Ligation of the intersphincteric fistula tract vs conventional surgery for anal fistula in Chinese patients

Abstract

BACKGROUND

Anal fistula is a common anorectal disorder for which conventional surgical procedures often result in relatively high recurrence and complication rates. Ligation of the intersphincteric fistula tract (LIFT), a sphincter-preserving technique, has emerged as a potential alternative.

AIM

To systematically evaluate and compare the clinical efficacy, safety, and postoperative outcomes of LIFT vs conventional surgical approaches in the management of anal fistula using evidence from randomized controlled trials (RCTs).

METHODS

In accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, we conducted a comprehensive systematic search of both Chinese and international databases to identify RCTs published during January 2014 to 2025. Studies were deemed eligible if they directly compared LIFT with conventional surgical approaches, such as seton placement, fistulotomy, and fistulectomy. The extracted data were analyzed using Review Manager; the methodological quality of the included trials was rigorously evaluated by using the Cochrane risk-of-bias tool.

RESULTS

In total, 107 RCTs involving 9401 participants met the inclusion criteria. LIFT yielded higher healing rates and significantly lower recurrence and complication rates than conventional surgery. Patients undergoing LIFT reported a lower postoperative pain, shorter wound-healing duration, and better preservation of the anal sphincter function. No significant difference was recorded in the operative time between the two groups.

CONCLUSION

The LIFT procedure demonstrated clear advantages over conventional surgical methods in terms of clinical efficacy, safety, and postoperative recovery, supporting the former’s role as an effective and sphincter-preserving treatment for anal fistula. Nevertheless, most available trials are limited by short follow-up durations and heterogeneous outcome definitions, underscoring the need for undertaking large, multicenter RCTs employing standardized endpoints.

Key Words: Anal fistula; Ligation of the intersphincteric fistula tract; Systematic review and meta-analysis; Clinical efficacy; Clinical outcomes

Core Tip: Ligation of the intersphincteric fistula tract offers a sphincter-preserving alternative to conventional surgery for anal fistula. This systematic review of randomized controlled trials demonstrates that the procedure improves cure rates, reduces recurrence and complications, shortens wound-healing time, and better preserves anal function. These findings highlight its potential as a preferred treatment option and provide strong evidence for clinical decision-making.

INTRODUCTION

Anal fistula represents a chronic, suppurative inflammatory disorder of the anorectal region that typically develops secondary to an infection of the anal glands. Obstruction and subsequent infection of these glands lead to crypt abscess formation and the creation of an abnormal tract connecting the anal canal with the perianal skin. Clinically, this disease is characterized by perianal pain, purulent discharge, and recurrent abscesses, which collectively contribute to substantial discomfort and morbidity. The global incidence of this disorder is estimated at approximately 10-20 per 10000 person-years, with a strong male predominance and peak onset at the age of 30-50 years[1,2]. In the absence of timely and standardized intervention, patients may experience recurrent infections, fibrosis, and progressive sphincter dysfunction, which can culminate in sphincter destruction and fecal incontinence, thereby severely impairing the quality of life of the patients[3].

The conventional procedures (seton placement, fistulotomy, fistulectomy, and musculocutaneous flap repair) remain the cornerstone of management but often entail partial division of the anal sphincter complex, increasing the risks of delayed wound healing, incontinence, and recurrence (10%-30%)[4,5]. To address these challenges, various sphincter-preserving procedures have been developed, including transanal opening of the intersphincteric space, endoscopic fistula closure, and laser ablation. Although these newer methods aim to reduce complications and improve functional preservation, their long-term efficacy remains inconsistent and inadequately supported by large-scale evidence[6-8].

In 2007, the ligation of the intersphincteric fistula tract (LIFT) procedure offers a promising, minimally invasive alternative designed to eradicate infection while preserving the sphincter integrity. This technique involves identifying and ligating the fistula tract within the intersphincteric space, thereby preventing the proximal spread of infection and maintaining the sphincter continuity[9]. Multiple clinical studies, including small randomized controlled trials (RCTs) and observational cohorts, have reported primary healing rates of 70%-90% and recurrence rates of 5%-20%, with fewer postoperative complications relative to those with conventional procedures[10-13]. Nevertheless, these data remain heterogeneous in terms of follow-up duration, patient selection, and outcome measures, and large, high-quality RCTs providing definitive evidence remain lacking[14-16].

