Handan Dincaslan

Successful treatment of central venous catheter infection due to Candida lipolytica by caspofungin-lock therapy.

Fungal infections, mainly represented by bloodstream infections (BSI) due to Candida spp., have maintained a constant incidence rate over the past 10 years, representing around 10% of catheter-related BSI (Kojic EM et al., Clin Microbial Rev 2004; 17: 255–67). The Infectious Diseases Society of America (IDSA) guidelines on Candida catheter-related BSI recommend the systemic antifungal therapy and catheter removal (Pappas PG et al., Clin Infect Dis 2009; 48: 503–35). This is warranted both by the ability of Candida spp. to form biofilms that greatly reduce antifungal activity and by the extremely high risk of metastatic infections, particularly endocarditis and retinitis (Viale P et al., J Chemother 2006; 18: 235–49). In clinical practice, catheter removal is not always easily performed, depending both on type of device (for tunnelled or totally implanted catheters, a surgical procedure is needed) and on the patient s condition (e.g. patients with severe platelet or coagulation factor deficit). For these reasons, antifungal-lock technique (ALT) alternative to the device removal is proposed (Mermel LA et al., Clin Infect Dis 2001; 32: 1249–72). ALT consists of catheter lumen replenishment by a selected antimicrobial agent and then locking it for a time to eradicate the microbes embedded in endoluminal biofilms (Angel-Moreno A et al., J Infect 2005; 51: e85–87). Treatment of catheter-related BSI due to Candida spp. with ALT has been tried in few cases (Mermel LA et al., Clin Infect Dis 2001; 32: 1249–72; Buckler BS et al., Pediatr Infect Dis J 2008; 27: 762–4; Arnow P et al., Am J Med 1991; 90: 128–30; Viale P et al., Clin Infect Dis 2001; 33: 1947–8; Benoit JL et al., Clin Infect Dis 1995; 21: 1286–8). Herein, to our knowledge, we report the first case of non-complicated Candida lipolytica fungaemia related to a Hickman catheter cured with intraluminal caspofungin in addition to systemic caspofungin therapy.

Soy Isoflavones Ameliorate the Adverse Effects of Chemotherapy in Children

Genistein sensitizes cancer cells to chemotherapy and radiation by modulating cell survival pathways. At the same time, genisteins antioxidant and anti-inflammatory effects may protect normal tissues from adverse effects of chemotherapy and radiation, which are largely due to oxygen-free radicals and inflammation. We conducted a small pilot study with a soy isoflavone mixture containing 8 mg of genistein in children receiving chemotherapy and/or radiation to investigate genisteins potential toxicity preventive effect. We monitored clinical and laboratory parameters in children with cancer who received their first cycle of chemotherapy without genistein and the subsequent cycles with genistein. Patients served as their own controls, and the clinical-laboratory data from the first cycle were compared to the data from subsequent cycles. Nine cycles of chemotherapy were administered without genistein and 57 cycles with genistein. Patients experienced less myelosuppression, mucositis, and infection when they received genistein with chemotherapy. During supplementation, serum genistein levels were 2 to 6 times higher compared to presupplementation levels. Patients who received abdominal radiation reported less pain and diarrhea when they took the genistein supplement. Further clinical investigation of soy isoflavones in pediatric cancer patients receiving chemotherapy and/or radiation should be conducted.

Retinoblastoma in Turkey: Results From a Tertiary Care Center in Ankara

PURPOSE To evaluate the presentation patterns and results of management of retinoblastoma at a tertiary care center in Ankara, Turkey, with special emphasis on globe conservation rate in unilateral and bilateral intraocular retinoblastoma. METHODS Patients were grouped according to the International Classification of Retinoblastoma. For intraocular retinoblastoma, group E and some group D eyes underwent primary enucleation. Secondary enucleation was performed after failure of chemoreduction, focal treatments, external beam radiotherapy (EBRT), and intra-arterial chemotherapy used in various combinations. For extraocular retinoblastoma cases, treatment consisted of enucleation/exenteration or orbital biopsy, high-dose chemotherapy, and EBRT to the orbit and metastatic sites. RESULTS During the study period from October 1998 to May 2010, 165 of 192 (85.9%) patients had intraocular disease and 27 (14.1%) patients had extraocular disease. In total, primary or secondary enucleation was performed in 70 of 94 eyes with unilateral retinoblastoma (74.5%) and in 34 of 142 eyes with bilateral retinoblastoma (23.9%). The overall globe conservation rate was 69.6%. Only one patient in the intraocular retinoblastoma group died of metastatic retinoblastoma to the central nervous system. Twenty of 27 patients (74.1%) with extraocular retinoblastoma were found to have metastasis to the central nervous system, bone, bone marrow, and/or lymph nodes. At a mean follow-up of 28.0 months (median: 12 months; range: 1 to 120 months), survival was 33.3% despite intensive treatment. CONCLUSIONS The overall risk of enucleation was 75% in eyes with unilateral retinoblastoma and 24% in eyes with bilateral retinoblastoma. Extraocular retinoblastoma carries a 75% risk of systemic metastasis and 67% risk of death.

