Effects of naso-gastric tube feeding on the nutritional status of children ...

European Journal of Clinical Nutrition (1998) 52, 494±500 ß 1998 Stockton Press. All rights reserved 0954±3007/98 $12.00 http://www.stockton-press.co.uk/ejcn

Effects of naso-gastric tube feeding on the nutritional status of children with cancer E den Broeder1, RJJ Lippens1, MA van't Hof 2, JJM Tolboom1, WA van Staveren4, Z Hofman3 and RCA Sengers1 1

Department of Pediatrics, University Hospital Nijmegen, the Netherlands; 2Department of Medical Statistics, University of Nijmegen, the Netherlands; 3Nutricia Research, Zoetermeer, the Netherlands; and 4Department of Human Nutrition, Agricultural University Wageningen, the Netherlands

Objective: To study the effect of suf®cient energy intake, by means of the protocolized administration of nasogastric tube feeding, on the nutritional status of a child with cancer. Design: A comparative experimental study. Setting: Tertiary care at the Centre for Pediatric Oncology, South East Netherlands, University Hospital, Nijmegen. Subjects: Seven children, newly diagnosed with cancer, were included in the experimental study and all completed the trial period. Fourteen patients were included in the retrospective study. They were randomly chosen from a group of patients previously treated for a malignancy at our department and who had received naso-gastric tube feeding for at least 16 weeks. Intervention: Protocolized (experimental group) vs non-protocolized (retrospective group) administration of naso-gastric tube feeding over a period of 16 weeks. The main difference was the amount of tube feeding administered. In addition to energy from other foods, children in the experimental group received 106 13% of their total daily energy requirements (TDER) by means of tube feeding, whereas children in the retrospective group had received 75 24%. Main outcome measures: Weight as a percentage of weight for height according to the 50th percentile of a healthy reference population ideal weight. Results: Weight, expressed as a percentage of the ideal weight, increased signi®cantly in the experimental group (18.2 8.4; P 0.01) and the retrospective study group (5.2 7.3; P 0.001). However, the increase was statistically signi®cant in favour of the experimental group (P 0.003), in which all the children reached their ideal weight, compared to 21% in the retrospective group. Conclusion: Aggressive protocolized nutritional intervention during the intensive phase of anti-cancer treatment, in the form of naso-gastric tube feeding that provides the child's total daily energy requirements, results in considerable improvement in the nutritional status. Descriptors: cancer; nutritional status; tube feeding; children; anthropometrics

Introduction A poor nutritional status is frequently observed in children with cancer at the time of diagnosis and during treatment of cancer. The incidence of malnutrition at diagnosis, caused by the presence of the tumour and several tumour related factors, varies from 6± 50% or even more depending on the tumour type, stage of disease and the criteria used to de®ne malnutrition (Donaldson, 1982; van Eys, 1979; Coates et al, 1986; Rickard et al, 1982, 1983a). Due to aggressive oncological treatment modalities, the nutritional status of a child with cancer will deteriorate rapidly, especially during the initial intensive phase of treatment, if no nutritional intervention is applied (Coates et al, 1986). This is the result of ongoing imbalance between energy intake and energy requirements due to nausea, vomiting, anorexia and increased energy expenditure (Coates et al, 1986; DonaldCorrespondence: Dr E den Broeder Received 22 August 1997; revised 9 January 1998; accepted 17 March 1998

son, 1982; van Eys, 1979; Nelson et al, 1994; Grant & Riviera, 1995). The basic nutritional problem in children with cancer is energy malnutrition which, if not treated, may result in chronic protein energy malnutrition (Coates et al, 1986; Donaldson, 1982; Filler et al, 1977, 1979). Administration of parenteral nutrition (energy) to children with cancer during the initial phase of treatment can maintain or improve their nutritional status, immunity and treatment tolerance. Intensive nutritional counselling was unable to achieve this (Donaldson et al, 1982; van Eys et al, 1979, 1980; Filler et al, 1977, 1979; Ghavimi et al, 1982; Hays et al, 1983; Rickard et al, 1979, 1980, 1983b, 1985, 1986, 1989; Szeluga et al, 1987). Nutritional counselling, with the aim of increasing oral energy intake, was only successful in maintaining an adequate nutritional status after the initial phase of treatment and during maintenance therapy (Rickard et al, 1980, 1985, 1989). So far, the use of nasogastric tube feeding, another well-known means of providing nutritional support, has received little attention in

