Ileal Pouch Anal Anastomosis and Crohn’s Disease

Ileal Pouch Anal Anastomosis and Crohn’s Disease Ismail Sagap, MB, BCh, MS, and Feza H. Remzi, MD, FASCRS Restorative proctocolectomy with ileal pouch–anal anastomosis is the surgical treatment of choice in ulcerative colitis and the majority of patients with familial adenomatous polyposis. The indication for restorative surgery in Crohn’s disease, however, is controversial. When ileal pouch–anal anastomosis is performed in a patient with Crohn’s disease, significant morbidities such as peripouch abscess, pouchitis, chronic fistulae, and strictures can develop and lead to pouch failure. However, some reports suggest that ileoanal pouch procedures can successfully treat certain cases of colonic Crohn’s disease, mainly patients without perianal and small intestinal diseases. Efforts continue to identify the clinical, histological, and endoscopic features that represent these Crohn’s patients who will benefit from restorative surgery. Semin Colon Rectal Surg 17:91-95 © 2006 Elsevier Inc. All rights reserved. KEYWORDS Crohn’s disease, ileal pouch–anal anastomosis

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ince its introduction by Parks and Nicholls,1 proctocolectomy with ileal pouch anal anastomosis (IPAA) has become the standard treatment for patients with ulcerative colitis and most of those with familial adenomatous polyposis. In many cases, the procedure cures the disease, maintains gastrointestinal continuity, and improves the patient’s functional outcome and quality of life.2 Although the complication rate ranges from 30 to 40%, the incidence of pouch failure declines with experience.3 Additionally, operations designed to salvage pouches or reconstruct them after failure, although difficult, may also produce good outcomes.4-6 The indication for restorative surgery in colonic Crohn’s disease, however, is controversial. It is often performed in patients who were initially diagnosed with ulcerative colitis but then were found to actually have Crohn’s colitis after IPAA. Distinguishing ulcerative colitis from Crohn’s disease of the colon may be difficult since the pathologic features of Crohn’s can be used to confirm the disease only 30% of the time. The presence of granulomas is thought to be the main pathognomonic histological feature, but most diagnoses are usually based on a combination of several features such as patchy inflammation, deep ulceration, and transmural lymphoid aggregation underlying nonulcerative mucosa. More patients are being diagnosed based on the presence of chronic relapsing and recurrent inflammatory activities occurring in other sites such as the small intestine and typical perianal disease appearance. Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio. Address reprint requests to: Feza H. Remzi, MD, Department of Colorectal Surgery, A-30, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195. E-mail: [email protected]

1043-1489/06/$-see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.scrs.2006.06.010

Crohn’s disease often recurs in the small intestines, especially in the pouch and perineal area, after IPAA. These result in stricture formation, perianal fistula, and signs and symptoms related to and similar to chronic pouchitis, which significantly increase the risk of pouch failure. In addition, the need of further small bowel resections in these patients is associated with a risk of short bowel syndrome. Hence, sphincter-saving and restorative procedures have been deemed concerning for patients with colonic Crohn’s disease. However, the fact is that Crohn’s disease mainly affects young individuals who may not be willing to live with a permanent stoma. Maintaining bowel continuity through ileal pouch anal anastomosis would indeed lessen the physical and psychological ailments seen in patients with Crohn’s disease and hence increase their quality of life. Unfortunately, there have not been uniform results in patients with colonic Crohn’s disease after pouch surgery. The failure rate can be as high as 60% in patients with a secondary diagnosis of Crohn’s colitis after IPAA, and it is often difficult to manage any complications that develop. On the other hand, IPAA has been reported to afford some benefit in selected cases of Crohn’s colitis without anal and other intestinal manifestations. Unfortunately, there have not been any distinctive clinical, histological, or endoscopic features that represent these Crohn’s patients who will benefit from restorative surgery.

