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Position Statement doi:10.1111/codi.

14054

The treatment of anal fistula: second ACPGBI Position


Statement – 2018
G. Williams*, A. Williams†, P. Tozer‡, R. Phillips‡, A. Ahmad§, D. Jayne¶ and
C. Maxwell-Armstrong**
*Royal Wolverhampton NHS Trust, Wolverhampton, UK, †Guy’s and St Thomas’ NHS Foundation Trust, London, UK, ‡St Mark’s Hospital, Harrow,
London, UK, §Leeds Teaching Hospitals NHS Trust, Leeds, UK, ¶University of Leeds, Leeds, UK, and **National Institute for Health Research
Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK

Received 3 December 2017; accepted 16 February 2018

Abstract

It is over 10 years since the first ACPGBI Position fistula that have been developed since the original publi-
Statement on the management of anal fistula was pub- cation.
lished in 2007. This second edition is the result of scru-
Keywords Anal sepsis, anal fistula, aetiology, investiga-
tiny of the literature published during this time; it
tion, surgical treatment
updates the original Position Statement and reviews the
published evidence surrounding treatments for anal

concentrated on publications after 2005, as the literature


Introduction
prior to that date was reviewed in the original Position
Anal fistula remains a perplexing condition for the col- Statement. Organized searches of the Cochrane Database,
orectal surgeon. The first ACPGBI Position Statement on PubMed, MEDLINE and Embase were performed using
this condition was published in 2007 [1] and was devel- keywords relevant to each section of this Position State-
oped after reviewing the literature on this subject span- ment. Searches were limited to articles published in Eng-
ning many decades. Strength of evidence and guidelines lish, with a few exceptions. Additional publications were
on management were drawn up, but in many instances retrieved from references cited in articles identified from
the level of evidence used to produce recommendations the primary search of the literature. Relevant papers were
was deemed to be low. In the years following that publi- retrieved and studied by members of the writing commit-
cation, the literature on anal fistula has expanded, both tee and incorporated into this review. All evidence was
with regard to our understanding of its aetiology (still far classified according to an accepted hierarchy of evidence
from confirmed) and its management, a flurry of new sur- and recommendations graded A to C on the basis of the
gical techniques have become available and there is level of associated evidence and/or noted as Good Prac-
greater understanding of treatments that were emerging tice and/or part of NICE/SIGN recommendation or
at the time of publication of the first position statement. Rapid Technology Appraisal (Table 1) [2].
This second Position Statement addresses the infor- This Position Statement is presented in sections deal-
mation that has become available since the first version ing with aspects of pathology, diagnosis and treatment.
and updates guidelines on the management of anal fis- The evidence is briefly summarized, where relevant,
tula. This Position Statement should be read in con- under the heading ‘Findings’ and this is followed where
junction with the original paper for a complete picture relevant by ‘Recommendations’.
of the literature on which both statements are based.

Aetiology
Methodology
The crypto-glandular theory espoused by Eisenhammer
This Position Statement is based on evidence obtained [3] and Parks [4] remains the most plausible explana-
from an extensive review of the literature. The authors tion for the initiating event in most cases of idiopathic
anal sepsis, and is widely accepted. This theory proposes
Correspondence to: Mr Graham Williams MCh FRCS, Royal Wolverhampton that sepsis originates as an infection in an obstructed
NHS Trust, New Cross Hospital, Wolverhampton, WV10 0QP, UK.
E-mail: graham.williams4@nhs.net anal gland, usually lying in the intersphincteric space.

Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31 5
The treatment of anal fistula (2018 update) G. Williams et al.

Table 1 Levels of evidence and grades of recommendation.

Level of evidence Grade of evidence

I Evidence obtained from a single randomized controlled A Evidence of Type I or consistent findings from multiple
trial or from a systematic review or meta-analysis of studies of Type IIa, IIb or III
randomized controlled trials
IIa Evidence obtained from at least one well-designed B Evidence of Type IIa, IIb or III and generally
controlled study without randomization consistent findings
IIb Evidence obtained from at least one other well-designed C Evidence of Type IIa, IIb or III but inconsistent
quasi-experimental study findings
III Evidence obtained from well-designed nonexperimental D Little or no systematic evidence
descriptive studies, such as comparative studies,
correlation studies and case studies
IV Evidence obtained from expert committee reports or GP Recommended good practice based on the clinical
opinions and/or clinical experiences of respected experience of the expert group and other professionals*
authorities, case reports

Adapted from Eccles and Mason [2].


*Previous experience and the literature in this area suggests that given the relative lack of evidence for many health care procedures,
expert opinion and professional consensus are likely to be an important part of this process.

Mitalas et al. [5] performed histological studies on the infection from an anal gland, the rate of fistula formation
fistula track in a series of nine patients with chronic fis- following presentation with an anal abscess is low. Two
tula undergoing exploration of the intersphincteric recent series have reported similar findings, with only a
space. None of the tracks contained evidence of anal third of patients presenting with an abscess going on to
gland tissue with mucin-producing cells. However, this form an anal fistula. Furthermore, neither study identified
does not disprove the theory, as it is quite plausible that any associated features that might have increased the risk
glandular epithelium was obliterated during the original of fistula formation, which was lower in diabetic patients
septic process. Whereas there has not been any recent [9,10]. A lower rate of 15.5% for fistula formation follow-
publication confirming this theory, equally there has ing an acute anal abscess has been calculated from hospital
not been a publication proposing a more plausible activity data [8], although this only included patients
explanation. Naldini et al. [6] performed endoanal undergoing surgery for an anal fistula and it is likely that
ultrasound scans on 175 patients with a chronic anal fis- the overall rate is higher as patients not seeking further
sure. They demonstrated an intersphincteric fistula in medical attention would not have been captured by this
91 (53%) patients and a transsphincteric fistula in 21 data set. Why some patients go on to establish a fistula
(12%) patients. The relevance of this finding is uncer- remains uncertain; possible reasons include persistent sep-
tain. Whilst it suggests a possible alternative aetiology sis, epithelialization of the track and hormone-mediated
for an anal fistula, its relevance is more likely to be an host response. Traditionally it has been assumed that per-
explanation for chronicity of an anal fissure. Why some sistence of sepsis drives fistula formation. However, earlier
people are more prone to anal sepsis remains unex- studies have shown a paucity of organisms in a fistula track
plained. Smoking within the last year seems to double [11,12] and more recent studies using molecular tech-
the risk of anal sepsis, but this effect disappears 5 years niques have shown a lack of bowel-related organisms in
after cessation of smoking [7]. What is less clear is the the fistula track. Tozer et al. [13] used in situ hybridiza-
explanation for persistence of the sepsis with formation tion to study the microflora of 18 idiopathic (cryptoglan-
of a fistula. dular) fistulas. Surprisingly, bacteria were not found in
Anal abscesses are a common surgical emergency, usu- close association with the luminal surface of any fistula
ally dealt with simply, by adequate incision and drainage. track. Similarly, in a series of 10 patients with transsphinc-
A recent study examining national hospital activity data teric fistulas, van Onkelen et al. [14] failed to identify bac-
puts the incidence of anal abscess at 20.2 per 100 000 teria in the fistula track using 16S rRNA sequencing in
population, although the actual incidence is likely to be nine patients. However, immunohistochemistry revealed
higher as these data do not include patients treated in the the presence of bacterial-derived proinflammatory pepti-
community [8]. Whilst the cryptoglandular theory doglycans in all bar one fistula, with evidence of host
assumes that an anal fistula has arisen from the spread of response in 6 out of 10. This raises the possibility that

6 Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31
G. Williams et al. The treatment of anal fistula (2018 update)

fistula formation and persistence represent a host response emerging over the last 10 years. Imaging methods include
to bacterial cell wall-derived peptidoglycans. It has been contrast fistulography, anal ultrasound, magnetic reso-
suggested (but with no evidence to confirm this) that cell nance imaging (MRI) and computed tomography (CT).
wall lipopolysaccharides activate proinflammatory cyto- Anal ultrasound may be carried out with or without three-
kine production, such as tumour necrosis factor a dimensional reconstruction and with or without ultra-
(TNFa), which could be enhanced by testosterone and sound contrast. MRI has been used with a pelvic phased
inhibited by oestrogen, providing an explanation for the array coil, an endoanal receiver coil and with or without
lower incidence of anal fistulas in women [15]. intravenous contrast, and most recently with assessment of
Epithelialization of the track has been hypothesized magnetization transfer. Each of these will be reviewed and
as a cause for persistence of an anal fistula, but it compared and recent evidence presented.
remains uncertain whether this is of primary aetiological
importance or a secondary phenomenon. van Koperen Fistulography
et al. [16] examined 18 fistula tracks and demonstrated
Finding
epithelialization in 15 patients, mostly around the inter-
nal opening. However, this series only included patients Fistulography provides only very limited information
with a low fistula undergoing fistulotomy. Mitalas et al. on fistula anatomy. (Level III)
[5] performed a similar study but on 44 patients with a
higher fistula involving the external sphincter. Epithe-
Recommendation
lialization of the external part of the track was observed
in 11 of 44 (25%) and of the intersphincteric part of Fistulography has been superseded by other imaging
the track in 2 of 11 (22%). Thus, epithelialization is modalities in the assessment of cryptogenic anorectal
uncommon within more complex fistulas. sepsis. (Grade B)
Another conundrum is the mechanism by which sepsis
Fistulography involves the injection of water-soluble
spreads around the anal canal to form fistulas of differing
contrast media directly into an external opening of a fis-
complexity. Whilst it is easy to envisage infection spread-
tula. This technique is of historical interest and has been
ing along paths of least resistance, such as the intersphinc-
superseded by other imaging techniques. No new infor-
teric space or circumferentially in the ischio-rectal fossas,
mation to support the use of fistulography has
it is more difficult to explain the spread of sepsis through
emerged.
the external sphincter to form a transsphincteric fistula
and to provide a logical explanation as to why some fistu-
las involve little sphincter muscle and others involve most
Computed tomography
of the external sphincter. A plausible explanation is that
infection follows fibres of the longitudinal muscle pene- Findings
trating the external sphincter, but this is by no means pro-
CT is inferior to MRI in the assessment of anal fistula,
ven. Surgical dogma assumes that the ‘deep postanal
but newer techniques can provide useful information
space’ is critical to the spread of sepsis around the anus,
in selected patients. (Level III)
and thus the key to eradicating a fistula was thought to be
adequate drainage of this space, as well as control of the
primary track. However, what constitutes the ‘deep post- Recommendation
anal space’ is disputed, with some going as far as to ques-
Thin-slice spiral CT may be helpful when MRI is
tion whether it exists as a distinct entity [17,18]. Recent
either not available or is contraindicated. (Grade C)
radiological and anatomical studies suggest there are sev-
eral potential, or actual, spaces around the anal sphincters CT scanning is inferior to MRI in its ability to differ-
that are likely to be important in the spread of infection. entiate between fibrosis and active disease and so has
To confuse the issue further, some of these ‘spaces’ can- limited value, except when assessing pelvic causes for
not be identified in the normal anal canal and only extrasphincteric tracks. Multiplanar imaging using thin-
become apparent once sepsis develops and localizes to slice spiral CT and intravenous contrast may be helpful
that area [18–22]. in cases where MRI is either not available or is poorly
tolerated, but the full extent of tracks may be underre-
ported due to failure to fill with contrast or plugging
Imaging
due to debris [23]. Whilst CT probably has similar sen-
Many imaging modalities are used in the investigation of sitivity to MRI for the detection of perianal abscesses, its
anal fistulas, with some subtle refinements in techniques role in the assessment of complex anal sepsis is limited.

Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31 7
The treatment of anal fistula (2018 update) G. Williams et al.

In recent years there has been significant interest in


Anal endosonography
assessing Crohn’s anal fistulation with ultrasound.
Findings Detection of the persistence of an internal opening on
anal ultrasound after anti-TNFa treatment for Crohn’s
Endoanal ultrasound has an established role in the
perianal sepsis may predict recurrence [35] and biologi-
assessment of anal fistulas. (Level IIa)
cal treatment guided by the findings of anal ultrasound
may be beneficial [36]; treatment directed by ultra-
Recommendations sound findings improves the success of fistula surgery
[37] and reduces recurrences in a similar way to MRI
Anal endosonography (ultrasound) may be the first
[38]. An endosonographic classification of perianal
line investigation for patients with an anal fistula that
Crohn’s disease has been developed, which in a large
is suspected to be complex. Patients with recurrent fis-
series led to a change in management in just under half
tula may benefit from anal endosonography, but MRI
of the 150 cases reviewed [39]. The endosonographic
will also be required. (Grade B)
differences in appearances between Crohn’s fistulas and
cryptogenic sepsis have been detailed, with wider
Anal endosonography and perineal sonography are
branched tracks and the presence of debris typical in
useful adjuncts to the assessment of perianal Crohn’s
Crohn’s fistulas [40]. The mean greyscale of a track on
disease. (Grade C)
endosonography may also be positively correlated with
Anal endosonography, using higher-frequency trans- the perianal Crohn’s disease activity index and assess-
ducers and volume image acquisition, is an established ment of fistula drainage in Crohn’s disease [41].
investigation for anal sepsis. When this technique is used The alternative approach of trans-perineal ultrasound
by enthusiasts to assess anal sepsis similar accuracy can has been used to assess anal fistulas with an accuracy of
be achieved to assessment by endocoil MRI, with an up to 86% for the detection of internal fistula open-
accuracy of over 80% [24] and near 100% concordance ings, both with Crohn’s disease[42] and idiopathic fis-
with surgery for simple cases and 68% for high fistulas tulation [43]. Furthermore, transvaginal scanning may
[25]. The height and type of fistula seen on ultrasound prove to be a useful adjunct to anal scanning for
compares well with the findings at examination under recto/ano-vaginal fistulation, with 100% positive pre-
anaesthesia (EUA; 91% accuracy for type and 92% accu- dictive value for simple fistulas and 90% for more com-
racy for classification of ‘high’ or ‘low’) [26,27]. plex cases [44].
Hydrogen peroxide infused into the external opening
of a fistula track acts as an ultrasonic contrast medium to
Magnetic resonance imaging
exaggerate the track and abscesses due to the formation
of the hyper-reflective gas bubbles. This increases the Findings
accuracy and detail of the fistula tracks imaging [28],
MRI is an accurate method of imaging anal fistula.
and may be very helpful for the delineation of supra-leva-
(Level 1)
tor sepsis, which is difficult to locate on clinical examina-
tion alone [26]. However, peroxide may have limited
additional benefit over and above that of multiplanar Recommendation
ultrasound [29] or noncontrasted trans-perineal scan-
MRI should be considered in any primary fistula
ning [30]. Other ultrasonic contrast agents (e.g. Levo-
deemed after clinical or endosonographic assessment
vist) have been used [31] but not widely adopted
to be complex. It should also be considered in
because of the low cost and easy availability of peroxide
patients with a recurrent anal fistula. (Grade A)
and no additional benefit being seen with the more
expensive agent. Magnetic resonance imaging is accepted as the
Accurate assessment of the site of the internal open- ‘gold-standard’ for the assessment of anal sepsis [1].
ing is dependent upon the criteria used for ultrasonic Indeed, where there is sepsis detected on MRI but not
definition [32]: budding of sepsis in the intersphincteric at EUA, MRI predicts recurrence of sepsis. Thus MRI
space towards the lumen, penetration of the internal improves clinical assessment by detecting previously
sphincter and, finally, whether a clear track is seen all missed secondary extensions and correctly assessing the
the way through the internal sphincter and into the level of fistula with respect to the sphincter complex
lumen [33]. Peroxide enhancement may increase the [45]. This may be further enhanced with novel three-
detection of internal openings and correct fistula classifi- dimensional modelling systems to show the full extent
cation to above 80% [24,33,34]. of the sepsis in relation to the anal sphincter complex

8 Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31
G. Williams et al. The treatment of anal fistula (2018 update)

[46]. The use of endocoils to improve resolution has diffusion-weighted scans may be able to assess fistula
been supplanted by the use of pelvic phased array coils, activity to produce an ‘apparent diffusion coefficient
particularly where more widely extensive sepsis or map’ [64].
supralevator sepsis is suspected [47,48]. It has been The slice orientation is crucial irrespective of the
suggested that observer agreement for the reporting of sequences used for obtaining images. An initial T2-
complex sepsis using MRI is only good in expert cen- weighted sagittal scan should be obtained to orientate
tres, making standardization of the slice planes vital the pelvis such that further axial and coronal scans can
[49], although expertise can be rapidly attained [50] be performed perpendicular and parallel to the long axis
with directed education. of the anal canal. The most useful planes are axial and
Independently of the use of pelvic phased array coronal [53,65–67]; scans orientated in the sagittal
coils, variation exists between units in the sequences plane are of limited value unless ano-vaginal fistulation
used to obtain images and whether or not contrast is suspected [68] or in distinguishing from a retro-rectal
agents are used. Rectal gadolinium-DTPA (diethylene- cyst, with its characteristic appearance. There is a learn-
triamine penta-acetic acid) has been used to help to ing curve for the interpretation of MRI, with an
identify tracks, with limited benefit [51,52], and saline increase in correct interpretation of up to 50% with
has been infused into tracks [53]. The insertion of a experience [65]. Whilst initial agreement in scan inter-
rectal balloon [54] during scanning may improve the pretation is acceptable (Ka = 0.7, good agreement)
detection of internal openings, although none of these [59], this can improve to Ka = 0.92 with a short period
techniques has been widely adopted. Intravenous of directed training [50].
gadolinium-DTPA is widely used to provide dynamic The use of MRI may predict recurrence of fistula
contrast enhanced MRI (DCEMRI) [55,56] with disease. Where EUA fails to find and treat sepsis sug-
equivalent benefit to images obtained by short tau gested on imaging, the sepsis often recurs, with the
inversion recovery (STIR) sequences [57]. The use of recurrence located at the site predicted by the preoper-
contrast aids in the differentiation between nonenhanc- ative imaging [69,70]. In addition, MRI classification
ing healed tracks and active disease that enhances. of fistulas into simple and complex is able to predict
Spencer et al. [56] directly compared sequences to the chance of recurrence much more accurately than
ascertain those that were most helpful. T1-weighted EUA alone (positive predictive value 73% vs 57%) [71].
sequence scans show anatomical detail together with When a surgeon always acts on the result of preopera-
sinuses and fistula tracks as hypointense structures, tive MRI, then the recurrence rate for complex fistulas
although T2 scans provide better signal differentiation is 16%, compared with 57% where the results of imag-
between active disease and fibrosis from inactive tracks. ing are disregarded [72]. It has been suggested that
STIR sequences are widely used and considered by preoperative MRI assessment has the potential to alter
many to be superior to T1- or T2-weighted scans for surgical practice in up to 10% of cases if used prospec-
the detection and delineation of sepsis [51,58,59]. tively for primary fistulas [73] and 21% if used in a
These have the advantage of suppressing the relatively mixed population of primary and secondary fistulas and
high signal from fat in the ischio-anal fossa, and so patients with Crohn’s disease [74].
highlighting sepsis [51]. It has been suggested that Several groups have devised grading systems based
STIR sequence scanning may not be able to detect on MRI. The St James’ system relates to the fistula
small abscesses that are seen on DCEMRI with T2- anatomy [75] and shows good concordance with surgi-
weighted axial images [55,56], but may be better for cal findings [76]. Van Assche et al. [77] have devel-
the detection of internal openings, especially when oped a MRI scoring system which includes assessment
combined with endoanal receiver coils [59]. An alter- of the type and number of tracks, the presence and
native to STIR sequence scanning is using T2-weighted type of extensions, collections and rectal wall thicken-
scans with spectral fat saturation inversion recovery ing and the signal intensity on T2-weighted scans. This
(SPIR); when these two techniques were compared, latter scoring system has been criticized for being
however, no added advantage was found with SPIR insensitive to changes in clinical state because the vari-
and sphincter detail was better with STIR [60]. ous factors which make up the score do not always
One drawback of using intravenous gadolinium is the change concordantly with each other. Clinical and radi-
rare complication of nephrogenic systemic fibrosis: the ological evaluation in patients with Crohn’s anal fistula
use of diffusion-weighted MR avoids this, although at treated with biological agents has shown that the latter
the cost of reduced tissue detail [61,62]. Further lags behind the former by 12 months [78]. Neverthe-
developments using magnetization transfer scanning may less clinical improvement is mirrored by improvement
offer an alternative to contrast scans [63]. However, in MRI appearances up to 1 year [79,80] and MRI

Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31 9
The treatment of anal fistula (2018 update) G. Williams et al.

may be valuable in predicting those patients who will


relapse following treatment with anti-TNF treatment
Treatment
[81]; studies evaluating the importance of changes in Surgery remains the mainstay of treatment of a non-
the volume of the fistula track and T2 signal intensity Crohn’s anal fistula, the aim being to cure the fistula
in predicting relapse are under way. while at the same time preserving anal sphincter func-
MRI is not always well tolerated, it is not universally tion. Various surgical approaches remain in use, indicat-
available and, when compared with anal endosonogra- ing that there is no ideal procedure applicable to every
phy, it is time-consuming. In general use, MRI is prob- patient. Since publication of the first edition of this
ably superior to anal ultrasound, with concordance with Position Statement [1] a number of new, minimally
surgery for ultrasound of 80% and MRI 90% [65,67– invasive approaches to surgical treatment have emerged.
69,82,83]. Ultrasound may be better at locating inter- Informed consent involves discussing surgical options
nal openings than non-endocoil MRI [82], but it does and their likely outcome with a patient, as well as the
have the drawback of not being possible in the presence consequences of any complications. This should include
of canal stenosis [84], and there are difficulties in differ- discussion about the risk of recurrence/persistence of
entiating old tracks from new sepsis, and misinterpreta- the fistula as well as alteration in anal control. A fistula
tion of intersphincteric sepsis as transsphincteric because can vary in complexity from being simple, involving
of acoustic shadowing [85]. The role of anal ultrasound only a small proportion of the anal sphincter, to com-
in assessing anorectal fistulation is uncertain; some plex, with multiple tracks involving more of the anal
report equal value with MRI (endocoil) [86] whilst sphincter. The surgeon should be able to identify the
others suggest limited value other than to demonstrate degree of complexity of the fistula and plan surgery
combined sphincteric defects [87]. accordingly. Complex fistulas should be treated by an
In summary, when comparing the different methods experienced surgeon, particularly when they are associ-
of imaging anorectal sepsis it is important to concen- ated with Crohn’s disease. (Level of evidence: Level IV,
trate on the questions that need to be addressed, not Grade GP).
forgetting that not all anal fistulas need investigation
as the majority are primary, simple and low and can
be fully assessed clinically and treated with surgery. Fistulotomy
Anal ultrasound has been shown to be able to differ- Findings
entiate between complex and simple sepsis [88–91].
Clearly not all patients need MRI, but there is strong Fistulotomy has an extremely high (95%+) cure rate,
evidence for the value of MRI assessment to direct as long as all tracks are dealt with. Sphincter division,
surgery for recurrent fistulas. Surgery directed by pre- even for low and intersphincteric fistulas, carries
operative MRI has a recurrence rate of 16% compared approximately a one in three chance of inadvertent
with surgery where MRI is not acted upon (recurrence loss of flatus and slight passive soiling, largely deter-
rate 57%) [72]. Primary cases that are suspected to be mined by internal sphincter division. Whilst division of
complex should have anal ultrasound scanning where the anorectal ring will lead to frank faecal inconti-
local expertise exists, and if features of complex fistula- nence, in expert hands laying open larger amounts of
tion or secondary extensions are present then MRI the external sphincter (preserving at least 2 cm of
should be obtained. All recurrent fistulas, except those cephalad sphincter) has outcomes similar to those after
with clearly simple recurrence on anal ultrasound, laying open of a low anal fistula. (Level III)
should have MRI. Sequences used should include T1
images to give details of sphincter anatomy and scans
with either fat suppression (STIR, SPIR) or dynamic Recommendations
contrast enhanced scans (DCEMRI). The scans should As a general rule, fistulotomy results in a reliable cure
be orientated along and orthogonal to the long axis of with good patient satisfaction, where 2 cm of proxi-
the anal canal (and not the long axis of the body), mal muscle remains intact and in the presence of a
facilitated by a T2 scout sagittal scan in the mid coro- ‘normal’ bowel habit, without urgency and in the
nal position. Axial and coronal scans are of most bene- absence of irritable bowel symptoms. (Grade C)
fit although sagittal images are of use in cases of ano/
rectovaginal fistulation. Recent scoring and grading Fistulotomy not only involves completely laying open
systems may prove useful in following response to bio- the fistula from one opening to the other and division
logical treatment in Crohn’s fistulas, and MRI images of all the anal sphincter below it, but also identification
should be used to guide surgery at the time of EUA. of all secondary tracks and their adequate drainage. It

10 Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31
G. Williams et al. The treatment of anal fistula (2018 update)

results in healing in more than 95% of patients [92,93], anterior fistula in a woman [99]. Thus careful patient
but concerns regarding impairment of ‘continence’ inhi- selection is crucial.
bit surgeons and patients from selecting this option. Determining the height of a fistula can also present a
The word ‘incontinence’ encompasses a wide spectrum, challenge. Some tracks travel obliquely cephalad, mean-
from the odd stain in the underwear, through inadver- ing that the internal opening gives a falsely low impres-
tent passage of flatus, to frank and devastating loss of sion of the height of the track through the external
stool with the prospect of a colostomy. Part of the con- sphincter [100]. It takes experience to be able to feel
sent process should include a detailed description of the the internal opening of a fistula, but the information is
various scenarios, rather than use the blanket-term ‘in- vital as only with it can an estimate be made of how
continence’. Certainly, incontinence has a negative many centimetres of muscle will be preserved after lay-
impact on quality of life [94] but so too does fistula ing open: the presence of a seton may help. The inter-
recurrence [95] and an endless cycle of failure and nal opening can be identified directly at operation, but
recurrence is to be avoided as assiduously as faecal if caudal/spinal anaesthesia has been used the proximal
incontinence. Early on in a patient’s surgical course sphincter loses its tone and a estimation of length may
even slight departure from a prior norm can be unac- be difficult. Light general anaesthesia, which can further
ceptable; later on, after failed procedures, the trade for be lightened, thereby inducing muscle contraction,
cure of the fistula is often welcomed. serves to circumvent this problem.
Assessing the likely degree of impairment of conti-
nence associated with fistulotomy before it takes place is
Fistulotomy in acute anorectal sepsis
one of the great difficulties in proctology, and numer-
ous studies have been directed at this question. Whereas Findings
division of the entire sphincter complex will result in
Immediate fistulotomy, although associated with a
total incontinence, preservation of the anorectal ring
lower recurrence rate than simple incision and drai-
alone will prevent major incontinence in most patients
nage, carries a risk of misjudgement of the depth of
[96]. It has been argued that progressively greater
the fistula. (Level I)
sphincter division leads to progressively greater impair-
ment of continence. However, incremental functional
loss has never been demonstrated and, as with liver Recommendations
resection, it is the volume of muscle left behind that is
Immediate fistulotomy should be undertaken only by
important and what determines continence.
experienced surgeons in patients in whom the internal
When division of the internal sphincter alone is
opening is obvious without probing, and the fistula is
compared with division of both internal and external
‘simple’. (Grade A)
sphincter, the same degree of impairment of conti-
nence is seen [97]. Manometric data support this,
A more conservative practice of simple abscess drai-
demonstrating that maximum resting pressure
nage in the majority of circumstances is safest. (Grade
decreases similarly whether the internal sphincter alone
GP)
or both sphincters are divided [97]. In the same
study, external sphincter division did lead to a reduc- Two meta-analyses have considered the question of
tion in maximum squeeze pressure, but as long as a immediate fistula treatment at acute anorectal abscess
minimum length of external sphincter is maintained a drainage. Quah et al. [101] examined five randomized
consistent level of impairment can be predicted, controlled trials (RCTs) and a subsequent Cochrane
regardless of the degree of internal and/or external review added a sixth non-English language trial [102].
sphincter division performed. There is a one in three Both identified lower recurrence rates of anorectal sep-
risk of flatus incontinence and marking of the under- sis (abscess or fistula) with immediate fistula treatment.
wear [92,93] that is governed by the internal sphinc- This is perhaps not too surprising. In the five studies
ter. The literature on lateral anal sphincterotomy for analysed by Quah et al. [101], patients treated with
fissure supports this assertion [98]. There are specific abscess drainage alone presented with subsequent
groups of patients in whom the minimum amount of abscess or fistula in between 14% and 40% of cases,
remaining muscle required is greater, as a consequence whereas immediate fistula treatment reduced recurrence
of looser/more frequent stool now, or the risk of it to between 0% and 10%. Impairment of continence
in the future, such as in irritable bowel syndrome or varied significantly in the immediate treatment arm
Crohn’s disease, or in whom the length of muscle across the studies, from as high as 40% in some to
present will not permit further division, such as an zero in others. Two of the five studies found a

Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31 11
The treatment of anal fistula (2018 update) G. Williams et al.

