Definition of Malnutrition

• Malnutrition is condition resulting from a

combination of varying degrees of under- or
overnutrition and inflammatory activity,
leading to abnormal body composition and
diminished function
• A new definition is under development by
ESPEN!!!

Soeters et al. Clin Nutrition 2008

New Definition
<<Proposal ESPEN>>
• Step 1: Risk Screening
(NRS 2002, MUST, MNA…)
• Step 2: Diagnosis of Malnutrition
BMI <18,5kg/m2
or
Weight loss >10% (indefinite time)/>5% last 3
months combined with either
BMI<20(<70y)/22(>70y) or
FFM <15 and 17kg/m2 in women and men, respect
Cederholm et al. Clinical Nutrition 2015
 Consequence of Undernutrition
• Poor nutritional status lead to an increase in
the rate of:
• In-hospital complications
• Length of hospital stay
• Mortality
• Costs
• Re-admissions
• Reduction QOL
Malnutrition Universal Screening Test (MUST)

• Its main disadvantages is that the recent food intake is not included,
and calculations of the percentage weight loss, and of the BMI, have
caused problems in some units
 Nutritional Risk Screening (NRS-2002)
Answer
• Is BMI < 20.5? YES NO
• Has the patient lost YES NO
weight during the last
3 months?
• Is the dietary intake
reduced in the last YES NO
week
• Is the patient severely YES NO
ill? (e.g. ICU)
If ‘No” to all questions, re-screened at weekly intervals
If “Yes” to any questions, the final screening is performed
Kondrup et al, Clin Nutr 2003
 Nutritional Risk Screening (NRS-2002) Final Screening
• (Risk of Malnutrition)
Absent Score 0 Normal nutritional status

Mild Score 1 Weight loss>5% in 3 months

or
Food intake below 50-75% normal requirement in preceding week

Moderate Score 2 Weight loss > 5% in 2 months

or
BMI 18,5-20,5+ impaired
general condition or

Food intake below 25-50% normal requirement in preceding week

Severe Score 3 Weight loss > 5% in 1 months

(>15% Iin 3 months) or
BMI< 18,5- impaired general
condition or

Food intake below 0-25% normal requirements in preceeding week

Kondrup et al. Clin Nutr 2003
 Nutritional risk screening
ESPEN-NRS 2002
• Impaired nutritional status
• Weight loss% over time, food intake, BMI
(Score 0-3)
• Severity of disease
• Mild to severe (Score 0-3)
• Age over 70 years : add 1 point
• If the total score is 3 or more nutritional
support is indicated
Kondrup et al. Clin Nutri 2003
 NRS 2002:
4 question and outcome
• The4 initial questions of the NRS 2002
robustly identify nutritional risk and are strong
predictors of morbidity and mortality
hospitalised patients
• These 4 questions are roust indicators for
subsequent poor outcomes

Tangvik, et al. Clin Nutri, 2014

 Nutritional risk screening/ partial assessment
Mini Nutritional Assessment (MNA)
I. Screening (14 points)
(food intake, weight loss, BMI, mobilitiy)
> 12 not at risk
<11 possible malnutrition

II. Assessment (16 points)

(life style, number of meals, mode of feeding, MAC
etc.)
17-23.5 at risk
<17 malnutrition

Guigoz and Vellaz, 1999

MNA Screening Form (MNA-SF)
1. Ha appetite & food intake
declined in past 3
months?
2. Weight loss in past 3
months?
3. Mobility problems?
4. Acute illness or major
stress in last 3 months?
5. Neurophysiological
problems: Dementia or
depression?
6. Body mass index (BMI)
(kg/m2)?
If you can not use BMI you can
use the calf circumference
(<31cm)!

Rubenstein et al. J gerontol 2001

 Nutritional risk screening subjective
global assessment (SGA)
• Patient’s history (weight loss, change in dietary
intake, GI-symptoms, functional capacity)
• Physical examination (muscles, subcutaneous fat,
edema, ascites)

Clinician’s overall judgement

• Good nutritional status
• Moderate malnutrition
• Severe malnutrition
 Nutritional assessment
Step to be taken
• Measure body composition (body cell mass)
• Measure or evaluate inflammatory activity
and disease activity
• Measure function:
– Muscle strength
– Cognitive function (mood, concentration, memory,
etc)
– Immune function
 Measure body composition: simple
methods
• Anthropometric tools (FFM, FM)
• Creatinine-height index (FFM)
• BIA (FFM, TBW)
 Laboratory testing
Can be useful for
• Assessment of inflammation and severity of
disease
– Hb (sensitive but not specific)
– Albumin (sensitive, specific and quantitative)
– Lymphocytes (sensitive, specific but not
quantitative)
 Limitation of serum protein
• These proteins are manufactured by the liver;
hepatic insufficiency may affect their
production (not true in stable cirrhosis)
• Serum concentrations of visceral proteins
decline due to disease related increases in
distribution space (eg. ECW/EVS) and possibly
due to increased breakdown independent of
nutritional status
Infectious complications and albumin
• Serum Albumin reflects disease
severity and is a good predictor of
outcome but is not a very good
indicator of nutritional status
Function

• Muscle-Strength

• Mobility
Muscle Strength
 Muscle strength
Is a good predictor of outcome:
• In chronic situations:
– Aging
– Organ failure (renal failure, COPD, heart failure)
• In acute situations:
– Surgery or trauma
– Second hit (superimposed infection when already
subject to inflammatory activity)
 Handgrip strength and outcome
Lower handgrip strength at hospital admission is
associated with:
• Longer hospitalization time
• No difference in men and women
• No difference in surgical and medical patients
 Handgrip strength as a predictor of
nutritional status in hospital
• HGS and PG-SGA correlated
significantly
• HGS can independently predict nutrition
status and change nutrition status defined
by PG-SGA score and category, although
future longer term research is required to
confirm the use of HSG as an early
detection tool for malnutrition risk
 Measurement Immune Function
• Lymphopenia and DHR are not good
parameters for the nutritional assessment

