The Adelaide & Meath
Hospital
Incorporating the National
Children’s Hospital
Trinity College Dublin
Nutrition & Pancreatic cancer
Dealing with exocrine insufficiency and options for feeding
AUGIS 15th Annual Scientific Meeting, Belfast 2011
Sinead Duggan
siduggan@tcd.ie
Centre for Pancreatico-Biliary Diseases &
Trinity Centre for Health Sciences, AMNCH, Dublin
Financial support: Health Research Board Ireland
Presentation outline
Cachexia and severe
malnutrition in pancreatic
cancer
Dealing with exocrine
dysfunction in pancreatic
cancer
1. Cachexia and severe
malnutrition in
pancreatic cancer
Nutritional problems in pancreatic cancer
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Pain
Constipation
Obstruction
Indigestion
Malabsorption
Diabetes
Post-surgery
Anorexia
Tissue Wasting
Weight Loss
Loss of compensatory
increase in feeding
Cancer AnorexiaCachexia
Syndrome
Cachexia:
From Greek
kakos (“bad”)
hexis (“condition”)
Cachexia process is multifactorial and
incompletely understood
Uomo et al. JOP. J
Pancreas (Online) 2006;
7(2):157-162.
Differs from simple starvation
Incidence of Cancer Cachexia (Tinsdale 1999, Gibney 2005)
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
rea
c
n
Pa
s
Ga
ck
tal
us
e
c
g
/N
ha
Re
d
/
p
a
o
l
so
He
Co
Oe
ic
str
ng
Lu
o
Pr
te
st a
B
s
rea
t
Weight loss in cancer:
Does it matter?
The physical effects
Quality of life
Fitzsimmons et al (1999). Development
of a disease specific quality if life module
to supplement the EORTC core QOL
questionnaire, the QLC-C30 in patients
with pancreatic cancer, European Journal
of Cancer Care. 95:6
Cachexia
worsens
prognosis
Pancreatic cancer:
Resectable disease
Nutritional intervention in cancer
Pre-cachexia
Weight loss < 10%
Nutritional intervention works
Does it work?
Cachexia
Weight loss > 10%
Conventional nutritional
intervention may not work
Nutritional
intervention
Patients with gastric
/ colorectal cancer
Mean weight loss of
7.2% & 5.5% at
baseline
Individual support vs.
standard care
Statistically
significant at 12 and
24 months
Nutritional
intervention
Weight
QOL
SGA
Head and Neck Cancer (n=60)
Regular, intensive dietetic counselling by dietitian
+ ONS
or usual care (Nutrition booklet, no
individualisation)
2.6% & 3.6% weight loss at baseline
Management of cancer cachexia
Nutrition ineffective?
• 2 large randomised controlled trials of ONS in cachectic
cancer patients concluded that weight/ body composition,
QOL, survival, response rate fail to improve despite increases
in nutrient intake
• “The metabolic alterations that occur in these patients seem to prevent the
effective use of additional calories supplied, resulting in ongoing wasting”
• Options?
– Megace, corticosteroids, β2-adrenoceptor agonists, thalidomide,
melatonin, growth hormone, insulin, NSAIDs
– Eicosapentaenoic acid (EPA)
Barber MD. The pathophysiology and treatment of cancer cachexia.
Nutrition in clinical practice (2000) 17:203-209
Megace
Megestrol acetate for treatment of anorexia-cachexia syndrome
Berenstein G, Ortiz Z. (Cochrane Review)
+
• Used to improve
Megace better than placebo for appetite
and weight gain
appetite and gain weight
in cancer-related
cachexia
• Mechanism unknown
• 32 trials reviewed
• >5,000 patients
No dosing guidelines
Weight gain adipose tissue
No conclusion of Quality of life,
functional ability
EPA
• Role in membrane, receptor, enzyme function
• Precursors for prostanoid synthesis
• Helps to down-regulate the inflammatory response associated
with cancer-induced weight loss
• Focus of many recent trials
EPA studies
N=24 Advanced Pancreatic Ca
Weight losing (mean 19-21%)
No significant
changes in
weight / LBM
Energy expenditure and Physical activity
significantly increased in EPA group (but not in
control)
EPA
N=200 Pancreatic Ca; weight losing ~19-20%
Randomised to 2 cans per day of control or EPA; 8 weeks
Both groups demonstrated halting weight
loss/gain of Lean Body Mass
Compliance
issues
mean intake
1.4 cans
• Post-hoc analyses:
– Significant correlation between EPA intake and weight gain / lean body
mass gain
– Control group: no such correlation
Only patients who took
recommended 1.5-2 cans EPA
supplement per day gained
weight / LBM
Quality of Life:
Intake of EPA supplement
correlated positively with
QOL
Ryan et al,
Annals of
Surgery, vol
249, 2009
• PRCT: Examine effect of peri-operative EPA enriched EN vs
standard
• Inclusion: Adults with resectable oesophageal cancer
• 2.2g/ day of EPA vs nil (control)
• Both groups fed
55
Results: Body Composition Analysis
56
31
*
55
54
*
30
2952
52
51
50
Standard
9
*
8.5
8
7.5
7
EPA
Standard
50
26
25
Pre op Day -5
POD 21
*P<0.05
Pre op Day
28 -5
POD 21 51
27
53
EPA
Leg Muscle Mass
53
Trunk Fat Free Mass (Kg)
Whole Body Fat Free Mass (Kg)
54
ProSure
EPA
Control
Standard
Lean Body Composition Changes
EPA Enriched
0 kg
+0.2 kg
Standard EN
EPA resulted in anabolism
/ maintenance of muscle
mass in patients with
oesophageal cancer
0 kg
8%
0.2 kg (p=0.01)
1.4 kg (p=0.03)
0.3 kg (p=0.05)
“severe” wt loss
39%
Patient presenting with cancer
Nutritional Goals
- Preserve LBM
- Functional ability
- Physical activity
- Quality of life
Weight loss: less than 10%
Pre-Cachexia
Weight loss: more than 10%
Cachexia
Nutrition Options ?
