Risk factors and long-term prognosis for colorectal strictures in ulcerative colitis

Table 1 Basic information and clinical characteristics of the study population, mean ± SD/n (%)

	Stricture group			Non-stricture group	1P value	2P value
	All stricture cases	Malignant stricture group	Benign stricture group
Number of patients	116	10	106	822
Male	58 (50.0)	6 (60.0)	52 (49.1)	474 (57.7)	0.119	0.092
Age at diagnosis, year (median, IQR)	38.97 (30.52-49.39)	36.06 (32.19-42.39)	40.69 (29.36-51.95)	34.50 (26.61-47.14)	0.020	0.016
≥ 40	57 (49.1)	3 (30.0)	54 (50.9)	310 (37.7)	0.018	0.009
Disease duration, year (median, IQR)	11.55 (7.13-18.74)	25.39 (19.38-32.39)	10.75 (6.81-15.69)	8.96 (5.67-13.59)	< 0.001	0.005
Follow-up time, year (median, IQR)	9.85 (4.25-17.22)	24.10 (19.17-32.37)	7.95 (3.70-14.42)	8.65 (4.87-12.82)	0.373	0.660
Montreal classification					0.068	0.023
E1 (proctitis)	23 (19.8)	0 (0.0)	23 (21.7)	104 (12.7)
E2 (left-sided colitis)	28 (24.1)	3 (30.0)	25 (23.6)	253 (30.8)
E3 (pancolitis)	65 (56.0)	7 (70.0)	58 (54.7)	465 (56.6)
Smoking status					0.736	0.961
Active smoker	7 (6.0)	0 (0.0)	7 (6.6)	58 (7.1)
Former smoker	19 (16.4)	0 (0.0)	19 (17.9)	154 (18.7)
Nonsmoker	90 (77.6)	10 (100.0)	80 (75.5)	610 (74.2)
Family history of IBD	4 (3.4)	1 (10.0)	3 (2.8)	39 (4.7)	0.532	0.519
Family history of CRC	3 (2.6)	0 (0.0)	3 (2.8)	33 (4.0)	0.623	0.744
History of appendectomy	2 (1.7)	0 (0.0)	2 (1.9)	16 (1.9)	1.000	1.000
Weight loss	81 (69.8)	6 (60.0)	75 (70.8)	544 (66.2)	0.435	0.347
Extraintestinal involvement	27 (23.3)	3 (30.0)	24 (22.6)	112 (13.6)	0.006	0.013
Arthropathy	4 (3.4)	0 (0.0)	4 (3.8)	40 (4.9)	0.499	0.618
Skin lesions	7 (6.0)	0 (0.0)	7 (6.6)	25 (3.0)	0.165	0.108
Oral ulcer	12 (10.3)	1 (10.0)	11 (10.4)	44 (5.4)	0.034	0.039
Ophthalmopathy	1 (0.9)	0 (0.0)	1 (0.9)	4 (0.5)	0.484	0.455
Thrombosis	9 (7.8)	1 (10.0)	8 (7.5)	13 (1.6)	< 0.001	< 0.001
PSC	2 (1.7)	1 (10.0)	1 (1.2)	10 (1.2)	0.989	1.000
Hemoglobin, g/L	103.78 ± 23.59	108.10 ± 20.43	103.38 ± 23.91	111.63 ± 26.28	< 0.001	< 0.001
CRP, mg/L (median, IQR)	11.82 (2.20, 43.65)	4.61 (2.57, 20.35)	12.41 (2.10, 44.23)	9.27 (2.07, 33.00)	0.374	0.268
ESR, mm/hour (median, IQR)	23 (12, 46)	15 (7, 16)	24 (12, 49)	20 (9, 40)	0.171	0.097
Treatment until stricture or the end of follow-up
5-ASA	111 (95.7)	10 (100.0)	101 (95.3)	811 (98.7)	0.053	0.034
Systemic glucocorticoids	98 (84.5)	7 (70.0)	91 (85.8)	611 (74.3)	0.017	0.009
Immunomodulators	32 (27.6)	2 (20.0)	30 (28.3)	202 (24.6)	0.483	0.404
Biologics	25 (21.6)	0 (0.0)	25 (23.6)	314 (38.2)	< 0.001	0.003

¹Statistical comparisons were conducted between stricture and non-stricture groups.