• They are not recommended tbe assessed,

because the data are very controversial
 Measurement Cognitive function
• To be develop
• No consensus
• No easy method
• Clinical impression
• Quality of life determined by:
– Muscle function
– Immune function
– Cognitive function
 QoL
• QoL is not easy to define or to measure
• QoL is based on the patients perceptions of
well-being
– Physical (mobility, muscle strength)
– Psychological (anxiety, depression)
– Symptoms (pain, weight loss, appetite loss,
nausea, constipation, diarrhea)
– Social (isolation)
 Conclusion
• For screening consensus has been reached regarding stepwise
evaluation of the risk to become or to be malnourished
• Assessment of nutritional state consist of three defined steps:
– Measurement of body composition (fat free mass.body cell
mass)
– Assessment of inflammatory activity
– Measurement of function
• Muscle force
• Immune function
• Cognitive function
• Treatment should be targeted to treat the specific risk problem
of the patient
– Nutrition
– Inflammation
– Training of muscle function
Nutritional Screening and Assessment
 The importance of evaluating body
composition
• Quantification
– Nutritional assessment
– Evaluating the risk for complication of different
diseases eg. CVD, impaired outcome etc.
• Monitoring
– Evaluating medical and nutritional treatments
– Evaluating changes in growth or aging
 Body Compartments
Body weight

FM FFM/lean mass

FM BCM ECM

• FM= Fat mass

• FM = Fat free mass
• BCM = Body cell mnass
• ECM = Extracellular mass
 Body Compartments
Body weight Body weight or BMI
does not describe
FM FFM qualitative changes

FM BCM ECM
Models of Body Composition
 Molecular Model : Normal Body Composition
• 12 kg storage fat (triglycerides)
• Subcutaneous
• Intramuscular Fat 15 kg
• Intraabdominal 3kg essential fat
• Bone marrow lipids Fat
• CNS lipids Protein 12,8 kg

• 45% structural protein Minerals and

Glycogen 4,2 kg
• Collagen
• Dermis
• Wall of blood vessels 55% cells and circulating protein Fat free
body mass
Water 4,2 kg
• Glycogen storres 73% water
• 500g in muscle
• 200g in liver

• Total body water (TBW) = 60% of body weight

• Intracelluler fluid = 66% TBW 70-kg man
• Extracelluler fluid (ECF) = 33% TBW
• ECF = interstitial fluid (80% ECF) plasma (20% ECF)
 Normal Body Composition:
• A good nutritional state is a situation in which
body composition is normal and in which normal
function is present
• Normal body cell mass (BCM) is the major
determinant of an adequate nutrititional state:
– Actively metabolizing part of the body
• Normal macronutrients, electrolytes, trace-
elements, vitamins/ normal organ sizes
• Reference values for body compartments (e.g.
FFM) are available
 Changes in body composition:
• Disease-related malnutrition/cachexia, weight
loss undernutrition
• Overnutrition/obesity
• Disease
• Aging
• Growth
 Body cell mass shrinks during
inadequate intake or depletion
• Due to less
Body weight
intake or
uptake of food
than required
FM FFM/lean mass • Due to
inflammatory
activity even
FM BCM ECM
during
adequate
intake or
FM= Fat mass/lean mass uptake of food
FFM= fat free mass
BCM= body cell mass
ECM= extracell mass
Sarcopenia in Obese Cancer Patient
- n =250
- Age Ø 63.9 ± 10,4
yrs
- BMI Ø 34,3 ± 4.4
kg/m2 (range : 30.0-
55.0)
- sarcopenic obesity:
15%
- Higher mortality
- HR = 2.4 [95% CI:
1.5,3.9]
- (stratified according
to age, sex, tumor
entity and – stage as
well as weight loss)

Prado et al Lancet Oncology 2008 9:629-35

 Changes in body composition with age: fat mass increases,
fat free mass and muscle mass decrease cell mass shrinks
during inadequate intake or depletion
80

Age 25 Age 70
70

Fat 14% Fat 14%

60

50

40
Water 61% Water 61%

30

20

10 Cell solids 19% Cell solids 19%

Bone mineral 6% Bone mineral 6%
Kg
 Body composition measurement
• The Two
FM FFM= lean mass compartment model
• The trhere
FM BCM ECM
compartment model
• The four
FM BCM ECW
B
O compartment model
N
E
 Body composition measurement
• BED-SIDE METHODS • RESEARCH METHODS
• Anthropometry • Underwater weighing/ Air
• Bioelectrical impedance Displacement Plethysmography
measurement • In vivo neutron activation analysis
(IVNAA)
• Total body potassium counting
(40K)
• Isotopedilution
• Dual X-ray energy absorptiometery
(DEXA)
• Magnetic resonance tomography
(MRT)
BED SIDE METHODS: Anthropometry
 Anthropometry : mid upper arm
circumference and triceps skinfold

