Download The Effect of Cancer on Nitrogen, Electrolyte

[CANCER RESEARCH 37, 2348-2353, July 1977]
The Effect of Cancer on Nitrogen, Electrolyte, and Mineral
Metabolism1
George L. Blackburn,2Baltej S. Maini, Bruce R. Bistrian,and WilliamV. McDermott,Jr.
Nutrition/Metabolic Laboratory, Cancer Research Institute, New England Deaconess Hospital/Harvard Medical School, Boston, and Sidney Farber Cancer
Institute, Boston, Massachusetts 02215
Summary
The metabolic relationships between electrolytes, mm
erals, and cancer show no general abnormalities. Specific
disorders of metabolism may be produced by hormone
secreting tumors, and an increased utilization or excretion
of minerals and electrolytes may result. Patients with cance.r
@ndmalnutrition lose significant amounts of nitrogen and
4at. The attrition of visceral protein represents the most
clinically significant tissue loss. The resulting nutritional
conditions of marasmus and kwashiorkor account in part
for the marked impairment of cell-mediated immunity. Basal
energy expenditure in patients is not inordinately high, nor
do different tumor groups need classification according to
energy expenditure in the patients. Patients require an in
take of 30 to 35 kcal/kg to meet their energy requirements.
Protein intake, the most important factor in effecting weight
gain, is effective when 1.5 to 2.0 g/kg are supplied daily.
This represents about 16 to 20% of the total energy expendi
ture.
Forced feeding programs, e.g. , total parenteral nutrition
or enteral hyperalimentation, are often required to over
come anorexia. Response to therapy takes several weeks. A
positive or successful response includes the closure of fis
tulae, completion of radiotherapy or chemotherapy, recov
ery from anorexia or stomatitis, a subjective feeling of well
being, and an improvement in the quality of life. Failure to
respond by these objective criteria is associated with a poor
prognosis in the experience of the nutrition support service.
Introduction
In the past few years medicine has made significant ad
vances in understanding the pathogenesis of cancer. Along
with a more complete picture of tumor metabolism has
come a greater therapeutic sophistication; surgery, radio
therapy, chemotherapy, and immunotherapy give the pa
4
tient
a better
prognosis.
Recently,
the
nutritional
aspects
of
cancer metabolism and therapy have been appreciated,
stimulating new research in this direction. The purpose of
this paper is to present the relationship between cancer and
the basic body nutrients including nitrogen, minerals, and
I
Presented
at
the
Conference
on
Nutrition
and
Cancer
Therapy,
Novem
bar 29 to December 1, 1976, Key Biscayne, Fla. Supported in part by NIH
Research Grant GM22691. Data analysis was performed on PROPHET and
was sponsored by the Chemical/Biological Information Handling Program of
the Division of Research Resources, NIH (RR-76). This is Paper 586 from
the Cancer Research Institute of the New England Deaconess Hospital.
2 Presenter.
2348
To
whom
requests
for
reprints
should
be
addressed.
electrolytes. This relationship forms the basis of specific
nutritional therapies to combat the changes in basic body
nutrients that influence carcinogenesis.
Electrolytes and Minerals
Thus far, no abnormalities in electrolyte and mineral me
tabolism of tumors or host can be generalized to all types of
cancer. Therefore specific anomalies will be reported when
they exist, but we emphasize cautious interpretation of
these preliminary data.
Sodium and Potassium. Hypokalemia often accompanies
mucin-secreting , potassium-losing adenocarcinomas of the
colon. Weight loss and catabolism also result in potassium
and sodium losses in the urine (33). As the lean body mass
is restored, potassium requirements increase; a rise in the
total body potassium is an excellent indicator of an anabolic
state (33, 40). Other alterations in potassium metabolism
are noted as an indirect effect of tumors causing hypoglyce
mia, namely, insulinomas and retroperitoneal tumors.
