Journal of Crohn's and Colitis, 2024, 18, 1556–1582

https://doi.org/10.1093/ecco-jcc/jjae089
Advance access publication 15 June 2024
Ecco Guideline/Consensus Paper

ECCO Guidelines on Therapeutics in Crohn’s Disease:

Surgical Treatment
Michel Adamina,a, Silvia Minozzi,b Janindra Warusavitarne,c, Christianne Johanna Buskens,d,
Maria Chaparro,e, Bram Verstockt,f,g, Uri Kopylov,h, Henit Yanai,i,j, Stephan R. Vavricka,k
Rotem Sigall-Boneh,l,m, Giuseppe S. Sica,m,n Catherine Reenaers,o, Georgios Peros,p
Konstantinos Papamichael,q, Nurulamin Noor,r, Gordon William Moran,s,t, Christian Maaser,u

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Gaetano Luglio,v Paulo Gustavo Kotze,w, Taku Kobayashi,x, Konstantinos Karmiris,y,
Christina Kapizioni,aa Nusrat Iqbal,bb, Marietta Iacucci,cc, Stefan Holubar,dd, Jurij Hanzel,
ee,ff,
João Guedelha Sabino,gg Javier P. Gisbert,e, Gionata Fiorino,hh, Catarina Fidalgo,ii,
Pierre Ellu,jj Alaa El-Hussuna,kk, Joline de Groof,ll Wladyslawa Czuber-Dochan,mm,
María José Casanova,e, Johan Burisch,nn,oo, Steven Ross Brown,pp Gabriele Bislenghi,qq,
Dominik Bettenworth,rr Robert Battat,ss, Raja Atreya,tt, Mariangela Allocca,uu,
Manasi Agrawal,vv,ww, Tim Raine,xx, Hannah Gordon,yy Pär Myrelid,zz,
a
Department of Surgery, Cantonal Hospital of Fribourg & Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
b
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
c
Department of Colorectal Surgery, St Mark’s Hospital, London, UK
d
Department of Surgery, Amsterdam UMC, Location VUMC, Amsterdam, The Netherlands
e
Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad
Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
f
Department Gastroenterology & Hepatology, University Hospitals Leuven, KU Leuven, Belgium
g
Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
h
Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
i
IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
j
Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
k
Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
l
Pediatric Gastroenterology and Nutrition Unit, The E. Wolfson Medical Center, Holon, Israel
m
Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, University of Amsterdam,
Amsterdam, The Netherlands
n
Department of Surgery, Università Tor Vergata, Roma, Italy
o
Gastroenterology Department, Chu Liege, Liege, Belgium
p
Department of Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
q
Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School,
Boston, MA, USA
r
Department of Medicine, University of Cambridge, Cambridge, UK
s
National Institute of Health Research Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals,
Nottingham, UK
t
Translational Medical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK
u
Outpatients Department of Gastroenterology, University Teaching Hospital Lueneburg, Lueneburg, Germany
v
Department of Public Health, University of Naples Federico II, Naples, Italy
w
Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná [PUCPR], Curitiba, Brazil
x
Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
y
Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Greece
aa
Department of Gastroenterology, Attikon University Hospital, Athens, Greece
bb
Department of Surgery, Worcestershire Acute Hospitals NHS Trust, Worcester, UK
cc
APC Microbiome Ireland, College of Medicine and Health, University College of Cork, Cork, Ireland
dd
Department of Colon & Rectal Surgery, Cleveland Clinic, Cleveland, OH, USA
ee
Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia
ff
Department of of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
gg
Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium

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ECCO Consensus Guidelines on Surgery in Crohn’s Disease 1557

hh
IBD Unit, San Camillo-Forlanini Hospital, Rome, Italy
ii
Division of Gastroenterology, Hospital Beatriz Ângelo, Loures Division of Gastroenterology, Hospital da Luz, Lisboa, Portugal
jj
Division of Gastroenterology, Mater Dei Hospital, l-Msida, Malta
kk
OpenSourceResearch Organization [OSRC.Network], Aalborg, Denmark
ll
Colorectal Surgery, Royal Surrey NHS Foundation Trust, Guildford, UK
mm
Florence Nightingale Faculty of Nursing-Midwifery and Palliative Care, King’s College London, London, UK
nn
Gastrounit, Medical Division, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
oo
Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and
Hvidovre, Hvidovre, Denmark
pp
Department of Surgery, Sheffield Teaching Hospitals, Sheffield, UK
qq
Department of Abdominal Surgery, University Hospitals Leuven, Belgium
rr
CED Schwerpunktpraxis, Münster and Medical Faculty of the University of Münster, Münster, Germany
ss
Division of Gastroenterology, Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada
tt
First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
uu
IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele, Gastroenterology and Endoscopy, Milan, Italy
vv
Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

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ww
Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University,
Copenhagen, Denmark
xx
Department of Gastroenterology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
yy
Translational Gastroenterology and Liver Unit, Gastroenterology Office, University of Oxford, Oxford, UK
zz
Department of Surgery and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
Corresponding author: Prof. Dr Michel Adamina, MD, PD, MSc, EMBA HSG, FEBS, FASCRS, Department of Surgery, Cantonal Hospital Fribourg, Chemin des
Pensionnats 2-6, 1752 Villars-sur-Glâne, Switzerland. Tel.: +41 26 306 25 10; Email [email protected]

Abstract
This article is the second in a series of two publications on the European Crohn’s and Colitis Organisation [ECCO] evidence-based consensus on
the management of Crohn’s disease. The first article covers medical management; the present article addresses surgical management, including
preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both
articles together represent the evidence-based recommendations of the ECCO for Crohn’s disease and an update of prior ECCO Guidelines.
Keywords: Crohn’s disease; surgery; inflammatory bowel disease [IBD]

1. Introduction medical management17; the present article is focused on sur-

gical management while covering both medical and surgical
The incidence and prevalence of Crohn’s disease [CD] is on
management of perianal CD. These two articles together rep-
the rise globally, with increases in incidence ranging from
resent the evidence-based recommendations of the ECCO for
4% to 15% yearly over the past three decades.1 CD is a life-
CD, and update prior Guidelines published in 2020.18,19 The
long disease and optimal management is multidisciplinary
present Guidelines follow the GRADE methodology in terms
and interprofessional, and has become increasingly complex.
of framing clinically relevant questions to draw evidence-
Surgery is a major therapeutic avenue in this context. Indeed,
based statements and recommendations. However, due to the
half of patients with CD undergo one or more operations
peculiarities of the surgical literature, appraisal of the system-
during their lifetime. Patients with CD often suffer from mal-
atically researched literature was conducted according to the
nutrition and psychological comorbidities, and may have to
Oxford Centre for Evidence-Based Medicine, which grades
accept and live with a stoma.2–5 Many different medications
from evidence level [EL]1: systematic review of randomised
and combinations thereof are reshaping clinical practice, and
controlled trials, to EL5: expert opinion.20 This allowed us to
refined surgical techniques, tailored approaches, and a wider
formulate statements and practice recommendations that can
acceptance of a surgical alternative benefit patients. Hence,
effectively inform and guide clinical management.
the best possible outcomes are currently achieved within dedi-
cated expert centres providing personalised medicine.6–10 The
European Crohn’s and Colitis Organisation [ECCO] provides 3. Perianal Crohn’s disease
an interdisciplinary framework with these evidence-based
3.1. Medical approaches
Guidelines to inform and guide practice and clinicians caring
for patients with CD. The present Guidelines focus on surgery
for CD, including pre- and perioperative aspects, and pro- Statement 3.1: ECCO CD Treatment GL - SURGICAL [2024]
vides technical advice for a variety of common clinical pres- We do not recommend use of antibiotics as monotherapy
entations. Further, ECCO Guidelines offer guidance on most for treatment of complex perianal fistulae in patients with
aspects of interdisciplinary and interprofessional care for CD CD [EL4]
in separate publications.11–16
Although antibiotics are widely used in the treatment of
perianal CD, most available studies are uncontrolled.21
2. Methods To our knowledge, only one randomised controlled trial
A detailed description of the methodology used is presented [RCT] compared placebo with antibiotics in perianal fistulae
in the Supplementary materials. This article is the second in a [Supplementary Table 1]. Remission at Week 10 was observed
series of two publications on the ECCO evidence-based con- in 1/8 [12.5%] versus 3/17 [17.6%] patients treated with pla-
sensus on the management of CD. The first article covered cebo or antibiotics, respectively (relative risk [RR]: 1.41; 95%
1558 M. Adamina et al.

confidence interval [CI]: 0.17–11.54). Complete healing was on clinical outcomes. Some retrospective data suggest that fis-
observed in 3/10 [30%] patients treated with ciprofloxacin tula healing is more likely in patients with higher infliximab
and 0/8 patients treated with metronidazole.22 Uncontrolled trough levels, suggesting the need for personalised dosing in
data and data from studies on combination therapy with anti- this setting.34–38
tumour necrosis factor [TNF] suggest that ciprofloxacin can
improve the efficacy of anti-TNF in the short term, with good
safety but with no impact on longer-term healing rates.23,24 Statement 3.4: ECCO CD Treatment GL - SURGICAL [2024]
Importantly, despite the lack of evidence to support their role We suggest use of adalimumab for induction and mainten-
as monotherapy in closing perianal fistulae, antibiotics are in- ance of remission in complex perianal fistulae in CD [EL3]
dicated and recommended to treat and control perianal sepsis.
Fistula healing in the subgroup of patients with
enterocutaneous or perianal fistulae [or both] at base-
Statement 3.2: ECCO CD Treatment GL - SURGICAL [2024] line [n = 117] was a secondary endpoint of the CHARM
We suggest against using thiopurines as monotherapy double-blind, placebo-controlled, randomised trial.39 A sub-
[azathioprine, mercaptopurine] for treatment of complex sequent post hoc analysis, that focused specifically on the

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perianal fistulae in patients with CD [EL3] efficacy of adalimumab over time in this subgroup, con-
firmed the superiority of adalimumab over placebo [RR:
The effect of azathioprine [AZA] on fistula healing in peri- 2.57; 95% CI: 1.13–5.84] for fistula healing after 56 weeks39
anal CD has been numerically reported in RCTs in 18 pa- [Supplementary Table 3]. Data from CHARM, combined
tients only.25–28 A meta-analysis on this limited group of with data from the open-label extension study ADHERE, re-
patients demonstrated that AZA is not superior to placebo vealed that there was no significant increase in serious AEs
for fistula healing [RR: 2.00; 95% CI: 0.67–5.93].29 Another for patients treated with adalimumab [RR: 1.21; 95% CI:
study reported complete fistula closure in 9/29 [31%] fis- 0.43–3.38].40–43 Data were insufficient to ascertain main-
tulae during mercaptopurine therapy, in contrast to 1/17 tenance of fistula healing beyond 56 weeks, resolution of
[6%] with placebo-treated fistulae30 [Supplementary Table 2]. perianal sepsis, stoma-free survival, and quality of life. In
Nevertheless, these data could not be incorporated in the a retrospective multicentre analysis evaluating 46 patients
pooled analysis, as they were reported as number of fistulae [83% with complex fistula] naïve to anti-TNF therapy, 72%
closing rather than number of patients who had complete of patients responded to adalimumab [54% remission, 18%
fistulae closing. With the availability of effective anti-TNF partial response] at 6 months and 49% of patients main-
agents, it seems inappropriate to recommend any further tained response at 12 months [41% remission, 8% partial
randomised, placebo-controlled trial studying the efficacy of response].44 Additional data suggested that adalimumab may
AZA in complex perianal fistulae. have a role in patients who failed infliximab because of im-
munogenicity [either primary non-responders or secondary
loss-of-response]. The open-label CHOICE trial indeed
Statement 3.3: ECCO CD Treatment GL - SURGICAL [2024] demonstrated that complete fistula healing [mainly perianal
We recommend infliximab for the induction and mainten- fistula] could be achieved in 39% [34/88] of patients who
ance of remission in complex perianal fistulae in CD [EL2] initiated adalimumab after infliximab failure.42 This finding
has also been reported in a limited case series.41 Some retro-
Infliximab was the first agent shown to be effective in a RCT spective data suggest that fistula healing is more likely in pa-
for inducing closure of perianal fistulae and for maintaining tients with higher adalimumab trough levels, suggesting the
this response over 1 year. Complete response [defined as the need for personalised dosing in this setting.35,37,40,45
absence of any draining fistulae at two consecutive visits at
least 4 weeks apart] was observed in 4/31 [12.9%] placebo-
treated patients versus 29/63 [46%] infliximab-treated pa- Statement 3.5: ECCO CD Treatment GL - SURGICAL [2024]
tients [RR: 3.57; 95% CI: 1.38–9.25].31 Subsequently, the There is insufficient evidence to recommend use of
ACCENT II trial evaluated the efficacy of infliximab [5 mg/ certolizumab pegol as a treatment for complex perianal fis-
kg every 8 weeks] in a maintenance trial in 195 patients who tulae in patients with CD [EL4]
had a response [defined as a reduction of 50% of draining
fistulae in two visits at least 4 weeks apart] at Week 14 after Certolizumab pegol [CZP], a pegylated humanised Fab’ frag-
open-label induction treatment with infliximab. A complete ment that targets TNF-α, was evaluated for treatment of CD
response was maintained until Week 54 in 19/99 [19.2%] in two RCTs [PRECISE 1 and PRECISE 2]. The PRECISE
placebo-treated patients versus 33/96 [34.4%] infliximab- 1 study included 662 patients with moderate-to-severe CD,
treated patients [RR: 1.79; 95% CI: 1.10–2.92].32 A recent who were randomly assigned to receive either CZP 400 mg
meta-analysis of the existing data revealed that infliximab or placebo subcutaneously at Weeks 0, 2, and 4, followed by
was effective in inducing [RR: 3.57; 95% CI:1.38–9.25] administration every 4 weeks up to Week 26.46 Fistula closure
and maintaining clinical fistula healing [RR: 1.79; 95% was a secondary endpoint; 30% [14/46] of patients in the
CI:1.10–2.92]33 with no significant risk of serious adverse CZP group achieved closure versus 31% [19/61] in the pla-
events [AEs] as compared with placebo [RR: 1.31; 95% CI: cebo group. According to this study, CZP did not show a sig-
0.11–15.25, Supplementary Figure 1]. A combined evalu- nificant benefit for fistula closure.
ation of both RCTs for safety revealed a risk of serious AEs The PRECISE 2 trial included 668 adults with
of 18.9% [33/175 patients] in the placebo groups versus moderate-to-severe CD47 and used the same induction
11.9% [24/201 patients] in the infliximab groups. Overall, therapy as in PRECISE 1. Patients with clinical response
the most recent meta-analysis [2023] provided low certainty [reduction of ≥ 100 from baseline score on the Crohn’s
ECCO Consensus Guidelines on Surgery in Crohn’s Disease 1559

