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Objective: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare subgroup of embryonal tumors of childhood central nervous system (CNS) tumors. It has been reported that approximately 75-98% of patients with AT/RT have somatic changes (deletion, point mutation, loss of heterozygosity) in the SMARCB1/INI1 gene localized in 22q11.2 and also one-third of the patients have germline mutations. This study aimed to investigate the SMARCB1/INI1 mutations, a tumor suppressor gene associated with this tumor, in patients with AT/RT. Material and Methods: The demographic, clinical, pathological features and SMARCB1/INI1 mutations of patients diagnosed at Ege University between 2010-2015 were evaluated. DNA was isolated from pathological preparations of tumor tissue of all cases and peripheral blood of accessible patients, and all exonic regions for the SMARCB1/INI1 gene were reproduced by polymerase chain reaction, and DNA sequence analysis was performed after control by gel electrophoresis. Pathogenicity of the variations found was evaluated according to American College of Medical Genetics 2015 criteria. Results: 7/10 patients were diagnosed as AT/RT of CNS, 2/10 as soft tissue RT, and 1/10 as the renal RT. In 77% of the patients, loss of SMARCB1/INI1 protein expression was detected by immunohistochemical methods in tumor tissue and mean survival was 5 months (1-69 months, SE: 9.29 months). The mutation was detected in SMARCB1/INI1 in tumor tissue of four patients and median survival was 5.5 months (1-15 months, SE: 2.95 months). The median survival of patients without a mutation in the SMARCB1/INI1 gene was found to be 10.5 months (1-81 months, SE: 14.6 months). Conclusion: The median survival time of the patients with SMARCB1/INI1 mutation seems to be shorter than the ones without the mutation. Unlike previous publications, in our patient group diagnosed as AT/RT, no germline mutation was detected in the SMARCB1/INI1 gene. Copyright © 2020 by Türkiye Klinikleri. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Amaç: Her yıl Dünyada 0-19 yaş arası yaklaşık 300.000 olgu kanser tanısı almaktadır. Gelişmiş ve gelişmekte olan ülkelerde çocukluk çağı kanserlerinin dağılımı ve sağ kalım hızlarında belirgin farklılık bildirilmektedir. Bu çalışmada amacımız merkezimizde kayıtlı olan çocukluk çağı kanser olgularının epidemiyolojik özelliklerini ve sağ kalım hızlarını değerlendirmektir.Gereç ve Yöntem: Merkezimizde 1992-2017 tarihleri arasında 0-19 yaş arasında kanser tanısı alan 4602 hastanın verileri Ege Üniversitesi Kanserle Savaş ve Araştırma Merkezi kayıtları kullanılarak geriye dönük olarak değerlendirildi. Yaşa, cinsiyete, yıllara göre tümör dağılımları ve genel sağ kalım hızları değerlendirildi.Bulgular: Olguların %55,3’ü erkek, %44,7’si kız ve erkek/kız oranı 1,23/1 idi. Olguların ortalama tanı yaşı 5,6 yıl idi. Merkezimizde en sık lösemi (%25,6), ikinci sıklıkta santral sinir sistemi tümörleri (%23,4), üçüncü sıklıkta ise lenfomalar (%14,2) görülmekteydi. Olguların ortalama izlem süresi 41,4 ay (0-316 ay) idi. Tüm olgular için beş yıllık genel sağ kalım hızı %74 saptandı.Sonuç: Merkezimizdeki kanser tiplerinin dağılımı ve genel sağ kalım hızları literatür ile benzerdir. Ülkemiz verileri ile karşılaştırıldığında genel sağ kalım hızlarımızın daha iyi olduğu görülmüştür. Bu sonuçlar sağ kalım hızlarının bölgeden bölgeye değiştiğini, bu değişimde hasta ve hasta yakınının farkındalık düzeyinin, gerekli tedaviye ulaşabilme imkanının ve multidisipliner merkezlerin varlığının önemini düşündürmektedir., Aim: Approximately 300.000 children between the ages of 0-19 diagnosed with cancer every year in the world. The distribution and survival rates of childhood cancers are significantly different in developed and developing countries. The aim of this study to evaluate the epidemiological characteristics and survival rates of childhood cancer cases registered in our center.Materials and Methods: Recordings of 4602 patients diagnosed with cancer between 0-19 years of age at our center between 1992 and 2017 were evaluated retrospectively using the registry of Ege University Cancer Control and Research Center. Distribution of cancer groups and overall survival rates were evaluated according to age, sex and years.Results: Median age was 5.6 years. 55,3% of the cases were male, 44,7% were female and the male/female ratio was 1.23/1. Leukemias (25.6%), central nervous system tumors (23.4%), and lymphomas (14.2%) were the most common tumors in our center. The median follow-up period was 41.4 months (0-316 months). The 5-year overall survival rate for all patients was 74%.Conclusion: The distribution of cancer types and overall survival rates in our center are similar with those reported in the literature. Compared with the cancer registry of our country, our overall survival rates were found to be better. These results suggest that survival rates vary from region to region, and the importance of awareness of the patient and his/ her relatives, access to the treatment and the presence of multidisciplinary centers.

Mutations in the interleukin-21 receptor (IL-21R) gene are recently defined as primary immunodeficiency diseases. IL-21R defects result in combined immunodeficiency by affecting the functions of innate and adaptive immune system components.A six-year-old girl was admitted to our hospital with complaints of chronic diarrhea that started after the newborn period and generalized rash over the last three months. She had severe respiratory distress due to Cytomegalovirus (CMV) pneumonia requiring mechanical ventilation and was diagnosed as combined immunodeficiency at another hospital at the age of four. Her physical examination on admission revealed erythematous rash on cheeks, extremities, gluteal region, and lymph node enlargements in cervical, axillary, and inguinal regions. CMV DNA and stool

Langerhans cell histiocytosis (LCH) is a rare disorder. Uncontrolled clonal proliferation of langerhans cells leads to a diversity of clinical manifestations. Low dose Radiotherapy (RT) is used mainly for osseous manifestations as a sole treatment or in combination with surgery/chemotherapy/steroids. Altough the mechanism of action of RT is an unresolved issue, it’s usually used in adjuvant/palliative settings, also as first-line local therapy with curative intent in unresectable or resectable cases in case surgery would result in functional compromise. This study is conducted to review indications, dose-fractionation schedules, clinical characteristics and outcomes of LCH patients received local RT mainly for osseous lesions. the medical records of biopsy proven all LCH patients referred to our center and treated with RT between 2000-2016 were evaluated retrospectively. Disease-free survival (DFS), local control and side effects were defined as study end-points. There was 35 patients, 21 of them were children. At presentation 65.7% had single systemsingle bone, 20% had single system-multiple bone, 15% had multisystem disease.Soft tissue extension were detected in 16 children, 4 adults (p= 0.013).Mean radiation dose was 10.8 Gy. Median follow-up from the date of biopsy was 105 months (range= 8-204) in children and 88 (range:31-245) in adults (log rank p:0.029).Complete response rate was 97%. 11 children and 1 adult experienced relapse (p= 0.05), median interval for relapse was 9months in children, 19months in adults. the most common relapse pattern was as single system-multiple bone (58.3%). Local control was 97.1%. Median disease free survival was 85 months. Low dose local RT seems to be effective and safe in multidisciplinary management of LCH., Langerhans hücreli histiositozis (LCH), langerhans hücrelerine benzer dentritik hücrelerin çeşitli organlarda birikimi ve kontrolsüz klonal çoğalması ile karakterize, nadir görülen bir hastalıktır. Düşük doz radyoterapi (RT) ağrılı ve stabil olmayan kemik lezyonları ve kemik dışı yumuşak doku lezyonlarının tedavisinde tek başına ve/veya cerrahi, kemoterapi, steroidlerle birlikte kullanılmaktadır. Etki mekanizması halen net olarak anlaşılmamıştır. RT genelde adjuvant ve palyatif endikasyonlarda, ayrıca rezeke edilemeyen veya cerrahinin fonksiyonel hasar yaratabileceği rezektable olgularda küratif amaçlı olarak kullanılmaktadır. Bu çalışmada, çoğunlukla kemik lezyonlarına yönelik lokal RT uygulanan LCH tanılı olgularda klinik özellikler, RT endikasyonları, doz-fraksiyonizasyon şemaları ve tedavi sonuçlarının araştırılması amaçlanmıştır. 2000-2016 tarihlerinde kliniğimizde RT uygulanan biopsi ile kanıtlanmış tüm LCH tanılı olguların tedavi ve izlem kayıtları geriye dönük olarak değerlendirilmiştir. Hastalıksız sağkalım, lokal kontrol ve geç yan etki çalışmanın sonlanım noktaları olarak belirlenmiştir. 35 olgu saptanmıştır. Ortanca yaşı 12 (6-27), 21 olgu (%60) pediatrik yaş grubundadır. Olguların %65.7’sinde tek sistem-tek kemik tutulumu, %20’sinde tek sistem-çoklu kemik tutulumu, %15’inde çoklu sistem tutulumu saptanmıştır. Pediatrik yaş grubundaki olguların 16’sında ve erişkinlerin 4’ünde kemik lezyonlarına yumuşak doku uzanımının eşlik ettiği tespit edilmiştir (p= 0.013). Ortanca RT dozu10,8 Gy’dir. Patolojik tanı tarihinden itibaren olan ortanca izlem süresi pediatrik olgularda 105 (18-195), erişkinlerde 88 (31-245) aydır. Tam yanıt oranı %97’dir. İzlemde 11 pediatrik, 1 erişkin olguda yineleme saptanmıştır (p= 0.05), yineleme için geçen ortanca süre pediatrik olgularda 9ay, erişkin olguda 19aydır.Ortanca hastalıksız sağkalım 85 ay (52-117) olarak tespit edilmiştir. En sık yineleme paterni tek sistem-çoklu kemik tutulumu olarak izlenmiştir.Lokal control %97.1’dir. Ortanca hastalıksız sağkalım 85 aydır. LCH’de düşük dozda RT multidisipliner tedavinin bir parçası olarak, etkin lokal kontrol sağlayabilen, güvenilir bir tedavi seçeneğidir.