Pars pro toto methods

 Anthropometry : mid upper arm
circumference and triceps skinfold

Pars pro toto methods

 Body fat distribution
• People store body fat in two general
ways; either above or below the waist
• In both men and women, excess intra-
abdominal adipose tissue correlates
strongly with cardiovascular disease,
dyslipidemia, hypertension, stroke and
type 2 diabetes
• Documenting body fat distribution, in
conjunction with BMI, is important to
assess risk
Body fat distribution and waist
circumference
• Waist circumference
correlates strongly with
intra-abdominal adipose
tissue as assessed by CT
and MRI
• Upper body obesity
defined as a waist
circumference:
– ≥102 (94) cm for men
– ≥ 88 (80) cm for women
• Waist for hip ratio
- ≥ 1 for men
- ≥ 0,85for women
BIA : biophysical principles
BIA : calculation of compartments
 BIA : calculation of compartments
• Determination of total body water
• Calculation of fat free mass
• Estimation of body cell mass and fat mass
• In subject without significant fluid and
electrolyte abnormalities when using
appropriate equations (age,sex,ethnicity)
• BIA cannot be recommended in abnormal
hydration, in subjects at extremes of BMI
ranges (16-34 kg/m2) or in the elderly
ESPEN -GUIDELINES Bioelectrical impedance analysis. Review of principles & methods. Clin Nutr 2004: 23: 1226-1243. Utilisation in
clinical practice. Clin Nutr 2004: 23: 1430-1453
BIA : clinical relevance of phase angle
• Correlates with
nutritional status
• Correlates with
muscle mass and
function
• Correlates with
disease severity
•  Prognostic
impact!
BIA : clinical relevance of phase angle
• Correlates with nutritional status
• Correlates with muscle mass and
function
• Correlates with disease severity
•  Prognostic impact!
Bioelectrical vector analysis (BIVA)
 Bioelectrical vector analysis
• Evaluation of hydration status and cell mass
and integrity
• Comparison with reference populations
• No equation-inherent errors
• No weight needed
 Underwater weighing
Air displacement plethysmography
Dual energy X-ray absorptiometry
(DEXA)
Assessment of:
• Fat mass,
• Fat free mass (appendicular
lean mass  sarcopenia)
• Bone
• Disadvantages:
• State of hydration may
affect results
• Radiation exposure : 10 mSi
(transatlantic flight: 100
mSi)
 MRI OR CT Scan
• Assessment of (regional):
• Fat (and fat distribution!), fat free mass and
regional muscle mass
Invivo neutron activation analysis
(IVNAA)
Assessment of:
nitrogen as
indicator of
whole body
protein
Isotope dilution
 Summary
Methods for measuring:
Fat mass
• Subcutaneous skin folds measurements: pars
pro toto
• Fat distribution: waist circumference, waist-
to-hip ratio
• DEXA
• MRI, CT Scan
• Underwater weighing
• Air displacement plethysmography
 Summary
Methods for measuring:
• Body cell mass or whole body protein
• BIA
• Total body potassium counting
• In vivo neutron activation analysis
• Bone mass
• DEXA
• In vivo neutron activation analysis
Components of energy expenditure –
adult person-
Energy Expenditure
Principle of Indirect Calorimetry
Indirect Calorimetry
 Indirect Calorimetry
• Energy expenditure can be calculated both
from VO2 and VCO2
• Calculation from VO2 and VCO2
• EE = 3.94 VO2 + 1.11 VCO2
 Indirect calorimetry
• Energy expenditure can be calculated both from
VO2 and VCO2
• Calculation from VO2 and VCO2
• EE = 3.94 VO2 + 1.11 VCO2
RQ= VCO2 /VO2
• Calculation from VO2
• EE = 3.94 VO2 + 1.11 RQ VO2
• EE = VO2 (3.94 +1.11 RQ) – Moderately
dependent on RQ
 Indirect calorimetry
• Energy expenditure can be calculated both from VO2 and
VCO2
• Calculation from VO2 and VCO2
• EE = 3.94 VO2 + 1.11 VCO2
RQ= VCO2 /VO2
• Calculation from VO2
• EE = 3.94 VO2 + 1.11 RQ VO2
• EE = VO2 (3.94 +1.11 RQ) – Moderately dependent on RQ
• Calculation from VcO2
• EE = (3.94 VCO2/RQ) + 1.11 VCO2
• EE = VCO2 (3.94/RQ +1.11)– Highly dependent on RQ
Relationship between heart rate and
energy expenditure
Postprandial State
Adaptation to fasting (7 days)
Adaptation to fasting
Stress Reaction
Negative energy balance
–catabolic reaction-
 Malnutrition
Lack of
substrate

Impaired wound
healing
Wound dehiscence
 Negative energy balance
• Adaptation
 Negative energy balance
Adaptation Inflammation

Healing problem

Muscle wasting
 Energy reserves are clinically
important

Obese diabetic patient with sternal wound

dehiscence wound healing and weight reduction
Measurement of food energy content
Bom calorimetry
Measurement of heat produced during burning the
food items

The heat released from the burned food

 Metabolizable energy content in food
Carbohydrates : 3,75-4 kcal/g
Lipids : 9 kcal/g
Proteins : 4 kcal/g (dependent on amino
acid composition)

Particularly in the case of proteins there is

difference between bomb calorimetry and
metabolizable energy (due to urea production)
 Positive energy balance

• Consequences are dependent on functional status

Muscle gain is dependent in function

Short, KR, et al. AM J Physiol 2004

 Positive Energy Balance
• Glycogen stores repletion
• Lipid deposition
• Growth
• Wound healing
• Muscle gain – only in the case of training

Chronic overfeeding and low activity leads to a

development of obseity
 Energy intake and expenditure during
nutrition intervention
Condition Energy balance
Malnourished or depleted patient early phase EI < EE
Obese stable patient EI < EE
Stable adult patient EI = EE
Critical illness (ICU) EI = EE
Malnourished or depleted patient later recovery phase EI > EE
neonate EI >> EE
Growing child EI > EE
Convalescence after critical or acute illness EI > EE
Recovery after surgery EI > EE
 Energy intake and expenditure during
nutrition intervention
Condition Energy balance
Malnourished or depleted patient early phase EI < EE
Obese stable patient EI < EE
Stable adult patient EI = EE
Critical illness (ICU) EI = EE
Malnourished or depleted patient later recovery phase EI > EE
neonate EI >> EE
Growing child EI > EE
Convalescence after critical or acute illness EI > EE
Recovery after surgery EI > EE
Usually watching the
patients and common
sense is more
important than
expensive methods

Frequently, common
sense is not common
 Case Scenario 1
A 69 years old woman
Cholangiocarcinoma stage IV
• Carcinomatosis peritonei, lung
metastasis
• Plan: Palliative chemotherapy
• Loss of appetite, early satiety,
fatigue, dysgeusia, constipation
• Bed-bound for 50% of daytime
• Able to eat less than half of usual
dieet for months
• Usual BW 60kg (-6 months ago)
• Actual BW 45.8 kg
• Ht 154 cm (BMI 7)
 Methods to assess body composition
• Anthropometry
• Under-water weighing
• DEXA
• Bioelectrical impedance analysis (BIA)
• ?
Case Scenario 1
 Micronutrient deficiency
protein-energy malnutrition (PEM)
Classification of PEM Body mass index (kg/m2)