Naso-gastric tube feeding in children with cancer E den Broeder et al

children with cancer, even though the enteral route is more physiological, cheaper, safer and easier than the parenteral route (Lukens, 1984). In our department, naso-gastric tube feeding has been used to provide nutritional support for many years. Although some improvement was observed in the nutritional status of children receiving naso-gastric tube feeding, the effects were often rather unsatisfactory. This is in contrast with the ®ndings of Smith et al, 1992 who found adequate tube feeding to be very effective for improving the energy intake and nutritional status of ®ve newly diagnosed, malnourished children with various types and stages of cancer. We therefore retrospectively assessed the use of naso-gastric tube feeding and its effect on the nutritional status of a group of children who had been treated for cancer at our department in the past. Subsequently, an experimental study was set up that eliminated the causes for the unsatisfactory improvement in the nutritional status deduced from the retrospective study. The aim of this study was to assess whether a normal weight for height could be achieved and/or maintained in a child with cancer during the initial, intensive phase of anticancer treatment by means of adequate, protocolized nasogastric tube feeding covering at least 100% of a child's total daily energy requirements. Furthermore, we evaluated the effect of adequate coverage of the total daily energy requirements on a child's tolerance of anti-cancer treatment. Data from the retrospective and experimental study are included in this paper, in order to compare the differences in ef®cacy of protocolized and non-protocolized naso-gastric tube feeding on the nutritional status of a child with cancer. Patients and methods Patients Experimental study group. Patients were recruited from a group of children newly diagnosed and treated for any

type or stage of childhood cancer between 1st December 1995 and 1st March 1996. Children were included if they were between 1 ±18 y of age, if they had lost more than 5% of their weight at diagnosis and/or if their oral intake had decreased to 80% of the total daily energy requirements during one week and/or if it was not possible to improve the present state of malnutrition within one week. Inclusion led to the administration of tube feeding over a period of 16 weeks. Children who had received any kind of nutritional therapy at the time of diagnosis and/or those who required more than 12 600 kJ (3000 kcal) per day were excluded. Children diagnosed with acute lymphoblastic leukaemia, lymphoma or a brain tumour were also excluded due to frequent use of high dose corticosteroids. Seven patients were included in the experimental study group and all completed the 16 week trial period (3 male and 4 female; mean age 6.77 4.52 y, Table 1). Informed consent was obtained as approved by the Medical Ethics Committee of the University Hospital in Nijmegen.

Retrospective study group. Patient ®les were used for data collection in the retrospective study group. These were selected at random from a group of patients who had been treated at the University Hospital Nijmegen for any type or stage of childhood malignancy in the period between 1983 and 1993. Inclusion criteria were: age of between 1 and 18 y, naso-gastric tube feeding for a period of at least 16 weeks during treatment for their malignancy and the same diagnoses as the children in the prospective group. Fourteen patients were included (11 male and 3 female; mean age 5.75 4.74 y) (Table 1). Therapy for each type of tumour was generally multi modal and conformed to international study protocols, and all the patients had received courses of cytotoxic drugs which caused nausea and vomiting. Anti-emetics were required by all the patients in the two groups.

Table 1 Descriptives of patients at diagnosis

Experimental group

Patient (no.)

Sex (M/F)

Age (y)

Diagnosis and stage

1 2 3 4 5 6 7

F F M F M F M

2.0 2.4 4.1 4.6 8.9 12.0 12.3

Hepatoblastoma Nephroblastoma III Nephroblastoma IV Ewing sarcoma AML Rhabdomyosarcoma IV Ewing sarcoma

Mean s.d. Retrospective group

Mean s.d.

