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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1056_Библиотеки_им_академика_М_И_Перельмана.pdf
376 I. E. Gecim
Steele SR, Kumar R, Feingold DL et al (2011) Practice parameters for the management of perianal
abscess and fistula-in-ano. Dis Colon Rectum 54:1465–1474
Stellingwerf ME, van Praag EM, Tozer PJ, Bemelman WA, Buskens CJ (2019 Jun) Systematic
review and meta-analysis of endorectal advancement flap and ligation of the intersphincteric
fistula tract for cryptoglandular and Crohn’s high perianal fistula. BJS Open 3(3):231–241
Tan K-K, Tan IJ, Lim FS, Koh DC, Tsang CB (2011) The anatomy of failures following the ligation
of intersphincteric tract technique for anal fistula: a review of 93 patients over 4 years. Dis Colon
Rectum 54(11):1368–1372
Tan KK, Alsuwaigh R, Tan AM, et al (2012) To LIFT or to flap? Which surgery to perform
following seton insertion for high anal fistula? Dis Colon Rectum 55:1273–7
van der Hagen SJ, Baeten CG, Soeters PB, van Gemert WG (2006) Long-term outcome following
mucosal advancement flap for high perianal fistulas and fistulotomy for low perianal fistulas:
recurrent perianal fistulas: failure of treatment or recurrent patient disease? Int J Color Dis 21(8):
784–790
Visscher AP, Schuur D, Roos R, Van der Mijnsbrugge GJ, Meijerink WJ, Felt-Bersma RJ
(2015 May) Long-term follow-up after surgery for simple and complex cryptoglandular fistulas:
fecal incontinence and impact on quality of life. Dis Colon Rectum 58(5):533–539
Wallin UG, Mellgren AF, Madoff RD, Goldberg SM (2012) Does ligation of the intersphincteric
fistula tract raise the bar in fistula surgery? Dis Colon Rectum 55:1173–8
Anal Fistula: Glue and Paste Injection
24
Klaus E. Matzel and Birgit Bittorf
Contents
1 Introduction . ............... .................................................................. 378
2 Fibrin Glue ..... ............................. ............................ .................... 378
3 Collagen Paste ... . ................................... ........................................ 386
4 Conclusion ................................................................................... 388
5 Cross-References .......................... ............................................. ..... 388
References ............................ ............................................... ............ 389
Abstract
The use of glue or paste as a sealant for anal fistula is an attractive treatment
concept, as it can effect closure without jeopardizing fecal continence or inter-
fering with potential future interventions. Multiple substances have been explored
in the past, with fibrin glue and collagen paste being the most recent. This chapter
presents the findings of non-randomized controlled studies with ≥25 patients and
available randomized controlled trials. Evidence for the clinical effectiveness of
fistula closure with fibrin glue is low; for collagen paste, data are even fewer.
Available information is heterogeneous with regard to indication, outcome mon-
itoring, and assessment. Study methodology varies widely. Randomized trials
with fibrin glue indicate that the clinical benefit is limited. Despite this, the
therapeutic concept of fistula closure with glue and paste remains of interest
because of its very low invasiveness.
Keywords
Anal fistula · Paste · Glue · Anal fistula sealing
K. E. Matzel (*) · B. Bittorf
Department of Surgery, University Erlangen, Erlangen, Germany
e-mail: Klaus.Matzel@uk-erlangen.de
© Springer Nature Switzerland AG 2022
C. Ratto et al. (eds.), Anal Fistula and Abscess, Coloproctology,
https://doi.org/10.1007/978-3-030-76670-2_26
377
378 K. E. Matzel and B. Bittorf
1 Introduction
The aim of anal fistula treatment is twofold: to remove the fistula tract and to
preserve continence function. Over the years, multiple techniques have been advocated: some declined in popularity, and several remained as part of the current
surgical armamentarium. The fact that there are still several techniques not only
reflects the complexity of the condition, but also indicates that no perfect solution
has yet been found.
Conceptually, filling a fistula tract with foreign material offers several advantages:
It closes the fistula tract in a technically easy manner; and the anal sphincter complex
is not damaged (or, if so, in a very limited way), thus reducing the risk of postinterventional fecal incontinence. Also, the impact on potential further interventions
is minimal.
