[Show abstract][Hide abstract] ABSTRACT: Background:
There are a few published studies about prognostic markers of Epstein-B virus (EBV) related to outcomes in pediatric Hodgkin Lymphoma (HL).
We aimed to investigate the prognostic value and effect of EBV on survival by using biopsy materials in children and adolescents diagnosed with HL.
Patients and Methods:
EBV LMP-1 expression was examined using immunohistochemical methods in 58 tumor samples. Clinical features, overall survival (OS) and failure free survival time (FFS) were compared between EBV LMP-1 positive and negative patients.
In 20 (35%) patients tumors were LMP-1 positive. When compared with patients above 10 years old, EBV LMP-1 was often positive in patients under 10 years old (30% vs. 70%, P = 0.02). In our most cases having B symptoms and advanced stage, EBV positiveness in Hodgkin Reed-Stenberg cells (H-RS) was not a significant determinant for survival (P = 0.78). Half of the past clinical trials in childhood HL reported longer survival rates in EBV LMP-1 positive patients. In some trials similar to our results there was no significant relationship between EBV and prognosis.
The reason of diminished EBV positiviness may be related to technical methods such as not using immunohistochemical and in situ hybridization for EBER antigen but in laboratory conditions painting of control tissues with EBV impair this probability. In addition, cases enrolled to our study were living in Istanbul where social and economical factors are improved rather than generally.
Full-text · Article · Dec 2015 · Iranian Journal of Pediatrics
[Show abstract][Hide abstract] ABSTRACT: Immune thrombocytopenia (ITP) is an acute self-limited disease of childhood, mostly resolving within 6 months irrespective of whether therapy is given or not. Treatment options when indicated include corticosteroids, intravenous immune globulin (IVIG), and anti-RhD immunoglobulin. We reviewed our 32 years' experience for first-line therapy of acute ITP. Five hundred forty-one children (mean age: 5.3 years) diagnosed and treated for ITP were evaluated retrospectively. Among 491 acute ITP patients, IVIG was used in 27%, high-dose steroids in 27%, low-dose steroids in 20%, anti-D immunoglobulin G (IgG) in 2%, and no therapy in 22%. When the initial response (platelets >50 × 10(9)/L) to first-line treatment modalities were compared, 89%, 84%, and 78% patients treated by low-dose steroids, high-dose steroids, and IVIG responded to treatment, respectively (P > .05). Mean time to recovery of platelets was 16.8, 3.8, and 3.0 days in patients treated with low-dose steroids, high-dose steroids, and IVIG, respectively (P < .0001). Thrombocytopenia recurred in 23% of low-dose steroid, 39% of high-dose steroid, and in 36% of IVIG (P < .0001) treatment groups. Of 108 patients who were observed alone, 4 (3%) had a recurrence on follow-up and only 2 of these required treatment subsequently. Recurrence was significantly less in no therapy group compared with children treated with 1 of the 3 options of pharmacotherapy (P < .0001). Response rates were similar between patients treated by IVIG and low- and high-dose steroids; however, time to response was slower in patients treated with low-dose steroids compared with IVIG and high-dose steroids.
No preview · Article · Jul 2015 · Pediatric Hematology and Oncology
[Show abstract][Hide abstract] ABSTRACT: Malignant rhabdoid tumor is a rare and malignant tumor of childhood. Generally it originates from the kidney and central nervous system, but occasionally it may arise from the orbit. Differential diagnosis from other childhood soft tissue sarcomas should be done. We report here an 8-week-old female infant with malignant rhabdoid tumor of the orbit who was treated with chemotherapy and surgery. The 8 week-old girl was referred to our hospital with a history of right proptosis first noted at birth. Physical and laboratory evaluation of the patient was normal except for right proptosis. The mass was removed surgically. Histopathologic examination and immunohistochemical findings of the specimen were evaluated as malignant rhabdoid tumor. Chemotherapy was administered. While in clinical remission, she succumbed during a febrile episode. Malignant rhabdoid tumor can rarely originate from the orbit. Malignant rhabdoid tumor should be kept in mind in the differential diagnosis of orbital masses, and surgery, chemotherapy and local radiotherapy should be used as combined therapy due to the poor prognosis.
