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Int. J. Cancer: Supplement 11, 73–75 (1998)
r 1998 Wiley-Liss, Inc.
Publication of the International Union Against Cancer
Publication de l’Union Internationale Contre le Cancer
AGGRESSIVE ORAL, ENTERAL OR PARENTERAL NUTRITION:
PRESCRIPTIVE DECISIONS IN CHILDREN WITH CANCER
Paul B. PENCHARZ*
Division of Gastroenterology and Nutrition, Research Institute, Hospital for Sick Children, Departments of Paediatrics
and Nutritional Sciences, University of Toronto, Toronto, Canada
Over the past 18 years, our laboratory has been interested
in the pathogenesis of energy imbalance caused by a variety of
diseases. Our view is that a clear understanding of the various
factors causing negative energy balance, which in turn results
in malnutrition, is the most effective way of designing preventive and therapeutic nutritional strategies. Thus, in cancer,
one of the common factors is anorexia, due either to the
primary tumor or to the effects of cancer therapy. Currently
there is little evidence of increased resting energy expenditure in children with cancer, except in cases with very high
tumor burden. Conversely, there are suggestions of a failure
to down-regulate resting energy expenditure in the presence
of reduced food intake in patients with cancer. Damage to the
gastrointestinal tract, due to the effects either of the tumor
or of tumor therapy, may result in maldigestion and/or
malabsorption. Thus, as a result of a combination of reduced
intake, reduced absorption and increased needs, the child
with cancer may become malnourished. Prevention and
treatment are dependent on the type of cancer and the
pathogenesis of the negative energy balance. In broad terms,
we try as far as possible to use external routes. With the
advent of percutaneously placed gastrostomies and gastrojejunal tubes, we use these methods increasingly to provide
nutritional support. Only in patients whose gastrointestinal
tract cannot be used do we turn to i.v. feeding. In these
patients, the placement of a central venous line is required,
but great care must be taken to avoid infection. Whatever
form of nutritional support is used, whether enteral or
parenteral, we measure the body composition and energy
expenditure in the patient, so that the nutritional therapy can
be tailored to the child’s specific needs. Using these approaches, we are having significant success in preventing
and reversing malnutrition in children with cancer and
those undergoing bone-marrow transplantation. Int. J. Cancer
Supplement 11:73–75, 1998.
r 1998 Wiley-Liss, Inc.
mediated through cytokines, including tumor necrosis factor (TNF).
Some interesting insights have been obtained in animal studies,
when infusion of TNF resulted in both anorexia and weight loss.
There was no down-regulation of energy expenditure associated
with this anorexia and weight loss, hence energy expenditure, the
unit of lean mass, was not decreased (Hoshino et al., 1991). Other
studies have shown that fat metabolism tends to be suppressed in
favor of glucose metabolism (Sakurai et al., 1993; Beisel, 1995).
This is in fact a futile cycle and does waste energy. Lean mass
appears to be affected differentially, with more wasting of skeletal
mass than of visceral protein mass (Cohn et al., 1981; Emery et al.,
1984).
Children with cancer are at a risk of suffering from undernutrition (Kien and Camitta, 1981), which, if severe, affects
tolerance of therapy and may influence the overall survival of the
patient. An important difference between nutritional support in
children and in adults is that children, particularly those who are
younger and smaller in size, have fewer reserves and therefore are
at higher risk of developing malnutrition (Zlotkin et al., 1985;
Pencharz, 1988; Wilson and Pencharz, 1997). Chronic diseases in
childhood and/or their treatment can also have an adverse effect on
growth (Zlotkin et al., 1985). All these considerations need to be
kept in mind when managing the nutritional care of an infant or
child with cancer.
ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) AS A MODEL
FOR METABOLIC DISTURBANCES
PATHOGENESIS OF NUTRIENT IMBALANCE
Cancer, like other chronic diseases, can affect nutrient balance
adversely by a combination of factors. Cancer or cancer therapy
can result in anorexia, vomiting or mal-digestion/mal-absorption,
the net result being the reduction of absorbed nutrient intake.
