Ongoing assessment of nutritional status in children with malignant disease.

The nutritional status of a child on cancer therapy influences both tolerance of and response to treatment. However, it is difficult to assess nutritional status on a daily basis because an accurate quantitation of the calorie intake is difficult. Anthropometric and biochemical parameters are prone to error and often reflect past rather than current nutritional status. In practice, a subjective clinical assessment is usually relied upon. This study objectively appraises the value of such an assessment. Based on clinical symptoms that alter oral intake and absorption of food, a scoring system was designed to assess nutritional status on a day to day basis. A symptom score (SS) of 10 implied "normality"; 0 indicated maximum debility. Over a 2-year period 511 daily scores were recorded in 30 patients aged 0.7-17.5 years. Patients were studied at presentation and during treatment for acute lymphoblastic leukemia (ALL, n = 14; solid tumors receiving megatherapy with autologous bone marrow rescue (ABMR, n = 8), and chemotherapy for different tumors (miscellaneous, n = 8). The SS was compared with other nutritional parameters, including sequential anthropometric indices, serum albumin, insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), and whole-body protein turnover (WBPT) using [1-(13) C]leucine. The mean SS was reduced at diagnosis for all leukemic patients (median score = 8), improved during first remission (p < 0.002), fell to a minimum during febrile neutropenia (p = 0.0009), and improved with clinical and hematological recovery (p = 0.0009). A reduction in SS was related to fever (p < 0.001) and a fall in neutrophil count (p < 0.001). There was no correlation with anthropometric indices or IGF-I and IGFBP-3 levels. Paired WBPT studies in 9 patients showed that SS correlated well with protein breakdown (p = 0.026). The results suggest that the ongoing nutritional status of children with malignancy undergoing chemotherapy is best assessed using simple clinical parameters.

Changes in protein turnover, IGF-I and IGF binding proteins in children with cancer.

Changes in insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) were correlated with protein synthesis and breakdown using [1-13C]leucine before chemotherapy and during subsequent febrile neutropenia (FN) in eight children with cancer, aged 6.3-17.5 y. IGF-I levels were similar to age-matched controls before chemotherapy (mean +/- SEM: 250+/-28 and 228+/-22 microg l(-1), respectively). During FN, IGF-I fell to 156+/-22 microg l(-1) (p = 0.02), and rose to 276+/-27 microg l(-1) with recovery at 6 months (p = 0.004). Similarly, IGFBP-3 decreased from 4.0+/-0.2 mg l(-1) before chemotherapy to 3.0+/-0.3 mg l(-1) during FN (p = 0.01), and returned to 4.1+/-0.2 mg l(-1) at 6 months (p = 0.01). IGF-I correlated with IGFBP-3 (r = +0.7, p < 0.001). Scanning densitometry showed a decrease in IGFBP-3 from 94 to 54% during FN, when the presence of IGFBP-3 protease activity was observed. Compared with normal human serum, IGFBP-2 was elevated throughout the study. IGFBP-1 increased from 14.6+/-3.5 to 30.6+/-2.8 microg l(-1) (p = 0.004), whereas serum insulin decreased from 26.5+/-6.8 to 7.8+/-0.8 mU l(-1) (p = 0.03) before and during FN, respectively. Whilst IGF-I and IGFBP-3 fell, daytime growth hormone increased from 3.3+/-0.6 to 6.7+/-0.8 mU l(-1) (p=0.01), and cortisol from 197+/-48 to 594+/-98 nmol l(-1) (p = 0.005). Albumin decreased from 47+/-2 to 38+/-2 g l(-1) (p = 0.004) and improved to 47+/-2 g l(-1) with recovery (p = 0.003). Protein synthesis increased from 4.5+/-0.4 to 5.0+/-0.6 g kg(-1)d(-1) before chemotherapy and during FN, while protein breakdown rose from 5.4+/-0.4 to 6.3+/-0.4 kg(-1)d(-1). Increasing protein breakdown was related to falling IGF-I and IGFBP-3 levels. Modification of IGFBP-3 by circulating proteolytic activity may alter IGF bioavailability, allowing protein synthesis to increase during periods of severe catabolic stress.

Central venous catheter tip position and malfunction in a paediatric oncology unit.

