Surgery of Simple and Complex Anal Fistulae in Adults: A Review of the Literature for Optimal Surgical Outcomes

Abstract

Anal fistulas are common anorectal conditions, and surgery is the primary treatment option. In the last 20 years of literature, there exist a large number of surgical procedures, especially for the treatment of complex anal fistulas, as they present more recurrences and continence problems than simple anal fistulas. To date, there are no guidelines for choosing the best technique. We conducted a recent literature review, mainly the last 20 years, based on the PubMed and Google Scholar medical databases, with the goal of identifying the surgical procedures with the highest success rates, lowest recurrence rates, and best safety profiles. Clinical trials, retrospective studies, review articles, comparative studies, recent systematic reviews, and meta-analyses for various surgical techniques, as well as the latest guidelines of the American Society of Colon and Rectal Surgeons, the Association of Coloproctology of Great Britain and Ireland, and the German S3 guidelines on simple and complex fistulas were reviewed. According to the literature, there is no recommendation for the optimal surgical technique. The etiology, complexity, and many other factors affect the outcome. In simple intersphincteric anal fistulas, fistulotomy is the procedure of choice. In simple low transsphincteric fistulas, the patient's selection is crucial in order to perform a safe fistulotomy or another sphincter-saving technique. The healing rate in simple anal fistulas is higher than 95% with low recurrence and without significant postoperative complications. In complex anal fistulas, only sphincter-saving techniques should be used; the optimal outcomes are obtained by the ligation of the intersphincteric fistulous tract (LIFT) and rectal advancement flaps. Those techniques assure high healing rates of 60-90%. The novel technique of the transanal opening of the intersphincteric space (TROPIS) is under evaluation. The novel sphincter-saving techniques of fistula laser closure (FiLac) and video-assisted anal fistula treatment (VAAFT) are safe, with reported healing rates ranging from 65% to 90%. Surgeons should be familiar with all sphincter-saving techniques in order to face the variability of the fistulas-in-ano. Currently, there is no universally superior technique that can treat all fistulas.

Full text

Review began 02/07/2023
Review ended 03/01/2023
Published 03/08/2023
© Copyright 2023
Charalampopoulos et al. This is an open
access article distributed under the terms of
the Creative Commons Attribution License
CC-BY 4.0., which permits unrestricted use,
distribution, and reproduction in any
medium, provided the original author and
source are credited.
Surgery of Simple and Complex Anal Fistulae in
Adults: A Review of the Literature for Optimal
Surgical Outcomes
Anestis Charalampopoulos , Dimitrios Papakonstantinou , George Bagias , Konstantinos Nastos ,
Markos Perdikaris , Savvas Papagrigoriadis
1. Third Department of Surgery, "Attikon" University General Hospital/National and Kapodistrian University of Athens,
School of Medicine, Athens, GRC 2. Rectal and Pelvic Surgery, Metropolitan General Hospital Athens, Athens, GRC
Corresponding author: Anestis Charalampopoulos, achalaral@med.uoa.gr
Abstract
Anal fistulas are common anorectal conditions, and surgery is the primary treatment option. In the last 20
years of literature, there exist a large number of surgical procedures, especially for the treatment of complex
anal fistulas, as they present more recurrences and continence problems than simple anal fistulas. To date,
there are no guidelines for choosing the best technique. We conducted a recent literature review, mainly the
last 20 years, based on the PubMed and Google Scholar medical databases, with the goal of identifying the
surgical procedures with the highest success rates, lowest recurrence rates, and best safety profiles. Clinical
trials, retrospective studies, review articles, comparative studies, recent systematic reviews, and meta-
analyses for various surgical techniques, as well as the latest guidelines of the American Society of Colon
and Rectal Surgeons, the Association of Coloproctology of Great Britain and Ireland, and the German S3
guidelines on simple and complex fistulas were reviewed.
According to the literature, there is no recommendation for the optimal surgical technique. The etiology,
complexity, and many other factors affect the outcome. In simple intersphincteric anal fistulas, fistulotomy
is the procedure of choice. In simple low transsphincteric fistulas, the patient’s selection is crucial in order
to perform a safe fistulotomy or another sphincter-saving technique. The healing rate in simple anal fistulas
is higher than 95% with low recurrence and without significant postoperative complications. In complex
anal fistulas, only sphincter-saving techniques should be used; the optimal outcomes are obtained by the
ligation of the intersphincteric fistulous tract (LIFT) and rectal advancement flaps. Those techniques assure
high healing rates of 60-90%. The novel technique of the transanal opening of the intersphincteric space
(TROPIS) is under evaluation. The novel sphincter-saving techniques of fistula laser closure (FiLac) and
video-assisted anal fistula treatment (VAAFT) are safe, with reported healing rates ranging from 65% to
90%. Surgeons should be familiar with all sphincter-saving techniques in order to face the variability of the
fistulas-in-ano. Currently, there is no universally superior technique that can treat all fistulas.
Categories: Gastroenterology, General Surgery
Keywords: surgery, endorectal advancement flap, laser fistulotomy, video-assisted anal fistula treatment,
fistulotomy, fistulectomy, complex anal fistula, simple fistula, fistula-in-ano, anal fistula
Introduction And Background
An anal fistula (AF) is an abnormal communication between the anorectal canal and the peri-anal skin. It is
part of the natural history of the perianal abscess. The main characteristics of a fistula are the following: (a)
the presence and location of the internal opening (IO) at the anorectal canal, (b) the presence of an external
opening at the anal/perianal skin, and (c) the presence of a fistulous tract of various length and route
affecting the anorectal sphincter system: internal, external, and levator ani (puborectalis) muscles.
Secondary tracts and abscess cavities connected with the fistulous tract are not excluded.
Even though AF is a common condition in anorectal surgery, it is a rare disease [1] with a prevalence of
fewer than 5 cases/10,000 per 10,000 people. The most common etiologies are cryptoglandular AF and the
second most common anorectal Crohn’s disease (CD). Other etiologies, such as iatrogenic trauma,
infections, and malignancy, present a lower incidence and prevalence.
The pathogenesis of AF still remains unclear; in cryptoglandular AF [2], histological, microbiological,
molecular, and host factors are related to the development and persistence of AF, while in anorectal CD, the
trans-mural inflammatory process contributes to the formation of anorectal abscess and AF.
Cryptoglandular fistulas should be distinguished from secondary etiologies due to differences in surgical
outcomes, which mainly depend on the underlying disease. AF affects more middle-aged patients with a
male-to-female ratio of 2/1. To date, the only acceptable cutting-sphincter surgical procedure in use is
fistulotomy in simple AF. In complex AF, many sphincter-saving procedures are in use for the treatment of
AF, and the guidelines leave several options.
1 1 1 1
1 2
Open Access Review
Article DOI: 10.7759/cureus.35888
How to cite this article
Charalampopoulos A, Papakonstantinou D , Bagias G, et al. (March 08, 2023) Surgery of Simple and Complex Anal Fistulae in Adults: A Review of
the Literature for Optimal Surgical Outcomes. Cureus 15(3): e35888. DOI 10.7759/cureus.35888