Metabolic disturbances can affect nutrient metabolism and result in
inefficient use of nutrients. In some instances, energy expenditure is
increased (Dempsey et al., 1984), but the available data for
childhood cancer suggest that this occurs only when there is a high
tumor burden (Stallings et al., 1989). In adults there are some
tumors that appear to have more widespread metabolic effects,
which are not fully understood. However, they are thought to be
MALNUTRITION IN CANCER PATIENTS
Malnutrition in pediatric cancer patients is not very common, at
least in industrialized societies. Kien and Camitta (1981) reported
on a prospective study of out-patients and in-patients. The prevalence of malnutrition in the out-patients was quite low, and
consisted mostly of the wasting of fat mass. Conversely, in the
in-patient population, the prevalence of wasting was higher and
could be as high as 20% of their population. In this group there was
wasting of muscle mass and of fat mass. More detailed body
composition studies conducted in adults permitted measurements
of total body potassium, nitrogen, water spaces and fat mass (Cohn
et al., 1981). Interestingly, these authors showed that, in most
cancer patients, weight loss is associated with loss of water and
potassium, with some fat-mass loss and relative preservation of
total body nitrogen. This implies that the lean mass lost is primarily
skeletal muscle.
There are few studies of the effects of cancer or cancer therapy
on the protein and energy metabolism of children. Work by Kien
and Camitta (1987) showed an increase in protein turnover in
children presenting with acute lymphoblastic leukemia, also a
highly significant correlation between resting energy expenditure
and whole-body protein synthesis. Our group has also studied
effects of ALL on protein energy metabolism and the changes seen
with treatment (Stallings et al., 1989; Vaisman et al., 1993). The
majority of the children, who were studied at diagnosis, had no
changes in resting energy expenditure. However, a small group
with hepatosplenomegaly and high tumor burden had an increase in
resting metabolic rate (Stallings et al., 1989). Over the first 2 weeks
of treatment, this hypermetabolism disappeared as the total tumor
volume reduced. Protein synthesis and turnover were increased at
presentation, and changed little in response to the first 2 weeks of
therapy. Urinary urea excretion doubled in response to therapy over
the first week, and remained high to the end of 2 weeks of
treatment.
*Correspondence to: Division of Gastroenterology and Nutrition, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8,
Canada. Fax: (416) 813-4972.
E-mail: paul.pencharz@sickkids.on.ca
PENCHARZ
74
Subsequently, we studied children with ALL who were in
remission on maintenance therapy consisting of oral 6-mercaptopurine (6 MP) and methotrexate given intravenously (Vaisman et al.,
1993). 6-mercaptopurine increased protein synthesis by approximately 50%. However, 6 MP had no affect on fasting use of
carbohydrate or fat. Conversely, the addition of methotrexate
resulted in inhibition of carbohydrate utilization and promotion of
fat utilization. This was also evident in the fed state.
NUTRITIONAL SUPPORT
Nutrient deficiency develops over a period of time, depending on
the degree of negative balance and the amount of nutrient-energy
reserve available. Therefore, with infants, it is important to be
vigilant and to intervene early, whereas with adolescents, who have
much larger reserves, there is more time to wait (Zlotkin et al.,
1985; Pencharz, 1988; Wilson and Pencharz, 1997). We regard
nutritional assessment as an important process in making a
diagnosis with a view to intervention and treatment, and in
monitoring that treatment. Nutritional anthropometry is used
principally: careful measurements of weight and height are important, since from these parameters it is possible to calculate weight
as a percent of ideal weight for height (Moore et al., 1985). We
have also found mid-arm parameters to be very helpful, since the
combination of mid-arm circumference and triceps skin fold allows
the calculation of fat reserves from the triceps skin fold, and of
muscle-protein reserves from the arm-muscle circumference or
area (Pencharz, 1988). Per unit of body weight, requirements for
protein (amino acids) and energy are higher in infants than they are
in older children, and children have higher requirements than
adolescents, ranging from 2.5 grams of protein/kg/day in infants
down to 1 to 1.5 in adolescents. Similarly, energy requirements
range from a high of 90 to 100 kilocalories/kg in infants to a low
level of 40 kilocalories/kg in adolescents.