In this context, we conducted a systematic review and meta-analysis of RCTs, designed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, to critically assess the comparative effectiveness and safety of LIFT vs conventional surgical techniques for anal fistula. This study aimed to integrate the available evidence regarding cure rates, recurrence, postoperative complications, pain levels, wound-healing duration, anal sphincter function, and operative time, thereby establishing an updated and evidence-based framework for clinical decision-making in the management of anal fistula.

MATERIALS AND METHODS

Protocol registration

This systematic review was prospectively registered in International Prospective Register of Systematic Reviews (No. CRD420251053697)[17]. The protocol was developed in accordance with the PRISMA guidelines and prespecified a detailed methodological framework for comparing the effectiveness of LIFT with conventional surgery in patients with anal fistulas[18].

Search strategy

A comprehensive literature search was conducted across both international and Chinese databases, combining electronic retrieval with manual searches. The databases included China National Knowledge Infrastructure, Wanfang, VIP, and PubMed, covering publications from January 2014 to January 2025. The electronic search strategy incorporated both Medical Subject Headings (MeSH) and free-text terms. The primary search components included: (1) “Anal fistula”, including exploded MeSH terms such as “Anal Fistula”, “fistula surgery”, and “fistula operation”; (2) “Ligation of the intersphincteric fistula tract”, comprising exploded MeSH terms such as “LIFT” and “sphincter interspace ligation”; (3) “Conventional surgery”, containing exploded MeSH terms such as “fistulotomy”, “seton”, and “fistula incision”; and (4) “Randomized controlled trials”, including exploded MeSH terms such as “randomized controlled trial”, “RCT”, and “clinical trial”. These components were combined using the Boolean operator: 1 AND 2 AND 3 AND 4.

All retrieved titles and abstracts were independently screened by two reviewers (Li X and Cheng YC) to identify potentially eligible studies, with subsequent full-text assessments performed in duplicate to minimize any selection bias. To ensure completeness and methodological rigor, the reference lists of included articles and relevant systematic reviews were examined for additional or gray literature. Furthermore, Zhi CC and Wang XL manually screened high-impact journals in colorectal surgery and gastroenterology for potentially relevant studies not captured in database searches. Zheng LH also reviewed major clinical trial registries, including the World Health Organization International Clinical Trials Registry Platform (https://www.who.int/clinical-trials-registry-platform) and the Chinese Clinical Trial Registry (http://www.chictr.org.cn), to identify ongoing or unpublished RCTs pertinent to this topic.

Eligibility criteria

PICOS framework: P (population): Patients diagnosed with anal fistula; I (intervention): LIFT; C (comparison): Conventional surgical techniques other than LIFT; O (outcomes): Primary outcomes: Cure rate, recurrence rate, and complication rate. Secondary outcomes: When available, postoperative pain, wound-healing time, anal sphincter function, operative duration, and overall clinical effectiveness; S (study design): RCTs.

Inclusion criteria: Eligible studies met the following conditions: (1) RCT study design; (2) Participants were diagnosed with anal fistula based on clearly defined or internationally accepted diagnostic criteria; (3) Fistula complexity was classified according to the American Society of Colon and Rectal Surgeons 2022 guidelines; (4) The intervention compared the LIFT procedure with conventional surgical techniques addressing the same clinical indication; and (5) At least one of the predefined primary or secondary outcomes was reported. Studies published primarily between January 2014 and January 2025 were included, with supplemental searches extending to database inception to ensure comprehensiveness. Most included RCTs focused on patients with cryptoglandular fistulas. No cryptoglandular etiologies such as Crohn’s disease, tuberculosis, trauma, or malignancy were either excluded or rarely reported. Consequently, the findings of this review predominantly reflect outcomes in cryptoglandular anal fistulas.

Exclusion criteria: Past studies were excluded if they lacked accessible full-text reports, represented duplicate publications or overlapping datasets (the earliest or most complete version was retained), or contained incomplete data or major methodological errors (the most accurate dataset was used when available).

