The Management of Pouchitis and Cuffitis

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The Management of Pouchitis and Cuffitis

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1. Dr. Matt. Johnson Prof R.J.Nicholls Dr. A.Forbes Prof P.Ciclitira The Management of Pouchitis and Cuffitis

2. Proctocolectomy UC 10-20% all UC patients For medical refractory disease or dysplasia FAP Mean age at diagnosis of cancer = 39y

5. A Pouch

6. Pathological changes within a normal Healthy Pouch 6/52 plasma cell infiltration raised eosinophils Later = lymphocyte infiltration 6/12 Villous atrophy >6/12 “Normal adaptation” with cell influx stabilizing Tendency to colonic metaplasia “colonic type mucosa”

7. Pouch Flora Prox jejunum 103 (cfu/g of dry stool) Ileum 105-8 Pouch 107-10 Caecum 1011-12 {Nicholls RJ, 1981}{Tabaquhali S, 1970}

8. Pouch Flora The proportion of anaerobes increases distally Ileum = 1:1 (Anaerobe : aerobe) Caecum = 1000:1 {Philipsin, 1975} Ileal Pouch = 100:1 Colonic type flora (bacterioides, bifidobacteria) {Shepherd NA, 1989}

9. Bowel Flora 10x as many bacteria as cells in the body 1kg of our weight {Farrell RJ,2002} 55% of stool “the neglected organ” {Bocci V,1992} Bacterial profiles are genetically determined and remain stable lifelong {van de Merwe JP, 1988}

10. Pouchitis

11. Endoscopic Findings in Pouchitis Oedema Granularity Friable Loss of vascular Mucosal exudates Ulceration These changes can be patchy Inflammation is often worse in the posterior/dependent segment of the pouch)

12. Histological Pouchitis Definitions 1986 Moskowitz Histopathological Scoring System > 4 = Pouchitis Acute Acute PMNC infiltration into the crypts and surface epithelium (3/3) Mild Moderate + Crypt Abscesses Severe + Crypt Abscesses Superficial ulceration (3/3) <25% of field 25-50% >50% Chronic Chronic (lymphocytic) infiltration (3/3) Degree of villous atrophy (3/3)

13. Pouchitis Symptoms A) Post Op Stool Frequency B) Rectal Bleeding C) Faecal Urgency* +/- Cramps D) Fever (unusual) * usually due to inflammation at the distal/efferent limb of the pouch There is often poor correlation between symptoms and either the endoscopic or histology appearance

14. Pouchitis Disease Activity Index, Sandborn 1994 >7 = Acute Pouchitis

15. Clinical Pattern After 6/12 patients fall into 3 catagories; No pouchitis (45%) Episodic Pouchitis (42%) Chronic Pouchitis (13%) = > 4/52 Relapsing / Remitting (>3-4 a year) Antibiotic Dependent Persistent / Refractory Pouchitis

16. Causes of Pouchitis Known Causes of Pouch Inflammation Crohn’s Ischaemia Radiation Specific pathogenic infections (CDT, CMV) Localised infection (pelivic abscess) ?Reaction to secondary bile acids ?Stasis (no association found) Dysbiosis (alteration in the balance of the normal bowel flora)

17. Bacterial Aetiology for IBD - UC In 1989 a case report with active refractory UC Rx= Antibiotics and an enema of “normal” faecal bacteria Benefits were maintained for 6 months {Bennet JD, 1989} Antibiotics Reduce severity and duration of UC {Dickinson RJ, 1985}{Mantzaris GJ, 1994}{Turunen UM, 1998}{Present DH, 1998}{Cummings JH, 2001} Improve Pouchitis - endoscopy and histology {Madden MV, 1994}{Kmiot WA, 1993}{Hurst RD, 1996/8}{Shen B, 2001}{Scott AD, 1989}{Gionchetti P, 1999}{Mimura T, 2002}

18. Treatment of Acute Pouchitis Metronidazole 1-2g PO for 7/7{MaddenMV,1994} 55% SEs = N+V, abdo discomfort,headache, skin rash, metallic taste, disulfiram like reaction with Xol, peripheral neuropathy Metronidazole suppositories (40-160mg/d) {Isaacs 1997} Ciprofloxacin 500mg bd PO 7/7 {Shen 2001} 7/7 course < 14/7 course < combination Cipro + Metro {Mimura T, 2002} Cipro + Rifampicin {Gionchetti P, 1999} Prophylactic doses (increased resistance)

