Effects of modified ligation of intersphincteric fistula tract on intestinal barrier function in patients with transsphincteric anal fistula

Abstract

BACKGROUND

The treatment for transsphincteric anal fistula (TAF) remains challenging. Effective therapies that achieve high efficacy and low recurrence while preserving anal sphincter function are still lacking.

AIM

To analyze the effects of modified ligation of intersphincteric fistula tract (LIFT) on infection-related parameters and intestinal barrier function in patients with TAF.

METHODS

A total of 101 patients with TAF admitted to the First Affiliated Hospital of Jinan University between January 2022 and June 2024 were retrospectively enrolled. Patients were grouped according to the treatment received: The control group (n = 49) underwent conventional anal fistulectomy, whereas the research group (n = 52) underwent modified LIFT. Clinical efficacy, surgical outcomes (e.g., operation time, hospitalization, wound healing time, and postoperative scar area), anal sphincter function assessed using Wexner score, pain intensity assessed using Visual Analogue Scale, infection-related parameters, including white blood cell count, C-reactive protein, and procalcitonin, intestinal barrier function, including diamine oxidase and D-lactic acid, complications, including anal canal deformity, anal edema, infection, constipation, and urinary retention), and the one-year recurrence rate were compared between groups.

RESULTS

Compared with the control group, the research group exhibited a significantly higher total effective rate, shorter operation time, hospitalization, and wound healing time, a smaller postoperative scar area, lower postoperative Wexner and Visual Analogue Scale scores, lower levels of infection-related parameters, and reduced overall complication and one-year recurrence rates. Postoperative intestinal barrier function indicators were comparable between groups.

CONCLUSION

These findings suggest that modified LIFT demonstrates reliable efficacy and safety in patients with TAF.

Key Words: Modified ligation of intersphincteric fistula tract; Transsphincteric anal fistula; Infection-related parameters; Intestinal barrier function; Retrospective analysis

Core Tip: This retrospective study evaluated and safety of modified ligation of intersphincteric fistula tract in patients with transsphincteric anal fistula. Compared with conventional anal fistulectomy, modified ligation of intersphincteric fistula tract achieved superior efficacy and surgical outcomes. It improved anal sphincter function, alleviated pain, reduced the risk of complications and one-year recurrence rates, and significantly attenuated surgery-related inflammatory responses.

INTRODUCTION

Anal fistula is a chronic anorectal disorder characterized by an abnormal connection between the anal canal and perianal skin, affecting approximately 10 individuals per 100000 population and occurring predominantly in males[1]. Typical symptoms include persistent or intermittent discharge of purulent, bloody, or mucous secretions from the external fistula opening, accompanied by local redness, swelling, fever, and pain[2]. Anal fistulas commonly arise as a chronic progression of perianal abscesses and originate from suppurative inflammation in the anal fossa. Without timely intervention, inflammation may spread to the pelvirectal, retrorectal, ischiorectal, perianal, and transsphincteric cavities[3]. Intestinal microecological disturbances in patients with anal fistula may impair intestinal barrier function and contribute to disease progression[4]. Common imaging modalities for anal fistula include fistulography, computed tomography, endoscopic ultrasound, and magnetic resonance imaging (MRI). Among these, MRI is generally preferred for complex or recurrent anal fistulas because of its superior soft-tissue resolution, high diagnostic accuracy, and ability to provide precise preoperative assessment[5]. Transsphincteric anal fistula (TAF), accounting for approximately 55.1%-87.9% of complex anal fistulas, typically requires sphincter-preserving surgery to minimize the risk of fecal incontinence[6]. Although various surgical approaches are available, an optimal approach that combines high efficacy, low recurrence, and preservation of anal sphincter function remains lacking[7]. Therefore, identifying surgical approaches for patients with TAF that achieve both radical cure and functional preservation is of considerable clinical importance. Ligation of the intersphincteric fistula tract (LIFT) is a commonly used procedure for anal fistula that interrupts the infection pathway by ligating and transecting the fistula tract within the intersphincteric space, followed by proximal closure and distal excision[8]. This procedure, applicable to complex and recurrent anal fistulas, is safe, effective, and associated with low risk of sphincter dysfunction and reduced pain[9]. However, dissection within the intersphincteric space carries an inherent risk of injury to the longitudinal muscle, which may compromise anal function[10]. This study proposed a modified LIFT procedure, which improves the clinical outcomes by performing a tunnel excision of the distal fistula tract on the external-opening side while preserving anal function sphincter.