Mutations in the interleukin-21 receptor (IL-21R) gene are recently defined as primary immunodeficiency diseases. IL-21R defects result in combined immunodeficiency by affecting the functions of innate and adaptive immune system components. A six-year-old girl was admitted to our hospital with complaints of chronic diarrhea that started after the newborn period and generalized rash over the last three months. She had severe respiratory distress due to Cytomegalovirus (CMV) pneumonia requiring mechanical ventilation and was diagnosed as combined immunodeficiency at another hospital at the age of four. Her physical examination on admission revealed erythematous rash on cheeks, extremities, gluteal region, and lymph node enlargements in cervical, axillary, and inguinal regions. CMV DNA and stool Cryptosporidium parvum were positive. Marginal zone lymphoma -negative for Epstein-Bar virus- was reported in the lymph node biopsy. Targeted next-generation sequencing Ion AmpliSeq (TM) primary immunodeficiency panel revealed a novel homozygous IL21R c.132delC (p.Ser45fs) mutation. This case is presented to emphasize that IL21R defects should be considered in the differential diagnosis of the patients with recurrent respiratory infections, chronic diarrhea, C. parvum infection, chronic liver disease, sclerosing cholangitis, and malignancy where early hematopoietic stem cell transplantation (HSCT) is life-saving. A total of eight cases with IL21R gene defects have been reported so far. The significance of this case is that it is the first case of malignancy among the published IL-21R deficient patients successfully treated with HSCT.

A 10-year-old girl was brought to the clinic with the complaint of a salmon-colored conjunctival lesion for 1 month. With the aid of histopathological evaluation and other tests, extranodal ocular adnexal marginal zone lymphoma was diagnosed. The patient was graded as T1bN0M0 according to AJCC and Stage 1 according to Ann Arbor classification. She was treated with external radiotherapy at 1.8 Gy/day for 17 days for a total dose of 36 Gy. She is in remission for 26 months and still being followed up.

Background/aims Pancreatic solid pseudopapillary tumor (SPT) is a rare neoplasm in children. In this study, we aimed to present our surgical strategy based on minimal resection by enucleation or limited resection in localized pancreatic SPT. Materials and methods We retrospectively analyzed the medical records of children who underwent surgical resection between October 2011 and September 2016. Results Five female patients with a median age of 15 years (range, 14-17 years) were operated. Tumors were located in the pancreatic head (n=4) or tail (n=1). The median greatest tumor diameter was 9 cm (range, 5-13 cm). All the patients were investigated with MRI before the resection to demonstrate the relationship between the tumor and the main pancreatic duct. Patients underwent enucleation (n=4) for head localization or local distal resection without splenectomy (n=1) at the pancreatic tail. At postoperative follow-up, major pancreatic leakage was observed in two patients and endoscopically treated. Surgical margins were negative in all patients. The median follow-up period was 44 months (range, 2-59 months) and no local recurrence or distant metastasis was observed in the postoperative period. Conclusion An optimal surgical strategy is still controversial in pancreatic SPT in children. Radical resections such as pancreaticoduodenoctomy or distal pancreatectomy with splenectomy result in loss of pancreatic tissue for endocrine and exocrine functions. Minimal resections such as enucleation or limited pancreatic resection with negative surgical margins should be performed in selected patients with no invasion to the main pancreatic duct or adjacent organs.

EgeUn###, The aim of this qualitative research study is to reveal children's and their mothers' views and experiences related to nasogastric tube feeding, which is the most frequently performed nutrition delivery method in pediatric oncology. The present study was carried out at an university pediatric oncology inpatient service. A total of three children and 14 mothers participated in the study. The analysis of the data was conducted according to Kolcaba's Comfort Theory. The findings resulting from the content analysis were explained under four main themes: (1) physical: includes the inability to be fed orally, nasogastric tube intervention, comfort because of feeding, medication administration, and satisfaction; (2) psychospiritual: includes anxiety, fear, distorted body image, and compliance; (3) sociocultural: includes conflicts with the child about feeding and advice on feeding via the nasogastric tube to other mothers and children; and (4) environmental: includes unrestricted/freedom of feeding. Gastroenterology professionals can also provide basic counseling and resources to children and mothers about the importance of maintaining an optimal weight and of enteral nutrition. © 2019 Society of Gastroenterology Nurses and Associates.

Amac : Bu calismada akut lenfoblastik losemi (ALL) on tanili olgularda t(12;21) translokasyonu gercek zamanli kantitatif revers transkriptaz polimeraz zincir reaksiyonu (qRT-PZR) yontemi kullanilarak kantite edildi. Hastalar ve yontemler : Ocak 2009 - Aralik 2013 tarihleri arasinda Ege Universitesi Tip Fakultesi Tibbi Biyoloji Anabilim Dali’na basvuran 175 pediatrik ve 138 eriskin olmak uzere toplam 313 olguya ait kan ve kemik iligi orneklerinde t(12;22) (p13;q22) translokasyonu RNA sonuclari kantitatif olarak degerlendirildi. Olgulara ait 75 kan ve 484 kemik iligi orneklerinden total RNA veya haberci RNA izole edildi. RNA izolasyonlarinin ardindan tamamlayici DNA sentezi gerceklestirildi. t(12;21) (p13;q22) translokasyon calismasi LightCycler t(12;21) Kit’i ile fuzyon transkripte ozgul bicimde tasarlanmis primer ve problarla (Way2Gene) uygun olacak sekilde gerceklestirildi. Son adim olarak, t(12;21) translokasyon sonuclarinin kantitatif olarak degerlendirilmesi gercek zamanli qRT-PZR yontemi kullanilarak LightCycler2 ile gerceklestirildi. Bulgular : Otuz dort pediatrik olgu orneginde (%19) ve 17 eriskin olgunun orneginde (%12) TEL-AML-1 (ETV6-RUNX1) pozitif bulundu. TEL-AML1 (ETV6-RUNX1) kantitasyon degeri ortalamasi pediatrik olgularda 0.90±3.21, eriskin olgularda ise 0.34±1.20 olarak belirlendi. Sonuc : Elde ettigimiz veriler, gercek zamanli qRT-PZR yontemi ile ALL hastalarinda yeni tani doneminde ve tedavi surecinde t(12;21) translokasyonunun kantitatif tayininin hem taninin kesinlestirilmesinde hem de molekuler remisyon saglanmasina yonelik tedaviyi yonlendirmesinde degerli bir yontem oldugunu desteklemektedir.

