Nutrition and pancreatic cancer Presentation by Sinead PowerPoint Presentation

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The Adelaide & Meath Hospital Incorporating the National Children’s Hospital Trinity College Dublin

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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

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Presentation outline Cachexia and severe malnutrition in pancreatic cancer Dealing with exocrine dysfunction in pancreatic cancer

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1. Cachexia and severe malnutrition in pancreatic cancer

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Nutritional problems in pancreatic cancer Pain Constipation Obstruction Indigestion Malabsorption Diabetes Post-surgery Cancer Anorexia-Cachexia Syndrome Cachexia: From Greek kakos (“bad”) hexis (“condition”) Anorexia Tissue Wasting Weight Loss Loss of compensatory increase in feeding

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Cachexia process is multifactorial and incompletely understood Uomo et al. JOP. J Pancreas (Online) 2006; 7(2):157-162.

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Differs from simple starvation

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Weight loss in cancer: Does it matter?

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The physical effects

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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

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Cachexia worsens prognosis Pancreatic cancer: Resectable disease

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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

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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

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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

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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

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Megace Megestrol 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

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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

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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)

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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

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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

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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

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*P<0.05 Results: Body Composition Analysis Trunk Fat Free Mass (Kg) Whole Body Fat Free Mass (Kg) Leg Muscle Mass * * *

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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

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Patient presenting with cancer Weight loss: less than 10% Weight loss: more than 10% Intensive nutrition input +ONS Regular follow-up Nutrition Options ? Standard Nutritional Intervention? Pre-Cachexia Cachexia Nutritional Goals - Preserve LBM - Functional ability - Physical activity - Quality of life Specialised nutrition ?Megace etc EPA feed

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2. Dealing with exocrine dysfunction in pancreatic cancer

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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

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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

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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

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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

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Indirect tests (Source: Australasian treatment guidelines for the management of PEI)

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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

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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

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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

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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)

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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

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Administering PERT

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-Lipase irreversibly denatured by pH<4 -Enteric-coated preparations developed -Coating only dissolves when pH is >5.5 Supplement: Alimentary Pharmacology & Therapeutics, 2010

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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 Kelly & Layer. Human pancreatic exocrine response to nutrients in health and disease. Gut 2005; 54(Supp VI):vi1-28 Imrie et al, Expert commentary: how we do it. Aliment. Pharm and Ther 2010; 32 (suppl 1): 21-25

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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

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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’

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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

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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

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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

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Thank you siduggan@tcd.ie Acknowledgments Dr Aoife Ryan – SJH Lorraine Watson