²Statistical comparisons were limited to the benign-stricture and non-stricture groups; the malignant-stricture group (n = 10) was summarized descriptively and omitted from the main analyses owing to its small size.

IQR: Interquartile range; IBD: Inflammatory bowel disease; CRC: Colorectal cancer; PSC: Primary sclerosing cholangitis; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; 5-ASA: 5-aminosalicylic.

Table 2 Prognostic outcomes of the stricture and non-stricture group, n (%)

	Stricture group			Non-stricture group (n = 822)	1P value	2P value
	All stricture cases (n = 116)	Malignant stricture group (n = 10)	Benign stricture group (n = 106)
Clinical activity until surgery or the end of follow-up					< 0.001	< 0.001
Clinical remission	31 (26.7)	3 (30.0)	28 (26.4)	372 (45.3)
Mild activity	28 (24.1)	6 (60.0)	22 (20.8)	220 (26.8)
Moderate activity	34 (29.3)	1 (10.0)	33 (31.1)	131 (15.9)
Severe activity	23 (19.8)	0 (0.0)	23 (21.7)	99 (12.0)
Steroid dependence	28 (24.1)	0 (0.0)	28 (26.4)	128 (15.6)	0.020	0.005
Steroid resistance	8 (6.9)	0 (0.0)	8 (7.5)	25 (3.0)	0.066	0.038
UC-related surgery	64 (55.2)	10 (100.0)	54 (50.9)	107 (13.0)	< 0.001	< 0.001
CRC	10 (8.7)			23 (2.8)	0.003
Severe intestinal complications	37 (31.9)	4 (40.0)	33 (31.1)	53 (6.4)	< 0.001	< 0.001
Bleeding	8 (6.9)	0 (0.0)	8 (7.5)	33 (4.0)	0.155	0.157
Perforation	5 (4.3)	1 (10.0)	4 (3.8)	9 (1.1)	0.024	0.077
Obstruction	21 (18.1)	2 (20.0)	19 (17.9)	6 (0.7)	< 0.001	< 0.001
Fistula	3 (2.6)	1 (10.0)	2 (0.5)	3 (0.4)	0.028	0.103
Toxic megacolon	4 (3.4)	0 (0.0)	4 (3.8)	4 (0.5)	0.010	0.004
All-cause mortality	4 (3.4)	2 (20.0)	2 (1.9)	20 (2.4)	0.738	0.993

¹Statistical comparisons were conducted between stricture and non-stricture groups.

²Statistical comparisons were limited to the benign-stricture and non-stricture groups; the malignant-stricture group (n = 10) was summarized descriptively and omitted from the main analyses owing to its small size.

UC: Ulcerative colitis; CRC: Colorectal cancer.

Table 3 Clinical features of benign and malignant strictures, n (%)

