Eiichi Nakao; Kenji Tatsumi; Nao Obara; Koki Goto; Hirosuke Kuroki; Akira Sugita; Kazutaka Koganei

doi:10.3393/ac.2025.00766.0109

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Original Article Inflammatory/benign bowel disease Long-term risk factors of stoma construction after loose seton placement for Crohn disease–associated perianal fistulas: Eiichi Nakao, Kenji Tatsumi, Nao Obara, Koki Goto, Hirosuke Kuroki, Akira Sugita, Kazutaka Koganei; Annals of Coloproctology 2025;41(6):565-572.
DOI: https://doi.org/10.3393/ac.2025.00766.0109
Published online: December 26, 2025

Department of Inflammatory Bowel Disease, Yokohama Municipal Citizen’s Hospital, Yokohama, Japan

Correspondence to: Eiichi Nakao, MD Department of Inflammatory Bowel Disease, Yokohama Municipal Citizen’s Hospital, 1-1 Mitsuzawa Nishi-machi, Kanagawa-ku, Yokohama 221-0855, Japan Email: fukushima.med.mismo@gmail.com

• Received: June 19, 2025 • Revised: August 5, 2025 • Accepted: September 4, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ARTICLE INFORMATION
Supplementary materials
REFERENCES

Abstract

Purpose
To evaluate long-term outcomes and identify prognostic factors for stoma construction following loose seton placement in patients with Crohn disease (CD)-associated perianal fistulas.
Methods
This single-center, retrospective study included 136 patients who underwent initial loose seton placement for CD-associated perianal fistulas between 1999 and 2021, with at least 3 years of follow-up. Patient demographics, anorectal findings, and perioperative pharmacotherapy were assessed. Prognosis was defined as the cumulative incidence of stoma formation. Independent risk factors were identified using multivariate logistic regression. The association between postoperative molecular-targeted therapy and stoma-free survival was further analyzed in patients with severe anal ulceration and rectal stricture (high-risk features). Kaplan-Meier curves and log-rank tests were used for comparisons.
Results
During follow-up, 42 patients required stoma construction. Severe anal ulceration (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.04–5.38; P=0.039), rectal stricture (OR, 2.84; 95% CI, 1.09–7.37; P=0.032), and absence of postoperative molecular-targeted therapy (OR, 0.36; 95% CI, 0.15–0.84; P=0.018) were independent risk factors. In patients with severe anal ulceration, the cumulative stoma construction rate was significantly lower with postoperative molecular-targeted therapy (P=0.018). No significant difference was observed in patients with rectal strictures (P=0.058).
Conclusion
Severe anal ulceration, rectal stricture, and absence of postoperative molecular-targeted therapy were independently associated with stoma construction. Postoperative molecular-targeted therapy improved stoma-free survival in patients with severe anal ulceration. Individualized treatment strategies, including early pharmacological intervention, may improve long-term outcomes and preserve anorectal function. Tailoring treatment according to lesion characteristics may reduce stoma formation and enhance quality of life in CD-associated perianal disease.
Keywords: Crohn disease; Rectal fistula; Drainage; Stoma; Risk factors

INTRODUCTION

Crohn disease (CD) is a chronic, immune-mediated disorder that can affect any part of the gastrointestinal tract, from the mouth to the anus. Studies from Japan, Europe, and the United States have reported that anal lesions occur in 30% to 50% of patients, often resulting in a substantial decline in quality of life [1, 2]. These lesions are also considered important indicators of disease activity, and many patients ultimately require surgical intervention. Among surgical options, the loose seton procedure offers distinct advantages. It provides effective drainage of infected tracts while preserving anal sphincter function, thereby maintaining long-term continence [3]. However, healing is generally prolonged, and complete fistula closure remains difficult to achieve. Recently, combination therapy with seton placement and anti–tumor necrosis factor (TNF)-α antibodies has demonstrated fistula closure rates exceeding 50%, leading to improved overall outcomes [4].

A subset of patients does not respond adequately to either medical therapy or local surgical interventions and eventually requires stoma construction. Reported stoma construction rates for CD-associated anorectal lesions range from 20% to 62%, underscoring the challenge of managing refractory disease [5–9]. Although several studies have shown the efficacy of combining seton placement with anti-TNF-α therapy in complex anorectal fistulas, the specific anorectal findings that predict poor outcomes remain poorly defined. Moreover, most available studies focus on short-term results, and long-term outcome data on this combined approach are limited [10–14].