Studies that assess the treatment of cryptoglandular AF present heterogeneity [3], without uniform
outcomes, and the comparisons between different procedures are quite difficult, but some surgical
procedures seem to be more superior to other techniques.
The aim of this review study is to identify the range of surgical procedures in use, the factors that affect the
surgeons’ choice, and also to collect data for the surgical procedures in use regarding the surgical outcomes
and the safety of the procedure, regarding the postoperative continence or other anal local complications.
We identify the most important, currently in-use surgical procedures for AF treatment from a large spectrum
of surgical procedures available. We provide data for successful individual therapy in patients with AF and a
strategy in surgery for optimal outcomes, based on the recent literature.
Review
Complexity systems of classification
There are many systems of classification of AF in the literature; the most common and important ones in use
are described here. Park’s system of classification [4], in place since 1976, belongs to the era before the
widespread use of imaging. It is a clinical/surgical system of classification of cryptoglandular fistulas that
defines AF into four main types: intershincteric, transsphincteric, suprasphincteric, and extrasphincteric
fistulas; the submucosal AF (simple entities without anal sphincter participation in fistula formation) were
not included in the original classification due to different etiologies; this classification has many variations
and references to other more complex entities. The most common AF are intersphincteric and
transsphincteric AF. The grade and types of fistulas in this classification system are described in Table 1.
Grade Description of
the fistula Characteristics
I Intersphincteric
Ia: low; Ib: high extension in rectal wall without an additional high opening in the rectum; Ic: high extension in rectal wall
with an additional high opening in the rectum ; Id: no external opening in the perianal skin in the type Ib or Ic; I e: high
extension in pelvic cavity; If: pelvic disease draining into the perianal skin through the intersphincteric space
II Transsphincteric IIa: all fistulas below the puborectalis muscle; IIb: fistula with a branch going high in ischiorectal fossa (infralevator) or high
through levator muscle (translevator) but not opening into the rectum
III Suprasphincteric Suprasphincteric fistula with or without a supralevator extension
IV Extrasphincteric
IVa: transsphincteric fistula with a branch going high through levator muscle (translevator) but opening into the rectum (type
IIb with an additional opening high in the rectum); IVb: extrasphincteric tract due to trauma; IV
c: extrasphincteric tract due to
anorectal disease like Crohn’s disease, ulcerative colitis, or carcinoma; IVd: pelvic disease draining into the perianal skin
after piercing through the levator muscle
TABLE 1: The Parks system classification for anal fistulas
Supralevator fistula could be present in grade I, II, or III. Translevator fistula could be present in grade II (IIb) or IV (IVa).
Another system of classification that belongs to the post-magnetic resonance imaging (MRI) era is the St.
James’s University Hospital (SJUH) system of classification. It is a descriptive system, and most radiologists
are familiar with the above system [5]. Based on the MRI evaluation of AF and the spectrum of imaging
features, AF was classified into five grades of complexity with an allocation of predictive value to MRI for
postoperative outcomes, according to secondary tracts and abscesses that increase the grade of the
complexity of AF. Grades I and II are simple fistulas with favorable surgical outcomes, and grades III and IV
are the complex transsphincteric AFs with more recurrences after surgery and an increased possibility for
incontinence problems. Grade V is the most complex AF; those are the translevator or supralevator, which
are surgical challenges but fortunately have a low incidence. The main characteristics of AF are shown in
Table 2.
2023 Charalampopoulos et al. Cureus 15(3): e35888. DOI 10.7759/cureus.35888 2 of 12

Grade Description of the fistula
IIntersphincteric: linear
II Intersphincteric: multiple tracts or associated abscess
III Transsphincteric: linear
IV Transsphincteric: multiple tracts or associated abscess
VSupralevator or translevator/extrasphincteric
TABLE 2: The St. James’s University Hospital classification of anal fistulas by MRI
Suprasphincteric fistulas was categorized along transsphincteric fistulas as grade IV.
In a recent study based on a large number of patients who underwent surgery for cryptoglandular AF, a
modified version of Park’s system classification [6] distinguishes AF into four stages of simple and complex
AF, incorporating: (a) changes in the description of AF; those transsphincteric were divided into low and
high transsphincteric AF, while suprasphincteric and extrasphincteric (internal opening of AF at the rectum)
were grouped into one type, (b) four independent risk factors were significant predictors of surgical failure;
secondary AF extensions, horseshoe AF, previous AF surgery, and anterior AF in women. The first three
types of AF were subdivided according to the presence or absence of predictive factors for surgical failure.
Thus, the failure rates in surgery were ranging from 2.3% in simpler AF up to 30.7% in more complex AF. The
modified Parks classification system is shown in Table 3.
Stage Characteristics
IIntersphincteric fistula not involving the external anal sphincter fibers
IA Simple linear, non-branching intersphincteric tract
IB Intersphincteric tract with at least one of the following: Horseshoe tract, secondary extensions and associated abscess cavities, anterior fistula
in female patients, history of previous surgery for anal fistula
II Low transsphincteric fistula involving less than 30% of external anal sphincter fibers
IIA Simple linear, non-branching low transsphincteric tract
IIB Low transsphincteric tract with at least one of the following: Horseshoe tract, secondary extensions and associated abscess cavities, anterior
fistula in female patients, history of previous surgery for anal fistula
III High transsphincteric fistula involving more than 30% of external anal sphincter fibers
IIIA Simple linear non-branching high transsphincteric tract
IIIB High transsphincteric tract with at least one of the following: Horseshoe tract, secondary extensions and associated abscess cavities, anterior
fistula in female patients, history of previous surgery for anal fistula
IV Unusual types of fistula: suprasshincteric and extrasphincteric
TABLE 3: The modified Parks classification system for crypto-glandular anal fistulas
Another new system of classification for AF was proposed by Garg [7], based on a large number of patients. It
seems to be more accurate than Park’s and SJUH's classification of AF [8] and classifies the severity of AF in
five main grades with important implications for further surgical management; all patients are classified
according to the preoperative MRI and the severity of AF [9]. The benefit is the correct classification of AF in
simple AF, where fistulotomy is a safe operation, and in more complex AF, where fistulotomy is
contraindicated and a sphincter-saving technique should be used. This system contains five grades of
complexity, etiology, and risk factors and provides treatment guidelines. The original system of classification
is shown in Table 4.
2023 Charalampopoulos et al. Cureus 15(3): e35888. DOI 10.7759/cureus.35888 3 of 12

