Update in Clinical Nutrition
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Transcript Update in Clinical Nutrition
Nutrition in Cancer
Pranithi Hongsprabhas MD.
Weight Loss in Cancer Patients
50% of CA pt lose wt
~ 70% of terminal stage CA pt
Wt loss is prognostic significant
Kondrup AJCN 2002, De Wys et al. Am J Med 1980, Andreyev et al. Eur J Cancer 1998
Frequency/Severity of Weight
Loss Associated with Cancer
100
Severe
90
Moderate
80
Minimal
70
60
50
40
30
20
10
0
Colon
Prostate
SCLC
DeWys et al. Am J Med 1980;69:491
NSCLC
Pancreas
Non
measurable
gastric
Mesurable
gastric
Cancer Cachexia: Myth
Anorexia-cachexia
syndrome is due to the
host lack of appetite and
or starvation
Anorexia-cachexia
happens because of tumor
consumes the host
nutrients
Progression of Cancer-induced
Weight Loss
Initiating
Factors
Normal
Mild Weight
Loss/ Anorexia
Metabolic
Changes
Moderate
Weight Loss/
Reduced activity
Below IBW
Severe Weight
Loss/ Cachectic
State
Muscle Wasting
Obvious
Death
Reduced
Survival
Cancer Cachexia
Syndrome of combined physiologic, metabolic
and psychological factors
Manifestations:
anorexia
progressive involuntary wt loss, wasting,
tissue depletion
Fatigue, poor performance
Anemia
More advance disease: higher risk of wt loss
Metabolic Response to
Starvation
Hormonal
Response
Starvation
Energy Expenditure
in to
Starvation
Nitrogen Excretion (g/day)
Hormone
12
Source
Change in Secretion
Norepinephrine
Sympathetic Nervous System
Norepinephrine
Adrenal Gland
Epinephrine
8
Thyroid Hormone T4
Normal Range
Adrenal Gland
Thyroid Gland (changes to T3
peripherally)
Partial Starvation
4
Total Starvation
0
10
20
Days
30
40
Long CL et al. JPEN 1979;3:452-456
Landberg L, et al. N Engl J Med 1978;298:1295.
Cancer Cachexia Anorexia
Syndrome (CACS)
Abdominal pain
Malabsorption
Taste alteration
Depression
Cachexia
Constipation
Radio/chemotherapy,
surgery side effects
Intestinal
obstruction
Derangement of
Metabolism
Increased
Decreased
• Lipolysis/lipid metabolism
• Lipogenesis
• Proteolysis
• LPL activity
• REE
• Protein synthesis
Lipolysis
TNF-, IFN-
LIF, TGF-β
increase of leptin
& altered orexegenic and
anorexegenic signals
Does cancer influence energy
expenditure?
Cancer itself does not have consistent
effect on REE
Increased
~ ¼ had 10% higher than
predicted
Unchanged
Decreased ~¼ had 10% lower than
predicted
Carbohydrate Metabolism
1925 Cori & Cori demonstrate
decreased glucose level
High anaerobic glycolysis
Glucose
to lactate
Increased lactate level
Lactate
Oxidized
15 %
Regenerate to glucose 85%
CHO Metabolism
Gluconeogenesis: increased
Lactate,
glycerol, alanine
Cannot be suppressed by
glucose supplement
Decreased glucose tolerance:
insulin resistance
Lipid Metabolism
Depletion of fat store
The proportion of wt loss: fat
loss
Associated with
hypertriglyceridemia
Mechanism
Increased lipolysis
Increased
FFA and glycerol
turnover
Normal or increased lipid oxidation
Decreased lipid clearance
Decreased
activity
lipoprotein lipase (LPL)
Protein Metabolism
Increased protein metabolism
Whole body protein turnover:
unchanged
Muscle tissue: largest pool
Muscle
protein loss, muscle wasting
Decreased protein synthesis
Cancer induced weight loss vs.
other types of weight loss
Cancer induced
Caloric deficiency
Lean body mass
Body fat
Caloric intake
TEE
REE
Protein degradation
Acute phase response
Body weight
Proteolysis inducing
factors (PIF)
Adapt from Kolter DP, Ann Int Med 2000;133:622
-
Does nutritional status influence the
clinical course and the prognosis?
Reduce QOL
Lower activity level
Increase treatment related adverse
reactions
Reduce tumor response to
treatment
Reduce survival
What are specific nutritional goals
in cancer patients?
Prevent and treating undernutrition
Enhancing anti-tumor treatment
effects
Reducing adverse effects of antitumor Rx
Improve QOL
Energy requirement
If REE cannot be measured, use rule
of thumb
Ambulant pt: 30-35 kcal/kg/d
Bedridden pt: 20-25 kcal/kg/d
Oncological Rx may modulate EE
Do cancer patients require a
distinct nutrient composition?
Standard formula are recommended
for EN of cancer pt
Protein
1 g/kg/d (minimum)
1.2-2 g/kg/d
Supplement with electrolyte,
vitamins and trace element
acording to RDA
When should EN be started?