The present study aimed to investigate the long-term clinical course of patients with CD-associated perianal fistulas treated with loose seton placement and to identify anorectal findings that predict poor outcomes, including the need for stoma construction. By clarifying long-term outcomes and risk factors, this study aims to inform future treatment strategies and improve the quality of life of patients with this challenging condition.

METHODS

Ethics statement

This study was approved by the Institutional Review Board of Yokohama Municipal Citizen’s Hospital (No. Z241202). Written informed consent was obtained from all participants before enrollment. All study procedures were conducted in accordance with the principles of the Declaration of Helsinki and all applicable local laws and regulations.

Study design and patients

This single-center, retrospective observational study included patients diagnosed with CD-associated anorectal fistulas who underwent an initial loose seton procedure at our institution between January 1999 and December 2021. Eligible patients were identified through the electronic medical record system using the International Classification of Diseases, 10th Revision (ICD-10) codes K50.0 and K50.1 and were required to have at least 3 years of follow-up after the initial surgery. Patients were excluded if stoma construction had been performed before or at the same time as the first seton placement, or if follow-up data were unavailable during the observation period.

Collected data included patient demographics, anorectal findings at the time of the initial seton placement, and the use of preoperative and postoperative medications. These anorectal findings, including rectal stricture and anal ulceration, were assessed exclusively at the time of the initial loose seton placement. Preoperative medications were defined as those administered within 3 months before surgery, whereas postoperative medications were defined as those initiated within 6 months after surgery.

Anal lesions were classified according to the system proposed by Hughes and Taylor [15], and fistulas were categorized using the American Gastroenterological Association (AGA) criteria [16]. Among the primary lesions described by Hughes and Taylor [15], cavitating ulcers and aggressive ulcerations were classified as severe anal ulcerations.

Treatment strategy

At our institution, surgical management of CD-associated perianal fistulas is limited to incision and drainage, loose seton placement, and stem cell therapy, with a primary focus on preserving anorectal function. Of these, the loose seton procedure serves as the first-line approach, providing continuous drainage while maintaining sphincter integrity. All procedures were performed under general anesthesia, in accordance with institutional policy to ensure adequate pain control and facilitate precise identification of fistula tracts. The entire fistula tract was identified and encircled with a vessel loop to allow adequate drainage. The seton was removed once local inflammation had subsided. Notably, none of the patients in this study met the clinical criteria for stem cell therapy. If disease progression occurred, reoperation or stoma construction was considered. Indications for stoma construction included persistent infection unresponsive to treatment and severe defecatory dysfunction. Patients were stratified into 2 groups based on whether stoma construction was required during follow-up: group A included patients who did not undergo stoma construction, while group B included those who ultimately required stoma construction. Details of surgical procedures for perianal lesions during the study period are provided in Supplementary Table 1.

Statistical analysis

All statistical analyses were conducted using EZR ver. 1.65 (Saitama Medical Center, Jichi Medical University), a modified version of R (The R Foundation for Statistical Computing) that incorporates statistical functions commonly applied in biostatistics [17]. Binary and categorical variables were expressed as counts and percentages, while continuous variables were presented as medians with interquartile ranges. Univariate analyses were performed to compare variables between the 2 groups. Binary and categorical variables were analyzed using Fisher exact test, and continuous variables were compared with the Mann-Whitney U-test. Variables with P<0.05 in univariate analysis were included in a multivariate logistic regression model to identify independent risk factors for stoma construction.

In subgroup analyses, cumulative stoma construction rates were estimated using the Kaplan-Meier method, and differences between groups were evaluated with the log-rank test. To adjust for multiple comparisons, the Bonferroni correction was applied, and statistical significance was defined as P<0.025.

RESULTS

Patient selection and baseline characteristics

As shown in Fig. 1, 136 patients who met the inclusion criteria were enrolled in this study. Of these, 52 patients did not require reoperation, and the seton could be removed in 37. In contrast, among the 84 patients who required reoperation, 42 underwent stoma construction during the follow-up period. Among the 42 patients who received a stoma, 26 underwent proctectomy at the time of stoma construction. An additional 9 patients initially received a diverting stoma but later required proctectomy due to disease progression. The remaining 7 patients also received a diverting stoma, but none have achieved stoma closure to date. Consequently, all 42 patients ultimately retained a stoma, and 35 (83.3%) underwent proctectomy.