Study selection, data extraction, and quality assessment

Two reviewers independently screened titles and abstracts to identify potentially eligible studies, followed by full-text evaluations based on the inclusion and exclusion criteria. From each included trial, the following data were extracted: First author, publication year, country or region, sample size, patient characteristics, diagnostic criteria, fistula classification, type of intervention, and primary and secondary outcomes (cure, recurrence, complications, pain, healing time, operative duration, anal function, and overall clinical effectiveness). The methodological quality of RCTs was assessed using the Cochrane risk-of-bias 2.0 tool. Disagreements were resolved through discussion or consultation with a third reviewer. The overall certainty of the evidence across outcomes was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.

Certainty of evidence

Risk-of-bias assessments were performed using the Cochrane risk-of-bias 2.0 tool, which evaluated randomization, allocation concealment, blinding, completeness of outcome data, and selective reporting across five domains of potential bias. The certainty of evidence for each outcome was subsequently graded in accordance with the GRADE approach[19]. Factors considered included the risk of bias, inconsistency, indirectness, imprecision, and potential publication bias. Evidence quality was categorized as high, moderate, low, or very low. All assessments were performed independently by two reviewers, with discrepancies resolved via consensus or arbitration by a senior reviewer to ensure objectivity and methodological rigor.

Statistical analysis

Meta-analyses were performed using Review Manager version 6.1. Between-study heterogeneity was evaluated using the Q test (with P < 0.05 indicating significant heterogeneity) and quantified with the I² statistic. A fixed-effect model was applied when I² ≤ 50%; otherwise, a random-effects model was used. For dichotomous outcomes, pooled effect estimates were calculated as relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs). The continuous outcomes were synthesized as weighted mean differences (MDs) with corresponding 95%CIs. Sensitivity analyses were conducted to explore the influence of individual studies on pooled estimates when heterogeneity was substantial.

RESULTS

Study selection

A total of 107 RCTs published between 2014 and 2025 met the inclusion criteria, encompassing 9401 patients in total. Of these, 4691 patients were treated using the LIFT procedure (experimental group), while 4710 underwent conventional surgical approaches (control group). The process of study identification and inclusion is illustrated in Figure 1.

Figure 1 The selection process of studies for the meta-analysis. CNKI: China National Knowledge Infrastructure; RCT: Randomized controlled trial.

Study characteristics

The included trials collectively covered a wide spectrum of fistula morphologies, such as high- and low-complex fistulas, high and low simple fistulas, trans-sphincteric and intersphincteric fistulas, as well as fistulas of glandular origin. Control interventions varied across studies, but most frequently included seton placement with fistulotomy, fistulectomy, conventional intersphincteric tract ligation, and standard fistulotomy. All studies were RCTs that directly compared the efficacy and safety of the LIFT procedure with at least one conventional surgical technique. The principal characteristics of these studies are summarized in Supplementary Table 1.

Primary outcomes (dichotomous variables)

Cure rate: Thirty-nine studies reported cure rate data. The pooled analysis demonstrated that the LIFT procedure was associated with a significantly higher cure rate than conventional surgical methods (RR = 1.08; 95%CI: 1.02-1.14; P = 0.0074). Moderate heterogeneity was observed (Q = 102.97; P < 0.0001; I² = 63.1%), suggesting some interstudy variation in effect estimates (Figure 2A; Table 1).

Figure 2 Forest plot. A: Cure rate. Forest plot depicting pooled relative risk (RR) of cure following ligation of the intersphincteric fistula tract (LIFT) vs conventional surgery, with 95% confidence intervals (CIs). Each square represents an individual study estimate, and the diamond indicates the overall pooled effect; B: Recurrence rate. Forest plot depicting the pooled RR for recurrence between LIFT and conventional surgery, with 95%CIs. A lower RR indicates reduced recurrence in the LIFT group; C: Complication rate. Forest plot comparing the complication rates between LIFT and conventional surgery. The pooled RR and 95%CIs demonstrate the safety profile of LIFT; D: Postoperative pain. Forest plot of pooled mean differences in the postoperative pain scores (Visual Analog Scale) between LIFT and conventional surgery, with 95%CIs. Negative values favor LIFT. LIFT: Ligation of the intersphincteric fistula tract; CI: Confidence intervals; RR: Relative risk.