DOES SERUM SOLUBLE VASCULAR ENDOTHELIAL GROWTH FACTOR LEVELS HAVE DIFFERENT IMPORTANCE IN PEDIATRIC ACUTE LEUKEMIA AND MALIGNANT LYMPHOMA PATIENTS

Vascular endothelial growth factor (VEGF) seems to play a central role in angiogenesis-lymphangiogenesis in hematological malignancies. There are limited data related to childhood hematologic malignancies. The aim of the study was to evaluate soluble VEGF (sVEGF) levels in children with acute leukemia and malignant lymphoma (ML) at diagnosis and in remission. The levels of serum sVEGF were measured by enzyme-linked immunosorbent assay (ELISA) in 20 children with acute leukemia, 33 children with different histopathological subtypes of ML, and 20 healthy controls. The levels of sVEGF at diagnosis (range 2 –1040 pg/mL; median 52 pg/mL) was significantly lower than in remission (range 136 –1960 pg/mL; median 630 pg/mL) in acute myeloid leukemia (AML) group (P = .018). The sVEGF levels at diagnosis (range: 2 –640 pg/mL; median 89 pg/mL) was significantly lower compared to remission values (range: 116 –1960 pg/mL; median 136 pg/mL) in patients with acute lymphoblastic leukemia (ALL) (P = .002). In ML group, including Burkitts lymphoma (BL), T-cell non-Hodgkins lymphoma (NHL), and Hodgkins lymphoma (HL), sVEGF levels at diagnosis were higher than remission levels, but there was no statistically significant difference (P >.05). On the other hand, there were significant difference between levels in active disease and control group, ie, BL versus control, T-cell NHL versus control, and HL versus control (P = .008, P = .043, P = .007, respectively). The authors noticed that sVEGF levels showed distinct behavioral pattern in different childhood malignancies at diagnosis and in remission. In acute leukemia and ML patients, VEGF acts through different pathophysiological mechanisms, in both bone marrow (BM) angiogenesis and lymphoid tissue lymphangiogenesis.

Selenium in the Prevention of Anthracycline-Induced Cardiac Toxicity in Children with Cancer

High cumulative doses of anthracyclines (300–500 mg/m2) used in the treatment of children with cancer may result in cardiotoxicity, a major long-term adverse effect that limits clinical usefulness of this class of chemotherapeutic agents. We assessed anthracycline-induced cardiotoxicity by measuring Pro-BNP levels and echocardiographic (ECHO) findings and investigated potential protective effect of selenium (Se) supplementation in a group of pediatric cancer patients. Plasma level of Pro-BNP was measured, and ECHO was performed in 67 patients (45 boys, 22 girls; ages 2–18 years; median age 12 years) after they completed anthracycline-containing chemotherapy. Serum Se level was measured in 37 patients. Eleven patients had high Pro-BNP levels and/or cardiac failure with Pro-BNP levels of 10–8,022 pg/mL (median 226.3 pg/mL; laboratory normal level is less than 120 pg/mL). Serum Se levels were low (20–129 mcg/L, median 62 mcg/L) in ten of these eleven patients. Eight of 10 patients with low Se and high Pro-BNP levels were supplemented with Se 100 mcg/day for a period of 4–33 months (median 6 months) which resulted in improvement in Pro-BNP and/or ECHO findings. These results suggest that Se supplementation may have a role in protection against anthracycline-induced cardiac toxicity.

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.

Challenges and differences in external radiation therapy for retinoblastoma: from standard techniques to new developments.

Aims The purpose of this study is to calculate the treatment plans and to compare the dose distributions and dose-volume histograms (DVH) for 6 external radiotherapy techniques for the treatment of retinoblastoma as well as intensity-modulated radiotherapy (IMRT) and fractionated stereotactic radiotherapy (Cyberknife). Methods Treatment plans were developed using 6 techniques, including an en face electron technique (ET), an anterior and lateral wedge photon technique (LFT), a 3D conformal (6 fields) technique (CRT), an inverse plan IMRT, tomotherapy, and conventional focal stereotactic external beam radiotherapy with Cyberknife (SBRT). Dose volume analyses were carried out for each technique. Results All techniques except electron provided similar target coverage. When comparing conformal plan with IMRT and SBRT, there was no significant difference in planning target volume dose distribution. The mean volume of ipsilateral bony orbit received more than 20 Gy, a suggested threshold for bone growth inhibition. The V20 Gy was 73% for the ET, 57% for the LFT, 87% for the CRT, 65% for the IMRT, 66% for the tomotherapy, and 2.7% for the SBRT. Conclusions This work supports the potential use of IMRT and SBRT to spare normal tissues in these patients.

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.

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.

Serum Basic Fibroblastic Growth Factor Levels in Children with Infantile Hemangioma

ObjectivesTo determine serum levels of basic fibroblastic growth factor (b-FGF) in hemangioma patients under 2 y of age.MethodsThe study group consisted of 43 children with infantile hemangioma and b-FGF levels were analyzed using ELISA.ResultsThe serum b-FGF levels were higher in hemangioma patients than in healthy control individuals (p 0.01). There were no differences between the lesion size, number of lesions, patient age and serum b-FGF levels.ConclusionsThus, b-FGF is an important growth factor that plays a central role in hemangioma, but determining b-FGF serum levels was not helpful in distinguishing between patients who require treatment and those who do not.