No preview · Article · Jan 2013 · Turk Patoloji Dergisi
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine whether iron deficiency (ID) is associated with zinc deficiency. One hundred patients with ID and/or iron deficiency anemia (IDA) and 100 healthy controls aged 6 months to 18 years who were examined at Cerrahpaşa Medical Faculty, Pediatric Outpatient Clinic were included prospectively. The association between zinc levels and hematological and biochemical parameters was examined. Serum zinc levels were lower in cases compared to controls, and the difference was statistically significant. Zinc deficiency was more frequent in children with ID and/or IDA (9.2%) than in controls (1%). There was no correlation between zinc levels and hemoglobin (Hb), hematocrit (Htc), mean corpuscular volume (MCV), ferritin, or total iron binding capacity (TIBC). However, there was a positive correlation between zinc levels and iron and transferrin saturation index (TSI). In our study, we detected significantly lower zinc levels in children with ID before the onset of clinical and laboratory findings of anemia.
No preview · Article · Jan 2013 · Cocuk Sagligi ve Hastaliklari Dergisi
[Show abstract][Hide abstract] ABSTRACT: Aim The aim of this study is to determine whether iron deficiency is associated with zinc deficiency.
Methods Ninety-eight patients with ID and/or IDA and 100 healthy controls who were examined at Cerrahpasa Medical Faculty, Pediatric and Child Health Department outpatient clinic were included prospectively in this study. Blood samples were collected from cases and controls for complete blood count, iron, TIBC, ferritin and zinc levels. The association between zinc levels and hematological and biochemical parameters were examined.
Results There was significant difference (p<0.05) between zinc levels of the cases and controls, serum zinc levels were lower in cases compared to controls. Zinc deficiency was more frequent in children with iron deficiency and/or anemia (9.2%) than those without iron deficiency (1%). In cases, no significant difference was found (p>0.05) between zinc levels in relation to the absence or presence of anemia. There was no correlation between zinc levels and Hb, Htc, MCV, ferritin or TIBC (p>0.05). However there was a positive correlation beween zinc levels and iron and TSI. In the control group, there was no statistical relation between zinc levels and Hb, Htc, MCV, iron, TIBC, TSI and ferritin levels (p>0.05).
Conclusion In our study, we detected significant lower zinc levels in children with iron deficiency before the onset of anemia. Therefore, we propose that the use of preparations containing both iron and zinc might be more effective in improvement of clinical signs of iron and zinc deficiency.
Full-text · Article · Oct 2012 · Archives of Disease in Childhood
[Show abstract][Hide abstract] ABSTRACT: Hereditary spherocytosis (HS) is a congenital hemolytic anemia which is characterized by spherocytes in peripheral blood and increased osmotic fragility test. The disease is caused by defects in red cell membrane cytoskeleton. In this study, we investigated erythrocyte membrane protein defects in 50 Turkish HS patients and 42 controls. We used sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) to identify the protein defects causing HS. The patients were from 27 families (39 kindred and 11 unrelated patients). They were aged between 6 months and 53 years and the mean age was 18.75 (±14.70) years. Protein deficiencies related to HS were demonstrated in 42% of study group. There was not any statistically significant relation between the protein deficiency and hemoglobin levels. Isolated or combined spectrin deficiency was the most common protein abnormality among our patients. Spectrin deficiency was detected in 22% of cases (11/50), ankyrin deficiency in 8% (4/50), protein 4.2 deficiency in 8% (4/50), combined spectrin and protein 4.2 deficiency in 2% (1/50), combined spectrin and ankyrin deficiency in 2% (1/50). Fifty-eight percent of cases (29/50) showed normal protein contents.
[Show abstract][Hide abstract] ABSTRACT: B-lineage acute lymphoblastic leukemia (B-ALL) is a common subtype of acute leukemia in children. PAX5 plays a central role in B-cell development and differentiation. In this study, we analyzed PAX5 expression levels, transactivation domain mutations/deletions in B-ALL patients (n=115) and healthy controls (n=10). Relative PAX5 mRNA levels were significantly increased in B-ALL patients (p<0.0001). PAX5 expression was also evaluated in three different B-ALL subgroups (pro B, Common B and Pre B ALL) and showed stage specific expression levels. Pro B (p=0.04) and pre B (p=0.04) patients showed significantly high PAX5 mRNA levels compared to stage specific controls. At least one deletion of exons 7-8 or 9 has been identified in the 41% of the patients. CD34 positivity in patients and presence of large deletions (Δ7/8/9) showed a significant correlation (p=0.05). None of our patients showed PAX5 point mutations, but two previously identified SNPs (rs3780135 and rs35469494) were detected. Our results support that PAX5 is a critical factor in B-ALL development and aberrant PAX5 expression especially at early stages may leads to leukemic transformation.