6.6 4.5 8 9 10 11 12 13 14 15 16 17 18 19 20 21

M M M F F M F M M M M M M M

1.1 1.1 1.5 2.0 2.8 2.8 3.7 3.8 4.9 8.3 9.2 11.0 13.8 14.6 5.8 4.7

Hepatoblastoma Nephroblastoma III Neuroblastoma IV Nephroblastoma III Aggressive ®bromatosis Rhabdomyosarcoma IV Neuroblastoma Ewing sarcoma AML Rhabdomyosarcoma II AML Ewing sarcoma PNET Ewing sarcoma

495


496

Methods Experimental study. Assessment of nutritional status and administration of naso-gastric tube feeding was performed according to a protocol. Nutritional status was evaluated by measuring weight and height. Weight of each patient was determined weekly from diagnosis onwards to the nearest 0.1 kg on an electronic scale (Berkel ED-60T), at approximately the same time each day. All the children were weighed without clothes and all the measurements were done by the same trained examiner. Height (length for children under 2 y of age) was measured approximately once every two weeks to the nearest 0.1 cm using a stadiometer (Holtain Ltd.). The amount of tube feeding to be administered was calculated weekly from the total daily energy requirements (TDER): TDER kcal=24 h basal metabolic rate kcal=24 h activity factor growth factor Basal metabolic rate for age, weight and sex was determined using tables published by Scho®eld. The activity factor ranged from 1.2 ± 1.7 depending on the physical activity of the child. The growth factor comprised the weight for height according to the age and sex speci®c 50th percentile divided by the actual weight and was used to correct for weight loss. Tube feeding provided the child with at least 100% of the daily energy requirements during the whole trial period (including courses of chemotherapy). The tube feeding routine was ¯exible, tailored to individual needs and was administered at hospital as well as at home. Oral feeding was permitted ad libitum, but the amount of tube feeding was always at least 100% of the child's requirements, so all oral intake provided additional energy. Tube feeding volume was built up over three consecutive days, and the formula was never diluted. If a child suffered from persistent vomiting, despite optimal application of anti-emetic treatment, the amount of tube feeding was decreased by 50%. As soon as the vomiting spells decreased, the amount of tube feeding was built up to the normal level. In the case of persistent diarrhoea, tube feeding was stopped for 24 h and an oral rehydration solution was administered. Subsequently, the level of tube feeding was gradually restored. Retrospective study. Data on weight, height and amount of tube feeding administered (energy intake) were collected from the patient ®les. Total daily energy requirements of each child were determined retrospectively in order to assess whether the energy intake of the child during the tube feeding period met the total daily energy requirements. Tube feeding had been started according to arbitrary criteria and the volume had been determined by the treating physician based on empirical experience and nocturnal tube feeding had been applied most frequently. During episodes of severe vomiting, tube feeding had been diluted and/or the volume had been reduced; the volume had also been reduced when a child resumed eating. Assessment of nutritional status. Weight was expressed as a percentage of the ideal weight in the two groups. Ideal weight was de®ned as the sex and age-speci®c weight for height according to the 50th percentile using Dutch reference values (Roede & Van Wieringen, 1985). Weight as a percentage of the ideal weight was determined weekly in

