Pouch Body Anastomotic Ulcerations Are Not Associated With an Increased Risk of Pouchitis

Introduction

Restorative proctocolectomy (RPC) with ileal pouch–anal anastomosis (IPAA) is the most common surgical treatment for patients with ulcerative colitis (UC) complicated by medically refractory disease or dysplasia. RPC with IPAA is performed in a 1-, 2-, or 3-stage approach that involves subtotal colectomy, proctectomy, and pouch construction. While inflammatory pouch disorders are the most common long-term complication after RPC with IPAA, structural pouch disorders may also occur.

Among structural pouch disorders, pouch body anastomotic ulcerations are frequently seen in practice but are infrequently described in the literature. Small case series have reported an incidence of pouch body anastomotic ulcerations of 3% to 15% and an association with hematochezia.^1-3 Although theorized to be secondary to local ischemia, the true pathogenesis of pouch body anastomotic ulcerations is unknown. Furthermore, whether pouch body anastomotic ulcerations have an impact on symptoms, development of pouchitis, or pouch outcomes has not been elucidated.

In an effort to better understand the significance of pouch body anastomotic ulcerations, the aim of this study was to report on the occurrence of pouch body anastomotic ulcerations in patients with UC or inflammatory bowel disease unclassified (IBDU) who underwent RPC with IPAA and study their impact on pouch outcomes.

Methods

We performed a retrospective review of patients with UC or IBDU complicated by medically refractory disease or dysplasia who underwent RPC with IPAA at Mount Sinai Hospital between January 2008 and December 2021 and at least 1 subsequent pouchoscopy. Patients <18 years of age or with a baseline diagnosis of Crohn’s disease before colectomy were excluded.

Medical charts were reviewed for patient demographics, medical and surgical history, and pouchoscopy reports. Data were collected systematically and entered into a standardized data collection sheet. Pouch body anastomotic ulcerations were defined as ulcerations along the vertical staple line in the pouch body noted during pouchoscopy. Pouchitis was defined as a modified Pouchitis Disease Activity Index score ≥5 using clinical and endoscopic subscores. The modified Pouchitis Disease Activity Index was calculated retrospectively for each patient using clinical and pouchoscopy notes. Cuffitis was defined as endoscopic evidence of mucosal edema, granularity, friability, loss of vascular pattern, mucosal exudate, and/or ulceration in the cuff. Pouch failure was defined as the need for a permanent diverting ileostomy or pouch excision with construction of an end ileostomy.

Descriptive statistics were performed to describe baseline characteristics of the study population and were reported as proportions or medians (with interquartile ranges [IQRs]) for categorical and continuous variables, respectively. Univariable and multivariable logistic regression for the primary outcomes of pouchitis and pouch failure was performed. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were reported.

Results

A total of 1183 pouchoscopy procedures were performed in 395 patients >18 years of age between 2009 and 2021. The most common indications for pouchoscopy procedures were surveillance (n = 454, 38.4%) and increased bowel movements (n = 205, 17.3%). The median pouch duration was 3.4 (IQR, 2.0-6.4) years, and 211 (53.4%) patients were male. Cohort demographics are provided in Table 1.

Table 1.

Clinical characteristic of pouch patients (N = 395)

Sex
Male	211 (53.4)
Female	184 (46.6)
Age at colectomy, y	38 (27-50)
Family history of IBD	87 (22.0)
Disease extent
Left sided	81 (20.5)
Extensive	314 (79.5)
Indication for colectomy
Medically refractory ulcerative colitis	336 (85.1)
Dysplasia/cancer	59 (14.9)
Number of surgical stages
One	36 (9.1)
2	151 (38.2)
3	208 (52.7)
IPAA anastomosis
Stapled	283 (71.6)
Hand-sewn	112 (28.4)
IPAA requiring surgical revision	61 (15.4)
Tobacco use at colectomy
Current	19 (4.8)
Former	80 (20.3)
Never	249 (63.0)
Unknown	47 (11.9)
Medications at index pouchoscopy
None	166 (42.0)
Antimotility agents	124 (31.4)
Antibiotics	82 (20.8)
Probiotics	15 (3.80)
Unknown	18 (4.56)

Values are n (%) or median (interquartile range).

Abbreviations: IBD, inflammatory bowel disease; IPAA, ileal pouch–anal anastomosis.

Of the 1183 pouchoscopy procedures performed, pouch body anastomotic ulcerations were identified in 77 (6.5%) procedures performed in 68 patients a median duration of 1.5 (IQR, 0.5-2.3) years after final surgical stage. Among these procedures, pouchitis was noted in 28 (36.4%) patients and cuffitis in 22 (28.6%). Pouch body anastomotic ulcerations were the only endoscopic finding in 26 (2.2%) pouchoscopy procedures performed in 23 patients. The most common indications for these pouchoscopy procedures were increased stool frequency (30.7%), dysplasia surveillance (23.1%), and hematochezia (15.3%).