disease activity index] were randomly assigned to receive A small clinical trial compared the efficacy of standard
CZP 400 mg or placebo every 4 weeks through Week 26. VDZ dosing versus standard dosing plus an additional dose
Among patients responding to induction therapy with at Week 10 in patients with one or more draining perianal
CZP, 28 of those randomised to CZP and 30 of those fistula at baseline.50 Fistula closure was observed at Week 30
randomised to placebo had draining fistulae at baseline. in 12 [42.9%] patients [seven patients in the standard and five
The primary endpoint of the fistula subanalysis was fis- patients in the additional VDZ dose group].
tula closure, defined as ≥ 50% closure at two consecutive In summary, the available evidence is of low quality and
post-baseline visits ≥ 3 weeks apart. At Week 26, 54% insufficient to recommend VDZ for complex perianal fistulae
[15/28] of CZP-treated patients achieved fistula closure in patients with CD. However, VDZ could be considered in
[per protocol] compared with 43% [13/30] of placebo- patients refractory or intolerant to anti-TNF therapy. Further
treated patients; the difference was not statistically sig- studies with appropriate design are warranted to determine
nificant [p = 0.069]. At Week 26, 36% of patients in the the benefit of VDZ in the treatment of complex perianal
CZP group achieved complete fistula closure compared fistulae.
with 17% in the placebo group [p = 0.038]. Among pa-
tients who achieved the predefined criteria for fistula

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closure, there was a higher numerical proportion of pa- Statement 3.7: ECCO CD Treatment GL - SURGICAL [2024]
tients who received continuous treatment with CZP There is insufficient evidence to recommend use of
compared with those who initially underwent induction ustekinumab as a treatment for complex perianal fistulae
therapy followed by placebo. However, these differences in CD [EL4]
were not statistically significant for the small sample size
analysed. Patients randomised to CZP in the maintenance The sole study comparing ustekinumab with placebo in
phase maintained a 50% fistula closure rate at Week 26 treating complex perianal fistulae was a post hoc pooled ana-
(11/15 [73%] patients vs 39% [5/15] patients; p = 0.069) lysis of data from the phase 2 CERTIFI and from the phase 3
and achieved 100% closure at Week 26 (10/15 [67%] pa- UNITI-1 and UNITI-2 trials. This analysis provided informa-
tients vs 4/13 [31%] patients; p = 0.064). The results from tion on the induction of fistula response and remission rates.51
these post hoc analyses suggest a possible effect of CZP in A total of 150 patients was treated with ustekinumab and 71
complex perianal fistulae in CD. However, possibly due to were treated with placebo. Due to the limited sample size,
limited sample size, the benefit of CZP over placebo was data from the final induction visit at Week 8 were aggregated
not demonstrated. across the three studies for evaluation. The analysis revealed a
higher proportion of fistula closure after 8 weeks of treatment
in the ustekinumab group [24.7%] compared with the placebo
Statement 3.6: ECCO CD Treatment GL - SURGICAL [2024] group [14.1%], although the observed difference did not reach
There is insufficient evidence to recommend use of statistical significance [p = 0.073]. This finding was confirmed
vedolizumab for the treatment of complex perianal fistulae in a meta-analysis [RR: 1.77; 95% CI: 0.93–3.37].49
in CD [EL4] In the maintenance phase, fistula response to treatment
was assessed at Weeks 22 and 44. However, all patients
Vedolizumab [VDZ], a gut-selective α4β7 integrin anti- included in the maintenance phase were either responders
body, was assessed for the treatment of complex peri- or non-responders to induction with ustekinumab, who
anal fistulae in an exploratory analysis of data from the were re-randomised to receive ustekinumab or placebo,
GEMINI 2 study.48 GEMINI 2 was a phase 3, random- which may bias the results. Among patients in the main-
ised, double-blind, placebo-controlled trial that consisted tenance phase, fistula response at Week 22 occurred in
of separate induction and maintenance phases. Following 9/19 [47%] patients in the ustekinumab group and in
a 6-week induction period with VDZ, responders were 6/20 [30%] patients in the placebo group of the CERTIFI
randomly assigned to receive either placebo [VDZ/pla- study, and in 12/15 [80%] and 5/11 [45.5%] patients,
cebo group] or VDZ [VDZ/VDZ group] and entered a respectively, at Week 44 in the IM-UNITI study. Despite
maintenance phase. Fistula closure was defined as the ab- the numerically higher proportion of fistula healing in
sence of clinically draining fistulae at Weeks 14 and 52. A patients treated with ustekinumab, no significant dif-
total of 57 patients with draining fistulae at the start of ferences were found. Moreover, being a post hoc ana-
the maintenance period were included in the analysis; half lysis, fistula response or remission was a secondary
of them previously failed anti-TNF therapy. By Week 14, outcome, making it an exploratory study with insuffi-
28% [11/39] of patients in the VDZ/VDZ group and 11% cient statistical power and a small sample size. In a recent
[2/18] of patients in the VDZ/placebo group achieved fis- meta-analysis that included 25 studies [most of which
tula closure. However in a meta-analysis, maintenance with were observational studies and 20% of them being ab-
VDZ did not reach statistical significance [RR: 2.54; 95% stracts], 24.7% of patients achieved clinical remission
CI: 0.63–10.29; p = 0.19].49 At Week 52, 31% in the VDZ/ of complex perianal fistulae at Weeks 8–12 and 41.9%
VDZ group and 11% in VDZ/placebo group had fistula at 12 months. 52 Overall, there is insufficient evidence to
closure. Despite the numerically greater proportion of fis- recommend ustekinumab for treatment of complex peri-
tula healing observed in patients treated with VDZ, no stat- anal fistulae in patients with CD. However, ustekinumab
istically significant differences were observed. This post hoc could be considered in patients with perianal fistulae
analysis has several limitations, including a small sample who are refractory or intolerant to anti-TNF agents.
size and inadequate statistical power. It is also biased by the Further studies with appropriate design are warranted to
induction phase with VDZ, and lacks a design specifically determine the benefit of ustekinumab in the treatment of
evaluating VDZ for fistula closure. complex perianal fistulae.
1560 M. Adamina et al.

and treatment with mesenchymal stem cells [MSC].55,58,60 In

Statement 3.8: ECCO CD Treatment GL - SURGICAL [2024] the largest studies, recurrence rates of 3–13% up to 1 year
There is insufficient evidence to recommend use of post-fistulotomy55,57,58,60 were reported. However, few studies
upadacitinib for the treatment of complex perianal fistulae provide robust data on continence and wound healing.
in CD [EL4] Other reports present data from heterogeneous populations,
including non-CD fistulae54,59 or those undergoing multiple
Upadacitinib [UPA] is currently the only JAK inhibitor ap- procedures prior to fistulotomy,62 highlighting the difficulty
proved for CD. Patients with moderate-to-severe CD were in drawing recommendations from such data. Therefore,
randomised to UPA 45 mg once daily or placebo for 12 weeks fistulotomy can only be recommended in simple, superficial,
in two phase 3 induction trials. Patients who achieved clinical or low anal fistulae with absence of proctitis and stable intes-
response after 12 weeks of UPA therapy were randomly as- tinal disease.
signed to receive UPA 30 mg or 15 mg or placebo once daily
for 52 weeks. Among 1021 enrolled patients, 143 patients
had fistulae at baseline [124 patients had perianal fistulae, Statement 3.11: ECCO CD Treatment GL - SURGICAL [2024]
19 had enterocutaneous fistulae]. Post hoc analyses published We suggest advancement flap as a treatment option for

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as an abstract reported that in patients with draining fistulae selected patients with CD and complex perianal fistulae in
at baseline, the proportion of patients with ≥ 50% reduction the absence of proctitis [EL4]
in draining fistulae at Week 12 was significantly higher with
UPA 45 mg compared with placebo (22/44 [50%] patients vs Fistula closure can be achieved by raising a flap of mu-
3/22 [13.6%] patients; p = 0.004). cosal tissue within the anus and lower part of the rectum.
Furthermore, complete resolution of draining fistulae The advancement flap [AF] is then used to cover the internal
at Week 12 was also significantly higher with UPA 45 mg opening of the fistula. CD patients with a single internal fis-
than with placebo (21/44 [47.7%] patients vs 2/22 [9.1%] tula opening and without proctitis or an anal stenosis are eli-
patients; p = 0.002). Numerically, a similar resolution pat- gible. A systematic review identified 11 retrospective studies
tern was seen in patients treated with either UPA 30 mg that reported data from 135 patients with CD perianal fis-
or 15 mg (1/11 [9.1%] and 3/17 [17.6%] patients, respect- tulae treated with an AF.63 The pooled success rate was 66%.
ively vs 0/8 [0%] placebo-treated patients). Closure of the However, results were heterogeneous, probably due to varying
external fistula opening at Week 52 was higher with either definitions of success and length of follow-up. In a more re-
UPA 30 mg or 15 mg (4/19 [21.1%] and 6/35 [17.1%] pa- cent meta-analysis, Stellingwerf et al. observed a weighted
tients, respectively vs 0/25 [0%] placebo-treated patients).53 overall success rate of 61% in CD patients.64 Results were not
Nevertheless, this post hoc analysis has several limitations, significantly different when compared with the success rate of
including small sample size and inadequate statistical power. ligation of the intersphincteric fistula tract [LIFT] procedure.
In summary, the available evidence is of low quality and Additional prospective and retrospective series not included
insufficient to recommend UPA as treatment for complex in the meta-analyses showed comparable clinical healing rates
perianal fistulae in patients with CD. Further studies with ap- with AF, ranging from 47% to 90%65–68 and recurrence rates
propriate design are warranted to determine the benefit of of ~15–20%. Two studies showed a higher clinical healing
UPA in the treatment of complex perianal fistulae. rate when AF was performed in patients treated with anti-
TNF/immunomodulators [75.0% vs 37.5%] and after seton
drainage.68 One study also showed a 100% success rate in
Statement 3.9: ECCO CD Treatment GL - SURGICAL [2024] diverted patients.66
There is lack of evidence to recommend use of risankizumab The disadvantage of AF is risk of impaired continence.
for the treatment of complex perianal fistulae in CD [EL5] The systematic review showed an acceptable postoperative
incontinence rate, which was higher in AF when compared
with the LIFT procedure [7.8% vs 1.6%].64 However, most
3.2. Surgical techniques prospective series revealed a postoperative higher incontin-
ence rate of up to 20% following AF. Conversely, one retro-
spective study reported a postoperative improvement in
Statement 3.10: ECCO CD Treatment GL - SURGICAL [2024] faecal continence.68
We recommend fistulotomy in carefully selected CD pa-
tients with a simple fistula in the absence of proctitis [EL4]
Statement 3.12: ECCO CD Treatment GL - SURGICAL [2024]
Studies on fistulotomy in CD are largely retrospective, single- We recommend ligation of the intersphincteric fistula tract
centre studies with specific eligibility criteria, including as a treatment option for selected patients with CD and
Parks classification: superficial, intersphincteric, or low complex perianal fistulae [EL3]
transsphincteric fistula54–60; absence of proctitis57,58; quies-
cent abdominal disease61; and a low number of daily bowel LIFT aims to achieve fistula closure by ligation of the fis-
motions.57 Few studies have compared the outcomes of tula tract in the intersphincteric plane, close to the internal
fistulotomy in these select patients with alternative surgical opening. A theoretical advantage of LIFT over AF in CD
procedures, which were mostly performed in patients with patients is that it does not involve surgery of the [diseased]
more complex or high anal fistulae. Due to this selection bias, mucosa. Patients with a single, non-branching fistula and a
these studies demonstrated improved healing and reduced re- well-epithelialised tract are preferably eligible.
currence rates in patients undergoing fistulotomy when com- Two systematic reviews and meta-analyses, both including
pared with sphincter-preserving procedures, seton removal, approximately 1300 patients, demonstrated a high clinical
ECCO Consensus Guidelines on Surgery in Crohn’s Disease 1561

success rate of 77% and 69% [range 47–95%], respectively,

after a median follow-up of over 1 year.64,69 However, there Statement 3.14: ECCO CD Treatment GL - SURGICAL [2024]
We recommend against anal fistula plug in the treatment of
was only a minority of patients with CD in these studies,
patients with complex perianal CD fistulae [EL4]
and these patients had a lower success rate of 53%. Included
studies were heterogeneous, with a wide range of outcomes
and follow-up times, which makes it difficult to draw firm Use of a collagen anal fistula plug [AFP] in patients with peri-
conclusions. The described recurrence rates were low [1.6%] anal CD fistulae was assessed in a single RCT including 106
and compared favourably to AF [7.8%]. patients, which compared AFP after seton removal with seton
Two retrospective and one prospective study published removal only.74 The fistula closure rate after 12 weeks in the
after the aforementioned meta-analyses reported results on AFP group was 33.3% in patients with complex fistulae and
an additional 95 patients with CD.68,70,71 Clinical closure 30.7% in patients with simple fistulae, as compared with
rates were comparable to the results previously published. 15.4% and 25.6% with seton removal alone, respectively.
However, data on recurrence were only reported in one These differences were not statistically significant. In add-
series, with a rate of 21%.70 Overall, this suggests a pos- ition, there was a trend towards more AEs in the AFP group
sible underreporting in the systematic reviews and meta- [17% vs 8%; p = 0.07], although cumulative AE rates at 12

