Cuff Inflammation Following Pouch Creation and Future Stricture, Fistula Development

Numerous advanced therapies have been introduced in recent years for the management of ulcerative colitis (UC), and it has been suggested that these novel therapies are contributing to a decreased need for colectomy among this patient population.¹ However, many individuals with UC still do not respond to medical management and require surgical intervention, most commonly in the form of a colectomy followed by the creation of an ileal pouch-anal anastomosis (IPAA) to restore intestinal continuity and prevent the need for an ileostomy.^2,3 In this approach, surgeons may elect to perform a stapled anastomosis without mucosectomy, which leaves a rectal remnant (cuff) and has been shown to improve functional outcomes.⁴

Although most patients with an IPAA report positive pouch health, inflammation of the pouch (pouchitis) and rectal cuff (cuffitis) are common and present with symptoms of increased frequency of bowel movements, urgency, and rectal bleeding.⁵ In addition to these symptoms, rectal cuff inflammation has been shown to increase the risk of pouch failure (pouch explant, pouch re-do, or diversion ileostomy), but it remains unknown by which specific mechanisms and clinical sequelae that this condition may be associated with poor long-term pouch outcomes.⁶

To address this gap in knowledge, Powers et al. conducted a retrospective cohort study of adult patients with inflammatory bowel disease (IBD) who underwent IPAA between January 2010 and December 2021. These patients were divided into cohorts based on whether they had demonstrated inflammation of the rectal cuff on one or more endoscopic evaluations (pouchoscopies) at any time following surgical completion. Outcomes of this study included the development of fistulas and strictures of the ileal pouch while excluding anastomotic and peri-anal disease. These diagnoses were recorded through review of imaging, endoscopic, and clinical visit data from electronic health records.

In total, this study identified 402 patients who met inclusion and exclusion criteria, with 182 (45%) patients in the endoscopic cuff inflammation cohort and 220 (55%) patients in the control cohort. Most patients included in this study were male (56.7%) and had been diagnosed with UC (93.8%). The overall median follow-up time was 3.2 (Interquartile range [IQR], 1.4-5.2) years after surgical completion, with the cuff inflammation cohort demonstrating a slightly longer follow-up (4.0 years; IQR, 2.3-6.2) compared to the control group (2.6 years; IQR, 1.2-4.5).

In total, 41 patients developed non-anastomotic strictures and 25 patients developed fistulas during the follow-up period. On univariable analysis, the development of non-anastomotic strictures and fistulas were both more frequent in the cohort with cuff inflammation (P = .001 and P = .032, respectively). Multivariable logistic regression models were fit to assess this relationship while controlling for potential confounders including pan-colitis disease distribution, duration of disease before colectomy, and history of extraintestinal (skin, eye, and joint) manifestations of IBD.

Controlling for these potential confounders, the endoscopic cuff inflammation cohort again demonstrated significantly higher odds of non-anastomotic strictures compared to individuals without cuff inflammation (Adjusted odds ratio [aOR], 3.47; 95% CI, 1.71 - 7.52; P <.001). For the development of fistulas, individuals with cuff inflammation had odds 2.57 times those of the cohort without cuff inflammation (aOR, 2.57; 95% CI, 1.11-6.47; P = .034). Additionally, a prior history of extraintestinal manifestations was significantly associated with fistula development (aOR, 2.82; 95% CI, 1.21-7.09; P = .020) but not strictures (P = .35).

From these results, this study suggests that endoscopic inflammation of the rectal cuff is associated with structural pathologies of the pouch, which may contribute to a higher risk of pouch failure. Patients undergoing pouchoscopy who are found to have cuff inflammation should therefore be monitored and treated for these specific structural conditions to limit the risk of long-term complications. Furthermore, this study suggests that extraintestinal manifestations may also predict structural pouch disease and should thus be considered when evaluating a patient’s risk for future pouch health.

Future directions from this study include performing time-to-event analyses given the varying follow-up times and considering whether more distal disease (anastomotic strictures, perianal fistulas) demonstrates the same trends noted in this study.

References:

1. ^{Ghoz H, Kesler A, Hoogenboom SA, et al. Decreasing Colectomy Rates in Ulcerative Colitis in the Past Decade: Improved Disease Control? J Gastrointest Surg. 2020;24(2):270-277. doi:10.1007/S11605-019-04474-9}
2. ^{Garcia-Planella E, Mañosa M, van Domselaar M, et al. Long-term outcome of ulcerative colitis in patients who achieve clinical remission with a first course of corticosteroids. Dig Liver Dis. 2012;44(3):206-210. doi:10.1016/J.DLD.2011.10.004}
3. ^{Ng KS, Gonsalves SJ, Sagar PM. Ileal-anal pouches: A review of its history, indications, and complications. World J Gastroenterol. 2019;25(31):4320. doi:10.3748/WJG.V25.I31.4320}
4. ^{Chambers WM, Mortensen NJMC. Should ileal pouch-anal anastomosis include mucosectomy? Colorectal Dis. 2007;9(5):384-392. doi:10.1111/J.1463-1318.2007.01211.X}
5. ^{Zezos P, Saibil F. Inflammatory pouch disease: The spectrum of pouchitis. World J Gastroenterol. WJG. 2015;21(29):8739. doi:10.3748/WJG.V21.I29.8739}
6. ^{Kayal M, Plietz M, Rizvi A, et al. Inflammatory Pouch Conditions Are Common After Ileal Pouch Anal Anastomosis in Ulcerative Colitis Patients. Inflamm Bowel Dis. 2020;26(7):1079-1086. doi:10.1093/IBD/IZZ227}