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Slide 1 - The Adelaide & Meath Hospital Incorporating the National Children’s Hospital Trinity College Dublin
Slide 2 - Nutrition & Pancreatic cancer Dealing with exocrine insufficiency and options for feeding AUGIS 15th Annual Scientific Meeting, Belfast 2011 Sinead Duggan Centre for Pancreatico-Biliary Diseases & Trinity Centre for Health Sciences, AMNCH, Dublin Financial support: Health Research Board Ireland
Slide 3 - Presentation outline Cachexia and severe malnutrition in pancreatic cancer Dealing with exocrine dysfunction in pancreatic cancer
Slide 4 - 1. Cachexia and severe malnutrition in pancreatic cancer
Slide 5 - 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
Slide 6 - Cachexia process is multifactorial and incompletely understood Uomo et al. JOP. J Pancreas (Online) 2006; 7(2):157-162.
Slide 7 - Differs from simple starvation
Slide 8 - ppt slide no 8 content not found
Slide 9 - Weight loss in cancer: Does it matter?
Slide 10 - The physical effects
Slide 11 - 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
Slide 12 - Cachexia worsens prognosis Pancreatic cancer: Resectable disease
Slide 13 - 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
Slide 14 - 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
Slide 15 - 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
Slide 16 - 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
Slide 17 - 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
Slide 18 - 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
Slide 19 - 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)
Slide 20 - 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
Slide 21 - 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
Slide 22 - 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
Slide 23 - *P<0.05 Results: Body Composition Analysis Trunk Fat Free Mass (Kg) Whole Body Fat Free Mass (Kg) Leg Muscle Mass * * *
Slide 24 - 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
Slide 25 - 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
Slide 26 - 2. Dealing with exocrine dysfunction in pancreatic cancer
Slide 27 - 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
Slide 28 - 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
Slide 29 - 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
Slide 30 - 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
Slide 31 - Indirect tests (Source: Australasian treatment guidelines for the management of PEI)
Slide 32 - ppt slide no 32 content not found
Slide 33 - 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
Slide 34 - 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
Slide 35 - 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
Slide 36 - 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)
Slide 37 - 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
Slide 38 - Administering PERT
Slide 39 - -Lipase irreversibly denatured by pH<4 -Enteric-coated preparations developed -Coating only dissolves when pH is >5.5 Supplement: Alimentary Pharmacology & Therapeutics, 2010
Slide 40 - 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
Slide 41 - 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
Slide 42 - 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’
Slide 43 - 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
Slide 44 - 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
Slide 45 - 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
Slide 46 - Thank you Acknowledgments Dr Aoife Ryan – SJH Lorraine Watson