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analyses. Another retrospective study demonstrated that in months follow-up were similar.
patients with a [predominantly] fibrotic tract after LIFT at A systematic review of 12 observational studies, including
magnetic resonance imaging [MRI], no reinterventions or 84 patients with CD, demonstrated an overall AFP success
recurrences were seen during long-term follow-up, which rate of 58%, with 14% recurrence after median follow-up of
also emphasises the requirement of radiological healing to 9 [3–24] months.75 However, there was no uniform definition
consider a patient healed.68 for fistula closure or follow-up regimen. The quality of evi-
The only prospective series included 46 patients with dence for this systematic review was low due to risk of bias
a mean follow-up of 33 months and demonstrated fistula and imprecision. Use of an AFP in patients with CD appears
healing in 65% of patients.71 Smoking at time of surgery to be relatively safe and may not affect continence [limited
was significantly associated with failure (hazard ratio [HR] data on continence reported].76 However, in studies using AFP
3.2), and a trend was seen towards increased failure in pa- for cryptoglandular fistulae, the abscess formation/sepsis rate
tients with active proctitis [HR 2.0]. No other factors [use of ranged from 4% to 29% and the plug extrusion rate from
biologics, prior seton drainage, type of fistula, previous repair 4% to 41%.77
attempts] appeared to influence LIFT healing.
Postoperative complications after LIFT were seen in up to Statement 3.15: ECCO CD Treatment GL - SURGICAL [2024]
14% of patients and were predominantly wound dehiscence. There is insufficient evidence to recommend use of video-
Incontinence rates appeared to be lower when compared with assisted anal fistula treatment, fistula-tract laser closure, or
AF. However, continence should be interpreted with cau- over-the-scope clip for achieving healing in complex peri-
tion, as there is a risk of underreporting in the literature. The anal fistulae in CD [EL5]
only retrospective series specifically examining postoperative
incontinence, in 37 patients demonstrated increased in-
continence in 16% of patients after LIFT, whereas 53% of The role of video-assisted anal fistula treatment [VAAFT] in
patients operated with LIFT and 43% with AF reported a the treatment of anal fistulae in CD has been investigated only
postoperative improvement in faecal continence.68 in small cohort studies. A first retrospective study, including a
mixed population of 84 patients with cryptoglandular and CD
fistulae [n = 11] with a limited median follow-up of 8 months,
Statement 3.13: ECCO CD Treatment GL - SURGICAL [2024] revealed a 27% healing rate in patients with CD.78 Data on
We recommend against the use of fibrin glue in the treat- postoperative complications and risk of postoperative incon-
ment of patients with complex perianal CD fistulae [EL4] tinence were lacking. A second retrospective study reported
an overall healing rate of 82% at 9 months follow-up.79
Fibrin glue for treatment of perianal CD fistulae was assessed However, these results are difficult to interpret due to the very
in an open-label RCT, with 71 patients randomised to instilla- limited sample size of 11 patients and by the fact that internal
tion of fibrin glue into the fistula tract or no further treatment opening closure was achieved by fashioning a rectal advance-
after seton removal.72 This RCT demonstrated a significant ment mucosal flap. Furthermore, in ~40% of patients, faecal
difference in overall clinical remission rate [38% for fibrin diversion [FD] was present at time of surgery. No patients
glue and 16% in the observation group; p = 0.04]. However, experienced postoperative morbidity or postoperative faecal
the length of follow-up in this RCT was only 8 weeks and was incontinence. VAAFT was further evaluated in a retrospective
insufficient for a definitive judgement on the true success rate. analysis of prospectively collected data of 25 patients with
The only retrospective series with adequate follow-up time anal fistulae refractory to multiple previous surgeries and ad-
[5 years] suggested an acceptable healing rate of 45% at 1 equate medical treatment with biologics.80 Of 25 patients, 21
year,73 but the single predictor for complete clinical remission [84%] had a statistically significant improvement in a quality-
was combination with medical therapy. This series also dem- of-life questionnaire before and 6 weeks after surgery, in par-
onstrated a worrisome cumulative incidence of iterative anal ticular in both pain and discharge scores; 81% agreed that
surgery of 54% within 5 years, suggesting a high recurrence the procedure was the right decision and no patient regretted
rate after fibrin glue. Despite the limited efficacy of fibrin glue undergoing the procedure. Reoperation was necessary in one
in daily clinical practice, a uniform characteristic of all studies patient [4%].
is the relatively good safety profile of this technique with no Fistula-tract laser closure [FiLaC] is a relatively new
reported injury to the sphincter muscles. sphincter-preserving technique initially reported in 2011.
1562 M. Adamina et al.

A systematic review published in 2022 identified six retro- chronic seton treatment should not be recommended as the
spective studies investigating FiLAC as a treatment option sole treatment for perianal CD fistulae.
for perianal CD on a total of 50 patients.81 There was het- The cutting seton, in which a non-absorbable thread is
erogeneity in length of follow-up, fistula characteristics, and inserted into the fistula tract and exteriorised through the
outcomes reported. The techniques used were only partially anorectal canal with subsequent tightening, causing gradual
described, particularly how to address internal opening[s] cutting through the anal sphincter, should not be used as
of the fistula, and included technical variations. The pooled many studies have shown associated complications, including
rate of primary healing among the studies was 68% [95% prolonged perianal pain and incontinence rates up to 58%.84
CI: 53.0–84.0%]. No postoperative complications or faecal
incontinence was observed, although not all studies reported 3.3. Combined approaches
these outcomes.
The role of over-the-scope clip [OTSC] in the treatment
of anal fistulae in CD has only been investigated in several Statement 3.17: ECCO CD Treatment GL - SURGICAL [2024]
small observational case series, often with mixed populations; We recommend seton drainage preceding medical or
the majority were cryptoglandular cases and fewer were surgical therapy for complex perianal CD fistulae [EL3].

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CD-related fistulae. Mennigen et al. reported a case series Combined anti-TNF therapy and seton removal could result
of 10 patients including data on six patients with CD.81 A in improved healing rates, faster time to healing, longer
total of 4/6 [66.7%] patients were on biologic therapy at the time to relapse, and a reduced need for surgery than either
time of OTSC and all these patients achieved fistula closure; therapy alone [EL3]
only one patient not receiving biologics healed. Although no
postoperative morbidity or faecal incontinence was observed, There were no RCTs comparing medical or surgical therapy
the OTSC may be spontaneously passed [2/6, 33%] or need with or without preceding seton drainage. Five system-
to be subsequently removed due to discomfort [1/6, 16.7%]. atic reviews were included.83,84,86–88 Most studies focused on
A study by Prosst and Joos reported OTSC in 100 patients anti-TNF therapy. One of the largest systematic reviews [42
(11 had inflammatory bowel disease [IBD]) with a closure studies] included studies assessing anti-TNF agents for peri-
rate of 45% in IBD.82 Overall, the OTSC was spontaneously anal fistulae. In most studies, anti-TNF was combined with
passed in 18 patients and appeared to be associated with a preceding seton placement, and it was suggested that com-
lower fistula closure rate of 33% [6/18 patients]. The OTSC bining seton drainage with an anti-TNF agent was superior.
needed to be removed or operatively explanted in 14 patients. These results are consistent with another, large, systematic re-
No significant postoperative morbidity or faecal incontinence view that revealed that a combination of surgical treatment
was reported. Although OTSC appears to be safe and may [including seton drainage] with medical therapy [anti-TNF
result in fistula closure in some patients, widespread adoption agents and immunomodulators] may have additional benefit
of this technique is currently limited by a paucity of data in on healing of perianal CD fistulae compared with surgery or
CD. medical therapy alone.88 One study showed that 75% of pa-
tients treated with anti-TNF therapy after prior seton place-
ment healed, compared with 63% of patients without initial
Statement 3.16: ECCO CD Treatment GL - SURGICAL [2024] seton.89 Another study revealed that patients with seton place-
We recommend against use of chronic seton treatment as ment prior to anti-TNF therapy had a better initial response
the sole treatment for perianal CD fistulae other than as [100% vs 82.6%; p = 0.014], lower recurrence rate [44%
palliation [EL3]. We recommend against a cutting seton due vs 79%; p = 0.001], and longer time to recurrence [13.5 vs
to the risk of incontinence [EL5] 3.6 months; p = 0.0001] compared with patients receiving
infliximab alone.90 Additionally, patients with seton place-
There are no RCTs or studies comparing seton drainage ment prior to anti-TNF therapy were less likely to require
with no treatment for perianal CD fistulae. Two systematic hospitalisation and had reduced health care costs.87 Studies
reviews, including 10 studies [n = 305 patients] on patients have also shown shorter mean time to healing,91,92 longer time
treated solely with seton drainage, reported varying re- to relapse,92 and reduced need for repeat surgery93 than with
sults.83,84 Complete closure rates ranged from 13.6% to 100% either therapy alone.
and recurrence rates from 0% to 83.3%. Timing of seton re- Timing of seton removal is largely variable and inconsistent
moval differed among studies [range 3 weeks to 40 months]. between studies, ranging from 4 to 27 weeks post-insertion.93,94
Included studies were prospective and retrospective cohort However, the heterogeneity and low quality of the mainly
studies and case series, and mostly of questionable quality. retrospective studies included should be considered.
Additionally, the PISA trial published in 2020 compared the In most studies, seton drainage was performed prior to sur-
following three treatment strategies: long-term seton drainage gical closure in patients with perianal CD fistulae. However,
alone, anti-TNF treatment, and surgical closure [the latter several small retrospective studies showed no association be-
two with prior seton drainage].85 The study was stopped by tween fistula healing rate after a LIFT procedure and prior
the data safety monitoring board because of futility. Seton seton placement or duration of seton drainage prior to
treatment was associated with the highest reintervention rate surgery.71,95
[10/15 seton vs 6/15 anti-TNF vs 3/14 surgical closure pa- A recent retrospective study analysed medical and sur-
tients; p = 0.02]. No substantial difference in perianal disease gical therapies to identify the optimal care strategy in 200
activity and quality of life was observed between the groups. patients. Seton drainage prior to anti-TNF therapy alone did
Interestingly, in the accompanying PISA prospective registry, not significantly increase the fistula closure [HR: 1.15; 95%
inferiority of chronic seton treatment was not observed for CI 0.61–2.32; p = 0.66]. The combination of seton placement
any of these outcome measures. This study suggested that and anti-TNF therapy followed by fistula closure surgery
ECCO Consensus Guidelines on Surgery in Crohn’s Disease 1563

within 52 weeks was the best management strategy for fistula engraft and transdifferentiate into healthy tissue.99 Allogeneic
healing in multivariate analysis [p = 0.02]. Cumulative prob- MSC from adipose tissue [Cx601-darvadstrocel; Alofisel] was
abilities of fistula closure following the latter combined ap- assessed in a phase 3 RCT that included 212 patients with re-
proach were 43.8%, 82.2%, and 93.7% at 1, 3, and 5 years, fractory, fistulising perianal CD.100 At Week 52, a significantly
respectively. Patients concomitantly treated with a combin- higher proportion of patients treated with darvadstrocel
ation of anti-TNF therapy and immunosuppression at surgery achieved combined remission when compared with controls
had the highest long-term closure rate.96 [56.3% vs 38.6%; 95% CI 4.2–31.2; p = 0.010]. Combined
Importantly, particularly in case of perianal sepsis, ad- remission was defined as closure of all treated external open-
equate seton drainage seems to be of key importance to create ings at clinical examination and absence of collections > 2 cm
optimal circumstances prior to starting medication or pro- at MRI. A study extension including 40 patients was pro-
ceeding to surgical closure. spectively conducted through Week 104.101 Clinical remission
was reported in 14/25 [56%] patients in the darvadstrocel
group and 6/15 [40%] patients in the control group, which
Statement 3.18: ECCO CD Treatment GL - SURGICAL [2024] was not statistically significant [95% CI: -15.5 to 47.5]. No
We recommend the combination of medical therapy with serious AEs were reported at Week 52 or Week 104. Due to

