Hikmet Gulsah Tanyildiz

Single-center experience with sirolimus therapy for vascular malformations.

ABSTRACT Vascular malformations (VMs) are described as congenital malformations of the vasculature derived from capillaries, veins, lymphatic vessels, arteries, or a combination of these vessels. They can cause significant morbidity resulting from soft tissue hypertrophy-related disfiguration, bony abnormalities, and even organ compromise. They are usually treated with various interventional procedures to achieve local control; however, the chance of success decreases as the anatomical distribution of the malformation widens. Unfortunately, medical treatment options have been quite limited in these patients. Sirolimus is an antiangiogenetic and antiproliferative pharmacologic agent that has been used for the management of VM in the last decade. We report 6 pediatric patients (4 with capillary lymphaticovenous malformations, 1 with lymphaticovenous malformation, and 1 with venous malformation) seen at our clinic within the last 2 years with lesions covering wide anatomical areas. After the patients had unsuccessfully undergone various treatments at various centers, they were treated at our facility with peroral sirolimus. The mean duration of treatment was 13 months, but in 3 patients, tapered dosing continues. Five patients achieved partial responses. The response to sirolimus treatment increased as the lymphatic component of the VM increased. All patients tolerated sirolimus well; side effects were acceptable. Sirolimus is a safe and effective medical treatment for widely distributed VMs with significant lymphatic components and no further local treatment option.

How should we monitor boys with testicular microlithiasis

ABSTRACT Testicular microlithiasis (TM), a rare condition characterized by calcification within the seminiferous tubules, is associated with benign and malignant disorders of the testis. We review current practices of following up pediatric patients diagnosed TM incidentally on scrotal ultrasonography (US). We analyzed retrospectively patient characteristics, family history, indications for US, pathological features, US findings, outcome, and follow-up. At our institution, 2875 scrotal US examinations were performed on 2477 children with various scrotal complaints from 2008 to 2015. Testicular microlithiasis was detected in 81 patients (i.e., an incidence of 3.27%). Every 6 months, each patient underwent a clinical and ultrasonographic evaluation as well as serum tumor markers determination to detect a potential malignancy. Seventy-eight patients who had undergone scrotal US at least twice were included in this study. We evaluated the US studies for the type of TM (diffuse and focal) and change in follow-up studies. Testicular microlithiasis was typically diffuse (n = 56, 71.8%) and bilateral (n = 45, 57.7%), and it was detected the most frequently in the 9–11-year age group (27 patients, 34.6%). The most common comorbid conditions included undescended testes (31 patients, 39.7%) and hydrocele (11 patients, 14.1%). We found that serum tumor markers were within normal limits both at diagnosis and upon follow-up. No testicular tumors or new abnormal symptoms developed during the clinical follow-up. There is no convincing evidence that TM alone is premalignant in a pediatric population. In terms of follow-up, we advise regular self-examinations and annual US in the absence of risk factors.

Vitamin D receptor polymorphisms in immune thrombocytopenic purpura

Vitamin D receptor (VDR) polymorphisms have been studied in immune‐mediated disorders, but not yet in immune thrombocytopenic purpura (ITP). We investigated whether VDR variants were associated with ITP in children.

The Correlation Between Pre-treatment Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Parameters and Clinical Prognostic Factors in Pediatric Hodgkin Lymphoma