Amaç: t(4;11), MLL-AF4 translokasyonu sonucu oluşan, 4q21 kromozomal bandına yerleşim gösteren AF4 geninin 11q23 kromozomal bandına yerleşim gösteren MLL genine füzyonu sonucu gelişen kromozomal bir anomalidir. Bu çalışmada, retrospektif olarak 2009-2013 yılları arasındaki akut lenfoblastik lösemi (ALL) hastalarındaki t(4;11) MLL- AF4 translokasyonunun analiz sonuçlarının incelenmesi amaçlandı. Gereç ve Yöntem: Ege Üniversitesi Tıp Fakültesi Tıbbi Biyoloji Anabilim Dalı’na 2009-2013 yılları arasında akut lösemi ön tanısıyla 176 çocuk (70 kız, 106 erkek) ve 144 yetişkin (60 kadın, 84 erkek) olgunun kan veya kemik iliği örnekleri incelendi. Bu olgulara ait 71 kan ve 473 kemik iliği örneğinin t(4;11) translokasyon RNA sonuçları, gerçek zamanlı RT-PCR yöntemi ile kantitatif olarak değerlendirildi. İlk aşamada, kan ve kemik iliği örneklerinden izole edilen total RNA veya mRNA’dan konvansiyonel bir PCR cihazı ile komplementer DNA sentezlendi. İkinci aşamada, gerçek zamanlı PCR cihazı ile t(4;11) kantitasyonu gerçekleştirildi. Olguların kantitatif olarak değerlendirilmesi, pozitif kontrol ve negatif kontrolün karşılaştırılması ile örneklerin negatif yada pozitif (pozitif olgu kopya sayısının referans kopya sayısına oranı) olması şeklinde yapıldı. Bulgular: Çalışmamızda 98’i takip hastası olmak üzere toplam 320 hasta t(4;11) MLL-AF4 translokasyonu için değerlendirildi. Çalışmaların sonucunda toplam 34 olgu (24 çocuk, 10 yetişkin) pozitif ve diğer örnekler negatif olarak bulundu. Sonuç: Bu değerlendirmenin sonuçları, RT-PCR yöntemi ile ALL hastalarında yeni tanı döneminde ve tedavi sürecinde t(4;11) MLL-AF4 translokasyonunun kantitatif tayini, hem tanının kesinleştirilmesinde hem de moleküler remisyon sağlanmasına yönelik tedaviyi yönlendirmesinde değerli bir yöntem olduğunu desteklemektedir., Aim: t(4,11) is a chromosomal abnormality formed by the translocation MLL-AF4, which is the result of the fusion of the AF4 gene, localized on 4q21 chromosomal band, to the MLL gene, localized on 11q23 chromosomal band. The aim of this study is to examine the results of the analysis of t (4;11) MLL-AF4 translocation in acute lymphoblastic leukemia (ALL) patients retrospectively. Materials and Methods: Peripheral blood or bone marrow samples of 176 children (70 girls, 106 boys) and 144 adults (60 women, 84 men) with a preliminary diagnosis of acute leukemia between 2009-2013 were analyzed in the Medical Biology Department of Ege University Faculty of Medicine. The translocation RNA results of 71 peripheral blood and 473 bone marrow samples of these patients were evaluated quantitatively for t(4;11) with real-time RT- PCR. t(4;11) quantitation was performed by real-time qRT-PCR instrument after the synthesis of complementary DNA with conventional PCR from total RNA or mRNA isolated from blood and bone marrow. Quantitative analysis of the patients was performed by comparing positive and negative controls and samples classified as positive or negative (the ratio of the number of positive copies to the number of reference copies). Results: A total of 320 patients, with 98 having also follow-ups, were evaluated for t(4;11) translocation. Totally 34 patients (24 children and 10 adults) were found positive and the other samples were negative. Conclusion: The assessment of these results supports that, quantitative determination of t(4;11) with RT-PCR method among newly diagnosed ALL patients and ALL patients undergoing treatment, is a valuable method for both confirming the diagnosis and guiding the treatment intended to achieve molecular remission.

Amac: Bu calismada, Ege Universitesi Tip Fakultesi Tibbi Biyoloji Anabilim Dali'na 2009-2013 yillari arasinda akut myeloid losemi (AML) on tanisi ile basvuran 402 olgunun (322 yetiskin, 80 cocuk) kan veya kemik iligi orneklerinin inv16 kantitasyon analizlerinin RT-PCR yontemi ile degerlendirilmesi amaclandi. Gerec ve Yontem: Hastalardan alinan kan ve kemik iligi orneklerinden total RNA/mRNA izolasyonunu takiben cDNA'lari elde edilerek revers-transkriptaz-polimeraz zincir reaksiyonu (RT-PCR) yontemiyle inv16 kantitasyonu LightCycler2 cihazinda gerceklestirildi. Bulgular: Dort yuz iki olgu, inv(16) CBFBETA-MYH11 inversiyonu acisindan degerlendirildi. Yapilan analiz sonucunda 12 (% 4) eriskin ve 7 (% 9) cocuk olmak uzere toplam 19 olguda inv16 pozitifligi saptandi. Sonuc: Inv16 kantitatif analizi, AML hastalarinin klinik degerlendirilmesinde, hastaligin seyri ve remisyon saglanmasina yonelik tedavi protokollerinin uygulanmasinda etkili bir yontem oldugunu desteklemektedir. AML hasta grubunu iceren daha genis kapsamli calismalar yapilarak elde edilen sonuclar desteklenmelidir.

WOS: 000410406300006, PubMed ID: 28387647, Objective: The management of childhood thyroid nodules is still a big challenge for clinicians. In this study, we aimed to present our surgical and endocrinological experience in more than one hundred pediatric cases. Methods: A retrospective analysis of patients admitted with a thyroid nodule between 2006 and 2014 was performed. Detailed ultrasonography and fine-needle aspiration biopsy (FNAB) were the cornerstones of the diagnostic approach. Results: One hundred-three children (72 female, 31 male) with a mean age of 13.1 +/- 3.6 years (3-18 years) were admitted to our center. Management strategy was surgery in 58 patients and follow-up in 45 patients. Mean nodule size was 17 +/- 12.7 mm (2-45 mm). The diagnoses were listed as benign solitary nodule (48 patients), thyroid carcinoma (26 patients), multinodular goiter (23 patients), Hashimoto thyroiditis (4 patients), and Graves' disease (2 patients). Surgical procedures were nodulectomy/lobectomy (32 patients), total thyroidectomy (TT) (13 patients), or TT+ neck dissection (13 patients). The rate of malignancy was 25% in the total group and 44% in the surgery group. The malignancy rate was higher in patients younger than 12 years compared to older children (41% vs. 17%, p = 0.040). Metastasis was seen in 38% of the malignant nodules. Postoperative complications were transient hypocalcemia (8%), permanent hypocalcemia (1.7%), and unilateral vocal cord paralysis (1.7%). Recurrence or mortality was not encountered in the 5.4 +/- 1.2-year follow-up period. Conclusion: Thyroid nodule in a child requires an aggressive diagnostic approach due to increased risk of malignancy and metastasis. Intraoperative frozen section examination must be done as a useful adjunct to determine the surgical strategy. Incidence of complications is small in thyroid surgery when performed by experienced surgeons.

Amaç: Kemik iliği transplantasyonu (KİT), pediyatrik hastalarda birçok malign ve malign olmayan hastalıkta kullanılmaktadır. Transplantasyon yapılan hastalarda gözlenen deri belirtileri, genellikle altta yatan primer hastalığa ya da uygulanan yoğun kemoterapi ve radyoterapi protokollerine bağlı olarak ortaya çıkmaktadır. Bu çalışmada, KİT yapılan pediyatrik olgularda mukokutanöz lezyonların tanımlanması amaçlanmıştır. Gereç ve Yöntem: Çalışmaya 2010-2011 yılları arasında KİT yapılması planlanan toplam 44 hasta dahil edilmiştir. Olguların ilk dermatolojik muayeneleri yapıldıktan sonra ilk ay içerisinde her hafta, takip eden 5 aylık süreçte ayda bir ve son 1,5 yılda ise her 3 ayda bir dermatolojik muayeneleri tekrarlanmıştır.Bulgular: Kırk bir olgu çalışmayı tamamladı. Toplam 41 olgunun yaş ortalaması 9,24 (minimum=1 yaş, maksimum=17 yaş); hastaların 26'sı (%64) erkek, 15'i (%36) kadındır. Görülme sıklığı oranlarına göre dermatolojik belirtiler mukozit (%75,6), kseroderma (%70,7), alopesi (%46,3), aftöz stomatit (%22), kutanöz hiperpigmentasyon (%22), tırnak bozuklukları (%24,3), enflamatuvar deri hastalıkları (%24,2), enfeksiyöz hastalıklar (%15,5), graft versus host hastalığı (%17,1) ve makülopapüler döküntü (%4,8) şeklinde sıralanmıştır. Sonuç: KİT hastalarında dermatolojik hastalıklar sıklıkla görülebilmektedir. Dermatolojik belirtilerin yakın takibi bu hasta grubunda tedavinin komplikasyonlarını azaltmada önemlidir, Background and Design: Bone marrow transplantation (BMT) is performed for many malign and non-malign diseases in pediatric patients. Cutaneous signs in transplant patients are usually encountered in the presence of underlying primary diseases or due to the intense conditioning regimens that include chemotherapy and radiotherapy protocols. In this study, it is aimed to define mucocutaneous changes in pediatric patients with BMT.Materials and Methods: A total of 44 patients, in whom BMT was planned between 2010 and 2011, were included in the study. Dermatological examinations were performed at the beginning of the study and were repeated once a week in the first month, once a month in the following 5 months; and once in every 3 months in the last 1.5 years of follow-up.Results: Forty-one patients were completed the study. The mean age of 41 patients was 9.24 years (range: 1-17 years). Of the subjects, 26 (64%) were male and 15 (36%) were female. Dermatological signs, in order of frequency, were mucositis (75.6%), xeroderma (70.7%), alopecia (46.3%), nail disorders (24.3%), inflammatory skin diseases (24.2%), aphthous stomatitis (22%), cutaneous hyperpigmentation (22%), graft versus host diseases (17.1%), infectious diseases (15.5%), and maculopapular rash (4.8%).Conclusion: Dermatological diseases can be frequently observed in BMT patients. Close monitoring of dermatological signs is important to minimize the complications of the treatment in this patient group

WOS: 000396198300003, Background and Design: Bone marrow transplantation (BMT) is performed for many malign and non-malign diseases in pediatric patients. Cutaneous signs in transplant patients are usually encountered in the presence of underlying primary diseases or due to the intense conditioning regimens that include chemotherapy and radiotherapy protocols. In this study, it is aimed to define mucocutaneous changes in pediatric patients with BMT. Materials and Methods: A total of 44 patients, in whom BMT was planned between 2010 and 2011, were included in the study. Dermatological examinations were performed at the beginning of the study and were repeated once a week in the first month, once a month in the following 5 months; and once in every 3 months in the last 1.5 years of follow-up. Results: Forty-one patients were completed the study. The mean age of 41 patients was 9.24 years (range: 1-17 years). Of the subjects, 26 (64%) were male and 15 (36%) were female. Dermatological signs, in order of frequency, were mucositis (75.6%), xeroderma (70.7%), alopecia (46.3%), nail disorders (24.3%), inflammatory skin diseases (24.2%), aphthous stomatitis (22%), cutaneous hyperpigmentation (22%), graft versus host diseases (17.1%), infectious diseases (15.5%), and maculopapular rash (4.8%). Conclusion: Dermatological diseases can be frequently observed in BMT patients. Close monitoring of dermatological signs is important to minimize the complications of the treatment in this patient group.