Table 1 Summary of evidence comparing ligation of the intersphincteric fistula tract vs conventional surgery for anal fistula.

Outcome	Studies (n)	Q	P value (Q test)	I2 (%)	95%CI of I2 (%)	RR	RR P value	RR 95%CI	MD	MD P value	MD 95%CI
Cure rate	39	102.97	< 0.0001	63.1	48.0-73.8	1.0762	0.0074	1.0198-1.1356
Recurrence rate	23	52.04	0.0003	57.7	32.8-73.4	0.6124	0.0323	0.3909-0.9595
Complication rate	31	13.07	0.9969	0.0	0.0-40.2	0.2536	< 0.0001	0.1994-0.3224
Overall effectiveness	67	128.13	< 0.0001	48.5	31.5-61.3	1.1385	< 0.0001	1.1094-1.1684
VAS	48	23290.42	0	99.8					-1.7216	< 0.0001	-2.1018 to -1.3415
Wound healing time	61	3691.79	0	98.4	98.2-98.6				-8.4489	< 0.0001	-9.7276 to -7.1702
Anal function	33	6307.39	0	99.5	99.5-99.6				-1.3793	< 0.0001	-1.9136 to -0.8451
Operative time	41	8043.29	0	99.5	99.5-99.6				3.7127	0.0914	-0.5975 to 8.0230

VAS: Visual Analog Scale; CI: Confidence interval; RR: Relative risk; MD: Mean difference.

Recurrence rate: Twenty-three RCTs provided recurrence data. The pooled estimate indicated a significantly lower recurrence rate following LIFT compared with conventional surgery (RR = 0.61; 95%CI: 0.39-0.96; P = 0.0323). Moderate heterogeneity was again present (Q = 52.04; P = 0.0003; I² = 57.7%; Figure 2B; Table 1).

Complication rate: A total of 31 studies evaluated postoperative complications. Meta-analysis revealed a markedly reduced complication rate in the LIFT group compared with the control group (RR = 0.25; 95%CI: 0.20-0.32; P < 0.0001). Heterogeneity testing suggested consistent findings across studies (Q = 13.07; P = 0.9969; I² = 0.0%), supporting the robustness of this outcome (Figure 2C; Table 1).

Overall clinical effectiveness: Sixty-seven trials assessed the overall clinical effectiveness. The pooled estimate demonstrated a significantly greater overall clinical success with LIFT when compared with conventional surgery (RR = 1.14; 95%CI: 1.11-1.17; P < 0.0001). Moderate heterogeneity was present (Q = 128.13; P < 0.0001; I² = 48.5%; Supplementary Figure 1; Table 1).

Secondary outcomes (continuous variables)

Postoperative pain: Forty-eight studies measured postoperative pain using Visual Analog Scale (VAS) scores. The pooled weighted MD indicated substantially less pain after LIFT (MD = -1.72; 95%CI: -2.10 to -1.34; P < 0.0001). Heterogeneity among studies was high (Q = 23,290.42; P < 0.0001; I² = 99.8%), likely reflecting variations in the pain assessment timing and postoperative care protocols (Figure 2D; Table 1).

Wound healing time: Sixty-one trials reported wound-healing duration. Patients undergoing LIFT experienced significantly faster healing than those who underwent conventional surgery (MD = -8.45 days; 95%CI: -9.73 to -7.17; P < 0.0001). Substantial heterogeneity (Q = 3,691.79; P < 0.0001; I² = 98.4%) suggested clinical and methodological differences across studies (Supplementary Figure 2; Table 1).

Anal function: Thirty-three studies evaluated postoperative anal function. The meta-analysis revealed superior preservation of anal function following LIFT (MD = -1.38; 95%CI: -1.91 to -0.85; P < 0.0001). Despite this consistent effect, heterogeneity remained considerable (Q = 6307.39; P < 0.0001; I² = 99.5%), which may be attributable to differing evaluation scales and follow-up durations (Supplementary Figure 3; Table 1).

