Hole in One Dr. S Sebastian Dept of Gastroenterology Hull

Outline … Epidemiology Epidemiology Diagnostic evaluation Diagnostic evaluation Surgical Management Surgical Management Medical Management Medical Management Algorithm Algorithm Clinical Cases Clinical Cases

Fistula: Definition… A communication between two epithelial-lined organs. A communication between two epithelial-lined organs. Small Intestine Large Intestine (Colon) Fistula

Types of fistulae… Types of fistulae… Perianal Other Rectovaginal Enteroenteric

Risk factors… Rectal inflammation Rectal inflammation Smoking Smoking Stricture Stricture ASCA ASCA

Just What Are We Talking About?

Perianal Fistulae: Parks’ Classification System A Superficial fistula B Intersphincteric fistula C Transsphincteric fistula D Suprasphincteric fistula E Extrasphincteric fistula E C A B D External anal sphincter

Simple vs. Complex Fistula Simple Superficial, intersphincteric, low transsphincteric single opening does not involve another organ Complex supra-, extra-, high trans-sphincteric multiple openings involves bladder or vagina

Why is a precise evaluation important? ``The key to successful management is to establish adequate drainage of all abscesses and to control fistula healing. An imaging modality should provide a virtual road map for this purpose``. Schwartz 2006

Diagnostic testing… MRI- Facilitates identification of tracts EUS- Visualize air in tracts CT- Evaluate for un-drained abscess EUA- Utilized for patients requiring surgical intervention diagnostic and therapeutic Colonoscopy- Identify presence of proctitis and proximal disease

What tests ?… EUA AloneEUS AloneMRI Alone 29/32 (91%) 29/32 (91%) 26/30 (87%) EUS + MRIEUS + EUAMRI + EUA 30/30 (100%) 32/32 (100%) 30/30 (100%) Schwartz et al 2001

MR of Ano-rectal disease

Treatment Options

Therapeutic goals… Control overall disease activity Control overall disease activity Maintain adequate nutrition Maintain adequate nutrition Improve quality of life Improve quality of life Reduce hospitalizations Reduce hospitalizations Induce and maintain closure of fistula Induce and maintain closure of fistula Minimise surgical interventions Minimise surgical interventions Maintain continence Maintain continence

Treatment considerations… Severity and impact of symptoms Severity and impact of symptoms Nutritional state Nutritional state Sphincter function Sphincter function Presence or absence of rectal disease Presence or absence of rectal disease Presence or absence of strictures or abscess Presence or absence of strictures or abscess Anatomy Anatomy Number and complexity of the tracts Number and complexity of the tracts

Perianal Crohn’s Disease – Surgical Treatment Options… Incision & Drainage Incision & Drainage Setons Setons Fistulectomy Fistulectomy Diverting procedure Diverting procedure Advancement Flap/Sleeve Advancement Flap/Sleeve Proctectomy Proctectomy Others- Fibrin glue, Plug Others- Fibrin glue, Plug

EUA… Explore and identify all tracts Explore and identify all tracts Hydrogen Peroxide and methylene blue Hydrogen Peroxide and methylene blue to facilitate identification of primary opening Determination of relationship to sphincter Determination of relationship to sphincter Treatment at the same sitting Treatment at the same sitting Avoid creating new tracts Avoid creating new tracts

Seton… Draining Seton Draining Seton prevents closure of primary and secondary openings prevents abscess formation Cutting Seton Cutting Seton slow fistulotomy to prevent wide scar minimizes incontinence painful

Medical Management

Metronidazole… Open Trials Open Trials 4 Trails with N= Trails with N=8-32 Complete healing in 50% alone or in combination Complete healing in 50% alone or in combination Only 30% able to withdraw Only 30% able to withdraw Side effects 70% Side effects 70% Controlled Trial Controlled Trial N=52 N=52 40% complete response 40% complete response Peripheral neuropathy 14% Peripheral neuropathy 14%

AZA/6-MP…

Cyclosporine… 10 open trials 10 open trials N=64 N=64 80% complete response 80% complete response Rapid action < 1 week Rapid action < 1 week 90% lose response on changing to oral treatment 90% lose response on changing to oral treatment

Infliximab- Initial trial… 27 P=0.002 P=0.021 * Present D, et al. N Engl J Med

Pretreatment2 Weeks 10 Weeks18 weeks 28 Present D, et al. N Engl J Med. 1999;340: Miracle cure ????