Grade Treatment guidelines
I: I-A: low-linear intersphincteric; I-B: low-linear transsphincteric (less than 1/3 of EAS
involvement). Fistulotomy should be possible in >95% of these AF.
II: low intersphincteric and transsphincteric AF (less than 1/3 of EAS involvement); II-A:
abscess; II-B׃ multiple tracts; II-C׃ horseshoe; II-D׃ supralevator: complete intersphincteric
supralevator AF; II-E: supralevator: Low transsphincteric (<1/3 EAS involvement) with
intersphincteric supralevator extension.
Fistulotomy should be possible >90% of these AF.
III: III-A: high linear transsphincteric fistula (>1/3 EAS involvement); III-B: fistula with
associated Crohn’s disease, sphincter injury, post-radiation exposure or anterior fistulae in
a female.
Fistulotomy should not be attempted. FPR or sphincter-
saving procedures: LIFT, VAAFT, AFP, TROPIS, OTSC,
or FiLac therapy should be done.
IV: complex high (>1/3 EAS involvement). Transsphincteric fistula with either: IV-A:
abscess; IV-B: multiple tracts; IV-C: Horseshoe.
Fistulotomy should not be attempted. FPR or sphincter-
saving procedures: LIFT, VAAFT, AFP, TROPIS, OTSC,
or FiLac therapy should be done. Preferably refer these
AF to a fistula expert.
V: V-A: transsphincteric (>1/3 EAS Involvement) with intersphincteric supralevator
extension; V-B: suprasphincteric fistula; V-C: extrasphincteric fistula.
Fistulotomy should not be attempted. FPR or sphincter-
saving procedures: LIFT, VAAFT, AFP, TROPIS, OTSC,
or FiLac therapy should be done. Preferably refer these
AF to a fistula expert.
TABLE 4: The Garg P. original classification system for anal fistulas
FPR: fistulotomy with primary reconstruction, EAS: external anal sphincter, AFP: anal fistula plug.
The characteristics of simple and complex anal fistulas
From a practical standpoint, all systems of classification of AF for diagnosis and further surgical
management describe two distinct conditions. The simple AF, where the fistulotomy is a safe operation with
high healing rates and no postoperative continence problems if the patients are correctly selected and
classified, and the complex AF, with significant participation of the anal sphincter muscle in the fistula
formation, present more recurrences after surgery and continence problems; thus, in surgery, only
sphincter-saving procedures should be used. Complex AF is the transsphincteric AF with the participation of
the external sphincter of more than 30% in fistula formation (the most common complex AF),
suprasphincteric AF, extraspincteric AF, horseshoe AF, recurrent AF, anterior AF in women, AF in relation
to inflammatory bowel diseases, pelvic radiation, and malignancy.
Studying the complexity of AF
Simple AF probably does not require preoperative imaging studies if the preoperative diagnosis is accurate.
All other AF, such as complex AF, anal CD, recurrent AF, immunosuppressive patients, and patients with
occult anal abscess or AF, according to the recommendations of the American Society of Colon and Rectal
Surgeons (ASCRS) [10], should be studied preoperatively by imaging studies.
The most useful investigation is an MRI with the fistula protocol. MRI is the optimal preoperative imaging
study [11], more sensitive than clinical evaluation, and comparable with endoanal ultrasounds (EUS) in the
distinction between simple and complex AF. A practical MRI radiologic report [12] provides surgeons with all
necessary information for the location of the internal opening of the AF, the external opening location, the
classification of AF, the presence of secondary tracts and abscesses, the evaluation of the supralevator space,
the presence or not of a previous sphincter injury, and the activity of the fistulous tract; it may be active
(with fluid or pus within the tract) or more fibrotic. This information has significant implications for further
surgical management. The assessment of the ischio-anal and ischio-rectal fossa [13] by the presence of a
fistulous tract reveals a complex AF of grade III or IV (transsphincteric or suprasphincteric); indeed, if the
fistulous tract traverses the lavatory ani muscle, it shows a more complex AF of grade V (supralevator or
translevator).
The endoanal three-dimensional ultrasound scan (3D EUS) or 2D has a supplementary role because of its
potential to be used multiple times for follow-up with the economy of costs and time resources. Three-
dimensional EUS and MRI [14] are accurate in simple AF; the results are comparable in complex AF; and MRI
is superior to EUS in the detection of secondary tracts.
Examination under anesthesia (EUA) is the traditional gold standard of assessment for the proctologist,
which is important for the choice of optimum surgical management. EUA in anal CD should be performed
2023 Charalampopoulos et al. Cureus 15(3): e35888. DOI 10.7759/cureus.35888 4 of 12

before the medical therapy [15], as the procedure gives the opportunity to drain an abscess or to place
drainage setons for the improvement of the local anal inflammatory process. EUA is the gold standard
procedure for the evaluation of anal CD [16], and EUA with MRI or EUS presents 100% diagnostic accuracy
[17] for the evaluation of anal CD.
Outcomes of surgery and the current practice of anal surgeons
Many factors are related to surgical outcomes [18], such as the experience of the surgeon, the complexity of
AF, the involvement of the anal sphincter muscles, the method of the surgical procedure, and many patient-
related factors.
On the other hand, the position of the anal surgical community presents significant differences not only in
the choice of surgical technique but also in the diagnostic procedures used for the evaluation of AF [19]. In a
recent international survey for the surgical practice and management of AF with a 74-item questionnaire,
there were broad technique variations in surgical practice, and it was difficult to reproduce and compare the
outcomes between different centers. Here are some interesting results of the study. Some 80% of
respondents consider fistulotomy the gold standard treatment for simple anal fistulas. The ligation of the
intersphincteric fistulous tract (LIFT) procedure with technical variations is performed by 38% of surgeons.
When an endorectal advancement flap is performed, full-thickness flaps are more commonly used than
partial-thickness flaps. Novel techniques such as video-assisted anal fistula treatment (VAAFT), fistula laser
closure (FiLac), and over-the-scope clips (OTSC) were used by less than 10% of the respondents. Only 1-4%
of surgeons were confident enough to perform one of the novel sphincter-saving techniques in patients with
anal CD.
Surgery of simple AF
Surgery is the only treatment option in AF, whereas in CD, where the anal canal is affected in 20-40% of
patients, medical agents contribute to the remission of the disease [20]; combined surgical therapy by
drainage setons with immunomodulators and anti-tumor necrosis factor (TNF) may contribute to AF
closure.
To date, the only acceptable sphincter-cutting procedure in use is fistulotomy in simple AF. It is probably the
most common operation in use, as simple AF accounts for 30-50% of all AF. The healing rates are more than
95%.
It is a safe and easy operation with continence preservation and low recurrence rates depending on the
presence of secondary tracts, the identification of the IO, and the etiology (cryptoglandular or anal CD).
In simple low transsphincteric fistulas (or low intersphincteric, as they were called in the past; defined as
grade II AF in MRI or low AF) containing less than 30% of the external anal sphincter, a fistulotomy may be
complicated by symptoms of incontinence [21], and the risk of impairment continence is one to five
patients; most patients present minor continence problems, but more severe problems are not excluded and
are dependent from the amount of external sphincter divided during fistulotomy. It is unknown what
amount of the external sphincter is divided that influences continence, but it seems that a division of the
external anal sphincter of more than 25% [22] is correlated with a high Fecal Incontinence Severity Index
score after fistulotomy. Continence problems may be transient or persistent. Thus, fistulotomy is not
completely harmless, as one to five patients will present continence problems; this percentage probably is
unacceptable in the era of numerous sphincter-saving procedures, and patients should be carefully selected
for a safe fistulotomy.
The correct distinction between a simple intersphincteric fistula and a low transsphincteric fistula, with the
evaluation of the amount of external sphincter participating in fistula formation, is crucial for the choice of
the surgical technique; the choice is between fistulotomy and another sphincter-saving procedure.
Another key point in the successful treatment of a simple AF is the integrity of the anal sphincteric system,
is the intersphincteric space alone affected, or is part of a more complex sphincter system involved? In the
former case, fistulotomy is adequate, and in the latter case, a sphincter-saving procedure for complex AF
should be performed.
To date, fistulotomy in simple AF has gained its position in the guidelines of the ASCRS, the German S3
guidelines [23], the Italian Society of Colorectal Surgery (SICCR) [24], and in the second Association for
Coloproctology of Great Britain and Ireland (ACPGBI) position statement for the treatment of AF [25], with
strong recommendations with level evidence 1B, 1B, 2B, and C, respectively. A careful selection of patients
is crucial to performing a safe fistulotomy.
Surgery of complex AF
In complex AF, only sphincter-saving procedures should be used. The goal of surgery is first to remove or
destroy the fistulous tract while preserving the integrity of the sphincters, and then to identify risk factors
2023 Charalampopoulos et al. Cureus 15(3): e35888. DOI 10.7759/cureus.35888 5 of 12

