Integration of nutrition support into oncologic treatment protocols for high and low nutritional risk children with Wilms' tumor. A prospective randomized study.

Benefits and risks of nutrition support were evaluated in 31 malnourished children with newly diagnosed Wilms' tumor managed according to the third National Wilms' Tumor Study protocol. Patients were classified at diagnosis as being at high nutritional risk (HNR, n = 19) or low nutritional risk (LNR, n = 12). Ten HNR patients were randomized to central parenteral nutrition (CPN) and nine HNR patients were randomized to peripheral parenteral nutrition (PPN) plus enteral nutrition (EN) for 4 weeks of initial intense treatment and EN (nutritional counseling, oral foods and supplements) thereafter. Thirteen HNR patients (seven CPN, six PPN) completed the protocol. Twelve LNR patients received EN; 11 Stage I malnourished patients were randomized to 10 or 26 weeks of chemotherapy. Dietary, anthropometric, and biochemical data were determined for HNR patients at weeks 0-4, 6, 13, 19, and 26 and for LNR patients at weeks 1, 2, 5, and 26. In HNR patients, adequate parenteral nutrition support reversed protein energy malnutrition (PEM), and prevented chemotherapy and radiotherapy delays due to granulocytopenia. CPN was superior to PPN in reversing PEM: energy intake, weight gain, and retinol binding protein were higher (P less than 0.05). LNR patients lost weight and fat reserves in the first 2 weeks of treatment; depletion persisted at week 5, and 25% had chemotherapy delays. Thereafter, EN reversed PEM in patients with both chemotherapy regimens. These data suggest that CPN is preferable during initial intense treatment for HNR patients, and that, although EN is ineffective in preventing depletion and treatment delays in the first 5 weeks of treatment for LNR patients, it is effective thereafter.

Role of selenium-dependent glutathione peroxidase in antioxidant defenses in rat alveolar macrophages.

Glutathione peroxidase is a crucial component of cellular antioxidant defenses. Using tertiary butyl hydroperoxide (tBOOH) as a model for oxidant stress in alveolar macrophages, we determined the effectiveness of glutathione peroxidase in preventing both cell "death" (lactate dehydrogenase release) and more subtle alterations in cell function. The KM of glutathione peroxidase for tBOOH was 54 microM, and the Vmax was 26 nmol/min/10(6) cells in alveolar macrophages. Concentrations of tBOOH greater than 100 microM caused lactate dehydrogenase release; however, a lag greater than 30 min was observed when with 10 mM tBOOH. With 200 microM tBOOH, the rate of decrease in membrane potential, measured by 3,3'-dipentyloxacarbocyanine iodide fluorescence, inversely correlated with glutathione peroxidase. Computer-enhanced microscopy showed that this fluorescence predominately was in mitochondria. NADPH fluorescence was altered in selenium-deficient alveolar macrophages; the tBOOH-dependent rate of NADPH oxidation was slowed, and higher concentrations of tBOOH were required to disturb the steady state NADPH/NADP+ ratio. Although alteration in NADPH or glutathione oxidation can reflect oxidant stress and can adversely affect cell function, such a change does not dictate irreversible injury. Nevertheless, irreversible injury by oxidants appears to involve an overwhelming of the glutathione-NADPH antioxidant system.

Advances in nutrition care of children with neoplastic diseases: a review of treatment, research, and application.

Within the last decade, significant advances have been made both in treating children with cancer and in providing proper nutrition support. Oncologic treatment and nutrition research and their application to the nutrition care of children with cancer are reviewed. Quality nutrition care is now possible because of an improved understanding of (a) the prevalence and significance of protein-energy malnutrition (PEM) in high-risk groups, (b) the staging and assessment of nutritional status, and (c) the efficacy and limitations of nutrition support options. Nutrition staging, assessment, and support should be integrated into treatment protocols for children with neoplastic diseases. Common risk factors for the development of PEM have been identified from serial monitoring of newly diagnosed children with a variety of tumors. Certain tumor types and their treatment can be classified within either low or high nutritional risk groups. A comprehensive nutrition program (intense nutrition counseling, favorite nutritious foods) is preferred for low nutritional risk groups but is ineffective in preventing or reversing PEM in high-risk groups. For high-risk patients, central parenteral nutrition (CPN) is the method of choice as a relatively short-term but important support measure that allows children to withstand long intervals of intense treatment during periods of growth and development. Current data suggest that bone marrow suppression may be attenuated and treatment tolerance improved with the use of CPN in selected children with advanced cancer (e.g., acute nonlymphocytic leukemia or advanced neuroblastoma).

Effect of nutrition staging on treatment delays and outcome in Stage IV neuroblastoma.

The effect of the state of nutrition of 18 children with Stage IV neuroblastoma at diagnosis and during initial therapy, was evaluated with respect to treatment delays, drug dosage alterations, tumor response, days to first event (relapse or death), and survival. All patients received similar therapy (CCSG protocol CCG 371). Based on nutrition staging at diagnosis, nine were classified as malnourished; four were randomized to receive total parenteral nutrition (TPN) and four peripheral parenteral nutrition plus enteral nutrition for 28 days (through 2 chemotherapy courses), and one died before randomization. Nine were nourished at diagnosis; seven received a comprehensive enteral nutrition program and two received TPN. By life-table analysis, the duration of remission was significantly greater in the nourished than the malnourished (P less than 0.01) and a trend towards improved survival was evident at one year (P = 0.08). The median length of survival for children nourished at diagnosis was approximately 12 months, whereas those malnourished had a median survival of only 5 months. Nine children remained nourished or were becoming renourished during the first 21 days of therapy, and one of these had treatment delays and decreased drug dosages. Seven were becoming malnourished or remained malnourished during this period and six had treatment delays (P less than 0.01). These data support the idea that nutrition staging at diagnosis and during initial treatment should be an integral part of protocol design and initial evaluation of children with Stage IV neuroblastoma.