order to assess deterioration or improvement in the nutritional status of the child. Changes in nutritional status in the experimental group were compared to changes in the retrospective group. In order to make a valid comparison between the two groups, it was necessary to determine whether the nutritional status, age, velocity of weight reduction, the number of weeks after diagnosis before tube feeding was initiated and the distribution of tumour types was the same when tube feeding was started. Assessment of side-effects of naso-gastric tube feeding and of tolerance to treatment. Episodes of nausea, vomiting and diarrhoea were noted in a weekly diary by the parents of the children in the experimental study group. For the retrospective study group, these data were retrieved from the patient ®les. Delays in chemotherapy, dose reductions of chemotherapeutics and episodes of fever with and without neutropenia were evaluated in the two groups. Statistical analysis. Differences between the two groups were compared using a t-test, comparison within the groups was made using a paired t-test. Results Initial comparison of the groups at the start of tube feeding At the initiation of tube feeding (week 0) there was no statistically signi®cant differences between the two groups for age, height, weight expressed as a percentage of the ideal weight, number of weeks after diagnosis that tube feeding had been started (Table 2), tumour type and the velocity of weight reduction in the weeks prior to tube feeding (6.9 6.3% per week and 2.3 4.5% per week for the experimental and retrospective group respectively). Comparison between the nutritional status of the two groups during 16 weeks of naso-gastric tube feeding Patients' data at the beginning and end of the tube feeding period are shown in Table 2. Mean weight as a percentage of the ideal weight in the two groups during the whole study period is shown in Figure 1. There was a signi®cant statistical increase in weight expressed as a percentage of the ideal weight in both the experimental (18.2 8.4%; P 0.001) and the retrospective study group (5.2 7.3%; P 0.01) after 16 weeks. However, the increase in the experimental study group was signi®cantly higher (P 0.003) than in the retrospective study group. Mean weight as a percentage of the ideal weight after 16 weeks was 109.9 3.9% and 96.4 7.2% in the experimental and retrospective study group, respectively. Mean energy intake by means of tube feeding, expressed as a percentage of the total daily energy requirements, was signi®cantly higher in the experimental group (106.0 13.0%) than in the retrospective group (75.0 24.0%). In the experimental study group, 7 out of 7 (100%) patients had reached their ideal weight within 16 weeks against 3 out of 14 (21%) in the retrospective study group. Two out of the 3 patients in the retrospective group who `reached' their ideal weight were already heavier than their ideal weight when tube feeding was started. A reduction in weight expressed as a percentage of the ideal weight was seen in 4 out of 14 (28%) patients in the retrospective group after 16 weeks.


Table 2

497

Data of each patient at the beginning and end of the tube feeding period Anthropometric variables at the beginning and end of the tube feeding period

Experimental group

Mean Standard deviation

End study period (week 16)

DIW16-0

Patient (no.)

Height (cm)

Weight (kg)

IW b (kg)

%IW c (%)

Height (cm)

Weight (kg)

IW (kg)

%IW (%)

(%)

1 2 3 4 5 6 7

1.0 1.0 1.5 1.5 2.0 7.5 14.0

80.0 99.0 106.0 108.0 151.1 153.7 151.4

8.9 16.1 15.3 16.0 29.9 49.8 33.0

10.7 15.3 17.5 17.9 38.0 44.6 38.1

83.2 105.2 87.4 89.4 78.7 111.7 86.6

85.0 102.4 107.5 110.0 151.6 154.5 152.5

12.4 18.4 19.1 20.0 42.1 52.9 42.9

11.9 16.3 17.9 18.5 38.3 45.2 38.8

104.2 112.9 106.7 108.1 109.9 117.0 110.6

21.0 7.7 19.3 18.7 31.2 5.3 24.0

4.1 2.4

121.3 27.9

24.1 13.2

26.0 12.7

91.7 11.2

123.4 26.6

29.7 14.6

26.7 12.5

109.9 3.9

18.2 8.4

1.0 7.0 15.0 3.0 80.0 3.0 7.0 8.0 4.0 1.0 1.0 11.0 8.0 4.0

76.0 77.0 87.0 82.0 96.0 101.0 102.0 94.0 107.0 139.0 116.0 143.0 152.2 157.0

11.5 9.1 11.1 10.8 10.2 14.3 15.7 11.5 16.8 28.5 23.2 28.0 36.1 32.0

10.1 10.3 12.7 11.1 14.4 16.0 16.1 14.3 17.8 30.7 20.6 33.1 39.2 42.8

113.9 88.3 87.4 97.3 70.8 89.4 97.5 80.4 94.4 92.8 112.6 84.6 92.1 74.8

78.0 78.3 88.5 85.0 98.5 97.0 104.0 97.0 108.0 139.5 116.5 143.0 153.0 159.0

11.6 9.8 12.6 11.6 14.3 14.7 16.9 12.0 17.0 30.9 22.6 30.0 38.5 39.9

10.6 10.6 13.0 11.9 15.1 15.0 16.7 16.7 18.1 31.0 20.8 33.1 39.6 44.4

109.4 92.5 96.9 97.5 94.7 98.0 101.2 80.0 93.7 99.7 108.7 90.6 97.2 89.9

74.5 4.2 9.5 0.2 23.9 8.6 3.7 70.4 70.7 6.9 73.9 6.0 5.1 15.1

5.6 4.1

109.2 23.6

18.5 8.5

20.7 10.7

91.2 9.8

110.4 23.2

20.2 8.8

21.2 10.8

96.4 6.5

5.2 7.3

Mean Standard deviation Retrospective group

Start tube feeding (week 0)

