(CANCER RESEARCH 37, 2359-2364, July 1977]

Summary

Host starvation is a common accompaniment to the presence of cancer. Diminished intake is a major contributor tothis starvation and does not require that the oropharynx orgastrointestinal tract be the primary site. There is suggestive evidence that the normal adaptive mechanisms of thenontumor-bearing host to starvation that result in bodyprotein conservation are not functioning in the tumor-bearing host. Cancer cachexia has some similarity to the metabolic disturbances of host metabolism that are seen inmajor injury or sepsis. The growing tumor shows little respect for normal constraints of host tissue growth. With thewidespread availability of methods of total parenteral nutrition, the interrelationship of nutrition and host-tumorgrowth assumes greater importance.

The starvation that accompanies cancer is so well-recognized as to be entitled “cancercachexia.―Cachexia alonethat syndrome of emaciation, debilitation, and malnutrition—is seen in many other diseases, but, apart from thyroid disease, none ennobled as a distinctive cachexia entity.The significance of such cachexia has long been neglected,but with the advent of an effective means of reversal byaggressive use of i.v. total parenteral nutrition, cancercachexia is no longer obligatory (7).

To determine whether or not the starvation that accompanies cancer is an entity of itself, or simply a manifestationof the malnutrition that accompanies any severe illness, isdifficult. Patients with gastrointestinal neoplasms have aclear reason for malnutrition, i.e., inadequate intake basedon organic pathology that prevents either the ingestion ordigestion of food. In the gastrointestinal tract, however,weight loss is often seen as a reflector of a “hidden―cancersuch as cancer of the pancreas. In other small primarylesions not involving the gastrointestinal tract, such as carcinoma of the lung, weight loss is a similar, almost invariable accompaniment of the presence of cancer. The degreeof debility and malnutrition often seems to far exceed thatwhich might be reasonably expected on the grounds of theextent of the neoplastic process.

To examine the problem of cancer cachexia, basic bodycomposition, energy and protein reserves, and the effect ofsimple starvation on these entities must be reviewed beforeexamining the effect of superimposition of cancer.

As a result of the work of Moore et al. (18, 20) and Cahill etal. (5, 6), which has recently been reviewed (19), we can

, Presented at the Conference on Nutrition and Cancer Therapy, Novem

bar 29 to December 1, 1976, Key Biscayne, Fla.

make some statements about body composition and bodytissue reserves. Table 1 gives the distribution of the bodycell mass as it is divided into muscle, viscera, supportingtissue, and the red cell mass. Body cell mass makes upapproximately 55% of total body weight and is equivalent toabout 10 to 13 kg of actual protein. Caloric stores, on theother hand, are predominantly maintained in the 13 or 14 kgof fat that the well-developed, often mythical 70-kg mancarries around (Chart 1).

In acute starvation, there is early rapid proteolysis withamino acid mobilization from muscle, gluconeogenesis,and the production of urinary urea nitrogen. This urinaryurea nitrogen, about 12 g a day, is equivalent to the loss ofapproximately 75 g of muscle protein, or 320 g of wetmuscle mass. The continuation of this simple starvationcatabolism of muscle mass would mean that, in 10 days ofunabated loss, 15% of the total muscle mass would be lost;unabated for 20 days, 30% of the muscle mass would betotally consumed.

Obviously, this process does not continue in as rapid acatabolic fashion as man undergoes adaptation to starvation. His initial urinary losses of nitrogen fall back and arereflected, not just as urea, but predominantly as ammonianitrogen. Renal ammoniagenesis from glutamine increasesto aid excretion of the excess acid resulting from utilizationof the ketones, /3-hydroxybutyrate and acetoacetate, as fuel(2, 22). This starvation adaptation is accompanied by theability of the brain to adapt to the use of ketone bodies (23).Some small quantities of glucose are still produced bygluconeogenesis, but the drain on muscle is markedly diminished, with total urinary nitrogen falling to approximately 3 g/day. Man has, by this adaptation, begun to liveoff his major source of stored energy, fat. With adaptation,chronically starving man will lose approximately 400 g ofmuscle mass in 20 days, or about 2% of total body musclemass, allowing survival for long periods of time in thechronic fasting state.