Background Between cancer treatment courses, children who have not developed any complications or neutropenia are sent home until the start of the next treatment protocol. Objective The aim of this study was to describe the experiences of parents in the home care of children who had been recently diagnosed with cancer and were undergoing cancer treatment but had been discharged from the hospital between treatment protocols. Methods The study was carried out at Ege University, Turkey. Twelve parents of 12 children between 0 and 18 years of age participated in an in-depth interview. The data were analyzed according to Orem's Self-care Deficit Theory. Results The main themes were basic conditioning factors, self-care agency, and self-care needs. Some parents changed their place of residence because of the cancer treatment, focused on the recovery of the child, and experienced fear, perception difficulties, and difficulties related to self-care needs. Conclusions Parents report difficulties with extreme emotions and dilemmas in maintaining their daily routines of life secondary to fear of infection and challenges with feeding their children. Implications for nursing A well-planned discharge education, home visits, and telephone consultation interventions are essential to meet the needs of children and their parents who are at home between treatment courses.

The aim of the study is to the determine the profiles of cell cycle genes and a new candidate oncogene of URG4/URGCP which play role in leukemia, establishing the association between the early prognosis of cancer and the quantitation of genetic changes, and bringing a molecular approach to definite diagnosis. In this study, 36 newly diagnosed patients' with ALL-AML in the range of 0-18 years and six control group patients' bone marrow samples were included. Total RNA was isolated from samples and then complementary DNA synthesis was performed. The obtained cDNAs have been installed 96 well plates after prepared appropriate mixtures and assessed with LightCycler ® 480 Real-Time PCR quantitatively. CHEK1, URG4/URGCP, CCNG1, CCNC, CDC16, KRAS, CDKN2D genes in the T-ALL group; CCND2, ATM, CDK8, CHEK1, TP53, CHEK2, CCNG2, CDK4, CDKN2A, E2F4, CCNC, KRAS genes in the precursor B-ALL group and CCND2, CDK6 genes in the AML group have shown significant increase in mRNA expression level. In the featured role of acute leukemia the regulating signaling pathways of leukemogenesis partially defined, although identification of new genetic markers in acute leukemia subgroups, will allow the development of early diagnostic and new treatment protocols. © 2012 Springer Science+Business Media Dordrecht.

The development of acquired inhibitors against the factor VIII protein in childhood period, is a very rare disorder in nonhemophiliac persons but may be clinically important condition due to potential serious bleedings. We have investigated acquired hemophilia development frequency in children with potential high risk groups. Totally 483 nonhemophiliac children including healthy controls were enrolled the study. Age range was 2 to 20 years and mean age was 11 ± 5.4 years. Risk groups for acquired hemophilia were selected among sick children with transfusion dependent ß- thalassemia major (n= 75), children with malignancy (n= 55), asthma bronchiale (n= 65), type I insulin dependent diabetes mellitus (n= 63), collagen tissue disorders (n= 35). Age-matched 190 healthy children were selected as for healthy control group. Inhibitor tests were performed by the method of Bethesda assay. We have found only two patients who had acquired factor VIII inhibitor among 483 children. These two patients were solid tumor (osteosarcoma) and type I insulin dependent diabetes mellitus. Other risk groups and healthy controls have not inhibitor positivity. As a conclusion, acquired inhibitors should be considered for the differential diagnosis of unusual bleeding episodes in patients who had risk factors of all age groups including childhood period.

This study was carried out in 28 patients (10 female, 18 male) diagnosed with acute leukemia, and aimed to investigate the abnormalities of endocrine system. Twenty-five of 28 patients were acute lymphoblastic leukemia and 3 were acute non-lymphocytic leukemia. Sixteen children were treated using BFM-90 chemotherapy protocol, and the rest with various regimens. Two patients were exposed to 12-13 Gy of total body irradiation followed by bone marrow transplantation. All patients were in remission at least five years. One (3%) of 28 patients had short stature and 4 (14%) had obesity. Pubertal status was retarded in 2 (7%) patients. Glucose intolerance, secondary hypothyroidism and hypergonadotropic hypogonadism were detected in 2, 1 and 2 patients, respectively. TSH response to TRH test was exaggerated in 1 and blunted in 3 patients.Bu çalışmaya akut lösemi tanısı almış ve en az 5 yıldır remisyonda olan 28 hasta (10 kız, 18 erkek) dahil edildi ve bu olgularda endokrin yan etkiler araştırıldı. Yirmibeş hasta akut lenfoblastik lösemi, 3 hasta akut non-lenfositik lösemi tanısı almıştı. Onaltı çocuğun tedavisinde BFM-90 tadavi protokolü kullanılırken diğerleri farklı tedavi rejimleri aldılar. İki hastaya 12-13 Gy total vücut ışınlaması sonrası kemik iliği transplantasyonu uygulandı. Yirmisekiz hastadan birinde (%3) boy kısalığı, dördünde (%14) obezite mevcuttu. Hastaların ikisinde (%7) gecikmiş puberte, ikisinde glukoz intoleransı, birinde sekonder hipotroidizm ve ikisinde de hipergonadotropik hipogonadizm saptandı. Bir olguda TRH testine abartılı TSH yanıtı, 3 olguda baskılanmış yanıt gözlendi.

Hyperleukocytosis, defined as a peripheral leukocyte count ≥ 100x109/L, is seen in 5-20% of newly diagnosed cases of childhood leukemia and is a poor prognostic factor. In this study, we aimed to examine the presenting clinical and laboratory features, complications, and treatment outcome of 47 children with acute lymphoblastic leukemia (ALL) and hyperleukocytosis who were diagnosed and treated in four medical centers of İzmir between January 1990 and January 2001. The median age was 5.0 years (range: 0.1-16.3 years). Median white blood cell count was 495x109/L (range: 107x109/L- 794x109/L). Forty-two of 47 patients (90%) had hepatosplenomegaly, 5 (11%) had respiratory distress, 3 (6%) had neurologic symptoms, 3 (6%) had diffuse cervical lymphadenopathy, and 3 (6%) had acute renal failure at admission. Ten of 47 patients (21%) had central nervous system involvement, and 17 (36%) had mediastinal mass. Ten patients (21%) had coagulopathy and 15 patients (32%) had metabolic complications (8 patients had hyperuricemia, 4 had hyperphosphatemia, 2 had hyperuricemia, hyperphosphatemia and hypercalcemia, and 1 had hypocalcemia) before the initiation of therapy. Forty of 47 patients (85%) with hyperleukocytosis were effectively managed with intravenous hydration, alkalinization, and allopurinol therapy. Early death during remission induction therapy occurred in 5 patients (11%) with respiratory distress and sepsis. Kaplan-Meier estimates of event free survival and overall survival were 37.0% and 40.5%, respectively.Periferik kanda lökosit sayısının ≥100x109/L olması ile karakterize hiperlökositozis, çocukluk çağı lösemilerinde %5-20 oranında görülebilen ve prognozu kötü olarak etkileyen bir risk faktörüdür. Bu çalışmada, 1 Ocak 1990-1 Ocak 2001 tarihleri arasında İzmir’deki 4 merkezde tanı alıp tedavi edilmiş ve tanı sırasında hiperlökositoz saptanmış 47 akut lenfoblastik lösemili (ALL) çocuğun klinik ve laboratuvar bulguları, gelişen komplikasyonlar ve sağkalımlarının araştırılması amaçlandı. Olguların ortanca yaşı 5.0 yaş (0,1-16,3 yaş) idi. Ortanca beyaz küre sayısı 495x109/L (107x109/L-794x109/L) bulundu. Tanı anında olguların 42’sinde (%90) hepatosplenomegali, 5’inde (%11) respiratuvar distres, 3’ünde (%6) nörolojik semptomlar, 3’ünde (%6) diffuz servikal lenfadenopati, 3’ünde (6%) akut böbrek yetmezliği bulguları vardı. On olguda (%21) santral sinir sistemi, 17 olguda (%36) mediastinal tutulum mevcuttu. Tedavi başlamadan önce 10 olguda (%21) koagulopati, 15 olguda (%32) metabolik bozukluk (8 olguda hiperürisemi, 4 olguda hiperfosfatemi, 2 olguda hiperürisemi, hiperfosfatemi ve hiperkalsemi, 1 olguda hipokalsemi) saptandı. 40 olguda (%85) intravenöz hidrasyon, alkalinizasyon ve allopurinol tedavisi ile hiperlökositoz kontrol altına alındı. İndüksiyon tedavisinin ilk 15 gününde 5 olgu (%11) respiratuvar distres ve sepsisle kaybedildi. Olguların hastalıksız ve genel sağkalımlarının sırasıyla %37,0 ve %40,5 olduğu saptandı.