Among the 23 patients with only pouch body anastomotic ulcerations on pouchoscopy, the median hemoglobin was 11.9 (IQR, 9.8-12.5) g/dL. Six (26.1%) had a previous diagnosis of pouchitis and 3 (13.0%) had a previous diagnosis of cuffitis. The median follow-up for these patients was 3.93 (IQR, 2.29-5.90) years. Within this group, 6 (26.0%) patients subsequently developed pouchitis and 2 (8.7%) subsequently developed cuffitis. On univariable analysis, staple line ulcers were not significantly associated with development of pouchitis (OR, 1.42; 95% CI, 0.80-2.52) or pouch failure (OR, 1.23; 95% CI, 0.49-3.12). Among all patients, staple line ulcers remained on subsequent pouchoscopy procedures in 6 (8.8%) patients.

Discussion

In this large single-center study of 1183 pouchoscopy procedures performed in 395 patients with UC or IBDU who underwent RPC with IPAA, pouch body anastomotic ulcerations were present in 77 (6.5%) procedures. The most common indication for pouchoscopy in patients with isolated pouch body anastomotic ulcerations was increased stool frequency, an interesting finding given the otherwise normal pouch. Reassuringly, pouch body anastomotic ulcerations were not associated with subsequent pouchitis or pouch failure.

Although the etiology of pouch body anastomotic ulcerations is unknown, their development is largely theorized to be related to underlying ischemia. Previous studies have postulated that the mucosa of the pouch body anastomosis is compressed during surgery, leading to ischemia and ulcer formation.¹ However, pouch body anastomotic ulcerations may appear years after surgery and proceed to disappear and then reappear. Hence, the transient ischemia that occurs during surgery may not be enough to explain their occurrence. Pouch body anastomotic ulcerations may also be secondary to staple-related granuloma formation and the local mucosa’s response to foreign material. Finally, there may be inflammatory factors at play that have yet to be determined, as there is histologic evidence of inflammation in biopsies taken from pouch body anastomotic ulcerations.^1,2

Ileocolic anastomotic ulcerations commonly occur in patients with Crohn’s disease, with incidence rates as high as 50%.⁴ There is much debate as to whether these ulcers are a consequence of ischemia, inverted vs everted staple lines, or Crohn’s disease recurrence.^4,5 Regardless, multiple studies have shown that ileocolic anastomotic ulcerations in patients with Crohn’s disease independently predict disease progression.^4,6 In contrast, pouch body anastomotic ulcerations have not been shown to impact pouch outcomes. Whether these 2 types of anastomotic ulcerations reflect ischemia or inflammation or type of anastomosis (inverted vs everted) remains to be elucidated.

This study had a number of strengths including a large sample size with over 1100 pouchoscopy procedures and strict definitions of pouch body anastomotic ulcerations, pouchitis, cuffitis, and pouch failure. This study’s major limitation was patient loss to follow-up, as it was restricted to patients who had their RPC with IPAA and pouchoscopy at Mount Sinai Hospital. Patients who may have had pouchoscopy procedures at different institutions were excluded, and assessment for the presence of pouch body anastomotic ulcerations or inflammatory pouch outcomes was not possible.

Conclusions

Patients with isolated pouch body anastomotic ulcers may present with clinically significant symptoms such as increased stool frequency and hematochezia that overlap with those of pouchitis and cuffitis. Pouchoscopy is necessary to delineate these diagnoses and avoid empiric treatment with antibiotics or suppositories. Further studies are necessary to elucidate the pathophysiology of pouch body anastomotic ulcerations and develop appropriate therapy.

Author Contributions

M.H., M.K.—conception/design of study. M.H., M.P., M.K.—data collection. M.H., M.K.—interpreting data. M.H., M.K.—drafting manuscript. M.H., M.P., S.K., P.S., A.G., M.C.D., M.K.—editing manuscript.

Funding

M.K. is supported via National Institutes of Health K23DK127241-01A1, a Crohn’s and Colitis Foundation Litwin Grant, and a Rainin Health Innovator Award.

Conflicts of interest

M.K. has served as a consultant or on an advisory board for GoodRx, Pfizer, AbbVie, and Fresenius. M.C.D. has served as a consultant for AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim International, Bristol-Myers Squibb, Celgene, Eli Lilly, F. Hoffman-La Roche, Genentech, Gilead, Janssen, Pfizer, Prometheus, Takeda, and UCB; has received research grants from Pfizer, AbbVie, Janssen, and Prometheus; and has ownership interest in Trellus and licensing fees from Takeda. All other authors disclose no conflicts.