An audit of 151 central venous catheters (CVCs) in 118 children with malignant disease was carried out over 20 months. The types included 31 valved silastic (Groshong), 58 non-valved silastic (Hickman), and 62 non-valved polyurethane (Cuff Cath) CVCs. There was no difference between the three groups with regard to the clinical diagnosis. The mean patient age at catheter insertion was 5.5 years and the mean weight 21.6 kg. None of the catheter types were associated with an increased risk of problems at insertion, migration, mechanical damage, blockage, sampling, or catheter infection. The incidence of catheter infection was 1.4/1,000 catheter days. Exit-site infection was less frequent with Groshong CVCs (P <0.05), which were in situ for the shortest period. The risk of problems with blood sampling was significantly increased in those catheters whose tip was sited outside the right atrium (P <0.005). For the 60 CVCs removed electively, the mean duration in situ was similar for all catheter types; 43 were removed following a problem. Of these, Groshong catheters were in situ for the shortest period (P = 0.05), probably as a result of delayed anchoring of the cuff. The tip position was the single most important determinant in the correct functioning of CVCs, irrespective of the type of catheter. Intraoperative screening of the tip position at catheter insertion is therefore mandatory for optimal catheter functioning.

High incidence of hypertension in children presenting with acute lymphoblastic leukemia.

Although hypertension is a complication of acute lymphoblastic leukemia (ALL), its true incidence in this disease is unknown. In this study the blood pressure profiles in all children newly diagnosed with ALL were reviewed over an 18-month period. Fourteen (46%) from a total of 30 patients were found to be hypertensive at presentation (n = 8) or during induction chemotherapy (n = 6). A patient with significant hypertension developed generalized convulsions; the rest were asymptomatic. Six patients were managed with antihypertensive drugs. Four patients with hypertension had renal enlargement on the initial ultrasound scan, which returned to normal when hematologic remission was achieved. One patient without hypertension had bilateral renal enlargement, but this persisted despite achieving remission. All patients with hypertension were normotensive at follow-up 2 to 18 months after induction chemotherapy. The presence of hypertension before therapy and its association with renal enlargement suggest that the leukemic process is an important etiologic factor. In all cases therapy aggravated or unmasked the elevation in blood pressure. Considering the high incidence of susceptible patients, increased awareness and prompt management may avoid possible life-threatening complications.

Non-Hodgkin's lymphoma and Klinefelter syndrome.

Patients with a 47, XXY karyotype (Klinefelter syndrome) appear to have an increased risk of developing a malignancy in adulthood, usually cancer of the breast, extragonadal germ cell tumor, and acute nonlymphoblastic leukemia. There is growing evidence to show that these patients also have an increased risk of developing a malignancy in childhood. There are reports describing the development of acute lymphoblastic leukemia, retinoblastoma, and rhabdomyosarcoma in children with a 47, XXY or mosaic 47, XXY/46, XY karyotype. We report a child with a bone metastasizing, B-cell lineage, non-Hodgkin's lymphoma (NHL) who was found to have a 47, XXY karyotype in both the tumor and constitutional cells.

Ganciclovir treatment of congenital cytomegalovirus infection: a report of two cases.

Ganciclovir has been shown to be effective against cytomegalovirus (CMV) in vitro, but its role in the treatment of congenital cytomegalovirus infection is unknown. We describe its use in the management of two cases of congenital CMV infections. The drug was well tolerated and virus shedding in the urine was eliminated, though hepatosplenomegaly and neurodevelopmental delay persisted in both cases.

Late follow-up of lung function after whole lung irradiation for Wilms' tumour.

Radiotherapy is known to have acute and long term deleterious effects on lung tissue. However, pulmonary irradiation is an established treatment in advanced childhood tumours with pulmonary metastases not responsive to chemotherapy. In this study eight patients with Wilms' tumours and lung metastases treated with whole lung irradiation (1200-1837 cGy) and chemotherapy were reassessed clinically, radiologically and with lung function tests 6-26 years after radiotherapy. One patient was breathless after mild exertion, four after strenuous exercise and three were asymptomatic. Clinically all had small chests and four of five females had underdeveloped breasts. A chest radiograph showed clear lung fields in all cases. Lung volumes, especially total lung capacity (TLC) and vital capacity (VC), were decreased when compared with predicted values for age and height. However, gas transfer per unit lung volume (KCO) was normal. This study suggests that pulmonary irradiation in childhood results primarily in underdevelopment of the thorax and that diffuse interstitial lung fibrosis is not a significant feature at this dose level.