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surgical fistula closure in amenable patients with complex the high cost of darvadstrocel, the costs and potential benefits
perianal fistulae, as surgical closure results in improved should be considered on a case-by-case basis of the clinical
long-term outcomes [EL3] situation.
A meta-analysis published in 2018 that included three
Two RCTs and one retrospective study investigated sur- studies suggested that MSC of different origin significantly
gical closure of the fistula tract in combination with medical improved healing of perianal fistulae when compared with
therapy. A first multicentre RCT compared seton removal control at 6 to 24 weeks (odds ratio [OR]: 3.06; 95% CI:
and surgeon’s choice of closure with seton removal alone in 1.05–8.90; p = 0.04) and numerically at 24 to 52 weeks
patients treated with adalimumab. There was no difference [OR: 2.37; 95% CI: 0.90–6.25; p = 0.08].102 No significant
in clinical closure at 12 months [surgery 56.3% vs control increases in AEs [OR: 1.07; 95% CI: 0.61–1.89; p = 0.81]
65.4%; p = 0.48] or in secondary outcomes measuring quality were observed in treated patients. Limitations of the avail-
of life, continence, and AEs. Patients with surgical closure ex- able studies on MSC in perianal CD include heterogeneity in
perienced longer disease duration and were more likely to protocols [allogeneic or autologous MSC, bone marrow- or
have been previously treated with infliximab, suggesting more adipose tissue-derived MSC], low number of patients, varying
aggressive disease. Most patients [79%] were treated with fi- definitions of fistula healing, and lack of consensus on defin-
brin glue with limited efficacy in perianal CD. In addition, the ition of perianal fistula healing in MRI. Further studies based
study was underpowered and robust conclusions could not be on robust, well-defined, radiological targets are needed to
drawn from these data.97 evaluate the role of MSC on the natural history of perianal
In the patient preference PISA II trial,9 94patients were en- fistulising CD. Results from the phase 3, RCT, ADMIRE-CD
rolled [38 patients with surgical closure and 56 with anti-TNF II will provide additional information.103 Although the results
therapy].8 At 18 months, radiological healing was significantly of the ADMIRE-CD II were not yet published at the time
more common after surgical closure (12/38 [32%] patients) of writing the present Guidelines, the sponsor announced
than after anti-TNF therapy (5/56 [9%] patients; p = 0.005). in a press release dated 17 October 2023 that the primary
Clinical closure was not significantly different between the endpoint of combined remission at 24 weeks in complex
two treatments [68% vs 52%, respectively; p = 0.076]. Fewer perianal CD fistulae treated with darvadstrocel was not met.
patients required a reintervention and the perianal disease These inconclusive results were also presented at ECCO 2024
activity index was significantly lower after surgical closure. on 23 February 2024. The safety profile for darvadstrocel was
Long-term results after a median follow-up of 5.7 years consistent with prior studies, and no new safety signals were
showed no recurrences in patients with radiological healing; identified. The final results of ADMIRE-CD II will help pos-
recurrence was observed in 41% of patients with clinical ition this treatment in the management of complex perianal
closure without radiological healing.98 fistulae in CD.
A retrospective study of 226 patients found no difference
in healing when patients underwent a variety of surgeries
alone compared with those undergoing surgery with concur- Statement 3.20: ECCO CD Treatment GL - SURGICAL [2024]
rent infliximab [60% vs 59%, respectively]. Surgical proced- We suggest autologous adipose-derived stem cells may be
ures included seton drainage [50%], fistulotomy [41%], fibrin used as a treatment option in complex perianal CD [EL4].
glue [6%], advancement flap [2%], and collagen plug [1%]. There is insufficient evidence to recommend use of platelet-
However, time to healing was 6.5 months after combination derived factors or stromal vascular fraction in complex peri-
therapy [surgery and infliximab] and 12.1 months after sur- anal CD [EL5]
gery alone [p < 0.0001].91
Autologous stem cells [ASC] have the advantage of originating
Statement 3.19: ECCO CD Treatment GL - SURGICAL [2024] from the patient undergoing treatment, as opposed to donor-
There are conflicting data on allogenic adipose-derived based therapy, thus making ASC readily available and less
stem cell therapy for the induction and maintenance of re- costly. ASC may be injected in a similar manner as allogeneic
mission in complex perianal fistulae in CD [EL5] MSC, mixed with fibrin glue, or loaded onto a fistula plug.
The most recent systematic review summarising results
The efficacy of MSC in treatment of perianal fistulae CD is me- of four RCTs demonstrated increased clinical healing rates
diated by anti-inflammatory properties and by the capacity to of ASCs when compared with control patients treated with
1564 M. Adamina et al.

fibrin glue alone [OR: 3.19; 95% CI: 1.05–9.65; p = 0.04].104 including advancement flap [rectal, vaginal, or Martius flap],
Unfortunately, it is difficult to draw firm conclusion for pa- fibrin glue, collagen plug, or gracilis muscle interposition and
tients with CD, as only 20 patients with CD were included in performed during the first year in 10 patients [8%], trans-
these studies and most patients had a short follow-up of only lating into a higher closure rate in multivariate analysis
8 weeks. There are no studies that directly compared autolo- [adjusted RR: 2.02; 95% CI 1.25–3.26; p = 0.004]. A retro-
gous with allogeneic stem cells for perianal CD fistulae. spective study of 166 patients who underwent operations for
The best evidence on the use of ASCs for perianal CD fis- anogenital fistulae revealed an overall fistula healing rate of
tulae comes from various prospective case series, including 71.7% [n = 119] with a median follow-up of 5.5 [1.2–9.8]
a total of 110 patients.105–110 Although treatment protocols years.114 Nearly one-third of patients [33.1%] achieved com-
varied substantially, most involved curettage of the fistula plete healing after first surgery, 51.8% [n = 86] after the
tract, suturing of the internal opening [with or without an second, and 62.1% [n = 103] after the third operation.
advancement flap], and filling of the fistula tract with ASCs. A recent systematic review found nine studies that reported
Most studies allowed a second injection of ASCs in patients healing, success, or closure [range 14–81%] across multiple
with incomplete closure. Clinical healing rates, defined as no surgical procedures; seven studies reported success rates ran-
suppuration from the external orifices, ranged from 33% ging from 50% to 75%.115 However, those studies were of

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to 91%. However, most of these series lacked an adequate low quality and had limited sample sizes, various concomi-
follow-up [range 2–12 months], with recurrence rates rarely tant medical therapies, heterogeneous fistula and patient char-
described. The largest study included 30 patients and showed acteristics, outcomes considered, and definition of outcomes.
a closure rate of 83.3% with a recurrence rate of 33%.109
Despite the additional requirement of harvesting cells via
liposuction to obtain ASC, the procedure appeared safe. Statement 3.22: ECCO CD Treatment GL - SURGICAL [2024]
The most common AEs were postoperative pain, abscess, We suggest faecal diversion with a defunctioning ileos-
or bleeding.104 There were no significant differences in AEs tomy or colostomy for treatment of refractory, complex
when compared with the control group [OR: 1.06; 95% CI: perianal CD [EL4]
0.71–1.59; p = 0.77].
There are also some studies that investigated the effects of Patients with treatment-refractory perianal CD may benefit
injecting freshly collected, microfragmented, autologous adi- from faecal diversion [FD] with a diverting ileostomy or col-
pose tissue, platelet-derived growth factors, or stromal vas- ostomy. Indeed, FD is associated with a high early clinical re-
cular fraction into perianal CD fistulae.108,110,111 Feasibility sponse rate and an improved quality of life, although FD often
was demonstrated in most patients and results appeared com- becomes permanent. A systematic review of 16 retrospective
parable to ASCs, with clinical healing ranging from 38% to studies with 556 patients with perianal CD found that FD is
67%. Harvesting, preparation, and administration of these associated with early clinical response in 63.8% [95% CI:
tissues are described as easy, inexpensive procedures with 54.1–72.5%].116 However, stomas were often permanent and
minimal AEs. Again, these series suffer from small patient only 16.6% [95% CI: 11.8–22.2%] of patients ultimately
numbers and brief follow-up and lack description of recur- had successful ostomy reversal. The rate of proctectomy after
rence rates. Further studies are required to define the true po- failure of temporary diversion was 41.6% [95% CI: 32.6–
tential of these approaches. 51.2%]. Proctitis was associated with increased risk of per-
manent diversion.
One study compared FD plus local procedures for perianal
Statement 3.21: ECCO CD Treatment GL - SURGICAL [2024] CD [n = 13] with local procedure without FD [n = 26].117
We suggest medical treatment in anogenital and Complete resolution of perianal CD was observed in 11
rectogenital CD fistulae, and counselling for surgical closure [85%] patients with FD versus five [19%] patients without
in selected patients with CD [EL5] FD. Of the FD patients, six [46%] had stoma reversal, of
whom three [50%] remained disease free, one [17%] required
Anogenital and rectogenital fistula are complex and disabling successful additional local procedures, and two [33%, 15%
conditions that are better managed by an experienced multi- overall] required re-diversion. Thus only 4/13 [31%] of FD
disciplinary team. No RCTs or prospective studies were found patients ultimately had stoma reversal. Another study, of 21
that compared anti-TNF agents alone versus anti-TNF agents patients, showed that although some patients may achieve
and surgery combined to treat these fistulae. complete healing, many do not; initial improvement was fol-
A post hoc analysis of the ACCENT II study identified 25 lowed by plateau in seven [33%], temporary improvement in
women with ano- or rectovaginal fistulae.112 This study dem- six [29%], no effect in four [19%], and healing in four [19%]
onstrated that infliximab is more effective than placebo in patients.118 In this study, 11 [52%] patients subsequently had
prolonged closure [defined as non-draining fistula at Week proctocolectomy, six [28.6%] had their stoma in situ, and
14]; 13/29 [44.8%] fistulae responded to induction regimen four [19%] had stoma reversal. In a large series of 138 pa-
with infliximab and were closed. From Weeks 14 to 46, tients who had initial FD, a total of 63 [45%] underwent
among responders in the infliximab maintenance group, the subsequent total proctocolectomy, 45 [33%] had their stoma
proportion of rectovaginal fistulae that closed ranged from without proctectomy, and 30 [22%] had stoma reversal.119
54.5% to 90.0% compared with 28.6% to 42.9% in the pla- Independent predictors of lack of stoma reversal included
cebo group. proctitis [OR: 7.5; 95% CI: 2.4–33.4], one or two seton
A French, retrospective, multicentric, observational study, placements [OR: 3.3; 95% CI: 1.4–8.8], and two or more
including 131 consecutive patients treated with anti‐TNF seton placements [OR: 6.9; 95% CI: 1.2–132.5]. Biologics
agents for 1 year, found that 37% of patients had complete were not associated with stoma closure [p = 0.25].
clinical fistula closure, 22% had partial response, and 41% Few studies examined quality of life before and after FD
had no response.113 Complementary surgery was allowed, in perianal CD. In a series of 34 patients with FD, compared
ECCO Consensus Guidelines on Surgery in Crohn’s Disease 1565

with similar patients without FD, patients with FD had fewer healed at 12 weeks, and delayed healing was observed in 35
perianal CD symptoms [44% vs 79%; p < 0.05], higher [26%] and non-healing in 29 [21%] patients.124 Preoperative
Gastrointestinal Quality of Life index scores [68 vs 62 points; perianal sepsis was an independent predictor of a delayed-
p < 0.001], and higher gastrointestinal [GI] symptoms sub- or non-healing wound [p = 0.001], suggesting FD prior to
scores [81 vs 67; p < 0.0001] compared with non-diverted proctectomy.128 For non-healing perineal wounds with meta-
patients.120 The most recent meta-analysis, evaluating 1578 static CD, hyperbaric oxygen therapy may be an option.132
patients managed in the biologic era, similarly concluded
that FD improved symptoms and quality of life, and bowel 3.4. Practice points
continuity could be successfully restored in a quarter of the Fistula treatment should start with insertion of a seton fol-
patients.121 lowed by medical treatment [preferably anti-TNF]. In the ab-
sence of proctitis, patients should be counselled for surgical
closure.
Statement 3.23: ECCO CD Treatment GL - SURGICAL [2024] Perianal fistulae in CD can have a substantial detrimental
We suggest proctectomy for treatment of refractory, impact on patient quality of life. Current biological under-
complex perianal CD despite defunctioning stoma [EL4] standing of perianal fistulising CD remains inadequate, and