The effects of cancer on sodium metabolism are nonspe
cific. Alterations are an indirect effect such as those ob
served in oat-cell carcinomas of the lung and hypothalamic
tumors, both of which result in inappropriate antidiuretic
hormone secretion, water retention, and hyponatremia.
Tumors that produce adrenocorticotropic hormone also re
suit in water and electrolyte abnormalities.
Calcium. Changes in calcium metabolism are secondary
to hormonal changes or are a consequence of bone de
struction. Hypercalcemia is associated with parathyroid tu
mors, cancer metastatic to bone with primaries in the breast
and thyroid, and with multiple endocrine adenomatosis.
Hypocalcemia occurs as a sequela of malnutrition and is
associated with hypoalbuminemia.
Magnesium. The role of magnesium in cancer is obscure.
The regression of malignant tumors with hypomagnesemia
and hypokalemia secondary to long-term dialysis in renal
failure has been observed (38). The association remains
occult. Breast cancer specimens have contained high levels
of magnesium, the significance of which is not known (42).
Iron. Sideropenic anemia with visceral lesions, e.g., brit
tie nails, koilonychia, glossitis, papillary atrophy of the
tongue, oral fissures, a small mouth with narrow lips, a
smooth facial skin, atrophic gastritis, achlorhydria, and
postcricoid dysphagia as seen in the Plummer-Vinson syn
drome, is causally related to iron deficiency. The incidence
of hypopharyngeal cancer in women in northern Sweden is
influenced by the presence of Plummer-Vinson syndrome;
CANCERRESEARCHVOL. 37
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Nitrogen , Electro!ytes, and Minerals in Cancer
both these conditions have decreased in prevalence since
nutritional repletion , specifically including iron , became
widespread (28). Also, in areas of the world where iron
deficiency is common, the incidence of gastric carcinoma is
5 times as common as that in the United States; other
variables may play a role (52). Vitale (53) has pointed out the
interaction between immunodeficiency and iron depletion;
the relationship between immunodeficient mechanisms in
iron deficiency and carcinogenesis remains as an interest
ing area of research.
Trace Minerals. Numerous suggestions have been ad
vanced and studies carried out regarding the role trace
minerals might play in cancer metabolism (2, 15, 18). Of
interest is the postulation that mineral deficiency may acti
vate certain procarcinogens and thereby influence oncoge
nesis (53). Elevated zinc levels have been observed in bron
chogenic and colonic cancer. In contrast, lowering of zinc
levels is seen in a variety of infective and other disease
states (35, 51).
Extensive studies investigating the role of copper in can
cer have been carried out (25, 34). Copper levels are ele
vated in Hodgkin's disease; a fall was noted in patients who
responded to therapy (24). Copper levels have been found
to be elevated in several types of tumors, and the signifi
cance is at present unknown. Correlation of nickel levels
with oral cancer, arsenic with laryngeal carcinoma, and
lead with leukemia, lymphomas, and ovarian cancer has
been attempted in order to define the role of these trace
metals in oncogenesis and diagnosis (2, 35). An excellent
review of this subject has been provided by Schwartz (43).
Mineral Therapy. In designing an adequate nutritional
support plan, the importance of providing adequate
amounts of sodium, potassium, chloride, and phosphate in
conjunction with protein must be emphasized. In an excel
lent study by Rudman et a!. (40), withdrawal of one or more
of the above macronutrients when given with protein in a
program of i.v. hyperalimentation led to impaired retention
of the other elements. Although weight gain continued, it
largely consisted of adipose tissue, and little or no increase
in visceral protein and lean body mass occurred. Guidelines
for electrolyte and mineral requirements to provide optimal
repletion of the malnourished patient are shown in Table 1
and have been discussed elsewhere (19).
This brief review primarily indicates that, although some
@
Table 1
Daily mineral requirements(parenteral
use)MineralDose/dayaSodium60-80
information is available on electrolyte and mineral Jevels in
cancer patients, little evidence exists to indicate their pre
cise role in the pathogenesis of cancer. Given this limited
information, the main effort is directed at correcting defi
ciencies by selecting a proper nutritional plan. The role of
nitrogen in cancer has been studied more extensively and
will be discussed subsequently.