Normal ≥ 18.5

Mild 17.0-18.4

Moderate 16.0-16.9

Severe <16.0
Cut-off point for reduced muscle mass
Examples of recommended thresholds for reduced muscle mass
Males Females
Appendicular skeletal muscle index (ASMI, < 7.26 < 5.25
kg/m2)

ASMI, kg/m2 <7 <6

ASMI, kg/m2
DXA <7 < 5.4
BIA <7 < 5.7
Fat free mass index (FFMI, kg/m2) < 17 < 15

Appendicular lean mass (ALM, kg) < 21.4 < 14.1

Appendicular lean mass adjusted for BMI = < 0.725 < 0.591
ALM/BMI
Cut-off point for reduced muscle mass
• Examples of recommended threshold for reduced muscle mass
Males Females
Appendicular skeletal muscle index (ASMI, < 7.26 < 5.25
kg/m2)

ASMI, kg/m2 <7 <6

ASMI, kg/m2
DXA <7 < 5.4
BIA <7 < 5.7
Fat free mass index (FFMI, kg/m2) < 17 < 15
Appendicular lean mass (ALM, kg) < 21.4 < 14.1
Appendicular lean mass adjusted for BMI = < 0.725 < 0.591
ALM/BMI

FFMI (kg/m2) = 32.4/(1.54)2. = 13.66 > > low muscle mass

 How much you can eat?

Standar meal:
• 2000 kcal, protein 60 g, CHO 290 g, fat 70 g
 How much you can eat?

Standar meal
• 2000 kcal, protein 60 g, CHO 290 g, fat 70 g

A half of standard meal will be:

• 1000 kcal, protein 30 g, CHO 145 g, fat 35 g
How to calculate energy expenditure?
 Calculation of energy expenditure
Harris-Benedict equation:
• REE for female = 9.6 (Wt) + 1.8 (Ht) – 4.7 (age) + 655
= 9.6 (45.8) + 1.8 (154) – 4.7 (69) +
655
= 1048 kcal/day
Activity factor: 1.2 (low activity, cofined to bed)
Stress factor: 1.2 (malignancy)
Total Energy expenditure = 1.2 x 1.2 x 1048 = 1508.5
kcal/day
 Calculation of energy expenditure
• Energy balance = Energy intake – TEE
= 1000 – 1508.5
= - 508.5 kcal/day
How Calculate Protein Balance?
 Calculation of protein balance
• Given 24 h urine urea nitrogen of this patient
is 6,7 g
 Calculation of protein balance
• Given 24 h urine urea nitrogen of this patient
is 6.7 g
Marker of preotein g/day interpretation
breakdown

24 urine urea nitrogen 5-10 Normal fed state or

mild catabolism

10-15 Moderate catabolism

> 15 Severe catabolism

 Calculation of protein balance
• Given 24 h urine urea nitrogen of this patient is 6.7 g
• Total nitrogen loss = urinary nitrogen loss + non
urinary nitrogen loss
= 6.7 + 2
= 8.7 g/day
1 g nitrogen is 6.25 g protein
Therefore, protein loss = 8.7 x 6.25 = 54.4 g/day
 Consensus findings
• Definition and diagnosis
• Cancer cachexia is defined as a multifactorial
syndrome characterized by an ongoing loss of
skeletal muscle mass (with or without loss of fat
mass) that cannot be fully reversed by conventional
nutritional support and leads to progressive
functional impairment. The pathophysiology is
characterized by a negative protein and energy
balance driven by a variable combination of reduced
food intake and abnormal metabolism. Consensus
statements for diagnosis are presented in the panel.
Pre-cachexia Cachexia Death

Normal weight loss > 5% or BMI < 20
and weight loss > 2% or
sarcopenia and weight loss >
weight loss > 5% 2%
Anorexia and Often reduced food
metabolic intake/systemic inflammation
change
Refractory Cachexia
Variable degree of cachexia
Cancer disease both
procatabolic and not
responsive to anticancer
treatment
Low performance score < 3
month expected survival

Panel diagnosis of cancer cachexia

• Weight loss > 5% over past 6 month (in absence
of simple starvation) or
• BMI < 20 and any degree of weight loss > 2 % or
• Appendicular skeletal muscle index consistent
with sarcopenia (males < 7-26, females <5-45
kg/m2 and any degree of weight loss > 2%
Muscle wasting and survival following
pre-operative chemoradiotherapy for
locally advanced rectal carcinoma
Result
• A wide distribution in change of body
composition was observed
• Loss skeletal muscle mass during
chemoradiotherapy was independently
associated with disease-free survival (HR
0.971; 95% CI; 0.946-0.996; p = 0.025)
• And distant metastasis-free survival (HR 0.942;
95% CI; 0.898-0.988; p = 0.013)
 Muscle wasting and survival following
pre-operative chemoradiotherapy for
locally advanced rectal carcinoma
Result
• A wide distribution in change of body composition was
observed
• Loss skeletal muscle mass during chemoradiotherapy was
independently associated with disease-free survival (HR
0.971; 95% CI; 0.946-0.996; p = 0.025)
• And distant metastasis-free survival (HR 0.942; 95% CI;
0.898-0.988; p = 0.013)
Conclusions
• Loss of skeletal muscle mass during NACRT in rectal cancer
is an independent prognostic factor for disease-free
survival and distant metastasis-free survival following
curative intent resection
• yet….