Table 1 summarizes the patients’ background factors and anorectal findings at the time of the initial seton procedure. Group A had a significantly higher proportion of patients with the ileal type and initial procedures performed after 2010, whereas group B showed a significantly higher incidence of severe anal ulceration as the primary lesion and rectal stricture as a secondary lesion.

Preoperative and postoperative medical therapy

There were no significant differences in the use of preoperative medical therapy between the 2 groups. However, a greater proportion of patients in group A received postoperative molecular-targeted therapy, suggesting that postoperative administration of molecular-targeted therapy may have contributed to improved clinical outcomes (Table 2).

Multivariate analysis of risk factors for stoma construction

Multivariate analysis identified 3 independent predictors of stoma construction: severe anal ulceration (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.04–5.38; P=0.039), rectal stricture (OR, 2.84; 95% CI, 1.09–7.37; P=0.032), and absence of postoperative molecular-targeted therapy (OR, 0.36; 95% CI, 0.15–0.84; P=0.018) (Table 3).

Subgroup analysis

As shown in Fig. 2A, among patients with severe anal ulceration, the cumulative stoma construction rate was significantly lower in those who received postoperative molecular-targeted therapy (P=0.018). A similar trend was observed in patients with rectal strictures (Fig. 2B); however, the difference was not statistically significant (P=0.058).

DISCUSSION

This retrospective study evaluated prognostic factors associated with long-term stoma construction in patients who underwent loose seton placement for CD-associated perianal fistulas. The analysis showed that severe anal ulceration, rectal stricture, and absence of postoperative molecular-targeted therapy were independently associated with a significantly increased risk of stoma construction. Furthermore, subgroup analysis revealed that, among patients with severe anal ulcerative lesions, those who received postoperative molecular-targeted therapy had a significantly lower cumulative incidence of stoma construction.

Cavitating ulcers and aggressive ulcerations indicate high inflammatory activity in CD and are characterized by deep tissue destruction, extensive ulceration, and a propensity for fistula formation through infiltration of surrounding structures [15]. These lesions frequently involve the anal sphincter, profoundly impairing the local healing environment, contributing to resistance to conservative therapy, and leading to delayed or refractory healing. In the present study, patients with severe ulcerations had a significantly higher rate of stoma construction. These findings align with previous reports recommending early proctectomy in refractory anorectal disease, with up to 25% of patients ultimately undergoing this procedure [18, 19].

Interestingly, even among high-risk patients with severe anal ulceration who were otherwise predisposed to stoma construction, postoperative molecular-targeted therapy was associated with a lower incidence of stoma formation. This suggests that, even in inflammation-dominant lesions, postoperative molecular-targeted therapy may reduce the likelihood of stoma construction and improve long-term outcomes.

The findings concerning patients with rectal strictures also merit attention. In this study, rectal stricture was significantly associated with a higher risk of stoma construction. This association likely reflects the progression of chronic local anorectal inflammation, leading to fibrotic stricture formation, defecatory dysfunction, and infectious complications that often necessitate surgical intervention. Xu et al. [20] reported that approximately 32% of patients with CD-associated perianal fistulas presented with anorectal stenosis, and identified high Crohn’s Disease Activity Index (CDAI) scores and older age at diagnosis as significant risk factors. They also emphasized that fibrotic changes were predominant in strictures and that conservative treatment was generally ineffective. Consistent with these findings, our study demonstrated no statistically significant difference in cumulative stoma construction rates between patients with and without postoperative molecular-targeted therapy among those with rectal strictures (P=0.058). These results suggest that biologic therapy has limited efficacy in controlling disease progression in fibrotic-dominant strictures, underscoring the importance of tailoring therapeutic strategies according to lesion morphology. Furthermore, our study found that patients with colonic or ileocolonic disease had a higher incidence of stoma construction compared with those with isolated ileal disease. This observation is consistent with previous reports, including the study by Singh et al. [21], which demonstrated that colonic involvement is associated with more severe anorectal manifestations and higher surgical burdens. Together, these findings suggest that the anatomical distribution of intestinal disease influences the severity and prognosis of perianal involvement, reinforcing the need for individualized treatment strategies that consider both lesion morphology and disease location.