Purpose To evaluate the results of radiotherapy and the prognostic factors affecting local control in nonextremity Ewing sarcomas. Methods Between 1995 and 2011, 44 patients with nonextremity Ewing sarcomas were treated with radiotherapy. Tumor localizations were pelvis in 23, spine in 13, thoracic region in 5, and cranium in 3 patients. Tumor size was ≥8 cm in 56.8% of patients. Distant metastases were present in 19 of the patients at the time of diagnosis (43.1%). All patients were treated with 12 weeks of neoadjuvant chemotherapy followed by surgery and radiotherapy (45-54 Gy) or radiotherapy alone (54-64.8 Gy). Radiotherapy was applied due to microscopic residue (R1) in 5 patients after the operation and macroscopic tumor in 39 patients (macroscopic residue [R2] and nonresectable tumor). Results Median follow-up was 49 months (range 9-195). Local failures developed in 7 patients (15.9%) and local control at 5 years was 81.4%. Local recurrence was detected in 6 patients (6/38) who did not have residual tumor after RT. Progression was detected in 1 patient (1/6) who had residual tumor. All those patients with local failure experienced further distant metastases. Possible prognostic factors such as age (≤17 vs >17), tumor localization, tumor volume (≤8 cm vs >8 cm), and M status at diagnosis (0 vs 1) were not related to local control. Conclusions Radiotherapy, either alone or adjuvant to surgery, provides local control in 80% of nonextremity Ewing sarcomas and plays an important role in treatment.

The aim of this study was to assess the prognostic value of MIB-1 and p53 in the pediatric medulloblastoma group. Forty-two pediatric medulloblastoma cases diagnosed in a single institution during the past 10 years were evaluated. Follow-up data were available for 35 patients. The immunoreactivity of MIB-1 ranged from 10% to 95%; p53 immunoreactivity was found in five cases. Of the 35 patients with follow-up, 34 patients received a combination of chemotherapy and radiotherapy, while one received chemotherapy alone. The follow-up period ranged from 5 to 64 months. Of the 35 patients, 21 were alive without any evidence of recurrent disease, three were alive with evidence of recurrent disease and 11 died of disease during follow-up. The mean survival for these 11 patients was 21.9 ± 10.4 months. Of the 35 cases, 16 had MIB-1 value of 25% or lower and 19 had a value of 26% or more. Of the 16 cases with low MIB-1 value, six died of disease; of the 19 cases with high MIB-1 value, five died of disease. The statistical difference between MIB-1 and prognosis was not significant. Three of the 35 (8.5%) cases were found to be positive with p53 protein; no correlation was observed between p53 immunoreactivity and prognosis. It appears that the MIB-1 value and p53 immunoreactivity have no relation with prognosis in pediatric medulloblastomas. However, it is convenient to support these findings with large series.

This study aimed to investigate the association of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms with serum drug levels and toxicities after high-dose methotrexate (MTX) infusion. The study included 37 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma. Serum MTX levels and toxicities of bone marrow, liver and kidney were analysed. Genotype analysis of the C677T and A1298C gene polymorphisms from genomic DNA of the subjects was performed by real-time PCR. Subjects with MTHFR polymorphism for C677T (CT, TT) had significantly higher MTX levels at 24 h (p = 0.009), and these genotypes did not seem to cause toxicity. Subjects with MTHFR polymorphism for A1298C (AC, CC) had significantly higher MTX levels at 48 h (p = 0.02), and had more grade III/IV anemia (p = 0.02), thrombocytopenia (p = 0.0001), elevated AST levels (p = 0.04) and frequent febrile neutropenic episodes (p = 0.004). The present study suggests that A1298C gene, but not C677T polymorphism is associated with MTX-related toxicity.

The purpose of this study was to evaluate late cardiac toxicity by comprehensive echocardiographic study, and to determine whether plasma atrial natriuretic peptide and brain natriuretic peptide levels might be indicators of neurohumoral activation. The study included 49 long-term survivors and 21 controls. A wide variety of echocardiographic parameters were measured or calculated. Plasma peptide levels were determined. Patients had significant changes in different echocardiographic parameters that are suggestive of LV systolic and diastolic dysfunction. Plasma peptide levels were not increased. The authors have found significant subclinic cardiotoxicity by echocardiography. Survivors seem to have normal plasma natriuretic peptide levels in long-term period.

Aim: In this study, it was aimed to evaluate the analysis of inv16 blood and bone marrow samples quantitively by reverse transcriptase polymerase chain reaction (RT-PCR) method of 402 patients (322 adult, 80 children) prediagnosed as acute myeloid leukemia (AML), who were admitted to Ege University Faculty of Medicine, Department of Medical Biology between years 2009-2013. Materials and Methods: cDNA's were obtained following the total RNA/mRNA isolation which were taken from patients' blood and bone marrow samples and quantitaion of inv16 were performed by reverse transcriptase RT-PCR method at LightCycler2. Results: Four hundred and two cases were evaluated in terms of inv(16) CBFBETA-MYH11 inversion. As a result of the analysis, a total of 19 patient were determined inv16 positivity includes 12 adult (% 4) and 7 children (9%). Conclusion: Inv16 of quantitative analysis is supported to be an effective method for clinical evaluation of patients with AML, regarding remission of disease and implimentation of the treatment protocols toward achieving remission. More studies with AML patients are required for confirmation of the results., Amaç: Bu çalışmada, Ege Üniversitesi Tıp Fakültesi Tıbbi Biyoloji Anabilim Dalı'na 2009-2013 yılları arasında akut myeloid lösemi (AML) ön tanısı ile başvuran 402 olgunun (322 yetişkin, 80 çocuk) kan veya kemik iliği örneklerinin inv16 kantitasyon analizlerinin RT-PCR yöntemi ile değerlendirilmesi amaçlandı. Gereç ve Yöntem: Hastalardan alınan kan ve kemik iliği örneklerinden total RNA/mRNA izolasyonunu takiben cDNA'ları elde edilerek revers-transkriptaz-polimeraz zincir reaksiyonu (RT-PCR) yöntemiyle inv16 kantitasyonu LightCycler2 cihazında gerçekleştirildi. Bulgular: Dört yüz iki olgu, inv(16) CBFBETA-MYH11 inversiyonu açısından değerlendirildi. Yapılan analiz sonucunda 12 (% 4) erişkin ve 7 (% 9) çocuk olmak üzere toplam 19 olguda inv16 pozitifliği saptandı. Sonuç: Inv16 kantitatif analizi, AML hastalarının klinik değerlendirilmesinde, hastalığın seyri ve remisyon sağlanmasına yönelik tedavi protokollerinin uygulanmasında etkili bir yöntem olduğunu desteklemektedir. AML hasta grubunu içeren daha geniş kapsamlı çalışmalar yapılarak elde edilen sonuçlar desteklenmelidir.

Pediatric oncology patients can present with various skin lesions related to both primary disease and immunosuppressive treatments. This study aimed to evaluate the cutaneous side effects of chemotherapy in pediatric oncology patients. Sixty-five pediatric oncology patients who were scheduled to undergo chemotherapy from May 2011 to May 2013 were included in the study. Three patients were excluded from the results, as 2 patients died during treatment and 1 patient withdrew from the study; therefore, a total of 62 patients were evaluated for mucocutaneous findings. Patients were grouped according to their oncological diagnoses and a statistical analysis was performed. There was no statistical significance in the incidence of cutaneous side effects of chemotherapy among the different diagnostic groups. Awareness among dermatologists of the possible cutaneous side effects of chemotherapy in pediatric patients and their causes can promote early diagnosis and treatment in this patient population.