Full-text · Article · Aug 2011 · Leukemia research
[Show abstract][Hide abstract] ABSTRACT: Neuroblastoma is the most common extracranial solid tumour in childhood. Neuroblastoma is sometimes seen with neuro-fbromatosis. A one year old boy was investigated for fever, anemia, subcutaneous soft tissue nodules, exophtalmus, horizontal nystagmus, café-au lait spots, hepatosplenomegaly and lymphadenomegaly and was referred to Pediatric Hematol-ogy-Oncology clinic. The patient was initially diagnosed as neurofbromatosis and juvenile myelomonocytic leukemia but his final diagnosis was neuroblastoma. Neurofbroma and neuroblastoma both originate from neural crest cells and they share a common pathogenesis. It is important to evaluate children who are diagnosed as neurofbromatosis for neuroblas-toma especially when there is a fast growing mass. Radiology and urine catecholamine levels may be helpful in diagnosis.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to assess the demographic data and treatment results of children who were diagnosed with Burkitt lymphoma and treated according to the Berlin-Frankfurt-Münster-95 (BFM) protocol in a single institution. A total of 48 patients (37 boys, 77%) with a median age of 8 years (range 2 to 16 years) at diagnosis, were evaluated. Primary tumor sites were abdomen (70.8%), head and neck (22.9%), peripheral lymph node (2%), bone (2%), and testis (2%). The 5-year overall survival (OS) and event-free survival (EFS) were 78.1±4% and 76.6±6%, respectively. In univariate analysis, hemoglobin level less than 10 g/dL, cerebrospinal fluid (CSF) positivity and dialysis requirement at diagnosis were found to be important reverse predictor factors for EFS (P; 0.001, 0.001, 0.004, respectively). In multivariate analysis, hemoglobin level less than 10 g/dL and dialysis at diagnosis were found to be important reverse predictor factors for EFS (P; 0.0001). The EFS of our patients was lower than the values achieved with BFM-95 protocol in other centers. This study provides evidence that low hemoglobin level, CSF positivity and dialysis at diagnosis were important predictor factors for EFS in children with Burkitt lymphoma.
No preview · Article · Oct 2010 · Journal of Pediatric Hematology/Oncology
[Show abstract][Hide abstract] ABSTRACT: The NOTCH signaling pathway plays important role in the development of multicellular organisms, as it regulates cell proliferation, survival, and differentiation. In adults, it is essential for the T- or B-lymphocyte lineage commitment. NOTCH1 and FBXW7 mutations both lead the activation of the NOTCH1 pathway and are found in the majority of T-ALL patients. In this study, the mutation analysis of NOTCH1 and FBXW7 genes was performed in 87 pediatric T-ALLs who were treated on the ALL-BFM protocols. In 19 patients (22%), activating NOTCH1 mutations were observed either in the heterodimerization domain or in the PEST domain and 7 cases (10%) demonstrated FBXW7 mutations (2 cases had both NOTCH1 and FBXW7 mutations). We also analyzed the relationship of the mutation data between the clinical and biological data of the patients. NOTCH1 and FBXW7, NOTCH1 alone were found correlated with lower initial leucocyte counts which was independent from the sex and T- cell immunophenotype. However, NOTCH1 and FBXW7 mutations were not predictive of outcome in the overall cohort of pediatric T-ALLs.
[Show abstract][Hide abstract] ABSTRACT: It is well known that survivors of acute lymphoblastic leukemia (ALL) show a tendency to become overweight. Cranial irradiation (CRT), is considered to be the primary risk factor for development of obesity.
The aim of our study was to evaluate body mass index (BMI) and serum leptin levels in survivors of childhood ALL.
Subjects (Group I) consisted of 93 survivors of childhood ALL (53 males > or = 9 years old, 40 females > or = 8 years old) diagnosed between January 1975 and December 2002 in the Hematology-Oncology Division in Cerrahpasa Medical Faculty, Istanbul University after a follow up 10.21 +/- 4.90 (mean +/- SD) years. Fifty healthy individuals of similar chronological age were taken as controls (29 males, 21 females). Seventy-four subjects had received radiotherapy (Group IA) and 19 had not (Group I B).
