Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Litta, 2021

SR and meta-analysis of RCTs

Literature search up to April 2020.

1. Ho (1998)
2. Ho (2001)
3. Shahbaz (2002)
4. Lindsey (2002)
5. Sahakitrungruang (2011)
6. Nazeer (2012)
7. Jain (2012)
8. Kamal (2012)
9. Wang (2012)
10. Chalya and Mabula (2013)
11. Sheikh (2015)
12. Saber (2016)
13. Ganesan (2017)
14. Shahid (2017)
15. Mittal (2018)
16. Gupta (2018)
17. Anan (2019)
18. Sahai (2019)
19. Sanad (2019)

Study design:

All studies were RCTs

Setting and Country:

Proctology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168 Rome, Italy

Source of funding and conflicts of interest:

The authors declare that they have no confict of interest, and no funding from any organization for the submitted work.

Inclusion criteria SR:

• Studies with any number of cases analyzing any surgical treatment for simple AFs as defined by commonly adopted guidelines;
• Prospective, retrospective, observational studies, and randomized clinical trials;

Exclusion criteria SR:

• Reviews, meta-analyses, trial proposals, thesis articles, technical notes, commentaries, letters, and meeting abstracts.
• Articles concerning complex, recto-vaginal or anovaginal, tuberculosis- and IBD-related AFs, as well as any study where data on simple AFs could not be extrapolated.

66 studies included. Eventually, 19 studies were included for the purpose of this guideline.

Important patient characteristics at baseline:

Total N per study

1. N = 103
2. N = 100
3. N = 50
4. N = 7
5. N = 50
6. N = 150
7. N = 40
8. N = 76
9. N = 11
10. N = 162
11. N = 262
12. N = 200
13. N = 60
14. N = 60
15. N = 75
16. N = 30
17. N = 60
18. N = 28
19. N = 60

N, mean age

1. 41.1 vs 41.2
2. 42 vs 37
3. 32.1
4. NR
5. 43.2 vs 40.6
6. NR
7. 34.5 vs 34.3
8. NR
9. NR
10. 37.8 vs 38.6
11. 32.5 vs 33.5
12. NR
13. NR
14. 35.8 vs 38.4
15. 41.5 vs 45.2
16. 35.5
17. 38.3 vs 43.5
18. 41
19. 41.4

Sex M/F per treatment group:

1. 49/3 vs 41/10
2. 21/2 vs 5/1
3. 24/1
4. NR
5. 23/2 vs 4/1
6. NR
7. 4/1 vs 9/1
8. 190/82
9. 15/4
10. NR
11. 76/6 vs 74/6
12. All M vs All M
13. All M vs All M
14. NR
15. 4/1 vs 13/1
16. 31/6 vs 35/3
17. 28/2
18. 4/1 vs 13/2
19. 5/1

Groups comparable at baseline?

Yes.

Describe intervention:

1. Fistulotomy
2. Chemical ayurvedic seton
3. Fistulotomy
4. Fistulotomy
5. Fistulotomy
6. Fistulotomy
7. Fistulotomy with marsupialization
8. Fistulotomy
9. SDPC suture dragging and pad compression
10. Fistulotomy with marsupialization
11. Fistulotomy
12. Fistulotomy
13. Fistulotomy
14. Fistulectomy and suture
15. Fistulotomy
16. Fistulectomy
17. Fistulotomy
18. Fistulectomy
19. Fistulotomy + phenytoin 2% and sitz baths

Describe  control:

1. Fistulotomy with marsupialization
2. Fistulotomy
3. Fistulotomy with primary closure
4. NR
5. Fistulotomy with marsupialization
6. Fistulectomy
7. Fistulectomy
8. Fistulectomy
9. Fistulotomy
10. Fistulectomy
11. Fistulectomy
12. Fistulectomy
13. Fistulectomy
14. Fistulectomy
15. Fistulectomy
16. NR
17. Fistulotomy with marsupialization
18. NR
19. Fistulotomy + sitz baths

End-point of follow-up:

Average weighted follow-up is 14.7 (1 to 77) months.

For how many participants were no complete outcome data available?

(intervention/control)

Not reported.