Nitrogen. A favorable nitrogen economy depends upon
the ability of an organism to regulate the synthetic and
catabolic processes involving numerous and different pro
teins with the goal of maintaining a relatively constant body
protein mass (36, 54). In the presence of cancer this homeo
stasis is disturbed. The malignant tumor seems to inappro
priately metabolize both dietary and host proteins, resulting
in the wasting of lean body mass (32). Tumors may act as
nitrogen and energy traps; their growth is preferential to that
of the host. Amino acids incorporated into the tissue of the
tumor do not appear to be recycled as is normally the case.
Thus any dietary deficiencies, particularly protein, have
their greatest impact on host homeostasis.
Although a tumor will respond to nutritional changes, it
exhibits a greater degree of autonomy than does normal
tissue (1, 48). The adaptive response to insufficient dietary
intake in the noncancerous patient is the sparing of visceral
protein while utilizing fat and skeletal protein;.this initiates
the onset of adult marasmus. A similar response occurs
when a tumor is present; in hypocaloric states, visceral
protein and tumor are spared at the expense of cannibaliz
ing peripheral tissues (37).
Nitrogen balance studies in patients with neoplastic dis
ease have produced results that are difficult to interpret (13,
55). Thirty to 100% of all patients with advanced cancer
have negative nitrogen balance. Other patients with active
disease are in nitrogen equilibrium or even positive balance
while they continue to lose weight. This suggests that the
enlarging neoplasm is retaining nitrogen while the host
tissues are losing it. This corroborates the suspicion that
tumors derive nitrogen not only from the diet but from the
host (17).
Anorexia is a major cause of weight loss (Chart 1). Gold
(20) has suggested
that growing
preferentially
con
PATHOGENESIS
OF CANCER
CACHEXIA
I
DYSPHAGIA
ANOREXIA
mEqPotassium60-100
tumors
sume glucose in their glycolytic cycle. When stored glyco
(CANCER)1N@
ILLNESS
TUMOR HYPERMETABOLISM
ANERGY
DYSFUNCTION
NAUSEA/VOMITING
mEqMagnesium8-16
mEqCalcium9-18
mEqPhosphorus25-35
mMIron1Zinc2Manganese0.4Copper1Chromium10
I PPORT@'@M
NUTRITIONAL
SU
ANTINEOPLASTIC
THERA@
MORBIDITY
MORTALITY
I. Improved
metabohc
function
a immunestatus
@
plasmaproteins
@gCobalt
@gIodine0.056a
(as Vitamin B12)20
2.Improved
work
performance
3. Improved
qualityof life
4. Improved response to therapy
Dose
JULY
in mg
unless
otherwise
noted.
Chart 1. Interrelationships of cancer and nutrition.
1977
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2349
G. L. Blackburn et al.
gen and dietary carbohydrate cannot meet this require
ment, a considerable loss of amino acid would occur for
gluconeogenesis to provide fuel for this low-energy-yielding
anaerobic cycle. Weight loss has been correlated to
high Con cycle activity (23); the extra energy expended is
but a small fraction of the total energy expenditure. This
tumor metabolism cannot account for the observed weight
loss and malnutrition. Clearly, the important factor is to
overcome anorexia by providing an adequate diet of protein
and calories.
