1 / 39

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.

silver
Download Presentation

The Management of Pouchitis and Cuffitis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related