significant difference in impairment of continence fistulas have been considered in more detail in another
between the two study arms, but at meta-analysis no publication [105].
such difference was seen. Both therefore advocate
immediate fistula treatment. However, a more cautious
Marsupialization
approach may be preferable, particularly in less experi-
enced hands. Findings
The literature, including observational studies as well
Marsupialization after fistulotomy is associated with a
as these RCTs, consistently describes a lower ‘recurrence’
significantly shorter healing time (Level I) and a
rate in patients in whom immediate fistulotomy is under-
shorter duration of wound discharge. (Level I)
taken. But some 40% of patients with an abscess where
culture revealed gut-related organisms never go on to
develop a fistula [103], which suggests potential Recommendations
overtreatment in a significant minority. Ho and Tang
The wound edges of the laid open fistula track should
studied only patients with an abscess who had a demon-
be marsupialized to aid healing and reduce wound dis-
strable internal opening, and in the abscess drainage only
charge. (Grade A)
arm, just 10 of 49 patients had recurrence [104]. What
this means is that the remaining 39 patients (80%) would Marsupialization is a simple procedure which
have been exposed to the risks of fistulotomy without ben- improves wound healing. It is also used as part of the
efit. wound shaping which some surgeons use to prevent
A reasonable compromise may be for an experienced early bridging and allow adequate drainage of the
surgeon to undertake immediate fistulotomy in simple wound. Four randomized trials have demonstrated that
fistulas when the abscess is recurrent and where drai- marsupialization of the fistulotomy wound reduces time
nage alone seems unlikely to resolve matters. But this to wound healing [107–110]. Ho et al. [108] demon-
relies on the detailed preoperative counselling, usually strated a faster healing time (6 vs 10 weeks, P < 0.001)
employed in the outpatient clinic, and which is less in 103 patients randomized to fistulotomy vs fistulo-
likely to be successful for a patient suffering a painful tomy with marsupialization. A higher squeeze pressure
acute abscess and having little time to consider the was also seen in the marsupialized group, but the clini-
options prior to urgent surgery. cal relevance of this is unclear. Pescatori et al. [110]
studied 46 patients in the same way and found less
bleeding as well as a quicker reduction in wound size in
Fistulotomy in inflammatory bowel disease
the marsupialized group. More recently, Jain et al.
Findings [109] randomized 40 patients to fistulectomy or fistulo-
tomy with marsupialization, demonstrating faster
Most surgeons would avoid fistulotomy in a patient
wound healing (around 5 weeks vs around 7,
with Crohn’s disease and an anal fistula. (Level III)
P = 0.003) and earlier cessation of wound discharge.
Chalya et al. [107] found similar results in 162 patients
Recommendations randomized between the same procedures.
Careful consideration should be undertaken before
performing fistulotomy in Crohn’s disease, even for a Setons
‘low’ fistula. (GP)
The evidence supporting the use of setons in the man-
Fistulotomy in Crohn’s disease is uncommon, and a agement of anal fistulas was comprehensively reviewed
recent survey of UK surgeons indicated that around in the original position statement on anal fistula [1].
half would occasionally consider fistulotomy but only Essentially a seton can be used in three main ways in
3% did so frequently and more than a third would the treatment of an anal fistula, with myriad variations
never do so [105]. van Koperen et al. [106] undertook of technique between published series. The seton can
fistulotomy in a group of patients with low fistulas in be inserted and tied loosely over the sphincter to drain
Crohn’s disease with a recurrence rate of 17% and the track and allow sepsis to settle before it is removed,
impairment of continence in two-thirds, both worse in the hope that the fistula will heal (loose seton). The
than the outcomes seen in idiopathic fistulas, which seton can be used to divide the sphincter muscle slowly
may explain the reticence of most UK surgeons to per- to eradicate the fistula (cutting seton) and the seton can
form fistulotomy. This particular group of complex be used as a long-term drain to provide palliation of

12 Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31
G. Williams et al. The treatment of anal fistula (2018 update)

symptoms from the fistula, where other techniques are eventually removed after a median of 4 months; how-
deemed unsuitable. ever, it is not clear how many fistulas healed, although
there was deterioration in anal control reported. Sub-
has et al. [114] used a silk seton as a loose seton,
Loose seton
which the patient was instructed to rotate through
Findings 360° in each direction on a daily basis. Twenty-four
patients were followed for a mean of 45 months (but
A loose seton, used as sole treatment, results in fistula
only by questionnaire and telephone interview), with
healing in only a small proportion of patients. Higher
18 (75%) fistulas healing, 9 once the seton extruded
healing rates are achieved by staged fistulotomy after a
spontaneously and 9 after low fistulotomy of the resid-
period of seton drainage. (Level III)
ual track: two patients developed incontinence of liq-
uid stool only. Kelly et al. [115] followed a series of
A loose seton can be used to treat ‘high’ and complex
200 patients treated with a polybutylate (EthibondTM)
anal fistulas with low risk to diminishing anal control.
suture, with a recurrence rate of 6% and a low rate of
(Grade B)
incontinence. However, follow-up was short
A number of series of patients treated with a loose (6 months) and detail of how changes in anal control
seton continue to be reported, often with subtle varia- were defined and assessed was lacking. Furthermore,
tion in technique and all highlighting the relative although the loose seton controlled symptoms, most
safety of this technique as regards alteration in anal patients ended up requiring a second procedure to lay
control. However, convincing evidence of fistula heal- open the residual fistula track. Follow-up is not
ing following simple removal of a loose seton is scant, described in any detail and four patients (6%) were
and often an additional procedure is required to said to have experienced ‘minor’ incontinence.
achieve fistula healing. Galis-Rozen et al. [111]
reported a series of 77 patients, 17 of whom had
Cutting (tight seton)
Crohn’s disease and were treated with a loose seton
alone. Of the 60 patients with non-Crohn’s fistulas, Findings
only 4 healed without further surgery and 20 (46%)
A tight seton inserted into a transsphincteric fistula
healed following second-stage fistulotomy. However, a
will result in healing in upwards of 90% of patients.
similar proportion of patients either had recurrence or
There is some risk of diminishing anal control that is
did not heal following seton placement, possibly
influenced by the height of the internal opening and
reflecting the complexity of fistulas included in this
the amount of muscle encompassed in the seton.
series. In a similar manner, Lim et al. [112] described
(Level III)
an intriguing modification of the loose seton tech-
nique. The primary track was re-routed into the inter-
sphincteric space, by dividing the mucosa and internal Recommendations
sphincter below the internal opening and placing a
A tight seton can be used to treat selected ‘high’ and
seton around the external sphincter in the intersphinc-
complex anal fistulas where other techniques are either
teric plane, before closing the internal opening,
not suitable or have failed. The patient should be
mucosa and divided internal sphincter over the seton.
counselled carefully as to the risk of permanent incon-
Fifty-three patients were treated by this technique,
tinence. (Grade B)
with a reported recurrence rate of 13% and inconti-
nence reported by two patients. However, follow-up A tight seton has been used where a surgeon is
was mostly by telephone contact and no clinical assess- unwilling to perform fistulotomy because it is thought
ment was made to confirm healing of the fistula. An that too much sphincter will be divided in the process
alternative approach was reported by Pinedo et al. and the risk of incontinence is high. A variety of tech-
[113] in 18 patients with transsphincteric fistulas. The niques have been described, all with the same principle,
external part of the track was laid open to the outer namely slow division of the sphincter encompassed by
surface of the external sphincter and an internal the seton, with progressive caudal migration of the track
sphincterotomy was performed to lay open the inter- and eventual extrusion of the seton. Much is made of
sphincteric element of the track. A loose elastic seton the theory that this slow division with a foreign material
was inserted in the remaining track through the exter- generates fibrosis around the sphincter as it is divided,
nal sphincter and removed when the internal opening limiting separation of the sphincter ends and healing of
had migrated to the anal verge. All setons were the muscle cephalad to the seton as it descends the anal

Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31 13
The treatment of anal fistula (2018 update) G. Williams et al.

canal. This is in contrast to the springing open of the follow-up duration was not specified, but was likely to
sphincter ends that occurs with primary fistulotomy. have been short. A similar study by Kamrava et al.
Attractive as this theory sounds, there is little or no evi- [125] used silk, but tightening of the seton was con-
dence to substantiate improved sphincter morphology trolled by the patient. Recurrence was 10% and only 1
and function over immediate fistulotomy. Anecdotal of 47 patients was reported to have new problems with
comparison of ultrasound appearances of the sphincters control, although definitions used for assessing control
after cutting seton suggest less sphincter separation than were loose and follow-up was short. Using a thin elec-
after fistulotomy, but it is uncertain if like is being com- trical cable tie as a seton is intriguing: Memon et al.
pared with like [116]. Rosen and Kaiser [117] used [122] reported a series of 79 patients with transsphinc-
data from Ritchie et al. [118] to demonstrate an associ- teric or suprasphincteric fistulas, with a recurrence rate
ation between the rate of incontinence and the interval of 5% and no reported change in continence. However,
between seton tightening, which they interpreted as no details were given as to the level of discomfort expe-
supporting evidence that slow sphincter division pre- rienced by the patients, who required on average six
serves sphincter function. However, this requires a large tightenings of the seton and an average of 12 weeks for
leap of faith, as the data used were very heterogeneous, healing to occur. Hammond et al. [121] used a silastic
with different definitions of incontinence and periods of vessel and nerve sloop as a ‘snug’ seton in a series of 29
follow-up. patients. The seton cut through the enclosed tissue in
Evidence in favour of the use of a cutting seton is 15 patients, but 14 patients required a superficial fistu-
still based on case series, and no specific randomized lotomy to finally remove the seton. There were no
trial of tight setons vs other surgical options has been recurrences identified, and 10 patients (34%) experi-
performed. Most studies suffer from a number of enced early minor incontinence, which persisted in 4 of
flaws, usually involving the definition of end-points, 16 patients followed for a median of 42 months. Leven-
limited follow-up and low numbers. A variety of differ- toglu et al. [120] used a rubber glove as a ‘hybrid’
ent materials have been used as tight setons, including seton; this was not tied as tightly as a traditional cutting
silk [119], rubber bands, rubber surgical glove seton with the same intention as Hammond et al.
[116,120], silastic vessel sloop [121] and electrical [121]. Side tracks were dealt with by a modified Hanley
cable tie [122]. Each modification is designed to make technique, using Penrose drains. With this technique
tightening the seton simple as well as avoiding the there was one recurrence over a mean follow-up of
need for a general anaesthetic. Similarly, some authors 20 months and no significant change in the Cleveland
perform internal sphincterotomy prior to seton inser- continence score. Ege et al. [116] used the cuff from a
tion [123,124] and others encompass both the exter- rubber glove as a ‘hybrid’ seton, tied snugly over the
nal and internal sphincters in the seton, after removing denuded external sphincter following internal sphinc-
skin and anoderm beneath the seton [116]. Whichever terotomy. They followed 128 patients, with the seton
technique is employed, the internal sphincter will even- extruding after a mean of 19 days, suggesting that
tually be divided by the seton as it cuts through the many fistulas were low. Complete healing occurred at
fistula track and overlying sphincter. Vial et al. [123] 3 months in all patients and only two patients returned
performed a meta-analysis on a number of case series with a recurrent fistula after a minimum of 12 months’
looking at recurrence rates and alteration in anal con- follow-up. However, in common with other studies, it
trol after use of a cutting seton, with and without is unclear as to how tightly the seton was tied over the
sphincterotomy at time of seton insertion. They con- sphincter. Izadpanah et al. [124] described a technique
cluded that recurrence rates were similar (at less than they called a ‘pulling seton’ in a large series of 201
5%), but overall incontinence was higher after sphinc- patients in whom they divided the internal sphincter
terotomy (25%) than after seton insertion without and the external part of the fistula, before tying a seton
sphincterotomy (6%). However, these results should be over the remaining external sphincter muscle. The
interpreted with considerable caution as the studies patient was instructed to tug on the seton four times a
were very heterogeneous, with different follow-up peri- day. Using this technique, they reported a recurrence
ods and different methods of assessing changes to rate of 5% and no permanent gas or faecal incontinence.
incontinence. However, follow-up was short and postoperative assess-
Raslan et al. [119] collated 51 patients treated with ment of continence was limited. Rosen and Kaiser
a tight silk seton, with a recurrence rate of 10% and [117] reported on 121 patients with a transsphincteric
incontinence to flatus of 16% and liquid stool of 6%. fistula treated by tight seton. Initial healing occurred in
However, details as to the anatomy of the fistulas trea- 90% of patients, rising to 98% after further surgical pro-
ted and how continence was assessed are absent and cedures. Interestingly, 17 patients with preexisting

