Arzu Okur

Resveratrol and Adipose-Derived Mesenchymal Stem Cells Are Effective in the Prevention and Treatment of Doxorubicin Cardiotoxicity in Rats.

Anthracyclines can cause severe cardiac toxicity leading to heart failure. The aim of this study was to determine the effects of cardioprotective polyphenolic compound resveratrol (RES) and adipose-derived mesenchymal stem cells (ADMSCs) on cardiac tissue of rats treated with doxorubicin (DOX). Forty-two female and three male Wistar–Albino rats were included in the study. The study groups and the control groups were as follows: Group I: DOX; Group II: DOX + RES; Group III: DOX + ADMSCs; Group IV: DOX + RES + ADMSCs; Group V: Sham operation; and Group VI: normal saline. ADMSCs obtained from male rats were defined with stem cell markers [CD11b/c(−), CD45(−), CD90(+), CD44(+), and CD49(+)]. DOX 12 mg/kg intraperitoneally (i.p.) was injected as a single dose in female rats. Resveratrol 100 mg/kg was injected three times i.p. in Groups II and IV. ADMSCs 2 × 106 cells/kg/dose were labeled with bromodeoxyuridine (BrdU) and injected i.p. for a total of three times in Groups III and IV. When the study was terminated after 4 weeks, the beating hearts were connected to a Langendorff setup and records were obtained for 30 minutes. Histopathological, immunhistochemical, and immunofluorescent examination with H&E, Troponin I, and BrdU stains were also performed. Also, ADMSCs were demonstrated in the myocardium of transplanted rats. Left ventricle functions and myocardial histology demonstrated significant impairment in DOX only group compared to groups with ADMSCs (P < .05). We suggest that RES and ADMSCs were successful in the prevention and treatment of the doxorubicin cardiomyopathy in rats. The hypothetical mechanisms of regeneration are multiple, including cell differentiation and autocrine/paracrine effects of ADMSCs.

EFFECTS OF ORAL GLUTAMINE SUPPLEMENTATION ON CHILDREN WITH SOLID TUMORS RECEIVING CHEMOTHERAPY

In recent years, there have been reports that glutamine support improves immune functions in adult patients with malignancy, but there is a lack of data in children. Oral glutamine support of 4 g/m2/day was given to 21 children with various solid tumors, aged 1–17 years (9.86 ± 5.38) for all 5 days of a chemotherapy course. The same parameters in another course of the same protocol without glutamine supplementation were considered as controls. There were significant improvements of some nutritional and immunological parameters in the glutamine-supplemented course. Also glutamine seemed to reduce antibiotic necessity. Oral glutamine supplementation could be considered in children with solid tumors receiving chemotherapy.

Clinical characteristics and treatment results of pediatric B-cell non-Hodgkin lymphoma patients in a single center.

The aim of this study was to evaluate and compare the clinical characteristics of the B-cell non-Hodgkin lymphoma (NHL) patients and therapeutic efficacy of modified NHL BFM-90 and NHL BFM-95 protocols in the authors’ center. From January 1993 to December 2003, 61 newly diagnosed children with B-NHL were enrolled to the study. The patients were stratified by risk factors and treated either with a modified B-NHL BFM-90 or BFM-95 protocols. The use of 1 or 3 g/m2 of methotrexate instead of 5 g/m2/24 h was the only important modification in BFM-90 protocol. Sixty-one children (12 girls, 49 boys) with a median age of 6.5 years (range: 2.5–16) were treated in the center. There were 14 patients in stage II, 28 in stage III, and 19 in stage IV. The most common initial primary tumor sites were abdomen, head, and neck. Forty-five patients were treated with modified B-cell BFM-90 and 16 patients were treated with B-cell BFM-95 regimens. The 5-year overall survival (OS) for all patients was 85.8%, and event-free survival (EFS) was 82.8%. The 5-year OS rates in modified BFM-90 and in BFM-95 protocols were 85.2 and 87.5%; the 5-year EFS rates in these 2 protocols were 84.6 and 70%, respectively (p >.05). Factors associated with lower EFS by univariate analysis were bulky disease, risk groups, and LDH level ≥ 500 IU/L. By multivariate analysis only LDH level was significant. In conclusion, the treatment results in this study were similar to those of BFM group.

