinophilia with tissue damage. The lymphocytic HES variant can precede malignant clonal T-cell disease in adults but it is extremely rare to be the presenting feature of lymphomas in children. Here we present a 2.5-year-old boy with HES and mediastinal T-cell anaplastic lymphoma kinase (ALK) negative systemic anaplastic large-cell lymphoma. Mature and immature eosinophils without blasts were shown on bone marrow aspiration while biopsy revealed malignant infiltration. The patient responded well to initial corticosteroid therapy, but high-risk features make a challenge of finding the cure in this extremely rare case.

Extraskeletal Ewing sarcoma of the mesocolon in a child.

Ewing sarcoma (ES) is a malignant neoplasm usually affecting the skeletal system. Extraskeletal ES is a rare tumor. To date, only 1 case of primary mesocolon ES has been previously reported in an adult. Herein, we present the first case of ES in the mesocolon in a child.

High-risk CD117-positive gastrointestinal stromal tumor of the colon in a 12-year-old girl: adjuvant treatment with imatinib mesylate.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the alimentary tract rarely observed in children. The treatment of choice for GIST is surgical resection. Although the prognosis of GISTs with low malignant potential is excellent, high-malignant-potential GISTs have a high rate of recurrence. Prognostic factors such as tumor size, mitotic rate and presence of metastases may provide an indication for adjuvant imatinib mesylate (IM) treatment. Here we present a young patient with a large GIST with high-risk features who is in complete remission after surgical excision and adjuvant IM treatment. This patient is the only colon-located CD117-positive case where IM was administered. The exact indications as well as the optimal dose and duration of IM need to be clarified with the contribution of new cases and the growing experience of this rare disease.

Familial synchronous bilateral teratoid Wilms tumor with elevated alpha-fetoprotein level.

Familial Wilms tumor is a rare entity that accounts for only 1-2% of all Wilms tumor cases, with an earlier age of onset and an increased frequency of bilateral tumors. Teratoid Wilms tumor is a variant of nephroblastoma with a predominance of heterologous tissues comprising more than 50% of the tumor volume. Wilms tumor does not usually secrete any specific tumor marker and all teratoid Wilms tumor cases previously reported were sporadic non-secreting neoplasms. Here we describe an infant with familial synchronous bilateral teratoid Wilms tumor whose serum alpha-fetoprotein level was elevated. To our knowledge, this extremely rare type of case is reported for the first time in the literature.

Institutional experience of paediatric high-grade central nervous system tumours: an analysis of 74 patients and review of the literature.

AIM OF THE STUDY: Although the survival for children with certain central nervous system (CNS) tumour types has improved through current surgical and adjuvant treatment modalities, the prognosis of many high-grade tumours remains poor despite aggressive treatment. The aim of this study is to analyse patients with high-grade brain tumours in our institution to determine the histopathology, clinical characteristics, treatment modalities, and survival. MATERIAL AND METHODS: A total of 74 patients with a diagnosis of high-grade brain tumour were analysed. There were a total of 31 patients with embryonal tumours, 27 patients with high-grade glial tumours, 12 patients with brain stem gliomas and 4 patients with other high-grade brain tumours. RESULTS: There were 48 (65%) boys and 26 (35%) girls (ratio: 1.85) with a median age of 99.7 months (range = 2-204 months). The median follow-up period was 19 months (range = 1-204 months). Tumour recurrence was observed in 38 patients (51.4%). The overall survival rate and event-free survival rate of our patients were 27% and 19.5%, respectively. CONCLUSIONS: Pediatric high-grade CNS tumours have a very aggressive behaviour and a significant number of children eventually succumb to disease despite multimodal treatment. There is a need of more effective therapeutic approaches for these tumours with poor prognosis. The future improvement in childhood high-grade brain tumour management depends on a better understanding of the molecular genetics and biology of brain tumours.

The evaluation of CD99 immunoreactivity and EWS/FLI1 translocation by fluorescence in situ hybridization in central PNETs and Ewing's sarcoma family of tumors.