Operative time: Forty-one trials compared the operative duration. The pooled estimate showed no significant difference between LIFT and conventional surgery (MD = 3.71 minutes; 95%CI: -0.60 to 8.02; P = 0.0914). High heterogeneity (Q = 8043.29; P < 0.0001; I² = 99.5%) likely reflects procedural variations and surgeon expertise across centers (Supplementary Figure 4; Table 1). Forest plots for primary outcomes (cure, recurrence, and complication rates and postoperative pain) are presented in Figure 2, while the secondary outcome plots (healing time, anal function, operative time, and overall clinical effectiveness) are shown in the Supplementary Figures 1-4.

Sensitivity analyses

Sensitivity analyses were performed to assess the stability of the pooled results. Exclusion of individual studies did not materially affect overall estimates or their 95%CIs, confirming the robustness of the meta-analytic findings (Figure 3; Supplementary Figures 5-11). For continuous outcomes, the pooled MDs for postoperative pain (MD = -1.72; 95%CI: -2.10 to -1.34) and wound-healing time (MD = -8.45 days; 95%CI: -9.73 to -7.17) consistently excluded zero, reinforcing their statistical significance. Similarly, the pooled MD for anal function (MD = -1.38; 95%CI: -1.91 to -0.85) remained stable across iterations, indicating minimal influence of any single trial on the aggregated results.

Figure 3 Sensitivity analysis for complication rate. Leave-one-out analysis was conducted by sequentially omitting each of the included studies. The pooled relative risk and 95% confidence intervals remained stable, indicating that no single trial significantly influenced the overall estimate. CI: Confidence interval.

Publication bias

Funnel plots generated for all eight analyzed outcomes (Figure 4) demonstrated generally symmetrical distributions, indicating no substantial asymmetry suggestive of small-study effects. Egger’s regression analyses yielded intercept P > 0.05 across all outcomes, providing no statistical evidence of publication bias.

Figure 4 Funnel plots for publication bias assessment. Funnel plots evaluating the potential publication bias across the following eight outcomes: Healing time, postoperative pain, operative time, overall clinical effectiveness, anal function, recurrence rate, complication rate, and cure rate. Symmetrical distributions suggest no significant risk of publication bias.

Certainty of evidence

The certainty of evidence was evaluated by applying the GRADE approach. For the primary outcomes, the cure rate was supported by moderate-certainty evidence, downgraded one level due to the identified risks of bias and inconsistency across trials. Similarly, the recurrence rate was evaluated as moderate certainty, reflecting limitations in the study quality and moderate heterogeneity. In contrast, the complication rate was assessed as low certainty, with downgrades applied for multiple domains, including the risk of bias and inconsistency, yielding reduced confidence in the pooled estimate. Among the secondary outcomes, most were rated as moderate certainty, indicating a fair degree of confidence in the observed associations. However, operative time was downgraded for imprecision, as reflected by wide CIs and a lack of statistical significance (Table 2).

Table 2 Summary of Evidence for ligation of the intersphincteric fistula tract vs conventional surgery-continuous outcomes.

Outcome	Number of studies (RCTs)	LIFT group (n)	Conventional group (n)	Effect (95%CI)	Certainty of evidence	Reasons for downgrading
Dichotomous outcomes
Cure rate	39	1379/1762	1273/1764	RR = 1.08 (1.02-1.14)	Moderate	Serious risk of bias, inconsistency
Recurrence rate	23	96/1047	139/1048	RR = 0.61 (0.39-0.96)	Moderate	Serious risk of bias, inconsistency
Complication rate	31	75/1325	295/1326	RR = 0.25 (0.20-0.32)	Low	Serious risk of bias, imprecision
Overall clinical effectiveness	67	2568/2709	2221/2709	RR = 1.14 (1.11-1.17)	Moderate	Serious risk of bias, inconsistency
Continuous outcomes
Postoperative pain (VAS)	48	2086	2134	MD = -1.72 (-2.10 to -1.34)	Moderate	Serious risk of bias, inconsistency
Wound healing time (days)	61	2588	2640	MD = -8.45 (-9.73 to -7.17)	Moderate	Serious risk of bias, inconsistency
Anal function (score)	33	1300	1347	MD = -1.38 (-1.91 to -0.85)	Moderate	Serious risk of bias, inconsistency
Operative time (minutes)	41	1789	1811	MD = 3.71 (-0.60 to 8.02)	Moderate	Serious risk of bias, inconsistency

VAS: Visual Analog Scale; RCT: Randomized controlled trial; LIFT: Ligation of the intersphincteric fistula tract; CI: Confidence interval; RR: Relative risk; MD: Mean difference.