In Group I, BMI was significantly higher than in Group II (21.65 +/- 4.02 vs 20.31 +/- 3.49, p = 0.04). However, BMI was significantly higher only in Group I A (21.83 +/- 4.27) than in Group II (p = 0.032). Leptin levels were significantly higher in Group I A females than in Group II females. There was a significant correlation between BMI-SDS and serum leptin levels in group IA females.
Leukemia treatment leads to obesity. Higher leptin levels in girls may suggest that sex may be a differentiating factor for this late effect.
No preview · Article · Jul 2010 · Journal of pediatric endocrinology & metabolism: JPEM
[Show abstract][Hide abstract] ABSTRACT: To standardize diagnosis and treatment of childhood Wilms tumor (WT) in Turkey.
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.
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.
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.
No preview · Article · Apr 2010 · Pediatric Hematology and Oncology
[Show abstract][Hide abstract] ABSTRACT: Sialoblastomas are very rare congenital tumors of the salivary gland that usually occur in parotid or submandibular glands. They can be benign or malignant histologically. The recommended treatment for sialoblastoma is the excision of tumor totally and widely. Alternative therapies for sialoblastoma treatment remains controversial, chemotherapy may be an alternative treatment for relapsed or metastatic sialoblastomas. In this report we describe a malignant and relapsed sialoblastoma at cheek region.
No preview · Article · Mar 2010 · International Journal of Pediatric Otorhinolaryngology Extra
[Show abstract][Hide abstract] ABSTRACT: The authors evaluated the possible effect of DNA repair genes, XPD (Xeroderma pigmentosum group D) codon (312 and 751) and XRCC1 (X-ray repair cross-complementing group 1) codon (194 and 399) SNPs (single-nucleotide polymorphisms) on the risk of childhood B-cell lymphoma.
The polymorphisms were analyzed in 33 patients with BL cases and in 52 healthy, age-matched controls using PCR-RFLP method.
The authors observed no association between variation in the XPD codon Asp312Asn, Lys751Gln, and XRCC1 codon Arg399Gln polymorphisms and B-cell lymphoma for any parameter. In contrast, tryptophan allele frequency in control and patient groups was 0.10 and 0.03 respectively (p = .04). The frequency of XRCC1 194Arg/Trp genotype in B-cell lymphoma was significantly lower than that in controls (p = .005). No significant relationship was found between genotypes and stage, lactate dehydrogenase, or bone marrow involvement.
XRCC1 194Trp allele may be associated with a protective effect against development of childhood B-cell lymphoma. However, these results were based on a small number of case and further studies should be done.
No preview · Article · Oct 2009 · Pediatric Hematology and Oncology
[Show abstract][Hide abstract] ABSTRACT: Polymorphisms have been identified in several DNA repair genes. These polymorphisms may effect DNA repair capacity and modulate cancer susceptibility. In this study, we aimed to determine the four polymorphisms in two DNA repair genes, xeroderma pigmentosum complementation group D (XPD) and X-ray repair cross-complementing group 1 (XRCC1), in a sample of Turkish patients with childhood acute lymphoblastic leukemia (ALL), and evaluate their association with childhood ALL development. We used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), to analyze XPD Asp312Asn, XPD Lys751Gln, XRCC1 Arg194Trp, and XRCC1 Arg399Gln polymorphisms in 70 patients with childhood ALL and in 75 disease-free controls, who were of a similar age. No significant differences were observed among the study groups with regard to the XPD codon 312, XPD codon 751, XRCC1 codon 194, and XRCC1 codon 399 polymorphisms. However, the combined XRCC1 Arg194Trp/Trp194Trp variant genotypes were associated with increased risk for ALL in females (OR=5.47; 95% CI=1.49-20.10; p=0.008). This finding indicates that females carrying XRCC1 194Trp allele are at increased risk of developing childhood ALL. These results suggest that the risk of childhood ALL may be associated with DNA repair mechanisms, and understanding these mechanisms will help identify individuals at increased risk of developing childhood ALL, and also should be lead to improved treatment of ALL.
