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1. Dr. Matt. Johnson
Prof R.J.Nicholls
Dr. A.Forbes
Prof P.Ciclitira The Management ofPouchitis 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 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
22. 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
23. 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
24. 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
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