Objective: To compare standardized uptake values (SUV) derived from pre-treatment 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging and clinical prognostic factors in pediatric patients with Hodgkin lymphoma (HL). Methods: Pre-treatment FDG PET/CT findings of 28 children with HL were evaluated in this retrospective study. Metabolic tumor volume (MTV), SUVmax normalized by weight (SUVweight), lean body mass (SUVlbm), body surface area (SUVbsa) and plasma glucose levels of tumors (SUVglucose) were calculated using pre-treatment FDG PET/CT scan images. These metabolic parameters were correlated with clinical factors [age, sex, number of lymph node groups, presence of splenic involvement, bulky mediastinal disease, Ann Arbor stage, serum white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), serum albumin and hemoglobin levels]. Results: SUVbsa, SUVlbm, SUVweight, SUVglucose and MTV were higher in patients with stage III-IV disease, bulky tumor and ≥3 lymph node groups (p<0.05). SUVbsa and SUVglucose were higher in patients with splenic involvement (p<0.05). There was no significant correlation between these metabolic parameters and sex, ESR, levels of albumin and WBC (p>0.05). SUVbsa and SUVlbm were higher in patients with anemia (p<0.05). Additionally, significant increases were detected in SUVweight, MTV, and SUVglucose with increasing age (p=0.005, p=0.027, and p=0.009, respectively). SUVbsa and SUVlbm had no significant correlation with age (p>0.05). Conclusion: Metabolic parameters derived from pre-treatment FDG PET/CT may have an important role in predicting high-risk disease in patients with HL. Also, SUVbsa and SUVlbm may be better markers than SUVweight in the quantitative evaluation of FDG PET/CT scans in pediatric patients.

A Rare Presentation of Paraovarian Sclerosing Stromal Tumor with High Mitotic Activity

BACKGROUND Sclerosing stromal tumor is an extremely rare type of benign ovarian sex cord stromal tumor. CASE The benign characteristic of this tumor is well known but we present an uncommon case of paraovarian sclerosing stromal tumor with high mitotic activity. RESULTS AND CONCLUSION Despite this potential malignancy, our patient was treated successfully with enucleation only.

Imatinib Mesylate-Related Treatment Results in Optic Glioma: Single Center Experience

Objective: Optic gliomas are histologically benign and well differentiated pilocytic astrocytomas. The histopathologic features of the tumor are important prognostic markers that affect survival rates in association with location, the age of the patient, and neurofibromatosis type-1. Chemotherapy is the most important choice in the treatment and the clinicians’ goal is to stay as far away from radiotherapy as possible. The combination of vincristine and carboplatin, which is a safe and long-lasting safe treatment plan that sets the stage for radiotherapy and surgeon avoidance, is one of the first choice standard treatment approaches. However, in these treatments, refractory disease, imatinib mesylate, a multi-tyrosine kinase inhibitor with a low rate of systemic side effects can be added as an important option. It can be used safely in pediatric patients. Because of small number of studies reported in this area, we wanted to share our good results regarding the use of imatinib mesylate with clinicians. Material and Methods: A total of 16 patients with optic glioma who were diagnosed between 2007-2017 at our oncology clinic were included in the study. Results: When clinically and radiologically progressive disease was present after two cycles of the vincristine carboplatin combination, imatinib (270 mg/m2 oral) treatment was added for 1-2 years until stable disease or regression findings 2 Tanyıldız HG ve ark.

Epidemiological features and risks of hemangiomas

Şahin G, Düzcan-Kilimci D, Tanyıldız HG. Epidemiological features and risks of hemangiomas. Turk J Pediatr 2017; 59: 664-669. Hemangiomas are the most common benign tumors of childhood. The known risk factors in developing hemangiomas are female gender, prematurity and low birth weight. Our study was designed to investigate prenatal and natal risk factors in addition to the above factors that would potentially affect development of hemangiomas. Two hundred forty hemangioma patients and 100 healthy controls were included in the study. Both groups were interviewed for age, gender, prenatal characteristics (presence of maternal pregnancy hypotension, hypertension and hyperemesis, parental smoking habits) as well as natal characteristics (delivery, birth weight, gestational age) and maternal-paternal age. Hemangiomas were mostly localized in the head and neck. Risk of developing hemangioma was higher in girls and in firstlings. History of hyperemesis during pregnancy increased incidence of hemangioma. Post-term delivery was found to be protective against developing hemangioma. We are in the opinion that there is a need for wider studies with a bigger sample size so as to detect other risk factors.