No preview · Article · Jun 2009 · Leukemia research
[Show abstract][Hide abstract] ABSTRACT: The aim of our study was to show how the progression and severity of Familial Mediterranean Fever (FMF) is affected by procoagulant activity and alterations in the markers of thrombosis and fibrinolysis. The study cohort comprised 64 FMF patients who were classified as attack-free patients (Group 1; n = 34 patients, aged 3-19 years) and attack patients (Group 2; n = 30 patients, aged 3-21 years). All patients were on colchicine treatment with the exception the newly diagnosed patients in Group 2. A total of 14 healthy subjects between 5-12 years of age were enrolled as controls (Group 3). Laboratory tests, including leukocyte and thrombocyte counts, erythrocyte sedimentation rate, CRP, fibrinogen, PT, aPTT, Factor VIII, vW factor, D-dimer, P-selectin, tPA and PAI-1, were carried out on all patients. Inflammation continued both during the attack and attack-free period in FMF. The prolongation of PT was observed during attacks (PT = 13.6 s in Group 2, and PT = 12.6 s in Group 3; p = 0.002). tPA levels increased in FMF patients (tPA levels of group 1, 2 and 3 were 12.6, 13.2 and 9.7 ng/ml, respectively; p = 0.01). P-selectin was lower in both patient groups than in the control group. During attack periods PAI-1 levels increased (PAI-1 level of Group 1: 89.6 ng/ml and PAI-1 level of Group 2: 335.7 ng/ml, p = 0.000). Inflammation with increased acute phase reactants continued during both attack and attack-free periods in FMF patients. Prolongation of PT and differences in tPA and P-selectin levels suggest that hypercoagulability may have a role in the etiopathogenesis of FMF. It may be possible to use PAI-1 as a marker for the attacks of FMF.
No preview · Article · Apr 2008 · European Journal of Pediatrics
[Show abstract][Hide abstract] ABSTRACT: Aim: After vascular injury, if integrity of circulatory system could not be maintained and blood coagulation does not initiated, bleeding occurs. Excessive blood loss is a result of conjenital or acquired disease of platelets, endothelial cells or coagulation factors. Bleeding is a severe symptom threatening families forcing them to go an emergency department. Material and Method: In this study, we investigated 78 patients complaining from bleeding who came to emergency ward of Cerrahpasa Medical Faculty Hospital in İstanbul, between January 1998 and January 2003. Results: Hematuria is the most common bleeding symptom (20/78 ; 26%). Urinary tract infection was the etiological reason in 30% of these patients. Gastrointestinal bleeding ( hematemesis, melena and hematochezia) was seen in 20 (26%) cases. Acute gastoenteritis was the reason for hematochezia (33%) while gastritis, esophagitis and ulser were the etiological verifications of melena and hematemesis. Epistaxis was the third most common reason for bleeding (18/78; 23 %) with upper respiratory tract infections found in 60 %. Skin bleedings ( petechiae 10/78; ecchymosis 4/78) were detected in 18 % patients. Idiopathic thrombocytopenic purpura was the reason in 80%. Malignacy was evaluated in 10 % whilst traumatic injury was the reason in 50 %. Often hemorrhagic diatesis was the differential diagnosis when bleeding was seen from mucosa, into soft tissue, or as hemartrosis. No patient was lost due to bleeding. Conclusions: Bleeding is an urgent situation for diagnosis and treatment. The most common etiological factors must be taken into consideration in order to avoid unnecessary expensive laboratory evaluation with a good history and clinical verifications for an exact diagnosis.
No preview · Article · Sep 2006 · Turk Pediatri Arsivi
[Show abstract][Hide abstract] ABSTRACT: In this study, the authors aim to describe the survival and clinical characteristics of 141 retinoblastoma cases treated at Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey, between 1981 and 2004.
The authors retrospectively analyzed the clinical records of 141 children (177 eyes) diagnosed with retinoblastoma and treated between 1981 and 2004. Information on gender, laterality, age at diagnosis, presenting signs, spread of tumor, treatment modality, survival rate, and family history were collected.
A total of 105 cases (74.5%) were unilateral and 36 cases (25.5%) were bilateral. The mean age overall at the time of diagnosis was 25 months; in unilateral cases, 29 months; and in bilateral cases, 16 months. The most common presenting signs were leukocoria (116 cases, 82%), strabismus (14 cases, 10%) and proptosis (11 cases, 8%). A total of 28 cases had orbital extension, nine patients had central nervous system invasion, and five cases exhibited bone marrow involvement. In total, 16 patients (11%) had a family history of retinoblastoma. One case developed a secondary neoplasm. The 3 year cumulative survival rate of 141 patients was 89.69% (unilateral, 90.74%; bilateral 87.35% P = 0.9371, P > 0.05, log rank test).
The study's survival rate was similar to developed countries. The success in higher survival rates is based on the authors multidisciplinary team approach done by the same group and the support of the authors' clinic and government in sponsoring the medical insurance of all patients.
Full-text · Article · Aug 2006 · Pediatrics International