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The Adelaide & Meath Hospital Incorporating the National Children’s Hospital Trinity College Dublin
The Adelaide & Meath Hospital
Incorporating the National Children’s Hospital
Trinity College Dublin
Nutrition & Pancreatic cancerDealing with exocrine insufficiency and options for feeding
AUGIS 15th Annual Scientific Meeting, Belfast 2011
Sinead [email protected]
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• Pain• Constipation• Obstruction• Indigestion• Malabsorption• Diabetes• Post-surgery
Cancer Anorexia-Cachexia Syndrome
Cachexia:From Greekkakos (“bad”) hexis (“condition”)
• Anorexia• Tissue Wasting• Weight Loss• Loss of compensatory
increase in feeding
Cachexia process is multifactorial and incompletely understood
Uomo et al. JOP. J Pancreas (Online) 2006; 7(2):157-162.
Differs from simple starvation
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
Pancreas
Gastric
Oesophagus
Head/Neck
Colo/RectalLung
ProstateBreast
Incidence of Cancer Cachexia (Tinsdale 1999, Gibney 2005)
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
Does it work?
Pre-cachexia
Weight loss < 10%
Nutritional intervention works
Cachexia
Weight loss > 10%
Conventional nutritional intervention may not work
Individual support vs. standard care
Statistically significant at 12 and 24 months
Patients with gastric / colorectal cancer
Mean weight loss of 7.2% & 5.5% at baseline
Nutritional intervention
Nutritional intervention
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
Weight
QOL
SGA
Management of cancer cachexiaNutrition 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
MegaceMegestrol acetate for treatment of anorexia-cachexia syndrome
Berenstein G, Ortiz Z. (Cochrane Review)
• Used to improve
appetite and gain weight
in cancer-related
cachexia
• Mechanism unknown
• 32 trials reviewed
• >5,000 patients
+Megace better than placebo for appetite
and weight gain
-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
• Post-hoc analyses:– Significant correlation between EPA intake and weight gain / lean
body mass gain – Control group: no such correlation
Quality of Life:
Intake of EPA supplement correlated positively with
QOL
Compliance issues
mean intake 1.4 cans
Only patients who took recommended 1.5-2 cans EPA
supplement per day gained weight / LBM
• 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
Ryan et al, Annals of Surgery, vol 249, 2009
*P<0.05
Results: Body Composition Analysis
Tru
nk F
at
Fre
e M
ass (
Kg
)
Wh
ole
Bod
y F
at
Fre
e M
ass
(Kg
)Leg
Mu
scle
Mass
* *
*
Lean Body Composition Changes
EPA Enriched Standard EN
8% “severe” wt loss 39%
0.2 kg (p=0.01)
1.4 kg (p=0.03)
0.3 kg (p=0.05)
0 kg
+0.2 kg
0 kg
EPA resulted in anabolism / maintenance of muscle
mass in patients with oesophageal cancer
Patient presenting with cancer
Weight loss: less than 10% Weight loss: more than 10%
Intensive nutrition input+ONS
Regular follow-up
Nutrition Options ?
StandardNutritional
Intervention?
Pre-Cachexia Cachexia
Nutritional Goals
- Preserve LBM
- Functional ability
- Physical activity
- Quality of life
Specialised nutrition
?Megace etcEPA feed
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 testsFaecal test
Breath testsUrinary testsBlood 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 test
-100g fat for 3-5 days-Weigh food
-keep dietary records-Stools collected over 72-
96 hours
-Ingested lipids liberate CO2
following hydrolysis-Not fully validatedDo not differentiate between pancreatic 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
Study details (Thanks to Lorraine Watson, MSc. Project)
% of exocrine insufficient
subjects
Method of testingexocrine insufficiency
Pancreatic cancer subjects onlyMatsumoto & Traverso , 2006 68% Faecal elastaseKato et al , 1993 92 % Secretin testIhse et al , 1977 87% Duodenal tube, Lundh
meal to measure lipase conc.
Pancreatic cancer subjects & subjects other conditionsSato et al , 1998 46 % BT-PABAOhuchida, 2007 66 % ChymotrypsinOhtsuka et al, 2001 26 % ChymotrypsinPancreatic cancer subjects post resection onlyKato et al, 1993 80 % Secretin testPancreatic cancers & subjects with other conditions post resectionTran et al , 2008 88% (76%
severe)Faecal elastase
Norback et al, 2007 100% (92% severe)
Faecal elastase
Sato et al, 1998 75 % BT-PABAOhtsuka et al , 2001 50% Chymotrypsin
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
• 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 palliative pancreatic cancer
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
-Lipase irreversibly denatured by pH<4
-Enteric-coated preparations developed
-Coating only dissolves when pH is >5.5
Supplement: Alimentary Pharmacology & Therapeutics, 2010
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– Skin reactions
• Mouth and perianal irritation, intestinal allergic reaction
• Fibrosing colonopathy – Methacrylic Acid Copolymer
May result from
underlying disease
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