Surgical success (healing rate)

F I: 75/75 (100%)

   C: 75/75 (100%)

H I: 30/32 (93.7%)

     C: 41/44 (93.2%)

K I: 117/131 (89.3%)

   C: 111/131 (84.7%)

L I: 98/100 (98%)

   C: 100/100 (100%)

M I: 29/30 (96.7%)

     C: 30/30 (100%)

O I: 36/38 (94.7%)

    C: 30/37 (81.1%)

Pooled RR (95% CI)

RR 1.00 (95% CI 0.95 to 1.04)

Incontinence (major incontinence)

F I: 0/75 (0%)

   C: 0/75 (0%)

H I: 0/32

    C: 0/44

M I: 0/30 (0%)

     C: 0/30 (0%)

O I: 0/38 (0%)

    C: 0/37 (0%)

Author’s conclusion

Surgical treatment of simple AFs by sphincter-cutting procedures provides excellent cure rates, even if a certain morbidity should be expected. Postoperative continence impairment is not a negligible risk, which could have a detrimental efect on both patients’ QoL and satisfaction. The adoption of sphincter-sparing procedures could be useful in selected patients, and this should be better evaluated in future prospective studies with adequately long follow-up.

Stellingwerf (2019)

SR and meta-analysis of  RCTs, cohort studies, and case series.

Literature search up to 13 September 2017

1. Mushaya (2012)
2. Madbouly (2014)

Study design: RCT

Setting and Country:

Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Source of funding and conflicts of interest:

No funding or conflict of interest.

Inclusion criteria SR:

• All RCTs, cohort studies and case series (more than 5 patients) describing the AF or LIFT procedure in patients with high perianal fistula of cryptoglandular and/or Crohn’s origin were included.

Exclusion criteria SR:

• Studies not reporting success or recurrence rates and length of follow-up, animal studies, reviews, case reports and letters were excluded. Other exclusion criteria were patients aged less than 18 years, those with a stoma, low perianal fistula, rectovaginal and rectourethral fistulas, fistulas without an external opening, and fistulas due to other aetiologies such as malignancy, trauma or human immunodeficiency virus infection. Combinations of techniques or other variants of the techniques, such as anocutaneous flaps, core-out fistulectomy or dissection of the tract before the actual procedure, were excluded.

2 studies included

Important patient characteristics at baseline:

Number of patients; characteristics important to the research question and/or for statistical adjustment (confounding in cohort studies); for example, age, sex, bmi, ...

N, median age

1. 48 (25 to 70) years
2. Mean (SD): 45 (14) vs 41 (12)

Sex n (%):

1. N = 4 (13%) vs N=21 (77%)
2. N = 16 (46%) vs N = 12 (34%)

Groups comparable at baseline?

Yes.

Describe intervention:

1. LIFT
2. LIFT

Describe  control:

1. Advancement flap
2. Advancement flap

End-point of follow-up:

1. 16 months (8 to 31)
2. 12 months

Overall success rate defined as no presence of a persisting or recurrent fistula after minimum follow-up of 3 months

1. I:23/25 (92%)
   C: 13/14 (92.9%)
2. I: 26/35 (74.3%)
   C: 23/35 (65.7%)

Effect measure: RR (95% CI)

1. RR 0.99 (95% CI 0.82 to 1.91)
2. RR 1.13 (95% CI 0.83 to 1.54)

Recurrence

B.     I: 2/25 (8.0%)

        C: 1/14 (7.1%)

        RR 1.12 (95% CI 0.11 to 11.28)

Incontinence

1. I: 0/25 (0%)

C: 1/14 (7.1%)

2. I: 0/35 (0%)

C: 5/35 (14.3%)

Effect measure: RR (95% CI)

1. RR not estimable
2. RR not estimable

Author’s conclusion:

Because of limited available data, future studies should investigate the applicability of the LIFT procedure in patients with active proctitis, and assess further its role in Crohn’s perianal fistula, in particular in comparison with chronic seton drainage and biological therapy, as investigated in the PISA trial

Balciscueta (2017)

SR and meta-analysis of  RCTs / retrospective, and prospective studies.

Literature search up to December 2015.

1. Khafagy (2010)

Study design: RCT

Setting and Country:

Colorectal Unit, Department of General and Digestive Surgery, Arnau de Vilanova Hospital, C/ San Clemente n 12, 46015 Valencia, Spain

Source of funding and conflicts of interest:

Not reported.