Start TF a (weeks from diagnosis)

8 9 10 11 12 13 14 15 16 17 18 19 20 21

a

TF Tube feeding. IW Ideal weight Weight for height according to 50th percentile. c %IW Weight as percentage of ideal weight. b

Figure 1 Mean weight as a percentage of the ideal weight in the two groups during naso-gastric tube feeding.

Occurrence and severity of side-effects associated with naso-gastric tube feeding In the experimental study group, occurrence and frequency of vomiting varied greatly between the children but no severe cases of vomiting were observed. Vomiting frequency increased after the initiation of chemotherapy and ceased approximately one week after the completion of every chemotherapy course. Vomiting was often preceded by a spell of nausea, but nausea attacks were more frequent than vomiting attacks.

Diarrhoea was also observed, especially in the younger children. After the initiation of tube feeding many of them suffered from diarrhoea for the ®rst 1± 2 weeks whereafter their stools normalized. The older children did not suffer from this initial `diarrhoea phenomenon'. In most children, occasional spells of diarrhoea were seen during the further course of treatment, but the frequency varied considerably. Nausea, vomiting and diarrhoea were observed in all the children in the retrospective group. It was, however, not


498

possible to accurately assess the frequency of occurrence, except for the frequency of vomiting during hospitalisation. Episodes of vomiting were more frequent and more severe in the retrospective group than in the experimental group during courses of chemotherapy. Effects of nutrition on anti-cancer treatment tolerance The average number of chemotherapy courses given during 16 weeks of tube feeding was the same in the two groups. Delays in chemotherapy occurred in 3 of the 7 patients in the experimental group (43%) against 11 of the 14 patients (78%) in the retrospective group. There were no dose reductions in the patients in the experimental group during the trial period, whereas there were reductions in 3 patients in the retrospective group (21%). None of the children in the experimental group had a combination of a delay in chemotherapy and dose reduction against 4 of the 14 children (29%) in the retrospective group. Episodes of fever combined with leucopenia were seen in 57% (4 out of 7) of the patients in the experimental group; this percentage hardly differed from the 64% (9 out of 14) in the retrospective group. An important observation was that the percentage of patients with episodes of fever without leucopenia was much smaller in the experimental group than in the retrospective group: 57 (4 out of 7) against 86% (12 out of 14), respectively. The results obtained for this study with this protocol should ®rst be con®rmed in a larger study group. Discussion As the prognosis for curing childhood cancer has improved signi®cantly over the years, the necessity of maintaining a good nutritional status during therapy has become more and more evident in order to ensure normal growth and development of these children. Furthermore, a poor nutritional status has been associated with an impaired tumour response to treatment and outcome of disease (Donaldson et al, 1981; van Eys, 1982; Rickard et al, 1983a), reduced therapy tolerance (Coates et al, 1986; van Eys, 1979; Filler et al, 1977; Hays et al, 1983; Rickard et al, 1983a, 1985), impaired immunological function (van Eys, 1979; van Eys et al, 1980) and a reduced state of well-being and performance (Donaldson et al, 1981; van Eys, 1979; Mauer et al, 1990). The aim of nutritional intervention must therefore be the prevention of therapy-related malnutrition and the added effects of protein energy malnutrition (PEM). It must also promote growth and a sense of well-being during the course of primary treatment. The ef®cacy of nutritional intervention should be judged on these goals rather than on its in¯uence on ultimate survival. Results from this study demonstrate that enteral tube feeding was able to considerably improve the nutritional status of children with cancer, both in the experimental and in the retrospective group. Tube feeding was well-accepted by all the children, in contrast with suggestions made by Rickard et al (1982, 1986), that the insertion and the presence of a naso-gastric tube is psychologically too traumatic for pre-school children. The improvement in nutritional status, expressed in terms of weight as a percentage of the ideal weight, was de®nitely more impressive in the experimental group (all the children reached their ideal weight) than in the retrospective group. According to Coates et al (1986) the difference in response to nutritional support may be due to differences in age, tumour type, intensity and kind of oncological treatment. These factors

