FRIDAY, NOVEMBER 1, 2013 RITZ-CARLTON HOTEL, TORONTO

CASE!BASED WORKSHOPChronic Refractory Pouch Dysfunction (based on a true patient case)

A 44-year-old male is referred to you from a preeminent Canadian gastroenterologist for a second opinion on a history of chronic pouchitis. He initially had ulcerative colitis diagnosed in 2006 and after an aggressive course he failed corticosteroid therapy and underwent an ileo-pouch and anal anastomosis in 2009. You do not have the report to know if it was a hand-sewn or stapled anastomosis. Following the pouch surgery he had problems with frequent bowel movements, up to 20 times per day. He would manage the frequency on his own with cipro!oxacin and metronidazole. He had tried topical mesalamine without bene"t.

His laboratory investigations are normal. A previous sigmoidoscopy demonstrated mild pouchitis.

While the patient gets some symptomatic improvement with the above antibiotics he is requesting better control. Before the patient can see you he has to travel to Dubai on business.

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Decision Node 1 What therapies would you suggest his gastroenterologist

try empirically while he is away and awaiting your appointment?1,2,3

While he is away the patient continues his cipro!oxacin and metronidazole until he is at his best clinical state and then starts VSL#3 9 billion BID for 8 weeks. He has no response to the VSL#3. A physician in Dubai gives him hydrocortisone foam enemas with some variable response with a decrease in bowel movements from 20 to 12 per day. He has returned to Canada and is now in your o#ce.

Decision Node 2 What tests do you need and why?

Where do you want to biopsy and why?4

What special stains, if any, do you want to send your biopsies for?5

Pouchoscopy shows moderate circumferential distal pouch erythema with super"cial ulceration up to 10 cm. The proximal pouch from 10 to 20 cm appears normal. The distal pouch biopsy shows chronic active in!ammation consistent with chronic pouchitis and the proximal pouch biopsies show mild active in!ammation. There are no special stains. The a$erent limb is not seen or biopsied.

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FRIDAY, NOVEMBER 1, 2013 RITZ-CARLTON HOTEL, TORONTO 18

Decision Node 3 Does this information help you make further decisions?6

What is your diagnosis?

What other investigations might be considered?7

A computed tomography (CT) scan (not enterography) shows thickening of the neo rectum with rectal mucosal enhancement and stranding of the surrounding fat.

Decision Node 4 Is the CT scan adequate?7

Would you have preferred a CT scan or a CT enterography in this case? Why?

Would an MRI have been more appropriate? Why or why not?

What therapy would you use at this point?8,9

He is started on a 12-week tapering course of prednisone (starting dose = 40 mg/d) with a marked decrease in his frequency and on in!iximab induction at 5 mg/kg weeks 0, 2, and q 8 weeks maintenance. He has an excellent immediate response to this treatment with bowel movements falling from 20 to 5 per day.

The prednisone is tapered to zero and he remains on maintenance in!iximab. However, within 9 months he is losing response and the in!iximab is escalated to q4 weeks, but alas, no response occurs. He is again having 20 bowel movements per day.

During month 7 of in!iximab treatment he developed a 3 cm perianal abscess that required surgical drainage.

Six weeks after the in!iximab dose escalation he has a repeat pouchoscopy. It once again demonstrates moderately severe distal pouch in!ammation up to 10 cm and a proximal pouch that is endoscopically normal. The a"erent limb is seen, biopsied, and is completely normal. Laboratory investigations are again all normal.

Decision Node 4 What is your diagnosis and de!nitive therapy at

this point?10

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In follow-up, with severe diarrhea and perianal excoriation the patient undergoes a defunctioning ileostomy. Diarrhea stops. Pouchoscopy demonstrates a healed mucosa with no ulceration. The patient is happy but hates the ostomy.

FRIDAY, NOVEMBER 1, 2013 RITZ-CARLTON HOTEL, TORONTO19

References1. Gionchetti P, Rizzello F, Morselli C, Poggioli G, Tambasco R, Calabrese C, Brigidi P, Vitali B, Straforini G, Campieri M. High-dose probiotics for the

treatment of active pouchitis. Dis Colon Rectum 2007;50:2075–82; discussion 2082–4. [Epub 2007 Oct 13.]

2. Shen B, Brzezinski A, Fazio VW, Remzi FH, Achkar JP, Bennett AE, Sherman K, Lashner BA. Maintenance therapy with a probiotic in antibiotic-dependent pouchitis: experience in clinical practice. Aliment Pharmacol Ther 2005;22:721–8.

3. Tyler AD, Knox N, Kabakchiev B, Milgrom R, Kirsch R, Cohen Z, McLeod RS, Guttman DS, Krause DO, Silverberg MS. Characterization of the gut-associated microbiome in in!ammatory pouch complications following ileal pouch-anal anastomosis. PLoS One 2013;8:e66934.

4. Shen B. Pouchitis: what every gastroenterologist needs to know. Clin Gastroenterol Hepatol 2013 Apr 16. pii: S1542–3565(13)00483-7. doi: 10.1016/j.cgh.2013.03.033. [Epub ahead of print]

5. Navaneethan U, Bennett AE, Venkatesh PG, Lian L, Hammel J, Patel V, Kiran RP, Remzi FH, Shen B. Tissue in"ltration of IgG4+ plasma cells in symptomatic patients with ileal pouch-anal anastomosis. J Crohns Colitis 2011;5:570–6. [Epub 2011 Jun 24.]

6. Ben-Bassat O, Tyler AD, Xu W, Kirsch R, Schae$er DF, Walsh J, Steinhart AH, Greenberg GR, Cohen Z, Silverberg MS, McLeod RS. Ileal pouch symptoms do not correlate with in!ammation of the pouch. Clin Gastroenterol Hepatol 2013 Sep 26. pii: S1542–3565(13)01432–8. doi: 10.1016/j.cgh.2013.09.027. [Epub ahead of print]

7. Khanna R, Wu X, Shen B. Low levels of vitamin D are common in patients with ileal pouches irrespective of pouch in!ammation. J Crohns Colitis 2013;7:525–33. [Epub 2012 Sep 8.]

8. Viazis N, Giakoumis M, Koukouratos T, Anastasiou J, Katopodi K, Kechagias G, Anastasopoulos E, Saprikis E, Chanias M, Tribonias G, Karamanolis DG. Long term bene"t of one year in!iximab administration for the treatment of chronic refractory pouchitis. J Crohns Colitis 2013;7:e457–60. [Epub 2013 Mar 21.]

9. Li Y, Lopez R, Queener E, Shen B. Adalimumab therapy in Crohn’s disease of the ileal pouch. In!amm Bowel Dis 2012;18:2232–9. [Epub 2012 Mar 8.]

10. Wu B, Lian L, Li Y, Remzi FH, Liu X, Kiran RP, Shen B. Clinical course of cu#tis in ulcerative colitis patients with restorative proctocolectomy and ileal pouch-anal anastomoses. In!amm Bowel Dis 2013;19:404–10.