for the recurrence of AF.
The outcomes of surgery in complex AF present more recurrences and continence problems than in surgery
of simple AF. Numerous factors are reported in the literature as risk factors for recurrence after surgery [26].
They are factors related to AF anatomy and other anal comorbidities (previous anal surgery and eventual
sphincter damage, anal CD, post-radiotherapy AF), numerous preoperative and intraoperative factors, and
factors related to postoperative complications and care.
In a recent meta-analysis [27], many factors of major or minor significance for recurrence are described;
high-risk factors for recurrence are a high transsphincteric fistula, a missed IO at surgery, and horseshoe
extensions. This evidence comes from high-quality observational studies. Other risk factors associated with
the recurrence of AF are the presence of secondary tracts, prior anal surgery, and seton placement.
In a case-series study with 483 patients about the long-term results of surgical treatment of AF [28], the
recurrence rate for complex AF with various surgical procedures was 18%, with a requirement of up to three
reoperations before complete healing.
In the last 20 years, several surgical procedures have been used for complex AF, some of them popular and
others less so. In the literature, the surgical outcomes, healing rates, recurrence rates, and incontinence
rates vary between studies for any specific technique; heterogeneity in the etiology and grade of the
complexity of the AF in patients studied, as well as the methodology of studies, explain the differences in
surgical outcomes. The majority of the studies are retrospective, case-series, or non-randomized control
studies with various inclusion criteria.
In a systematic review and meta-analysis of surgical interventions for high crypto-glandular AF [29], the
best surgical technique could not be identified, and there was a need for more randomized control trials.
Surgeons should be familiar with several procedures available for AF treatment in order to be able to choose
the most suitable surgical technique after imaging and classification. At the moment, a universally optimal
surgical procedure cannot be identified.
Most common operations for complex anal fistulas
Cutting Seton
The Hippocratic technique was more popular in the past, but it is now practiced less [30] due to reported
high rates of incontinence. In the previous meta-analysis (since 2009), the incontinence rates varied from
12% to 30% in transsphincteric AF and 53% in suprasphincteric AF. The recent recommendation for the
technique in selected patients is weak with evidence 2C, according to the practice guidelines of the ASCRS.
There have been no studies in the last 10 years on the current use of the method in complex AF.
Drainage (Loose) Seton
This is useful and often necessary in the acute phase of anal/perianal sepsis. It helps to improve local clinical
symptoms and downstage the complexity of the AF. Drainage setons may stay for weeks, months, or years
according to the local evolution of sepsis. They are commonly used in fistulizing anorectal CD control in
combination with medical agents. The failure of surgical or medical therapy with refractory anal fistulizing
symptoms may require eventual radical surgical therapy with proctectomy and permanent colostomy. There
are no new publications to provide recommendations for the method in practice guidelines, except in
fistulizing anal CD for long-term control of the disease (strong recommendation, evidence 1B).
Plugs in Fistula
They are minimally invasive techniques; however, they have healing rates [31,32] in complex AF of 50% or
less one year after surgery. The successful healing rates decrease with time. Plugs are not an adequate
treatment for complex AF.
Glue Sealants
There is an increased failure of healing [33] with time after the performance of this procedure; the healing
rates are 14%, 16 months after surgery. There have been no new publications on the method in the last 10
years. The method may be used only in exceptional cases, according to the German S3 guidelines for AF.
In both procedures, glue sealants and plugs remain in use only for selected patients and only in combination
with other sphincter-saving procedures.
Rectal Advancement Flaps (RAF)
2023 Charalampopoulos et al. Cureus 15(3): e35888. DOI 10.7759/cureus.35888 6 of 12

The procedure includes the curettage of the fistulous tract, the closure of the IO with sutures, and its
obliteration by a rectal flap [34]. Partial-thickness RAF of any shape, whether rhomboid or elliptical, is the
most common in use, and the shape does not influence the failure rates. The failure rates in the literature
vary from 15 to 60%. The majority of patients postoperatively present with some degree of incontinence.
The procedure is repeatable if the first mucosal RAF fails, and it may be used in recurrences after other
sphincter-saving techniques, e.g., LIFT.
In a systematic review and meta-analysis [35] of the use of RAF and ligation of the intersphincteric fistula
tract (LIFT) for cryptoglandular AF and anal CD, RAF had similar and comparable outcomes with LIFT
regarding the healing rates, but incontinence was statistically significant in RAF more than in LIFT, with a
lack of data for recurrences.
In another review and systemic meta-analysis [36] of RAF in complex cryptoglandular AF, the pooled rate of
recurrence was 21%, with rates of 7.4%, 19%, and 30.1% for full-thickness, partial, and mucosal flaps,
respectively. Indeed, all flaps caused some incontinence, which was increased by the flap's thickness. RAF
and LIFT may be used to treat AF in anal CD.
In the most recent ASCRS guidelines, evidence 1B has a strong recommendation for treating RAF.
LIFT
This procedure, with many variations, has gained popularity in the last 10 years as it is easily performed,
safe, cheap, without significant postoperative incontinence, and has high healing rates of 60-90%. In a
simplified variation, the main surgical steps [37] are the division and ligation with sutures of the fistulous
tract at the level of the intersphincteric space. Failure of the procedure does not exclude a repeat operation.
The procedure may be used in both complex and simple low transsphincteric AF.
In a review study and meta-analysis [38], with the majority of patients (92.36%) having transsphincteric AF
and long-term follow-up, LIFT showed favorable short- and long-term outcomes, a low postoperative
complications rate of 1.88%, an overall mean healing rate of 81.37%, an overall healing period of 8.15 weeks,
and AF recurrence in 7.58% of patients in the studied reports.
In a recent meta-analysis [39] with a large number of patients, examining 26 studies with a mean follow-up
of 16 months, the overall success rate, complications rate, and incontinence rate were 76%, 14%, and 1.4%,
respectively, with risk factors for recurrence being the existence of a horseshoe fistula, anal CD, and previous
anal surgery.
The LIFT procedure may also be used [40] in anal CD; in a recent study with a long follow-up period, the
healing rates were at 65%, and the majority of patients already had a seton placement before LIFT. LIFT
gains a position in the treatment of complex transsphincteric AF in the recent guidelines of the ASCRS with
a strong recommendation of evidence 1B.
Transanal Opening of the Intersphincteric Space (TROPIS)
It is a novel surgical sphincter-saving technique [41], the newest in the literature since 2017, with reported
healing rates >90% without postoperative incontinence for complex AF. It has good long-term outcomes in
follow-up. The procedure is suitable for high-grade complex AF [42] as well as supralevator ones. TROPIS is
also recommended for horseshoe AF.
The procedure is of intelligent design, easily performed, and focused on treating surgically the
intersphincteric fistulous tract. It involves laying open the fistula tract and secondary healing. The method
competes with LIFT [43]. Both techniques, LIFT and TROPIS, present optimal surgical results with different
surgical approaches; LIFT is focused on the closure of the IO of the fistulous tract, and TROPIS opens the
intersphincteric space.
In a systematic review article on the efficacy and safety of sphincter-saving techniques [44] in complex AF,
TROPIS may have the highest cure rates. The TROPIS represents a variation of the old Parks’ technique
which requires to be tested by more surgeons and longer follow up in order to find its position in current
practice and the guidelines.
Stem Cells Therapy of AF
This is an expensive treatment that is only suitable for highly selected patients with refractory anorectal
fistulizing CD without any response to other conventional therapies. There are few reports in the literature
with a limited number of patients.
In a multi-centric study [45] from six Spanish hospitals with 24 patients, there was an improvement in AF
2023 Charalampopoulos et al. Cureus 15(3): e35888. DOI 10.7759/cureus.35888 7 of 12