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previous classification systems have not provided clear guid-
Proctectomy may be recommended in many patients with peri- ance on therapy in clinical practice. A new classification pre-
anal CD. However, proctectomy is associated with a substan- sented in Figure 1 identifies four groups of patients.133 Key
tial risk of a non-healing perineal wound in the short term and elements include stratification according to disease severity
a risk of colonic or small-bowel recurrence in the long term. and desired outcome. This classification can guide patients
In a series of 127 patients with perianal CD, proctectomy was and clinicians in decision making on a ‘treat to patient goal
required in 32 [25.2%] patients.122 Several studies discussed basis’ by a combined medical and surgical approach.
independent risk factors for proctectomy, including age at first All treatment should start with insertion of a seton to
perianal fistula [p < 0.02], perianal fistula at the time of CD control sepsis and create a patent tract, followed by med-
diagnosis [p < 0.04], three or more fistulae during follow-up ical treatment [preferably anti-TNF with high trough level].
[p < 0.01], and proctitis [p < 0.0001].123 Other studies also re- After good response to anti-TNF therapy, seton removal
ported malignancy in the setting of perianal CD as an indica- can be considered within 2–8 weeks to aim for closure with
tion for an oncological proctectomy.123–125 medication only.134 Although clinical closure can be achieved
Proctectomy for perianal CD is typically performed as an in up to 60% by medication, it should be noted that MRI
abdominoperineal resection [APR] with a colostomy or as a closure is rare [< 10%], with high risk of recurrence and sur-
total proctocolectomy with end-ileostomy in case of extensive gical reintervention.135 MRI closure is more frequently seen
colonic involvement.122–127 In terms of extent of bowel resec- after surgical closure under anti-TNF therapy [up to 40%],
tion in the setting of perianal CD, a single study examined with no recurrences after long-term follow-up in case of a
APR with colostomy and reported a clinical recurrence rate of completely fibrotic tract on MRI.98 Therefore, in absence of
colonic CD of 22% for an endoscopic colonic recurrence rate proctitis, amenable patients should be counselled for surgical
of 29%; overall, 5% of patients required completion total closure. For patients with an intersphincteric or low trans-
colectomy.127 It is important to note that proctocolectomy sphincteric single fistula tract, fistulotomy can be considered
does not cure CD; a multicentre, retrospective study of total as this procedure will have the highest success rate.
proctocolectomy with end-ileostomy, including 193 patients In case of complex perianal fistulae, AF or LIFT can be
with refractory perianal CD, reported a 23% small-bowel re- offered, depending on fistula characteristics. Stem cells can be
currence within 2 years.126 Independent risk factors for re- an alternative, particularly in patients with multiple internal
currence included CD diagnosis at age < 18 years [HR: 2.56; openings or pre-existing complaints of incontinence.
95% CI: 1.40–4.71] and previous small-bowel resection [HR: In case of anti-TNF failure and surgically refractory fis-
2.61; 95% CI: 1.42–4.81]. tulae, more experimental approaches [such as hyperbaric
Proctectomy for IBD is often performed as an intersphincteric oxygen therapy or new medical approaches] can be at-
dissection, limiting the size of the perineal incision.122–127 The tempted, ideally in the context of a prospective clinical trial.
intersphincteric groove may not be identifiable due to scar- An algorithm to guide the management of perianal CD is
ring in up to 78% of patients with perianal CD, limiting the illustrated in Figure 2.
ability to perform an intersphincteric dissection and affecting
wound healing.125 Indeed, delayed perineal wound healing
is often observed after proctectomy in perianal CD.124,128–131
4. Surgical management of abdominal
When wounds are left open to heal by secondary intention, an Crohn’s disease
uncommon practice nowadays, only 58% of perineal wounds 4.1. Preoperative optimisation
of patients with IBD were healed after 6 months of dressing
changes.129 Wound irrigation has also been explored in the
1980s, and half of perineal CD wounds were healed at 30 Statement 4.1: ECCO CD Treatment GL - SURGICAL [2024]
days compared with 87% after APR for cancer in the absence We recommend elective bowel resection over emergency
of radiotherapy.131 Male gender was a risk factor for delayed surgery in patients with CD [EL2]
healing, particularly when the drain exited through the wound
instead of laterally. Higher success rates were observed when A meta-analysis of cohort series including 75 971 CD pa-
myocutaneous flaps were used, although patients are still at tients from 15 countries reported a significantly lower mor-
risk for subsequent fistulisation [20% in a small study].130 tality among patients who underwent elective [0.6%; 95%
In a large series of 126 patients, 72 [53%] wounds were CI: 0.2%–1.7%] vs emergent surgery [3.6%; 95% CI:
1566 M. Adamina et al.

Class 2c-i: early and Class 3: severe disease Class 4a: repair
Class 2a: repair rapidly progressive with exhausted Symptomatic sinuses
Symptomatic fistulae suitable disease perineum and or wounds suitable
for combined medical and Early and rapidly adverse features for combined medical
surgical closure or repair progressive disease Severely symptomatic and surgical closure or
(including seton removal) destructive to the disease (despite repair and patient goal
and patient goal is fistula perineum or to quality defunctioning), is sinus closure
Class 1: minimal disease closure of life (or both), such with irreversible perineal
Minimal symptoms and that early intervention destruction, or symptoms
anorectal disease burden, with defunctioning limiting quality of life so
requiring minimal ostomy and sometimes markedly that proctectomy
intervention over time early proctectomy is is required
Class 2: chronic required
symptomatic
fistulae
These patients will align
with one of three groups,
Perianal fistulising according to their goals, as Defunctioning Protectomy Class 4: perineal symptoms
Crohn's disease well as their symptoms after proctectomy
and impact on quality of
life, fistula anatomy,

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and anorectal disease
burden Class 2c-ii: gradually Class 4b: symptom
debilitating disease control Chronic
Gradually debilitating symptoms related
symptomatic fistulae to sinuses or wounds that
Class 2b: symptom unsuitable for surgical affect quality of life
control Chronic repair, which cause and that are unsuitable
symptoms related to severe symptoms, for surgical repair, or
fistulae (pain and limiting quality of patient goal is symptom
discharge) that affect life so markedly that control
quality of life. Fistulae are defunctioning ostomy
currently unsuitable for is required to restore
surgical repair, and quality of life. Patient
patient goal is symptom goal is symptom control
control

Figure 1 Classification of perianal fistulising Crohn’s disease. At any moment throughout its disease course, perianal fistulising Crohn’s disease can be
classified into one of four classes.133 [Reprinted with permission from Elsevier, License Number 5760781248280].

1.8%–6.9%], highlighting the importance of perioperative biologics, or combinations thereof, with a higher likelihood
optimisation and avoidance whenever possible of emergent of undrained abscesses, fistulae, or both at time of emergency
surgeries.136 surgery. Drainage of an abscess and relieving obstruction,
together with preoperative optimisation, should be initiated
immediately on admission, as described in recent prospective
Statement 4.2: ECCO CD Treatment GL - SURGICAL [2024] cohort series142,143 and advised in ECCO topical reviews.144,145
Pre-operative optimisation should be initiated, followed by Preoperative optimisation of an emergency CD patient and
re-assessment of the patient for surgical intervention [EL3] transfer of care from the acute to the specialised/elective set-
ting is key to improving short- and long-term postoperative
A recent meta-analysis showed that emergency bowel resection outcomes. On the other hand, free bowel perforation is one
is associated with a higher risk of overall postoperative com- of the few situations where urgent surgery may be mandatory,
plications and abdominal septic complications.137 This is con- as bowel perforation is a very rare but serious and potentially
sistent with a European Society of Coloproctology prospective life-threatening complication in CD. The literature is charac-
snapshot audit, in which emergency surgical intervention terised by low-quality, heterogeneous studies based on histor-
was associated with unfavourable postoperative outcome.138 ical data. A study from Korea estimated the incidence to be
Another, recent, multicentre, international, observational 2.15% in the Korean CD population.146
study concluded that emergency intervention in patients with There are two important points to consider when CD leads
an abdominal abscess increased the risk of postoperative com- to bowel perforation.
plications and abscess recurrence.139 Moreover, patients under-
going emergency surgery for CD have a higher rate of stoma
formation.140,141 Last, laparoscopic surgery in the emergency 1. Bowel-wall thickness: bowel-wall thickening in CD oc-
setting has a higher conversion rate and involves resection of curs due to chronic inflammation and scarring and dif-
longer segments of small bowel, which is a concern in CD due fers from ischaemic bowel perforation, which occurs
to a lifetime risk of short bowel.140 when there is a decreased blood supply to the bowel, po-
The drivers behind these unfavourable outcomes may be tentially resulting in a perforation. Symptoms, diagnostic
patient status and the environment of care typical of an emer- approach, and treatment may also differ between these
gency situation. Emergency resection [within 48 h of admis- conditions.
sion] is performed on tissue characterised by profuse oedema 2. Size of perforation: bowel perforation in CD can vary
and acute inflammation, in a patient often in an unstable con- in size and presentation. Some cases may involve small
dition, by a team that may not be specialised in IBD or even or microscopic perforations, others can present as larger
colorectal surgery. Patients with CD who undergo emergency perforations. Timely diagnosis and appropriate treat-
operation typically have a severe form of disease, are mal- ment can prevent further complications and improve
nourished, and are often on steroids, immunomodulators, outcomes.
ECCO Consensus Guidelines on Surgery in Crohn’s Disease 1567

Perianal fistula abscess

Seton drainage I&D +

antibiotics

Start anti-TNF

No proctitis Proctitis

Single internal Multiple

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opening internal
openings

Superficial Transsphincteric
[intersphincteric] tract
tract

Fistulotomy Surgical closure Stem cells Seton removal

under anti-TNF under medical
[AF or LIFT] treatment

Fistula recurrence

Class 2a [repair]: Class 2b [symptom control]

- Consider approach outside - Medical treatment
guideline [VAAFT/OVESCO] - Chronic seton
- Experimental therapies - Experimental therapies

Figure 2 Treatment algorithm for Class 2A CD fistulae aiming for repair.

A small-bowel perforation can, in very selected situations and

under supervision of an experienced colorectal surgeon, be Statement 4.5: ECCO CD Treatment GL - SURGICAL [2024]
managed conservatively. This mandates a very close clinical We suggest conservative treatment following successful
follow-up and the capacity to operate immediately should the percutaneous, image-guided drainage of an intra-abdominal
patient deteriorate. abscess in carefully selected cases. A low threshold for sur-
The early involvement of a multidisciplinary team consisting gery is recommended in the event of medically refractory
of an IBD gastroenterologist, an IBD surgeon, a radiologist, cases [EL4]
and a dietitian is mandatory in emergency presentation of
CD, due to the complexity of the disease and management. Penetrating CD, complicated by intra-abdominal abscesses
[IASC], represents a complex condition requiring involve-
ment of interventional radiologists, gastroenterologists, and
Statement 4.3: ECCO CD Treatment GL - SURGICAL [2024] surgeons. An [elective] operative approach appears indicated
We recommend control of sepsis prior to abdominal sur- in most patients, as conservative management leads to com-
gery for CD [EL3] plete abscess resolution in less than 30% of selected cases,
whereas delayed elective surgery is associated with improved
postoperative outcomes, avoidance of a stoma, and abscess
recurrence.147–149
Statement 4.4: ECCO CD Treatment GL - SURGICAL [2024] Observational studies indicate that failure to control IASC
We suggest use of intravenous antibiotics and percutan- preoperatively increases the risk of postoperative complica-
eous, image-guided drainage as the first-line treatment for tions, anastomotic leaks, postoperative sepsis, and stoma for-
intra-abdominal abscesses related to CD [EL3] mation, resulting in an increased length of hospital stay.139,150–152
Percutaneous drainage [PD] under ultrasonographic or
1568 M. Adamina et al.

computed tomography [CT] guidance may be the primary 4.2. Practice point
approach for treatment of well-defined abscesses. Successful Whenever possible, elective surgery is preferable to an emer-
drainage rates of 74–100%, allowing avoidance of emer- gency procedure in both fistulising and obstructive CD. The
gency surgery in 14–85% of patients, were reported.18 PD control of IASC is multidisciplinary and draws from inter-
with antibiotics to control IASC resulted in better quality of ventional radiology, infectious disease, gastroenterology, and
life than surgery alone, provided abscesses were completely surgery. Imaging [sonography, CT, MRI], swift drainage,
drained.139,150,153 PD and antibiotic therapy should be com- antibiotics, intensified perioperative therapy, and specialist
bined with perioperative optimisation, including nutritional care are the mainstays of treatment. PD is mostly a bridge
support and stopping or decreasing corticosteroids. Despite intervention rather than a definitive solution; elective sur-
PD, these patients still present with higher morbidity than gery performed 2–4 weeks thereafter minimises postoperative
those without preoperative IASC.140 complications and need for a stoma.
It is worth noting that when performed by specialised, Primary conservative management of bowel obstruction
high-volume, IBD surgeons, early laparoscopic surgery [< 1 includes rehydration, nasogastric decompression, imaging,
week after admission] was safe, feasible, and associated with and consideration of high-dose steroid therapy. Frequent
similar morbidity rates when compared with delayed sur- monitoring and surgical consultation are critical. Surgery can