Subgroup analyses

Subgroup analyses stratified by fistula position and complexity (Supplementary Table 2) provided additional insights into the comparative performance of LIFT. For high-position fistulas, LIFT yielded a slightly higher cure rate (RR = 1.14; 95%CI: 1.01-1.29; P = 0.040) and a significantly lower complication rate (RR = 0.30; 95%CI: 0.16-0.60; P < 0.001). Conversely, low-position fistulas revealed no significant difference in the cure rate between the groups (RR = 1.04; 95%CI: 0.92-1.18; P = 0.54). In terms of fistula complexity, the LIFT procedure provided modest improvements in the cure rate for complex fistulas (RR = 1.08; 95%CI: 0.99-1.18) and a substantially lower complication rate (RR = 0.35; 95%CI: 0.25-0.49; P < 0.001), while outcomes for simple tracts were largely comparable to conventional surgery. Collectively, these findings suggest that LIFT may be particularly advantageous for anatomically complex or high-position fistulas where sphincter preservation is clinically prioritized.

DISCUSSION

This systematic review and meta-analysis synthesized findings from 107 RCTs encompassing 9401 patients, offering a comprehensive evaluation of the comparative efficacy and safety of LIFT vs conventional surgery for anal fistula. The pooled results consistently indicated that LIFT confers distinct advantages in terms of the healing rate, recurrence, complication profile, and postoperative recovery metrics. The discussion below contextualizes these findings within the existing literature, explores potential mechanisms, and highlights methodological limitations and directions for future research.

The healing rate in the LIFT group was modestly but significantly higher than that in the control group (RR = 1.08; 95%CI: 1.02-1.14). This aligns with the initial healing rates of 80%-90% reported by Elshamy et al[20] and compares favorably with the 70%-80% success rates commonly reported with traditional seton placement and fistulotomy techniques[21,22]. The improved outcomes with LIFT may stem from the procedure’s anatomic precision: By ligating the intersphincteric tract at its origin, LIFT effectively eradicated the source of infection while maintaining sphincter integrity. This preservation of the sphincter complex sustains local vascular perfusion and tissue tension, both of which are critical for epithelial regeneration and healing.

LIFT was associated with a significant reduction in postoperative recurrence (RR = 0.61; 95%CI: 0.39-0.96), which is consistent with the results reported across several cohort studies and RCTs[23-26]. This effect likely reflects the anatomical precision of LIFT, which ligates the fistula tract within the intersphincteric space, effectively occluding the main tract and potentially limiting the residual infection pathways. Unlike conventional seton placement, which depends on gradual tissue cutting and tension modulation, LIFT targets specific anatomical points, reducing the likelihood of retained fistula remnants and recurrence. Nevertheless, variations in follow-up duration across studies (6-36 months) limit the comparability of long-term recurrence outcomes. Standardized follow-up intervals and uniform definitions of recurrence are recommended for future trials.

The pooled analysis demonstrated a marked reduction in complication rates with LIFT (RR = 0.25; 95%CI: 0.20-0.32), highlighting a substantial decrease in the adverse events, including incontinence, infection, and persistent postoperative pain, based on high-quality RCT data[27,28]. Mechanistically, smaller incisions, reduced intraoperative bleeding, minimized exudation, and preservation of sphincter continuity likely contribute to these favorable outcomes. A notable limitation, however, is the inconsistency in complication definitions and grading among studies. Adoption of standardized classification systems, such as the Clavien-Dindo framework, would enhance comparability across trials.

