Keywords anal fistula - seton - LIFT - intersphincteric
Introduction
The aim of surgery for anal fistula is to eradicate local septic foci and promote
healing of the fistula tract while preserving adequate anal continence. The treatment
of complex anal fistula, considered as those not solved with a simple fistulotomy,
still represents a major surgical challenge. Several surgical techniques have been
described, albeit the vast majority associate fair-moderate healing rates.
In 2007, Rojanasakul described a new sphincter-preserving technique, ligation of the
intersphincteric fistula tract (LIFT),[1 ] modifying a classical surgical approach, the intersphincteric via, previously described
in 1993.[2 ] The procedure is aimed at the cryptoglandular source of infection within the intersphincteric
space.
The LIFT procedure has gained popularity in the last decade for its low-complexity,
easy-to-learn technique and high definitive healing rate reliably exceeding 70%, with
little impact on anal continence.[3 ]
[4 ]
[5 ] In addition, approximately one third of recurrences occur in the form of an intersphincteric
fistula, which represents a downstage in complexity, transforming the initial challenging
anal fistula surgery into a second manageable intervention.[6 ]
The LIFT technique is based on the dissection and ligation of the fistulous tract
in the intersphincteric plane, for which consistent tissues and the absence of abscesses
in this space are necessary. For this reason, some authors have recommended the placement
of a seton prior to the LIFT procedure as a bridge therapy, with the intention of
increasing fibrosis and the consistency of the fistulous tract, in addition to removing
collections within the intersphincteric space.[7 ]
[8 ]
In the absence of randomized studies on the usefulness of a seton as a bridge to the
definitive LIFT procedure in the treatment of complex anal fistula, we performed a
systematic review of the published literature with the aim of answering the following
specific question according to the problem, intervention, and comparison (PICO) framework:
compared with patients who undergo a direct LIFT procedure for fistula-in-ano, do
patients who undergo seton placement as a bridge to a deferred LIFT procedure have
a better success rate?
Methods
A systematic review of the literature was performed following the Meta-analyses Of
Observational Studies in Epidemiology (MOOSE) recommendations[9 ] (Appendix A ).
Data Sources and Search Strategy
A systematic search of standard electronic databases, including MEDLINE (PubMed),
EMBASE, Web of Science, Cochrane Library and Google Scholar, was conducted for pertinent
studies. In addition, the bibliographic references from selected studies were examined
as a further search tool to find additional articles. Articles in all languages were
considered for inclusion. A combination of MeSH terms and keywords was used to identify
the target studies: LIFT OR ligation of intersphincteric fistula tract AND seton OR sedal AND anal fistula OR fistula-in-ano . The last search was performed on December 15, 2019.
Eligibility Criteria
Four reviewers (C. P. G., I. A. A., T. P. B., and Y. S. A.) independently screened
the literature according to the inclusion and exclusion criteria. The defined inclusion
criteria for full review included: 1) studies analyzing LIFT procedure, including
patients with preoperative seton placement, and reporting outcomes on healing rate
and recurrence 2) definitions of fistula definitive healing and treatment failure
were specified in the study. According to the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) guidelines, the predetermined exclusion criteria
were: 1) study population smaller than 20 patients; 2) patients with anal fistula
and Crohn disease; 3) modified LIFT procedures (BIO-LIFT, LIFT with anal flap, etc.);
and 4) follow-up of less than 3 months. Discordant views were managed by review of
original sources and discussion.
Data Extraction
We developed a data abstraction tool to capture the following data from each study:
the names of the authors, title of the study, journal in which the study was published,
country and publication date, study design, sample size, age and gender of the patients,
follow-up time, percentage of recurrence and/or cure with and without seton use. Several
authors were contacted and required to supply additional information for completion
of data quantitative analysis.[10 ]
[11 ] A proportion of authors were contacted but no response was obtained (Appendix B ).
Quality and risk of bias assessment in individual studies
Each study was independently appraised by two investigators (I. A. A. and T. P. B.)
using the Newcastle-Ottawa Scale (NOS)[12 ] for non-randomized studies. We performed the evaluations according to the three
main items of study population selection , comparability and “assessment
of
outcomes . A study can be awarded a maximum of four stars for selection, two stars for comparability and three stars for outcome categories. The studies were grouped in terms of good quality, weak quality, and
poor quality, according to the Agency for Health Research and Quality (AHRQ).[13 ] If discrepancies were present, a consensus was reached by soliciting the help of
a third author (C. P. G.).