NUTRITIONAL
SUPPORT
OFCANCER
PATIENTS
PARENTERALENTERALHOMEDIScHARGED@!DISCHAR
171A&W
&@JP.•
_____
_____
Neckendmoo'
Esophoqus
Lymphosorco@rto
Lurtq
8,'ecsi
6U/8/odder
Poncrecs
/81//cry
Uterus/Cervix
Co/ce—Rectc/
Diet
TOTAL• 27
The 3 energy-containing dietary components are carbo
hydrate, fat, and amino acids. The 1st 2 provide nonprotein
energy. The latter is necessary if there is to be protein syn
thesis. Three hundred to 400 g of body protein are broken
down each day. The reutilization rate of amino acids availa
ble from the normal degradation of body protein is between
70 and 80%. Those tissues in which turnover rates are high
(e.g., gut and liver) are at a greater advantage when
competing for a limited amount of amino acid compared to
the less labile proteins (7). Given the limited repair of body
cell mass (150 g/day), this process takes considerable time
to produce significant changes.
Hyperalimentation, whether it is provided enterally or
parenterally, can replete most malnourished cancer patients,
given adequate time. We recently studied 66 adult patients
with advanced solid tumors who were referred to the Nutri
tion Support Service at the New England Deaconess Hos
pital (8). The purpose of the study was to categorize the
nature and degree of malnutrition, formulate an optimal
nutritional therapy plan for each patient, and to identify the
factors preventing an adequate response to both cancer
and nutritional therapy (31, 44, 48).
Patient Assessment. The patients were classified ac
cording to a number of criteria. Tumor types are listed in
Chart 2. The basal energy expenditure was calculated using
the Harris-Benedict formula which takes into account age,
sex, height, and weight (41). Anthropometric measure
ments which included triceps skinfold (an estimator of fat
reserves), arm muscle circumference, and creatinine/
height ratio (independent estimators of body cell mass)
were recorded (4). Serum transferrin and albumin levels as
well as total lymphocyte counts were used to assess visceral
proteinfunction(3,4, 6).Immunological statuswas evalu
ated by delayed hypersensitivity skin testing with Candida,
streptokinase-streptodornase, and mumps antigens (5, 29,
46).
A wide variety of tumors were present. All patients had
lost at least 10% of their usual weight. Chart 2 shows the
degree of weight loss. In addition, no significant hyperme
tabolism was present, and nitrogen loss could not be cate
gorized according to tumor type. These patients were seen
at all phases of their cancer treatment programs, whether
surgery, chemotherapy, or radiotherapy. These observa
tions suggest that some generalizations and nutritional
guidelines for protein and calorie therapy are possible.
Using these aforementioned techniques of nutritional as
2350
AGE Mecn
Rcnge
BEE.mon
/itinqe
22
8
2
7
63
36—9162
32—781315 48—7457
941—18641420
1167—17011375
970—168518±620±726±66.2
x Weight
Loss
WEIGHT64/N Macn
@c@@nqe
0—1714
10—23
Chart 2. Patient distribution in various tumor groups. Basal energy cx
penditure (BEE) calculated on the basis of height, weight, age, and sex. GU,
genitourinary.
sessment, an objective classification of malnutrition can be
made. Chart 3 characterizes these patients according to key
nutritional criteria. Substantial losses of fat mass were ob
served; fewer than 25% of the patients had a normal triceps
skinfold (12.5 mm). Deficits in lean body mass were consid
erable, although not as widespread as adipose tissue loss.
The most physiologically significant tissue losses were from
the viscera, indicated by the low albumin, transferrin, and
total lymphocyte count, a finding seen in advanced states of
malnutrition. A combined marasmus and kwashiorkor-like
syndrome characterizes this population (3). Poor visceral
function, the most serious consequence of protein-calorie
malnutrition, is accompanied by the marked impairment of
cell-mediated immunity as demonstrated by the measure
ment of delayed hypersensitivity skin tests (Table 2; Refs. 5,
45, and 46).
Biochemical Assessment. A record of blood sugar, urea
nitrogen , creatinine, sodium , potassium , chloride, bicar
bonate, and magnesium was kept. Liver function tests were
performed weekly; this included albumin and transferrin.
Complete blood counts were done daily, and lymphocyte
levels were checked weekly. Cultures were done when nec
essary, and clinical charts recording weight, subjective re
sponses to therapy, and significant events were maintained.