The role of postoperative molecular-targeted therapy in managing CD-associated perianal disease is also important. The European Crohn's and Colitis Organisation (ECCO) guidelines recommend continuation of pharmacological therapy following surgery and emphasize that anti-TNF-α agents, particularly in combination regimens, are effective in promoting fistula healing and reducing recurrence of CD-associated perianal disease [22]. In this study, patients who received postoperative molecular-targeted therapy generally had lower stoma construction rates, supporting its potential benefit, especially in inflammation-dominant lesions. However, the efficacy of biologics in advanced lesions such as severe anal ulceration, rectovaginal fistulas, and rectal strictures remains uncertain. Bouguen et al. [23] reported that anti-TNF-α therapy achieved ulcer healing in approximately 80% of patients with cavitating ulcers, whereas Wallenhorst et al. [24] described limited efficacy under similar conditions. For rectovaginal fistulas, Sands et al. [25] reported a 45% fistula closure rate at 3 months following anti-TNF-α therapy in the ACCENT II trial, while Parsi et al. [26] documented a complete response rate of only 14% in a comparable cohort. These findings indicate that the therapeutic effect of biologics may vary depending on lesion morphology, particularly the distinction between inflammatory and fibrotic disease.

Unlike previous studies that focused primarily on short-term endpoints such as fistula closure or ulcer healing, our study employed stoma construction as a long-term, objective outcome directly linked to quality of life, with a median follow-up of more than 100 months. The results suggest that postoperative molecular-targeted therapy may help reduce the need for stoma construction in inflammation-driven disease, whereas its effectiveness is limited in fibrotic lesions. This highlights the need for individualized treatment strategies based on lesion characteristics.

Limitations

Several limitations of the present study should be acknowledged. First, this was a single-center retrospective study with a relatively small sample size. Nonetheless, the strength of this study lies in the detailed evaluation of prognostic factors, such as severe anal ulceration and rectal stricture, which have not been extensively investigated in previous research. Future multicenter studies are warranted to validate these findings in larger cohorts. Second, treatment strategies, including the use of molecular-targeted therapy, evolved over the long study period (1999–2021). The decision to initiate postoperative molecular-targeted therapy was not standardized and was left to the discretion of the attending physicians, potentially introducing confounding factors that may have influenced the observed treatment effects. Third, there is the possibility of selection bias, as this study was conducted at a specialized referral center for inflammatory bowel disease. Patients with more severe perianal disease, such as refractory anal ulcers or rectal involvement, were more likely to undergo seton placement and be referred to our institution. This referral pattern may have contributed to the higher-than-expected rate of stoma formation compared with previous reports.

Conclusions

This study identified key risk factors for stoma construction following seton placement in patients with CD-associated anal fistulas. Our findings also suggest that postoperative molecular-targeted therapy may help reduce the risk of stoma formation in high-risk patients. These insights highlight the importance of individualized treatment strategies and may contribute to the optimization of therapeutic approaches for CD-associated perianal disease.

ARTICLE INFORMATION

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Funding

None.

Acknowledgments

The authors thank would like to express our gratitude to Keiko Fukushima for her help with data collection.

Author contributions

Conceptualization: EN; Investigation: all authors; Methodology: EN; Supervision: KT; Validation: KG, HK; Writing–original draft: EN; Writing–review & editing: all authors. All authors read and approved the final manuscript.

Supplementary materials

Supplementary Table 1.

Details of surgical procedures performed for perianal lesions during the study period (n=136)

ac-2025-00766-0109-Supplementary-Table-1.pdf

Supplementary materials are available from https://doi.org/10.3393/ac.2025.00766.0109.

Fig. 1.

Flowchart showing patient selection and outcomes following initial loose seton placement for Crohn disease–associated perianal fistulas.

Fig. 2.

Subgroup analysis for cumulative stoma construction. (A) The cumulative stoma construction rate was significantly lower in patients with severe anal ulceration who received postoperative molecular-targeted therapy (P=0.018, log-rank test). (B) A nonsignificant trend toward reduced stoma construction in patients with rectal stricture who received postoperative molecular-targeted therapy (P=0.058, log-rank test).

