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Background: While the majority of ulcerative colitis (UC) patients who undergo total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) have favorable outcomes, a proportion may subsequently develop Crohn's disease of the pouch or small intestine de novo that persists even after a permanent ileostomy. The aim of the study is to evaluate potential factors associated with the de novo development of CD of the small intestine proximal to an ileostomy created for pouch failure in patients who undergo IPAA.
Methods: UC patients who underwent TPC/IPAA and subsequent long-term/permanent ileostomy (secondary ileostomy) creation for a failed ileal pouch were compared to those who underwent TPC / end ileostomy (primary ileostomy). A total of 123 eligible patients were identified from our Pouch Registry (primary ileostomy group, N = 57 and secondary ileostomy group, N = 66). Demographic and clinical variables were compared. Outcomes including the development of CD, non-CD related strictures, the requirement of the use of CD-related medications, ileostomy-associated hospitalization, ileostomy failure with stoma revision or relocation, and short-gut syndrome were compared. Step-wise logistic regression models were used.
Results: The median follow-up for the cohort was 5 (range: 2.0-8.0) years. Eighteen pre-stoma factors were compared between the secondary ileostomy and the primary ileostomy groups. Younger age at diagnosis and surgery of UC, family history of IBD, extensive UC, toxic megacolon/fulminant colitis, preoperative symptom of severe diarrhea (more than 10 times per day), preoperative anti-TNF biological therapy, arthralgia/arthropathy, and staged surgery were more common in patients who underwent secondary ileostomy after a failed pouch, than those in the primary ileostomy group (p<0.05). There were no differences in smoking, body mass index, preoperative steroid/immunomodulators use, preoperative history of anemia/blood transfusion, duration from UC diagnosis to colectomy, and indication of colectomy (refractory UC vs. neoplasia) between the two groups (p>0.05). Adverse outcomes in both groups are listed in Table 1. Risk factors for de novo small bowel CD on logistic regression model are listed in Table 2.
Conclusions: Some patients with underlying UC who develop pouch failure develop CD of the small intestine that might indicate or contribute to an ileostomy. Knowledge of the factors associated with development of CD after IPAA may allow for an informed choice when evaluating patients for IPAA vs. TPC/EI.
Table 1. Postoperative outcomes statistics: secondary vs. primary ileostomies

Variables	All cases (N=123)	Secondary Ileostomy Group (N=66)	Primary Ileostomy Group (N=57)	P value
De novo small bowel CD	35	30 (45.5%)	5 (8.8%)	<0.001
CD-related stricture	28	23 (34.8%)	5 (8.8%)	0.001
Non-CD-related stricture	15	13 (19.7%)	2 (3.5%)	0.006
Stoma relocation/revision	19	15 (22.7%)	4 (7.0%)	0.016
Postoperative steroid use	9	8 (12.1%)	1 (1.8%)	0.037
Postoperative immunomodulator use	12	11 (16.7%)	1 (1.8%)	0.005
Postoperative anti-TNF biological therapy	12	10 (15.2%)	2 (3.5%)	0.030
Parastomal hernia	19	14 (21.2%)	5 (8.8%)	0.057
Stoma prolapse	8	6 (9.1%)	2 (3.5%)	0.284
Small bowel obstruction	37	32 (48.5%)	5 (8.8%)	<0.001
Small bowel resection/ stricturoplasty for strictures	40	32 (48.5%)	8 (14.0%)	<0.001
Short-gut syndrome	4	3 (4.5%)	1 (1.8%)	0.623
Postoperative TPN use	10	8 (12.1%)	2 (3.5%)	0.104
Ileostomy-associated hospitalization	47	38 (57.6%)	9 (15.8%)	<0.001
Post-enterocutaneous fistula	9	6 (9.1%)	3 (5.3%)	0.502

Table 2. Risk factors for de novo CD in patients with primary Ileostomy or secondary Ileostomy: Multivariable logistic analysis

Variables	N	Odds Ratio	95% Confidence Interval	P value
Secondary ileostomy	30 (85.7%)	8.229	2.432-27.845	0.001
Family history of IBD	23 (65.7%)	9.144	3.133-26.688	<0.001
History of preoperative weight loss	17 (51.5%)	3.716	1.232-11.209	0.020
Age at surgery	123	0.986	0.951-1.022	0.450
Age at diagnosis of UC	123	0.974	0.937-1.012	0.178
History of preoperative transfusion	11 (31.4%)	2.806	0.768-10.260	0.119