The situation changes considerably with the superimposition of any major insult. With major injury, the ability tocontinue to conserve lean tissue masses is lost, and thepatient moves into a hypercatabolic state in excess of thatseen with acute fasting. It should be emphasized that, whenspeaking of major injury or insult, we are not talking of themild elective operation taking place in a fit, healthy person,where nitrogen losses and subsequent lean tissue mass lossare often little different from the effects of acute fasting (1).This injury may be a major surgical procedure or a majorepisode of sepsis. The most classical examples are seen inmajor burns, but are not uncommonly seen in patients withand without cancer who have major septic episodes. Theacute tissue mass loss from severe trauma, which may

JULY 1977 2359

Uncomplicated Starvation versus Cancer Cachexia1

Murray F. BrennanSection of Surgical Metabolism, Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20014

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wt(kg)Muscle23Viscera8Supporting

tissue6ABCmass2Total39

M. F. Brennan

Table 1

Body cell mass of healthy man (55% total body weight)be emphasized that many patients that are thought to bechronically starving have been admitted to a hospital andrehydrated, thereby often showing much less weight lossthan one might expect for the length of relative starvation.This is not to be falsely interpreted, as many of these patients merely reflect the electrolyte and fluid retention thataccompanies rehydration following long-term, or evenshort-term, starvation. This is commonly seen with theacute weight gain that accompanies the first few days ofparenteral hyperalimentation (Chart 2).

The addition of cancer to the situation makes interpretation much more difficult. All of the events previously described may occur in the cancer patient, but the importantquestions are (a) is the patient starving primarily because oflack of intake, or inability to digest and absorb? and (b)does the cancer patient adjust to starvation as does normalman? There is little question that, in many cancer patients,much of the weight loss and apparent starvation can bedirectly attributed to the lack of intake p.o. This is nowreadily reversible by the use of TPN2 (7). The typical intakeof a group of inhospital patients over the 2 weeks precedingcommencement of TPN is illustrated in Table 4. This highlyselect group emphasizes what little intake many inhospitalcancer patients receive either as a consequence of theirprimary disease, or related to the side effects of their aggressive therapy. Most of these patients had already received a 2-week course of aggressive nutritional repletionP.O. where possible, using liquid and elemental oral dietary

formulas. Support for the fact that this group of patientswere nutritionally depleted, even after these attempts, isreflected in their weight loss (Table 5). Unfortunately, theability to characterize degrees of malnutrition in these complex patients on multimodality therapy is difficult. Standardparameters of protein and albumin concentrations are poorreflectors of protein synthesis and can be widely distortedby intravascular volume depletion and the use of albumininfusion as a means of volume expansion (Table 6). Thesedifficulties are indicated by the wide range of values forconventional determinants in a group of cancer patientsprior to instigation of TPN, rendering such profiles of littlevalue in generic terms. In individual patients, however,these determinations (corrected for renal function and volume dependence) and those of the acute phase reactants,trace metals and vitamins, can provide biochemical supportfor clinical malnutrition.

There is considerable evidence that a specific tumorinduced anorexia and inadequate intake are present in alarge percentage of patients with cancer (4, 10, 11). Thisparticular syndrome has been examined on many occasionsexperimentally (3, 17) and has led to various experimentsdesigned to modify and examine the hypothalamic mechanisms that control food intake. There seems to be little goodevidence that invasive mechanisms can arrest the hypephagia. Clinically, the vicious cycle of decreased intake,decreased motor activity, lethargy, apathy, and further decreased food intake is a common event. Other workers (21)have attempted to correlate food intake during tumorgrowth with the progressive incapacity to undertake the

2 The abbreviation used is: TPN, total parenterai nutrition.

BODY WEIGHT CALORIC EQUIVALENCE

reach as great as 15 to 20 g of nitrogen per day is, in fact,equivalent to 400 to 500 g of wet muscle mass (9). Such aninsult, if perpetuated for 10 days, can result in a loss of 23%of the total lean tissue mass and a comparable percentageofthe body storeof protein.

