1. Case Studies in Luminal Gastroenterology Adam Harris Consultant Gastroenterologist The Spire Tunbridge Wells Hospital

2. Luminal Gastroenterology Learning objectives: 1.Avoiding foregut complications of NSAIDs 2.Understanding new dietary option in IBS 3.Understanding latest drug treatments in constipation

3. Case Study 1 87 yr old woman with OA, nocturnal joint pains, angina & bleeding DU 1999 Needs pain relief – what do you recommend?

4. NSAIDs & Bleeding ulcers PMH of ulcer bleeding who use NSAIDs are at highest risk (20%) of re-bleeding Use NSAID plus standard dose PPI Despite this 4-8% will re-bleed in 6 months Chan et al. New Engl J Med 2002; 347:2104-10.

5. NSAIDs High Risk of Complications PMH PUD or bleed >65 yrs Longterm use; high dose More than one NSAID Co-prescribed steroids, clopidogrel or warfarin Serious co-morbidities

6. Risk of gastro-duodenal ulcer Placebo + Aspirin Naproxen + Aspirin Celecoxib + Aspirin 8%27%19%

7. NSAIDs & PPIs 4 points to remember: 1.PPIs decrease risk of NSAID-associated GU & DU cf placebo 2.PPIs equally effective whether non-selective NSAIDs or COX-2 inhibitors 3.PPI co-therapy is effective in healing & preventing recurrent ulcers with long term NSAIDs 4.PPIs decrease risk of NSAID-associated bleeding

8. Aspirin 4 points to remember: 1.Aspirin increases risk of UGIB 4 fold 2.Aspirin + other NSAID increases risk 8 fold 3.No difference in RR with EC or “junior” 4.Eradication of H pylori decreases risk of ulcer Lai et al. New Engl J Med 2002; 346: 2033-38 McQuaid KR, Laine L. Am J Med 2006; 119: 624-38 Arora G et al. Clin Gastro Hepatol 2009; 7: 725-35

9. Case Study 2 24 yr old female with 1-2 year of recurrent low abdominal pain, bloating & intermittent watery diarrhoea Unemployed & lives alone Normal examination Blood tests, urine & stool culture normal Faecal calprotectin <50

10. Low FODMAP diet Fermentable, Oligo-, Di-, Mono-saccharides and Polyols Comprise fructose, lactose, fructans, galactans & polyols Low FODMAP diet developed at Monash University in Melbourne, Australia

11. FODMAPs in diet Fructose eg fruits, honey, corn syrup Lactose eg diary Fructans eg wheat, onion, garlic Galactans eg beans, lentils, legumes Polyols eg sorbitol, avocado, apricots, plums

12. Low FODMAP FODMAP CHO trigger changes in fluid content & bacterial fermentation in bowel leading to symptoms in susceptible individuals Follow low FODMAP diet to eliminate fermentable carbohydrates; trained dietician required. Eliminate from diet for trial period then re-introduce each FODMAP carbohydrate gradually & record symptoms Reported (by enthusiasts) that up to 70% of patients report improvement in symptoms

13. Case Study 3 28 yr old woman with 5 yr history of constipation (BO 2 x/wk) with straining & passage of hard stool; bloating & low abdo discomfort No incontinence. No neurological illness. Examination & blood tests normal. Tried fibre, lactulose, Movicol, Senna, bisacodyl with limited or no benefit.

14. Differential Diagnosis?

15. IBS-C Idiopathic Slow Transit Constipation Functional Outlet Obstruction

16. Investigation?

17. Colonic Transit Marker Study IBS-C ISTC Functional Outlet Obstruction

18. Treatment Options IBS-C linaclotide (Constella) ISTC prucalopride (Resolor) Functional Outlet Obstruction Further assessment; surgery; biofeedback

19. Prucalopride 5-HT 4 receptor agonist with entero-colonic kinetic activity; not a laxative Women only Works within 2-3 hours ↑ spontaneous bowel movements: 67% vs 39% placebo (p<0.001) Improves symptoms of pain, bloating, straining & tenesmus

20. Prucalopride 2mg od for 28 days If no response: do not continue 1mg od: women>65 yr; liver/renal failure AE: nausea; headache; abdo pain; diarrhoea Cost: 28 x 2mg ≈ £60

21. Linaclotide Guanylate cyclase-C agonist Reduces visceral hypersensitivity, increases intestinal secretion & accelerates transit Treatment of moderate-severe IBS-C in adults One capsule (290 mcg) od 30 mins before meal Interaction: OCP, thyroxine Adverse effect: diarrhoea (<20%) Cost: £37.56 for 28 days

22. Linaclotide 47% decrease in abdo pain over 26 weeks (p<0.001 vs placebo) 1 40% improvement in bloating over 26 weeks (p<0.0001 vs placebo) 1 Increase in spontaneous bowel movements from 1.7 to 5.7 weekly over 12 weeks (p<0.0001 vs placebo) 2 Improvement in QoL (p<0.01 vs placebo) 1. Quigley EM et al. Aliment Pharmacol Ther 2013; 37:49-61 2. Chey WD et al. Am J Gastroenterolo 2012; 107: 1702-12

23. Luminal Gastroenterology Learning objectives: 1.Avoiding foregut complications of NSAIDs 2.Understanding new dietary option in IBS 3.Understanding latest therapies in constipation