1900 2000

Undernutrition Undernutrition
&
overweight
Obesity
 n= 450 undernourished

PG-SGA

29%
Overweight/obese

BMI ≥ 25 kg/m2

63%
 Prevalence and clinical implications of
sacrcopenic oesity in patients with solid tumours
of the respiratory and gastrointestinal tract: a
population-based study
CT Scans
Sarcopenicoesity (15%)
• “independent predictor
of survival irrespective
of age, sex, and
functional status”
Bioelectrical Impedance Analysis

Body
Composition
Phase Angle

• Cell membrane integrity

• Cellularity
• Cell function
Disease activity/ cell function
• Spontaneous PA
(time spent sitting /
lying, time standing,
time walking and
number of steps
day) of cancer
patients at different
stages of disease
(n=75) and healthy
volunteer (n=20)
Multimodal supportive care
Oncology
outcome
measures
hierarchy
Pre-cachexia Cachexia Death

Normal weight loss > 5% or BMI < 20
and weight loss > 2% or
sarcopenia and weight loss >
weight loss > 5% 2%
Anorexia and Often reduced food
metabolic intake/systemic inflammation
change
Refractory Cachexia
Variable degree of cachexia
Cancer disease both
procatabolic and not
responsive to anticancer
treatment
Low performance score < 3
month expected survival

Panel diagnosis of cancer cachexia

• Weight loss > 5% over past 6 month (in absence
of simple starvation) or
• BMI < 20 and any degree of weight loss > 2 % or
• Appendicular skeletal muscle index consistent
with sarcopenia (males < 7-26, females <5-45
kg/m2 and any degree of weight loss > 2%
Early intervention: pre or early
cachexia
 The obesity paradox in cancer
• Median survival of 175 patients according to BMI of body composition
classification
The Obesity paradox in cancer (2)
 Nutrition
• Main goal is promote energy balance and optimise
protein intake
• Usual deficits are approx. 300 – 400 kcal/d and 0,5g
Protein/Kg/d
• Best approach is with normal food
• Can use convesional oral supplement but recent meta-
analysis did not show benefit after correction for
heterogeneity*
• EPA enrich supplements used during scemotherapy
result in increase energy and protein intake, increase
LBM (1,6kg) and improves appetite and fatigue**
Oral Nutritional Interventions in Malnourished Patients
with cancer: a systematic review and Meta-analysis
 Why treat cachexia during
chemotherapy?
….a window of opportunity?
• Commencement of chemotherapy is a portal
of entry to supportive oncology
• Poor nutritional status associated with
adverse oncological outcomes
• Chemotherapy can induce further loss of
muscle mass and this may limit treatment
• Respone to chemoteraphy may decrease
tumor-related catabolic drivers and enhance
the efficacy of cachexia intevention
 Anti-inflammatory treatment
• NSAIDs are generally well tolerated. Recent
systemic review suggested possible
improvement in weight, performance status
and QoL but heterogeneity preclude meta
analysis
• EPA probably best administered during
chemotherapy
 Exercise
• Improved lower and upper limb sttregth (20%)
• Increase lean body mass (1 Kg)
• Improve HRQoL including physical functioning,
role functioning, social functioning, and
fatigue
 Exercise regiment
• Home-based
• Combine aerobic (x2/w) and functional
resistance (x3/w) exercise
• Delivered by initial interview with trained HP
supported by standardized booklet
• Supervision dependent on centre
 Compliance
• Drug treatment…………………………………………70
– 80% compliance
• Nutritional supplement……………………………… 0
– 70% compliance
• Aerobic exercise…………………………………………. 0
– 75% compliance
• Resistance exercise……………………………………… 0
– 50% compliance
 Interdisciplinary
rehabilitation (10 – 12w)
in advanced cancer (n=188)
 Summary
• No simple solution
• Cachexia therapy should be integrated in overall
oncology management
• Early intervention
• Professional and nurse need adequate knowledge
on nutrition and exercise
• Assesment should be linked to treatment
• Goals shpuld be realistic
• Multimodal care pathway are self eviden but still
to be evidence based
 Current limitations of anti-cancer
strategies
• Too much focus on tumor cell, minimal on the human body
attached to them (i.e., up to 40% of cancer patients receive
chemotherapy in the last month of life, but ASCOquality
standards recommend <10%)
• Excessive toxicity
• High cost = financial toxicity of cancer (i.e., sipuleucel-T
yields 4 month survival advantage in advanced prostate
cancer at 93,000 USD per course of treatment)
• Questionable cost-effectiveness (i.e., new drugs approved
after demonstration of survival extension by 15 days)
• Study design (i.e., survival as the ultimate outcome)
• Statistical analysis or “the seductive certainty of
significance”
Nutritional intervention with fish oil provides a
benefit over standard of care for weight and
skeletal muscle mass in patients with nonsmall
cell lung cancer receiving chemotherapy

2.5 g/day of
EPA + DHA
 ORIGINAL ARTICLE
Oral nuttitional supplements containing n-3
polyunsaturated fatty acids affects quality of life and
functional status in lung cancer patients during
multimodality treatment: an RCT
Normal protein anabolic respone to
hyperaminoacidemia in insulin-
resistant patients with lung cancer
cachexia
Spesific nutrient and tumor growth
• Do nutrient stimulate the growth of cancer
cells?
• Does nutritional support in cancer patients
accelerate tumor growth in a clinically
relevant manner?
• Do malnourished cancer patients live longer
than wellnourished cancer patients?
Brain tumor initiating cell adapt to
restricted nutrition through
preferential glucose uptake
Caloric restriction and differential
stress respone in oncology
Major problem = malnutrition
Pharmalogic topics
 Appetite stimulation
• Corticosteroid
• Progestins
• Cannabinoids
• Ghrelin
• Cyproheptadine
• Brached-chain amino acids
• Herbal medicine,bitter
Corticosteroid
 Progestins: Effect on WEIGHT in
patients with cancer cachexia (11 RCT)
 Progrestins
Cochrane metaanalysis 2005
31 RCT (n=4123 MA) vs PLAC: appetite +, weight +

Metaanalysis 2008
30 RCT (n=4430) MA vs PLAC: appetite +, weight +,
survival Ø, QoL Ø

MA: Megestrol acetate

PLAC: placebo
 Progestins
Megestrolacetate 160-1600 mg
Medroxyprogesterone acetate 300-1200 mg

Stimulation of appetite
Increase in body weight, but no increase in LBM
Improve QoL

Side effects: Thromboembolism (5%)