These metabolic events are summarized in Table 2, wheretheoretical calculations and predictions are made to describe the length of time required under varyin,g conditionsof starvation that would result in loss of 50% of either thetotal muscle mass or the total body cell mass. It can be seenthat the addition of sepsis or major injury results in rapidcatabolism and must be accompanied by the rapid demiseof the patient unless arrested and/or corrected. Looked atin a different way, we can more simply gauge these lossesas they are reflected by body weight change. A single,prolonged episode of major sepsis extending over 30 dayscan result in the loss of 30% of total body weight (Table 3).Many studies have attempted to quantitate weight loss withloss of lean tissue. It would appear that, regardless of theamount of weight loss, protein makes up approximately10% of the total, and fat, 20% (14). From these and otherstudies, attempts have been made to correlate weight losswith survival (26). It has been suggested that 30% bodyweight loss is almost invariably fatal; however, the rarepatient may survive weight loss as extensive as 50% of totalbody weight. The converse is also true, in that other catabolic patients are seen who have lost a lesser percentage oftheir body weight in a rapid, fulminating course that haspreceded death. It is the rapidity and severity of the weightloss that is the most reliable predictor of outcome. It should

MALE71.5 Kg

16@ 3(JYrs. Old

Chart 1. Body fuel reserves.

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Daysto lose50% of to

Nitrogenloss/dayEquivalentprotein lossEquivalentlean tissuetalMuscleBodycell(9)(9)(g)massmassAcute

starvation10632804169Chronicstarvation31984137232Sepsis/major

in201255602134juryMonth

prior star15944201635vation+ sepsis

Weightloss under varying catabolicstates30-daywtlossaNitrogen

loss/day(g)(kg)MBAcutestarvation1013.5Chronic

starvation38.3Sepsis/majorinjury2017.3―

CarbohydrateProte (g)inFat(g)TotalcalP.O.84±12―27±528±6777±157i.v.107

±400428±15aMean± SE.

wt(kg)Pre-illness63.9±2.5―Pre-TPN51.8±2.1Loss12.1±1.6a

Mean ± SE..

Biochemical indicesin cancer patients beingconsidered forTPNMean±SE.RangeTotal

protein(g/100ml)

Serum albumin(g/100ml)

BUN―(mg/100ml)

Insulin (microunits/mI)

Glucagon (pg/ml)6.09

3.36

18

27

118±

0.07

± 0.07

± 1

± 13

± 33(3.8-8.3)

(1 .9 -5.4)

(1-152)

(6—88)

(10-600)

Uncomplicated Starvation versus Cancer Cachexia

Table 2Body energystores: depletion times for varying catabolic rates

Table3 Table4Mean daily intake prior to commencement of TPN

12.66.3

23.Oa

a Often minimized by water and electrolyte gain.

b A, assumed appropriate energy expenditure: 1 , 1500 cal/day; 2,

1200cal/day; 3, 3500cal/day. B, stableenergyexpenditureof 1800cal/day.

85

0

,- 60

2

55

50

4000

3500

@ 3000

@ 2500U

@ 2000l'J

0@ 1500a.

@ 1000

500

0

Table5Weight loss of cancer patients prior to commencement of TPN(n =

34)

70

Table 6

a BUN, blood urea nitrogen.

motor activity of feeding. While this entity clearly appears toexist, it cannot always account for the major portion of thedecrease in food intake in the animal model. It should beemphasized that reduction in food intake in the normalanimal has no effect on the total motor activity, so that it canbe inferred that decline in activity of the tumor-bearinganimal is not a consequence of the decline in food acquisitionper Se.