EndpointPlaceboInfliximabp Median time to loss of response* 14 wk>40 wk.0001 Complete response at Week 30* (no draining fistulae) 27%48%.002 Complete response at Week 54 (no draining fistulae) 22%38%0.02 Infliximab Maintenance Therapy in Fistulizing CD: Results… Sands B et al. NEJM. 2004

2005

Seton + Infliximab vs. Infliximab Alone…. EUA + Seton then infliximab Infliximab alone Fistula healing100%82.5% Recurrence rate44%79% Recurrence interval 13.5 mo3.6 mo Regiero et al Inflam B Disease 2003

Adalimumab: Complete Healing of Draining Fistulas N=70

Tacrolimus … Randomised controlled trial Randomised controlled trial N = 48 N = weeks 10 weeks 0.2mg/kg/day 0.2mg/kg/day Sandborn W et al Gastroenterology 2003

Medical Therapeutic Options for Perianal Fistulae in CD Antibiotics Antibiotics - Flagyl - Cipro Immunomodulators Immunomodulators –Azathioprine /6-MP –Cyclosporine –Methotrexate Infliximab Infliximab Adalimumab Adalimumab Tacrolimus Tacrolimus Possible EfficacyProven EfficacyNo Efficacy Aminosalicylat es Corticosteroids Natalizumab Certolizumab

Physical exam + colonoscopy + MRI/EUS/EUA Simple fistula Multiple (complex) fistula or abscess No rectal inflammation Rectal/colon inflammation EUA with seton Cipro/Flagyl ± fistulotomy Cipro/Flagyl, AZA/6MP or infliximab 6MP/AZA and infliximab Tacrolimus Proctectomy or colectomy with colostomy or ileostomy Failure Perianal Fistula Therapy

Prescriptions are Written on Paper… Not in Stone Until we can predict course in individual patients… Advance to more potent, more toxic agents if no initial response or relapse

Clinical Case 1 19 yr male with a 3 month history of Crohn’s ileocolitis presents with perianal pain & discharge 19 yr male with a 3 month history of Crohn’s ileocolitis presents with perianal pain & discharge Meds:Entocort 9mg+Mesalamine 3gm/day Meds:Entocort 9mg+Mesalamine 3gm/day A recent colonoscopy revealed active Crohn’s disease in the rectum, transverse colon, right colon and ileum. A recent colonoscopy revealed active Crohn’s disease in the rectum, transverse colon, right colon and ileum. On PEx: indurated perianal fistula draining purulent fluid. On PEx: indurated perianal fistula draining purulent fluid. What definitive test will you do next? What definitive test will you do next?

Clinical Case 1: MRI- Suprasphincteric fistula MRI- Suprasphincteric fistula Metronidazole 500mg po bid and Ciprofloxacin 500mg po bid are started. Metronidazole 500mg po bid and Ciprofloxacin 500mg po bid are started. What now? What now? –6MP/Azathioprine –Infliximab? –EUA and seton? –Fistulectomy

Clinical Case 1 Contd. Pt receives 1 week of Cipro/Metronidazole and undergoes and EUA. Pt receives 1 week of Cipro/Metronidazole and undergoes and EUA. Surgeon finds a suprasphincteric fistula with abscess. The abscess is drained and a seton is placed. Surgeon finds a suprasphincteric fistula with abscess. The abscess is drained and a seton is placed. What next? What next? AZT/6-MP ? AZT/6-MP ? Infliximab ? Infliximab ? AZT + Infliximab ? AZT + Infliximab ? Antibiotics ? Antibiotics ? Do nothing ? Do nothing ?

Clinical case 1 Contd. Infliximab 0,2,6 5mg/kg is administered. Shortly before the third infliximab dose the fistula stops draining and the track is “tight” on the seton. The seton is removed. Infliximab 0,2,6 5mg/kg is administered. Shortly before the third infliximab dose the fistula stops draining and the track is “tight” on the seton. The seton is removed. Continuing on infliximab 8 weekly Continuing on infliximab 8 weekly Complete closure of the fistula clinically and on repeat MRI Complete closure of the fistula clinically and on repeat MRI

Clinical case 2 27 yr old girl with 8 yr history of Crohn`s disease – Ileocolonic and duodenal 27 yr old girl with 8 yr history of Crohn`s disease – Ileocolonic and duodenal In remission with azathioprine for the last 3 yrs In remission with azathioprine for the last 3 yrs Father has Crohn`s disease with fistula Father has Crohn`s disease with fistula Recently started smoking Recently started smoking On examination- anal stricture, anal skin tag On examination- anal stricture, anal skin tag `` What is my risk of developing a fistula?`` `` What is my risk of developing a fistula?``