Inclusion criteria SR:

• The inclusion criteria were complex anal fistulas of cryptoglandular origin treated with rectal advancement flap. In order to assess the effect of surgery on the incidence of incontinence, we only included full-continent patients before surgery.

Exclusion criteria SR:

• published before 1985, case reports enrolling less than 15 patients, studies with insufficient data or with no outcomes of interests, and studies with other procedure of the anal fistulas as well as anal fistulas of different cryptoglandular origin. When the same cohort of patients was enrolled in different studies, only the most recent publication with long-term follow-up was included.

1 study included

Important patient characteristics at baseline:

1. N = 40

Mean age

1. Not reported.

Sex:

1. Not reported.

Groups comparable at baseline?

Yes.

Describe intervention:

1. Mucosal advancement flap

Describe  control:

1. Partial thickness advancement flap

End-point of follow-up:

1. 12 months

Surgical success

1. I: 20/20 (40%)

C: 18/20 (10%)

RR 2.00 (95% CI 0.90 to 2.08).

Incontinence

1. I: 0/20 (0%)

C: 2/20 (10%)

RR not estimable

Author’s conclusion:

1. Full-thickness rectal advancement flaps offer better results regarding the recurrence than mucosal or partial flaps.

2. All flaps cause some incontinence, which increases with the thickness of the flap. Most of these alterations are minor symptoms.

3. The results did not suggest diferences in recurrence and incontinence between core-out and curettage.

Xu (2016)

SR and meta-analysis of  [RCTs / cohort / case-control studies]

Literature search up to: not reported.

1. Gafar (2013)
2. Nazeer (2012)
3. Bhatti (2011)
4. Sheikh (2015)
5. Filingeri (2004)
6. Kronborg (1985)

Study design: RCT

Setting and Country:

Emergency Department, The First Affiliated Hospital of Guangxi Medical University, Nanning City, People’s Republic of China

Source of funding and conflicts of interest:

The authors declare that they have no competing interests.

Inclusion criteria SR:

• All randomized controlled trials, which compared fistulotomy with fistulectomy treatment methods for low anal fistula, and which reported operative time, healing time, complications, recurrence and incontinence, were included.

Exclusion criteria SR:

• Abstracts, letters, case reports, comments, and conference proceedings were excluded in the review. Studies on patients with complex anal fistula, intestinal tuberculosis, Crohn’s disease or infected with HIV who were treated by fistulotomy/fistulectomy and patients undergoing additional procedure along with fistulotomy/fistulectomy were also excluded from the study.

6 studies included

Important patient characteristics at baseline:

N total per study

1. N = 36
2. N = 150
3. N = 50
4. N = 262
5. N = 20
6. N = 37

N, mean age

Not reported.

Sex:

Not reported.

Groups comparable at baseline?

Yes.

Describe intervention:

1. Fistulectomy
2. Fistulectomy
3. Fistulectomy
4. Fistulectomy
5. Fistulectomy
6. Fistulectomy

Describe  control:

1. Fistulotomy
2. Fistulotomy
3. Fistulotomy
4. Fistulotomy
5. Fistulotomy
6. Fistulotomy

End-point of follow-up:

1. 4 months
2. 10 months
3. 6 months
4. 6 months
5. 6 months
6. 12 months

Effect measure: RR, RD, mean difference [95% CI]:

A:

B:

…

Pooled effect (random effects model / fixed effects model):

…. [95% CI …to…] favoring ….

Heterogeneity (I²):

Author’s conclusion:

In brief, according to the meta-analysis, there is no conclusive evidence to show which method is better for simple anal fistula. Future randomized trials when pooled further in the meta-analysis may answer this question.

Litta (2021)

Yes

“The aim of this systematic review was to assess the surgical treatment of simple AFs by sphincter-cutting and sphincter-sparing techniques, and specifcally—(1) peri-operative features and morbidity, (2) clinical results in terms of efcacy, (3) the risk of postoperative continence impairment and impact of surgery on patients’ QoL”.

