Gurses Sahin

DNA repair XRCC1 Arg399Gln polymorphism alone, and in combination with CYP2E1 polymorphisms significantly contribute to the risk of development of childhood acute lymphoblastic leukemia

It is now well established that genetic polymorphisms impairing the DNA repair capacity can disrupt the genomic integrity and potentially modulate individuals susceptibility to various cancers. In this study, we investigated the possible association of X-ray repair cross-complimenting group 1 (XRCC1) Arg399Gln and Arg194Trp variants with the risk of incidence of childhood acute lymphoblastic leukemia (ALL) in Turkish population comprised of 190 healthy controls and 167 ALL patients. For Arg399Gln polymorphism, the heterozygous (Arg/Gln) and homozygous mutant (Gln/Gln) genotypes were significantly more common in the ALL patients than the controls (OR: 1.6, p=0.04). Particularly, the Gln399Gln genotype significantly increased the risk of disease up to 2.0-fold (OR: 2.0, p=0.04). Besides, Gln399Gln genotype has been found to be associated with considerably increased risk of ALL among females (OR=2.9, p=0.03). In case of codon 194 polymorphism, no significant associations have been found with risk of childhood ALL. In addition, none of the combinations of XRCC1 codon 194 and 399 polymorphisms have been found to be significantly associated with childhood ALL risk. In the scope of this study, we have also showed that the co-presence of XRCC1 codon 399 and CYP2E1*5B and *6 polymorphisms (data for CYP2E1 polymorphisms drawn from previously published study conducted in our lab) in the same individuals considerably increased the risk for childhood ALL to 3.7-fold with borderline significance (p=0.049). The observed combined effect was considerably more prominent among females (OR=17.4, p=0.001) and need to further investigation. This is the first study showing combined associations of XRCC1 399Gln, CYP2E1*5B and *6 alleles with the risk of development of childhood ALL.

Significance of Genetic Polymorphisms at Multiple Loci of CYP2E1 in the Risk of Development of Childhood Acute Lymphoblastic Leukemia

Background/Aims: The molecular etiology of childhood acute lymphoblastic leukemia (ALL) is likely to involve interactions between environmental factors and genetic make up. Understanding these interactions between various predisposing genes for the risk of developing childhood leukemia is of considerable importance. CYP2E1 is a susceptible gene in this respect, especially for its capacity to bioactivate many procarcinogens including benzene and N-nitrosodimethylamine. The CYP2E1 gene possesses several polymorphisms in humans, and among them, CYP2E1*5B and *6 have been shown to be associated with increased risks of several chemical-induced diseases. There are limited and contradictory data on the association between the CYP2E1*5B variant allele and childhood ALL, and none on such associations of CYP2E1*6 and*7B variant alleles. The aim of this study was to investigate the possible association of CYP2E1*5B, *6 and *7B alleles, alone or in combination, with the risk of incidence of childhood ALL in a Turkish population. Methods: The genotypes for both polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism techniques on 207 healthy controls and 168 patients. Results: Neither locus was associated with the occurrence of childhood ALL. On the other hand, when both CYP2E1*5B and *6 alleles were considered together, the risk of childhood ALL increased significantly (2.9-fold; OR = 2.9, 95% CI 1.0–8.5; p < 0.05). Moreover, the presence of at least 2 variant alleles of any combination increased the risk significantly 3.9 times, suggesting a combined effect (OR = 3.9, 95% CI 1.4–11.0). Conclusion: Individuals carrying combinations of CYP2E1*5B, *6 and *7B variants together are likely associated with the risk of developing childhood ALL.

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.

Vitamin B12 Deficiency Mimicking Acute Leukemia in a Child

Tanyildiz HG, Malbora B, Yesil S, Candir MO, Bozkurt C, Sahin G. Vitamin B12 Deficiency Mimicking Acute Leukemia in a Child. Deficiency of vitamin B12 is an important cause of megaloblastic anemia and bone marrow depression. Morphological and functional changes in bone marrow are observed related with vitamin B12 deficiency. Most importantly dysplastic changes can be mistaken as myelodysplastic syndrome or acute leukemia. In adult cases of vitamin B12 deficiencies mimicking acute leukemia were reported. Our case is an alerting example of vitamin B12 deficiency in children mimicking acute leukemia with dysplastic findings.

Successful Treatment of Macroglossia Due to Lymphatic Malformation With Sirolimus.

Objective: To evaluate the effectiveness and safety of sirolimus therapy in a child with macroglossia due to lymphatic malformation. Methods: Sirolimus treatment was applied to the patient with an initial dosing of 0.8 mg/m2 per dose, administered orally, twice daily at approximately 12-hour intervals. Results: After 9 months of sirolimus therapy, there was a nearly complete resolution of lymphatic malformation. The last evaluation was performed 6 months after withdrawal of treatment, and the lesion had almost completely resolved. Conclusion: This article presents a novel approach to the treatment of lymphatic malformation of the tongue using sirolimus, which appears to be safe and effective for the management of complex cases.

Serum Ca 125 levels in children with acute leukemia and lymphoma

Ca 125 is a tumor marker for the diagnosis and monitoring of ovarian carcinoma. We investigated serum Ca 125 levels in 44 children with leukemia and 59 children with lymphoma at initial presentation and 4 weeks after chemotherapy. Serum Ca 125 levels were measured chemilumimetrically with a sandwich enzyme-linked immunosorbent assay. The incidence of elevated serum Ca 125 levels was significantly higher in children with leukemia (14 children) and lymphoma (26 children) than in the healthy children (2 children). In the patients with non-Hodgkins lymphoma (NHL) who had abdominal involvement and/or serous membrane involvement (ascides, pleural, pericardial effusion) at presentation, serum Ca 125 levels were significantly higher than in the patients without abdominal and/or serosal involvement. Serum Ca 125 levels were impressively increased in the patients with Burkitts lymphoma (BL) in whom abdominal and/or serous membrane involvement were observed more frequently than the other types of lymphoma. The increased serum Ca 125 levels in the patients returned to normal 4 weeks after chemotherapy when they achieved complete remission. In conclusion, serum Ca 125 seems to be a good indicator for serous membrane involvement and it seems to be a promising tumor marker in the assessment of therapeutic response in children with leukemia and NHL.

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.

Two Case Presentations Infected by Trichosporon asahii and Treated with Voriconazole Successfully

Background. Trichosporon asahii is an opportunistic fungus that causes infections in immunosuppressed patients. Neutropenia developing due to malignancies is an important risk factor for fungal infection. Case Report. We present two pediatric oncology cases successfully treated with voriconazole after T. asahii infection that is known to cause fatal sepsis and invasive fungal infection. Conclusion. There is no conclusive evidence that the antifungal agent voriconazole is effective in the neutropenic patients infected with Trichosporon asahii. Liposomal amphotericin B has also been reported to be inadequate for treatment. We believe that our patients were successfully treated and survived because the antifungal agents were started early and properly, although the infection can be fatal in up to 80% of cases despite treatment.

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.

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.