14 Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31
G. Williams et al. The treatment of anal fistula (2018 update)

continence problems improved following surgery, indi- may explain heterogeneity in the significance of risk fac-
cating that the presence of a fistula can cause continence tors identified in different studies.
problems (possibly by discharge through the track).
Only eight patients developed new problems with anal
Transanal advancement flap
control. These excellent results should be interpreted
with some caution as follow-up of these patients was Findings
short (mean 5 months).
The success rate of transanal advancement flap is of
In summary, a variety of materials have been used as
the order of 60%. (Level III)
a cutting seton, with most series reporting successful
healing of the fistula and recurrence rates of the order
of 10% after short-term follow-up. It is uncertain if Recommendations
internal sphincterotomy is a necessary part of the proce-
Transanal advancement flap can be used to treat an
dure. It is likely that sphincter division (even slow divi-
anal fistula where simple fistulotomy is thought likely
sion) will inevitably lead to some diminution in anal
to result in unacceptable impairment of continence.
control, which may not become apparent immediately.
(Grade B)
Ritchie et al. [118] collated a large number of series
and calculated an average incontinence rate of the order The transanal rectal advancement flap procedure has
of 12%. several advantages over other treatments for anal fistula.
Division of the external sphincter is avoided with less
risk of impairment of continence, and defects of the
Advancement flaps
contour of the anal canal, such as a keyhole deformity,
Advancement flap surgery is a well-established tech- are avoided and healing is quicker than after fistulo-
nique with reliable outcomes in experienced hands. tomy. Additional procedures can be incorporated into
The technique should be considered in patients in the operation, such as sphincteroplasty, without the
whom fistulotomy would result in a compromise to need for a protective colostomy. Failure of the repair
continence that would be deemed unacceptable to the does not usually lead to worse symptoms, although the
patient, and with a track morphology that is likely to internal sphincter at the level of the anorectal junction
yield success. An advancement flap may also be used to will have been disrupted to a certain extent and the anal
close an anorectal or recto-urethral fistula. As well as canal will be somewhat more rigid as a result of scar tis-
disconnecting the fistula from the gut, a flap technique sue. This could result in functional impairment.
is effective as it brings a layer of healthy native tissue Relative contraindications to the transanal rectal
to cover the internal opening, following control of sep- advancement flap procedure include: the presence of
sis. Adequate vascularity of the flap and tension-free proctitis – especially in patients with Crohn’s disease;
anastomosis, placed well beyond the site of the (ex- undrained sepsis and⁄or persisting secondary tracks; an
cised) internal opening, are key to success. Advance- anorectal fistula with a diameter > 3 cm; malignant or
ment flaps can be taken from the rectum (transanal radiation-related fistula; a fistula of less than 4 weeks’
advancement flap) or from the perianal skin (cutaneous duration; and an associated stricture of the anorectum
advancement flap). Also described are the transanal [132]. Stricture, tissue loss and scarring of the anorec-
sleeve advancement flap (TSAF) and the Delorme’s- tum may impair the surgeon’s access and may make flap
style advancement flap. This is similar to the TSAF repair technically impossible.
but, as in the Delorme’s procedure for rectal prolapse, The surgical technique for endoanal advancement flap
after mucosal mobilization the muscle wall is advanced procedures has been described in earlier publications
and sutured down to the internal anal sphincter distal [133–135] and was summarized in the previous position
to the internal opening of the fistula. This procedure is statement [1]. Whilst many surgeons would use mechani-
facilitated by internal intussusception and would not cal bowel preparation prior to surgery, and consider the
be a tension-free repair without it [126]. The presence use of a defunctioning stoma to cover the procedure,
of internal intussusception or perineal descent may there is no evidence base to support these approaches. A
facilitate advancement flap repair. semi-circular flap is most commonly used as this avoids
A number of factors have been identified as risk fac- ischaemia at the corners. The majority of authors describe
tors for failure of an advancement flap procedure. These a U-shaped flap, while a minority use an inverted U-
include, smoking [127,128], a flap for a recurrent fis- shaped flap. The flap consists of mucosa, submucosa and
tula [127], Crohn’s disease [129], horseshoe abscess a varying degree of circular muscle from none to the full
[130] and high BMI [131]. Differing study populations rectal wall thickness, depending on the author. There has

Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31 15
The treatment of anal fistula (2018 update) G. Williams et al.

been limited evidence from individual studies to support fistula, and the methods of repair. Long-term follow-
the logical assertion that more muscle means greater vas- up is essential for assessing recurrence accurately.
cularity and therefore success, at the cost of a greater risk Advancement flap procedures are safe. Early case series
of impairment of continence, but pooled data from a suggested efficacy in around 70% of patients [132–
recent meta-analysis suggest that this is correct [136]. 134,138–144]. However, more recent randomized
controlled trial data, often vs the anal fistula plug, and
The transanal sleeve advancement flap procedure larger series, suggest healing in a smaller proportion,
The TSAF takes the concept of flap advancement one perhaps of the order of 50–60% [145–147]. A recent
step further by mobilizing the circumference of the anal multicentre randomized trial of 94 patients from Scan-
canal. It has been used for a subgroup of patients with dinavia found a primary success rate (defined as clinical
severe complex fistulas associated with Crohn’s disease healing), at a median of 12 months of follow-up, of
[137]. The technique is similar to the transanal flap pro- 62% of 40 patients. A full-thickness flap was used and
cedure described above, but in addition a 90–100% cir- patients had a single, non-complex high transsphinc-
cumferential incision is made at or just below the dentate teric track and after only a single previous fistula oper-
line to create a sleeve of the full thickness of the bowel ation (probably seton insertion). The comparator
wall. This is then mobilized proximally into the suprale- group, treated with a fistula plug, achieved clinical suc-
vator space until sufficient mobility is achieved to allow cess in only a third of patients. MRI confirmation of
the flap to be advanced distally into the anal canal with- healing was not reported in either arm [148]. This
out tension. Its distal edge is then sutured with absorb- study represents a robustly performed assessment of
able sutures to the epithelium of the anal canal below the transanal rectal advancement flap surgery in well-
level of the internal opening. This technique may offer an selected patients, and is a realistic report of the tech-
alternative in selected patients with fistulation in Crohn’s nique. A recent meta-analysis including 26 studies and
disease without proctitis, for whom the only alternative is 1655 patients indicated an increasing success rate
proctectomy with permanent stoma. (avoidance of recurrence) with increasing thickness of
the flap raised, although there was significant hetero-
geneity between studies [136]. The pooled recurrence
The cutaneous advancement flap procedure
rate was 21%, but ranged from 0% to 47%. Core out
Findings vs curettage of the track did not influence outcome.
The cutaneous advancement flap procedure has a simi-
lar success rate to endoanal flap, but the theoretical Continence impairment
risk of avoiding ectropion formation. (Level III) There is great heterogeneity in how continence is assessed
following advancement flap surgery. Early studies found
little impairment of continence but some authors suggest
Recommendations
minor incontinence may occur in around a quarter of
The cutaneous advancement flap procedure is an alter- patients [149]. Meta-analysis suggests a greater likelihood
native to rectal advancement flap repair of a high fis- of continence impairment with full-thickness flaps (20%)
tula. (Grade B) than mucosal or partial thickness flaps (10%), although
the impairment was generally minor [136].
The cutaneous advancement flap appears to have a
similar success rate to endoanal flap procedures, with
the theoretical advantage that by moving skin into the Fibrin glue
anal canal, mucosal ectropion is avoided [138–141].
Findings
The technique for the procedure has been described
elsewhere [138–141]. The use of fibrin glue to treat anal fistulas is associated
with variable success, but does not threaten conti-
Postoperative management of flap procedures nence. It remains uncertain as to which fistulas are
There is no consensus on the role of anti-diarrhoeal suitable for fibrin glue treatment. Success (fistula heal-
agents or antibiotics in the early postoperative period. ing) is low when the fistula track is short. (Level I)
Normal anal wound management should be carried out.