19. Other Treatments to Consider Pentasa 2g bd PO {Tytgat GN,1988}{Shepherd NA, 1989} Budesonide 9mg PO {Shepherd NA, 1989} Budesonide suppositories {Boschi, 1992} 60% relapse Azathioprine {MacMillan 1999} Bismuth Subsalicylate {Tremaine 1998} Glutamine / Butyrate (SCFA) enemas/suppos {de Silva HJ, 1989} Allopurinol 300mg bd PO {Levin KE, 1992}

20. Probiotic Therapy for Pouchitis VSL 3 (Gionchetti 1994) 4x lactobacilli 3x bifidobacteria 1x Strep Salivarius 1x S. thermaphiles Remission can be maintained in 92.5% at 9/12 Vs 0% in the placebo group

21. Probiotic Trials in Acute Pouchitis High dose of probiotics is effective in the treatment of mild pouchitis. A pilot study. Amanidini C, Gionchetti P et al. Digestive and Liver Disease 2002; 34 (Suppl. 1):A96 Abstract Positive results NB = Not written up into a paper ?why

22. Probiotic Trials in Chronic Pouchitis Oral bacteriotherapy as maintainance therapy in patients wih chronic pouchitis: a double blind placebo controlled trial. Giochetti P, et al. Gastroenterology 2000; 119:305-309

23. Trials of Probiotics as Prophylaxis Prophylaxis of pouchitis onset with probiotic therapy: a double blind placebo controlled trial. Giochetti P, et al. Gastroenterology 2000; 124: 1202-1209

24. Probiotics as od Maintainance Once daily high high dose probiotic therapy maintaining remission in recurrent/refractory pouchitis. Mimura T, et al. GUT 2004; 124: 108-114

25. Probiotic Therapeutic Mechanisms Increasing the acidity (increases SCFAs) Altering the hosts immune response at the GI mucosa Produce antibiotic like substances (bacteriocins) Increased IgA + IL 10 (anti-inflammatory) Decreases IFNg and TNFa (pro-inflammatory) Induces T cell shift towards Th2 (anti-inflammatory) May competitively inhibit adherence of potentially pathogenic bacteria Increase intestinal mucus production Produce SCFAs and vitamins

26. What’s on Offer

27. VSL#3 Trial in Chronic Pouchitis Recently managed to acquire funding for 10 local patients to receive 1 year of VSL#3 May be able to import for GPs who are prepared to pay The group will be closely monitored to assess Cost / Benefit ratio Primary Culture Assays and PDAI before and 3/12 Assess long term outcome If successful we will assess the effects of terminating after 3-6/12

28. Where’s the Future Heading Pre-biotics “Non-Digestible Food (NDF) ingredients that beneficially effect he host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, that can improve host health” 1 {Gibson G. 1995} Such CHO – soluble fibre A) Encourages growth of beneficial (saccharolytic) bacteria B) Attract harmful (proteolytic) bacteria away from mucosa (gut wall) by saturating the adhesin-CHO binding sites

29. Prebiotics Side Effects Flatulence + Bloating Rx = Gradually increase fibre with time Gradual increase in Bifidobacterium Decrease freely available NDF Decreases gas formed by other bacteria

30. Prebiotics and the Pouch Inulin 24g a day for 21/7 (crossover trial)1 Decreased inflammation in 19/19 pouches Welters C. et al. Effect of dietary inulin supplementation on inflammation of pouch mucosa in patients with ileal pouch anal anastamosis. Diseases of the colon and rectum 45: 621-627

31. Natural Prebiotics Nutraceuticals = “functional foods” Inulin / Fructo-oligosaccharides / Lactulose Transgalacto-oilgosaccharides Chicory (boiled root = 90% inulin) Jerusalem artichoke Onion Leek Garlic Asparagus Banana (cereals eg. Oatmeal)

33. Conclusion Pouch histology can help guide the medical management Acute pouch inflammation associated with Anaemia Iron deficiency Chronic pouch inflammation associated with Folate, Vitamin D and B12 deficiencies Benefits of correcting deficiencies Prevent potential long term complications Anecdotal considerable improvement in the QOL

34. FAP Pouches

36. Cuffitis Almost exclusive to those with a stapled anastamosis There is a 60% risk of leaving residual rectal mucosa behind when stapling a pouch with a 1-2cm anal transition zone Even after mucosectomy there is a 20% of residual islands of rectal mucosa left on the rectal cuff

37. Cuffitis Symptoms Urgency Diarrhoea (Frequency) Burning Pain (pre/post-defecation) Tenesmus

38. Treatment of Cuffitis Is similar to the treatment of proctitis Mesalazine suppositories / enemas Predsol suppositories / enemas ? Lignocaine gel Consider Metronidazole suppositories

39. Pre – Pouch Ileitis Pentasa granules / PO Azathioprine Other Immuno-modulators

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