are not likely to have caused the difference in nutritional response between the two groups in this study, because there was only a slight difference in age between the two groups, the distribution of tumour types was matched as far as possible and all the children underwent long periods of intensive chemotherapy. An insuf®cient energy intake seemed to be the main contributing factor to the development of a poor nutritional status, because it rapidly improved when suf®cient amounts of energy were supplied. An energy intake of 75% of the total daily energy requirement was not enough for children with cancer to reach their ideal weight, as was demonstrated in the retrospective group: 8 out of 14 children received less than 75% of their daily energy requirement, some even as low as 40%. Nevertheless four of these children did gain weight. An explanation might be that the children were permitted to eat and drink in addition to the tube feeding administered resulting in a suf®cient oral energy intake in these four children. Unfortunately it is not possible to describe the oral intake of the retrospective group, as no food diary was kept at the time. Although all the children in the experimental group reached or exceeded their ideal weight, future research should determine whether this weight gain was the result of an increase in fat mass, fat free mass or both. Another question that has to be addressed is what the feeding strategy should be towards previously obese children. According to the de®nition of ideal weight used in this article, some of the children were still overweight when tube feeding was started. This was due to the fact than criteria for recruitment into the study included 5% weight loss compared to the weight at diagnosis and/or an oral intake of 80% of the total daily energy requirement during one week. Losing fat might not be the problem but in losing weight they also lose lean body mass which leads to an overall deterioration of condition. What should be the energy and protein intake of these children and what should be their ideal weight? It is dif®cult to distinguish side-effects of naso-gastric tube feeding from side-effects of chemotherapy treatment, because vomiting, nausea and diarrhoea can be caused by naso-gastric tube feeding or chemotherapy. With respect to nausea and vomiting, it is reasonable to assume that chemotherapy was the main contributing factor, because vomiting started after the initiation of chemotherapy. Frequency of vomiting subsequently increased and ceased approximately one week after the completion of a chemotherapy course and did not recur until the next chemotherapy course. The appearance of diarrhoea during treatment could be explained by causes other than of tube feeding for example chemotherapeutics, gastro-intestinal infections and the cutting of teeth in younger children. There were no spells of diarrhoea in which naso-gastric tube feeding could be pointed out as the sole cause, except in the youngest children who often suffered from diarrhoea during the ®rst few weeks of administration. Their intestinal tract seemed to need more time to adjust to the enteral feeding product than that of older children. The frequency and severity of vomiting during courses of chemotherapy was higher in the retrospective group than in the experimental group. Due to the larger volume of tube feeding administered in the experimental group, in order to ensure an adequate energy intake, one would expect the frequency and severity of vomiting to be higher in the experimental group. This was not the case, however.


Several factors might have contributed to this: (1) The improved availability and ef®cacy of anti-emetics over the past few years has obviously led to better control of the adverse side-effects during courses of chemotherapy; (2) A poor nutritional status of a child with cancer leads to reduced therapy tolerance (Coates et al, 1986; van Eys, 1979; Filler et al, 1977; Hays et al, 1983; Rickard et al, 1983a, 1985). The nutritional status of the children in the retrospective group was poorer than that in the experimental group at the same point during treatment, which might account for the difference in severity and frequency of vomiting; (3) Protocolized administration of tube feeding leads to optimisation of anti-emetic protocols, as the goal is to be able to administer suf®cient amounts of energy to provide the child's TDER. Furthermore, a great deal of effort was spent on each individual child to ®nd the most suitable administration schedule. The overall better condition of the children in the experimental group led to a signi®cant reduction of the number of patients with episodes of fever outside periods of bone marrow depression. It did, however, not lead to fewer experimental group patients with episodes of fever combined with bone marrow depression. It can be concluded that the children in the experimental study, with an optimal nutritional condition, were less susceptible to infections. Since the study groups were small, we cannot yet extrapolate this to other groups. Conclusions A practical implication of this study is that the primary key to improving the nutritional status of a child with cancer to a satisfactory point is the administration of suf®cient amounts of energy. In contrast with the results obtained in the retrospective study group, the results in the experimental study group demonstrated that it is very feasible to achieve satisfactory improvement of nutritional status using the following protocol: for children to obtain their ideal weight it is necessary to apply an intensive and aggressive naso-gastric tube feeding protocol. Amounts of energy should be calculated, as explained in the method section, to ensure 100% coverage of the total daily energy requirements. The amount of energy administered should be adjusted when the condition of the child improves and he or she becomes more active. To achieve ideal weight, the nutritional status and performance status of each child must be assessed regularly and intensively. Contributors E den Broeder, RJJ Lippens, WA van Staveren JJM Tolboom and Z Hofman designed the study. E den Broeder was the principal investigator, managed the study, interpreted the results and wrote the drafts and ®nal version of the paper. RJJ Lippens, WA van Staveren, JJM Tolboom and RCA Sengers contributed to the interpretation of the results and the writing of the manuscript. E den Broeder is the guarantor and is accountable for all parts of the manuscript.