Data synthesis and statistical analysis
Statistical analysis was performed with Review Manager (RevMan) v. 5.3 (Copenhagen:
The Nordic Cochrane Center, Copenhagen Denmark). The odds ratios (ORs) were calculated
from the original data. Values were expressed with a 95% confidence interval (CI).
Heterogeneity among the included studies was qualitatively evaluated using chi-squared
test based on the Q test. A p -value < 0.05 showed that there was no significant heterogeneity between the studies.
The level of heterogeneity between the studies was calculated using the I2 statistic. An I2 < 30% was considered to define low heterogeneity. Given the homogeneity of the included
data, according to I2 test, the Mantel-Haenszel (M-H) method and the fixed-effects model were used for
the quantitative analysis of the dichotomous variables. In addition, a sensitivity
analysis was performed by clustering the studies according to the number of patients
included and according to the NOS quality. The presence of publication bias was assessed
using a funnel plot and the Begg and Egger tests.
Results
A systematic search of the literature was conducted from the date of description and
publication of the LIFT surgery in March 2007 until December 2019. After review of
the title and abstract, 49 articles were fully assessed for eligibility, and, finally,
10 studies, representing a total study population of 772 patients, were included for
qualitative and quantitative analysis ([Fig. 1 ]).[6 ]
[10 ]
[11 ]
[14 ]
[15 ]
[16 ]
[17 ]
[18 ]
[19 ]
[20 ] The median age of the included patients was 44 years, and the female/male ratio
was 23%/77%.
Fig. 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses Flow chart of
the study selection.
Most of the excluded studies had a small sample size (< 20 patients), an absence of
differential or stratified outcomes data between those in whom a seton was placed
prior to LIFT procedure and of those who did not. A small number of studies that included
mixed modified LIFT techniques (Bio-LIFT, associated flaps, etc.) or also included
patients with anal fistula in Crohn disease. All the included studies were retrospective,
such as cohort studies or case series, and comprehended patients treated between 2007
and 2016. Half of the included studies were from the USA. The median number of patients
per study was 44 (R.I. 35–76). The median follow-up was greater than 1 year in all
studies except in 2, both reporting a median follow-up time of more than 3 months.[16 ]
[18 ] The majority of the included patients were diagnosed with trans-sphincteric fistulas,
although some cases of recto-vaginal and posterior horseshoe fistulas were also considered
([Tables 1 ] and [2 ]). All papers contained a definition of the complete fistula healing and treatment
failure criteria. However, few studies assessed the potential impact on continence
impairment or complications related to the use of setons.
Table 1
Characteristics of the included studies and patients
Author
Country
Year
Study design
Center(s)
Duration
Pacients
Age
Gender (F/M)
Follow-up (months)
NOS
AHRQ
Espin
Spain
2011
Retrospective
Single center
?
29
49 (26–83)
16/13
18 26–83)
4
Fair
Wallin
USA
2012
Retrospectivee
Multicenter
2007–2011
93
43(21–76)
36/57
19 (44–55)
6
Fair
Liu
USA
2013
Retrospective
Single center
2008–2011
38
42
10/28
26 (3–44)
3
Poor
Wang
USA
2013
Retrospective
Single center
2011–2012
71
41 (18–71)
16/55
4(2–13)
5
Fair
Ye
China
2014
Retrospective
Multicenter
2012–2013
41
45 (17–59)
15/28
15 (12–24)
4
Fair
Sileri
Italy
2014
Retrospective
Multicenter
2010–2012
26
41 (30–65)
10/16
20 (16–24)
6
Fair
Hall
USA
2014
Retrospective
Multicéntrico
2011–2013
43
45 (31–59)
?/?
3
3
Poor
Placer
Spain
2017
Retrospective
Single center
2008–2016
55
46 (34–61)
24/31
32 (6–51)
7
Good
Sugrue
USA
2017
Retrospective
Multicenter
2005–2015
241
46 (18–78)
?/?
9 (1–125)
7
Good
Vander M.