The second question is whether or not the tumor-bearinghost can adapt to chronic starvation in the manner seen innormal man. In chronic starvation, with conversion to a “fatfuel economy,―one sees a decrease in oxygen consumption and a greater decrease in carbon dioxide production,so that the respiratory quotient falls toward 0.7. In thetumor-bearing host, there is some evidence that the fall inCO2 production (30) does not occur. While these changesare small, when taken in the light of a chronic, malnourished tumor-bearing host, they become of much greater

10 20 30 40 50 60DAYS

27 6 18 26 6 16 20AUG SEP SEP SEP OCT OCT OCT78 76 76 76 76 76 70

Chart 2. Weight gain versus days on TPN; high caloric intake required forweight maintenance in a nonseptic, at rest, patient with extensive intraabdominal diffuse histiocytic lymphoma. Note the acute weight gain of rehydration in the 1st few days of TPN.

JULY 1977 2361

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M. F. Brennan

significance. In a similar manner to the studies performed intrauma (16) where the quantity of 14C-Iabeled gluconeogenic precursor appearing as glucose was examined, studies in the tumor-bearing host have suggested that the abilityof simple substrates to decrease gluconeogenesis in thecancer-bearinghost are to some degree impaired.Inaddition, there is an increase in the apparent recycling of pyruvate and lactate to glucose (28), an increased oxidation oflabeled acetoacetate by neoplastic tissues (30), and aslower disappearance rate of glucose in the cancer-bearinghost, which is consistent with other data on impaired glucose tolerance. In vitro, there is an increase in [14C]glucoseappearance from amino acid precursors in tumor tissue(25). This is surprisingly analagous to the situation seen insevere sepsis (16). A voluminous literature exists as to thepresence or absence of multiple abnormalities of substratemetabolism in the tumor-bearing host (8, 12, 13).

More supportive evidence for the inability to arrest normalamino acid-derived gluconeogenesis and inferential evidence as to the existence of increased metabolic need inthe cancer patient can be seen by examining some patientswho are fed TPN iv. during their cancer course (Chart 2).Despite the ingestion of 3000 to 4000 cal in a patient withdiffuse histiocytic lymphoma, and adequate quantities ofnitrogen (Chart 3), no weight gain was obtained, althoughweight loss was not manifest. The patient was not hypermetabolic from conventional causes, such as increased

0

•-600

I'J2

20

015

2

2 10

0

2

stress or exercise, and was afebrile and biochemically stable, factors not exclusive of but suggesting the absence ofsepsis. The measured basal metabolic rate in this patientwas only minimally elevated at 115% of predicted normal.The analogy to the postoperative patient is seen in Charts 4and 5, where a patient 2 weeks poststernal resection forosteogenic sarcoma is unable to be maintained by peripheral nitrogen and nonprotein calories, and, even with theaddition of 3500 cal and 15 g of nitrogen, barely maintainsweight and nitrogen balance. Such observations raise thequestion as to whether the apparent continued increase incaloric need of such patients is a reflector of the continuedpresence of neoplasia. Forced-feeding experiments p.o. inpatients with cancers (28) emphasize the often increasedcalories and nitrogen that are required for positive energyand nitrogen balance, in malnourished, inactive, near-terminal patients. This variability of need is also seen in patients fed i.v. (Charts 2 to 5). Calculations of oxygen consumption in other studies have further suggested that thedecreased oxidative metabolism that appears in normal patients with starvation is not seen in the cancer patient (11).

so

.- 70

66

60

4000

3500

3000

@ 2500C-,

z 2000‘Li

0@ 1500

2@ 1000

600

00 10 20 30 40 50

ORYS10 20 30 9 19 29

60 RUG RUG RUG SEP SEP SEP76 76 76 76 76 76

26 Chart 4. Nonprotein caloric intake of a patient 2 weeks post-sternal resecOCT tion for osteosarcoma. Note the inability to maintain weight by “peripheral―76 parenteral nutrition (period of intralipid intake) and maintenance of body

weight requiring 3500 to 4000 cal.