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gery [within 3 weeks after initial admission, including PD in be deferred in most cases but should be considered during
28% of patients].154 However, steroid treatment before PD follow-up. Definitive non-surgical management may be suc-
and short waiting interval [< 2 weeks] were associated with cessful but must be carefully balanced and discussed with the
a higher risk of abscess recurrence, and anaemia and long individual patient.
waiting interval [> 4 weeks] increased the risk of stoma con-
struction.154 Overall, performing surgery 2–4 weeks after suc-
cessful PD was associated with the lowest risk of postoperative Statement 4.7: ECCO CD Treatment GL - SURGICAL [2024]
IASC.139 Identifying patients who may be treated without We recommend preoperative nutritional assessment and
surgery is challenging and currently relies on clinical judg- identification of nutritional risk by IBD-dedicated dietitians
ment rather than on evidence. In general, medically refractory for patients with CD who need surgery [EL2]
disease, presence of stenosis, or an enterocutaneous fistula
represent clear indications for surgery.153
Statement 4.8: ECCO CD Treatment GL - SURGICAL [2024]
Statement 4.6: ECCO CD Treatment GL - SURGICAL [2024] When feasible, enteral nutrition should be the strategy of
We recommend endoscopic balloon dilatation as a treat- choice for preoperative optimisation in patients with CD
ment option for small-bowel strictures < 5 cm in length [EL3]
when technical expertise is available [EL2]
Malnutrition is common in patients with CD requiring sur-
In a review of 1463 patients with CD who underwent gery and is a risk factor for adverse postoperative outcomes
3213 endoscopic balloon dilatation [EBD] procedures, a and complications. Systematic nutritional risk screening
stricture length < 5 cm was mostly amenable to EBD and [body mass index, unintentional weight loss, reduced dietary
associated with a surgery-free outcome; every additional intake, illness severity], together with perioperative nutri-
centimetre in stricture length increased the need for sur- tional support, may mitigate the perioperative risks associ-
gery by 8% [p = 0.008].155 This is consistent with other ated with malnutrition. An ECCO consensus and topical
reviews.156–158 Inflammation, disease activity, type of stric- review on perioperative dietary therapy in CD concluded
ture, balloon diameter, and duration of inflation did not than exclusive enteral nutrition [EEN] represented a valid
affect outcomes.155,157 preoperative optimisation strategy for reducing complica-
Whereas therapeutic success can be achieved after a single tions and improving nutritional status in patients with CD,
dilation, several dilations may be necessary to resolve ob- likely by modulating inflammatory status and improving mi-
structive symptoms; however, repeat dilation may reduce crobial composition.145,164–166
quality of life.159,160 Although accessory endoscopic tech- The benefits of preoperative EEN have been consistently
niques, including local steroid injection, cutting procedures reported, leading to a marked reduction of postoperative
[eg, Argon beaming], and stent implantation have been pro- morbidity [21.9% vs 73.2%; OR: 0.09; 95% CI: 0.06–0.13;
posed to improve resolution,155 the evidence is weak. Some p < 0.01], although data on biochemical optimisation are
retrospective cohort studies suggested that combined therapy still debatable.167–169 Conversely, the role of parenteral nutri-
with anti-TNF and EBD may prevent intestinal stricture re- tion [PN] in the preoperative optimisation strategy is more
currence and surgery in hospitalised patients with CD.161,162 debated.170 Importantly, EEN requires dedicated nutritional
An unresolved controversy is the dilatation efficacy of support and high patient compliance to be successful.
primary versus anastomotic strictures. Identification of pre- The use of PN in the perioperative period should be re-
dictive factors for the long-term success of EBD may assist served for patients unable to tolerate EEN, who do not meet
clinical decision making and an individualised treatment ap- their nutritional requirements with EEN, or in whom EEN
proach in stricturing CD.163 is contraindicated.171 In a recent, prospective, multicentric,
In conclusion, short-term therapeutic success of EBD is cohort study, preoperative EEN reduced morbidity for in-
high in a selected group of patients when technical expertise fection and temporary stoma requirement in malnourished
is available. However, the impact on long-term quality of life, patients with CD.165 In another recent cohort study, patients
need for repeat dilatations, and strictureplasty or bowel re- receiving preoperative PN had significantly lower rates of
section is less clear. non-infectious complications [OR: 0.07; 95% CI: 0.01–0.80;
ECCO Consensus Guidelines on Surgery in Crohn’s Disease 1569

p = 0.03]. A subset of frail patients with severe CD, who did probably represents heterogeneous populations, different
not tolerate EEN and required PN, presented a similarly outcomes, and inconsistent definitions of outcomes. Most
high rate of IASC and primary stoma as when upfront sur- evidence is concentrated on infliximab and adalimumab.178
gery was elected. Hence, the advantage of providing PN to The PUCCINI trial is the largest prospective trial to date and
this subgroup of frail patients is questionable, as these pa- revealed no difference in the rate of any infection between pa-
tients may benefit from an early surgical approach followed tients using biologic therapy and those not so.179 Detectable
by nutritional replacement.172 Therefore, early surgery with preoperative serum concentrations of anti-TNF agents also
postoperative optimisation may be considered in frail, se- did not increase the risk of surgical site or overall infection
verely ill patients who do not tolerate EEN and accept a rates.179 Hence, anti-TNF therapy can be continued prior to
diverting stoma. surgery.

4.4. Vedolizumab
Statement 4.9: ECCO CD Treatment GL - SURGICAL [2024] Although initial retrospective data suggest that VDZ leads
We recommend that steroids should be tapered whenever to an increased risk of postoperative infection, subsequent
possible before surgery to reduce the risk of complications studies showed no increased risk. These data were confirmed

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[EL2] by most, but not all, recent meta-analyses.180–183 The latest
of these showed no significant differences in overall compli-
Previous ECCO Guidelines have reported that treatment cations [OR: 1.04; 95% CI: 0.48–2.24],181 infectious com-
with > 20 mg prednisolone daily for > 6 weeks increases the plications [OR: 1.00; 95% CI: 0.37–2.69], or surgical site
risk of postoperative septic complications.11,18,173 Whereas infections [OR: 1.45; 95% CI: 0.33–6.32] for those receiving
there is no large RCT confirming this position, one large, VDZ preoperatively. Therefore, VDZ can be continued prior
multicentre, cohort study and numerous retrospective co- to surgery.
hort studies have identified this risk [summarised in three
meta-analyses].174–176 4.5. Ustekinumab
Indeed, preoperative steroid use was a significant risk Although one meta-analysis focused on ustekinumab and
factor for major complications, including an overall increased postoperative complications, the comparator was patients
risk of postoperative complications [OR: 1.41; 95% CI: receiving anti-TNF therapy.184 No difference in complica-
1.07–1.87] and a specifically increased risk of postoperative tions and infectious complications were identified. The only
IASC [OR: 1.68; 95% CI: 1.24–2.28].175,177 Patients who re- cohort study comparing ustekinumab with non-biologic
ceived > 40 mg perioperative oral steroids had the highest risk therapy revealed that preoperative use of ustekinumab is an
of overall complications [OR: 2.04; 95% CI: 1.28–3.26]. A independent risk factor for intra-abdominal sepsis [OR: 2.93;
meta-analysis confirmed an almost doubling of total wound 95% CI: 1.16–7.40; p = 0.02].185 Although further studies are
infections [OR: 1.70; 95% CI: 1.38–2.09].174 Similar to the required to confirm the safety of ustekinumab and surgery,
results from the large, multicentre, cohort study, an increased current data suggest that cessation before surgery may not
risk for anastomotic leak was also observed [OR: 1.51; 95% be necessary.
CI: 1.02–2.25].176 There is no available evidence of the possible impact of
Steroids should be reduced before surgery as part of a preoperative use of CZP, rizankizumab, or JAK inhibitors
preoperative optimisation strategy in combination with nu- on postoperative morbidity in patients with CD undergoing
tritional optimisation and drainage of sepsis. If this is not abdominal surgery. The safety of continuing newer biologic
possible, consideration should be given to a staged procedure agents prior to surgery remains unknown.
with a temporary stoma.
4.6. Practice points
Statement 4.10: ECCO CD Treatment GL - SURGICAL [2024] Preoperative optimisation is a key element in successful man-
We recommend against cessation of biologics prior to
agement of complex situations and chronic disease. Many
surgery, as current evidence suggests that preopera-
aspects of optimal perioperative care are generic and common
tive treatment with anti-TNF therapy [EL3], vedolizumab
to all abdominal procedures,186 although some aspects are
[EL3], and ustekinumab [EL4] does not increase the risk of
particularly important in the context of CD [venous thrombo-
postoperative complications in patients with CD undergoing
embolism prophylaxis, nutrition, iron management, drug
abdominal surgery
management, minimally invasive approaches, and bowel- and
sphincter-sparing techniques].187,188 High-dose steroids should
be tapered to reduce surgical morbidity, but current biologic
therapy can safely be continued perioperatively.
4.3. Anti-TNF therapy
Use of biologics in patients with CD undergoing surgery re- 4.7. Surgical techniques
mains controversial. Concern exists over the desired modu-
lation of the immune response and the potential to increase
postoperative complications. Several retrospective studies re- Statement 4.11: ECCO CD Treatment GL - SURGICAL [2024]
garding anti-TNF agents have been published over the past We recommend a laparoscopic approach as the first line in
20 years. Some suggested an increased incidence of compli- abdominal surgery for CD [EL2]
cations in patients receiving anti-TNF agents preoperatively,
and other studies showed no difference. Several meta-analyses A Cochrane review of two randomised trials189,190 showed no
have also reported varying conclusions.178 Several prospective difference in complications between laparoscopic and open
studies also reached inconsistent conclusions. This variation surgery for CD. A more recent review191 showed a benefit
1570 M. Adamina et al.

for patients operated by laparoscopy, with fewer complica- [OR 0.6; p = 0.01]. However, there were no statistically sig-
tions and lower rate of incisional hernia. This review included nificant differences in leak rates, endoscopic and symptomatic
both randomised trials and observational studies. Although recurrence, or reoperation for recurrence.197
this may potentially introduce some bias, based on strong A meta-analysis compared 396 stapled side-to-side anas-
evidence for the benefits of laparoscopy, particularly in rela- tomoses with 425 hand-sewn end-to-end anastomoses and
tion to reduced adhesions, the current evidence strongly sup- found that stapled side-to-side anastomoses outperformed
ports recommending laparoscopy as the first-line approach. in all endpoints, namely overall postoperative complications
Laparoscopic resection for recurrent CD is also feasible but [OR: 0.54; 95% CI: 0.32–0.93], anastomotic leak [OR: 0.45;
is associated with higher risk for conversion.192 Importantly, 95% CI: 0.20–1.00], recurrence [OR: 0.20; 95% CI: 0.07–
in the absence of expertise to perform laparoscopic surgery, 0.55], and reoperation for recurrence [OR: 0.18; 95% CI:
emergency operations should not be delayed. 0.07–0.45].198
A network meta-analysis of 11 trials and 1113 patients
further substantiated the superiority of stapled side-to-side
Statement 4.12: ECCO CD Treatment GL - SURGICAL [2024] anastomosis regarding overall complications, clinical recur-
We recommend laparoscopic resection as an alternative to rence, and reoperation for recurrence. However, the choice

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infliximab [EL2] or adalimumab [EL4] therapy in patients of anastomosis technique did not seem to affect leak rates,
with limited terminal ileal or ileocaecal disease surgical-site infections, mortality, or length of hospital stay.199
A more recent systematic review suggested that stapled side-
A randomised, controlled, open-label, multicentre trial as- to-side anastomoses may lower the risk of surgical recurrence
signed 143 patients with non-stricturing CD of the terminal in CD, potentially reducing rates of reoperations compared
ileum to receive either laparoscopic ileocaecal resection with hand-sewn end-to-end anastomoses [OR: 0.22; 95% CI:
[n = 73] or infliximab [n = 70]. At 12-month follow-up, 0.05–0.95].200 In case of emergency bowel resection, a retro-
quality of life and body image perception were compar- spective study involving 92 bowel resections recommended
able.193 Patients treated with infliximab had fewer days use of stapled side-to-side anastomoses, which was associated
of sick leave from work. Serious complications related to with fewer endoscopic recurrences than use of hand-sewn
treatment occurred in four resected patients versus two in end-to-end anastomoses [OR: 38.12; p = 0.01].201 This was
the anti-TNF group. Crossover among groups was needed corroborated by another retrospective study.202 However, a
in 37% of patients treated with infliximab and in 26% of recent multicentre, retrospective, observational study exam-
those who underwent surgery. Long-term data from the ran- ining 427 intestinal anastomoses in CD found no significant
domised trial revealed no surgical recurrence in the surgery difference in postoperative complications.203
group after 5 years, whereas 50% in the anti-TNF group Overall, the quality of the studies included in systematic
had surgery at 5 years.194 A recent meta-analysis suggests reviews and meta-analyses was notably limited, with only a
reduced risk of overall and surgical recurrence and reduced minority of patients participating in RCTs and heterogeneous
use of postoperative biologic therapy if surgery is performed populations studied. Despite this limitation, the prevailing
early.195 Based on these data, early surgery has a benefit in pa- consensus leans toward a preference for stapled side-to-
tients with limited terminal ileal CD and represents a reason- side anastomosis, which is associated with lower rates of
able alternative to escalating medical therapy. Patients should postoperative complications and allows for an intracorporeal
be advised early about a surgical option. anastomosis. Furthermore, it was suggested that the diam-
eter of the anastomosis may be a significant risk factor for
Statement 4.13: ECCO CD Treatment GL - SURGICAL [2024] recurrence, as a wider anastomosis is thought to be associated
We suggest stapled side-to-side anastomoses in small-
with a reduced likelihood of clinical and surgical recurrences.
bowel or ileocolic resections for CD [EL3]
Importantly, the width of the anastomosis is determined by
its inlet, more than by the length of a staple line or a suture
line. Endoscopic appraisal of an early recurrence should con-
Surgeons place great importance on the technical aspects sider the type of anastomosis healing. Indeed, stapled [everted
of their work, which can be influenced by various factors, mucosa] and hand-sewn [inverted mucosa] have a different
including their training, personal experience, available re- healing pattern and healing time, which should neither be
sources, and the clinical scenario. The choice of the optimal confused endoscopically with an early recurrence, nor lead
anastomosis technique in small-bowel and ileocolic resections to overtreatment.
has been a subject of controversy. In recent years, there has
been a growing body of evidence supporting the use of side-
to-side anastomosis, and this support has been consistent Statement 4.14: ECCO CD Treatment GL - SURGICAL [2024]
over time. We suggest that the Kono-S anastomosis can be an alterna-
A significant meta-analysis on 661 patients operated for tive surgical approach to other types of anastomoses after
cancer and CD revealed a significantly higher anastomotic leak ileocaecal resection [EL3]
rate in end-to-end anastomoses compared with side-to-side
anastomoses [OR: 4.37; p = 0.02]. This was also observed in Kono-S anastomosis was first described in 2011 as a new,
the subgroup of ileocolic anastomoses [OR: 3.8; p = 0.05].196 hand-sewn, anti-mesenteric, functional, end-to-end anasto-
Furthermore, overall postoperative complications [OR: 2.64; mosis designed with the aim to reduce anastomotic CD recur-
p < 0.001] and hospital stay length were higher [by 2.81 days; rence after ileocaecal resection.
p = 0.007] when an end-to-end anastomosis was performed. In the first retrospective study,204 Kono-S anastomosis was
A subsequent meta-analysis confirmed the superiority of side- associated with a reduction in both median endoscopic re-
to-side anastomosis in overall postoperative complications currence score [Rutgeerts’ score] and surgical recurrence rate
ECCO Consensus Guidelines on Surgery in Crohn’s Disease 1571