Table 1.

Patient and disease characteristics in all cases (n=136)

Characteristic	Group A (n=94)	Group B (n=42)	P-value
Sex			0.500
Male	72 (76.6)	35 (83.3)
Female	22 (23.4)	7 (16.7)
Age (yr)
At diagnosis of Crohn disease	22.0 (18.3–27.8)	20.0 (17.0–24.8)	0.120
At seton drainage	33.0 (26.3–38.8)	30.0 (24.0–39.0)	0.390
Year of initial seton placement^a			0.026^*
<2010	16 (17.0)	15 (35.7)
≥2010	78 (83.0)	27 (64.3)
Location			0.004^*
Ileal	14 (14.9)	0 (0)
Colonic	11 (11.7)	10 (23.8)
Ileocolonic	69 (73.4)	32 (76.2)
Duration of perianal disease (mo)	27.5 (4–74)	37.5 (4–64)	0.900
Severe anal ulceration^b			0.026^*
Absent	71 (75.5)	23 (54.8)
Present	23 (24.5)	19 (45.2)
Rectal stricture			0.016^*
Absent	82 (87.2)	29 (69.0)
Present	12 (12.8)	13 (31.0)
Connection with other organs (bladder, vagina)			0.087
Absent	93 (98.9)	39 (92.9)
Present	1 (1.1)	3 (7.1)
Presence of fistula^c			0.073
Absent	25 (26.6)	5 (11.9)
Present	69 (73.4)	37 (88.1)
No. of primary openings	1 (1–2)	1 (1–2)	0.290
No. of secondary openings	2 (2–3)	2.5 (2–4)	0.670
No. of setons placed	3 (2–4)	3 (2–4)	0.760
Postoperative follow-up (mo)	103.0 (63.5–158.8)	153.5 (98.8–182.8)	0.002^*

Values are presented as number (%) or median (interquartile range). Group A, patients who did not undergo stoma construction; group B, patients with stoma construction.

^aInitial seton placement was categorized based on the year 2010 to reflect the potential shift in treatment paradigms following the wider introduction of molecular-targeted therapies.

^bSevere anal ulceration was defined as cavitating ulcer or aggressive ulceration based on the classification by Hughes and Taylor [15].

^cTypes of fistulas included high intersphincteric, high transsphincteric, extrasphincteric, or suprasphincteric fistula; cases were classified as “present” if at least one of these types was observed.

^*P<0.05.

Table 2.

Preoperative and postoperative medical therapy (n=136)

Characteristic	Group A (n=94)	Group B (n=42)	P-value
Preoperative medical therapy
Immunomodulators^a			0.810
Absent	76 (80.9)	36 (85.7)
Present	18 (19.1)	6 (14.3)
Molecular-targeted therapy^b			0.210
Absent	66 (70.2)	34 (81.0)
Present	28 (29.8)	8 (19.0)
Postoperative medical therapy
Immunomodulators^a			0.360
Absent	73 (77.7)	36 (85.7)
Present	21 (22.3)	6 (14.3)
Molecular-targeted therapy^b			0.037*
Absent	51 (54.3)	31 (73.8)
Present	43 (45.7)	11 (26.2)

Values are presented as number (%). Group A, patients who did not undergo stoma construction; group B, patients with stoma construction.

^aImmunomodulators included azathioprine, 6-mercaptopurine, or methotrexate.

^bMolecular-targeted therapy included biologic agents (e.g., anti–tumor necrosis factor α antibodies such as infliximab or adalimumab, ustekinumab, or vedolizumab) and small molecule inhibitors (e.g., JAK inhibitors such as tofacitinib).

*P<0.05.

Table 3.