References Coates TD, Rickard KA, Grosfeld JL & Weetman RM (1986): Nutritional support of children with neoplastic diseases. Surg. Clin. North Am. 66, 1197 ± 1212.

Donaldson SS, Wesley MN, DeWys WD, Suskind RM, Jaffe N & van Eys J (1981): A study of the nutritional status of pediatric cancer patients. Am. J. Dis. Child 135, 1107 ± 1112. Donaldson SS, Wesley MN, Ghavimi F, Shils ME, Suskind RM & DeWys WD (1982): A prospective randomized clinical trial of total parenteral nutrition in children with cancer. Med. Pediatr. Oncol. 10, 129 ± 139. Donaldson SS (1982): Effects of therapy on nutritional status of the pediatric cancer patient. Cancer Res. 42, Suppl., S729 ± S736. Eys J van (1979): Malnutrition in children with cancer. Incidence and consequence. Cancer 43: 2030 ± 2035. Eys J van (1982): Effect of nutritional status on response to therapy. Cancer Res. 42, Suppl., S747 ± S753. Eys J van, Copeland EM, Cangir A, Taylor G, Teitell-Cohen B, Carter P & Ortiz C (1980): A clinical trial of hyperalimentation in children with metastatic malignancies. Med. Pediatr. Oncol. 8, 63 ± 73. Filler RM, Dietz W, Suskind RM, Jaffe N & Cassady JR (1979): Parenteral feeding in the management of children with cancer. Cancer 43, 2117 ± 2120. Filler RM, Jaffe N, Cassady JR, Traggis DG & Das JB (1977): Parenteral nutritional support in children with cancer. Cancer 39, 2665 ± 2669. Ghavimi F, Shils ME, Scott BF, Brown M & Tamaroff M (1982): Comparison of morbidity in children requiring abdominal irradiation and chemotherapy, with and without total parenteral nutrition. J. Pediatr. 101, 530 ± 537. Grant MM & Rivera L (1995): Anorexia, cachexia, and dysphagia: the symptom experience. Semin. Oncol. Nurs. 11, 226 ± 271. Hays DM, Merrit J, White L, Ashley J & Siegel SE (1983): Effect of total parenteral nutrition on marrow recovery during induction therapy for acute nonlymphocytic leukemia in childhood. Med. Pediatr. Oncol. 11, 134 ± 140. Lukens JN (1984): The use of nutritional therapy. Am. J. Ped. Hem. Oncol. 6, 261 ± 265. Mauer AM, Burgess JB, Donaldson SS, Rickard KA, Stallings VA, Eys J van & Wininck M (1990): Special nutritional needs of children with malignancies: a review. J. Parenter. Enteral. Nutr. 14: 315 ± 324. Nelson KA, Walsh D & Sheenan FA (1994): The cancer anorexia-cachexia syndrome. J. Clin. Oncol. 1, 213 ± 225. Rickard KA, Baehner RL, Coates TD, Weetman RM, Provisor AJ & Grosveld JL (1982): Supportive nutritional intervention in pediatric cancer. Cancer Res. 42, Suppl., S766 ± S773. Rickard KA, Coates TD, Grosfeld JL, Weetman RM & Baehner RL (1986): The value of nutrition support in children with cancer. Cancer 58, 1904 ± 1910. Rickard KA, Corcoran Becker M, Loghmani ES, Grosfeld JL, Jaeger Godshall B, Weetman RM, Coates TD, Detamore Lingard C, Matchett White N, Bartlett Foland B, Yu P-L, McGuire W, Provisor AJ, Oei TO & Baehner RL (1989): Effectiveness of two methods of parenteral nutrition support in