Impotence
Vaginal spotting or
bleeding
Hypertension,
Hyperglyvemia
Edema
Adrenal insuffiviency
 Cannabinoids
• Marijuana stimulates appetite (mainly
smoking)
– Marijuana extract
– Delta-9-tetrahydrocannabinol = THC/ dronabiol
• Stimulation of appetite with 5 – 20 mg
• Effect on mood, nausea, pain
• Use regulated by narcotics law
– Side-effect: dizziness, slurred speech
Dronabinol (D) vs megastrolacetate (M)
vs combination (C)
in patients with cancer cachexia (4 wk)
 Cannabinoids
• RCT: n= 164 cancer cachexia, 6 weeks:
Cannabis estract (5 mg THC)
Vs THC (5 mg)
Vs placebo:
App φ, QoLφ
 Cannabinoids
• RCT: n=21 cancer patients with sesory
alteration, 18 days:

Dronabinol (5 mg THC)
Vs placebo:

Taste +, appetite +
Energy intake +, protein intake +
Ghrelin and Analogues
Ghrelin and Analogues
Anamorelin: Romana trials
Exercise as anabolic signal!
 Anti-inlamatory agents
• Corticostreroids
• Progestagens
• Cannabinoid
• Non-steroidal anti-inflammatory drugs (NSAID)
• N-3 fatty acids
• Anti-cytokines
• Melatonin
• Antioxidants
NSAID
The Refeeding Syndrome – prevention
• Identify patients at risk
• Correct and monitor phosphorous / K, Na, Cl,
Mg
• Nutritional support: “start slow (<50% of
calculated energy) and advance slow”
• Supplement vitamins (B1, B6, B12)
 NSAID in cancer cachexia
• Systematic review: 13 students (6 controlled
studies)
– Studies are small
– Suboptimal design
– Many studies without comparator
– In 11/13: stabilization or improvement of WT or
LBM
• NSAIDS may improve weight in cancer patients
• Evidence is too frail to recommend
 N-3 fatty acids
• Cochrane systematic review
• On 5 RCT: insufficient data

but: poor compliance

only short trials
• Systematic review Colomer et al.
• On 17 clinical trials: >1.5g/d fish oil
 appetite +, weight + QoL
+
but: not based on RCTs
Ons with fish oil in NSCLC
Ruxolitinib (janus kinase ½ inhibitor)
Effect on body weight in MPN
Ruxolitinib (JAK ½-inhibitor)
Effect on cytokines
 Anticatabolic agents
• Insulin and insulin sensitivity modulators
• Growth hormone, secretagogues, IGF-1
• Anabolic androgenic steroids and SARMs
• Proteasome inhibitors
• β-receptor modulators
• β-hydroxy β-methylbutyrate and amino acids
• Adenosine triphosphate (ATP)
• Anti-myostatin
• Selumetinib (tyrosine kinase inhibitor)
Anabolic androgenic steroid / SARMs
 Key Messages I
• To improve appetite, relieve psychological
distress and chronic pain
• Optimize gastrointestinal function and relieve
nausea
• All anticachectic agents should be
accompanied by exercise training
 What is Enteral Nutrition ?
• Nutritional support that implies the use of
“dietary foods for special medical purposes”
(European legal regulation of the commission
directive 1999/21/EC and 2013/609/EC
• Feeding via:
– Nasogsatric / enteral tube
– Percutaneous (gastric or jejunal) tube
– Oral nutritional supplements
 General indications of EN
• Anticipated inadequate oral food intake for
more than 7 days
• Present or immine malnutrition
 What is severe nutritional risk?
• Subjective Global Assessment (SGA) Grade C or
NRS 2002 >= 3
(or scoring high in other screening tools)
• BMI < 18,5 kg/m2 *
• Weight loss > 10% within 6 months
• Serum albumin <30 g/l **
*<20 kg/m2 in geriatric patients
** (with no evidence of hepatic or renal
dysfunction)
Clinical signs of malnutrition
Loss of:
• Masticatory muscles
• Subcutaneous fat
• Small hand muscles
 Specific indications of EN: advanced
incurable disease
Indication / Recommendation Grade

Provide enteral nutrition in order to C

minimize weight loss as long as the
patient consents and the dying phase
has not started
When the end of life is very close B
most patients only require minimal
amounts of food and little water to
reduce thirst and burger
 Contraindications of EN I
• Gastrointestinal:
• Intestinal obstruction/ileus
• Intestinal ischemia
• Severe peritonisis
• Nausea/vomiting
• malabsprption
 Contraindications of EN II
Metabolic:
• Diabetic ketoacidosis
• Diabetic coma
• Hepatic coma

Circulatory:
• Severe acute cardiac insufficiency
• Shock of any origin
 Conclusion I
• The goal of EN is prevention/treatment of
malnutrition to improve outcome
• Main indications of EN are:
– Inadequate oral intake for >7 days
– Present / imminent malnutrition
• Main contraindications of EN are:
– Severe dysfunction of the GI tract
– Metabolic / circulatory instability
 Complications of EN
• Gastrointestinal
• Aspiration
• Metabolic
• Tube related
 Complications of EN
Problem Frequency
Compliance 10-40%
Tube misplacement / Up to 50%
occlusion
Nausea / vomiting 10-15%
Diarrhoea 25-50%
Infections Rare
Metabolic complications ?
Aspiration ?
 Reasons for diarrhea during EN
• Bolus application
• High delivery rate
• High osmolality
• Bacterial contamination of the formula diet
• Formula diet is too cold
• Gastrointestinal infections
• malabsorption
 Work up of diarrhoea during EN
• Switch to continuous application
• Decrease the delivery rate (temporarily)
• Avoid bacterial contamination ( change drip
line daily, deliver formulae within 6-10 hours)
• Review prescriptions (prokinetics, antibiotics,
antacids, atropine etc)
• Exclude GI infections (stool culture,
Clostridium Difficile)
• In malabsorption change to low molecular
diets
• If Diarrhoea persists change to a fibre-free EN
formula
Reasons for impaired gastric emptying
during EN
• Pre-existing diseases:
– Diabetes mellitus
– Vagotomy
– Systemic scleroderma
– Myopathies
• Acute disease related:
– Pain and stress
– Pancreatitis
– Spinal cord injury
– Extensive trauma, abdominal surgery, burn injuries
• Medication :
– Opioids
– anticholinergics
Work up of nausea/vomiting during EN