Since decades, various substances have been applied as paste or glue installations.
Some have been used as an element of a combined technique, such as mucosa
advancement flap. Regardless of the substance applied, the operative intervention
commonly starts after the control of sepsis with a thorough removal of the epithelium
in the fistula tract, granulation tissue, and debris (also seton removal if it had been
placed earlier for drainage and to decrease inflammatory activity). Most commonly,
curettage is used for epithelium removal and debridement. The handling of the inner
fistula opening after filling varies: techniques used for closing differ.
Certain filling substances, such as Cyanoacrylat and BioGlue
serum albumin [BSA] and glutaraldehyde) (Barillari et al. 2006; Jain et al. 2008;de
la Portilla 2008), can be considered historic; fibrin glue and collagen paste are
treatment options of current interest.
®
(purified bovine
2 Fibrin Glue
Since the first description of fibrin glue for the treatment of anal fistula in the early
1990s (Hjortrup et al. 1991; Abel et al. 1993), multiple studies have be en published,
and no significant difference has been demonstrated between commercially available
and autologous fibrin glue (Park et al. 2000). The design of the studies varies (see
Table 1 for reports with more than 25 patients (Cintron et al. 1999; Cintron et al.
2000; Patrlj et al. 2000; Sentovich 2001; Jurczak et al. 2004; Gisbertz et al. 2005;
Singer et al. 2005; Maralcan et al. 2006; Ellis and Clark 2006; Witte et al. 2007;
Tyler et al. 2007; Adams et al. 2008; van Koperen et al. 2008; de Parades et al. 2010;
Garcia-Olmo et al. 2009; Altomare et al. 2010; Queralto et al. 2010; Yeung et al.
2010; de Oca et al. 2011; Maralcan et al. 2011; Herreros et al. 2012; Mishra et al.
2013; Cestaro et al. 2014)), the majority being retrospective (N ¼ 10), several
prospective (N ¼ 8), and some randomized and comparative (N ¼ 4). Follow up
ranges from 3.5 to 54 months.
The inclusion criteria vary: Most of the studies include simple and complex
fistulae. Rectovaginal fistulae are mentioned in 3 and Crohn’s fistula in 6. Outcome
reporting differs significantly: Although all studies report on fistula healing (with
24 Anal Fistula: Glue and Paste Injection 379
Follow-up(months)
Impaired
continence
(%)
Recurrence
(%)
Prospective 61 (I: 82; II:62) n.a. n.a. 12
(18–36)
Retrospective A: 21; B: 40; 31 n.a. 0 27
n.a. n.a. 12
75)
n.a. 7
n.a.;
(continued)
2x abscess
54
Table 1 Results of fibrin glue installation in studies with 25 patients*
et al. 1999)
(12/76)
2000 76 I–IV 16
Cintron (Cintron
et al. 2000)
Crohn‘s
(%) Study design Healing (%)
1999 26 I, II, III 8 (2/26) Prospective 81 n.a. n.a. 3.5
Cintron (Cintron
Study Year N Fistula type
2000 69 I, II 0 Retrospective 74 (I: 77; II: 70) n.a. n.a. 28
Patrlj (Patrlj et al.
10 Prospective 60 10 (3/29) 0 22 (6–48)
2003 48 Simple/
2000)
Sentovich (Sentovich
complex
2004 31 II, III n.a. Retrospective 75 n.a. 0 9
2001)
Jurczak (Jurczak
et al. 2004)
2005 27 I, II 0 Retrospective 33 n.a. 0 6
2005 75 n.a. 12.5
Gisbertz (Gisbertz
et al. 2005)
Singer (Singer et al.
(2/24)
2006 36 I, II, III 0 Prospective 78 (I: 44; II: 91; III:
2005)
Maralcan (Maralcan
Yes n.a. Simple 56; complex
I-IV
2006 28 n.a. 0 Randomized 54 n.a. n.a. 22
2007 34 Subcutaneous,
2007 89 II, III 0 Retrospective 55 n.a. n.a. n.a.
et al. 2006)
Ellis (Ellis and Clark
2006)
Witte (Witte et al.
