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 Duggansiduggan@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• 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

Thank yousiduggan@tcd.ie

AcknowledgmentsDr Aoife Ryan – SJH

Lorraine Watson