Spectrum of Inflammatory Process after IPAA and Outcome It is often difficult to make discrete preoperative clinical and pathologic distinctions between ulcerative colitis and 91

92 Crohn’s colitis. This fact is especially true after medical therapy has been instituted. The standard preoperative diagnosis of Crohn’s disease is usually based on the presence of epithelial granuloma or focal chronic ileitis, the presence of deep ulceration, patchy inflammation with rectal sparing, focal chronic ileitis, and/or transmural lymphoid aggregation in nonulcerated areas. Unfortunately, it may not be easy to definitively distinguish Crohn’s disease from ulcerative or indeterminate colitis, especially since fewer than 30% of patients present with classic features. In approximately 8 to 10% of cases, the pathologic diagnosis is changed from ulcerative colitis to Crohn’s disease after IPAA.4-6 In addition, endoscopic and clinical features that resemble Crohn’s disease may be found after IPAA in patients with confirmed ulcerative or indeterminate colitis diagnosis in the proctocolectomy specimen. These Crohn’s-like features consist of prepouch patchy ileitis or afferent loop ulcers, strictures, and small intestinal fistulae.4,7 Occasionally, long linear and deep ulceration are also present within the pouch. These histological characteristics are also the features of chronic pouchitis. In these instances, subsequent medical or surgical management can be difficult and also challenging without the pathologic confirmation of Crohn’s disease in existing ulcerative or indeterminate colitis diagnosis in the proctocolectomy specimen. In general, chronic pouchitis is more likely to respond to nonoperative treatments such as antibiotics and antiinflammatory agents. Furthermore, pouchitis occurs more commonly with Crohn’s disease than with ulcerative colitis.8 This may be related to the fact that patients’ symptoms and endoscopic findings are similar and there is no definitive test to differentiate between the two diagnoses. The treatment for recrudescent Crohn’s disease within the pouch may require more than antibiotics and antiinflammatory agents. It is therefore prudent to try to confirm the diagnosis by putting the clinical, endoscopic, and pathologic data all together before deciding on a treatment regimen. Classic pathologic and clinical features of Crohn’s disease have been studied in attempts to predict disease behavior and assess the indication for restorative procedures. Morpugo9 and coworkers followed 92 consecutive patients in whom the preoperative diagnosis was changed from ulcerative colitis to Crohn’s disease after IPAA. The mean follow-up was 82 months, and the pattern of recurrence was assessed. Granulomas were detected in 47.5% of the proctocolectomy specimens, and there was no difference in the rates of small intestinal and perianal diseases between the patients with and without granulomas. However, extracolonic involvement was significantly higher (among the patients with segmental colitis than in those with pan-colitis, 63% versus 12%). Disease recurred in 55% of the study patients, leading to pouch loss rates of 23 and 11% in the granulomatous and nongranulomatous groups, respectively. The rate of recurrence was also high in the patients with segmental colitis and multiple site involvement. This study concluded that granulomatous and segmental colitis manifestations are signs of aggressive Crohn’s disease and should preclude restorative procedures. The term “indeterminate colitis” was used to label pathologic features (ie, unusual distribution of inflammation, deep

I. Sagap and F.H. Remzi linear ulcerations, fissures, transmural inflammation, creeping fat, and retention of goblet cells) found in proctocolectomy specimens.10 An estimated 10 to 20% of patients with a preoperative diagnosis of indeterminate colitis were later diagnosed with Crohn’s disease when they developed Crohn’slike features such as small bowel disease or perineal fistulizing disease. A report by Koltun11 and coworkers revealed that the diagnosis of indeterminate colitis was associated with significant perineal disease more so than ulcerative colitis (28% versus 0.4%), which resulted in more pouch failures among the indeterminate group (50% versus 3%). A study by McIntyre12 and coworkers reported similar findings. In their study—which consisted of 72 patients with indeterminate colitis and 1232 patients with ulcerative colitis—they found that stool frequency and incontinence rates were equivalent between the two groups. However, the rate of pouch failure was higher in the indeterminate group (19% versus 8%) at a mean follow-up of 56 months, possibly because the patients diagnosed with indeterminate colitis probably had Crohn’s disease. This would mean that proctosigmoidectomy and IPAA should be recommended with caution to patients with an established preoperative diagnosis of indeterminate colitis. On the other hand, Delaney and coworkers13 compared 115 patients with indeterminate colitis with a matched group of 231 patients with ulcerative colitis, all of whom underwent IPAA. The mean follow-up period was 3.4 years for the indeterminate colitis group and 5.5 years for ulcerative colitis group. The percentage of patients with classic features of Crohn’s disease at the time of follow-up was similar between the two groups. The overall pouch failure rates were similar as well: 3.4 and 3.5%. Although there were more patients with perineal diseases in the indeterminate group (3.5% versus 0.5%), the difference was not statistically significant. Functional pouch outcomes and patient quality of life also were similar. The study concluded that indeterminate colitis should not preclude IPAA. Brown14 and coworkers in Toronto compared 1135 patients with ulcerative colitis, 36 with Crohn’s colitis, and 21 with indeterminate colitis in a 10-year cohort of inflammatory bowel disease patients undergoing IPAA. The mean follow-up times were 98, 83, and 59 months, respectively. Complication rates were significantly higher in the Crohn’s disease group: 64% versus 43% for the indeterminate group versus 22% for the ulcerative group. The difference between the indeterminate group and ulcerative colitis group was not statistically significant. The Crohn’s group had the highest rates of pelvic sepsis, fistula, and disease in the small intestine. As a result, this group had the highest rates of pouch failure, but the functional outcome was similar across all three groups. Inflammatory processes such as chronic pouchitis, cuffitis, or strictures after IPAA may present in all spectrum of inflammatory bowel disease related colitis. The presence of Crohn’s disease leads to significant morbidity related to stricturing, fistulizing, and inflammatory small bowel disease and increases the risk of pouch failure. The management of these