drain, with complete healing at 30%; the method could be repeated in a few weeks if active AF remains. In
another multi-centric European study [46], there was significant local control and remission of the disease
in 50% of patients; complications reported were proctalgia and anal abscess.
New minimally invasive sphincter-saving techniques for complex AF
treatment
OTSC Proctology Device
It is a new endoscopic sphincter-saving technique [47] for the closure of the IO of the AF with a nitinol
closure clip. The technique may be used in combination with other techniques such as VAAFT and fistula
laser closure (FiLac) with a synergic effect.
Small studies exist, with a small number of patients and without long-term results. In a case study with 22
patients and long-term follow-up at three years [48], the complete healing rate of AF was 59%, the majority
of clips were removed after 3-12 months (mean time of 5.8 months), and few clips remained in situ. No
incontinence was reported, and one patient presented with burning after defecation and after the removal of
the clip. The recurrence rate with active AF was 41%.
Other case studies with a small number of patients report higher rates of healing at 70% [49]. The procedure
was performed in refractory AF with previous surgery, including patients with anal CD.
Another study reports healing rates [50] of 79% (short-terms outcomes) when the procedure was performed
as first-line therapy, with lower healing rates at 45% and 20% in AF due to inflammatory bowel diseases and
recto-vaginal fistulas, respectively. Indeed success rates in recurrent cases were 26%. The method cannot be
evaluated at the moment, without any position in guidelines for AF therapy.
FiLaC Therapy
A fistula tract ablation technique with an approximate success rate of 60% or any more. Outcomes are better
when the fistulous tract is of short length (3 cm) [51] with success rates at 58.3%, while in long fistulous
tracts (>3 cm), the success rates decrease to 16.6%. The procedure does not treat secondary tracts or abscess
cavities.
In another recent retrospective study [52] with AF of crypto-glandular etiology with 175 patients and long
follow-up, healing rates at 66.8% is reported. In the majority of patients (81.8%) a seton was placed before
FiLac for a mean period time of 14 weeks. Routine MRI or EUS before FiLac therapy was performed to
exclude abscess cavities (contraindication for FiLac). The healing rates ranged from 51.5% up to 70.4% in
patients with seton placement prior to FiLac therapy. Suprasphincteric AF was more difficult to treat, with a
longer operative time. The method did not treat the IO; when it was enlarged due to seton, it was closed by
some stitches in a few patients. The method as a noninvasive technique has also been used in anal CD [53],
with a few cases reported in the literature.
In a meta-analysis [54] for the safety and efficacy of FiLac, with a two-year follow-up in transsphincteric
and also recurrent AF in 454 patients, the healing rate, complication rate, and incontinence rate were 67.3%,
4%, and 1%, respectively.
In another meta-analysis [55] of the effectiveness of the FiLac, with 476 patients, 60% of whom had previous
anal surgeries, the success and complication rates were 63% and 8%, respectively.
Despite the new technique of FiLac therapy for AF, new emerging data [56] exist regarding the variations of
the technique, the selection of patients, outcomes, and complications. To date, the procedure may be
performed in simple and complex AF, in anal CD, and in recurrent AF. The method may be
repeated. Another similar new laser procedure is photo dynamic therapy (PDT) [57] with success rates of
80% with few cases reported in the literature at the moment.
The minimally invasive nature and the possibility of repeating the procedure have made it attractive to
surgeons and patients and it has earned a position in the newest guidelines (2022) of the ASCRS with weak
recommendation 2C, mainly due to lack of long-term outcomes. No recommendation in the oldest
guidelines of the ACGBI and German S3 guidelines.
VAAFT
It is a new sphincter-saving technique without any significant postoperative complications or incontinence
that has high healing rates. It is the only endoscopic procedure with visual access into the lumen of the
fistulous tract. It provides the opportunity to concurrently treat the IO, secondary tracts, and abscess cavities
with ablation of the fistulous tract.
2023 Charalampopoulos et al. Cureus 15(3): e35888. DOI 10.7759/cureus.35888 8 of 12