Given the limited available evidence, this study compared the clinical efficacy and safety of the modified LIFT with those of conventional anal fistulectomy in patients with TAF, seeking to provide evidence-based guidance for surgical decision-making.

MATERIALS AND METHODS

General data

This retrospective study included 101 patients with TAF admitted to the First Affiliated Hospital of Jinan University between January 2022 and June 2024. The control group (n = 49) underwent conventional anal fistulectomy, whereas the research group (n = 52) underwent the modified LIFT. No statistically significant differences were observed in baseline characteristics between the two groups (P > 0.05), indicating clinical comparability.

Inclusion and exclusion criteria

Inclusion criteria: Diagnosis of TAF based on multiplanar MRI findings[11]; eligibility for surgical treatment and fulfillment of surgical indications[12]; no history of perianal surgery; and complete clinical records.

Exclusion criteria: Concurrent anorectal diseases; coagulation disorders; malignant tumors; severe hepatic, renal, or other vital organ dysfunction; cardiovascular or circulatory diseases; mental disorders or impaired communication ability; pregnancy or lactation; poor treatment compliance; or withdrawal from the study for any reason.

Treatment method

All procedures were performed by the same surgical team after routine preoperative assessment. Patients received a liquid diet 1 day preoperatively and underwent bowel preparation after meals and again on the day of surgery. Combined spinal-epidural anesthesia was administered in the lithotomy position, followed by routine disinfection and sterile draping.

The control group underwent conventional anal fistulectomy. The patient was positioned in the right lateral decubitus position and received epidural block anesthesia. After the confirmation of effective anesthesia and routine anal disinfection, the internal and external fistula openings were identified using a probe. The fistula tract and surrounding wall tissue were incised, and the wound margins were carefully trimmed. The wound cavity was packed with sterile vaseline gauze and covered with a pressure dressing.

The research group underwent modified LIFT. First, a JA flexible fistula probe (ball tip 2.5 mm/perforated 1.0 mm, suturable) was inserted into the fistula tract to delineate it. A 1.5-2.0 cm curved incision was made along the ipsilateral intersphincteric groove. Then, the internal and external sphincters were bluntly dissected until the fistula tract was identified and adequately mobilized. The proximal and distal ends of the tract were clamped with two hemostats, and the tract was divided between the clamps. The proximal stump was ligated with absorbable sutures and buried to ensure complete closure of the internal opening. For the distal segment, tunnel excision beyond the external sphincter was performed, followed by thorough curettage of the residual tract wall. The intersphincteric incision was then closed with absorbable sutures, and the external opening was enlarged to facilitate drainage before routine dressing placement.

Outcome measures

Efficacy: Clinical efficacy was categorized as cured, improved, or ineffective. Cure was defined as resolution of clinical symptoms with complete wound healing and closure of both internal and external anal fistula openings. Improvement was defined as symptom relief with incomplete wound healing and incomplete closure of both internal and external anal fistula openings. Ineffectiveness was defined as no improvement or worsening of clinical symptoms. The total effective rate as calculated as the sum of cured and improved cases.

Surgery parameters: Operation time, hospitalization, wound healing time, and postoperative scar area were recorded for both groups.

Anal sphincter function: Anal sphincter function was assessment preoperatively and postoperatively using the Wexner score (range: 0-20), with lower scores indicating better anal sphincter function[13].

Pain intensity: Pain severity was assessed preoperatively and postoperatively using the Visual Analogue Scale (VAS; range: 0-10), with higher scores indicating greater pain intensity[14].

Infection-related parameters: Fasting venous blood samples (5 mL) were collected preoperatively and on postoperative day 3. Serum white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) levels were measured using a fully automated biochemical analyzer.

Intestinal barrier function: Serum D-alanine oxidase (DAO) levels were measured preoperatively and on postoperative day 3 using enzyme-linked immunosorbent assay. D-lactic acid (D-lac) levels were determined preoperatively and postoperatively using enzymatic spectrophotometry.

