Effects of Malnutrition on Neutrophil/Mononuclear Cell Apoptotic Functions in Children with Acute Lymphoblastic Leukemia.

BACKGROUND: Recent studies claim that apoptosis may explain immune dysfunction observed in malnutrition. OBJECTIVE: The objective of this study was to determine the effect of malnutrition on apoptotic functions of phagocytic cells in acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Twenty-eight ALL patients (13 with malnutrition) and thirty controls were enrolled. Neutrophil and mononuclear cell apoptosis of ALL patients and the control group were studied on admission before chemotherapy and repeated at a minimum of three months after induction of chemotherapy or when the nutritional status of leukemic children improved. RESULTS: The apoptotic functions of both ALL groups on admission were significantly lower than those of the control group. The apoptotic functions were lower in ALL patients with malnutrition than those in ALL patients without malnutrition, but this was not statistically significant. The repeated apoptotic functions of both ALL groups were increased to similar values with the control group. This increase was found to be statistically significant. CONCLUSIONS: The apoptotic functions in ALL patients were not found to be affected by malnutrition. However, after dietary intervention, increased apoptotic functions in both ALL patient groups deserve mentioning. Dietary intervention should always be recommended as malnutrition or cachexia leads to multiple complications. Enhanced apoptosis might originate also from remission state of cancer.

Biologic tumor behavior in pilocytic astrocytomas.

PURPOSE: The aim is to describe the behavior of pilocytic astrocytoma (PAs) and its effects on patient prognosis by using flow cytometric, immunohistochemical and cytogenetic methods. We also aim to find out whether there is any difference between differently localized tumors by the above mentioned analyses. METHODS: We studied DNA index, expression of p53, p16, pRb, MMAC/PTEN1, VEGF, MIB-1 index and chromosomal anomalies which can be detected by array comparative genomic hybridization (CGH) technique. We analyzed the association of the results of these studies with clinical prognosis and tumor localization. We included 53 patients (18 cerebellar, 20 chiasmatic/hypothalamic and 15 hemispheric). Samples were studied from paraffin embedded tumors. RESULTS: We found that PAs are mostly diploid and ploidy pattern does not affect the prognosis. The expression of p53, p16, pRb, MMAC/PTEN1 and VEGF was not significantly different between different localizations and could not predict the prognosis. Frequently seen copy number aberrations (CNAs) are: amplification in 1p36.33, 2p11.2, 9p11.2, 9q12, 16p11.2, 19q13.12-q13.2, Xp22.2-p21.3, Xp11.3-p11.22, Xq11.1-q12, Xq13.1, Xq21.1-q21.31, Xq22.3, Xq26.3 and homozygous deletion in 2p11.2, 8p23.1, 16p12.3. Among them, 2p11.2 amp, 9p11.2 amp and 1p36.21 hom del were correlated with prognosis. Moreover, we found a significant correlation between 16p11.2 amp and tumor localization. CONCLUSIONS: Differently localized PAs have different properties which make them behave with different biological aggressiveness. PAs demonstrate a significant amount of CNAs that can be detected by a high-resolution study. However, tumor suppressor genes p53, p16, pRb, MMAC/PTEN1 and expression patterns do not play a significant role in PAs.

Clinical features and management of carboplatin-related hypersensitivity reactions in pediatric low-grade glioma.

PURPOSE: The effectiveness of carboplatin and vincristine chemotherapy in the treatment of low-grade glioma (LGG) is well established. However, carboplatin hypersensitivity reactions (CHR) are a major problem leading to premature cessation of therapy. We aimed to investigate the clinical features and the management strategies in CHR, retrospectively. METHOD: Fifty LGG patients treated between October 1997 and January 2008 with carboplatin and vincristine were included in the study. Clinical features, management strategies, influence of demographic factors on CHR, and success rate in terms of continuation with carboplatin therapy were evaluated. RESULTS: CHR were observed in 20 (40%) patients and grade I reactions were the most common. The median number of carboplatin doses administered at the first episode of CHR was nine (range 1-41). Only younger age was found to be correlated with the presence of CHR. Nine patients had carboplatin desensitization protocol; eight patients were given various combinations of premedication while three had no modification. Treatment was terminated in five patients due to CHR. Overall success rate was 75%. CONCLUSIONS: This is the largest single-center study conducted to investigate the frequency and the management strategies in patients with CHR who were treated with the same chemotherapy protocol for LGG. Premedication and desensitization were the preferred modifications in case of CHR. Overall, the success rate for carboplatin continuation is high in comparison to previous studies. Carboplatin can be continued successfully in many cases with CHR if reactions are managed in a timely fashion.

Invasive respiratory aspergillosis is a treatable disease with early diagnosis and aggressive therapy.

This study aimed to document outcome of invasive respiratory aspergillosis (IRA) in pediatric malignancy patients. Patients with febrile neutropenia episodes followed between January 2003 and May 2007 were enrolled. Antifungal therapy was added to those who were still febrile on the 5th day of febrile neutropenia treatment. Patients were screened with computerized tomographies. IRA was identified in 22 of 98 patients. There were 13 males and the mean age was 97 months. Proven infection was established in 3, probable in 7, and possible in 12 patients. Liposomal amphotericin B was administered to all patients and was successful in 10 patients. Modifications with caspofungin or voriconazole were done in liposomal amphotericin B failures. The median duration of antifungal therapy was 5.5 months. The median follow-up time was 29 months. There was no evidence of IRA in 12 patients after completion of cancer chemotherapy. Six patients died due to underlying disease, whereas IRA was either in remission or stable disease. Four patients were lost due to IRA. The remission rate for IRA was 82%. Survival at 37 months was 55% (95% confidence interval 25-47 months). The amount of time that absolute neutrophil count after initiation of treatment for IRA remained at zero was found to be an independent prognostic factor on survival (P = .01). These results suggest that early diagnosis and aggressive treatment may increase the successful outcome of IRA.