Amaç: Bu çalışmada, Ege Üniversitesi Tıp Fakültesi Tıbbi Biyoloji Anabilim Dalı’na 2009-2013 yılları arasında akut myeloid lösemi (AML) ön tanısı ile başvuran 402 olgunun (322 yetişkin, 80 çocuk) kan veya kemik iliği örneklerinin inv16 kantitasyon analizlerinin RT-PCR yöntemi ile değerlendiril mesi amaçlandı. Gereç ve Yöntem: Hastalardan alınan kan ve kemik iliği örneklerinden total RNA/mRNA izolasyonunu takiben cDNA’ları elde edil erek revers -transkriptaz -polimeraz zincir reaksiyonu (RT-PCR) yöntemiyle inv16 kanti tasyonu LightCycler2 cihazında gerçekleştiril di . Bulgular: Dört yüz iki olgu , inv(16) CBFBETA-MYH11 inversiyonu açısından değerlendiril di . Yapılan analiz sonucunda 12 (% 4) erişkin ve 7 (% 9) çocuk olmak üzere toplam 19 olguda inv16 pozitifliği saptan dı . Sonuç: I nv16 kantitatif analizi, AML hastalarının klinik değerlendirilmesinde, hastalığın seyri ve remisyon sağlanmasına yönelik tedavi protokollerinin uygulanmasında etkili bir yöntem olduğu nu desteklemektedir. AML hasta grubunu içeren daha geniş kapsamlı çalışmalar yapılarak elde edilen sonuçlar desteklenmelidir., Aim: In this study, it was aimed to evaluate the analysis of inv16 blood and bone marrow samples quantitive ly by reve rse transcriptase polymerase chain reaction (RT-PCR ) method of 402 patients (322 adult, 80 children) prediagnosed as acute myeloid leukemia (AML), who were admitted to Ege University Faculty of Medicine, Department of Medical Biology between years 2009 -201 3. Materials and Methods: cDNA’s were obtained following the total RNA/mRNA isolation which were taken from patients’ blood and bone marrow samples and quantitaion of inv16 were performed by reverse transcriptase RT-PCR method at LightCycler2. Results: Four hundred and two cases were evaluated in terms of inv(16) CBFBETA -MYH11 inversion. As a result of the analysis, a total of 19 patient were determined inv16 positivity includes 12 adult (% 4) and 7 children (9%).Conclusion: Inv16 of quantitative analysis is supported to be an e ffective method for clinical evaluation of patients with AML, regarding remission of disease and implimentation of the treatment protocols toward achieving remission. More studies with AML patients are required for confirmation of the results.

Secondary malignant neoplasms (SMN) in CNS tumor survivors has become problem of increasing concern over the last 20 years. These tumors usually occur in a different site from the primary brain tumor several years after treatment.We report secondary cranial malignant neoplasms in three patients who were treated with irradiation and chemotherapy for their primary brain tumors. The first case is a male survivor of an orbital rhabdomyosarcoma who developed a meningioma 8 years later. The other two cases are female survivors of ependymomas who were irradiated at the age of 3 and developed secondary gliomas 8 and 17 years after therapy respectively.Patients carry a risk of developing SMNs many years later since irradiation is still an important part of the treatment. An SMN may have a benign course, as in meningioma, or be a dilemma for the patient, as in glioblastoma.

We aimed to demonstrate whether enteral nutrition (EN) is feasible in daily practice of hematopoietic stem cell transplantation (HSCT).Nutritional records of 100 patients were evaluated. Patients with poor oral intake were fed by EN with tube. A total of 79 patients required nutritional support. Of them, 71 were fed by EN only. Five were fed by EN plus parenteral nutrition (PN),three were fed by PN only. Median duration of EN was 21 days. In the EN only group, 68% gained or maintained their weight. EN should be considered as a feasible option for nutrition support in children undergoing HSCT. Pediatr Blood Cancer 2012; 59: 1327–1329. © 2012 Wiley Periodicals, Inc.

The authors report rare and different types of lung tumors in 4 children. The first case is an 8-year-old boy with mucoepidermoid carcinoma, the second case is a 9-year-old girl with neuroendocrine carcinoma, the third is a 14-year-old girl with fetal lung adenocarcinoma (FLAC), and the last is a 16-year-old girl with bronchioloalv eolar carcinoma. Among these tumors, FLAC has not been reported in children so far. Each tumor type displayed a different prognosis in the follow-up period. In the differential diagnosis of primary lung tumors, carcinoid tumor, bronchogenic carcinoma, and pulmonary blastoma are frequently encountered, but these rare tumor types should be borne in mind.

WOS: 000336304000001, Dysregulation of microRNA (miRNA) expression contributes to the pathogenesis of several clinical conditions. The aim of this study is to evaluate the associations between miRNAs and childhood acute lymphoblastic leukemia (ALL) to discover their role in the course of the disease. Forty-three children with ALL and 14 age-matched healthy controls were included in the study. MicroRNA microarray expression profiling was used for peripheral blood and bone marrow samples. Aberrant miRNA expressions associated with the diagnosis and outcome were prospectively evaluated. Confirmation analysis was performed by real time RT-PCR. miR-128, miR-146a, miR-155, miR-181a, and miR-195 were significantly dysregulated in ALL patients at day 0. Following a six-month treatment period, the change in miRNA levels was determined by real time RT-PCR and expression of miR-146a, miR-155, miR-181a, and miR-195 significantly decreased. To conclude, these miRNAs not only may be used as biomarkers in diagnosis of ALL and monitoring the disease but also provide new insights into the potential roles of them in leukemogenesis., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S076], The authors would like to thank the Scientific and Technological Research Council of Turkey (TUBITAK) for financial support under Grant 109S076.

Amaç: Akut promyelösitik lösemi (APL), akut myeloid löseminin (AML) iyi tanımlanmış alt tipidir ve spesifik olarak t(15;17)(q22;q12) translokasyonu ile karakterizedir. t(15;17), 15. kromozom üzerinde bulunan promyelösitik lösemi (PML) ve 17. kromozomda lokalize retinoik asit reseptör alfa (RARA) genlerinin füzyonu sonucu oluşur. Translokasyon varlığı, konvansiyonel sitogenetik, floresan in situ hibridizasyon analizi (FISH) ve sıklıkla gerçek zamanlı kantitatif revers transkriptaz polimeraz zincir reaksiyonu (qRT-PCR) yöntemiyle saptanır. Bu çalışmada, anabilim dalımıza başvuran APL ön tanılı olgulara ait kan ya da kemik iliği materyallerinden t(15;17) translokasyonunun gerçek zamanlı qRT-PCR ile kantitasyonu amaçlanmıştır. Gereç ve Yöntem: Çalışmaya 2009-2013 yılları arasında başvuran 79 çocuk (7.28±5.20 yaş; 45 E, 34 K) ve 359 yetişkin (47.71±15.57 yaş; 193 E, 166 K) olgu dahil edilmiştir. Olguların kan ya da kemik iliği materyallerinden total RNA izolasyonunu takiben cDNA sentezi gerçekleştirilmiştir. Sonrasında, qRT-PCR ile t(15;17) translokasyonu çalışılıp, kantite edilmiştir. Bulgular: Çocuk olgulardan 2'si (%3), toplamda 6 test (%5) t(15;17) için pozitif olarak belirlenmiştir. Bu olgulara ait t(15;17) kantitasyon değeri ortalaması, 0.0002±0.0003’tür. Yetişkin olguların 26'sı (%7), toplamda 30 test (%8) t(15;17) için pozitif olarak belirlenmiştir. Bu olgulara ait t(15;17) kantitasyon değeri ortalaması, 0.067±0,144’tür. Sonuç: qRT-PCR’ın konvensiyonel sitogenetik çalışmalara göre üstünlüğü, tüm çalışma basamaklarının test esnasında eş zamanlı olarak izlenebilmesi ve oluşan amplikonların kantitasyonunun yapılabilmesidir. t(15;17) kalitatif tayininin klinikteki önemi, tanının kesinleştirilmesinde, tüm trans-retinoik asit ve trioksid arsenik tedavisine yanıtın öngörülmesi ve tedavinin yararlılığının bilinmesinde, minimal rezidüel hastalığın (MRH) takibi ve relapsın erken evrede belirlenebilmesidir., Aim: Acute promyelocytic leukemia (APL) is a well-defined subtype of acute myeloid leukemia (AML) specifically characterized by the t(15;17)(q22;q12) translocation. t(15;17) results in the fusion of the genes, promyelocytic leukemia (PML) on chromosome 15 and retinoic acid receptor alpha (RARA) located on 17th chromosome. Translocation is detected by conventional cytogenetic, fluorescence in situ hybridization analyses (FISH) and often a real time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) method. In this study, quantification of t(15; 17) translocation via real time qRT-PCR was aimed in blood or bone marrow materials belonging to APL pre-diagnosed cases that appealed our department. Materials and Methods: Seventy nine children (7.28 ± 5.20 years; 45 M, 34 F) and 359 adults (47.71 ± 15.57 years; 193 M, 166 F) were included in the study between the years 2009-2013. Following total RNA isolation from blood or bone marrow materials of the cases, cDNA synthesis was carried out. Then, t(15; 17) translocation was studied by qRT-PCR and quantitated. Results: Two cases from children (3%), and in total 6 tests (5%) were detected positive for t(15;17). The average t(15;17) quantification value was 0.0002 ± 0.0003. Twenty six cases of the adults (7%), in total 30 tests (8%) were determined as t(15;17) positive. Average t(15;17) quantification value of these cases was 0.067 ± 0.144. Conclusion: The superiority of qRT-PCR compared to conventional cytogenetic studies can be found in the fact that all working steps can be monitored simultaneously during the test and the resulting amplicons can be quantitated. The clinical significance of t(15;17) qualitative determination is, confirmation of the diagnosis, all trans-retinoic acid and trioxide arsenic treatment response prediction and treatment efficacy knowledge in addition to minimal residual disease (MRD) monitoring and ability to identify relapse at early ages.