Complications: The incidences of anal canal deformity, anal edema, infection, constipation, and urinary retention were observed and recorded.

One-year postoperative recurrence rate: Patients were followed-up for one year through outpatient visits or telephone interviews to assess anal fistula recurrence.

Statistical analysis

Statistical analyses were performed using SPSS version 26.0. Categorical variables are presented as n (%) and compared using the χ² test; Fisher’s exact test was used when expected frequencies were < 5. Continuous variables are expressed as mean ± SD. Between-group comparisons were performed using the independent-samples t-test, and within-group comparisons preoperatively and postoperatively were performed using the paired t-test. For non-normally distributed data, the Mann-Whitney U test was applied. A two-sided P < 0.05 was considered statistically significant.

RESULTS

Baseline data in the two groups

As shown in Table 1, no significant differences were observed between the two groups regarding sex, age, disease duration, body mass index, number of fistulas, or American Society of Anesthesiologists classification (P > 0.05).

Table 1 Baseline data in the two groups, n (%)/mean ± SD.

Item	n	Control group (n = 49)	Research group (n = 52)	χ2/t/Z	P value
Gender				0.219	0.640
Male	56	26 (53.06)	30 (57.69)
Female	45	23 (46.94)	22 (42.31)
Age (years)	101	44.73 ± 6.82	46.90 ± 7.44	1.525	0.130
Disease duration (months)	101	8.00 (6.00, 11.00)	8.50 (5.00, 11.00)	-0.423	0.672
BMI (kg/m2)	101	22.00 (20.00, 24.00)	23.50 (21.00, 25.75)	-1.581	0.114
Number of fistulas (n)	101	3.00 (2.00, 3.00)	2.00 (2.00, 3.00)	-1.039	0.299
ASA classification				0.965	0.617
I	35	18 (36.73)	17 (32.69)
II	41	21 (42.86)	20 (38.46)
III	25	10 (20.41)	15 (28.85)

BMI: Body mass index; ASA: American Society of Anesthesiologists.

Efficacy in the two groups

As presented in Table 2, the numbers of patients who were cured, improved, and experienced no effect were 16, 20, and 13, respectively, in the control group, and 22, 25, and 5, respectively, in the research group. The total effective rate was significantly higher in the research group than in the control group (90.38% vs 73.47%; P = 0.026).

Table 2 Efficacy in the two groups, n (%).

Item	Control group (n = 49)	Research group (n = 52)	χ2	P value
Cured	16 (32.65)	22 (42.31)	-	-
Improved	20 (40.82)	25 (48.08)	-	-
No effect	13 (26.53)	5 (9.62)	-	-
Total effective rate	36 (73.47)	47 (90.38)	4.929	0.026

Surgery parameters in the two groups

As shown in Figure 1, the operation time was 46.27 ± 5.82 minutes in the control group and 37.69 ± 4.09 minutes in the research group. The length of hospitalization was 7.00 (5.00, 10.00) days and 5.00 (3.25, 7.00) days, respectively; wound healing time was 21.59 ± 6.61 days and 12.73 ± 4.13 days, respectively; and postoperative scar area was 2.81 ± 0.96 cm² and 1.83 ± 0.64 cm², respectively. Compared with the control group, the research group demonstrated significantly shorter operation time, hospitalization, and wound healing time, as well as smaller postoperative scar area (all P < 0.05).

Figure 1 Surgery parameters in the two groups. ^aP < 0.05, ^bP < 0.01 vs the control group. A: Comparison of operation time between the two groups; B: Comparison of hospital stay between the two groups; C: Comparison of wound healing time between the two groups; D: Comparison of postoperative scar area between the two groups.

Anal sphincter function and pain intensity in the two groups

As shown in Figure 2, the preoperative Wexner scores were 5.00 (4.00, 7.00) in the control group and 6.00 (5.00, 8.00) in the research group, while the corresponding postoperative scores were 3.00 (2.00, 4.00) and 2.00 (1.00, 2.00), respectively. The preoperative VAS scores were 4.00 (3.00, 4.50) and 4.00 (3.00, 5.00), respectively, whereas the postoperative VAS scores were 2.00 (1.00, 2.00) and 1.00 (1.00, 2.00), respectively. No significant between-group differences were observed in preoperative Wexner or VAS scores (P > 0.05). Following treatment, both scores decreased significantly in each group (P < 0.05) and were significantly lower in the research group than in the control group (P < 0.05).