Recommendations
Fistula recurrence after advancement flap procedures
It is difficult to compare published series as there is With variable and mostly low rates of healing, fibrin
often great variation in the type and complexity of glue is not recommended for routine use in anal

16 Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31
G. Williams et al. The treatment of anal fistula (2018 update)

fistulas, but may be considered where other surgical continence score in the seton group. Many studies have
options are not feasible. (Grade C) investigated the use of repeat glue application to
increase healing rates, even up to four applications
Various autologous and commercial preparations of
[166]. A prospective study of fibrin glue for simple
fibrin glue have been used to treat anal fistulas. Autolo-
transsphincteric and intersphincteric fistulas showed that
gous glues are formed from the patient’s own blood,
repeat glue treatment decreased the overall recurrence
whilst commercially available glues are a mixture of clot-
rate from 23% to 7.6% [167]. Conversely, other authors
ting factors, aprotinin and calcium (Beriplast; CSL
have reported that repeated applications of fibrin glue
Behring, Pennsylvania, USA; Tisseel; Baxter Healthcare,
are unlikely to succeed [168] and other studies have
Deerfield, Illinois, USA), or are synthetic glues, such as
shown an adverse outcome when fibrin glue is com-
cyanoacrylate (Glubran; GEM SRL, Viareggio, Italy).
bined with an endorectal advancement flap [169].
The glues are applied to fill the fistula track and provide
Various strategies have been suggested to improve
a bridge for fibroblasts and stromo-vascular cell in-
the healing rates with glues. Local sepsis should be
growth to produce healing. Their ease of use, minimal
eradicated with the use of preoperative setons, the track
risk to continence and repeatability make them an
should be thoroughly curetted and the track irrigated
attractive option, especially in patients at high risk of
with either saline or hydrogen peroxide. Preoperative
sphincter dysfunction [150,151].
bowel preparation has not consistently shown a benefit.
A wide range of healing rates with fibrin glues have
Suturing the internal or external openings shut has been
been reported, ranging from 14% to 94% [152,153].
advocated, but not shown to confer a significant benefit
Variability in disease complexity, fistula anatomy and
[152].
surgical technique makes comparison of the results from
It has been suggested that high failure rates with the
randomized trials difficult to interpret [154–156]. A
glue may be a consequence of the glue not being
meta-analysis has not shown any statistical difference
retained in the fistula track [170,171]. To overcome
with the use of fibrin glue, compared to other conven-
this, some authors have recommended the use of stool
tional surgical treatments, in terms of fistula recurrence
softeners and avoiding straining and exercise in the
or incontinence [157].
postoperative period, although there are no data to sup-
Some authors have reported better healing rates in
port this. Other explanations for failure of fibrin glue
longer tracks, suggesting that shorter tracks (< 3.5 cm)
include early resorption/degradation within 5–10 days
are less likely to retain the glue [155,158], but this has
of application, providing insufficient time for established
been contradicted in other reports [159–161]. Techni-
healing [165,171]. A Phase I trial using Permacol
cal errors have been suggested for failure, including
glue, which incorporates fibres suspended in fibrin glue
inadequate curettage and washout to remove all
to provide a physical scaffold for host cell proliferation
infected and epithelialized tissue [155,161,162], or
after glue absorption, has shown promising results, but
incomplete filling of the track with the glue to ensure
more, randomized, data are required [165]. Newer
occlusion [155].
autologous fibrin sealants have not shown any increased
Like other fistula treatments, recurrence rates with
efficacy compared with conventional glues, with healing
fibrin glue increase with the length of follow-up. A long-
rates of up to 40% [172]. Research continues into the
term follow-up study showed that up to 26% of patients
use of stem cell autologous suspensions for fistula appli-
who were symptom free at 6 months went on to develop
cation and the ADMIRE CD study used fibrin glue as
recurrence at an average of 4.1 years [163]. However,
the scaffold for allogeneic mesenchymal stem cell treat-
on several occasions the recurrence was at a different site,
ment of Crohn’s anal fistulas [173]. This may represent
suggesting that a new fistula had formed. The highest
the main role for fibrin glue in the future.
probability of failure appears to occur in the first
6 months following treatment, so 6 months should be
the minimum follow up period [152,161,164,165].
A multicentre trial randomized patients to fibrin glue Fistula plugs
or seton treatment for transsphincteric fistulas and Findings
showed a 38% healing rate in the fibrin glue group,
compared with 87% in the seton group [150]. Patients The initial reported high success rates of anal fistula
who had a recurrence after fibrin glue were further ran- plugs have not been maintained in later series, but,
domized to repeat glue treatment or a loose seton. A similar to fibrin glue, anal fistula plugs do not threaten
further 50% healed with repeat glue treatment. Notably, continence. It remains uncertain as to which fistulas
there was a significant worsening in the Cleveland Clinic are best suited to fistula plug treatment. (Level I)

Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31 17
The treatment of anal fistula (2018 update) G. Williams et al.

Recommendations prevent early extrusion of the plug, which had been


reported as a cause for failure in some studies [177].
Accepting that rates of healing are variable, an anal fis-
There was no evidence to support the routine use of a
tula plug is an option for treating transsphincteric fis-
rectal mucosal flap to cover the plug. Suturing of the
tulas, especially where surgical options are considered
plug has been facilitated by modification of the original
to have a significant risk of jeopardizing continence.
plug design to incorporate an internal ‘button’.
The additional cost of the plug should be taken into
Initial encouraging results from Johnson et al. [178]
account when considering this surgical treatment.
reporting closure rates of up to 87% have not been repro-
(Grade C)
duced in later studies, which have presented mixed
Anal fistula plugs (AFPs) are bioprosthetic or syn- results. A randomized trial comparing the fistula plug
thetic materials used to occlude the fistula track, block- with endorectal advancement flap (ERAF) was closed
ing the internal opening and preventing faecal material prematurely due to a high incidence of recurrence in the
from entering. They provide a physical scaffold for in- plug arm [179]. In another RCT, comparing an acellular
growth of host regenerative and immune cells to pro- dermal matrix (ADM) plug vs ERAF, a healing rate of
mote healing and repair. The plugs degrade over a per- 82% was reported in the ADM group, with lower rates of
iod of several weeks, by which time the repair process is recurrence (ADM plug 4% vs ERAF 28%) [180]. A sub-
established. sequent meta-analysis comparing the plug with ERAF
failed to show any difference in recurrence rates or com-
Types of plug. Several fistula plugs have been developed plications [181]. However, a recent robust multicentre
commercially, but the BioDesign Surgisis Anal Fistula RCT of 94 patients with a transsphincteric fistula
Plug (Cook Medical, Bloomington, Indiana, USA), demonstrated clinical healing at 12 months in only 38%
composed of acellular, lyophilized porcine intestinal (15 of 44 patients) treated by collagen plug, compared
submucosa, is the most established. Other plugs include with 66% (27 of 41 patients) treated by ERAF [148].
the GORE Bio A Fistula Plug (Flagstaff, Arizona, A potential disadvantage with the plug is the cost of the
USA), a composite of polyglycolic acid and device, but this may be offset by a shorter hospital stay. In
trimethylenecarbonate synthetic polymers [174], which a study comparing fistula plug against ERAF, healing rates
has now been withdrawn by the manufacturer, the were similar, but the costs associated with ERAF were
Pressfit plug (Deco Med s.r.l., Venice, Italy), which is higher due to a longer duration of hospital stay [182].
made from acellular dermal matrix, and the Curaseal In a recent UK multicentre study (the NIHR FIAT
AF device (CuraSeal, Inc., Santa Clara, California, trial) 152 patients were randomized to receive the Cook
USA), which incorporates a silicone disc to reinforce Biodesign fistula plug and compared with 152 patients
occlusion of the internal fistula opening. Secure anchor- receiving surgeon’s preference [cutting seton, ERAF, fis-
ing of the plug at the internal opening is a critical fea- tulotomy or ligation of intersphincteric fistula track
ture in the design of all these plugs. (LIFT)]. Similar clinical fistula healing rates were
observed at 12 months’ follow-up (plug 54% vs sur-
Surgical technique. Reported success rates for fistula geon’s preference 57%). Early plug extrusion remained a
healing with plugs vary, ranging from 24% to 88% problem, despite the adoption of best surgical technique,
[175], reflecting differences in patient selection, plugs occurring in 15% of cases. Rates of incontinence were low
used, surgical technique, definition of healing and in both groups and there was no statistical difference in
length of follow-up. In 2007, a Consensus Conference quality of life as measured by the FIQoL and EQ-5D
was held to establish uniformity in the indications and scoring systems. Complications rates were similar
techniques for insertion of the Cook Medical fistula between the two groups, with the exception of increased
plug [176]. It concluded that all types of ano-cutaneous early postoperative pain in the plug group, presumably
fistula were suitable for plug treatment, with associated with suturing to the internal anal sphincter.
transsphincteric fistulas being the ideal indication. The fistula plug has been successfully used in combi-
Emphasis was placed on the prior control of associated nation with other procedures, including the LIFT pro-
sepsis and the use of seton drainage for 6–12 weeks cedure. In a large, multicentre RCT, the LIFT–plug
preoperatively. Debridement or curettage of the track procedure was found to result in statistically significant
was discouraged, although gentle brushing to de- higher healing rates compared with LIFT alone (LIFT–
epithelialize the track was subsequently recommended, plug 94.0% vs LIFT 83.9%; P < 0.001) [183].
with saline or hydrogen peroxide irrigation being Most studies have included variable follow-up after
optional. Secure suturing of the plug to the internal surgery, ranging from 3 to 12 months. A long-term fol-
opening/internal sphincter was considered important to low-up study, using MRI to assess fistula healing at

18 Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31
G. Williams et al. The treatment of anal fistula (2018 update)