Ileal pouch anal anastomosis and Crohn’s disease

6 (19.3) — 4 (33.6) 21 (35.0) 11 (27.0) (29.0) 5 (16.0) — 1 (8.3) 9 (15.0) — (12.0) — 12 (52.1) — 11 (18.0) 26 (49.0) 8 11 (47.9) 4 49 (89.0) 15 (51.0) 59 122.4 76 46 113 153

Years

1996 2001 2002 2003 2001 2004

Authors

Panis Mylonakis De Oca Hartley Regimbeau Braveman

Numbers in parentheses are percentages.

36 — 35 33 36 26

Clinically Diagnosed CD Pathological Diagnosed CD Mean Follow-Up (months) Mean Age (years) No. of Patients

Table 1 Complications and Pouch Failure Rates of IPAA in Crohn’s Colitis

Apart from incontinence and excessive bowel frequency, the principal causes of pouch failure in patients with Crohn’s disease are severe perineal disease, recurrent sepsis, outlet strictures, and fistulae. The outcome tends to be poorer when both clinical and pathologic features are present versus histological evidence only.15 These clinical presentations of severe perineal disease, recurrent sepsis, outlet strictures, and small bowel involvement lead to pouch excisions and re-diversions in a larger number of patients whose diagnoses were missed before IPAA. In addition, relapsing obstructive symptoms such as constipation and persistent nausea and bloating are common in dysfunctional pouches of Crohn’s disease. Reoperative surgery, especially a redo pouch with an abdominoperineal disconnection, might be best avoided in patients with Crohn’s disease and multiple intestinal involvements due to the risk of short bowel syndrome. Table 1 lists the complication and pouch failure rates of several studies from high volume centers. In selected patients with limited proximal intestinal disease or where minor reconstruction is required, however, pouch salvage maybe feasible. Pouch salvage operations may be considered when overall reservoir function is good. These operations include stricture dilation, perianal abscess drainage, and long-term seton usage for abscess, and flap procedures for fistulae such as pouch–vaginal fistulae. Crohn’s inflammation often recurs within the perineum and the pelvic cavity after IPAA. Since severe, multiple complex fistulae can develop resulting in pouch failure, which is why IPAA is generally contraindicated in patients with Crohn’s disease.16 Data suggest that IPAA patients with a preoperative diagnosis of Crohn’s colitis generally have a 40 to 45% chance of pouch failure and often develop continuous lifetime morbidities.17 In contrast, Panis18 and coworkers reported a low complication rate (19%) from selected patients with Crohn’s colitis (n ⫽ 31) who did not have perineal and small intestinal disease. In that prospective study, inflammation within the pouch occurred in six patients, two (6.4%) who required subsequent pouch excisions. Short- and longterm complications occurred in 16 and 19% of cases, respectively. Histological features of granulomas and chronic ileitis were associated with a 14% complication rate, whereas those without these features had a 30% complication rate. Perfect continence was achieved in 74% of cases. Ten patients (32%) required antidiarrheal medication. Overall sexual function was good. The mean follow-up was 5 years.

Short-term Any Complication

Management and Outcome of Crohn’s Disease after IPAA

31 23 12 60 41 153

Long-term Crohn’s Related Complication (%)

Total Failure (%)

morbidities should be based on results from histological examination. However this is not always possible where the combination of clinical, pathologic, and endoscopic data is usually needed to establish the diagnosis. Once this is achieved, a treatment plan can be employed to produce the best outcome.