Figure 2  Anal sphincter function and pain intensity in the two groups. ^aP < 0.05, ^bP < 0.01 vs before treatment; ^cP < 0.05 vs the control group. A: Comparison of the Wexner scores between the two groups; B: Comparison of Visual Analogue Scale scores between the two groups.

Infection-related parameters in the two groups

As shown in Figure 3, the preoperative WBC counts were (9.31 ± 2.70) × 10⁹/L and (8.40 ± 3.22) × 10⁹/L in the control and research groups, respectively, increasing postoperatively to (12.37 ± 3.55) × 10⁹/L and (10.50 ± 3.70) × 10⁹/L. The preoperative CRP levels were 15.68 ± 3.72 mg/L and 14.86 ± 3.71 mg/L, respectively, increasing postoperatively to 22.29 ± 4.91 mg/L and 19.29 ± 5.04 mg/L. The preoperative PCT levels were 1.43 ± 0.49 μg/L and 1.41 ± 0.45 μg/L, respectively, increasing postoperatively to 2.90 ± 1.15 μg/L and 2.35 ± 0.87 μg/L. No significant between-group differences were observed in preoperative WBC, CRP, or PCT levels (P > 0.05). All three parameters increased significantly postoperatively in both groups (P < 0.05), but postoperative levels were significantly lower in the research group (P < 0.05).

Figure 3 Infection-related parameters in the two groups. ^aP < 0.05, ^bP < 0.01 vs before treatment; ^cP < 0.05 vs the control group. A: Comparison of white blood cell count between the two groups; B: Comparison of C-reactive protein between the two groups; C: Comparison of procalcitonin between the two groups. WBC: White blood cell; CRP: C-reactive protein; PCT: Procalcitonin.

Intestinal barrier function in the two groups

As shown in Figure 4, the preoperative DAO levels were 4.83 ± 1.8 ng/L and 4.54 ± 2.08 ng/L in the control and research groups, respectively, increasing postoperatively to 5.64 ± 2.05 ng/L and 5.61 ± 2.17 ng/L. The preoperative D-lac levels were 5.57 ± 1.41 ng/L and 5.33 ± 1.58 ng/L, respectively, increasing postoperatively to 6.51 ± 2.51 ng/L and 6.53 ± 2.22 ng/L. No significant differences in DAO or D-lac levels were observed between groups preoperatively (P > 0.05). Both indicators increased significantly postoperatively in each group (P < 0.05), but no significant between-group differences were detected postoperatively (P > 0.05).

Figure 4 Intestinal barrier function in the two groups. ^aP < 0.05, ^bP < 0.01 vs before treatment; ^cP < 0.05 vs the control group. A: Comparison of D-alanine oxidase between the two groups; B: Comparison of D-lactic acid between the two groups. DAO: D-alanine oxidase; D-lac: D-lactic acid.

Complications and one-year postoperative recurrence rate in both groups

As presented in Table 3, analysis of complications, including anal canal deformity, anal edema, infection, constipation, and urinary retention, showed that the overall complication rate was significantly lower in the research group than in the control group (9.62% vs 24.49%, P = 0.046). Additionally, the one-year postoperative recurrence rate was significantly lower in the research group than in the control group (1.92% vs 14.29%, P = 0.028).

Table 3 Complications and 1-year postoperative recurrence rate in both groups, n (%).

Item	Control group (n = 49)	Research group (n = 52)	χ2/Fisher’s	P value
Complication
Anal canal deformity	1 (2.04)	0 (0.00)	-	-
Anal edema	3 (6.12)	1 (1.92)	-	-
Infection	3 (6.12)	1 (1.92)	-	-
Constipation	2 (4.08)	1 (1.92)	-	-
Urinary retention	3 (6.12)	2 (3.85)	-	-
Total	12 (24.49)	5 (9.62)	3.987	0.046
Recurrence
Recurrence at 1 year postoperatively	7 (14.29)	1 (1.92)	-	0.028