The prognostic importance of TGF-β, TGF-β receptor, and fascin in childhood solid tumors

ABSTRACT Fascin plays a role in tumor metastasis under the influence of TGF-β, each potentiating the effect of the other. We retrospectively investigated whether there was a prognostic relationship between TGF-β and fascin, and disease stage, local recurrence, metastasis tendency, and response to treatment. Twelve neuroblastomas, 17 osteosarcomas, 14 Ewings sarcomas, 15 rhabdomyosarcoma cases, and 8 rare solid tumors were included. Serum TGF-β levels were high at the time of diagnosis in all groups (p = .015) and decreased significantly during remission (p = .008). Serum TGF-β values in the relapse period rarely reached high levels at the time of diagnosis and even stayed under the control group values (p = .017). When TGF-β receptor expression in tumor tissues was evaluated, the association of TGF-β receptor positivity with metastatic disease and advanced stage was striking. We found that 88% of rhabdomyosarcoma cases with alveolar histopathology expressed the TGF-β receptor, and the association between TGF-β receptor positivity and alveolar histopathology seemed to be a negative prognostic marker. When fascin levels were evaluated in childhood solid tumor tissue, the risk of relapse increased when the fascin total score at diagnosis was >4. This is one of the few studies including prognostic markers such as serum TGF-β, tissue TGF-β, TGF-β receptor, and fascin in pediatric solid tumors. Considering the poor prognosis of advanced stage pediatric solid tumors and the need for biomarkers to predict which patient might need more intensive therapy or warrant closer follow-up afterward, we think that TGF-β, TGF-β receptor, and fascin expression have an important prognostic role.

Vitamin D Receptor (vdr) Polymorphisms in Pediatric Patients Presenting With Hodgkin’s Lymphoma

Vitamin D receptor (VDR) polymorphisms are found more commonly in some tumor types than in healthy individuals, suggesting that some polymorphisms (Cdx2, Fok1, Bsm1, Apa1, Taq1) contribute to tumor development. There is no previous report on VDR polymorphism in Hodgkin’s lymphoma (HL) patients. VDR polymorphism patterns in 95 pediatric HL cases with 100 healthy controls were compared. No statistically significant difference was found between the patient group and control group in terms of Cdx2, Fok1, Bsm1, Apa1, and Taq1 polymorphisms (P>0.5). Our findings suggest that VDR polymorphisms may not play a role in HL development.

Can Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography Be Used As a Useful Method to Evaluate the Treatment Response to Neoadjuvant Therapy Combined With Sorafenib and Anti-VEGF in Children Diagnosed With Metastatical Bone Sarcoma?

Background The prognosis is still poor for patients with a metastatic bone tumor and new treatment approaches (anti-VEGF and tyrosine kinase inhibitors vs) are therefore needed. Objectives The aim of our study was to evaluate how the primary and metastatic lesions of our patients with a bone tumor were affected by these treatments and to determine the importance of the 18F-FDG PET method. Patients and Methods Twenty metastatic bone tumor cases were included. Sorafenib and anti-VEGF were added to the standard treatment in cases with widespread metastatic disease at diagnosis or after neoadjuvant chemotherapy showing less than 90% tumor necrosis in the surgical sample. Positron emission tomography (PET) imaging was performed at diagnosis, the preoperative period following neoadjuvant chemotherapy, during postoperative follow-up, and when treatment was discontinued. Results The primary treatment region median SUVmax level decreased from 7.35 to 2.5 in the living patients (n = 16) while there was no significant decrease in the patients who succumbed to the disease (P < 0.001). Comparison of the pre- and post-treatment metastasis region median SUVmax levels in patients with metastatic involvement showed a decrease from 2.1 to 0 in the surviving patients but only from 4.8 to 3.2 in the deceased patients (P < 0.01). Survival results indicated that 28.6% of the patients receiving classical treatment only died while all the patients receiving additional sorafenib and anti-VEGF survived. Conclusions 18F-PET may be a useful technique before and during the follow-up of neoadjuvant treatment in pediatric metastatic bone tumor patients. The addition of sorafenib and anti-VEGF to classical treatment has a favorable contribution to the response and therefore the survival duration.