Ewing's sarcoma family of tumors (ESFTs) are indicated by malignant, small, round and blue cell tumors of the bone and soft tissue. Gene rearrangements between EWS gene on chromosome 22q12 and members of the ETS gene family are common in and specific to ESFTs. Another defining characteristic of ESFTs is their membranous expression of the CD99. In contrast, such translocations and immunoreactivity are not found in central primitive neuroectodermal tumors (cPNETs). The aim of this study was to investigate the detection of EWS/FLI1 translocations and CD99 immunoreactivity in order to evaluate their clinicopathological features and their roles in the differential diagnosis of these tumors. In this study, we investigated CD99 immunoreactivity using immunohistochemistry and Ewing's sarcoma / Friend leukaemia virus integration 1 (EWS/FLI1) translocation using the fluorescence in situ hybridization (FISH) method in 23 cases. CD99 expression was detected in 10/11 (90%) ESFT cases and 2/7 cPNET cases. In 18 cases EWS/FLI1 translocation was examined using the FISH method. The EWS/FLI1 translocations were detected in 7/8 (87.5%) ESFTs cases, whereas non of 8 cPNET cases were detected with this translocation. One case could not be classified as either central or peripheral, showed EWS/FLI1 translocation. There was a statistically significant difference in CD99 expression (p = 0.0013) and EWS/FLI1 translocation (p = 0,002) between cPNETs and ESFTs cases. In conclusion, CD99 expression and EWS/FLI1 translocation are specific and sensitive markers in the diagnosis of ESFTs. However, these were often not found in cases of cPNET. Therefore, in the diagnosis of ESFTs, clinical, radiological, histopathological and immunohistochemical parameters should always be evaluated together.

Clinical significance of serum vascular endothelial growth factor, endostatin, and leptin levels in children with lymphoma.

BACKGROUND: A number of clinical studies conducted in adults have demonstrated the prognostic significance of angiogenic factors in malignancies, however, only a limited number of studies have been conducted in children. The aim of this study was to determine serum vascular endothelial growth factor (VEGF), endostatin, and leptin levels in children with lymphoma and to investigate whether these factors provide prognostic information. PROCEDURE: Serum samples from 36 children with lymphoma (non-Hodgkin lymphoma (NHL) N = 21, Hodgkin lymphoma (HL) N = 15) were collected at diagnosis and during remission. Serum samples were also collected from 18 healthy children as the control group. Serum VEGF and endostatin levels were quantified by using enzyme-linked immunosorbent assay (ELISA) and serum leptin by immunoradiometric assay. RESULTS: The serum VEGF levels were found elevated in patients compared to controls (P = 0.033), while endostatin and leptin levels were lower in patients than in controls (endostatin, 43.9 ± 5.8 ng/ml vs. 123.6 ± 13.5 ng/ml, P < 0.001; leptin, 5 ± 1.5 ng/ml vs. 6.7 ± 1.2 ng/ml, P = 0.013). VEGF levels declined (pre, 151.6 ± 55.9 pg/ml vs. post, 16.2 ± 7.9 pg/ml, P = 0.041), while endostatin and leptin levels increased in patients who achieved remission (33 of 36 patients) when compared to pre-treatment levels (endostatin pre, 43.1 ± 5.9 ng/ml vs. post, 65.9 ± 6.8 ng/ml, P = 0.047; leptin, pre, 5.3 ± 1.6 ng/ml vs. post, 9.8 ± 2.7 ng/ml, P = 0.012). Serum VEGF, endostatin, and leptin levels were not predictive of survival. CONCLUSION: Serial measurement of serum VEGF, endostatin, and leptin levels could potentially be used to predict response to treatment or progressive disease in children with lymphoma.

Early diagnosis of anthracycline toxicity in asymptomatic long-term survivors: dobutamine stress echocardiography and tissue Doppler velocities in normal and abnormal myocardial wall motion.

AIMS: Asymptomatic long-term cancer survivors treated with anthracycline were investigated for late anthracycline cardiotoxicity using dobutamine stress echocardiography (DSE) and tissue Doppler (TD) velocities. METHODS AND RESULTS: The study comprised 20 asymptomatic patient and 18 healthy children as the control group. Twenty patients were divided into two groups according to the myocardial wall motion during DSE: Group 1 (normal myocardial wall motion; six girls and five boys) and Group 2 (abnormal myocardial wall motion: nine boys). Intravenous dobutamine infusion was started at a dose of 5 µg/kg/min (D5) and gradually increased to 10 (D10), 15 (D15) and 20 µg/kg/min (D20). Echocardiographic assessment was performed at rest and after each dose of dobutamine infusion. Abnormal myocardial wall motion was observed at rest in 3 patients and during DSE in six patients. There were no significant differences between the patients and control groups at rest except the end systolic wall stress and mitral deceleration time measured by conventional methods; however, both patients group showed significant differences of systolic and diastolic functions at D20. In patients groups, systolic and diastolic functions of interventricular septum (IVS) and systolic function of left ventricle (LV) and right ventricle (RV) TD velocities showed significant changes compared with control group at rest. Significant differences of diastolic functions of IVS and RV were noted during dobutamine infusion in abnormal myocardial wall motion compared with other groups. CONCLUSION: LV, RV and IVS TD velocities systolic function at rest and during DSE can provide valuable information for early detection of subclinical cardiac toxicity. TD velocities of diastolic functions during DSE are a valuable parameter for assessment of subclinical cardiac toxicity in patient with abnormal wall motion.