The effectiveness of the sequential use of deferiprone and desferrioxamine (DFO) in children with thalassaemia major was examined. Seven thalassaemic children in whom urinary iron induced by deferiprone was sufficient to maintain a negative iron balance were enrolled in the long-term trial. Deferiprone at a dose of 75 mg/kd/day in 3 divided doses was given for 4 school days a week. The group was given DFO at a dose of 40–50 mg/kg/day s.c. over 8–12 h with a battery-operated pump for 2 days at the weekend. In addition to the safety variables, they were monitored for serum ferritin levels at 2-month intervals and hepatic iron concentrations in liver tissues were determined at the beginning and the 6th month of therapy. The severity of hepatic damage was graded according to the Knodell hepatic activity index and the fibrosis was quantified. None of the patients suffered adverse effects of the therapy but a transient increase in serum ALT levels was noted. A nonsignificant decline in serum ferritin was observed (p = 0.08), a significant reduction in hepatic iron concentration was also determined (p = 0.03). The hepatic activity index in liver tissues of the patients at the 6th month of the sequential therapy significantly decreased (p = 0.03) whereas fibrosis scores did not differ significantly (p = 0.25).

A male infant was born with a 1 × 3 cm reddish lesion under his umbilicus which enlarged within a month and was associated with consumptive coagulopathy. A diagnosis of Kasabach-Merritt syndrome (KMS) was made. After no response to prednisolone and interferon-α treatment, 8 Gy of radiotherapy (2 Gy. day −1 ) was applied. The clinical status improved and the lesion decreased by 95%. This case illustrates the potential use of radiotherapy in the management of KMS. Radiotherapy is a relatively simple and inexpensive treatment modality which should be considered for lesions that have failed to respond to medical treatment.

Beta (beta) globin gene analysis was performed in 54 homozygous beta-thalassemia patients followed up in the Pediatric Hematology Department of Medical School of Ege University. The spectrum of beta-thalassemia alleles and their effect on clinical severity of disease were investigated. Twelve different mutations were determined in our patients. The six most frequent alleles, IVSI-110 (G-A), IVSI-6 (T-C), IVSI-I (G-A), IVSII-745 (C-G), Cd39 (C-T), and FSC8, account for 80.6% of all the disease genes. Eleven percent of the chromosomes could not be identified with the probes used in this study. In 38 patients both of whose beta-thalassemia alleles were identified, the beta-thalassemia alleles were found to be the major determinant of the clinical severity of disease. The clinical progress of disease was also closely related to the degree of iron overload.

This descriptive and case–control study was carried out in a pediatric oncology outpatient clinic to determine the school-related physical, social, and psychological problems and problems experienced in academic achievement of children treated for cancer. The sample of the study consisted of 56 Turkish patients with cancer, aged 7–18 years, who were in remission and attending school as well as their parents, a control group of patients who did not have cancer, and their teachers. A Child Information Form, a Child Health Questionnaire Parent’s Form of 50 questions, a Behavior Evaluation Scale for Children, and Young People and a Teacher’s Report Form were used as data collection tools in the study. Of the children, 30.3% experienced various physical difficulties stemming from cancer therapy that affected their school life. The number of late enrollments, the number of children repeating a grade, and the rates of school absenteeism were also found to be higher in the survivors than in the controls.

Myelofibrosis with myeloid metaplasia, or agnogenic myeloid metaplasia (AMM) is a chronic myeloproliferative disorder characterized by fibrosis of the bone marrow accompanied by aniso- and poikilocytosis, leukoerythroblastosis and hepatosplenomegaly with extramedullary hematopoiesis. Agnogenic myeloid metaplasia is very rare in children. In this report, two cases of AMM in whom the onset of the illness were at 3 and 12 months of age, are presented. Both had severe anemia, hepatosplenomegaly and bone marrow fibrosis. Lymph node biopsy of the first patient and liver biopsy of the second revealed extramedullary hematopoiesis. They were treated with an intravenous high dose of methylprednisolone (daily 30 mg/kg for 3 days, 20 mg/kg for 4 days, 10 mg/kg for 1 week, 5 mg/kg for 1 week). A complete improvement of hematological and clinical findings was observed.

The levels of soluble interleukin-2 receptors (sIL-2R) and tumor necrosis factor (TNF) were determined in the serum of 61 children with hematological malignancy, including 20 patients with leukemia and 16 with lymphoma in active state of malignancy, and 20 patients with leukemia and 5 with lymphoma in complete remission. In addition, serum samples from 15 healthy children were used as controls. It was found that the mean serum levels of sIL-2R and TNF were significantly increased in active malignancy (207.0 +/- 17.1 pmol/L for sIL-2R; 209.7 +/- 35.0 pg/mL for TNF) compared to the remission status and normal controls (P < 0.001). No such difference was observed between leukemia and lymphoma groups. It was concluded that serum sIL-2R and TNF are of potential value in the diagnosis and follow up of patients with neoplastic diseases.

Mesenchymal hamartoma is a rare pediatric liver tumor. The tumor is mainly cystic but occasionally a solid component is seen. Therefore the tumor can be divided into two forms: (a) cystic predominant, and (b) stromal predominant. In this report, CT and MR features of stromal predominant type mesenchymal hamartoma are presented. (C) 2002 Elsevier Science Ltd. All rights reserved.

Background Multi-systemic acute side effects occur, in response to intensive therapies that have been applied in childhood malignancies in recent years. Amifostine has rarely been used in the childhood cancers as a multisystemic protective agent for minimizing these side effects. Procedure In this study, the effectiveness of amifostine in combination with chemotherapy for childhood cancer treatment has been researched. Of 11 subjects (2.5 months–17 years) 4 subjects had leukemia, 4 had solid tumor, and 3 had lymphoma. For these 11 subjects, 29 chemotherapy courses were given in combination with amifostine, and 20 without amifostine. Their hematological, gastrointestinal and hepatic toxicity were evaluated according to the WHO toxicity criteria. Amifostine was given intravenously in a dose of 740 mg/m2, one to three consecutive days depending on the chemotherapy regimen. Results The hemoglobin, leukocyte, and platelet levels of the two groups were not statistically different. However, when comparing the courses of the patients receiving the same medications at the same doses, in the group with amifostine, mean erythrocyte transfusion requirement was significantly reduced (P = 0.025). In 31% of the courses with amifostine and 50% of the courses without amifostine, febrile neutropenia developed. Gastrointestinal system and hepatic toxicity was significantly reduced in the courses with amifostine with respect to those without it (P = 0.001). Vomiting, hypotension and nausea were the only side effects related to amifostine. Conclusion Use of amifostine during the treatment of childhood cancers with intensive chemotherapy and/or radiotherapy significantly reduced the erythrocyte transfusion requirements of the patients as well as gastrointestinal and hepatic toxicity. Pediatr Blood Cancer 2009;52:829–833. © 2009 Wiley-Liss, Inc.

Melanotic progonoma or melanotic neuroectodermal tumor is a rare tumor in infancy. This lesion has to be considered in the differential diagnosis of benign or malignant lesions of calvarium. The authors present a case of a 4-month-old infant with left retroauricular mass. The patient had a subcutaneous mass that is fixed to the underlying skull. CT and MRI scans showed left occipitotemporal expansile mass. The tumor was removed by surgery. A tumor, brownish-black in color, was diagnosed as melanotic progonoma. The patient remained symptom-free for the last 2 years after complete surgery. Extracranial subcutaneous masses involving the skull are uncommon in infants. Benign or malignant lesions may occur as lumps on calvarium. Physical examination and some laboratory findings are helpful in the assessment of patient. Benign or malignant lesions can be differentiated by craniography, CT, or MRI scans, but exact diagnosis of melanotic progonoma is made by histopathology and immunostaining, as was in the presented case. Cranial vault progonomas have a better outcome by complete surgery. The tumors usually do not recur in long-term period.

PubMed ID: 18293058, The aim of this study is to evaluate (1) the human telomerase-specific reverse transcriptase (hTERT) mRNA expression in childhood acute leukemia, (2) the association between the hTERT mRNA expression with the patients' characteristics and the known prognostic factors and (3) the correlation of the patients' survival with the initial hTERT mRNA value at diagnosis. A total of 40 newly diagnosed patients consist of children [31 cases with acute lymphoblastic leukemia (ALL) and 9 cases with acute myeloblastic leukemia (AML)] were prospectively included into the study. The online real-time reverse- transcriptase PCR was used for the quantification of hTERT in bone marrow (BM). All cases were re-evaluated for their survival after 2 years. The highest hTERT mRNA value was observed in Pre B-cell ALL patients followed by B-cell ALL, T-cell ALL and AML. The hTERT mRNA relative ratio difference between the ALL and AML groups was significant. No significant association was found when hTERT mRNA expression was evaluated in relation with the hematological parameters (except hemoglobin level), blast percentages and the risk groups. No significant difference was determined between the rate of complete remission and relapse of cases with the hTERT mRNA values in all malignancy groups. Patients who had higher initial hTERT mRNA values showed significantly longer disease-free survival (DFS) and overall survival (OS) in ALL (P = 0.000 and 0.01, respectively). Although DFS and OS was longer in AML patients with lower initial hTERT mRNA, the difference was not significant. In conclusion, the hTERT mRNA expression values were not significantly associated with the known prognostic factors in children both with ALL and AML. hTERT mRNA value is a significant factor for childhood ALL at diagnosis in relation to the estimated survival. © 2008 The Japanese Society of Hematology., Acknowledgments This study was supported by Ege University Science and Technology Center.