	All stricture cases	Malignant stricture	Benign stricture	P value
Number of patients	116	10	106
Number of strictures				0.409
1	99 (85.3)	9 (90.0)	90 (84.9)
2	16 (13.8)	1 (10.0)	15 (14.2)
3	1 (0.9)	0 (0.0)	1 (0.9)
Male	58 (50.0)	4 (40.0)	54 (50.9)	0.822
Age at diagnosis, year (median, IQR)	38.97 (30.52-49.39)	36.06 (32.19-42.39)	40.69 (29.36-51.95)	0.426
Median age at diagnosis of stricture, year (median, IQR)	47.83 (36.65-60.16)	60.99 (50.58-63.38)	46.80 (36.01-58.10)	0.042
Median duration from diagnosis to stricture formation, year (median, IQR)	5.25 (2.45-12.76)	18.88 (16.29-24.75)	4.49 (2.27-9.64)	< 0.001
Location of the stricture				0.041
Rectum	31 (23.1)	4 (36.4)	27 (22.0)
Left colon	83 (61.9)	3 (27.3)	80 (65.0)
Right colon	20 (14.9)	4 (36.4)	16 (13.0)
Clinical activity until surgery or the end of follow-up				0.016
Clinical remission	31 (26.7)	3 (30.0)	28 (26.4)
Mild activity	28 (24.1)	6 (60.0)	22 (20.8)
Moderate activity	34 (29.3)	1 (10.0)	33 (31.1)
Severe activity	23 (19.8)	0 (0.0)	23 (21.7)
Steroid dependence	28 (24.1)	0 (0.0)	28 (26.4)	0.139
Steroid resistance	8 (6.9)	0 (0.0)	8 (7.5)	1.000
UC-related surgery	64 (55.2)	10 (100.0)	54 (50.9)	0.008
Severe intestinal complications	37 (31.9)	4 (40.0)	33 (31.1)	0.826
Bleeding	8 (6.9)	0 (0.0)	8 (7.5)	1.000
Perforation	5 (4.3)	1 (10.0)	4 (3.8)	0.368
Obstruction	21 (18.1)	2 (20.0)	19 (17.9)	1.000
Fistula	3 (2.6)	1 (10.0)	2 (0.5)	0.239
Toxic megacolon	4 (3.4)	0 (0.0)	4 (3.8)	1.000
All-cause mortality	4 (3.4)	2 (20.0)	2 (1.9)	0.037

IQR: Interquartile range; UC: Ulcerative colitis.

Table 4 Univariate and multivariate Cox regression analysis of risk factors for colorectal stricture formation in ulcerative colitis¹

Variables	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Male	0.896 (0.621-1.293)	0.557
Age at diagnosis ≥ 40 year	2.273 (1.562-3.308)	< 0.001	2.197 (1.487-3.242)	< 0.001
Montreal classification		0.079		0.228
E1 (proctitis)	1		1
E2 (left-sided colitis)	0.555 (0.319-0.963)	0.036	0.610 (0.347-1.073)	0.087
E3 (pancolitis)	0.846 (0.525-1.362)	0.491	0.780 (0.478-1.275)	0.322
Extraintestinal involvement	2.077 (1.346-3.205)	< 0.001	2.072 (1.326-3.239)	0.001
Hemoglobin	0.986 (0.979-0.992)	< 0.001	0.988 (0.980-0.995)	0.001
CRP	1.007 (1.002-1.011)	0.003	1.004 (0.999-1.010)	0.145
ESR	1.008 (1.001-1.015)	0.028	0.995 (0.986-1.004)	0.301
Treatment until stricture or the end of follow-up
5-ASA	0.406 (0.163-1.012)	0.053	0.214 (0.077-0.595)	0.003
Systemic glucocorticoids	1.895 (1.145-3.135)	0.013	2.360 (1.325-4.203)	0.004
Immunomodulators	0.985 (0.654-1.482)	0.942
Anti-TNF-α	0.764 (0.450-1.298)	0.320	0.911 (0.517-1.604)	0.746
VDZ	0.370 (0.199-0.689)	0.002	0.382 (0.203-0.720)	0.003
UST	0.049 (0.0-5887.28)	0.614	0.000(0.0-2.4E+163)	0.961

¹Model assumptions were validated: Proportional hazards assumption satisfied (global P = 0.274), and multicollinearity absent (all variance inflation factor < 2.5).

HR: Hazard ratio; CI: Confidence interval; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; 5-ASA: 5-aminosalicylic; anti-TNF-α: Anti-tumor necrosis factor-α; VDZ: Vedolizumab; UST: Ustekinumab.