[The role of dobutamine stress echocardiography in early diagnosis of cardiac toxicity in long-term survivors of asymptomatic children treated with anthracycline]. / Antrasiklin ile tedavi edilen yasayan asemptomatik çocuklarda uzun dönemde gelisebilecek kardiyotoksisitenin erken tanisinda dobutamin stres ekokardiyografinin yeri.

OBJECTIVE: Long-term survivors of asymptomatic children treated with anthracycline may have cardiac toxicity without clinical findings. The subclinical cardiac toxicity could be evaluated by dobutamine stress echocardiography (DSE) with exploring effective and safe doses of dobutamine. METHODS: Twenty asymptomatic survivors (mean age: 19.2+/-4.0 years) treated with cumulative dose of 282.1+/-125.9 mg/m2 of anthracycline were compared with 18 age-matched healthy volunteers. Total time completed this treatment was 10.2+/-2.2 years. This was a cross-sectional case-controlled study and patient and control groups were evaluated at the time of routine appointments. Echocardiographic studies were performed before and after each dobutamine infusion of 5, 10, 15, 20 microg/kg/min. STATISTICAL ANALYSIS: Mann-Whitney U test was used to evaluate the difference between the groups. ANOVA for repeated measurements test was used to compare each measurement of control and patients groups and Bonferroni posthoc test was used for correction. RESULTS: Hemodynamic changes are observed at the dobutamine doses of 15 microg/kg/min in the patient group. Before dobutamine infusion in the patient group only isovolumic relaxation and contraction times values were prolonged comparing to the control group. After the infusion of dobutamine ejection fraction, shortening fraction, left ventricular posterior wall thickening (%LVPWt), end-systolic wall stress (ESS), interventricular septum systolic thickening, left ventricular end-systolic and end-diastolic diameters, mitral acceleration (AT) and deceleration times values were deteriorated in the patient group compared to the control group (p=0.05 for all). The highest differences between the groups were observed in the %LVPWt, ESS and AT values at the end of test. CONCLUSION: The DSE is an effective and safe method to demonstrate the late anthracycline cardiotoxicity. Echocardiographic evaluation should be made at rest and dobutamine dose of 20 microg/kg/min. In the early diagnosis of late cardiac toxicity; assessment of %LVPWt, AT and ESS values in addition to standard echocardiographic examination could be the guidance for early diagnosis of late cardiac toxicity.

Treatment of Wilms tumor: a report from the Turkish Pediatric Oncology Group (TPOG).

AIM: To standardize diagnosis and treatment of childhood Wilms tumor (WT) in Turkey. METHODS AND PATIENTS: Between 1998 and 2006, WT patients were registered from 19 centers. Patients <16 years with unilateral WT whose treatment started in first postoperative 3 weeks were included. Treatments were stage I favorable (FH) and unfavorable histology (UH) patients, VCR + Act-D; stage IIA FH, VCR + Act-D; stage IIB FH, VCR + Act-D + radiotherapy (RT); stage III-IV FH, VCR + Act-D + adriamycin (ADR) + RT; stages II-IV UH tumors, VCR + Act-D + ADR + etoposide + RT. RESULTS: 165/254 registered cases were eligible (bilateral, 5.9%) [median age 3.0 years; M/F: 0.99; 50/165 cases < or =2 years]. 9.7% cases had UH tumors. Disease stages were stage I 23.6%; IIA 36.4%; IIB 5.5%; III 22.4%; IV 12.1%. Cases >2 years had significantly more advanced disease. 1/11 cases with recurrent disease died; 2/165 had progressive disease, 2/165 had secondary cancers, and all 4 died. In all cases 4-year OS and EFS were 92.8 and 86.5%, respectively. Both OS and EFS were significantly worse in stage IV. CONCLUSIONS: Despite problems in patient management and follow-up, treatment results were encouraging in this first national experience with a multicentric study in pediatric oncology. Revisions and modifications are planned to further improve results and minimize short- and long-term side effects.