The VAAFT procedure was proposed by Meinero et al. [58], who presented outcomes in 136 patients with
complex AF in 2011, excluding CD and simple AF. The healing rate was 87.1% one year after surgery. Three
years later, in a book chapter by the same author [59], based on 203 patients with complex and recurrent AF,
the advantages of VAAFT were claimed to be: a large number of patients did not require preoperative
assessment of fistula anatomy by MRI. In 59.6% of patients, secondary infections and abscesses were treated
simultaneously and successfully during the procedure. Easy and rapid detection of the IO was achieved
within five minutes in most patients (84.2%); in the remaining patients, it was detected by viewing the light
of the fistuloscope inside the lumen of the anorectal canal. There was a short operative time of a median 30
minutes. The majority of patients had prior surgery, and the healing rates were 93.2% with a one-year
follow-up. There were only minimal postoperative complications, which were treated conservatively. There
was no incontinence. The majority were discharged on the same day of surgery. The lost time from work was
up to three days.
The procedure rapidly gained popularity worldwide; it is also expanded [60] in the pediatric population and
anal CD, which may be combined [61] with RAF. There is [62] a palliative effect in the main local anal
symptoms, such as pain and discharge, in patients with anal CD and complex refractory AF undergoing
VAAFT. At the moment, cases of anal Crohn’s disease reported in the literature are few, and if the equipment
is available, the technique is expanded to other surgical entities [63], such as the pilonidal sinus.
In a case study [64] with 41 patients with complex cryptoglandular AF, the primary healing rate was 70.7%,
the method was repeatable in recurrences, and the secondary healing rate was 83% using various techniques
for the closure of the IO; closure with RAF had more recurrences than stapler closure, and OTSC had no
recurrences but with a small number of patients.
In another case study [65] with 104 patients (those with secondary etiologies were excluded) and a three-
year follow-up, the success rate was 84.4%. Recurrences were treated by the same procedure and were
completely healed; the only risk factor for recurrence was the advanced age (>50 years).
In 2017, there was the first meta-analysis [66] on the efficacy of VAAFT in cryptoglandular complex AF, with
success rates of 76%, minimal incontinence, a short hospital stay, and low complication rates.
In a recent systematic review and meta-analysis of the efficacy and safety of VAAFT [67], the recurrence rate
was 14.2% with a follow-up of nine months, probably related to previous AF surgery and the method of
closure of the IO of the fistulous tract; there were fewer recurrences after the use of staplers or sutures than
in closure with RAF. The complication rate was 4.8%, the majority was of Clavien-Dindo severity score I or
II, and no incontinence was reported in any study of this systematic review.
The latest meta-analysis [68] reports success, recurrence, and postoperative complications rates of 83%,
16%, and 11%, respectively, and recurrent cases vary according to the method of closure of the IO; the
closure of the internal opening of the fistulous tract may be performed in several ways, and the RAF closure
may be more susceptible to recurrences than other methods of closure. This observation may be biased as
the advancement flap is used in insecure local conditions for the closure of the internal opening, while other,
more simple techniques are used in safe local conditions. To date, there are no guidelines for the preferable
option for the closure of the IO of the AF; local anal conditions around the internal opening, such as
extensive fibrosis due to previous surgery or an inactive IO, should be well estimated for a secure closure;
linear or semicircular staplers, sutures, OTSC or LIFT combined with VAAFT is a solution. If the closure is
insecure, then an advancement flap is the last solution.
Conclusions
During treatment for AF, there are a wide range of surgical procedures and a wide range of different anal
conditions. Twelve surgical procedures are currently in use for the AF treatment, with an emphasis on new
sphincter-saving procedures with high healing rates >60-80% and without any significant position in
guidelines as they are in their infancy. Indeed, high diversity in local anal conditions exists regarding the
grade of complexity and the existence or not of risk factors for recurrence such as secondary tracts, abscess
cavities, horseshoe tracts, anterior AF in women, and anal trauma (previous anal surgery); these factors
should be detected and treated during surgery. The etiology is another factor that increases the diversity of
patients. Finally, surgery has multiple goals. First, the surgeon should eliminate during surgery any detected
risk factor for recurrence. Second, in the era of sphincter-saving techniques, one should respect the anatomy
and integrity of the anal sphincter system to avoid postoperative continence problems, and finally, one
should choose a suitable procedure to treat the fistulous tract and assure a safe closure of the internal
opening. The next point is the most crucial in the decision-making process for further surgery; after studying
the complexity, a safe fistulotomy or sphincter-saving procedure should be used, where literature and
guidelines leave several options for treatment. An experienced anal surgeon should assure a safe closure of
the internal opening by choosing the most suitable procedure; many ways exist, such as laser therapy,
VAAFT, LIFT, OTSC, RAF, and semicircular staplers. This concept of a safe closure of the internal opening
has dominated for decades as the principal rule in the treatment of anal fistulas. On the other hand, new
operations such as TROPIS recommend a lay-open technique with excellent surgical outcomes. This
operation is the newest in literature and tries to find its position in the international surgical community
2023 Charalampopoulos et al. Cureus 15(3): e35888. DOI 10.7759/cureus.35888 9 of 12

and guidelines. More studies and literature data are needed to determine the final position of the newest
techniques, such as laser therapy, VAAFT, OTSC, and TROPIS. This review study emphasizes new surgical
techniques as they present optimal surgical results
in the literature without any significant position in guidelines and probably will be the preferred procedure
next year.
Additional Information
Disclosures
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the
following: Payment/services info: All authors have declared that no financial support was received from
any organization for the submitted work. Financial relationships: All authors have declared that they have
no financial relationships at present or within the previous three years with any organizations that might
have an interest in the submitted work. Other relationships: All authors have declared that there are no
other relationships or activities that could appear to have influenced the submitted work.
References
1. García-Olmo D, Van Assche G, Tagarro I, et al.: Prevalence of anal fistulas in Europe: systematic literature
reviews and population-based database analysis. Adv Ther. 2019, 36:3503-18. 10.1007/s12325-019-01117-y
2. Sugrue J, Nordenstam J, Abcarian H, Bartholomew A, Schwartz JL, Mellgren A, Tozer PJ: Pathogenesis and
persistence of cryptoglandular anal fistula: a systematic review. Tech Coloproctol. 2017, 21:425-32.
10.1007/s10151-017-1645-5
3. Machielsen AJ, Iqbal N, Kimman ML, et al.: Heterogeneity in outcome selection, definition and
measurement in studies assessing the treatment of cryptoglandular anal fistula: findings from a systematic
review. Tech Coloproctol. 2021, 25:761-830. 10.1007/s10151-021-02452-5
4. Parks AG, Gordon PH, Hardcastle JD: A classification of fistula-in-ano . Br J Surg. 1976, 63:1-12.
10.1002/bjs.1800630102
5. de Miguel Criado J, del Salto LG, Rivas PF, et al.: MR imaging evaluation of perianal fistulas: spectrum of
imaging features. Radiographics. 2012, 32:175-94. 10.1148/rg.321115040
6. Emile SH, Elfeki H, El-Said M, Khafagy W, Shalaby M: Modification of Parks classification of cryptoglandular
anal fistula. Dis Colon Rectum. 2021, 64:446-58. 10.1097/DCR.0000000000001797
7. Garg P: Comparing existing classifications of fistula-in-Ano in 440 operated patients: is it time for a new
classification? A retrospective cohort study. Int J Surg. 2017, 42:34-40. 10.1016/j.ijsu.2017.04.019
8. Garg P: Assessing validity of existing fistula-in-ano classifications in a cohort of 848 operated and MRI-
assessed anal fistula patients - Cohort study. Ann Med Surg (Lond). 2020, 59:122-6.
10.1016/j.amsu.2020.09.022
9. Garg P: Classification of anal fistula and abscess. Anal Abscess and Fistula BT. Coloproctology. Ratto C,
Parello A, Litta F, De Simone V, Campenni P (ed): Springer International Publishing, Cham; 2022. 69-91.
10.1007/978-3-030-76670-2_7
10. Gaertner WB, Burgess PL, Davids JS, et al.: The American Society of Colon and Rectal Surgeons clinical
practice guidelines for the management of anorectal abscess, fistula-in-Ano, and rectovaginal fistula. Dis
Colon Rectum. 2022, 65:964-85. 10.1097/DCR.0000000000002473
11. Sahni VA, Ahmad R, Burling D: Which method is best for imaging of perianal fistula? . Abdom Imaging.
2008, 33:26-30. 10.1007/s00261-007-9309-y
12. Ho E, Rickard MJ, Suen M, Keshava A, Kwik C, Ong YY, Yang J: Perianal sepsis: surgical perspective and
practical MRI reporting for radiologists. Abdom Radiol (NY). 2019, 44:1744-55. 10.1007/s00261-019-01920-9
13. Morris J, Spencer JA, Ambrose NS: MR imaging classification of perianal fistulas and its implications for
patient management. Radiographics. 2000, 20:623-35; discussion 635-7.
10.1148/radiographics.20.3.g00mc15623
14. Kołodziejczak M, Santoro GA, Obcowska A, Lorenc Z, Mańczak M, Sudoł-Szopińska I: Three-dimensional
endoanal ultrasound is accurate and reproducible in determining type and height of anal fistulas. Colorectal
Dis. 2017, 19:378-84. 10.1111/codi.13580
15. Schwartz DA, Pemberton JH, Sandborn WJ: Diagnosis and treatment of perianal fistulas in Crohn disease .
Ann Intern Med. 2001, 135:906-18. 10.7326/0003-4819-135-10-200111200-00011
16. Crepsi M, Colombo F, Foschi D: Surgical examination under anesthesia . Imaging of Perianal Inflammatory
Diseases. Tanolini M, Maconi G (ed): Springer Verlag, Milano; 2013. 67-74. 10.1007/978-88-470-2847-0_10
17. Schwartz DA, Wiersema MJ, Dudiak KM, et al.: A comparison of endoscopic ultrasound, magnetic resonance
imaging, and exam under anesthesia for evaluation of Crohn's perianal fistulas . Gastroenterology. 2001,
121:1064-72. 10.1053/gast.2001.28676
18. Schwandner O: [Quality indicators in the treatment of anal fistulas] . Chirurg. 2019, 90:270-8.
10.1007/s00104-019-0794-7
19. Ratto C, Grossi U, Litta F, et al.: Contemporary surgical practice in the management of anal fistula: results
from an international survey. Tech Coloproctol. 2019, 23:729-41. 10.1007/s10151-019-02051-5
20. de Groof EJ, Sahami S, Lucas C, Ponsioen CY, Bemelman WA, Buskens CJ: Treatment of perianal fistula in
Crohn's disease: a systematic review and meta-analysis comparing seton drainage and anti-tumour necrosis
factor treatment. Colorectal Dis. 2016, 18:667-75. 10.1111/codi.13311
21. Tozer P, Sala S, Cianci V, et al.: Fistulotomy in the tertiary setting can achieve high rates of fistula cure with
an acceptable risk of deterioration in continence. J Gastrointest Surg. 2013, 17:1960-5. 10.1007/s11605-013-
2198-1
22. Cavanaugh M, Hyman N, Osler T: Fecal incontinence severity index after fistulotomy: a predictor of quality
of life. Dis Colon Rectum. 2002, 45:349-53. 10.1007/s10350-004-6181-5
2023 Charalampopoulos et al. Cureus 15(3): e35888. DOI 10.7759/cureus.35888 10 of 12