at 5 years, with no safety issues. These findings were then context of steroid intake relies mostly on clinical grounds and
confirmed by a larger, international, multicentre, retrospective experience. There are limited data comparing strategies be-
study including 187 patients, reporting a 10-year surgical tween primary anastomosis or secondary anastomosis in pa-
recurrence-free rate of 98.6%.205 tients with CD treated with steroids.217 However, prolonged
Performing a Kono-S anastomosis was associated with [> 6 weeks] and high-dose [≥ 20 mg prednisolone equivalent]
longer operative time, similar short-term outcomes, and steroid use are associated with postoperative infectious com-
likely lower endoscopic recurrence rate than side-to-side plications, including anastomotic leakage.150,175,218,219
anastomosis.206 In another two retrospective cohort studies
following patients for up to 5 years, Kono-S anastomosis
was associated with a lower leak rate than end-to-end anas- Statement 4.17: ECCO CD Treatment GL - SURGICAL [2024]
tomosis207 or stapled anastomosis,208 which in the authors’ We recommend strictureplasty as an alternative treatment
opinion could explain the lower surgical recurrence rate ob- option to resection in small-bowel CD [EL2]
served in the long term.
More recently, early results from the first RCT209 com- Location of CD in the ileum, use of biologics before surgery,
paring Kono-S and side-to-side anastomoses demonstrated a and non-conventional strictureplasty [SP] predict early site-

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significant reduction in the 6-month endoscopic recurrence specific recurrence after SP.220,221 However, procedure-specific
rate and mean Rutgeerts’ score, comparable postoperative recurrence rates are available only for some SP techniques.222
outcomes, and a trend toward a reduced surgical recurrence The wide range of recurrence rates after SP [3–25%] reflects
rate, although this was not statistically significant. This and the variability of the population case mix and, most import-
other trials are still ongoing, with definitive results expected antly, of the follow-up length.221 An extended follow-up time
in the near future. [> 5 years] is mandatory to appraise the true outcome of SP.221
Several meta-analyses, including the aforementioned RCT Morbidity and postoperative hospital length of stay were
and observational studies, concluded that Kono-S anasto- similar for bowel resection and SP.222–224 Overall, the results
mosis was associated with a reduced endoscopic recurrence of SP compare well with the recurrence rate after bowel resec-
rate and comparable short-term outcomes.200,210,211 More tion, while preserving bowel length.
limited evidence suggested a reduction in surgical recurrence
and leak rate in Kono-S anastomosis than with conventional Statement 4.18: ECCO CD Treatment GL - SURGICAL [2024]
anastomoses. However, the most recent prospective study We suggest segmental colectomy in selected cases of co-
on Kono-S did not confirm a reduction in endoscopic recur- lonic CD [EL4]
rence rates and reported similar Rutgeerts’ scores and clin-
ical recurrence rates between conventional anastomosis and
When a single colonic segment is affected, a segmental colec-
Kono-S.212 Therefore, a definitive conclusion on the benefit of
tomy may be the recommended course of action. On the other
a Kono-S anastomosis cannot yet be made. Multicentre RCTs
hand, the involvement of multiple colon segments generally
are currently ongoing across the USA and Europe and will
indicates [sub]total colectomy. A meta-analysis compared 223
probably provide definitive answers on the role of Kono-S
cases of subtotal or total colectomies with ileorectal anasto-
anastomosis.213–215
mosis and 265 cases of segmental colectomies in CD.225 In
this analysis, there were no significant differences in recur-
Statement 4.15: ECCO CD Treatment GL - SURGICAL [2024] rence rates, complications, or need for a permanent stoma.
There is insufficient evidence to recommend extensive However, it is worth noting that recurrence occurred on
mesenteric excision in surgery for ileocecal CD [EL4] average 4.4 years later in patients who underwent a subtotal
or total colectomy [p < 0.001].
Extensive mesenteric excision may reduce the incidence of A recent meta-analysis included patients who underwent
recurrence after resection by possibly removing a ‘sump’ of segmental colectomy [n = 500], subtotal colectomy [n = 510],
pro-inflammatory substances from the vicinity of the anas- or total proctocolectomy [n = 426]. Complications were
tomosis. The current evidence for this is weak. Two system- more frequent after segmental colectomy compared with sub-
atic reviews addressed extensive mesenteric excision,200,210 but total colectomy [OR: 2.84; 95% CI: 1.16–6.96] and after
both only included one small, historical, case-control study.216 proctocolectomy compared with subtotal colectomy [OR:
This single, case-control study compared 30 patients under- 0.19; 95% CI: 0.09–0.38].226 This indicates that subtotal col-
going extensive mesenteric excision with a surgical recurrence ectomy is generally considered a safer procedure, although
rate of 2.9% at 5 years with a historical control group of 34 segmental colectomy resulted in fewer patients requiring per-
patients who had a 5-year recurrence rate of 40%.216 Several manent stoma [OR: 0.52; 95% CI: 0.35–0.77]. Subtotal col-
ongoing trials address the possible benefit of a wide mesen- ectomy had higher rates of CD recurrence [OR: 3.53; 95%
teric excision in the context of CD. Such an excision cannot CI: 2.45–5.10] and need for repeat surgery [OR: 3.52; 95%
currently be recommended in routine care. CI: 2.27–5.44] than total proctocolectomy. However, no sig-
nificant difference in recurrence was observed between seg-
mental and subtotal colectomy. In rare situations where two
Statement 4.16: ECCO CD Treatment GL - SURGICAL [2024] distinct colon segments are affected, it may be worth consid-
We suggest a temporary stoma formation in patients with ering two segmental resections as an alternative to subtotal
CD if they are not sufficiently optimised for surgery [EL4] colectomy, particularly for patients who have extensive small-
bowel loss.11
The decision to create a stoma [primary anastomosis and A recent retrospective analysis that included 55 [sub]total
protective stoma or no anastomosis and split stoma] in the colectomies and 30 segmental colonic resections indicated a
1572 M. Adamina et al.

trend towards increased postoperative complications after in an Irish population-based study, patients with IBD-related
segmental colectomy [Clavien–Dindo grade ≥ III] of 13.3% CRC were about 7 years younger at cancer diagnosis than
versus 7.3% after [sub]total colectomy. Additionally, there patients with non-IBD CRC, but survived about 3 years
was a trend toward higher rates of hospital readmissions longer. Older age, male sex, smoking, and advanced CRC
[13.3% vs 1.8%] and reinterventions [13.3% vs 3.6%] after grade and stage were independently associated with shorter
segmental resection compared with [sub]total colectomy.227 survival times. When propensity score matching was used to
Another recent, multicentre, retrospective study including 687 analyse outcomes, the survival times of CRC patients with
patients concluded that segmental resection was a safe option and without IBD were not significantly different.234 Taken
compared with total colectomy, with the additional benefit together, these results reveal that patients with IBD tend to
of reducing ostomy formation without increasing the risk develop CRC at younger ages than patients without IBD.
of surgical recurrence, particularly in the era of biologics.228 However, no effect of IBD on patient survival has been con-
However, the heterogeneity of the included patients was a sistently demonstrated.
limitation of this analysis. The risk of CRC in CD increases with longer disease dur-
A further, retrospective, single-centre study included 200 ation, extent of colitis, a familial history of CRC, coexistent
patients who underwent segmental colectomy. A surgical re- primary sclerosing cholangitis, and the degree and duration

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currence rate of 31% was observed. Risk factors of recur- of inflammation. CRC in CD tends to have higher histological
rence and subsequent [sub]total colectomy in multivariate grade and more often mucinous/signet-ring histological
analysis were the presence of three or more affected sites [HR: characteristics.11,230,235–237
2.47; 95% CI: 1.22–5.00; p = 0.018] and presence of perianal The previous ECCO-ESCP consensus on surgery for CD11
disease [HR: 3.23; 95% CI: 1.29–8.07; p = 0.006].229 recommended proctocolectomy in fit patients with pre-
In summary, the extent of colonic resection is determined by operative diagnosis of cancer or high-grade dysplasia, due
the clinical presentation [elective vs emergency surgery] and to the multifocal nature of dysplasia in CD colitis and the
by the number of colonic segments involved [unisegmental vs reported high rate of metachronous colon cancer after seg-
pancolitis]. Segmental colectomy is generally favoured when- mental surgical resection.238,239 However, caution is required
ever feasible, as this does not increase the risk of recurrence, when comparing cancer incidence between patients with CD
particularly in the modern era of biologics and when other undergoing regular colonoscopies and the general population
risk factors for recurrence [such as number of affected loca- offered cancer screening; lead time bias may overestimate a
tions and presence of perianal disease] are absent. possible causal association. Furthermore, the onset of CD is
often unclear, whereeas many cancers are diagnosed concomi-
tantly or immediately after a diagnosis of CD and thus have
Statement 4.19: ECCO CD Treatment GL - SURGICAL [2024] a debatable association with CD. Indeed, the incidence of
We suggest proctocolectomy as a treatment for metachronous CRC after segmental resection is much lower
CD-associated colorectal cancer or high-grade dysplasia than initially thought240–242 and the prior reported high rate
and segmental colectomy followed by endoscopic surveil- of metachronous cancer may be attributed to inadequate
lance in selected cases [EL3] surgery or even underestimation of synchronous tumours.
Furthermore, most of the available data originate from the
Patients with chronic inflammation of the large bowel are at early 1970s, when both endoscopic and therapeutic interven-
an increased risk of development of colorectal cancer [CRC], tions were very different from current standards.
as described in an European evidence-based consensus: IBD Therefore, segmental resections and endoscopic surveil-
and malignancies.230 Two meta-analyses of cohort studies have lance may be proposed in selected patients after proper con-
clarified the increased risk of CRC in patients with IBD.231,232 sent or in patients who are at high risk for surgery.
The pooled standardised incidence ratio [SIR] for CRC was Importantly, patients with CRC in CD should be operated
1.7 [95% CI: 1.2–2.2] in all patients with IBD and 1.9 in CD according to the principles of oncological surgery, including
[95% CI: 1.4–2.5]. However, the HR of CRC increased in all adequate lymphadenectomy.243,244 The same principles of
age groups [HR: 1.40; 95% CI: 1.27–1.53], consistent with oncological surgery should be considered in the presence of
a recent Scandinavian cohort study.232 There was higher risk a colonic stenosis, and long-lasting extensive CD colitis can
with extensive colitis and younger IBD diagnosis [age < 30 easily be missed upon endoscopic biopsy. Strictureplasty is
years], with a SIR of 6.4 [95% CI: 2.4–17.5] and 7.2 [95% not recommended in this context.11,238
CI: 2.9–17.8], respectively. Cumulative risks of cancer were
1%, 2%, and 5% after 10, 20, and > 20 years disease dur-
ation, respectively. Statement 4.20: ECCO CD Treatment GL - SURGICAL [2024]
These reports indicate that the risk of CRC is increased in We suggest a defunctioning stoma for non-acute refractory
patients with IBD, but not to the extent previously reported CD colitis, to delay or avoid the need for colectomy [EL5]
and not in all patients.
In a Danish cohort,233 CRC patients with CD had a lower The following two options may be discussed in the presence
frequency of Duke’s A- and B-stage tumours [36% vs 42%] of refractory CD colitis: a [sub]total colectomy, particularly as
and a higher frequency of Duke’s C- [31% vs 27%] and a potentially life-saving procedure in fulminant colitis, and a
D-stage tumours [23% vs 21%], whereas the frequency of defunctioning ileostomy to divert the faecal stream and allow
unknown-stage tumours [10%] resembled that of non IBD- for remission, together with intensified medical therapy.245 A
related CRC. The 5-year adjusted mortality rate ratios for diverting ileostomy may delay further procedures, facilitate
patients with ulcerative colitis [UC] or CD were increased by perioperative optimisation, and allow for a limited resection
1.14 [95% CI: 1.03–1.27] and 1.26 [95% CI: 1.07–1.49], re- if required at a later stage [ie, segmental colectomy]. The clin-
spectively, compared with patients without IBD. In contrast, ical scenario in which a diverting stoma is performed to aid
ECCO Consensus Guidelines on Surgery in Crohn’s Disease 1573

the management of extensive perineal disease is covered else- 4.9. Postoperative management
where and is not the focus of the present statement.
The literature preceding the biologic era reported initial
remission rates of up to 90%246–249 following creation of a Statement 4.22: ECCO CD Treatment GL - SURGICAL [2024]
defunctioning stoma, which is more than the 50–80% re- We recommend endoscopic surveillance within 6–12
ported in more recent series.250,251 Lasting restoration of months after surgical resection in CD [EL2]
bowel continuity/stoma reversal was effective in up to two-
thirds of patients, but was much lower when perianal disease A systematic review that included one unblinded RCT and
was also present [ie, 29–42%.]6,7 Surgical complications of four retrospective cohort studies revealed a lower recurrence
defunctioning stoma creation were in the expected range of rate in the endoscopy-based management group than in the
3–10% for stoma prolapse/hernia and < 5% for renal failure control group.260 Similarly, another systematic review con-
due to high-output stoma.251 Further bowel resection was re- cluded that mucosal changes can be observed in up to 73%
ported in up to half of the patients in recent series.250,251 Risk of cases within 1 year after surgical resection, when patients
factors for proctocolectomy were severe refractory perianal undergo endoscopic monitoring.261
disease, requirement for combined medical therapy, and a his- In a study that randomised 174 patients in a 2:1 ratio,