2007)
Tyler (Tyler et al.
2007)
380 K. E. Matzel and B. Bittorf
Follow-up(months)
Impaired
continence
(%)
Recurrence
(%)
16 (4/25) n.a. n.a. 38
Multicenter
(21–43)
n.a. n.a. 5.2 (1–16)
Retrospective Crohn’s: 0
High fistula: 28.6
(8/28)
Simple fistula: 41.7
(5/12)
37 0 54
Longterm: 63 (after
repeated injections)
Crohn‘s
Table 1 (continued)
(%) Study design Healing (%)
Study Year N Fistula type
2008 36 II 0 Retrospective 66 6 n.a. 6
Adams (Adams et al.
7.5
(3/40)
pouch-vaginal
2008 26 II (distal) 0 Retrospective 44 n.a. n.a. 13
2010 29 I, II, III, RVF 0 Retrospective 56 15 n.a. 12
2008)
Van Koperen (van
Koperen et al. 2008)
De Parades
(de Parades et al.
2010)
2009 25 II, III, RVF 29 Randomized
Garcia-Olmo
(Garcia-Olmo et al.
2010 38 II 0 Randomized 39 n.a. 0 12
2009)
Altomare (Altomare
2010 34 II, III 0 Retrospective 68 n.a. 0 34
2010 40 I, II, III, RVF,
et al. 2010)
Yeung (Yeung et al.
Queralto(Queralto
et al. 2010)
2011 28 II 0 Prospective 68 n.a. 0 20 (3–60)
2011 46 II, III 0 Prospective 87
2010)
De Oca (de Oca et al.
2011)
Maralcan (Maralcan
et al. 2011)
24 Anal Fistula: Glue and Paste Injection 381
n.a. 0 6
High: 57
n.a. Prospective Low: 81
2012 56 II, III 0 Randomized 37 n.a. n.a. 12
2013 30 II, III,
Herreros (Herreros
et al. 2012)
Mishra (Mishra et al.
recurrence
2014 26 I, II 0 Prospective 69 23 0 12
2013)
Cestaro (Cestaro
et al. 2014)
aAdapted from reference (Ommer et al. 2017), n.a. not available, RVF rectovaginal fistula
382 K. E. Matzel and B. Bittorf
Follow-up
(months)
Continence
impaired
(%)
Recurrence
(%)
Study
design Healing (%)
n.a. 0 17.1
(5.7–21.6)
Fibrin glue 50 (3/6),
conventional 100 (7/7),
p ¼ 0.06
Complex fistulas:
Fibrin glue 69 (9/13)
Conventional 13 (2/16)
p ¼ 0.003
n.a. n.a. 3.5
Bioprosthetic plug
87 (2/15)
p < 0.05
n.a. n.a. 22
(12–36)
glue 54
Flap alone 80
p < 0.05
n.a. n.a. 2
Fibrin glue 16 (4/25)
Fibrin glue + adipose-
derived stem cells
Multicentric
71 (17/24)
p < 0.001
n.a. 0 12
049
60
Seton 88 (21/24)
p ¼ 0.0007
(29–59)
20
Advancement flap
Table 2 Results of fibrin glue installation in randomized trials
N
M. Crohn
(%)
Fistula
type
glue)
(fibrin
Author Year
2002 19 I, II, III Yes Randomized Simple fistulas:
Lindsey (Lindsey
et al. 2002)
2006 10 II 0 Randomized Fibrin glue 40 (4/10)
Johnson (Johnson
et al. 2006)
2006 28 n.a. 0 Randomized Advancement flap + fibrin
Ellis (Ellis and
29 Randomized
RVF
2009 25 II, III,
Garcia-Olmoa
(Garcia-Olmo et al.
Clark 2006)
2009)
2011 38 II 0 Randomized Fibrin glue 39 (15/38)
Altomare (Altomare
et al. 2010)
2011 15 II, III 0 Randomized Fibrin glue 40 (6/15)
2000)
Van der Hagen
(Park et al.