2 (6.4) 12 (52.1) 2 (16.2) 7 (12.0) 3 (7.0) 9 (29.0)

93

I. Sagap and F.H. Remzi

94 Table 2 Functional Outcome of IPAA in Crohn’s Disease

Authors Panis et al. Mylonakis De Oca Hartley Regimbeau Braveman

Stool Continence Definitive Frequency No. of End Gas/Stool Need for Patients Ileostomy 24 h Night Perfect Discrimination Pads Use Leak Medicine Urgency 31 23 12 60 41 153

2 (6.4) 12 (52.1) 2 (16.6) 7 (12.0) 3 (7.3) 9 (29)

5 6 5 7 6 6

0.6 — — 2 — 1

(74) — — (31) (73) —

(84) — — — — (65.0)

(16) — — — (25) (45)

(11) — — — — (60)

(32) (50) — (56) (25) (50)

0 0 — — (8.0) —

Numbers in parentheses are percentages.

The same institution reported a 10-year Crohn’s diseaserelated complication rate of 35% and a pouch excision rate of 10% in 41 subsequent patients.19 This time, the Crohn’s disease recurrence rate was 35% and the pouch failure rate was 10%. Perfect continence was achieved in 73% of patients, and the overall functional outcome was good. Based on these results, the study proposed IPAA as an alternative surgical treatment for colorectal Crohn’s disease. However the critique of this study has been the lack of agreement that what has been called Crohn’s colitis could have been called indeterminate colitis in other studies. Table 2 summarizes the functional outcome of IPAA in Crohn’s disease patients in several studies. Good functional outcome was also reported in a small study by de Oca20 and coworkers. It consisted of 12 patients with a postoperative diagnosis of Crohn’s disease; these patients were compared with 100 patients with ulcerative colitis. After a mean follow-up period of 76 months for the patients with Crohn’s disease and 83 months for the patients with ulcerative colitis, the patients’ satisfaction rate was high with good physical and social improvements achieved. The long-term complications, functional outcomes, and quality of life were comparable with those of the ulcerative colitis patients. These results suggest that (1) IPAA may be used for Crohn’s disease that affects the colon and (2) the complication rates are acceptable. In addition, the prediction of outcome using clinical and pathological features suggests that patients with an established diagnosis of Crohn’s colitis have a better chance of pouch survival than those with secondary diagnoses.21,22 Due to the overlapping clinical, histological, and endoscopic findings of pouchitis and Crohn’s disease, managing relapsing inflammatory manifestations and reservoir dysfunction can be challenging in the postoperative period. Although pouchitis is mainly treated with antibiotics (eg, metronidazole and ciprofloxacin), any exacerbation of Crohn’s will require potent immune modifiers and antiinflammatory agents. According to recent reports on the use of infliximab—an antitumor necrosis factor (TNF-à) antibody—the drug is associated with good short-term and long-term clinical responses and satisfactory functional outcomes in refractory post-IPAA Crohn’s disease. Further surgical interventions may be avoided with effective medical therapy, which can increase a patient’s quality of life.23,24

Conclusions Significant morbidities are observed when IPAA is performed in patients with Crohn’s colitis, which lead to high pouch failure rates. Evidence suggests that, in certain cases, IPAA can successfully treat certain patients with Crohn’s colitis. Unfortunately, there have not been any definitive predictive factors to aid the practitioners to guide patients for a better outcome. However, the fact is that patients with Crohn’s disease who may not be willing to live with a permanent stoma and maintaining bowel continuity through ileal pouch anal anastomosis would indeed lessen the physical and psychological ailments seen in patients with Crohn’s disease and hence increase their quality of life. Therefore in patients with no perineal and small intestinal disease, one may give the choice of restorative proctecolectomy to patients with Crohn’s disease after clear and documented consenting.