Forty-eight-hr nitrogen balance studies were performed
weekly, and skin testing was done at 3-week intervals.
The criteria for a successful response to therapy were: (a)
completion of oncological therapy, (b) weight gain, (C) dis
charge from hospital, (d) improvements in visceral protein
status parameters , (e) preservation o r restoration of mm Unological response as measured by skin testing, (f) subjec
tive improvements in symptoms, and (g) closure of fistulae.
All patients were followed closely by the members of the
Nutrition Support Service. This team consists of a thera
CANCERRESEARCHVOL. 37
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@
:L@
Nitrogen, Electrolytes, and Minerals in Cancer
@
@
@
.
SKIN-FOLD
ARM-MUSCLE
.
CIRCUMFERENCEALBUMIN
THICKNESS
-
TOTAL
TRANSFERIN LYMPHOCYTE
L
COUNT
100
@
80
I..
‘
60
tam anabolism and positive nitrogen balance was (1.7 x
basal energy expenditure) for i.v. hyperalimentation and
(1.54 x basal energy expenditure) for enteral hyperali
mentation (9, 21). The difference in these 2 groups is due
to the continuous infusion of hypertonic glucose in the
parenteral case, which results in an obligate conversion of
some of the administered glucose to fat (30. 41).
Responseto NutritionalTherapy
@
@
@
Chart 4 shows the responses to the different types of
nutritional therapy in surviving patients. Due to the under
S •
S of Standard
weight and marasmic nature of these patients, weight gain
was an important indicator of a positive response to ther
Chart 3. Nutritional characterization emphasizes the physiologically sig
nificant loss of visceral protein (transferrin and total lymphocyte count) in
apy. The most significant changes during the 1st 3 weeks of
patients with loss of 15 to 25% of body weight.
therapy appeared in the visceral compartment. Perhaps the
most important result was that an average of 3.5 weeks was
Table2
required before a positive response demonstrated itself. No@
Delayedhypersensitivityskin testing
changes were seen in the 1st week of therapy. Given that
Control patientsCancer
patientsCandidaSKSD@CandidaSKSD(mm)(mm)(mm)(mm)05b000150011121044100818035165100103000847051610101256010Mean
length of therapy, patients gained an average of 6.2 pounds,
with a range of no weight change up to +17. There were no
differences in results between the enteral and parenteral
groups; the responses to anorexia, dysphagia, stomatitis,
and weight loss were similar.
Successful surgery occurred in 3 of 12 patients where
fistulae closed despite tumor in the anastomotic line. Re
sponse to chemotherapy was poor (40%) owing to the ad
vanced nature of the disease. Radiotherapy was more suc
cessful, particularly when compared to a 25% positive re
sponse in nonhyperalimented patients requiring 4000 rads
(11). Patients receiving total parenteral nutrition were in an
advanced stage of illness as reflected by a higher mortality
7.416.53.85.5
rate. Two episodes of catheter-related sepsis occurred in
a SKSD,
streptokinase-streptodornase.
the
series, necessitating the removal of the catheter. No
b p < 0.005
(x2
test)
for
number
of positive
skin
tests.
further septic problem developed, but both patients had
advanced cancer, were anergic, and soon succumbed to
peutic dietitian, a hyperalimentation nurse, a pharmacist,
tumor-related problems.
and a psychologist. Ambulatory patients were maintained
on nutritional support (enteral) at home. These 7 patients
were followed closely through weekly visits to the nutrition
@E/6HT
GA/N
LYMPHOCYTES
clinic.
I:, (@)
@7L
2000
On the basis of their nutritional profile, a nutritional sup
@>or@Q%% @A>ar.to75%but<90%
•>ar'Ia6O%but<75%
port plan was designed for each patient. The type of nutri
tional therapy was dictated by the severity of malnutrition
and the presence of a functional gastrointestinal tract.