23. Ommer A, Herold A, Berg E, et al.: German S3 guidelines: anal abscess and fistula (second revised version) .
Langenbecks Arch Surg. 2017, 402:191-201. 10.1007/s00423-017-1563-z
24. Amato A, Bottini C, De Nardi P, et al.: Evaluation and management of perianal abscess and anal fistula: a
consensus statement developed by the Italian Society of Colorectal Surgery (SICCR). Tech Coloproctol. 2015,
19:595-606. 10.1007/s10151-015-1365-7
25. Williams G, Williams A, Tozer P, Phillips R, Ahmad A, Jayne D, Maxwell-Armstrong C: The treatment of
anal fistula: second ACPGBI Position Statement - 2018. Colorectal Dis. 2018, 20 Suppl 3:5-31.
10.1111/codi.14054
26. Bakhtawar N, Usman M: Factors increasing the risk of recurrence in fistula-in-ano . Cureus. 2019, 11:e4200.
10.7759/cureus.4200
27. Mei Z, Wang Q, Zhang Y, et al.: Risk Factors for Recurrence after anal fistula surgery: a meta-analysis . Int J
Surg. 2019, 69:153-64. 10.1016/j.ijsu.2019.08.003
28. Burney R: Long term results of surgical treatment of anal fistula in a case series of 483 patients . Int J Surg
Open. 2021, 33:100350. 10.1016/j.ijso.2021.100350
29. Göttgens KW, Smeets RR, Stassen LP, Beets G, Breukink SO: Systematic review and meta-analysis of surgical
interventions for high cryptoglandular perianal fistula. Int J Colorectal Dis. 2015, 30:583-93.
10.1007/s00384-014-2091-8
30. Ritchie RD, Sackier JM, Hodde JP: Incontinence rates after cutting seton treatment for anal fistula .
Colorectal Dis. 2009, 11:564-71. 10.1111/j.1463-1318.2008.01713.x
31. Stamos MJ, Snyder M, Robb BW, et al.: Prospective multicenter study of a synthetic bioabsorbable anal
fistula plug to treat cryptoglandular transsphincteric anal fistulas. Dis Colon Rectum. 2015, 58:344-51.
10.1097/DCR.0000000000000288
32. Herold A, Ommer A, Fürst A, et al.: Results of the Gore Bio-A fistula plug implantation in the treatment of
anal fistula: a multicentre study. Tech Coloproctol. 2016, 20:585-90. 10.1007/s10151-016-1505-8
33. Buchanan GN, Bartram CI, Phillips RK, et al.: Efficacy of fibrin sealant in the management of complex anal
fistula: a prospective trial. Dis Colon Rectum. 2003, 46:1167-74. 10.1007/s10350-004-6708-9
34. Yellinek S, Krizzuk D, Moreno Djadou T, Lavy D, Wexner SD: Endorectal advancement flap for complex anal
fistula: does flap configuration matter?. Colorectal Dis. 2019, 21:581-7. 10.1111/codi.14564
35. Stellingwerf ME, van Praag EM, Tozer PJ, Bemelman WA, Buskens CJ: Systematic review and meta-analysis
of endorectal advancement flap and ligation of the intersphincteric fistula tract for cryptoglandular and
Crohn's high perianal fistulas . BJS Open. 2019, 3:231-41. 10.1002/bjs5.50129
36. Balciscueta Z, Uribe N, Balciscueta I, Andreu-Ballester JC, García-Granero E: Rectal advancement flap for
the treatment of complex cryptoglandular anal fistulas: a systematic review and meta-analysis. Int J
Colorectal Dis. 2017, 32:599-609. 10.1007/s00384-017-2779-7
37. Rojanasakul A: LIFT procedure: a simplified technique for fistula-in-ano . Tech Coloproctol. 2009, 13:237-
40. 10.1007/s10151-009-0522-2
38. Alasari S, Kim NK: Overview of anal fistula and systematic review of ligation of the intersphincteric fistula
tract (LIFT). Tech Coloproctol. 2014, 18:13-22. 10.1007/s10151-013-1050-7
39. Emile SH, Khan SM, Adejumo A, Koroye O: Ligation of intersphincteric fistula tract (LIFT) in treatment of
anal fistula: An updated systematic review, meta-analysis, and meta-regression of the predictors of failure.
Surgery. 2020, 167:484-92. 10.1016/j.surg.2019.09.012
40. Wood T, Truong A, Mujukian A, Zaghiyan K, Fleshner P: Increasing experience with the LIFT procedure in
Crohn's disease patients with complex anal fistula. Tech Coloproctol. 2022, 26:205-12. 10.1007/s10151-022-
02582-4
41. Garg P: Transanal opening of intersphincteric space (TROPIS) - a new procedure to treat high complex anal
fistula. Int J Surg. 2017, 40:130-4. 10.1016/j.ijsu.2017.02.095
42. Garg P: Understanding and treating supralevator fistula-in-ano: MRI analysis of 51 cases and a review of
literature. Dis Colon Rectum. 2018, 61:612-21. 10.1097/DCR.0000000000001051
43. Garg P: Comparison between recent sphincter-sparing procedures for complex anal fistulas-ligation of
intersphincteric tract vs transanal opening of intersphincteric space. World J Gastrointest Surg. 2022,
14:374-82. 10.4240/wjgs.v14.i5.374
44. Huang H, Ji L, Gu Y, Li Y, Xu S: Efficacy and safety of sphincter-preserving surgery in the treatment of
complex anal fistula: a network meta-analysis. Front Surg. 2022, 9:825166. 10.3389/fsurg.2022.825166
45. de la Portilla F, Alba F, García-Olmo D, Herrerías JM, González FX, Galindo A: Expanded allogeneic adipose-
derived stem cells (eASCs) for the treatment of complex perianal fistula in Crohn's disease: results from a
multicenter phase I/IIa clinical trial . Int J Colorectal Dis. 2013, 28:313-23. 10.1007/s00384-012-1581-9
46. Panés J, García-Olmo D, Van Assche G, et al.: Expanded allogeneic adipose-derived mesenchymal stem cells
(Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled
trial. Lancet. 2016, 388:1281-1290. 10.1016/S0140-6736(16)31203-X
47. Prosst R: Treatment by over-the-scope-clip . Anal Fistula and Abscess. Ratto C, Parello A, Litta F, De Simone
V, Campenni P (ed): Springer Nature, Cham; 2022. 433-449. 10.1007/978-3-030-76670-2_29
48. Dango S, Antonakis F, Schrader D, Radzikhovskiy A, Ghadimi MB, Hesterberg R: Long-term efficacy and
safety of a nitinol closure clip system for anal fistula treatment. Minim Invasive Ther Allied Technol. 2017,
26:227-31. 10.1080/13645706.2017.1282521
49. Mennigen R, Laukötter M, Senninger N, Rijcken E: The OTSC(®) proctology clip system for the closure of
refractory anal fistulas. Tech Coloproctol. 2015, 19:241-6. 10.1007/s10151-015-1284-7
50. Prosst RL, Joos AK: Short-term outcomes of a novel endoscopic clipping device for closure of the internal
opening in 100 anorectal fistulas. Tech Coloproctol. 2016, 20:753-8. 10.1007/s10151-016-1537-0
51. Lauretta A, Falco N, Stocco E, Bellomo R, Infantino A: Anal fistula laser closure: the length of fistula is the
Achilles' heel. Tech Coloproctol. 2018, 22:933-9. 10.1007/s10151-018-1885-z
52. Giamundo P, De Angelis M: Treatment of anal fistula with FiLaC(®): results of a 10-year experience with
175 patients. Tech Coloproctol. 2021, 25:941-8. 10.1007/s10151-021-02461-4
53. Alam A, Lin F, Fathallah N, et al.: FiLaC(®) and Crohn's disease perianal fistulas: a pilot study of 20
consecutive patients. Tech Coloproctol. 2020, 24:75-8. 10.1007/s10151-019-02134-3
2023 Charalampopoulos et al. Cureus 15(3): e35888. DOI 10.7759/cureus.35888 11 of 12

