Bengü Demirağ

Analysis of genetic and non genetic risk factors for cisplatin ototoxicity in pediatric patients

OBJECTIVE The aim of this study was to analyse the genetic and non genetic risk factors for cisplatin ototoxicity. METHODS This study was conducted on 72 children who received cisplatin based chemotherapy. Brock and Muenster classifications were used to evaluate ototoxicity seen in these children. 6 single nucleotide polymorphisms (SNP); ERCC1 rs 11615, GSTP1 rs1138272, GSTP1 rs1695, LRP2 rs 2075252, TPMT rs 12201199, COMT rs 9332377, were evaluated as genetic factors by real time PCR. Non genetic factors such as cranial irradiation, cumulative doses of cisplatin, age, gender, administration of other ototoxic drugs were analysed as well. By using Chi-square test, risk factors were matched with the ototoxicity classifications. Significant risk factors were reevaluated using logistic regression modelling. RESULTS According to univariate analyses, male gender, co-treatment with aminoglycosides and mutant genotype of GSTP1 rs1695 were significantly related with cisplatin ototoxicity. Logistic regression modelling analyses also showed that male gender, co-treatment with aminoglycosides were found to be significantly related with cisplatin ototoxicity. Mutant genotype of GSTP1 rs1695 was not found to be significant, but close to the level of statistical significance. CONCLUSION Male gender, co-treatment with aminoglycosides are significant risk factors for cisplatin ototoxicity in pediatric patients. Mutant genotype of GSTP1 rs1695 seems to be a genetic risk factor in univariate analyses, although not confirmed by multivariate analyses. Therefore, GSTP1 rs1695 SNP needs to be studied in larger series.

A Single Center's Experience with Candida parapsilosis Related Long-Term Central Venous Access Device Infections: The Port Removal Decision and Its Outcomes

Pediatric cancer patients have an increased risk of potentially life-threatening fungal infections such as Candida parapsilosis, associated with long-term CVADs. The Infectious Diseases Society of America (IDSA) guidelines on Candida catheter-related bloodstream infections recommend systemic antifungal therapy and catheter removal. In this study, we focused on our experience with antifungal failure due to totally implanted catheter-associated C. parapsilosis bloodstream infections. We investigated cases leading to port removal in pediatric malignancy patients and the associated patient outcomes. In the first phase of the study, a retrospective chart review was performed to collect patient information, including primary disease; time from hospitalization to port-related candidemia; antifungal drug choice; and the time at which port removal occurred. During the second phase, antifungal susceptibility tests for C. parapsilosis were performed in our microbiology laboratory. All patients had fevers and were neutropenic at the time of candidemia diagnosis. The mean duration between the first isolation of Candida parapsilosis from the port samples to the port removal was 9.75 ± 5.29 days for 11 patients. Patient fevers lasted for a mean time of 16.22 ± 6.51 days. The median recovery duration from fever after CVC removal was four days (range 2–12 days). The median duration for achieving negative blood cultures, following antifungal treatment was 18 days (range 10–27 days). Our data favored the removal of catheters in the presence of ongoing fever, as suggested by the guidelines, independent of the chosen antifungal treatment. Future studies with large samples are needed to evaluate the effects of catheter removal on mortality rates and patient outcomes.

Cytoprotective effects of amifostine in the treatment of childhood malignancies.

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.

Massive pericardial effusion due to intrapericardial mixed germ cell tumor in a premature baby.

Primary cardiac tumor is uncommon in childhood, with an incidence of 0.06–0.32%, and intrapericardial teratoma represents an exceptional rarity among these entities. Germ cell tumors (GCT) are rare, representing only 1–3% of childhood tumors. Twenty per cent of GCT are malignant and are associated with age and location. Extragonadal involvement accounts for nearly half of the cases. Anterior mediastinum is a common location of malignant germ cell tumors, yet pericardial and aortic adventitia involvement have been rarely reported. Here we report the case of a preterm twin baby boy with intrapericardial mixed germ cell tumor who presented with hydrops fetalis and pericardial effusion.

Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively. None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.

Spontaneous epidural and subdural hematoma in a child with afibrinogenemia and postoperative management.