12 months after plug insertion, showed radiological evi- ligate the intersphincteric fistula track, remove the fis-
dence of a persistent fistula in up to 21% of patients, tula track and then curette it from the external opening.
suggesting that reports of fistula healing at 12 months The external sphincter muscle defect is closed, as is the
are likely to be an overestimate [184]. intersphincteric wound.
Benefits in favour of the fistula plug include ease of Three RCTs have been reported [183,188,189]
use and lack of complications. No differences in compli- (Table 2). One only compared LIFT with a modifica-
cation rates have been reported between ERAF and tion of LIFT, rather than a standard treatment, whilst
AFP [181], with documented complications including the other two compared LIFT with a mucosal advance-
sepsis/abscess, recurrence and constipation ment flap. In addition, 18 case series have been
[183,185,186]. Unlike some other techniques, no study reviewed [187,190–206] (Table 3). A number of series
has reported a detrimental effect to continence follow- reporting fewer than 10 patients were disregarded for
ing use of a plug. Thus, the fistula plug is an option for the purposes of this position statement.
treating a transsphincteric fistula. Uncertainty in healing Madbouly et al. [189] randomized 70 patients to
efficacy is counterweighed by the lack of detrimental either LIFT or a mucosal advancement flap. Primary
effect on continence. The cost of the device might be healing was achieved in 33 (94%) patients undergoing
offset by shorter lengths of hospital stay. LIFT compared with 32 (91%) patients undergoing a
flap repair. Median healing times were 22.6 and
Novel techniques 32.1 days, respectively. After follow-up of 1 year, a suc-
cessful outcome was achieved in 26 (74%) of the LIFT
Findings group compared with 20 (66%) in the advancement flap
A number of novel surgical techniques for anal fistulas group (P = 0.58), highlighting the importance of long-
have been developed over the last 10 years. These term follow up in fistula surgery research. There was no
include the LIFT procedure, lasers, clips, video- significant difference in continence scores in this study.
assisted anal fistula treatment (VAAFT) and autolo- A similar, but smaller, study randomized 25 patients
gous adipose-derived stem cells. Evidence of efficacy is to LIFT and 14 to anorectal advancement flap [188].
scant and largely confined to personal series (Level III All patients had seton inserted prior to definitive sur-
evidence) with a paucity of RCTs performed to date, gery. Recurrences were seen in 2/25 and 1/14, respec-
and what is available is confined to the LIFT proce- tively. The authors concluded that LIFT was simple and
dure. Whilst initial work on other techniques looks safe, took significantly less time than a flap and patients
interesting, with minimal adverse events reported, returned to work earlier.
long-term follow-up needs to be reported as many Sileri et al. [194] reported 26 patients with complex
institutional series only document short/medium fol- fistulas, 19 of whom were healed at a minimum of
low-up, functional outcome data are limited and few 16 months following LIFT. The recurrences occurred
patient-reported outcome data are available. A degree between 4 and 8 weeks following surgery. They defined
of standardization is required in approaches using ‘complex’ as any track that was deeper than 30% of the
multiple concurrent treatments. Randomized evidence external sphincter, anterior fistula in women, recurrent
is needed before these new techniques will challenge fistula or preexisting incontinence. Only two patients
conventional approaches. had previously had a loose seton inserted prior to the
LIFT procedure. Another series of 40 patients with
transsphincteric fistulas deemed to be inappropriate for
Recommendation: fistulotomy underwent LIFT [205]. Success rates of up
to 74% were noted, although follow-up was short (a
The LIFT procedure is an option for treatment of a
mean of 18 weeks).
transsphincteric fistula, with or without insertion of a bio-
Ooi et al. [199] reported 25 patients who had
prosthetic graft in the intersphincteric space. (Grade B)
undergone LIFT. Ten of them had developed recur-
rence after previous fistula surgery. The primary and
It is too early to recommend the routine use of other
secondary end-points were cure rate and degree of
novel treatments for anal fistula. (Grade C)
incontinence, respectively. Primary healing was observed
in 17 (68%) patients at a median of 6 weeks. Seven
The LIFT procedure. The LIFT procedure was first patients had recurrence of their fistula, which presented
reported in 2007 [187], when healing was seen in 17 between 7 and 20 weeks’ postoperatively. There was no
of the first 18 patients reported. The principle is essen- reported incontinence. Liu et al. [204] recruited 38
tially to make an incision in the intersphincteric groove, patients between 2008 and 2011. At a median follow-

Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31 19
The treatment of anal fistula (2018 update) G. Williams et al.

Table 2 Randomized controlled trials of ligation of intersphincteric fistula track (LIFT; Level I evidence).

Median
Authors Trial design Numbers Healing rates follow up Incontinence

Han et al. LIFT vs LIFT plug 235 LIFT–plug 94.0% 6 months None
(2016) [183] LIFT 83.9%
Madbouly LIFT vs mucosal 70 LIFT 26/35 12 months No change in Wexner
et al. (2014) advancement flap Mucosal advancement score at 4 weeks
[189] flap 20/35 (P = 0.58)
Mushaya LIFT vs anorectal LIFT 25 Recurrences of 2/25 in 19 months One flap patient noted to
et al. (2012) advancement flap Flap 14 LIFT vs 1/14 in flap have minor incontinence
[188]

up of 26 months (26 patients had at least 12 months’ [190]. Healing was seen in 18/22 patients recruited at
follow-up), healing was seen in 23/38 (61%). One fail- a median follow-up of 19.5 months. The four unsuc-
ure occurred over 12 months after the index procedure, cessful cases were treated with fistulotomy. Although
with 80% of failures occurring within the first 6 months there was no comparison with patients with similar fis-
following the procedure. No intra-operative complica- tulas undergoing fistulotomy as sole treatment, the
tions or incontinence were noted. Increasing fistula authors reported a final healing rate of 100% and no
length was associated with decreased likelihood of heal- alteration in continence, which was assessed prospec-
ing. tively.
A recent large series (167 patients) reported a success A Chinese group recently reported on 43 patients
rate (healing) of 94% at a median follow-up of with ‘complex’ fistulas treated by LIFT, all of whom
12 months [198]. The majority of fistulas were were followed up for more than 1 year [201]. Healing
transsphincteric [150], and a number were recurrent of the fistula was seen in 36 of 43 (84%) patients; fail-
[33]. Ten patients who developed a recurrent fistula were ure, when seen, occurred a mean of 8.6 weeks after the
managed with a repeat LIFT procedure. Schulze et al. original procedure. In this series, eight patients had
[196] performed LIFT on 75 patients between May dehiscence or infection at the site of the intersphincteric
2008 and June 2013. All had undergone an initial proce- wound, with five patients requiring laying open. This
dure that involved drainage of sepsis, insertion of a loose complication is probably commoner than reported in
seton and partial fistulotomy. There were nine recur- many series.
rences, at a mean follow-up of 14.6 months, all of which Modifications to the LIFT procedure have been
were treated with repeat LIFT and biograft or anorectal described. The Bio-LIFT procedure, for example,
advancement flap. There were no subsequent recur- involves placing a biograft (usually a piece of collagen
rences. Recurrences were related to fistulas with multiple mesh) in the intersphincteric space following ligation of
tracks. Only one patient reported a change in continence. the intersphincteric fistula track. Success was reported in
An attempt has been made to determine whether 11 of 16 (63%) fistulas treated, at a median follow-up
LIFT is more effective in distinct fistula sub-types [197]. of 26 weeks [192]. A randomized trial comparing the
LIFT was performed in simple transsphincteric (five), two approaches in 235 patients reported healing rates at
complex fistulae (six) and recurrent cases postfistulotomy 6 months of 94% in the LIFT + biograft group, vs 84%
(six). The overall success rate at a mean follow-up of in the LIFT group alone [183]. The authors reported
11 months was 53%. Healing rates in the three groups that the addition of the graft had the advantage of
were four out of five, three out of six and two out of six, higher healing rates, decreased healing time and a lower
respectively. These numbers are too small to draw any early postoperative pain score. Another modification
conclusions, but intuitively LIFT should be more likely involves making a lateral incision from the external
to succeed in less complicated fistulas (as is the case for opening to the intersphincteric groove, ligating the fis-
all fistula treatments). There is general consensus that tula track within the intersphincteric space and complete
the presence of multiple tracks, diabetes mellitus, peri- excision of the external part of the fistula [195]. In a
anal collections and long tracks are all associated with a series of 39 patients treated in this way and followed for
higher chance of failure of LIFT. a mean of 15 months, 34 (87%) achieved healing.
LIFT has been employed as an alternative to fistulo- There was no change in continence, as measured by the
tomy in patients with low transsphincteric fistulas Cleveland Clinic score preoperatively and at 6 months

20 Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31
Table 3 Case series of ligation of intersphincteric fistula track (LIFT; Level III evidence).