Yes

“This review was carried out according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Statement (PRISMA) guidelines [10]. A literature research was performed using PubMed, Cochrane, and Google Scholar. “Simple anal fstula”, “low anal fstula”, “intersphincteric fstula”, “low transphincteric fstula”, “fstulotomy” were the search terms used. Studies were included if they provided any number of cases analyzing any surgical treatment for simple AFs as defned by commonly adopted guidelines

Yes

“Prospective, retrospective, observational studies, and randomized clinical trials were included, while reviews, meta-analyses, trial proposals, thesis articles, technical notes, commentaries, letters, and meeting abstracts were excluded. The time range covered was 1990–April 2020, and only articles written in English were selected. Additional articles responding to the inclusion criteria were extrapolated from the bibliography of relevant material via backward citation tracking.

Yes

“Among the included studies, 28 were prospective studies [21–25, 29, 38–40, 42, 44, 48, 51, 53, 56, 58–62, 64, 65, 68, 70, 71, 74–76], 19 were retrospective series [2, 8, 13–15, 18, 26–28, 33, 43, 45, 57, 63, 66, 67, 69, 72, 73], and 19 were randomized clinical trials (RCT) [16, 17, 19, 20, 30–32, 34–37, 41, 46, 47, 49, 50, 52, 54, 55] (Tables 1–2). The quality of the studies was generally low with a consistent risk of bias; the median score of the Jadad Scale for RCT was 3 (1–5), and only 2 studies had the highest possible score [52, 55]; the median MINORS score for non-comparative studies was 12 (3–16), with only one study that could be regarded as excellent [44], while the median MINORS score for comparative studies was 17 (8–21) (Tables 1, 2). Risk of bias of the selected studies could be attributed mainly to a retrospective design, difculty or impossibility of patients’ and operators’ blinding, small sample size, short follow-up, heterogeneity of the analyzed variables, absence of uniform defnition of the main outcomes (success rate, continence impairment).

Not applicable

Yes

“A risk of bias and quality assessment was performed for each article. For randomized studies, the Jadad scale was used (1–5 points, 1=poor and 5=excellent) [11], while for non-randomized studies, the Methodological Index for Non-Randomized Studies (MINORS) Scale for comparative (0–24 points, 0=poor and 24=excellent) or non-comparative (0–16 points, 0=poor and 16=excellent) studies was applied.”

The quality of the studies was generally low with a consistent risk of bias.”.

Yes

Unclear

Yes

Stellingwerf (2019)

Yes

“ The aim of this study was to evaluate both procedures for either indication in terms of overall success, recurrence and incontinence rates.”

Yes

“MEDLINE (PubMed), Embase (Ovid) and the Cochrane Library were searched systematically up to 13 September 2017 with the assistance of a clinical librarian. Medical subject headings (MeSH) and free-text terms used included ‘ligation’, ‘ligation of intersphincteric fistula tract’, ‘LIFT’, ‘advancement’, ‘rectal fistula’, ‘anal fistula’, ‘anorectal fistula’, ‘perianal fistula’ and ‘fistula-in-ano’. The search was limited to studies published in the English language. There were no restrictions considering the publication date, and no other methodological filters were applied. Further details of the search terms are provided in Appendix S1 (supporting information).”

Yes

“All RCTs, cohort studies and case series (more than 5 patients) describing the AF or LIFT procedure in patients with high perianal fistula of cryptoglandular and/or Crohn’s origin were included. A perianal fistula was considered to be high if the tract was too high to lay open (mostly positioned in the upper two-thirds of the external sphincter with an increased risk of incontinence). Studies not reporting success or recurrence rates and length of follow-up, animal studies, reviews, case reports and letters were excluded. Other exclusion criteria were patients aged less than 18 years, those with a stoma, low perianal fistula, rectovaginal and rectourethral fistulas, fistulas without an external opening, and fistulas due to other aetiologies such as malignancy, trauma or human immunodeficiency virus infection. Combinations of techniques or other variants of the techniques, such as anocutaneous flaps, core-out fistulectomy or dissection of the tract before the actual procedure, were excluded.”