• In case of cancer/antineoplastic therapy:

initiate adequate antiemetic therapy
• Exclude bowel obstruction
• review patients prescriptions regarding
nausea-inducing drugs
• If delayed gastric emptying is suspected:
reduce delivery rate, try prokinetic drugs
 Risk factors for aspiration during EN
• Neurological impairment
• Diminished gag reflexes
• Supine position
• Incompetenst lower esophageal sphincter
• Impaired gastric emptying
• High GI reflux
Prevention of aspiration during EN
• Prefer a semi-recumbent position (30-45o)
• Prefer nasojejunal tube feeding
• In the presence of clinical changes measure
reflux, adjust delivery rate

Pathologic reflux: >500 ml

Measures : adjustment/interruption of infusion
 Metabolic complications of EN
• Disturbances of the hydration status
(overhydration/dehydration)
• Hyponatremia/hypernatremia
• Hypo/hyperglycemia
• Refeeding syndrome
 The Refeeding Syndrome
• First described in
Far East prisoners of
war after the
second world war
• Starting to eat again
after a period of
prolonged
starvation seemed
to precipitate heart
failure
 The refeeding syndrome
Who is at risk?
• Severe malnutrition (BMI <18.5)
• Unintentional weight loss
>=10% within 3-6 months
• Minimum or no food intake in
the last 5-10 days
• Chronic alcohol abuse
• Cancer
• Patients with AIDS
• Malabsorption
• Gastric bypass
• Severe weght loss in obesity

 micronutrient
deficiency
Risk factors for refeeding syndrome
• The patient has one or more of the following O :
– BMI <16
– Unintended weight loss >15% for the pat 3-6 months
– Minimal or no food intake for 10 days
– Low levels of phosphate, potassium and magnesium
before starting nutritional support
• Or the patient has one or more of the following
– BMI <18.5
– Unintended weight loss >10% for the pat 3-6 months
– Minimal or no food intake for >5 days
– Histroy of alcohol or drug abuse
The Refeeding Syndrome - findings
• Hypophosphataemia
• Hypokalaemia
• Hypomagnesaemia
• Thiamine (and other vitamin) deficiency
• Fluid retention

Neuromuscular dysfunction
Hypoventilation
Metabolic acidosis
Cardiac arrhytmia
Wernicke’s encephalopathy
 Monitoring of Enteral Nutrition
Feed administration Daily
Fluid Balance Daily
Laboratory tests
•Na, K, Glucose Initially daily
•P, Ca, Urea, Creatinin, Initially twice / week
ALT, Blood count
Nutritional status Weekly / every 2nd week
•Weight, albumin
•Bioimpedance analysis
Functional status weekly
•Hand grip strength
HOSPITAL FOOD AND ORAL
NUTRITIONAL SUPPLEMENTS (ONS)
 Council of Europe Committee of
Ministers

• Ordinary food by the oral route should be the first

choice to correct or prevent undernutrition in
patients
• Sip feedings should not be used as a substitute for
the adequate provision of ordinary food, and
should only be used whre there are clinical
indications.
• Artificial nutritional support should only be
started when use of ordinary food fails or is
inappropriate
Types of hospitalized patients
Hospitalized patients

Nutritionally well

Nutritionally Vulnerable
 Nutritionally vulnerable
High risk of malnutrition due to:
• An acute or chronic illness affecting their appetite
and their nutritional intake
• Cognitive decline or limited ability to
communicate with the medical staff
• Increased or altered nutritional requirements due
to the underlying medical condition (e.g. surgery,
burns, trauma, diabetes, chronic kidney disease)
• Disturbed swallowing or chewing ability, poor
dentition or dysphagic patients
 Characteristics of hospital diets
• A minimum of 300 kcal per main meal and 500 kcal for an
energy dense meal and at least 18 g protein with each meal
• A minimum of two courses at the midday and evening
meals
• A vegetarian choice on each eating occasion
• A choice of portion sizes for all meals
• A variety of snacks, providing a minimum of 150 kcal, at
least twice a day. Fruits should always be a choice
• Standard recipes should be used
• An “out of hours” meal must be available for all patients
who missed their meal. The “out of hours meal should
provide at least 300 kcal and 18 g of protein”
Provision of nutrients for the
hospitalised adults
 Common thypes of hospital diets
• The standard diet
• Diets with altered nutritent
content
– Low residue, clear liquid
diets, full liquid ciets,
soft diet
• Diets with modified texture
– Blenderised, pureed diets
• Protein- and/or energy-
enriched dietsenergy
restricted diets
diets for specific medical
conditions
• Diets with increased meal
frequency
– e.g. for patients with
gastrectomy
• Elimination diets
– lactose-free, gluten-free,
diets free from specific
allergens, etc
• Diets for metabolic
disorders
– e.g. diet for phenylketonuria
 Food intake in 1707 hospitalised
patients: a prospective hospital survey

Protein intake
as % of
proteins
needs
Monitoring of nutritional intake
 Monitoring of nutritional intake
• Supervision of tray collection
38% of food from the kitchen was returned as waste
 Ensuring adequate nutritional intake
• Protected Mealtimes Policy (HCA)
“3 mealtimes free from avoidable and
unnecessary interruptions”
 Acceptance of hospital diets and
nutritional status among inpatients
with cancer
 Acceptance of hospital diets and
nutritional status among inpatients with
cancer
Malnutrition in Hospital
Meals consumption in the hospital and
probability of death
From food to parenteral nutrition
• All admissions: hospital
food. Ward nurses and
medical teams screen
patients
• Some patients require
oral nutritional
supplements: may
require assessment by
dietitians
• Enteral feeds: dietitians
• Nutrition support team
• Parenteral Nutrition
 Food fortification
• Fortification of food with
– Energy CHO Fat and
CHO
– Protein Fat
• Fat
• Butter/buttermilk
• Milk
• Cheese
• Sugar
• Supplements of CHO/
protein/fat
 Food Fortification
Pros Cons
• Cheap • May change tase. Sensory
• Does not alter food volume properties
• Easy in preparation • Not easy to provide disease
• Extra energy specific nutrients
• Needs action from
patient/caregiver
 Monitoring and improving intake
Fortification
Advantages Disadvantages
• Simpole • Cumbersome
• Inexpensive • Sensoreic limitation!
• Single macronutriens
can be added
• Nutritional intake is
enhanced
Oral nutritional supplements and food
fortification
If the patient is at risk of malnutrition or
malnurished