Congenital afibrinogenemia is a rare coagulation disorder that exhibits recessive inheritance. The prevalence of this disease is around 1 per 1 000 000, but it is increased in countries where consanguineous marriages are common. Umbilical cord bleeding during the neonatal period is generally the first manifestation of the disease, but a later age of onset is not uncommon. This disease may also be manifested by gastrointestinal, genitourinary, mucosal, muscular, articular, and intracranial bleeding during childhood. Intracranial hemorrhage is a rare condition, but it is the leading cause of death in patients with afibrinogenemia. In this report, we present the case of a 13-year-old female patient with afibrinogenemia who underwent an operation for spontaneous massive extradural and subdural hematoma.

Management of Childhood Thyroid Nodules: Surgical and Endocrinological Findings in a Large Group of Cases

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.

Varicella-Zoster Virus Infections in Pediatric Malignancy Patients: A Seven-Year Analysis

Primary varicella-zoster virus (VZV) infection is a benign self-limited disease. In this study, we review our experience in focusing on the outcome and treatment of VZV infection in pediatric malignancy patients. During the study period, a total of 41 patients with pediatric malignancy had been hospitalized with the diagnosis of VZV infection. All the patients were treated with intravenous acyclovir for a median of 7 days (ranging from 5 to 21 days). The calculated attributable delay of chemotherapy due to VZV infections was 8 days (ranging from 2 to 60 days). VZV-related complications were observed in 3 of 41 patients (7%) who suffered from acute respiratory distress syndrome, and one of them with hemophagocytic lymphohistiocytosis died due to respiratory failure despite acyclovir and broad-spectrum antimicrobial treatment plus supportive treatment. VZV infections are still important contagious diseases in pediatric cancer patients, because they cause not only significant mortality but also a delay in chemotherapy.

Developing the Scale for Quality of Life in Pediatric Oncology Patients Aged 13–18: Adolescent Form and Parent Form

PURPOSE This study aimed to develop the Scale for Quality of Life in Pediatric Oncology Patients Aged 13-18: Adolescent Form and Parent Form. METHODS We used the child and parent information form, Visual Quality of Life Scale, and our own scale, the Scale for Quality of Life in Pediatric Oncology Patients Aged 13-18: Adolescent Form and Parent Form. We finalized the 35-item scale to determine the items, received opinions from 14 specialists on the scale, and pilot-tested the scale in 25 children and their parents. We used Pearson correlation analysis, Cronbach α coefficient, factor analysis and receiver operating characteristics analysis to analyze the data. RESULTS The total Cronbach α of the parent form was .97, the total factor load was .60-.97 and the total variance was 80.4%. The cutoff point of the parent form was 85.50. The total Cronbach α of the adolescent form was .98, the total factor load was .62-.96, and the total variance explained was 83.4%. The cutoff point of the adolescent form was 75.50. As a result of the parent form factor analysis, we determined the Kaiser-Meyer-Olkin coefficient as .83, the Barlett test χ(2) as 12,615.92; the factor coefficients of all items of the parent form ranged from .63 to .98. The factor coefficients of all items of the adolescent form ranged from .34 to .99. As a result of the adolescent form factor analysis, we determined the KMO as .79, and the Barlett test χ(2) as 13,970.62. CONCLUSIONS Conclusively, we found that the adolescent form and the parent form were valid and reliable in assessing the childrens quality of life.

Complications of Central Venous Catheters in Children Undergoing Hematopoietic Stem Cell Transplantation in Turkey

Although central venous catheters (CVCs) have become an integral element of the care of patients undergoing hematopoietic stem cell transplantation (HSCT), the associated complications can lead to treatment delays and negatively affect the child and family’s quality of life. The aim of this study was to identify the types, rate of, and risk factors for the complications relating to CVCs used in children undergoing HSCT in Turkey. One hundred children were followed prospectively to track catheter-related complications in the transplantation unit. Overall, 186 complications were documented. The most frequent complications were catheter-related infections and malfunctions. Children who had nonhematological disease had a higher rate of complications than those with hematological disease. HSCT nurses should follow and apply evidence-based clinical practice guidelines to support the management of catheters. Nurse staffing ratios and workload may be an issue in developing countries. The authors believe that proper maintenance of CVCs contributes to the reduction of catheter-related complications despite these issues and that problems can be overcome by hiring experienced staff, appropriate nursing education, and by organizing and improving home care programs for HSCT patients.