Understanding Pouch Problems (in context) Kangaroo Club Dr Oliver Brain DPhil Consultant Gastroenterologist 7th Oct 2017

Overview Normal pouch function Pouchitis Structured approach to pouch dysfunction

‘Normal’ pouch function? 6-8 bowel movements per 24 h 1-2 bowel movements per night (approx 50% of patients) Lack of urgency / able to defer for 1 h Loose or semi-formed Occasional seepage at night Pouch function stabilises 1 year post surgery Fazio V etal Ann Surg 1995;222:120-127 Sagar PM, Pemberton JH Dig Dis 1997;15:172-188

What is normal?

What is normal? 80% people BO 1-2x per day

What is normal?

58 had constipation (IBS-C) Urgency 16%-31% Straining 5-23% 278 women Age 60 146 were ‘normal’ 72 had diarrhoea (IBS-D) 58 had constipation (IBS-C) Urgency 16%-31% Straining 5-23% Postprandial BO 25-34% Incomplete evacuation 13-32% Bharucha A et al Am J Gastroenterol 2008;103:692–698

58 had constipation (IBS-C) Urgency 16%-31% Straining 5-23% 278 women Age 60 146 were ‘normal’ 72 had diarrhoea (IBS-D) 58 had constipation (IBS-C) Urgency 16%-31% Straining 5-23% Postprandial BO 25-34% Incomplete evacuation 13-32% NB Prevalence of IBS ≈ 15% Bharucha A et al Am J Gastroenterol 2008;103:692–698

Problems Specific to the Pouch Pouchitis

What is pouchitis? What is pouchitis? Inflammation of the pouch Suggested by: stool frequency urgency bleeding incontinence Diagnosis confirmed by: Pouchoscopy Histology

PDAI Pouchitis is defined as a total score ≥7

Patterns of pouchitis Acute: ≤ 4 weeks Chronic: > 4 weeks Infrequent Relapsing Continuous Treatment responsive Treatment refractory

Pouchitis prevalence 50% of UC patients will have ≥1 acute episode1 Up to 60% suffer recurrent episodes pouchitis Prevalence of chronic pouchitis is 5-10%1 Pouch failure At 20 years pouch failure rates are 10-15%2 Pouchitis accounts for 10% of pouch failure3 1. Simchul et al World J Surg 2000. Stahlberg et al Dis Colon Rectum 1996. Lohmuller et al Ann Surg 1990. Salemans et al Dig Dis Sci 1992. 2. Tekkis et al Colorectal Dis 2010. Hahnloser et al Br J Surg 2007. Leowardi et al Lengenbecks Arch Surg 2010 3. Tulchinsky et al Ann Surg 2003

Why does pouchitis occur? Idiopathic Occurs in up to 50% of UC patients Rarely seen in FAP patients Genetic risk? Microbial risk / dysbiosis?

} Genetics of pouchitis Small, underpowered studies. IL1RA1 NOD22 TLR93 CD143 } Chronic relapsing pouchitis 1. Brett et al EJGH 1996; Carter et al Gastroenterology 2001. 2. Seghal et al Dis Colon Rectum 2010; Tyler et al Gastroenterology 2011 3. Lammers et al World J Gastroenterol 2005

} } Other Risk Factors Extensive / severe UC Pre-colectomy thrombocytosis Backwash ileitis Extra-intestinal manifestations pANCA positivity Non-smokers NSAID use Reflection of disease severity } Reflect PSC association Reviewed in Landy J et al Inflamm Bowel Dis 2012

Risk Factors PSC Associated with a 2-fold increase in risk of pouchitis1 Also associated with pre-pouch ileitis IgG4 may be associated with a subset of chronic pouchitis patients2 1.Zins BJ et al Am J Gastroetnerol 1995. Penna C et al Gut 1996. 2. Navaneethan U et al Gastrointestin Surg 2011

Aetiology Pouch mucosal adaptation and colonic metaplasia Part of a normal adaptive response Altered short chain fatty acid metabolism Anaerobic fermentation of PSAs Bile acids Conflicting data Microbiome

Microbiome Pouchitis only occurs once ileostomy closed Pouch is exposed to concentrations >106 times the TI1,2 Evidence of an altered microbial signature in pouchitis3, but there is significant study heterogeneity Antibiotics Probiotics 1. Nicholls et al Gut 1981. 2. Santavirta et al Int J Colorectal Dis 1991 3. Landy J et al Inflamm Bowel Dis 2012

Dysfunctional pouch What does this mean?

What does ‘dysfunctional pouch’ mean? Answers: a) Dysfunctional pouch = poorly functioning pouch from any cause b) Dysfunctional pouch = poor pouch function in absence of demonstrable pouchitis / inflammation c) Dysfunctional pouch = irritable pouch

Dysfunctional Pouch Obstruction: Stricture Functional obstruction Peri-pouch sepsis: Acute or historic Small volume pouch Irritable pouch – symptoms with a PDAI <7

Risk Factors for Pouch Dysfunction Patient-dependent IBS Weak sphincters Disease-dependent PSC Surgery-dependent Peri-pouch sepsis / anastomotic leak Anastomosis formation Small pouch volume

Patient 28 year old man Background UC and PSC diagnosed 6 years ago Colectomy for refractory colitis 3 years ago Post-operative anastomotic leak Best pouch function: 6x per day, 2x nocte Minimal urgency, occasional nocturnal accidents Currently 12x per day, 3x nocte Severe urgency, incontinence every other day Minimal response to antibiotics

Basic rationale for pouch assessment

Approach to Pouch Dysfunction Examination Diagnosis Therapy Refractory DRE Stricture Dilatation Hegar auto-dilatation Revision surgery Weak sphincter Loperamide Codeine End ileostomy Ano-rectal USS Pouchoscopy Inflammation

Approach to Dysfunctional Pouch Examination Diagnosis Therapy Refractory Revision surgery Pouch inlet / outlet obstruction Dilatation Pouchoscopy Small volume pouch Normal Revision surgery / ileostomy Poucho-defaecogram Functional outlet obstruction Medina catheter Bio-feedback Normal

Approach to Dysfunctional Pouch Examination Diagnosis Therapy Refractory Revision pouch surgery Pelvic MRI Pelvic collection Drainage Reassurance Dietary modification Anti-diarrhoeal meds Anti-spasmodic meds Anti-depression meds Irritable pouch syndrome Normal Ileostomy

Patient Pouch-anal anastomotic stricture (moderate) Dilated endoscopically MRI peri-pouch fibrosis Recovery of reasonable pouch function

Summary Many people with and without pouches have GI symptoms when surveyed. Pouch dysfunction can be due to both pouch-related and unrelated causes A structured approach to investigation and management is required