75

70

65

55

50

30 40 50DAYS

27 6 16 26 6 16AUG SEP SEP SEP OCT OCT76 76 76 76 76 76

Chart 3. Nitrogen intake (iv.) in patient of Chart 2.

2362 CANCERRESEARCHVOL. 37

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S

42 5 5S

@. S

SS S

SS S

SS S

24 5 5S 5S@ S S

S@ S

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S. n=91S55 55 S

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U • I I I I I I 15 10 15 31 25@@ 40

Rn@CalculatedTumorVolume(cmcu)Chart 7. Tumor weight versus volume relationship at time of sacrifice for

all animals, fed and starved. Measured weight and volume = 1/6 ir A―B.

Uncomplicated Starvation versus Cancer Cachexia

has been described, combining determinations of tumorvolume and tumor weight at the time of sacrifice. A regression line has been developed (Chart 7) that allows someprediction of tumor weight according to tumor volume priorto sacrifice. With the use of these calculations, very littledifference in total body weight between tumor-bearing andnon-tumor-bearing animals can be determined up to a timewhere the tumor was less than 7% of total body weight.During this time, there was no change in water content ofthe tumors. When one came to examine the effect on tritiated methyl thymidine incorporation into DNA corrected forquantity of DNA present, i.e., “specificactivity―of DNA,some considerable changes were evident (Chart 8). Thetumor increased its specific DNA activity throughout starvation, whereas the specific activity decreased in the liver DNAof both the tumor- and nontumor-bearing animals.

These data suggested to us that this was a further exampIe of the failure of the tumor to recognize normal hostcontrolling mechanisms and, in the presence of host starvation, the tumor was able to maintain its activity at the expense of the host. It should be emphasized that this was at a

5—. Tumor-bearing

0— ——0 Non-tumor bearing

so

76

0

I-. 70

‘Li2

66

60

10

‘LiC.)2

2

@ -50

z

10

50

2

). 0

0

@ .5

U @10

I9

@ @15

-10

-160 10 20 30 40 50

DAYS10 20 30 9 19 29AUG AUG AUG SEP SEP SEP76 76 76 76 76 76

Chart 5. Nitrogen balance during same period as Chart 5. Again, noteinability to maintain nitrogen balance by peripheral parenteral nutrition withthe use of iv. lipid.

Starved

0.5 5.10 10.15 15@20 20@25 24 48 72 96

DAYS HOURS

Chart 6. Total body weight change per day (mean ±SE.). Growth curvesfor fed and fasted tumor-bearing and nontumor-bearing animals.

In the animal model, starvation has been found to de

3 J. T. Goodgame, Jr., S. F. Lowry, J. J. Reilly, Jr. , D. C. Jones, and M. F.

Brennan. The Effect of Starvation on Tumor Activity and Host Growth,submitted for publication to CANCER RESEARCH.

crease total-body and liver weight in the animals bearing aFlexner-Jobling carcinoma. Tumor weight during the periodof starvation increased over prefasting control but increased to a lesser (although not significant) extent than thecomparable fed control (15). Liver weight in these studiesfell in the fasting tumor-bearing animal, whereas liver andtumor protein were the same in both fed and fasted tumorbearing animals. In our own laboratory, we have attemptedto obtain more accurate information (about cell cycle activity) than that reflected by tumor volume and tumor weightdeterminations. The latter determinations are imprecise andcannot correct for areas of necrosis and hemorrhage. Withthe use of a transplantable methylcholanthrene implanteds.c. in the thigh, the effects of brief-to-moderate (24 to 96hr) total starvation has been examined3 (25). Standardgrowth curves for tumor- and nontumor-bearing animalshave been constructed (Chart 6) and the effect of starvation

JULY 1977 2363

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M. F. Brennan

2. Aoki, T., Muller, W. A., and Cahill, G. F. Hormonal Regulation of Glutamine Metabolism in Fasting Man. Advan. Enzyme Regulation, 10: 145-151, 1972.