FEEDING ROUTES
Whenever possible, dietary therapy is to be preferred. However,
mucositis (including esophagitis and gastritis), as well as disturbances of intestinal motility, may make oral feeding difficult if not
impossible. In another chronic disease, cystic fibrosis (CF), we
found that a general clinic policy towards improving dietary intake
(high calorie and high fat; 30–40%) helped a great deal in avoiding
the need for gastrostomy or i.v. feeding. Oral supplements are used
widely, yet data regarding their effectiveness are largely absent. We
conducted a study in children and adults with CF to determine
whether ingestion of liquid supplements (such as Ensure, Pediasure
or Boost), in addition to improving dietary intake, increases their
energy intake (Kalnins et al., 1996), and found that it did not, in
fact, it simply displaced food. Conversely, supplemental
tube feeding by gastrostomy administered overnight, in similar
patients with CF, in addition to oral intake during the day, was able
to increase the total 24-hr intake and restore normal nutritional
status.
The advent of incisionless gastrostomy in the early 1980s has
transformed the ability to provide enteral nutritional support. First
was percutaneous endoscopic gastrostomy. One of the disadvantages of this technique, at least in cancer patients, is that the tube
has to be pulled through the esophagus. If there is disease of the
esophagus (such as mucositis), this might result in procedural
difficulties and potential complications. In our own center we
prefer to use radiologically placed gastrostomy tubes, and we
now have experience with over 800 such tubes being placed in
children with a wide variety of different conditions (Grunow et al.,
1994).
We use total parenteral nutrition (TPN) in a small proportion of
patients with cancer, particularly those undergoing bone-marrow
transplantation. We found that the use of central lines and
concentrated solutions to minimize the amount of fluid administered has been a highly successful way of providing nutritional
support. While we have been able to minimize the loss of lean
tissue and fat reserves, there remain many unanswered questions on
how to optimize such therapy. Due to the gastrointestinal disturbances in most of the children undergoing bone-marrow transplantation, fairly extensive periods of TPN are required. Having come
through the bone-marrow transplant successfully, some of these
patients in fact have feeding aversion and prove to be quite a
challenge in the restoration of oral feeding. We now use cyclical
TPN routinely and it has been helpful, in our experience, in getting
the majority of these patients back on to oral feeds. In a small
minority, we have had to turn to the placement of a percutaneous
gastrostomy tube as a means of providing supplemental feeding at
night. This allows the child’s feeding aversion to disappear
gradually over a period of months at home.
EFFECT OF DRUGS ON METABOLISM
We have alluded already to the effects of chemotherapy on
protein and energy metabolism. In relation particularly to energy
balance, there have been suggestions that steroids might affect
energy expenditure. However, carefully conducted studies showed
that steroids have no effect on energy expenditure (Zeitlin et al.,
1992). Conversely, ␤-adrenergic drugs, such as salbutamol, increase resting energy expenditure by 10 to 15%, and do so over a
period of some hours (Vaisman et al., 1987).
EFFECTS OF REFEEDING
In our experience, nutritional rehabilitation is successful only
when the patient is metabolically stable. Infection, for example,
interferes with nutrient utilization. Similarly, some cancers, presumably those that secrete a lot of humoral factors including cytokines,
disturb metabolism and thereby make nutritional rehabilitation
difficult. Taking Crohn’s disease as another situation in which
cytokines are secreted, we showed that, with effective therapy of
the disease, it was possible to rehabilitate the patient nutritionally,
restoring body composition to normal (Azcue et al., 1997).
Nevertheless, the resting metabolic rate was still moderately
increased per unit of lean mass. Care needs to be taken during
refeeding not to cause fluid overload and the development of
edema. In studies carried out in patients with anorexia nervosa, as a
model of otherwise uncomplicated malnutrition, we showed that,
during the early phases of refeeding, there was expansion in
extra-cellular fluid volume even without the appearance of clinical
edema (Vaisman et al., 1988). When refeeding a patient, with any
condition, we do so slowly, at least during the first week. After that
the level of energy and nutrients is moved up.
SUMMARY AND CONCLUSION
1. Both the tumor and the therapy can have adverse effects on
the nutritional status of children.
2. Generally, anorexia and other gastrointestinal side effects are
manageable.
3. With some tumors, the metabolic effects of cytokine overproduction remain a problem and, for adults with cancer,
thought is being given to using anti-cytokine therapy. Presently, there are no relevant data for children.
4. Graft vs. host disease in the bowel is an occasional but
significant problem in some children after bone-marrow
transplants.
5. Feeding aversion may be a long-term problem in the cancer
patient who requires prolonged therapy, e.g., after bonemarrow transplantation. This may necessitate the placement
of a gastrostomy tube for longer-term feeding.
NUTRITIONAL PRESCRIPTIONS IN CHILDREN WITH CANCER
75
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