Amaç: Over tümörleri çocuklarda nadirdir. Erişkinlerin aksine germ hücreli tümörler daha sık görülürler ve bir çoğu selimdir. Bu çalışmada over tümörü saptanmış hastalar tanı, tedavi ve sonuçları yönünden incelenmiştir. Yöntem: Kliniğimizde 1984-2004 yılları arasında over tümörü saptanan 30 kız (33 over) olgunun kayıtları geriye dönük incelenmiştir. Bulgular: Hastaların yaş ortalaması 10.7±3.43 (3-18 yaş) yıldır. Onaltı hastada sol, 11 hastada sağ ve 3 hastada bilateral over tümörü saptanmıştır. Histolojik tanılar, matür teratom (n=18), immatür teratom (n=1), disgerminom (n=8), mikst germ hücreli tümör (n=1), gonadoblastom (n=1), seröz kistadenom (n=1), müsinöz kistadenom (n=2) ve granüloza hücreli tümör (n=1) olarak belirlenmiştir. Karın ağrısı (n=18), karında şişkinlik (n=11) ve kusma (n=9) en sık başvuru yakınmalarıdır. Altı hasta akut karın bulguları ile başvurmuş ve acil girişim yapılmıştır. Yirmibir salpingo-ooferektomi, 6 ooferektomi, 6 tümör eksizyonu uygulanmıştır. Habis hücre kaynaklı tümörlerde ortalama izlem süresi 84.2±47.14 (8-144 ay) aydır. Evre 4 olan tek hasta ameliyat sonrası 6. yılda nüks nedeniyle kaybedilmiş, bir hasta ise takipsizdir. Selim hücre kökenli 2 olguda sırasıyla ilk operasyondan 6 ve 55 ay sonra karşı overde aynı histolojide tümör saptanmıştır. Sonuç: Çocuklarda belirlediğimiz over kaynaklı kitlelerin büyük çoğunluğunu germ hücreli tümörler oluşturmaktadır ve bir çoğu için cerrahi tedavi yeterli olmuştur. Akut ve kronik gastrointestinal sistem yakınmalarıyla başvuran kız hastalarda adneks ve ilişkili sorunların ayırıcı tanıda dikkate alınması önem kazanmaktadır., Aim: Tumors of the ovaries are uncommon in children. Most of them are benign and in germ cell origin, opposite to adults. In this study, children with ovarian tumors were rewieved in respect to their diagnosis, treatment and results. Method: The hospital records of 30 patients (33 ovaries) with ovarian tumors treated at our department between 1984 and 2004 were reviewed retrospectively. Results: The mean age was 10.7±3.43 (range; 3 to 18 years) years. The tumors were on the left, right and bilateral in 16, 11 and 3 patients, respectively. The histologic diagnosis of the tumors were mature teratoma (n=18), immature teratoma (n=1), dysgerminoma (n=8), mixed germ cell tumor (n=1), gonadoblastoma (n=1), serous cystadenoma (n=1), mucinous cystadenoma (n=2) and granulosa cell tumor (n=1). Abdominal pain (n=18), abdominal distention (n=11) and vomiting (n=9) were the most common symptoms. Six patients had acute abdominal findings requiring urgent surgery. The surgical procedures were salpingooophorectomy (n=21), oophorectomy (n=6), and total tumor excision with ovarian salvage (n=6). In malignant ovarian tumor group (n= 11); median fellow-up period was 84.2±47.14 months with a range of 8 to 144 months. One patient with Stage 4 tumor died 6 years later. One patient lost to follow-up in the malignant group. In two patients with diagnosis of mature cystic teratoma a new tumor was determined in the contralateral ovary with a similar histology after first operation 6th and 55th months, respectively. Conclusion: The majority of the patients had germ cell tumors in this series, and surgical treatment was all that was required for complete cure in most of them. The adnexial pathologies because of their devastating complications should be taken into consideration in differential diagnosis in young females presenting with acute or chronic gastrointestinal symptoms.

PubMed ID: 15621763, Human telomerase reverse transcriptase (hTERT) is the catalytic component of telomerase enzyme and has been shown to be associated with telomerase activity (TA). Although many studies in adult leukemia have established the importance of TA, very few have been reported in the children. In this study hTERT levels in childhood leukemia was evaluated and compared with the prognostic factors described before. The LightCycler instrument was used (online real-time PCR) for the quantification of hTERT in peripheral blood and bone marrow in 23 cases with acute lymphoblastic leukemia (ALL) and in 8 cases with acute myeloblastic leukemia (AML). Ten cases with normal peripheral blood (PB) and bone marrow (BM) were selected as control group. Cytogenetic analyses were available in 21 patients with leukemia. In all cases with acute leukemia and in control group, peripheral blood (PB) hTERT levels correlated significantly with bone marrow (BM) hTERT levels. Before treatment, patients with ALL had significantly higher hTERT levels than that of AML patients and control cases. Among patients with ALL, higher hTERT levels were observed in patients with pre-B leukemia, followed by B cell and T cell leukemia patients. Initially increased hTERT levels decreased to the nearly normal levels during remission in cases with ALL. No correlation was observed between the initial hTERT levels and the known prognostic factors except cytogenetic findings. Higher hTERT levels were detected in patients having karyotypic abnormalities which indicate poor prognosis. hTERT levels are significantly high in childhood ALL with the highest level of pre-B cell leukemia before treatment. Those high levels of hTERT decrease to almost normal levels in remission. hTERT levels might be useful in monitoring of leukemia in children. © 2004 Taylor & Francis Ltd.

The aim of this study was to evaluate the efficacy and safety of meropenem plus amikacin compared with piperacillin-tazobactam plus netilmicin for initial empirical antibiotic treatment of high-risk febrile neutropenia in children with cancer. Patients with hematologic malignancy (leukemia or stage III/IV non-Hodgkin lymphoma) who presented with fever and neutropenia (ANC < 500/mm3) and patients with solid tumors who presented with fever and severe neutropenia (ANC < 100/mm3) were considered to be at high risk and eligible for this study. In this prospective study, 33 patients with 50 febrile neutropenic episodes received i.v. neropenem (20 mg/kg every 8 h) plus amikacin (15 mg/kg/d in 2 divided doses) (in 31 episodes) or piperacillin/tazobactam (100 mg/4 mg/kg every 8 h) plus netilmicin (7 mg/kg every 24 h) (in 19 episodes). Clinical response was determined at 72 h and at completion of the therapy. The groups were comparable in terms of age, sex, initial ANC, use of growth factors, and classification of the infections. An infection was documented microbiologically in 12 episodes (39%) in the meropenem plus amikacin group and in 8 episodes (42%) in the piperacillin/tazobactam plus netilmicin group. Of the 22 microbiological isolates, 37% were gram-positives, 45% were gram-negatives, and 18% were fungi. Most of the clinically documented infections were of lower respiratory tract, gastrointestinal mucosa, or urinary tract origin. The mean duration of neutropenia was 9 days in both groups. Fever persisted for 1-30 days (mean 3 vs. 5 days). The success rate with initial empiric therapy was 52% in the meropenem plus amikacin and 42% in the piperacillin/tazobactam plus netilmicin group, respectively (p = .5). Total success rate (with or without modification) was 97% vs. 90% in the episodes. Three patients died due to infection (1 vs. 2 patients). No major adverse effects were observed in each group. Empirical therapy with meropenem plus amikacin or piperacillin/tazobactam plus netilmicin for high-risk febrile neutropenia is equally effective and safe in pediatric cancer patients.

WOS: 000186274000006, PubMed ID: 14604161, The aim of this study was to determine serum immunoglobulins, IgG subclasses, lymphocyte subsets, and serum protective antitoxin levels of tetanus and diphtheria, and to investigate specific antibody response to tetanus and diphtheria vaccines in children with cancer who have been treated for leukemias and solid tumors. Forty patients with different types of childhood malignancies were enrolled in this study and their lymphocyte subsets, serum Ig A, M, G and IgG subclass concentrations were determined at completion of chemotherapy and 6 months later. We measured serum diphtheria (D) and tetanus (T) antitoxin levels and investigated specific antibody responses against DT vaccines at 6 months. Only the leukemic children had low CD19+ cells at completion of chemotherapy and 6 months later. The patients with solid tumors had reduced CD4+ cells, but increased natural killer cells at completion of chemotherapy. Serum IgA and IgM levels were decreased in leukemic patients after chemotherapy. There were no IgG subclass deficiency. Forty-two per cent of the patients did not have protective serum T antitoxins. All patients produced high levels of DT antibodies by vaccination. Immune system changes recover by 6 months after cancer therapy in children. Children with solid tumors, as well as leukemias, should be followed-up in terms of immune deficiencies. A repeat dose of tetanus toxoid should be recommended at 6 months.