Cushing's syndrome due to a non-adrenal ectopic adrenocorticotropin-secreting Ewing's sarcoma in a child.

Ectopic ACTH syndrome (EAS) is extremely rare in the pediatric age group. Sarcomatous tumors causing EAS are even rarer. We report a 9 year-old girl presenting with Cushing's syndrome caused by ectopic ACTH production by a Ewing's sarcoma. This case illustrates that rapid appearance of Cushingoid symptoms, absence of growth retardation and the presence of hypokalemia are suggestive clues for ectopic ACTH production as the source of Cushing's syndrome.

False positivity of FDG-PET/CT in a child with Hodgkin disease.

Role of Positron Emission Tomography (PET) with F-18-2-fluoro-2-deoxy-D-glucose (FDG) in staging of Hodgkin disease is well established despite several controversies. We report a Stage III Hodgkin lymphoma patient with false positive FDG-PET/CT results. Seven-year-old male with Hodgkin lymphoma was in remission at end of chemotherapy. At third and fourth month of postchemotherapy follow-up, increased Gallium uptake and positive FDG-PET/CT in right lower quadrant of abdomen was observed. Open biopsy revealed lymphoid hyperplasia. He has been followed for 21 months without any evidence of disease. Despite its documented benefit, we believe that results of FDG-PET/CT should be interpreted with great caution in order to avoid unnecessary interventions.

Cardiac echinococcosis with intra-atrial localization.

Echinococcosis is a frequently encountered parasitic disease in the Mediterranean region, including Turkey. Cardiac disease is seen in 0.5-2% of patients. Usually the cysts are located within the pericardium or intramyocardially; intracavitary localization of the cyst is rarely seen. We herein report a patient who initially presented with hemoptysis and was echocardiographically diagnosed to have an intra-atrial hydatid cyst. Although patients with cardiac hydatid cysts may present with cardiac symptoms, symptoms typically involve other organ systems, following dissemination of the organism. Therefore, echocardiographic screening of patients who are diagnosed with echinococcosis, even if they have no cardiac symptoms, may ensure early diagnosis and prevent development of lethal complications, such as cyst rupture or embolization.

High-dose ifosfamide in relapsed pediatric osteosarcoma: therapeutic effects and renal toxicity.

BACKGROUND: Sixteen pediatric osteosarcoma patients, previously treated with conventional chemotherapy (including ifosfamide (IFX), 9 g/m(2)) were retreated with high-dose ifosfamide (HD-IFX, 14 g/m(2) per course), following relapse or development of a new bone tumor. The objective was to obtain responses and an improved event-free survival (EFS). PROCEDURE: HD-IFX was administered as described by Patel SR: J Clin Oncol 1997;15:2378. Efficacy of treatment was assessed initially after two to four courses. The interval between the courses was 3 to 4 weeks. Provided a response was obtained after two to four courses, treatment was continued for an additional eight courses unless progressive disease or an untoward event, for example, renal failure occurred. Tumor sites were: lung, (10) bone (9), and bone and soft-tissue (1). RESULTS: Response after two to four courses was 62.5%: CR 6 and PR 4. A total of 84 courses were administered to the 16 patients: (range 2-10, median 5.5 per patient). Median interval between courses was 28.5 days (range 15-90). Five patients were disease free at 15+ to 63+ months after induction and maintenance therapy. Fever and neutropenia occurred in 12 courses. Nephrotoxicity was a major toxic event and was characterized by creatinine levels at or above three times the upper limit of normal. It was unpredictable and occurred in four patients: two were reversible. The other two patients developed full-blown renal failure; one was treated with renal dialysis, but both eventually succumbed to osteosarcoma. Our past experience also indicated that two patients treated with IFX (9 g/m(2)/course) developed renal failure: one recovered and the other required a renal transplant. CONCLUSIONS: HD-IFX is effective in patients who have failed conventional chemotherapy including IFX (9 g/m(2)). Improved disease-free survival was achieved in 30% of patients. However, renal failure constitutes an important life-threatening complication and its development is unpredictable.

Association between DNA content and tumor suppressor gene expression and aggressiveness of atypical teratoid/rhabdoid tumors.

OBJECTS: Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive neoplasms that afflict infants and young children. The objective of this retrospective study was to determine the association between DNA content (DNA ploidy, cell cycle analysis), tumor suppressor gene (p53, pRb, p16, and MMAC/PTEN) expression and the biologic aggressiveness of these tumors. METHODS: Eight tumors from 7 patients (1 girl, 6 boys; median age 4+/-6.7 months) were studied. Two patients had DNA aneuploidy and 5 patients manifested diploid DNA content at diagnosis. The proliferative index of the tumors ranged from 10% to 28% (median, 12+/-6.4%). The single tumor with a low proliferative index (i.e., <10%) was aneuploid. Immunohistochemical evaluation of p53, pRb, p16, and MMAC/PTEN expression patterns showed that most of the tumors contained more cells with abnormal pRb and p16 expression than cells with abnormal p53 and MMAC/PTEN expression. Expression of tumor suppressor genes, however, was inhomogeneous. CONCLUSION: Our findings led us to conclude that AT/RT of childhood is characterized by a high proliferative index and DNA aneuploidy. The high expression of abnormal pRb and p16 and the low expression of abnormal p53 and MMAC/PTEN indicate alteration of the G1-to-S phase step in the cell cycle, which could be an explanation for the aggressive nature of these tumors.