Regarding the overall clinical effectiveness, LIFT exhibited a 14% relative improvement when compared with conventional surgery (RR = 1.14; 95%CI: 1.11-1.17). This composite outcome incorporates both objective healing measures and patient-centered indicators such as symptom relief and recovery time, providing a holistic assessment of the treatment efficacy[29]. These results underscore the importance of integrating patient-reported outcome measures in future trials. Nonetheless, variability in criteria for defining clinical effectiveness remains a limitation, highlighting the need for standardized evaluation frameworks.

For continuous outcomes, 48 studies reported postoperative pain using VAS scores. LIFT was associated with an average reduction in the VAS scores of 1.72 points (95%CI: -2.10 to -1.34), despite substantial heterogeneity (I² = 99.8%)[30,31]. Factors contributing to lower pain scores may include reduced surgical trauma, smaller incisions, and fewer postoperative dressing changes. Similarly, LIFT was linked to a shorter wound-healing time, with a mean reduction of 8.45 days when compared with conventional surgery (95%CI: -9.73 to -7.17)[32]. This quantitative synthesis of healing duration adds valuable precision to the existing literature; however, varying definitions of wound healing (e.g., complete epithelialization vs absence of discharge) indicates the need for future research to incorporate objective imaging assessments or digital wound measurement techniques.

A total of 33 studies assessed postoperative anal function, showing a mean decline of only 1.38 points following LIFT (95%CI: -1.91 to -0.85), which is consistent with the reported incontinence rates of 0%-5%[33-35]. These findings reinforce the sphincter-preserving advantage of LIFT, likely attributable to the maintained sphincter continuity and reduced muscle fiber disruption. Such evidence strengthens the functional outcome profile of LIFT and informs potential procedural refinements.

Operative time did not significantly differ between LIFT and conventional surgery (MD = 3.71 minutes; 95%CI: -0.60 to 8.02)[36-41], suggesting comparable technical complexity and efficiency. Although debates regarding the learning curve and surgical difficulty persist, this pooled estimate provides a useful reference for clinical practice and surgical training programs.

Recent studies from Western centers offer long-term perspectives on sphincter-preserving approaches for complex anal fistulas. Stellingwerf et al[42] conducted a systematic review and meta-analysis comparing endorectal advancement flap and LIFT for both cryptoglandular and Crohn’s high perianal fistulas, reporting overall healing rates of 60%-80% with preserved continence in the majority of cases. Similarly, Schiano di Visconte and Bellio[43] performed a prospective two-year comparative study of endorectal advancement flap vs collagen paste injection and found healing rates of 65% and 52%, respectively, with continence deterioration in 16% vs 5% of patients. These findings contextualize LIFT within broader sphincter-sparing strategies and highlight its role as an effective, function-preserving intervention for anatomically complex anal fistulas[44].

Long-term European data on sphincter-preserving techniques demonstrated substantial variability in the outcomes. Wilhelm et al[30] reported 5-year healing rates of 64%-70% following FiLaC™ (fistula laser closure). Similarly, Meinero et al[45] observed 2-year success rates of 60%-67% with video-assisted anal fistula treatment. Several case series evaluating the LIFT procedure and its biologically reinforced variant, BioLIFT, have reported long-term closure rates of approximately 62%-75% with excellent preservation of continence[46,47]. Collectively, these studies illustrate that although sphincter-preserving approaches generally maintain functional outcomes, the durability of fistula closure is highly technique-dependent and can vary considerably across patient populations and follow-up intervals.

In contrast, the Chinese RCTs included in this meta-analysis reported higher early healing rates (80%-90%) and low complication rates (< 5%), yet most studies had follow-up periods of ≤ 12 months. Integrating these findings with Western data suggests that LIFT achieves robust short-term efficacy and functional preservation. However, the evidence regarding long-term durability remains limited. These comparisons underscore the importance of multicenter trials with standardized follow-up periods of at least 24 months to evaluate sustained fistula closure and recurrence prevention. Although LIFT appears to outperform conventional surgery in the early postoperative period, long-term outcomes of different sphincter-preserving modalities are comparable, highlighting the necessity of harmonized and extended follow-up protocols.