and

Has a functional GI and can swallow safely

Until he/she can cover her/his needs by

nowmal food
Oral nutritional supplements
 Disease spesific formulas
• Liver disease
– ↑ Kcal, ↓ Na
– ↑ Kcal : N
– ↑ BCCA ↓ AAA
– Insoluble dietary fibre
– ↓ Cu, Fe kai Mn
• Renal disease
– Modified protein content
– ↓ Na, K, P
– ↑ Kcal
• Respiratory Failure
– ↑ fat/ ↓ CHO
– ↑ Kcal
– Dietary fibre
• Cancer cachexia
– ↑ prot and Zn
– ↓ Fat
– ↑ soluble dietary fibre
– Ω-3 fatty aciids (EPA/DHA)
– Antioxidants (Vit A, C, E, Se)
• Impaired glucose tolerance
(diabetes mellitus)
– ↓ CHO
– Fibre
– ↑ MUFA
 Encouraging appropriate, evidence-
based use of oral nutrition supplements
Recommendations for use of ONS in clinical practice
Consider ONS as part of the care plan for the treatment of
malnutrition
• Liquid ONS can be use if improvements in energy, protein
and micronutrient intake are require.
– Liquids supplements tend not to suppress appetite or voluntary
food intake and in some patient groups may stimulate food
intake
– A supplement containing a mix of macronutrients and
micronutrients is important
– Supplements with higher energy density may improve
compliance and nutrition intake
• For patients requiring longer term ONS, it is likely that a
variety of types of ONS and concomitant use of other
dietary strategies would be beneficial to maintain
improvement in nutritional intake
 Encouraging appropriate, evidence-
based use of oral nutrition supplements
Recommendations for use of ONS in clinical practice
• Consider ONS as part of the care for the treatment of
malnutrition
– Liquid ONS can be used to attenuate weight loss in the acutely ill
patient or aid weight gain in chronically ill patient.
Improvements in weight (>2 kg), esp.in the underweight, are
associated with improvements in nutritional intake
– High-protein ONS may be beneficial in preventing pressure ulcer
in high risk groups and in improving clinical outcome in
fractured neck of femur patients
– Liquid, ready-made, multi-nutrient supplements (-200-600 kcal
daily) can improve clinical outcome, reducing mortality and
complicatins, and heatlh care use
• Other oral nutritional support strategies include food
snacks, food fortification and dietary counseling
 Oral and sip feeding
Conclusions
• Malnutrition is a common problem in hospitalised patients
• Oral feeding, with either normal food or special and/or
fortified diets, is always the first choice to prevent or treat
undernutrition in patients
• Measures to enhance palatability, good quality and
appearance of hospital food should be taken
• Oral nutritional intake should be carefully monitored,
encouraged and supplemented either by energy dense food
choices or with food fortification, espicially in malnourished
patients
• Oral nutritional supplements (ONS) should be used for
patients who fail to cover their nutritional needs by
hospital food or food fortification
Phase Angle of Bioelectrical Impedance Analysis
as Prognostic factor in palliative care patients at
the National cancer institute in Mexico
• The aim of this study was to associate PA and survival
in palliative patients of the National Cancer Institute of
Mexico. We included 452 patients (women, 56,4%); the
average PA was 4.00. the most frequent disease was
gastric cancer (39.2%). Mean body mass index (BMI)
was 22.84. the average survival of patients with PA < 40
was 86 days, while in the group with PA > 40, it was 163
days (P>0.0001). PA showed significant possitive
correlation with survival time and BMI. Our result
corroborate the reliability of PA in Mexican population,
as an indicator of survival in palliative care patients
compared to the reported literature in other countries.
 Nutritional and fuctional factors as
prognostic of surgical cancer patients
• 60 oncology patients admitted for elective
surgery. Malnutrition was 28.3%, sarcopenia was
18.6% SPA was significantly lower among those
who had severe postoperative complications or
long hospital stays, while Handrip strenght and
sarcopenia showed no relationship with these
outcome. Malnutrition was also related to
postoperative outcomes.
• Conclusion: SPA can be considered a prognostic
factor in postoperative morbimortality for
patients with cancer.
 Excess baggage: sarcopenia, obesity,
and cancer outcomes
• Not surprisingly, the same factors that
affect sarcopenia also support the
development of obesity. The result is an
insidious vicious cycle in which people
become more obese and yet weaker, do
even less physical activity. Develop insulin
resistance, which each part of the cycle
reinforcing the next. Fat-mass gain and
muscle mass loss together leads to
sarcopenic obesity. Which leads to
accelerated disability, increased
inflammatory cytokine production, and
greater frailty. All this is only accelerated
by the presence of chronic illness such as
osteoarthritis, heart failure, diabetes or
cancer.
 Conclusion
• Cachexia is a multi-faceted syndrome, which is
characterized by muscle loss
• The pathogenesis is complex and related to
inflammation-mediated alterations of host
metabolism
• Early diagnosis is imperative to effectively treat
cachexia
• CT scan is the gold standard for assessing
muscularity, but new tools are being developed.
MULTIMODAL THERAPY FOR
CANCER CACHEXIA
 Cancer is collective name for more
than ane hundred distinct disease
• Global incidence: 12.6 million/yr (lung mmost
common)
• Global mortality: 7.5 million/yr
11.5 million/yr
Cachexia
Definition and classification of cancer
cachexia: an international consensus
 Life (breathing)

Reserve/ Clinical importance Self

recovery of muscle expression

Work/economic