54. Elfeki H, Shalaby M, Emile SH, Sakr A, Mikael M, Lundby L: A systematic review and meta-analysis of the
safety and efficacy of fistula laser closure. Tech Coloproctol. 2020, 24:265-74. 10.1007/s10151-020-02165-1
55. Frountzas M, Stergios K, Nikolaou C, et al.: Could FiLaC™ be effective in the treatment of anal fistulas? A
systematic review of observational studies and proportional meta-analysis. Colorectal Dis. 2020, 22:1874-
84. 10.1111/codi.15148
56. Adegbola SO, Sahnan K, Tozer P, Warusavitarne J: Emerging data on fistula laser closure (Filac) for the
treatment of perianal fistulas; patient selection and outcomes. Clin Exp Gastroenterol. 2021, 14:467-75.
10.2147/CEG.S269464
57. Arroyo A, Moya P, Rodríguez-Prieto MA, et al.: Photodynamic therapy for the treatment of complex anal
fistula. Tech Coloproctol. 2017, 21:149-53. 10.1007/s10151-016-1571-y
58. Meinero P, Mori L: Video-assisted anal fistula treatment (VAAFT): a novel sphincter-saving procedure for
treating complex anal fistulas. Tech Coloproctol. 2011, 15:417-22. 10.1007/s10151-011-0769-2
59. Meinero P, Mori L: Video-assisted anal fistula treatment (VAAFT) . Anal Fistula Principles and Management.
Abcarian H (ed): Springer, New York; 2014. 121-128. 10.1007/978-1-4614-9014-2_17
60. Pini Prato A, Zanaboni C, Mosconi M, et al.: Preliminary results of video-assisted anal fistula treatment
(VAAFT) in children. Tech Coloproctol. 2016, 20:279-85. 10.1007/s10151-016-1447-1
61. Schwandner O: Video-assisted anal fistula treatment (VAAFT) combined with advancement flap repair in
Crohn's disease. Tech Coloproctol. 2013, 17:221-5. 10.1007/s10151-012-0921-7
62. Adegbola SO, Sahnan K, Tozer PJ, et al.: Symptom amelioration in Crohn’s perianal fistulas using video-
assisted anal fistula treatment (VAAFT). J Crohns Colitis. 2018, 12:1067-72. 10.1093/ecco-jcc/jjy071
63. Milone M, Musella M, Di Spiezio Sardo A, et al.: Video-assisted ablation of pilonidal sinus: a new minimally
invasive treatment--a pilot study. Surgery. 2014, 155:562-6. 10.1016/j.surg.2013.08.021
64. Seow-En I, Seow-Choen F, Koh PK: An experience with video-assisted anal fistula treatment (VAAFT) with
new insights into the treatment of anal fistulae. Tech Coloproctol. 2016, 20:389-93. 10.1007/s10151-016-
1450-6
65. Regusci L, Fasolini F, Meinero P, Caccia G, Ruggeri G, Serati M, Braga A: Video-assisted anal fistula
treatment (VAAFT) for complex anorectal fistula: efficacy and risk factors for failure at 3-year follow-up.
Tech Coloproctol. 2020, 24:741-6. 10.1007/s10151-020-02213-w
66. Garg P, Singh P: Video-assisted anal fistula treatment (VAAFT) for complex anorectal fistula: efficacy and
risk factors for failure at 3-year follow-up. Int J Surg. 2017, 46:85-91. 10.1016/j.ijsu.2017.08.582
67. Emile SH, Elfeki H, Shalaby M, Sakr A: A Systematic review and meta-analysis of the efficacy and safety of
video-assisted anal fistula treatment (VAAFT). Surg Endosc. 2018, 32:2084-93. 10.1007/s00464-017-5905-2
68. Tian Z, Li YL, Nan SJ, Xiu WC, Wang YQ: Video-assisted anal fistula treatment for complex anorectal
fistulas in adults: a systematic review and meta-analysis. Tech Coloproctol. 2022, 26:783-95.
10.1007/s10151-022-02614-z
2023 Charalampopoulos et al. Cureus 15(3): e35888. DOI 10.7759/cureus.35888 12 of 12