Netherlands
2019
Retrospective
Single center
2013–2015
45
40 (24–67)
28/17
12 (6–24)
5
Fair
Abbreviations: AHRQ, Agency for Health Research and Quality; NOS, Newcastle-Ottawa
scale.
Table 2
Outcome of the LIFT procedure in the studies reviewed
Autor
Patients (N)
Fistula class
Recurrence
N (%)
Seton/No seton
Recurrence with seton N (%)
Recurrence without seton n (%)
Complications
Seton/No Seton
Espin
29
Transsphincteric
10 (35)
24/5
8 (33.3)
2 (40)
?/?
Wallin
93
?
56 (60)
70/23
44 (63)
12(52)
?/?
Liu
38
?
15 (38)
29/9
11 (38)
4 (44)
?/?
Wang
71
?
9 (12.7)
18/53
3 (16.6)
6 (11.3)
1/1
Ye
41
Transsphincteric
11 (27)
4/37
0 (0%)
11 (26.8)
0/0
Sileri
26
Trans/RV/horseshoe
7 (27)
5/21
2 (40)
5 (24)
?/?
Hall
43
Trans/RV/horseshoe
9 (21)
30/13
8 (26.6)
1 (7.7)
9
Placer
55
Trans/Supra
16 (29)
12/43
2 (16.6)
14 (32.5)
0/0
Sugrue
241
Transsphincteric
103 (42.7)
148/93
64 (51.2)
39 (51.3)
?/?
Vander
45
Trans/ano-vaginal
27 (60)
32/13
19 (59.3)
8 (61.5)
0/0
The qualitative assessment of the included studies in the analysis displayed a weak-quality
level according to the NOS tool. Furthermore, the AHRQ classification tool showed
two studies of good quality, two of poor quality, and eight of weak quality (Appendix C ).
There were no significant differences in fistula recurrence rate between patients
with and without seton placement before LIFT surgery (OR 1.02; 95%CI 0.73–1.43: p = 0.35). The I2 value was 9%, expressing high homogeneity of results among the selected studies.
The quantitative analysis of the included studies showed a weighted average of overall
recurrence of 38% (IQR 27–42.7%). Overall recurrence rate in patients with previous
seton placement was 40% (IQR 26.6–51.2%), in contrast to a 51.3% (IQR 31.3–51.3%)
recurrence rate in patients without prior seton use ([Fig. 2 ]).
Fig. 2 Forest plot for success with and without seton.
A sensitivity analysis was performed according to the number of patients included
in each selected study (more or less than 50 patients) and also stratified by the
NOS quality rating of analyzed studies. None of the compared subgroups showed advantages
with the use of a seton in terms of the healing or recurrence rates ([Figures 3, b, c, d ]). Publication bias was also assessed and reported using a funnel plot ([Fig. 4 ]). In addition, Begg (Z = 1.1657; p = 0.441) and the Egger (t = −0.8014, p = 0.441) tests were also performed for publication bias evaluation. All three tests
showed an absence of significant bias, which is consistent with the high homogeneity
found in the results of the included studies.
Fig. 3 Analysis of sensitivity forest plot. (a) Forest plot for success according to number
of patients (> 50 patients). (b) Forest plot for success according to number of patients
(< 50 patients). (c) Forest plot for success according to the Newcastle-Ottawa scale
(good quality). (d) Forest plot for success according to the Newcastle-Ottawa scale
(fair/poor quality).
Fig. 4 Funnel plot to assess publication bias.
Discussion
The present systematic review and meta-analysis shows that prior placement of a seton
as a bridge therapy to perform a definitive LIFT surgery for fistula-in-ano does not
seem to improve the long-term outcomes of the technique. However, the inherent risk
of bias of the included non-randomized studies should be considered when interpreting
the results.