When enteral hyperalimentation was indicated, a continu
ous drip through a mercury-tipped Silastic tube (Keofeed
Stomach Tube; Hedeco, Palo Alto, Calif.) was used. Defined
formula diets (Precision LR®,Doyle Pharmaceutical, Mm
neapolis, Minn.; Vivonex HN®,Eaton Laboratories, Nor
wich, N. V.; Isocal®,Mead Johnson & Co., Evansville, md.;
and Ensure®, Ross Laboratories, Columbus, Ohio) were
supplemented with protein (SCM®, Control Drug, Port
Reading, N. J.) or calories (Polycose®, Ross Laboratories;
medium-chain triglyceride caloric supplement, Eaton Labo
ratories), as necessary. Hyperalimentation i.v. (25% dex
trose and 4.25% Fre-Amine; McGaw Laboratories, Irvine,
Calif.) was carried out under standard guidelines. Trace
mineral supplements were provided as shown in Table 1.
The exact amount of calories and protein delivered to ob
0@
.
1600
:@•@
ALBUM/N
LEVELS
40@
0
1
0
@!O
SERUM
TRANSFERRIN
1mg/lOCal)
32
265
. 245
WEEKS
Chart 4. Response to nutritional support in surviving patients. Significant
(p < 0.05) results except for albumin occurred by the 2nd to 3rd week of
therapy.
JULY 1977
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2351
G. L. Blackburn et al.
Caloric requirements confirmed the fact that energy ex
penditures were similar to those observed in patients un
dergoing elective surgery (41). Optimal nutritional support
based on nitrogen balance showed caloric intake require
ments to be 130 to 150% of basal energy expenditure in
enterally fed patients and 175% of that in parenterally fed
patients (4, 21). After meeting the caloric requirements,
weight gain is largely dependent upon the level of protein
intake. The best results in terms of weight gain occurred
when an intake of 90 to 100 g of protein (1.5 to 2.0 g/kg/day)
accompanied a caloric intake of 40 to 45 kcal/kg/day.
mals exhibit a decreased tumor growth with a parallel de
dine in body growth. This correlation demonstrates the
similar effect of fasting on generalized host and tumor
metabolism. The modification of fasting by protein results
in tumor growth as well as preservation of animal growth
(48).
Regardless of the mechanism, protein-calorie malnutri
tion does develop in a large number of cancer patients (14).
The degree of imbalance between synthesis and catabolism
is dependent upon: (a) extent of nutritional depletion, (b)
total body protein mass, (c) rate of protein turnover, and (d)
alterations produced by cancer tissue.
Terepka and Waterhouse (49) have questioned the benefi
NitrogenMetabolism
in Cancer
cial effects of forced feeding . Although effective over the
short term, these therapies could not be maintained for
Cheraskin (11) studied the effect of diet on the response
prolonged periods of time. Feedings p.o. lasted 10 days and
of cervical carcinoma to [email protected] this randomized study
resulted in positive nitrogen balance accompanied by the
involving54 patients,a high-protein,
low-refinedcarbohy
retention of phosphate, calcium, sodium, and chloride. In
drate diet was compared to standard nutritional support.
the postsupplemental period , however, these returned to
Radiation response was significantly higher in those sus
equilibrium and finally became negative. Although the pa
tamed by the high-proteindiet.In addition,the radiation tients were encouraged by their weight gain, only 1 patient
response of the control group was progressively worse with
continued his effort successfully after the study. Nutrition
more advanced stages of uterine cancer, whereas the high support programs should and must be continued on an
protein group continued to respond favorably. Jewell and outpatient basis in order that the patients can be maintained
Hunter (27) noted depleted protein pools and net catabo
in the “fed―
state. Frequent monitoring and counseling, in
lism of labile and stable protein. These conditions presum
addition to individual alteration in feeding regimens to cater
ably favor tumor growth by making amino acids and energy to changing behavior patterns and taste sensations, are
available in abundance to the tumor. The studies by Jewell
essential.