Thyroid Abnormalities in Survivors of Childhood Cancer

Objective: To investigate the late side effects of childhood cancer therapy on the thyroid gland and to determine the risk factors for development of thyroid disorder among childhood cancer survivors. Methods: One hundred and twenty relapse-free survivors of childhood cancer (aged 6-30 years) were included in this study. The diagnoses of patients were lymphoma, leukemia, brain tumor, rhabdomyosarcoma and nasopharyngeal carcinoma (NPC). The patients were divided into two groups depending on the treatment: group 1-chemotherapy (ChT) only (n=52) and group 2-combination therapy of ChT + radiotherapy (RT) (head/neck/thorax) (n=68). Thyroid function tests, urinary iodine levels, and thyroid gland ultrasound examinations were evaluated in both groups. Results: Incidence of thyroid disease was 66% (n=79) in the survivors. The thyroid abnormalities were: hypothyroidism (HT) (n=32, 27%), thyroid nodules (n=27, 22%), thyroid parenchymal heterogeneity (n=40, 33%), autoimmune thyroiditis (n=36, 30%), and thyroid malignancy (n=3, 2%). While the incidence of HT and thyroid nodules in group 2 was significantly higher than in group 1, the incidence of thyroid parenchymal heterogeneity and autoimmune thyroiditis was similar in the two patient groups. HT and thyroid malignancy were seen only in group 2. In multivariate logistic regression analysis, a history of Hodgkin lymphoma (HL), brain tumor and NPC, as well as cervical irradiation and 5000-5999 cGy doses of radiation were found to constitute risk factors for HT. History of HL and 4000-5999 cGy doses of radiation were risk factors for thyroid nodules. Head/neck irradiation and treatment with platinum derivatives were risk factors for autoimmune thyroiditis. In univariate analysis, a history of NPC, cervical + nasopharyngeal irradiation, and treatment with platinum derivatives were risk factors for thyroid parenchymal heterogeneity. Conclusion: Our results indicate that there is especially an increased risk of HT and thyroid nodules in patients treated with combination therapy of ChT with head/neck/thorax RT. Although chemotherapeutic agents per se do not seem to cause HT, longer follow-up is needed to assess whether or not there is an increased risk for autoimmune thyroiditis and thyroid parenchymal heterogeneity after antineoplastic therapy.

MANAGEMENT OF PLEXIFORM NEUROFIBROMA WITH INTERFERON ALPHA

Plexiform neurofibroma is a relatively common but potentially devastating manifestation of neurofibromatosis type 1 (NF 1). A substantial number of plexiform neurofibroma causes morbidity. Various treatment modalities are considered to decrease pain. In this paper a case with plexiform neurofibroma causing severe pain and in whom alpha-interferon was used is presented.

A complication to be aware of: hyperkalaemia following propranolol therapy for an infant with intestinal haemangiomatozis.

Infantile haemangiomas, benign vascular tumours seen in 4–10% of infants are characterised by their spontaneous remission following a 3–9 month period of dynamic growth. Propranolol has been reported to be used as a successful treatment of severe symptomatic infantile haemangiomas. Hyperkalaemia has not been recognised as a serious effect of propranolol since recently. Here, we would like to portray a 2-year-old male patient with intestinal haemangiomatosis who presented with severe hyperkalaemia and was successfully managed with hydration, loop diuretics, potassium binding granules, inhaler β-2 agonists and insulin. To date, this is the first case of intestinal haemangiomatosis complicated with severe hyperkalaemia. Our case suggested the idea of close monitorisation of potassium levels as well as haemodynamic status at the initialisation of the propranolol treatment.