24 Anal Fistula: Glue and Paste Injection 383
024
7/12
80 (3/15)
p ¼ 0.03
n.a. n.a. 12
Adipose-derived stem
cells + fibrin glue 52
Stem cells 57
p ¼ 0.13
n.a. 0 12
42, partial 17)
Platelet-rich plasma
71 (complete 48, partial
23)
p ¼ 0.608
1/11
Adipose-derived stem
cells 50
p ¼ 0.129
2012 56 II, III 0 Randomized Fibrin glue 37
Herreros (Herreros
et al. 2012)
2019 24 I, II, III 0 Randomized Fibrin glue 58 (complete
de la Portilla (de la
Portilla et al. 2019)
0 Randomized Fibrin glue 26
IV
2020 21 II, III,
Garcia-Arranz
(Garcia-Arranz et al.
2020)
n.a. not available
384 K. E. Matzel and B. Bittorf
varying definitions) and provide length of follow-up, recurrence is only addressed in
5 and continence function in 10. The substance application is not uniform: Some
authors report repeated applications in cases of initial treatment failure.
Overall, the studies show a highly variable outcome, with healing rates in
cryptoglandular fistulae between 21% and 87% (long-term 63%), recurrence of
10 to 37%. (Impaired continence is not found but is more often not reported.)
A few randomized studies compare fibrin applications with other anal fistula
therapies (see Table 2 (Ellis and Clark 2006; Garcia-Olmo et al. 2009 ; Altomare et al.
2010; Herreros et al. 2012; Lindsey et al. 2002; Johnson et al. 2006; van der Hagen
et al. 2011; de la Portilla et al. 2019; Garcia-Arranz et al. 2020)): fibrin glue versus
conventional fistula treatment (e.g., fistul otomy or loose seton insertion with or
without subsequent advancement flap (Lindsey et al. 2002)); fibrin glue versus
anal suturable bioprosthetic fistula plug (Johnson et al. 2006); flap repair with fibrin
glue versus flap repair alone (Ellis and Clark 2006); fibrin glue alone or fibrin glue
plus 20 million expanded adipose-derived stem cells (ASCs) (Garcia-Olmo et al.
2009); fibrin glue versus cutting seton application (Altomare et al. 2010); fibrin glue
with and without closure of the internal fistula opening versus a mucosal advancement flap (van der Hagen et al. 2011); stem cells versus stem cells plus fibrin glue
versus fibrin glue alone (Herreros et al. 2012); autologously prepared platelet-rich
plasma versus fibrin glue alone (de la Portilla et al. 2019); ASCs plus fibrin glue
versus fibrin glue alone (Garcia-Arranz et al.
2020).
In a randomized comparative study, patients with simple (low fistulae) and
complex fistulae (high, Crohn’s, and low with compromised sphincter) underwent
either fibrin glue or conventional treatment consisting of fistulotomy or loose seton
insertion with or without subsequent advancement flap (Lindsey et al. 2002). At a
median follow-up of 17 months, fistula healing after primary fibrin glue was
observed in 42% (8/19). In five cases of second fibrin glue application after evaluation at 3 months, the healing rate was 80% (4/5). A cumulative success with one or
two fibrin applications was achieved in 63% (12/19). In simple fistulae, healing after
fibrin glue application was 50% (3/6), 100% (7/7) after fistulotomy (difference, 50%;
confidence interval, 10% to 90%; P < 0.06). The healing rate in complex fistulae was
69% (9/13), after conventional treatment 13% (2/16) (difference, 56%; 95% confidence interval, 25.9% to 86.1%; P < 0.003). No changes in baseline incontinence
score, maximum resting pressures, or squeeze pressures were found in either study
arm. Patient satisfaction was higher in the fibrin glue group.
A randomized comparison of fibrin glue and anal suturable bioprosthetic fistula
plug (Surgisis, Cook Surgical, Inc.) that included 25 patients (10 fibrin glue,
15 fistula plug) with high transsphincteric fistulae revealed that, at a follow-up of
3 months, 60% of the fibrin glue group had persistence of one or more fistulae versus
13% (2/15) in the plug group (P < 0.05) (Johnson et al. 2006).