DISCUSSION

This study demonstrated that modified LIFT achieved optimal therapeutic efficacy in patients with TAF, with a total effective rate of 90.38%. The procedure effectively alleviated clinical symptoms, promoted wound healing, and facilitating closure of both internal and external fistula openings. These benefits may be attributed to precise preoperative fistula exploration, which reduces the likelihood of missed secondary tracts, and thorough management of distal lesions, which promotes wound repair and closure of the external opening. Together, these features may contribute to improved treatment outcomes. Compared with conventional anal fistulectomy, the modified LIFT was associated with shorter operation time, hospitalization, and wound healing time, as well as smaller postoperative scar area, indicating superior surgical outcomes. These advantages are likely related to the limited incision length (1.5-2.0 cm) and the use of blunt dissection, which reduce tissue trauma and intraoperative bleeding. Furthermore, efficient fistula transection using vascular clamps enables reliable hemostasis and contributes to a shorter operation time. Modified LIFT also resulted in better postoperative anal sphincter function and lower pain scores. This may be explained by its enhanced sphincter-preservation design, as blunt dissection minimizes injury to sphincter fibers and their neural innervation. Additionally, the enlargement of the external opening facilitates adequate drainage, thereby effectively reducing postoperative fluid accumulation and alleviating pain.

WBC, CRP, and PCT are widely used clinical markers of infection and inflammation, and simultaneous elevations in these parameters are indicative of significant inflammatory or infectious processes[15,16]. Therefore, these markers were assessed as infection-related parameters in this study. The results showed that modified LIFT was associated with reduced surgical-related inflammatory response. This effect may be attributed to the precise and minimally invasive nature of blunt dissection with the intersphincteric space, which minimizes surgical trauma-related inflammation. Additionally, tunnel excision combined with thorough curettage to distal infectious may further reduce excessive postoperative local inflammatory responses. The two surgical approaches demonstrated comparable effects on intestinal barrier function, as reflected by DAO and D-lac levels. DAO, which is primarily synthesized by intestinal enterocytes, reflects intestinal mucosal integrity, with elevated levels indicating epithelial damage[17]. D-lac, a byproduct of bacterial metabolism, enters the bloodstream when intestinal permeability increases, indicating barrier leakage[18]. Notably, modified LIFT also reduced the incidence of complication, including anal canal deformity, anal edema, infection, constipation, and urinary retention, while lowering the one-year postoperative recurrence rates. These benefits were achieved through the blunt dissection and controlled incision length of the modified LIFT, which minimized unnecessary injury to the sphincter complex and surrounding soft tissues. Closure of the internal opening using ligation and buried sutures, along with tunnel excision of the distal external sphincter segment, may further contribute to infection prevention. Furthermore, this technique effectively suppressed inflammation and edematous granulation tissue through enhanced drainage and tunnel excision, thereby helping prevent anal edema.

Previous studies have investigated modifications and optimization strategies for anal fistula surgery. For example, Sirikurnpiboon et al[19] reported that adding partial fistula excision to conventional anal fistulectomy in patients with high TAF increased surgical success rate by 2%, although overall outcomes remained comparable to those of conventional anal fistulectomy. Similarly, Kang et al[20] proposed that a lateral-approach modified LIFT effectively preserves sphincter function in patients with TAF. Furthermore, Chen et al[21] demonstrated that LIFT using modified ligation materials is feasible, effective, and clinically safe for patients with transsphincteric or intersphincteric fistulas.

This study has several limitations that should be acknowledged. First, it was a retrospective study rather than a randomized controlled trial. The selection of surgical procedure may have been influenced by various confounding factors such as disease severity and economic conditions, potentially introducing selection bias. Future prospective randomized controlled studies are needed to minimize such confounding factors. Second, baseline comparisons included only general characteristics, including sex, age, and body mass index, without adjustment for other potential confounders, including smoking history. Future studies should prospectively incorporate more potential confounding factors to allow for intergroup comparisons and adjustments, thereby minimizing potential confounding bias in measurements.

CONCLUSION

In summary, although modified LIFT and conventional anal fistulectomy demonstrated comparable effects on intestinal barrier function, modified LIFT provided superior clinical efficacy in patients with TAF. It was associated with improved surgical outcomes, better preservation of anal sphincter function, alleviated postoperative pain, reduced complication risks, lower one-year recurrence rates, and suppressed surgery-related inflammatory responses.