PRIMITIVE NEUROECTODERMAL TUMOR OF THE KIDNEY IN A CHILD

Primary renal pimitive neuroectodermal tumor (PNET) is an extraordinarily rare neoplasm in childhood. It generally occurs in young adults and only a few pediatric cases have been reported. PNET in the kidney acts aggressively and the record shows poor therapeutic response. The authors present the case of a 16-year-old girl who was diagnosed with renal PNET and treated with high-dosage chemotherapy and peripheral blood stem cell transplantation (PBSCT).

Successful multimodal treatment for aggressive metastatic and recurrent fibrolamellar hepatocellular carcinoma in a child.

Fibrolamellar variant of hepatocellular carcinoma (FLHCC) does not have a favorable prognosis than conventional HCC, and there is no difference regarding the response to chemotherapy and the degree of surgical resectability. FLHCC commonly recurs after complete surgical resection, and there is a high rate of lymph node metastases. Herein, we report a 12-year-old girl with metastatic FLHCC with multiple recurrences aggressively treated with surgery, chemotherapy, and antiangiogenic agents. She is in complete remission after 4 years and 2 months after the diagnosis of metastatic FLHCC. The standard treatment of FLHCC is excision of the primary tumor and its metastases. Chemotherapy for FLHCC is controversial, and it has been suggested that cytoreductive chemotherapy was ineffective and adjuvant chemotherapy did not improve survival. Our patient with multiple recurrences was successfully treated with surgery, first-line chemotherapy with cisplatin and doxorubicin, second-line chemotherapy with 5-fluorouracil/interferon-&agr; combination, and adjuvant antiangiogenic agents like cyclophosphamide and thalidomide. As FLHCC patients have no underlying liver disease, they can tolerate higher doses of chemotherapy compared with conventional HCC patients. We support the use of repeated aggressive surgery with adjuvant chemotherapy and antiangiogenic therapy, which provided complete remission in our patient with metastatic and recurrent FLHCC.

Assessment of brachial artery reactivity, carotid intima-media thickness, and adhesion molecules in pediatric solid tumor patients treated with anthracyclines.

ABSTRACT The aim of this study was to determine subclinical atherosclerosis and endothelial functional disturbance with measurement of carotid intima-media thickness (IMT), brachial artery reactivity (BAR), and levels of serum adhesion molecules in children with solid tumors who were treated with anthracyclines and are actually in complete remission. Fifty patients who were in remission and 30 healthy children were included in the study. Mean ages of patient and control groups were 13.5 ± 4.7 years (range: 3–23 years) and 12.00 ± 4.3 years (range: 4–21 years), respectively. The patients were divided into 3 groups according to cumulative doxorubicin dose: Group 1, ≤100 mg/m2; Group 2, 101–299 mg/m2; Group 3, ≥300 mg/m2. The BAR and carotid IMT were measured in order to determine the endothelial function. The serum adhesion molecule levels in our patients and controls were also measured. The BAR of the patients with cumulative anthracycline dose ≥300 mg/m2 was significantly lower than the patients with cumulative anthracycline dose ≤100 mg/m2 and healthy controls (P =.005 and P =.003, respectively). Also, there was a negative correlation between brachial artery reactivity and increasing cumulative anthracycline dose (r = −.287, P =.044). We also found significant difference between the mean carotid IMT of the patients and the healthy children (P =.041). No statistically significant difference was detected between the serum levels of sICAM-1 (soluble intercellular adhesion molecule-1), sVCAM-1 (soluble vascular cell adhesion molecule-1), sE-selectin of the patients and controls. The use of anthracyclines in pediatric patients with cancer could result in increase of the carotid IMT and endothelial dysfunction.

Imaging features of Burkitt lymphoma in pediatric patients

Burkitt lymphoma is an aggressive and rapidly growing tumor that is curable and highly sensitive to chemotherapy. It can affect almost every tissue in the body, producing various clinical presentations and imaging appearances, according to the predilection of the different subtypes for certain sites. Awareness of its diagnostically specific imaging appearances plays an important role in rapid detection and treatment. In this pictorial review, we aimed to identify the most common imaging features of Burkitt lymphoma in pediatric patients.