improving muscle mass of children with neuroblastoma or Wilms' tumour. Cancer 64, 116 ± 125. Rickard KA, Detamore CM, Coates TD, Grosveld JL, Weetman RM, Matchett White N, Provisor AJ, Boxer LA, Loghmani ES, Oei TO, Yu P-L & Baehner RL (1983a): Effect of nutrition staging on treatment delays and outcome in stage IV neuroblastoma. Cancer 52, 587 ± 598. Richard KA, Foland BB, Detamore CM, Coates TD, Grosfeld JL, White NM, Weetman RM, Provisor AJ, Loghmani ES, Oei T, Yu P-L & Baehner RL (1983b): Effectiveness of central parenteral nutrition versus peripheral parenteral nutrition plus enteral nutrition in reversing protein-energy malnutrition in children with advanced neuroblastoma and Wilms' tumour: a prospective randomized study. Am. J. Clin. Nutr. 38, 445 ± 456. Rickard KA, Grosfeld JL, Coates TD, Weetman RM & Baehner RL (1986): Advances in nutrition course of children with neoplastic diseases: a review of treatment, research and application. J. Am. Dent. Assoc. 86, 1666 ± 1676. Rickard KA, Grosfeld JL, Kirksey A, Ballantine TVN & Baehner RL (1979): Reversing of protein-energy malnutrition in children during treatment of advanced neoplastic disease. Ann. Surg. 190, 771 ± 781. Rickard KA, Jaeger Godshall B, Loghmani ES, Cates TD, Grosfeld JL, Weetman RM, Detamore Lingard C, Bartlett Foland B, Yu P-L, Mcguire W, Provisor AJ, Oei TO & Baehner RL (1989): Integration of nutrition support into oncologic treatment protocols for high and low nutritional risk children with Wilms' tumour. Cancer 64, 491 ± 509. Rickard KA, Kirksey A, Baehner RL, Grosfeld JL, Provisor AJ, Weetman RM, Boxer LA & Ballantine TVN (1980): Effectiveness of enteral and parenteral nutrition in the nutritional management of children with Wilms' tumours. Am. J. Clin. Nutr. 33, 2622 ± 2629. Rickard KA, Loghmani ES, Grosfeld JL, Detamore Lingard C, Matchett White N, Bartlett Foland B, Jaeger B, Coates TD, Yu P-L, Weetman RM, Provisor AJ, Oei TO & Baehner RL (1985): Short- and long-term effectiveness of enteral and parenteral nutrition in reversing or preventing protein-energy malnutrition in advanced neuroblastoma. A prospective randomised study. Cancer 56, 2881 ± 2897.

499


500

Roede MJ & van Wieringen JC (1985): Growth diagrams 1980, Netherlands third nation wide survey. Tijdschr. Soc. Gezondheidszorg. 63, Suppl., 1 ± 34. Scho®eld WN (1985): Predicting basal metabolic rate, new standards and review of previous work. Hum. Nutr. Clin. Nutr. 39C, Suppl., 5±41 Smith DE, Handy DJ, Holde CE, Stevens MCG & Booth IW (1992): An investigation of supplementary naso-gastric feeding in malnourished children undergoing treatment for malignancy: results of a pilot study. J. Hum. Nutr. Diet. 5, 85 ± 91.

Szeluga DJ, Stuart RK, Brookmeyer R, Utermohlen V & Santos GW (1987): Nutritional support of bone marrow recipients: a prospective randomised clinical trial comparing total parenteral nutrition to an enteral feeding program. Cancer Res. 47, 3309 ± 3316.