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The Management of Pouchitis and Cuffitis

The Management of Pouchitis and Cuffitis. Dr. Matt. Johnson Prof R.J.Nicholls Dr. A.Forbes Prof P.Ciclitira. Proctocolectomy. UC 10-20% all UC patients For medical refractory disease or dysplasia FAP Mean age at diagnosis of cancer = 39y. A Pouch.

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The Management of Pouchitis and Cuffitis

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

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

  3. A Pouch

  4. 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”

  5. 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}

  6. 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}

  7. 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}

  8. Pouchitis

  9. 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)

  10. 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)

  11. 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

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

  13. 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

  14. 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)

  15. 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}

  16. 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)

  17. 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}

  18. 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

  19. Probiotic Trials in Acute PouchitisHigh 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

  20. Probiotic Trials in Chronic PouchitisOral bacteriotherapy as maintainance therapy in patients wih chronic pouchitis: a double blind placebo controlled trial. Giochetti P, et al. Gastroenterology 2000; 119:305-309 40 Patients Placebo n = 20 6g VSL 3 n = 20 n = 20 Relapse n = 3 n = 0 Remission after 9/12 n = 17

  21. Trials of Probiotics as ProphylaxisProphylaxis of pouchitis onset with probiotic therapy: a double blind placebo controlled trial. Giochetti P, et al. Gastroenterology 2000; 124: 1202-1209 40 Patients Placebo n = 20 6g VSL 3 n = 20 n = 8 40% Pouchitis n = 2 10% n = 12 60% Remission after 12/12 n = 18 90%

  22. Probiotics as od MaintainanceOnce daily high high dose probiotic therapy maintaining remission in recurrent/refractory pouchitis. Mimura T, et al. GUT 2004; 124: 108-114 36 Patients Placebo n = 16 6g VSL 3 n = 20 n = 15 93% Pouchitis n = 2, +1 15% n = 1 7% Remission after 12/12 n = 17 85%

  23. 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

  24. What’s on Offer

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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)

  30. 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

  31. FAP Pouches Healthy Inflamed

  32. Chart 1 Percentage of FAP Pouches with Histological Evidence of Significant Acute, and Mixed Inflammatory Changes 35 30 25 20 15 10 5 0 Acute Chronic Mixed Histological Inflammation Chart 2 Percentage of FAP Pouch Patients with PDAI Scores Diagnostic of Active Pouchitis 50 40 30 % 20 10 0 Histology Endoscopy Clinical PDAI PDAI Score and its Individual Components 55 of 190 had evidence of endoscopic inflammation Of those 55, 14% had a PDAI of >7 suggestive of active pouchitis This gave an overall prevalence of pouchitis in FAP pouches as 4%

  33. 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

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

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

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

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