3. Baillie, P., Millar, F. K., and Pratt, W. W. Food and Water Intakes andWalker Tumor Growth in Rats with Hypothalamic Lesions. Am. J. Physiol.,209: 293-300, 1965.

4. BIgnall, J. A., Jr. Bronchial Carcinoma: Survey of 317 Patients. Lancet,1: 786-790, 1955.

5. Cahill, G. F. Starvation in Man. New EngI. J. Med., 282: 668—675,1970.6. Cahill, G. F., Herrera, M. G., Morgan, A. P., Soeldner, J. 5., Steinke, J.,

Levy, P. L., Reichard, G. A., and Kipnls, D. M. Hormone Fuel InterRelationships during Fasting. J. Clin. invest., 45: 1751-1769, 1966.

7. Copeland, E. M., and Dudrick, S. J. Nutritional Aspects of Cancer. In: A.C.Hickey(ed.),CurrentProblemsinCancer,Vol.1•pp.31-51.Chicago:Year Book Medical Publishers, 1976.

@Hau,s 8. Con, C. F., and Con, G. T. The Carbohydrate Metabolism of Tumors. I.The Free sugar, Lactic Acid, and Glycogen Content of Malignant Tumors. J. Biol. Chem., 64: 11-22, 1925.

9. Cuthbertson, D. P., Fell, G. 5., Smith, C. M., and Tiistone, W. J. Metabolism after Injury: I. Effects of Severity, Nutrition and EnvironmentalTemperature on Protein, Potassium, Zinc, and Creatinine. Brit. J. Surg.,59: 926-931, 1972.

10. Donovan, H. Malignant Cachexia. Proc. Roy. Soc. Med., 47: 27-31 , 1954.11. Fenninger, L. D., and Mider, G. B. Energy and Nitrogen Metabolism in

Cancer. Advan. Cancer Res., 2: 229-523, 1954.12. Goodlad, G. A. J. Protein Metabolism and Tumor Growth. In: H. N.

Monroe and J. B. Alison (eds.), Mammalian Protein Metabolism, Vol. 2,pp. 415-444. New York: Academic Press, Inc. , 1964.

13. Gullino, P., Grantham, F. H., Courtney, A. H., and Losonczy, I. Relationship between Oxygen and Glucose Consumption by Transplanted Tumors in Vivo Cancer Res., 27: 1041-1052, 1967.

14. Kinney, J. M. Energy Requirements in Injury and Sepsis. Acta Anaesthesiol.Scand. Suppl.,55: 15-20,1974.

15. LePage, G. A., Potter, ‘a'.A., Busch, H., Heideiberger, C., and Huriburt.A. B. Growth of Carcinoma implants in Fed and Fasted Rats. CancerRes.,12:153—157,1952.

16. Long, C. L., Kinney, J. M., and Geiger, J. W. Non-Suppressability ofGiuconeogenesis by Glucose In Septic Patients. Metabolism, 25: 193—201, 1976.

17. Millar, F. K., White, J., Brooks, A. H., and Mider, G. B. Walker Carcinosarcoma 256 Tissue as a Dietary Constituent: Stimulation of Appetite andGrowth in the Tumor-bearing Rat. J. Nati. Cancer Inst., 19: 957-967,1957.

18. Moore, F. D. Metabolic Care of the Surgical Patient. Philadelphia: W. B.SaundersCo., 1959.

19. Moore, F. D., and Brennan, M. F. Surgical injury, Body Composition.Protein Metabolism and Neuroendocrinology. In: W. F. Bailinger (ed.),Manual of Surgical Nutrition, pp. 169-222. Philadelphia: W. B. SaundersCo.,1975.

20. Moore, F.D.,Olesen, K. H., McMurrey,J. D., Parker, H. V., Bail, M. A.,and Boyden, C. M. The Body Cell Mass and its Supporting Environment.Philadelphia: W. B. Saunders Co., 1963.