Intensive nutrition input
+ONS
Regular follow-up
Specialised
nutrition
?Megace etc
EPA feed
Standard
Nutritional
Intervention?
2. Dealing with
exocrine dysfunction
in pancreatic cancer
Exocrine function
• Normal fat digestion
– Fat digestion begins in the mouth (very limited) and stomach
(10-30% of all lipid breakdown1)
– Most fat digestion by pancreatic lipase
– Approx 20,000-50,000 units of lipase are needed to digest a
typical meal
• 2 key hormones
– CCK – triggers the release of pancreatic enzymes from the
pancreas
– Secretin – stimulates bicarbonate secretion form the pancreas
to ↑ pH (lipase inactivated in acidic environment)
• With pancreatic damage- lingual and gastric lipases cannot
compensate 100% for loss of pancreatic function
1. Layer P et al. Lipase supplementation therapy: standards, alternatives and perspectives.
Pancreas. 2003;26(1):1-7
Impaired digestion in pancreatic cancer
• Cancer in the head of the pancreas may obstruct the
pancreatic duct, impairing secretion
• Surgery (e.g. Whipple) changes the mechanical and secretary
process
• Damage to the intestinal mucosa (radiation therapy, surgery),
may reduce CCK release
• Motility disturbances may affect secretory and motor
functions of the GI tract
Signs and symptoms of malabsorption
• Steatorrhoea (foul smelling, fatty stools)
• Oily stools, undigested food in stools
• Diarrhoea
•
•
•
•
•
Weight loss
Bloating/ flatulence
Abdominal pain/ cramping
Dehydration
Electrolyte disturbances
Diagnosing malabsorption
• Usually clinically evident
– But malabsorption may exist even in the absence of
overt steatorrhoea
– Patients may reduce intake to counteract symptoms
• Direct tests
– Collecting pancreatic secretions via duodenal intubation
• Indirect tests
– Cheaper and easier to administer
– Less sensitive and less specific
– 4 categories
Indirect tests
Faecal test
Breath tests
Urinary tests
Blood tests
Indirect tests (Source: Australasian treatment guidelines for the management of PEI)
Faecal tests
Breath tests
Urine tests
Blood tests
3-day faecal fat test
Triolein breath test
Bentiromide
Trypsinogen
Steatocrit
Fluoresceine
Dilaurate
Faecal Chymotrypsin
Faecal Elastase-1
Sudan III stain
Gold standard: 3-day fat
-Ingested lipids
test
liberate CO2
-100g fat for 3-5 days
following hydrolysis
-Weigh food
-Not fully validated
-keep dietary records
Do not differentiate
-Stools collected over 72- between pancreatic
96 hours
and non-pancreatic
causes
-Use non-absorbable
substrates that are
specifically cleaved by
pancreatic enzymes
-Urine collection over
time period
-Superseded by
simpler blood tests
-Trypsin exclusively
synthesised by the
pancreas and small
amts released into
blood as tripsinogen
-Validated in CF
% of exocrine
insufficient
subjects
Method of testing
exocrine insufficiency
Matsumoto & Traverso , 2006
68%
Kato et al , 1993
92 %
Faecal elastase
Secretin test
Ihse et al , 1977
87%
Duodenal tube, Lundh
Study details
(Thanks to Lorraine Watson, MSc. Project)
Pancreatic cancer subjects only
meal to measure lipase
conc.