Clinical case 2 Cumulative incidence of fistula in Crohn`s disease? Cumulative incidence of fistula in Crohn`s disease? 5-15% 5-15% 20-40% 20-40% 40-60% 40-60% >75% >75%

Clinical case 2 Contd. 9 months later presents with peri-anal pain and swelling 9 months later presents with peri-anal pain and swelling I&D peri-anal abscess I&D peri-anal abscess Started on Cipro+ Flagyl Started on Cipro+ Flagyl Continuous leakage from the wound Continuous leakage from the wound MRI- Transphincteric fistula. No abscess MRI- Transphincteric fistula. No abscess Wants to start a family Wants to start a family What to do next What to do next Continue antibiotics + AZT ? Continue antibiotics + AZT ? Infliximab? Infliximab? EUA and Seton? EUA and Seton? Diversion procedure? Diversion procedure?

Clinical case 2 Contd. EUA and seton placed EUA and seton placed Flagyl Stopped and folic acid started Flagyl Stopped and folic acid started Discussion re: Infliximab – decided not to Discussion re: Infliximab – decided not to What Planning for pregnancy and delivery? What Planning for pregnancy and delivery? Normal delivery? Normal delivery? Elective LSCS? Elective LSCS? What to do after delivery ? What to do after delivery ? Continue AZT + Seton? Continue AZT + Seton? Infliximab and remove seton? Infliximab and remove seton? Infliximab with seton ? Infliximab with seton ?

Clinical case 3 37 yr old male with ileal Crohn`s disease over 10yrs now develops a perianal fistula 37 yr old male with ileal Crohn`s disease over 10yrs now develops a perianal fistula Well maintained on AZT 2.5 mg/Kg Well maintained on AZT 2.5 mg/Kg Colonoscopy reveals few aphthous ulcers in ileum. Rectum normal Colonoscopy reveals few aphthous ulcers in ileum. Rectum normal MRI – superficial fistula with no abscess MRI – superficial fistula with no abscess What is the most appropriate treatment here? What is the most appropriate treatment here?

Clinical case 3 contd. Increase dose of AZT ? Increase dose of AZT ? Seton placement and switch to 6-MP ? Seton placement and switch to 6-MP ? Seton placement and infliximab ? Seton placement and infliximab ? Infliximab and continue AZT ? Infliximab and continue AZT ? Fistulotomy and continue AZT ? Fistulotomy and continue AZT ?

Clinical case 4 36 yr old female presents with bloody diarrhoea and perianal abscess 36 yr old female presents with bloody diarrhoea and perianal abscess Abscess drained Abscess drained Sigmoidoscopy- rectal and sigmoid Crohn`s disease Sigmoidoscopy- rectal and sigmoid Crohn`s disease MRI- Transsphincteric fistula with abscess MRI- Transsphincteric fistula with abscess What next? What next?

Clinical case 4 Contd. Antibiotics + AZT? Antibiotics + AZT? EUA and seton + AZT? EUA and seton + AZT? EUA+Seton+ AZT+ infliximab? EUA+Seton+ AZT+ infliximab? Infliximab alone? Infliximab alone? Proctectomy and end-ileostomy? Proctectomy and end-ileostomy? No further treatment? No further treatment?

Clinical Case 5 23 yr old female with 5 yr history of Crohns presented with abdo pain, bloating, recurrent UTI 23 yr old female with 5 yr history of Crohns presented with abdo pain, bloating, recurrent UTI Colon- pinhole ileocaecal valve Colon- pinhole ileocaecal valve CT enterography- 25 cms ileal stricture with upstream dilatation and enterovesical fistula CT enterography- 25 cms ileal stricture with upstream dilatation and enterovesical fistula Current meds : 6-MP 100mg daily Current meds : 6-MP 100mg daily No prior surgery No prior surgery The most appropriate treatment at this point ? The most appropriate treatment at this point ?

Clinical Case 5 Contd. Increase dose of 6-MP? Increase dose of 6-MP? Switch to methotrexate? Switch to methotrexate? Infliximab 0,2,6 weeks? Infliximab 0,2,6 weeks? Steroids? Steroids? Ileal resection Ileal resection

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