Univariate and multivariate analysis of independent predictors associated with stoma construction

Factor	Univariate analysis		Multivariate analysis
Factor	OR (95% CI)	P-value	OR (95% CI)	P-value
Age at diagnosis of Crohn disease (<20 yr)	1.95 (0.92–4.13)	0.082
Male sex	1.53 (0.60–3.92)	0.380
Duration of perianal disease (>36 mo)	1.29 (0.62–2.68)	0.490
Two or more primary openings	1.45 (0.68–3.08)	0.330
Two or more secondary openings	1.41 (0.48–4.16)	0.540
Severe anal ulceration^a	2.56 (1.18–5.50)	0.017^*	2.37 (1.04–5.38)	0.039^*
Rectal stricture	3.06 (1.26–7.47)	0.014^*	2.84 (1.09–7.37)	0.032^*
Connection with other organs (bladder, vagina)	7.15 (0.72–70.90)	0.093
Type of fistula^b	2.68 (0.95–7.59)	0.063
Preoperative medical therapy
Immunomodulators^c	0.84 (0.32–2.21)	0.730
Molecular-targeted therapy^d	0.56 (0.23–1.35)	0.190
Postoperative medical therapy
Immunomodulators^c	0.58 (0.22–1.56)	0.280
Molecular-targeted therapy^d	0.42 (0.19–0.94)	0.034^*	0.36 (0.15–0.84)	0.018^*
Initial seton placement^e (<2010)	0.88 (0.46–1.67)	0.690

OR, odds ratio; CI, confidence interval.

^aSevere anal ulceration included cavitating ulcer or aggressive ulceration, which are deep and extensive lesions caused by Crohn disease.

^bTypes of fistulas included high intersphincteric, high transsphincteric, extrasphincteric, or suprasphincteric fistula.

^cImmunomodulators included azathioprine, 6-mercaptopurine, or methotrexate.

^dMolecular-targeted therapy included biologic agents (e.g., anti–tumor necrosis factor α antibodies such as infliximab or adalimumab, ustekinumab, or vedolizumab) and small molecule inhibitors (e.g., JAK inhibitors such as tofacitinib).

^eInitial seton placement was categorized based on the year 2010 to reflect the potential shift in treatment paradigms following the wider introduction of molecular-targeted therapies.

^*P<0.05.

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Long-term risk factors of stoma construction after loose seton placement for Crohn disease–associated perianal fistulas

Ann Coloproctol. 2025;41(6):565-572. Published online December 26, 2025

DOI: https://doi.org/10.3393/ac.2025.00766.0109

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Figure

Long-term risk factors of stoma construction after loose seton placement for Crohn disease–associated perianal fistulas

Fig. 1. Flowchart showing patient selection and outcomes following initial loose seton placement for Crohn disease–associated perianal fistulas.

Fig. 2. Subgroup analysis for cumulative stoma construction. (A) The cumulative stoma construction rate was significantly lower in patients with severe anal ulceration who received postoperative molecular-targeted therapy (P=0.018, log-rank test). (B) A nonsignificant trend toward reduced stoma construction in patients with rectal stricture who received postoperative molecular-targeted therapy (P=0.058, log-rank test).

Fig. 1.

Fig. 2.

Long-term risk factors of stoma construction after loose seton placement for Crohn disease–associated perianal fistulas

Characteristic	Group A (n=94)	Group B (n=42)	P-value
Sex			0.500
Male	72 (76.6)	35 (83.3)
Female	22 (23.4)	7 (16.7)
Age (yr)
At diagnosis of Crohn disease	22.0 (18.3–27.8)	20.0 (17.0–24.8)	0.120
At seton drainage	33.0 (26.3–38.8)	30.0 (24.0–39.0)	0.390
Year of initial seton placement^a			0.026^*
<2010	16 (17.0)	15 (35.7)
≥2010	78 (83.0)	27 (64.3)
Location			0.004^*
Ileal	14 (14.9)	0 (0)
Colonic	11 (11.7)	10 (23.8)
Ileocolonic	69 (73.4)	32 (76.2)
Duration of perianal disease (mo)	27.5 (4–74)	37.5 (4–64)	0.900
Severe anal ulceration^b			0.026^*
Absent	71 (75.5)	23 (54.8)
Present	23 (24.5)	19 (45.2)
Rectal stricture			0.016^*
Absent	82 (87.2)	29 (69.0)
Present	12 (12.8)	13 (31.0)
Connection with other organs (bladder, vagina)			0.087
Absent	93 (98.9)	39 (92.9)
Present	1 (1.1)	3 (7.1)
Presence of fistula^c			0.073
Absent	25 (26.6)	5 (11.9)
Present	69 (73.4)	37 (88.1)
No. of primary openings	1 (1–2)	1 (1–2)	0.290
No. of secondary openings	2 (2–3)	2.5 (2–4)	0.670
No. of setons placed	3 (2–4)	3 (2–4)	0.760
Postoperative follow-up (mo)	103.0 (63.5–158.8)	153.5 (98.8–182.8)	0.002^*