If undernutrition already exists
If it is anticipated that Pt will be unable
to eat for > 7 d
If an inadequate food intake (<60%) to
eat for > 10 d
Can EN maintain or improve
nutritional status in cancer patients?
Yes : In wt lost patients from
insufficient intake:
Gain
more wt, lost less wt1
improve or maintain nutritional
status2
maintain QOL
1.
Systematic review of ONS, counceling Baldwin et al, 2004
2. Cancer cachexia and GI cancer Bozzetti F1989 and Lindh A 1986.
3. GI and H& neck cancer. Isenring EA, 2004
Can EN maintain or improve
nutritional status in cancer patients?
In the presence of inflammation
Extremely difficult to achieve anabolism
Without effective antitumor Rx
impossible to reverse process
At least to maintain wt or minimize wt
loss
Additional intervention pharmacological
effort recommended to modulate
inflammatory response
Therapeutic challenges
Other types of weight
loss (caloric
deprivation)
Mechanical causes
Treatment related causes
Pcycholocical issues
Provision of energy
and protein can
promote weight gain
Ottery FD Cancer Practice 1994;2:123
Cancer induced weight
loss
Metabolic
abnormalities
No weight gain, even
when added energy
and protein provided
Can metabolic modulators
increase nutritional intake
Steroids (short term)
Improve
appetite
Nausea
Pain
Mechanisim: TNF-, IL-1
ADR: PUD, osteoporosis
Can metabolic modulators
increase nutritional intake
Progesterone
Improve appetite
Wt gain
QOL
Megestorol acetate, Medroxy- progesteone
acetate
ADR: fluid retention, thromboembolism
Can metabolic modulators
increase nutritional intake
ω 3 fatty acid
ω 3 fatty acid: less active pro-inflammatory
midiators
Improve appetite and body weight
Antagonized: Lipid mobilizing factors,
proteolysis inducing factors
Does supplementation with ω-3 fatty acid
have beneficial effect in cancer patients?
RCT : contradictory/controversial
Evidence level C
RCT :
improve survival/Non significant effect on wt
Did not improve wt or appetite
Non RCT: improve survival, side effect of CTX
Recent RCT: high dose EPA: wt stabilization,
wt gain
Unlikely to prolong survival in advance cancer
The result of further trials are awaited
Special situation
Perioperative EN
Radiotherapy
Chemotherapy
Transplantation
Advance stage/ incurable
Perioperative
Severe nutritional risk benefit from SNS
10-14 d prior to major surgery even if
surgery has to be delayed (A)
All CA pt undergoing major abdominal
surgery, preop EN preferably with
immune modulating substreates 5-7 d
independent of nutritional status (A)
ESPEN guidelines on EN Clin Nutr 2006
Radiotherapy
-ve effect of XRT on oral feeding
early SNS may lead to complete course of Rx
reduce morbidity in Rx of head & neck
cancer
PN failed to improve survival, infectious
complication and noninfectious complication
in abd XRT
EN reduce wt loss, digestive intolerance to
abd and pelvic XRT
Critical Reviews in Oncology:Hematology 34 (2000) 137–168
Is there indication for EN during radiotherapy
(XRT)or combined radiotherapy(cXRT)?
Yes, use intensive counceling and ONS to
increase intake (A)
to prevent Rx associated wt loss
To prevent interuption of XRT
in GI, head and neck area
If obstructive H&N or esophageal CA
interferes with swallowing: tube feeding is
preferred
TF is preferred if local mucositis is expected
(c)
Routine EN is not indicated during XRT of
other body regions (c)
ESPEN guidelines on EN Clin Nutr 2006
Is there indication for EN during
chemotherapy?
No
Routine
EN during CTX has no
effect on tumor response nor CTX
associated unwanted effects (b)
ESPEN guidelines on EN Clin Nutr 2006
Bone Marrow Transplantation
Nutritional consequences of BMT
N&V, mucositis, diarrhea
Venooclusive disease (VOD)
Graft vs. host dis (GVHD)
Metabolic abnormalities
Increased protein metabolism
Hyperglycemia
Hypertriglyceridemia
Electrolyte abnormalities
TPN: indicated
Is there an indication for EN in
advanced stages of incurable cancer
patients?
EN should be provided in order to
minimize wt loss, as long as pt consents
and the dying phase has not started (c)
When EOL is very close, most pt require
only minimal # of food and water to
reduce thirst and hunger (b)
ESPEN guidelines on EN Clin Nutr 2006
Risk of EN
Does EN feed the tumor?
No
reliable data
Theoretical considerations should
No influence of the decision to feed
a cancer patient
Conclusion
Complete improvement of nutritional state is
not attained in short time
Cancer Rx should not be postponed until
nutritional rehabilitation achieved
Nutritional Rx should be incorporated in to
the overall Rx as early as possible
Effort to improve nutritional and metabolic
status may morbidity and mortality in pts
who need surgery, XRx, XR-CTx