Author Number Types of fistula Healing rates Follow-up Comments


G. Williams et al.

Parthasarathi 167 150 transsphincteric 94% Median 12 months Seven patients underwent repeat LIFT
et al. (2016) [198] 16 intersphincteric (range 4–22) procedure
1 suprasphincteric Recurrence associated with diabetes
(33 recurrent) mellitus and perianal collections
Chen et al. 43 Uncomplicated transsphincteric 36/43 (84%) ≥ 12 months – median Eight had dehiscence or infection at the
(2016) [201] (29), horseshoe transsphincteric follow-up of wound site – five of these required
(10) and multiple fistulas (4) 26.2 months laying open procedures
Bastawrous et al. 66 procedures Transsphincteric 71% Median 21 weeks Modified LIFT – intersphincteric
(2015) [202] in 56 patients component de-roofed
Romaniszyn et al. 17 Transsphincteric, complex 8/17 (47%) Mean 11 months Best results seen in simple fistulas
(2015) [197] and recurrent
Schulze et al. 75 ‘Complex’ cryptogenic 66/75 (88%) Mean of 14.6 months LIFT following seton placement and
(2015) [196] Nine recurrences partial fistulotomy
diagnosed at a mean of One patient developed minor incontinence
9.2 months
Ye et al. (2015) 43 High transsphincteric 34/39 (87%, four lost to Mean of 15 months Modified LIFT
[195] follow up)
Sileri et al. 26 ‘Complex’ fistula 19/26 (73%) ≥ 16 months Complex defined as track crossing > 30%
(2014) [194] of external sphincter, anterior fistula in a
woman, recurrent fistula and preexisting
incontinence
Tan et al. (2014) [192] 13 patients Transsphincteric 11 healed Median of 26 weeks Four patients had a previous failed LIFT
with 16 fistulas BioLIFT was performed with insertion
of a bioprosthetic graft in the
intersphincteric space
Gingold et al. 15 Transsphincteric 9/12 (75%) at 2 months All had Crohn’s disease

Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31
≥ 12 months
(2014) [200] 8/12 (66%) at 12 months
Campbell et al. 20 Consecutive patients 14/20 (70%) at 1 month 18 months
(2013) [193] 16/20 (80%) at 3 months
Liu et al. (2013) 38 Transsphincteric 23/38 (61%) 26 months (range 3–44) Increased length of track associated with
[204] poorer healing
Van Onkelen et al. 22 Low transsphincteric 18/22 (82%) Median 19.5 months
(2013) [190]
Lehmann et al. (2013) 17 Recurrent transsphincteric 9/15 (60%) Median 13.5 months
[191]
The treatment of anal fistula (2018 update)

21
The treatment of anal fistula (2018 update) G. Williams et al.

postoperatively. An alternative approach is to de-roof

All fistulas were deemed unsuitable for


the fistula from internal opening to intersphincteric
groove and ligate the fistula track, while at the same
time preserving the external sphincter. This modified

No evidence of postoperative
LIFT was performed on a series 56 patients, with an
overall cure rate of 71%. True recurrence (5%) was
much less frequent than simple failure of the technique

No morbidity noted
and persistence of an active fistula track after the opera-
tion [202].
incontinence
laying open
Comments

LIFT has been used as treatment for recurrent fistu-


las [191]. Fifteen patients with recurrent transsphinc-
teric fistulas were followed up for 8–26 months
(median 13.5 months). At the end of follow-up, six
patients still had evidence of fistula, either persistence of
Median of 5 months

the original fistula (four patients) or recurrence (two


Mean healing time
Median 9 months
Median 22 weeks

patients). LIFT has also been used in selected patients


with Crohn’s disease, with 8 of 12 reported to be
was 4 weeks

healed at 12 months [200].


Follow-up

18 weeks

To conclude, to date there are a few randomized


studies as well as number of case series that attest to the
potential efficacy of LIFT. LIFT appears to be associ-
ated with less functional compromise than some tradi-
tional treatments of transsphincteric fistulas, although
recurrence/persistence rates are probably similar. One
in 17/25 (68%)

in 37/45 (82%)
Primary healing

Primary healing

of the advantages of the LIFT procedure is that of sec-


22/39 (56%)

17/18 (94%)
Healing rates

ondary success. Where a genuine downstaging of the


fistula from transsphincteric to intersphincteric takes
74–90%

place in a proportion of failures, allowing laying open of


this intersphincteric fistula, preserving the external
sphincter which would have been involved originally
[207]. Future work should focus on comparison with
Trans- and suprasphincteric
Unselected transsphincteric

standard treatments, paying particular attention to com-


Transsphincteric (n = 33)

(five recurrent fistulas)

paring similar fistulas and focusing on deeper fistulas,


Complex (n = 12)

where conventional treatments may be more problem-


Cryptoglandular

Transsphincteric

atic as regards functional outcome.


Types of fistula

Stem cell therapy. Autologous adipose-derived stem cells


may represent a novel treatment option for complex fis-
tulas, although as yet there is insufficient evidence to
attest to its efficacy. As a technique it may be used in
40 (41 procedures)

25 (10 recurrent)

isolation or in combination with fibrin glue or advance-


ment flaps. It has been used in patients with Crohn’s
disease. Allogeneic, expanded, adipose-derived stem
Number

cells have been used in a randomized, multicentre, dou-


ble-blind placebo-controlled study involving 212
39

45

18

patients [173]. The primary end-point was remission at


24 weeks. In the intention-to-treat analysis 53/107
Table 3 (Continued).

(50%) receiving stem cells achieved this, compared with


Rojanasakul et al.
Ooi et al. (2012)

36/105 (34%) in the placebo arm (P = 0.024). A sepa-


Shanwani et al.
(2012) [205]

(2010) [203]

(2010) [206]

(2007) [187]
Abcarian et al.

rate multicentre, single-blind trial randomized 200


Bleier et al.

patients to stem cells alone, stem cells in combination


Author

[199]

with fibrin glue or fibrin glue alone, following closure


of the internal opening [208]. There was no significant

22 Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31
G. Williams et al. The treatment of anal fistula (2018 update)

difference in healing rates between any of the groups, with a tightly applied metal clip. The most extensively
which were 40–50% at 12 months’ follow-up: no seri- investigated apparatus is the OTSC Proctology
ous adverse events were reported. A further small case (Ovesco Endoscopy AG, Tu72074 T€ ubingen, Ger-
series of seven patients reported healing rates of five out many), which employs a nitinol clip. A recent case-series
of seven at 6 months and four out of seven at a median has demonstrated healing in 18 of 20 (90%) fistulas at
of 46 months [209]. Long-term results of a Phase II 6 months [218]. This group consisted of 14 patients
trial in patients with Crohn’s disease reported healing with a transsphincteric fistula and 6 with suprasphinc-
rates of 75% at 24 months’ follow-up [210]. Recently teric fistulas, although details of the complexity of the
reported work looked at whether autologous mesenchy- tracks was not given. Two patients required removal of
mal stem cells could heal fistulas in Crohn’s disease if the clip as a result of delayed wound healing and dis-
applied in a bioabsorbable matrix [211]. At 6 months comfort. Another case-series of consecutive patients
10/12 patients had complete clinical healing. It is too from a single institution used the OTSC in refractory
soon to comment on the role of this complex treatment cases of anal fistula following previous surgery [219].
in the routine management of anal fistulas. Six of the 10 patients recruited had Crohn’s disease.
Seven patients’ fistulas were healed at a median follow-
Laser therapy. Laser therapy was described as a treat- up of approximately 8 months. The FISCLOSE trial is
ment option for anal fistula in the 1980s [212], and aimed at evaluating the efficacy and safety of a clip vs
more recently with a radial emitting laser probe [213], rectal mucosal advancement flap [220]. The aim is to
the principle being to destroy epithelial cells lining the recruit 46 patients to two centres. The primary out-
fistula track. It has been trialled in combination with come is healing at 3 months. Secondary outcomes
fibrin glue [214], although more recent work, using the include healing at 6 and 12 months, anal pain, faecal
laser in isolation, demonstrated healing in 9 of 11 incontinence and quality of life.
patients at a median of 7.4 months [213]. In this study, In a similar way to laser ablation, clipping the inter-
the internal opening was closed using a flap in combina- nal opening of a fistula is at an early stage of evolution,
tion with laser ablation. A further larger study, recruit- with a few encouraging case series having been pub-
ing 45 patients, found healing in 32 (71%) at a median lished (Level II/III evidence). Migration and pain,
of 30 months [215]. All patients underwent placement requiring removal of the clip at the request of patient,
of a loose seton prior to surgery, and 35 patients had a are significant risks that have been reported in the few
history of previous fistula surgery. A retrospective review studies which have been reported. Further larger stud-
of 50 patients treated by laser ablation showed ‘success’ ies, especially randomized trails against other sphincter-
in 41 (82%) at 12 months’ follow-up [216], which was preserving techniques, are required to establish whether
mostly by phone, consequently these results need inter- it has role in treatment of anal fistulas.
preting with caution. Wilhelm et al. [217] reported a
series of 117 patients treated with the radial fibre fistula Video-assisted anal fistula treatment. Video-assisted anal
laser closing (FiLaCTM) device. Patients in this series fistula treatment (VAAFT) consists of a diagnostic and a
were followed for a median of 25 months (minimum therapeutic phase. In the former, a fistuloscope and
6 months) with primary healing in 64% of patients. A obturator are used to identify the internal opening as
repeat procedure was performed in 31 patients who well as any secondary tracks and/or abscesses. The
failed initial treatment, with overall healing achieved in scope is inserted through the external opening and a
88% of patients. The treatment was associated with min- glycine-mannitol solution infused to enable opening of
imal alteration in anal control. the primary track and advancement under direct vision.
At present, laser ablation of a fistula track is in its The therapeutic phase involves destruction and cleaning
infancy, with evidence supporting its use confined to of the track using cautery and further irrigation. One of
a few case series (Level II/III evidence). The best the principles is closure of the internal opening using a
technique has not been established: for instance, is circular/linear stapler, OTSC or advancement/mucosal
surgical closure of the internal opening necessary prior flap. Cyanoacrylate may be used to reinforce the closure
to laser ablation? Further larger studies, especially ran- of the internal opening, though the track must be left
domized trails against other sphincter-preserving tech- open to allow secretions to drain.
niques, are required to establish its role in treatment Work from Italy reported on 136 patients undergoing
of anal fistulas. VAAFT over a 5-year period [221]. Ninety-eight patients
were followed up for a minimum of 6 months. Primary
Fistula clips. The principle of this technique is to deb- healing occurred in 72 (73%) patients within 2–
ride the primary track and close the internal opening 3 months of surgery, with no major complications seen.

Colorectal Disease ª 2018 The Association of Coloproctology of Great Britain and Ireland. 20 (Suppl. 3), 5–31 23
The treatment of anal fistula (2018 update) G. Williams et al.

Sixty-two patients were followed up for over a year, with common and are to be welcomed. As well as focusing
healing noted in 52 (84%). A further study from Singa- on surgical end-points (healing, alteration in anal con-
pore reported on 41 patients treated with VAAFT [222]: trol, etc.) future trials should also include data on
all were cryptoglandular in aetiology, though low inter- patient-reported outcome measures.
sphincteric fistulas and patients with abscesses were
excluded. A number of approaches were used to obliter-
ate the internal opening – stapling, advancement flap and
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