References 1. Parks AG, Nicholls RJ: Proctocolectomy without ileostomy for ulcerative colitis. BMJ 2:85-88, 1978 2. Michelassi F, Lee J, Rubin M, et al: Long-term functional results after ileal pouch-anal restorative proctocolectomy for ulcerative colitis. Ann Surg 238:433-445, 2003 3. Tulchinsky H, Hawley PR, Nicholls J: Long-term failure after restorative proctocolectomy for ulcerative colitis. Ann Surg 238:229-234, 2003 4. Fazio VW, Zif Y, Church JM, et al: Ileal pouch-anal anastomoses complications and function in 1005 patients. Ann Surg 222(2):120-127, 1995 5. Fazio VW, Wu J, Lavery IC: Repeat Ileal pouch-anal anastomosis to salvage septic complications of pelvic pouches: clinical outcome and quality of life assessment. Ann Surg 228(4):588-597, 1998 6. Galandiuk S, Scott NA, Dozois RR, et al: Ileal pouch-anal anastomosis. Reoperation for pouch-related complications. Ann Surg 212(4):446452, 1990 7. Goldstein NS, Sanford WW, Bodzin JH: Crohn’s-like complications in patients with ulcerative colitis after total proctocolectomy and ileal pouch-anal anastomosis. Am J Surg Pathol 21(11):1343-1353, 1997 8. Ettore GM, Pescatori, Panis Y, et al: Mucosal changes in ileal pouches after restorative proctocolectomy for ulcerative and Crohn’s colitis. Dis Colon Rectum 43:1743-1748, 2000 9. Morpugo E, Petras R, Kimberling J, et al: Characterization and clinical behavior of Crohn’s disease initially presenting predominantly as colitis. Dis Colon Rectum:918-924, 2003 10. Pezim ME, Pemberton JH, Beart RW Jr, et al: Outcome of “indeterminant” colitis following ileal pouch–anal anastomosis. Dis Colon Rectum 32:653-658, 1989 11. Koltun WA, Schoetz DJ Jr, Roberts PL, et al: Indeterminate colitis predispose to perineal complications after ileal pouch-anal anastomosis. Dis Colon Rectum 34:857-860, 1991

Ileal pouch anal anastomosis and Crohn’s disease 12. McIntyre PB, Pemberton JH, Wolf BG, et al: Indeterminate colitis: longterm outcome in patients after ileal pouch-anal anastomosis. Dis Colon Rectum 38:51-54, 1995 13. Delaney CP, Remzi FH, Gramlich T, et al: Equivalent function, quality of life and pouch survival rates after ileal pouch-anal anastomosis for indeterminate and ulcerative colitis. Ann Surg 236:43-48, 2002 14. Brown CJ, McLean AR, Cohen Z, et al: Crohn’s disease and indeterminate colitis and ileal pouch-anal anastomosis: outcome and pattern of failure. Dis Colon Rectum 48:1542-1549, 2005 15. Sagar PM, Dozois RR, Wolf BG: Long term results of ileal pouch-anal anastomosis in patients with Crohn’s disease. Dis Colon Rectum 39(8): 893-898, 1996 16. Hyman NH, Fazio VW, Tuckson WB, et al: Consequences of ileal pouch-anal anastomosis for Crohn’s colitis. Dis Colon Rectum 34(8): 653-657, 1991 17. Braveman JM, Shoetz DJ, Marcello PW, et al: The fate of the ileal pouch in patients developing Crohn’s disease. Dis Colon Rectum 47:16131619, 2004 18. Panis Y, Poupart B, Nemeth J, et al: Ileal pouch-anal anastomosis for Crohn’s Disease. Lancet 347:854-857, 1996

95 19. Regimbeau JM, Panis Y, Pocard M, et al: Long-term results of ileal pouch-anal anastomosis for colorectal Crohn’s disease. Dis Colon Rectum 44:769-778, 2001 20. de Oca J, Sanchez-Santos R, Rague JM, et al: Long-term results of ileal pouch-anal anastomosis in Crohn’s disease. Inflamm Bowel Dis 9(3): 171-175, 2003 21. Mylonakis E, Robert NA, Keighley MRB: How does pouch construction for a final diagnosis of Crohn’s disease compare with ileoproctostomy for established Crohn’s proctocolitis? Dis Colon Rectum 44:113-143, 2001 22. Hartley JE, Fazio VW, Remzi FH, et al: Analysis of the outcome of ileal pouch-anal anastomosis in patients with Crohn’s disease. Dis Colon Rectum 47:1808-1815, 2004 23. Geboes K, Rutgeerts P, Opdenakker G, et al: Endoscopic and histologic evidence of persistent mucosal healing and correlation with clinical improvement following sustained infliximab treatment for Crohn’s disease. Curr Med Res Opin 21(11):1741-1754, 2005 Nov 24. Orlando A, Colombo E, Kohn A, et al: Infliximab in the treatment of Crohn’s disease: predictors of response in an Italian multicentric open study. Dig Liver Dis 37(8):577-583, 2005 Aug