Considerable heterogeneity in continuous outcomes (I² > 90%) likely reflects the differences in patient-selection criteria, procedural modifications, definitions of outcomes, and duration of follow-up. Notably, several single-center Chinese RCTs lack detailed methodology regarding randomization or blinding, employing relatively short follow-up intervals (< 12 months), which may have led to the overestimation of effect sizes. Accordingly, the pooled estimates derived from these studies should be interpreted with caution. Future investigations should adopt standardized outcome measures, validated assessment tools, and multicenter designs with extended follow-up to enhance the reliability and comparability of findings.

Subgroup analyses provided additional insight into the potential influence of fistula type and anatomical position on the comparative performance of LIFT. For high-position fistulas, LIFT was associated with a modest increase in cure rate and a lower complication rate compared with conventional surgery, which may suggest a relative benefit when a larger proportion of the sphincter complex is involved and sphincter preservation is an important consideration. In contrast, among low-position fistulas, cure rates appeared generally comparable between LIFT and conventional approaches, although the complication profile tended to favor LIFT. With respect to fistula complexity, the LIFT procedure was linked to modest improvements in cure rate and a lower complication rate in complex fistulas, whereas outcomes for simple tracts were largely similar to those of conventional surgery. Taken together, these observations suggest that both fistula complexity and anatomy may modulate the relative effect of LIFT: The procedure may offer greater advantages in anatomically complex or high-position cryptoglandular fistulas, whereas in simple or low tracts, the choice of technique may depend more on surgeon experience, patient preference, and local practice patterns.

Finally, because the included studies predominantly addressed cryptoglandular fistulas, the generalizability of these findings to noncryptoglandular etiologies, including Crohn’s disease, tuberculosis, trauma, or malignancy, remains uncertain. Future research should incorporate etiologic stratification to determine whether the observed benefits of LIFT extend to these less common fistula subtypes, particularly regarding healing, recurrence, and functional outcomes.

Methodological reflections

This study was conducted in strict accordance with PRISMA and Cochrane guidelines, including comprehensive evaluations of risk of bias, sensitivity analyses, and publication bias. Despite the methodological rigor of this review, several important limitations warrant consideration. The substantial heterogeneity observed in continuous outcomes likely stems from variations in study design, data collection methods, outcome assessment tools, and follow-up durations across trials. Most of the included RCTs were relatively small, single-center investigations with incomplete descriptions of key methodological elements such as randomization procedures, blinding, and allocation concealment, which may have introduced selection and performance bias. Consequently, the certainty of evidence for several outcomes was downgraded in the GRADE assessment, emphasizing the need for well-designed, adequately powered multicenter RCTs that adhere to standardized research protocols. Furthermore, few trials differentiated between single-tract and multiple-tract fistulas; in most cases, the LIFT procedure was applied to the primary tract, with secondary extensions managed through ancillary closure techniques. This lack of morphological stratification could have influenced the pooled efficacy estimates and introduced unaccounted heterogeneity. Finally, the limited duration of follow-up (< 24 months) restricts the ability to comprehensively evaluate long-term recurrence, continence preservation, and sustained functional outcomes.

Future directions

Future research should address these gaps by following these steps: (1) Designing rigorously conducted multicenter RCTs with transparent randomization, blinding, and allocation concealment; (2) Developing and adopting standardized, clearly reported definitions for key outcomes, including healing, recurrence, postoperative complications, wound-healing time, and anal functional recovery, and using validated scoring systems (e.g., structured incontinence scales and widely accepted complication grading systems) to facilitate comparison across trials; (3) Incorporating substantially longer and more uniform follow-up periods to reliably evaluate long-term efficacy, recurrence, sphincter function preservation, and the durability of the LIFT procedure; and (4) Systematically reporting fistula morphology, particularly tract number and complexity, and exploring combined approaches that integrate LIFT with endoscopic, laser, or biologic techniques to further optimize efficacy and quality of life.

CONCLUSION

LIFT demonstrates clear advantages over conventional surgical approaches in terms of cure rates, recurrence, complication profiles, and postoperative recovery, establishing it as an effective treatment option for anal fistula. This meta-analysis provides robust evidence to guide clinical decision-making. However, the generally short follow-up periods and the non-standardized outcome measures in the existing trials highlight the need for large-scale, multicenter RCTs with extended follow-up and harmonized endpoints to validate and extend these findings.