The study comparing the combination of flap repair and fibrin glue versus flap
repair alone in a randomized setting (Ellis and Clark 2006) included 58 patients. An
anodermal advancement flap was performed in 22, a mucosal advancement flap in
36; 30 patients were treated with flap alone, and 28 with a combination of flap and
fibrin glue. In the latter group, 17 patients underwent mucosal advancement
flap, and
24 Anal Fistula: Glue and Paste Injection 385
11 anodermal advancement flap. At a median follow-up of 22 months, the fistula
recurrence rate in all the 58 patients was 32.6%, with a 20% (6/30) recurrence rate for
fistulae repaired with advancement flap alone and 46.4% (13/28) for fistulae repaired
by advancement flap with fibrin glue (P < 0.05).
In a randomized comparison of treatment of complex perianal fistulae (both
cryptoglandular [N ¼ 35] and associated with Crohn’s disease [N ¼ 14]) with fibrin
glue or fibrin glue plus 20 million expanded ASCs (Garcia-Olmo et al. 2009), fistula
healing at 8 weeks’ follow-up was found in 71% of patients (17/24) treated with
fibrin glue plus ASCs and in 16% of patients (4/25) who received fibrin glue alone
(P < 0.001). At 1 year, the recurrence rate in patients treated with ASCs was 17.6%.
In cases of persistent fistula at 8 weeks, a second dose of fibrin glue or fibrin glue
plus 40 million ASCs was applied. The healing rate was similar in patients with
Crohn’s disease and those with cryptoglandular fistulae. Quality of life scores were
higher in patients who received fibrin glue with ASCs.
In a comparison of patients with medium or high transsphincteric cryptoglandular
anal fistulae randomized to fibrin glue (N ¼ 38) versus cutting seton (N ¼ 25), a
minimum follow-up of 1 year demonstrated a healing rate of 88% in the seton group
and 39% in the fibrin glue group (P ¼ 0.0007) (Altomare et al. 2010). In case of
nonhealing patients, they were again randomized to seton treatment (N ¼ 15) or
fibrin glue (N ¼ 8). Overall healing rate for seton treatment was 74%, for fibrin glue
38%. Incontinence increased from 6 to 15 patients in the seton group (Mean
Cleveland Clinic Incontinence score 1.79 4.4 to 5.1 5.9 [P ¼ 0.0017]); no
significant changes in continence were seen after fibrin glue treatment. In the
23 patients in whom fibrin glue had failed, randomization to a second fibrin glue
injection (N ¼ 8) or seton treatment (N ¼ 15) was undertaken. Subsequent healing
was 50% in the fibrin group (4/8) and 60% (9/15) with seton use.
In a randomized study comparing fibrin glue (N ¼ 15) with a mucosal advancement flap (N ¼ 15) in complex cryptoglandular fistulae, the recurrence rate in the
group with mucosal advancement flap after seton drainage was 20% (3/15) at a
median follow-up of 52 months (26–60 months) and 60% (9/15) in the group with
fibrin glue after seton drainage at 49 months (29–59 months) (P ¼ 0.03). No new
onset of incontinence was observed (van der Hagen et al. 2011).
Another randomized comparative study (Herreros et al. 2012) revealed that, after
24 to 26 weeks, the healing rate after the application of 20 million ASCs after closure
of the internal fistula opening (64 patients) was 39.1%, after ASCs plus fibrin glue
after internal fistula closure (60 patients) 43.3%, and after fibrin glue alone after
closure 37.3% (59 patients). At 1-year follow-up, the corresponding healing rates
were 57.1%, 52.4%, and 37.3% (p ¼ 0.13). In cases of fistula persistence at
12 weeks, a second dose (40 million ASCs) was administered in the two stem-cell
treatment groups.
In a randomized study, the application of autologously prepared platelet-rich
plasma (PRP) (N ¼ 32) was compared with fibrin glue installation (N ¼ 24) for
high cryptoglandular anal fistulae without active sepsis. At 1-year foll ow-up for all
fistula types, the improved overall healing rate for PRP-treated cases was 71% and
for fibrin glue 58.3% (P ¼ 0.608), the complete healing rate 48.4% versus 41.7%,