21. Morrison, S. D. Limited Capacity for Motor Activity as a Cause forDeclining Food intake in Cancer. J. Natl. Cancer Inst. 51: 1535—1539,1973.

22. Owen, 0. E., Felig, P., Morgan, A. P., Wahren, J. , and Cahill, G. F. Liverand Kidney Metabolism during Prolonged Starvation. J. Clin. invest., 48:584-594, 1969.

23. Owen, 0. E., Morgan, A. P., Kemp, H. G., Sullivan, J. M., Herrera, M. G.,and Cahill, G. F., Jr. Brain Metabolism during Fasting. J. Clin. invest.,46: 1589-1595,1967.

24. Reilly, J. J., Jr., Goodgame, J. T. , Jr., Jones, D. C., and Brennan, M. F.DNA Synthesis in Rat Sarcoma and Liver: The Effect of Starvation. J.Surg. Res., 22: 281-286, 1977.

25. Shapot, V. S. Some Biochemical Aspects of the Relationship betweenthe Tumor and the Host. Advan. Cancer Res., 15: 253-286, 1972.

26. Studley, H. 0. Percentage of Weight Loss, a Basic Indicator of SurgicalRisk. J. Am. Med. Assoc., 106: 458-460, 1936.

27. Terepka, A. A. , and Waterhouse, C. Metabolic Observations during theForced Feeding of Patients with Cancer: Am. J. Med., 20: 225-238, 1956.

28. Waterhouse, C. How Tumors Affect Host Metabolism. Ann. N. Y. Acad.Sci., 230: 86-93, 1974.

29. Waterhouse, C. L., Fenninger, L. D., and Keutmann, E. H. NitrogenExchange and Caloric Expenditure in Patients with Malignant Neoplasms. Cancer, 4: 500-514, 1951.

30. Weinhouse, 5. Oxidative Metabolism of Neoplastic Tissue. Advan. Cancer Res., 3: 269-325, 1955.

Tw@

— L@itTwataBwitgAiim@[ivy ii Non-TenorBiulig Ailnals

* p―35Can'n.@eIwithCois@

I24Hows n Notes

Potiodal Sotnà on

Chart 8. Specific DNA activity in liver and tumor from tumor- and nontumor-bearing animals.

time when the tumor effects alone on the host were notclinically manifest. As starvation proceeds, the tumor-bearing host is further required to support tumor activity at theexpense of the host.

In summary, then, the tumor-bearing host seems lesswell-adapted to respond to an added insult of starvationthan the nontumor-bearing host. The nontumor-bearinghost has clearly defined mechanisms to conserve lean tissue mass and to preserve total body protein. The tumorbearing host seems less well able to utilize these lean tissue-conserving mechanisms and to decrease gluconeogenesis from protein stores in the presence of host starvation.This results in ongoing lean tissue mass destruction. Theseaspects in a tumor-bearing host are invariably compoundedby a decrease in intake and a variable decrease in efficientutilization of ingested nutrient.

The tumor, on the other hand, shows considerable disdam for any attempts at limitation of growth by substraterestrictionofthe host.

I would suggest that at the present time there is considerable information that would support and encourage thenutritional support of the host while other adjuvant methodsof attacking the tumor are used.

Whether or not nutritional support of the host will allowmore efficacious use of such adjuvants and consequentprolongation of meaningful survival remains to be criticallyexamined.

—@•-.•@--

References

Much of the work referred to here would not have been possible withoutthe active support of Dr. Francis D. Moore, Dr. George F. Cahill, Dr. J. T.Goodgame, Jr., Dr. S. F. Lowry, Dr. J. J. Reilly, Jr., C. Gorschboth, M. Maher,D. White, and 0. C. Jones.

1. Abbott, W. E., and Albertson, K. The Effect of Starvation, Infection andinjury, on the Metabolic Processes and Body Composition. Ann. N. Y.Acad. Sci., 110: 941-964, 1963.

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Cancer CachexiaversusUncomplicated Starvation

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