Pancreatic cancer subjects & subjects other conditions
Sato et al , 1998
Ohuchida, 2007
Ohtsuka et al, 2001
Pancreatic cancer subjects post resection only
Kato et al, 1993
Pancreatic cancers & subjects with other conditions
post resection
Tran et al , 2008
Norback et al, 2007
Sato et al, 1998
Ohtsuka et al , 2001
46 %
66 %
26 %
BT-PABA
Chymotrypsin
Chymotrypsin
80 %
Secretin test
88% (76%
severe)
100% (92%
severe)
75 %
Faecal elastase
50%
Chymotrypsin
Faecal elastase
BT-PABA
Faecal Elastase-1
• Widely used
• Cheap, non-invasive, widely
available
• Pancreatic enzyme that is not
degraded during digestion and
may be measured in the stool
• Not affected by enzyme use
• Does not require timed stool
collection
• Does not require special diet
Sensitivity limited
in mild pancreatic
insufficiency
PERT
• Pancreatic enzyme replacement therapy – the oral
administration of manufactured digestive enzyme
preparations for use in exocrine insufficiency
No guidelines on specific
doses, or specific patients
types suitable
PERT in palliative
pancreatic cancer
• RCT, double-blind, 21 patients with unresectable pancreatic cancer
• 50,000 units Lipase with meals, 25,000 units with snacks for 8/52
• Both groups were counseled on dietary intake
PERT in post pancreatic surgery patient
• Matsumoto & Traverso, Journal of Gastrointestinal Surgery, 2006
• 182 patients over 4.3 years, proximal PD
• Faecal-Elastase-1 measured in 138 patients
– Pre-op (n=138), 3+1 mth (n=40), 12+2 mth (n=22), 24+3 mth (n=20)
• Study conclusions
– A third of patients pre-op will have exocrine insufficiency
– Elastase levels further depressed in the majority post-op
– After PD, PERT should be given to all patients with pancreatic
cancer, especially those with impending adjuvant therapy
Administering PERT
Supplement:
Alimentary
Pharmacology &
Therapeutics, 2010
-Lipase irreversibly
denatured by pH<4
-Enteric-coated
preparations developed
-Coating only dissolves
when pH is >5.5
Dose and administration
• Preparations are dosed by lipid content
• Min dose of 25,000-50,000 per meal to reduce steatorrhoea to
<15g/ day to compensate for pancreatic insufficiency1
• Dietary assessment vital – check diet regularly and move to
protein supplementation early2
• Dose should be gradually increased until symptoms are
controlled2
• Try a PPI or H2 blocker
1. Kelly & Layer. Human pancreatic exocrine response to nutrients in health and disease. Gut
2005; 54(Supp VI):vi1-28
2. Imrie et al, Expert commentary: how we do it. Aliment. Pharm and Ther 2010; 32 (suppl 1):
21-25
Side effects and interactions
• Typically dose-related
• Common side-effects
– Nausea, vomiting, constipation, diarrhoea,
abdominal distension
• Uncommon side effects
May result
from
underlying
disease
– Skin reactions
• Mouth and perianal irritation, intestinal
allergic reaction
• Fibrosing colonopathy
– Methacrylic Acid Copolymer
Larger doses
in small
infants
Older
preparations
Current
suggested
practice
Imrie et al,
2010:
based on Layer
& Keller, 2003
‘At every step in the
algorithm, dietary intake
should be completely
reassessed, and diet and
pancreatic enzyme dose
altered if necessary’
Dietary assessment
• Type of food eaten (fat content)
•
•
•
•
Meals, snacks, liquids, supplements
Method of cooking
Volume of food at each meal
Timing, frequency of meals
• When enzymes are being taken
• How much taken at each time
• How are enzymes taken (crushed, sprinkled, whole)
•
•
•
•
•
PPI/ H2 Blockers
Symptoms post-prandially; malabsorption, constipation
Weight, weight history, muscle mass
Monitoring of micronutrients, particularly fat soluble vitamins
Requirement for supplementation: ONS, micronutrients, MCT-fat
Individualised patient education vital so they can alter enzymes
with changing circumstances
Patient information booklet on the use of
pancreatic enzymes
Produced by the Nutrition Interest Group of the Pancreatic Society
of Great Britain and Ireland, in conjunction with Abbott Nutrition
The pancreatic Society
of Great Britain and Ireland
• Both a Dietitian group (NIG) and a Clinical Nurse Specialist
group within this society
• 4th Annual Nutrition Symposium runs in conjunction with the
main annual meeting
• Dublin 1-2nd December
• Focus on nutrition in acute pancreatitis, chronic pancreatitis
and pancreatic cancer
• www.pancsoc.org.uk
Thank you
siduggan@tcd.ie
Acknowledgments
Dr Aoife Ryan – SJH
Lorraine Watson