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tory of more than one biologic drug. For these patients, early some underwent colonoscopy at 6 months with active
colectomy and end-ileostomy [as opposed to a defunctioning therapy and others did not undergo colonoscopy and re-
ileostomy] may be discussed. ceived standard care. At the 18-month time point, clinical
The following factors should be taken into account when recurrence was lower [37.7% vs 46.1%; RR 0.82; 95% CI:
a proctocolectomy is required and ileal pouch-anal anasto- 0.56–1.18] in the colonoscopy group and endoscopic recur-
mosis [IPAA] is considered. In general, more patients have rence was higher in the group that received standard care
postoperative pelvic sepsis and a higher pouch failure rate compared with those under active surveillance [67% vs
when compared with patients with IPAA for UC. Patients also 49%; p = 0.03].262
have more bowel movements and daytime incontinence when Another systematic review that included 26 prospective
compared with patients with IPAA for UC. It is worth noting studies reported the presence of mucosal lesions in up to 70%
that in selected patients with isolated CD colitis without of cases with a median endoscopic follow-up of 12 months.
small-bowel or perianal involvement, outcomes similar to pa- Notably, more than 50% of these lesions were located at the
tients with IPAA for UC can be obtained [no difference in anastomotic site. Interestingly, despite receiving medical treat-
pelvic sepsis, stool frequency, incontinence, score on quality- ment, 41% of patients exhibited significant lesions.263 These
of-life surveys, or pouch failure].11,252–256 findings are consistent with similar results presented by other
studies.264,265 Endoscopic monitoring within 6–12 months fol-
lowing surgical resection allows for identification of patients
Statement 4.21: ECCO CD Treatment GL - SURGICAL [2024] who may experience disease recurrence, even with ongoing
We recommend CD surgery is performed in high-volume medical therapy, enabling proactive intervention.
IBD centres [EL3]

The data and appreciation of the benefit of centralisa- Statement 4.23: ECCO CD Treatment GL - SURGICAL [2024]
tion of IBD surgery in high-volume centres is controversial. We suggest postoperative prophylactic medical therapy
Nationwide studies suggested lower mortality in high-volume after ileocolic resection in patients with CD at high risk of
centres, although patients who are frailer and sicker are recurrence [EL3]
overrepresented in these centres.257,258 The definitions of a
high-volume, expert centre and of referral criteria are particu- Prophylaxis for postoperative recurrence is recommended in
larly controversial. ECCO has defined quality-of-care criteria patients at high risk for recurrence. Thiopurines appear to be
and standards for the care of IBD patients, including patient more effective than placebo in preventing postoperative recur-
volume, in a position paper.259 rence, according to different studies.266 Infliximab was more
effective than placebo in preventing endoscopic, but not clin-
4.8. Practice points ical, recurrence in the prospective PREVENT trial.267 Overall,
When surgery becomes necessary, it is important to thor- anti-TNF agents are the most effective therapy in preventing
oughly assess the bowel, ideally preoperatively with MRI postoperative endoscopic recurrence.268 More recent evidence
enterography. MRI enterography may reveal a distinction from observational studies described the efficacy of biologics
between inflammatory strictures [amenable to intensified with different mechanisms of action [ustekinumab and VDZ]
medical therapy] and fibrotic strictures. Systematically as- in prevention of recurrence.269 A prospective study, pre-
sessing the bowel during surgery may identify further stric- sented in abstract form. demonstrated that VDZ was more
tures. To maximise bowel preservation, the IBD surgeon efficacious than placebo in preventing endoscopic recurrence.
should be familiar with the different kinds of strictureplasties, Patients treated with VDZ had a 77.8% chance of having a
including non-conventional strictureplasties. Nonetheless, lower Rutgeerts’ score than patients with placebo 6 months
strictureplasty of the colon is not recommended. after an ileocolic resection [p < 0.0001].270 A retrospective
The anastomotic technique of choice is not firmly es- multicentre study from Spain analysed postoperative recur-
tablished, although a stapled side-to-side anastomosis is rence rates in 40 patients treated with ustekinumab and 25
suggested in small-bowel or ileocolic resections. Whereas seg- treated with VDZ [all had previous exposure to anti-TNF].
mental colectomy is advisable when a single colon segment The cumulative probability of clinical postoperative recur-
is involved, an oncological proctocolectomy is recommended rence at 12 months after surgery was 32% and 30% for
when colonic dysplasia or a neoplasia is identified. ustekinumab and VDZ, respectively. The rate of endoscopic
1574 M. Adamina et al.

recurrence was 42% for ustekinumab and 40% for VDZ.271 Disclaimer
High-risk patients include those that smoke, have penetrating
The ECCO Guidelines are targeted at health care professionals
disease, or present with an IASC, fistula, or both.272,273
only and are based on an international consensus process.
This process includes intensive literature research as ex-
Statement 4.24: ECCO CD Treatment GL - SURGICAL [2024] plained in the methodology section and may not reflect subse-
We recommend extended thromboembolism prophylaxis quent scientific developments, if any, until the next Guidelines
following hospital discharge after CD surgery [EL2] update is prepared. Readers of the Guidelines acknowledge
that research about medical and health issues is constantly
Although thromboprophylaxis is well documented in patients evolving, and diagnoses, treatments, and dose schedules for
who have surgery after CRC, there is limited evidence in IBD. medications are being revised continually. Therefore, the
A recent systematic review suggested that postoperative deep European Crohn´s and Colitis Organisation [ECCO] encour-
vein thrombosis [DVT] risk was similar in IBD to that of pa- ages all readers to also consult the most up-to-date published
tients with advanced CRC. The risk was highest in those who product information and data sheets provided by the manu-
had a subtotal colectomy or a proctectomy. The dosage of low facturers, as well as the most recent codes of conduct and

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molecular weight heparin was also assessed in a single-centre safety regulations. Any treatment decisions are to be made
study, suggesting that a dose of 4000 IU/day of low molecular at the sole discretion and within the exclusive responsibility
weight heparin was insufficient for IBD patients.274 A minimal of the individual clinician and should not be based exclu-
duration of thromboprophylaxis of 2 weeks postoperatively sively on the content of the ECCO Guidelines. The European
was suggested.275 Crohn´s and Colitis Organisation [ECCO] and/or any of its
staff members and/or any consensus contributor may not be
held liable for any information published in good faith in the
5. Conclusion ECCO Consensus Guidelines. ECCO makes no representa-
There are many options and crossroads in decision making for tions or warranties, expressed or implied, as to the accuracy
surgery in CD. Some approaches have been tested over time or completeness of the whole or any part of the Guidelines.
and were described in these surgical Guidelines. Although ECCO does not accept, and expressly disclaims, responsibility
sufficient training, technical expertise, and an adequate case- for any liability, loss, or risk that may be claimed or incurred
load to achieve and maintain subspecialisation in IBD sur- as a consequence of the use or application of the whole or any
gery are important, the key to success in managing CD is a part of the Guidelines. When the Guidelines mention trade
multidisciplinary team, as no specialist alone can solve the names, commercial products, or organisations, this does not
CD equation. The present Guidelines have been written with constitute any endorsement by ECCO and/or any consensus
this interdisciplinary approach in mind and summarise the contributor.
currently available knowledge. The degree of certainty in
some aspects of surgery for CD is closer to eminence than evi-
dence, thus paving the way for further research and better an- Acknowledgements
swers. Consideration of patient lifestyle preference is integral We gratefully thank Dr Paul Freudenberger for the litera-
to shared decision making and key to achieve best standard ture search and full-text retrieval; Torsten Karge for sup-
of care. Revealing gaps in evidence is the first step, as research port on informatics and on the web Guidelines platform;
focused on clinical needs and gaps in the current evidence will and the ECCO Office for logistical and coordination sup-
inform Guideline updates. Meanwhile, dynamic integration port. We gratefully thank the EFCCA patient representa-
of gains in knowledge into the ECCO e-Guide will allow for tives: Bastien Corsat, Xavier Donnet, Evelyn Gross, Antonio
rapid dissemination. Guidelines provide guidance to the clin- Valdivia, Janek Kapper, and Lucie Lastikova who proactively
ician, who adapts expert knowledge, generic evidence, and collaborated in the development of these Guidelines. We
patient lifestyle preference to individualise care. It is hoped thank Ibrahim Ethem Gecim for his work in the abstract
that the present work will contribute to optimising care for screening process. We would like to thank and acknow-
patients with CD. ledge the ECCO National Representatives and additional
reviewers, who acted as external reviewers and provided
suggestions on the recommendations and supporting text
Funding to this document: Pascal Juillerat, Allesandra Soriano,
This project was initiated, funded, and supported by the Mark Samaan, Tiago Cúrdia Gonçalves, Edoardo Savarino,
ECCO. Federica Furfaro, Davide Giuseppe Ribaldone, Gulustan
Babayeva-Sadiqova, Aurelien Amiot, Gianmichele Meucci,
Iago Rodríguez Lago, Mathieu Uzzan, Gerassimos Mantzaris,
Conflict of Interest Beatriz Gros Alcalde, Vito Annese, Eduard Brunet Mas,
ECCO has diligently maintained a disclosure policy of poten- Maria Jose Garcia, Eirini Zach, John Marshall, Carla Felice,
tial conflicts of interest [CoI]. The conflict-of-interest declar- Maha Maher, Paul Pollack, Andreas Blesl, Negreanu Lucian,
ation is based on a form used by the International Committee Ferdinando D’Amico, Dimitrios Karagiannis, Patrick Allen,
of Medical Journal Editors [ICMJE]. The CoI statement is not Oliver Bachmann, Imerio Angriman, Anna Kagramanova,
only stored at the ECCO Office and the editorial office of Dahham Alsoud, Natália Queiroz, Usha Chauhan, Petra
JCC, but is also open to public scrutiny on the ECCO website Golovics, Chen Sarbagili, Lorenzo Bertani, Ulf Helwig, Clas-
[https://www.ecco-ibd.eu/about-ecco/ecco-disclosures.html], Göran af Björkesten, Ante Bogut, Anthony Buisson, Ignacio
providing a comprehensive overview of potential conflicts of Catalan-Serra, Aslı Çifcibaşı Örmeci, Marco Daperno, Mihai
interest of authors. Mircea Diculescu, Dana Duricová, Piotr Eder, Magdalena
ECCO Consensus Guidelines on Surgery in Crohn’s Disease 1575

Gawron-Kiszka, Ayal Hirsch, Ondrej Hradsky, Hendrik Laja, trointestinal and Abdominal Radiology [ESGAR]. Ecco-esgar
Sara Onali, Samuel Raimundo Fernandes, Christian Philipp guideline for diagnostic assessment in ibd part 1: initial diagnosis,
Selinger, Helena Tavares de Sousa, Svetlana Turcan, Sophie monitoring of known ibd, detection of complications. J Crohns Co-
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Author Contributions testinal and Abdominal Radiology [ESGAR]. Ecco-esgar guideline
for diagnostic assessment in ibd part 2: ibd scores and general prin-
MA, PM, HG, and TR coordinated the project; SM provided ciples and technical aspects. J Crohns Colitis 2019;13:273–84.
expert methodology advice, trained the working group mem- 16. Sturm A, Maaser C, Mendall M, et al. European crohn’s and colitis
bers, and performed the analysis of data; UK, BV, MC, CB, organisation topical review on ibd in the elderly. J Crohns Colitis
and JW coordinated the working groups; all the authors listed 2017;11:263–73.
contributed to the identification of relevant data and data 17. Gordon H. Ecco guidelines on therapeutics in Crohn’s Disease:
interpretation, and drafted and discussed the final recom- medical treatment. J Crohns Colitis 2024:jjae091. doi:10.1093/
mendations; all authors participated in the final consensus; ecco-jcc/jjae091.
18. Adamina M, Bonovas S, Raine T, et al. Ecco guidelines on
MA and PM drafted this manuscript.

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