Yes

Not applicable

Yes

“ The methodological quality of the RCTs was assessed by the Cochrane Collaboration’s tool for assessing risk of bias13. This tool focuses on selection bias, performance bias, detection bias, attrition bias, reporting bias and other bias, rated as low, high or unclear risk. For cohort studies, the Newcastle–Ottawa Quality Assessment Scale was used14. Stars were assigned in three different domains (selection, comparability and outcome), with a maximum total of nine stars. In the outcome domain, a minimum follow-up period of 3 months and a maximum proportion of 5 per cent of subjects lost to follow-up was considered acceptable. Studies were rated as good, fair or poor following the Agency for Healthcare Research and Quality (AHRQ) standard15, depending on the number of stars.”

Yes

Yes

“To assess the possibility of publication bias, funnel plots were created and evaluated for asymmetry.”

Yes

Balciscueta (2017)

Yes

“The aim of this study was to evaluate the recurrence and fecal incontinence rates after performing a rectal advancement flap, depending upon thickness flap (mucosal, partial, or full thickness) and treatment of the fistulous tract (core-out fistulectomy or curettage).”

Yes

“This investigation was conducted in accordance with the methodology of the PRISMA Statement Guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses) [8]. Medline (PubMed, Ovid), the Cochrane Library database, and ClinicalTrials.gov were searched, with no language restrictions. Studies from 1985 to December 2015 were recorded. It was supplemented with manual searches of relevant meeting reports, letters, and editorials. The following keywords were used: “fistula-in-ano,” anal fistula,” rectal flap,” and advancement flap.”

Yes

“ The inclusion criteria were complex anal fistulas of cryptoglandular origin treated with rectal advancement flap. In order to assess the effect of surgery on the incidence of incontinence, we only included full-continent patients before surgery.”

“The exclusion criteria were studies published before 1985, case reports enrolling less than 15 patients, studies with insufficient data or with no outcomes of interests, and studies with other procedure of the anal fistulas as well as anal fistulas of different cryptoglandular origin. When the same cohort of patients was enrolled in different studies, only the most recent publication with long-term follow-up was included.”

Yes

“ Study characteristics were summarized in Table 2. Twenty-six studies, published from 1985 to 2015, with a total of 1655 patients were included. Six studies concerned mucosal flaps, 13 partial-thickness, 3 full-thickness flaps, 1 combined different thicknesses, and 3 studies compared two types of flap: 1 mucosal vs partial thickness and 2 mucosal vs full thickness. Of the total of patients (1655), 663 patients were treated with mucosal flap, 768 patients with partial-thickness, and 224 with full-thickness flap. In 12 studies was performed a core-out of fistulous tract, in 7 curettage, in 3 studies both techniques, and in 4 studies the treatment was unknown. The mean follow-up duration was 30.3 months (95%CI 29–31.6) and ranged from 3 to 93.6 months.”

Not applicable

Yes

“The Newcastle-Otawa scale [9] was used to assess the quality of the studies on a scale of 0 to 9. The highest quality of study design was indicated with the maximum score of 9.”

Yes

Yes

“ the study was considered to have no publication bias.”

Unclear

Xu (2016)

Yes

“Therefore, we designed this meta-analysis, and the purpose is to compare the advantages and disadvantages of two kinds of surgical procedures. Operating time, healing time and postoperative complications, recurrence and incontinence were collected and analyzed in this manuscript.”

Yes

“We searched the Medline, EMBASE, Cochrane Library and Google. The literature searches were carried out using medical subject headings and free-text word: anal fistula, perianal fistula, fistula in anal, fistulotomy and fistulectomy. Language is limited to English. Randomized controlled trials (RCT) comparing fistulotomy versus fistulectomy treatment in patients with low anal fistula were used to do a search strategy.

Yes

“All randomized controlled trials, which compared fistulotomy with fistulectomy treatment methods for low anal fistula, and which reported operative time, healing time, complications, recurrence and incontinence, were included.”

“Abstracts, letters, case reports, comments, and conference proceedings were excluded in the review. Studies on patients with complex anal fistula, intestinal tuberculosis, Crohn’s disease or infected with HIV who were treated by fistulotomy/fistulectomy and patients undergoing additional procedure along with fistulotomy/fistulectomy were also excluded from the study.”

Yes

Not applicable

Yes

“The quality of randomized clinical trials was the Jadad Scale (1996).”

Yes

Unclear

Yes