and Hunter regarding the growth of 150-g female rats dem
Immunological alteration has been established as an
onstrated accelerated rates of albumin catabolism and de
important mechanism in the pathogenesis of cancer
creased levels of serum albumin. High-protein diets im
(39). Lymphocytic
activity and reactivity to skin antigens
proved albumin synthesis, although net catabolism per
correlate well with prognosis and response to therapy in
sisted. Thus tumor and visceral protein, which have higher
leukemia (22), Hodgkin's disease (47), lung cancer (26), and
rates of protein turnover and higher metabolic rates at rest, other tumors (16). It is well known that, in children and
survive longer or in preference to muscle. In cancer (37) or adults, the nutritional status can influence immunological
in mild trauma (10), normal liver protein function and weight
activity (29, 45). This can be reversed by adequate nutri
are maintained. Only the secretory proteins of the liver tional replenishment (17). This method remains an impor
albumin, transferrin, lipoproteins become depleted. For tant parameter of measuring visceral protein status; all pa
these proteins there is a lower priority for synthesis when tients who failed to respond to nutritional support were
compared to structural proteins and enzymes competing for anergic and subsequently died in hospital (24 of 66 pa
available amino acid substrates. After the depletion of mus
tients).
cle protein, the patient progresses to the advanced stages
There is inadequate evidence that specific deficiencies of
of marasmus, and the loss of visceral protein and immune
electrolytes and minerals exist in cancer. However, defici
competence becomes more obvious.
ences are part of the total picture of malnutrition, and all
nutrients including trace minerals must be administered to
In injury, a loss of skeletal muscle protein is a physiologi
cal response to injury, favoring the mobilization of labile produce an optimal utilization and retention. The current
protein pools to support visceral protein synthesis (10). This status of nitrogen, electrolyte, and mineral therapy dictates
response, primarily sympathetic mediated, is communi
nutrition prescriptions to contain a nitrogen/calorie ratio of
1/150 with 2000 to 2500 kcal/day. With appropriate electro
cated in part by active polypeptides found in plasma during
injury (12). Similarly, in cancer, tumors might produce or lyte and mineral intake, this therapy can, in 2 to 3 weeks,
result in a positive objective response in the absence of an
initiate similar kinds of polypeptides that are responsible for
overwhelming tumor burden. In this study, no evidence of
the protein depletion observed in advanced cancer patients.
selective stimulation of tumor growth in any patient was
Theologides (50) has proposed that cancer produces low
found by any criteria available to us. The paralleled in
molecular metabolites which render host metabolism cha
creased tumor cell mitosis produced by adequate nutrition
otic by affecting important allosteric transitions, activa
may be a desirable effect to maximize the efficacy of chem
tions, and inactivation of control mechanisms in various
otherapeutic programs. In contrast, malnutrition-induced
tissues.
In small animal tumors, the glycolytic rate and Con cycle depression of cell-mediated immunity can be expected to
have an adverse effect on cancer therapy. Optimal results
activity have been measured in a “fed―
group, a “fasted―
occurred with delivery of adequate nutrition as described
group, and a “fasted
plus protein―group. The fasted ani
2352
CANCER RESEARCH VOL. 37
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Nitrogen, Electrolytes, and Minerals in Cancer
herein. The delivery of a high concentration of nutrients
through forced feeding programs, either by the gastrointes
tinal tract or by total parenteral nutrition, results in im
proved organ function.
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28. Larsson, L-G., 5andstrom, A. , and Westling, P. Relationship of Plum
mer-Vinson Disease to Cancer of the Upper Alimentary Tract in Sweden.
Cancer Res., 35: 3308-3316, 1975.
29. Law, D. K., Dudrick,
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Prevalence of Malnutrition in General Medical Patients. J. Am. Med.
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2353
The Effect of Cancer on Nitrogen, Electrolyte, and Mineral
Metabolism
George L. Blackburn, Baltej S. Maini, Bruce R. Bistrian, et al.
Cancer Res 1977;37:2348-2353.
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