Characteristic	Group A (n=94)	Group B (n=42)	P-value
Preoperative medical therapy
Immunomodulators^a			0.810
Absent	76 (80.9)	36 (85.7)
Present	18 (19.1)	6 (14.3)
Molecular-targeted therapy^b			0.210
Absent	66 (70.2)	34 (81.0)
Present	28 (29.8)	8 (19.0)
Postoperative medical therapy
Immunomodulators^a			0.360
Absent	73 (77.7)	36 (85.7)
Present	21 (22.3)	6 (14.3)
Molecular-targeted therapy^b			0.037*
Absent	51 (54.3)	31 (73.8)
Present	43 (45.7)	11 (26.2)

Factor	Univariate analysis		Multivariate analysis
Factor	OR (95% CI)	P-value	OR (95% CI)	P-value
Age at diagnosis of Crohn disease (<20 yr)	1.95 (0.92–4.13)	0.082
Male sex	1.53 (0.60–3.92)	0.380
Duration of perianal disease (>36 mo)	1.29 (0.62–2.68)	0.490
Two or more primary openings	1.45 (0.68–3.08)	0.330
Two or more secondary openings	1.41 (0.48–4.16)	0.540
Severe anal ulceration^a	2.56 (1.18–5.50)	0.017^*	2.37 (1.04–5.38)	0.039^*
Rectal stricture	3.06 (1.26–7.47)	0.014^*	2.84 (1.09–7.37)	0.032^*
Connection with other organs (bladder, vagina)	7.15 (0.72–70.90)	0.093
Type of fistula^b	2.68 (0.95–7.59)	0.063
Preoperative medical therapy
Immunomodulators^c	0.84 (0.32–2.21)	0.730
Molecular-targeted therapy^d	0.56 (0.23–1.35)	0.190
Postoperative medical therapy
Immunomodulators^c	0.58 (0.22–1.56)	0.280
Molecular-targeted therapy^d	0.42 (0.19–0.94)	0.034^*	0.36 (0.15–0.84)	0.018^*
Initial seton placement^e (<2010)	0.88 (0.46–1.67)	0.690

Table 1. Patient and disease characteristics in all cases (n=136)

Values are presented as number (%) or median (interquartile range). Group A, patients who did not undergo stoma construction; group B, patients with stoma construction.

Initial seton placement was categorized based on the year 2010 to reflect the potential shift in treatment paradigms following the wider introduction of molecular-targeted therapies.

Severe anal ulceration was defined as cavitating ulcer or aggressive ulceration based on the classification by Hughes and Taylor [15].

Types of fistulas included high intersphincteric, high transsphincteric, extrasphincteric, or suprasphincteric fistula; cases were classified as “present” if at least one of these types was observed.

P<0.05.

Table 2. Preoperative and postoperative medical therapy (n=136)

Values are presented as number (%). Group A, patients who did not undergo stoma construction; group B, patients with stoma construction.

Immunomodulators included azathioprine, 6-mercaptopurine, or methotrexate.

Molecular-targeted therapy included biologic agents (e.g., anti–tumor necrosis factor α antibodies such as infliximab or adalimumab, ustekinumab, or vedolizumab) and small molecule inhibitors (e.g., JAK inhibitors such as tofacitinib).

*P<0.05.

Table 3. Univariate and multivariate analysis of independent predictors associated with stoma construction

OR, odds ratio; CI, confidence interval.

Severe anal ulceration included cavitating ulcer or aggressive ulceration, which are deep and extensive lesions caused by Crohn disease.

Types of fistulas included high intersphincteric, high transsphincteric, extrasphincteric, or suprasphincteric fistula.

Immunomodulators included azathioprine, 6-mercaptopurine, or methotrexate.

Initial seton placement was categorized based on the year 2010 to reflect the potential shift in treatment paradigms following the wider introduction of molecular-targeted therapies.

P<0.05.