The proposal of addressing the intersphincteric space as a surgical approach for anal
fistula surgery is already established as a result of the cryptoglandular infection
theory defining the source of most anal fistulas. In 1993, Matos et al. published
a series of 13 cases (8 high trans-sphincter and 5 suprasphincteric fistulas) in which
7 out of 13 cases experienced complete healing of fistula (54%) after a median follow-up
of 22 months (4–33).[2 ] Despite not having great diffusion, in 2007, Rojanasakul resumed the idea and described
a modified surgical technique, nowadays known as the LIFT procedure.[1 ]
To perform effective ligation of the intersphincteric tract, the existence of a mature
fistula tract and the absence of secondary tracks or active suppurative local septic
foci are mandatory. Thus, to obtain a more fibrous and consistent tract, some authors
have suggested the placement and maintenance of a non-cutting seton for a few weeks
prior to the definitive ligation of the fistulous tract.[15 ]
[21 ]
[22 ]
[23 ] However, some studies question the idea of the seton favoring the development of
a more consistent fistulous tract path.[7 ]
[24 ] Furthermore, in the original series of Rojanasakul, with more than 250 patients,
the use of a previous seton was not mentioned.[25 ]
The effect produced by a loose seton on the orifices and the tract of a fistula-in-ano
has been poorly documented. Mitalas et al. did not found a relationship between the
placement of a seton and the presence or development of epithelium in the fistulous
tract.[26 ] Moreover, curettage of the fistulous tract is considered a routine gesture before
the placement of a seton in fistula surgery, with the elimination of the epithelium
within the fistulous tract being one of the main purposes. However, the need to eliminate
nests of epithelial cells is still debated.[27 ] In addition, some studies have questioned this maneuver because of the risk of creating
additional secondary fistula tracts or false passage into the anal canal,[17 ] and because of the possible enlargement of internal fistulous orifices.[28 ] Moreover, only 2 studies have stratified their results according to the use of a
seton, with sample sizes of 71 and 43 patients, and found a similar percentage of
recurrence with and without seton use.[16 ]
[18 ]
Most of the studies included in the present meta-analysis showed that the placement
of a seton prior to the LIFT procedure had no effect on the outcome in terms of definitive
healing or recurrence rates of anal fistula. For many years, the use of seton prior
to LIFT surgery for fistula-in-ano has been a highly controversial subject. Sileri
et al. attributed worse results to the use of setons because of the possibility of
creating false tracts.[17 ] Tan et al. also reported worse results in their retrospective study including 24
patients who had a seton before the definitive LIFT procedure. The authors argued
that the healing of the inflammatory process around the seton could obliterate the
intersphincteric space, making subsequent dissection difficult and increasing the
risk of anal canal mucosa damage.[29 ] However, the same authors recommended the use of setons for selected cases, such
as in high transsphincteric or suprasphincteric fistulas, due to the downstaging effect
of the fistulous tracts. In contrast, Ye et al. recommended removing the seton before
LIFT surgery to maintain the integrity of the internal fistulous orifice.[19 ] Likewise, additional authors have supported the use of a seton as bridge treatment
for definitive LIFT procedure, considering the potential downstaging and shortening
of the fistulous tract, whose length could constitute a risk factor for recurrence.[15 ]
[30 ] Aboulian et al. also recommended the use of a seton as a bridge to surgery, but
only in the presence of a septic foci (i.e., abscess) and for a period of less than
8 weeks.[31 ]
The main weakness of the present study is the absence of randomized controlled trials
(RCTs) in the literature; therefore, the available studies were not designed to analyze
the specific role of seton placement in the LIFT procedure. Furthermore, since these
were not randomized studies, the fact that some LIFT procedures would have to be abandoned
due to the impossibility of making a good ligation of the fistulous tract due to the
lack of consistent tissue cannot be ruled out. Thus, these cases might not have been
included in the analyzed studies.
However, the exhaustive bibliographic search and the fulfilment of defined inclusion
and exclusion criteria allowed to obtain a highly representative study population
with homogeneous results that yielded, in the absence of RCTs, consistent and repeated
conclusions. In the absence of prospective, randomized studies, the current study
represents the first meta-analysis addressing the specific role of seton in LIFT surgery.
Conclusion
Seton as a bridge treatment prior to LIFT surgery does not significantly improve long-term
anal fistula healing outcomes. Ligation of the intersphincteric fistula tract surgery
can be performed safely and effectively with no previous seton placement. However,
the inherent bias of non-randomized retrospective studies should be considered for
results interpretation. Thus, additional prospective studies are required to clarify
the role of previous seton placement in LIFT surgery for fistula-in-ano.
