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Contents lists available at ScienceDirect

Digestive and Liver Disease

jou rna l h om epage: www.elsev ier .com/ locate /d ld

limentary Tract

one-like resection, fistulectomy and mucosal rectal sleeve partialndorectal pull-through in paediatric Crohn’s disease with perianalomplex fistula

irolamo Mattioli a,b,∗, Luca Pioa,b, Serena Arrigoa, Alessio Pini Pratoa,iovanni Montobbioa, Nicola Massimo Dismaa, Arrigo Barabinoa

Giannina Gaslini Institute, Genoa, ItalyDINOGMI, University of Genoa, Italy

r t i c l e i n f o

rticle history:eceived 24 February 2015ccepted 6 May 2015vailable online xxx

eywords:omplex fistulaone-like resectionaediatricerianal Crohn’s

a b s t r a c t

Background: Perianal abscesses and fistulae have been reported in approximately 15% of patients withpaediatric Crohn’s disease and they are associated with poor quality of life. Several surgical techniqueswere proposed for the treatment of perianal Crohn’s disease, characterized by an elevated incidence offailure, incontinence, and relapse.

Aim of our study was to present the technical details and results of our surgical technique in case ofrecurrent, persistent, complex perianal ano-rectal destroying Crohn’s disease not responding to medicaltreatment.Methods: Data of patients who underwent surgical treatment (cone-like resection, fistulectomy, sphincterreconstruction, endorectal advancement sleeve flaps like in Soave endorectal pull-through) for com-plicated high-level trans, inter or suprasphincteric fistulae between January 2009 and June 2014 wereretrospectively reviewed.Results: 20 surgical procedures were performed in 11 patients (males 72.7%) with transsphincteric (n = 5),intersphincteric (n = 4) and suprasphincteric (n = 2) fistulae. Three patients needed a second treatment.

Two patients needed more than 2 surgeries and one temporary colostomy. No patient presented analincontinence at 15 months’ median follow-up.Conclusions: Although several procedures may be required to obtain a complete remission of perianallesions, in our series the proposed surgical technique seemed effective and safe, preserving anal conti-nence in all treated cases and reducing the need of faecal diversion.

Gast

© 2015 Editrice

. Introduction

Paediatric Crohn’s disease (PCD) accounts for 20–25% of totaliagnosis of this inflammatory bowel disease, with an incidenceanging from 0.2 to 9.5:100.000 children in the United States.

Perianal disease has been reported in 8–15% of paediatricatients [1,2].

Complex fistula can have transsphincteric, suprasphincteric,ntrasphincteric and extrasphincteric perianal localization [3] and

Please cite this article in press as: Mattioli G, et al. Cone-like resectionthrough in paediatric Crohn’s disease with perianal complex fistula. D

epresents a challenge for paediatric surgeons.In recent years, magnetic resonance imaging (MRI) has become

n important instrument to evaluate complex fistula severity and

∗ Corresponding author at: Paediatric Surgery Unit, Istituto Giannina Gaslini, Largo. Gaslini 5, 16147 Genoa, Italy. Tel.: +39 010 56362217; fax: +39 010 3075092.

E-mail address: girolamomattioli@ospedale-gaslini.ge.it (G. Mattioli).

ttp://dx.doi.org/10.1016/j.dld.2015.05.003590-8658/© 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All

roenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

pelvic anatomy, providing indications for the correct type of sur-gical intervention. However, many false negative results and poorsensitivity of this tool have been reported [4,5].

Different approaches have been described for the treatment ofcomplex fistula in children, including simple drainage, mobilizationof tissue flaps, seton placement, fistulotomy, anus-sparing procto-colectomy, and defunctioning ileostomy [6–8]. However, the riskof complications remained high, with more than one procedure forrecurrence in 29–50% of cases [8–10].

Aim of this study was to report on the surgical technique usedin our institution, describing surgical details and main results.

2. Materials and methods

, fistulectomy and mucosal rectal sleeve partial endorectal pull-ig Liver Dis (2015), http://dx.doi.org/10.1016/j.dld.2015.05.003

2.1. Study population

All patients with diagnosis of perianal PCD admitted to ourInstitute for complex fistula (defined according to Bell criteria)

rights reserved.

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Fig. 1. Illustration of cone-like resection and rectal sleeve. IS, internal sphincter;ES, external sphincter; IF, intersphincteric fistula; TF, transsphincteric fistula; SS,

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ith recurrent/persistent, anorectal involvement not respondingo medical treatment, between January 2009 and June 2014 wererospectively included in a database.

Patients with simple fistula (subcutaneous fistula) werexcluded from the study.

This study was performed according to national ethical guide-ines and informed consent was obtained for surgical treatment andata collection from parents or guardians. Data including demo-raphics, previous surgical and medical treatments, surgical detailsf interventions, and clinical follow-up were retrospectively ana-yzed.

All patients were studied with pre-operative MRI. All patientsere continent before surgical procedures.

.2. Cone-like resection technique (CLR)

Peri-operative antibiotic prophylaxis with metronidazole wasdministered. Patients were placed in the lithotomy position undereneral anaesthesia without preoperative bowel preparation. Arobe was inserted through the fistula to measure the distance from

ts internal opening. The fistula tract was completely mobilized en-loc with the granulation tissue reaching the normal fatty tissueear the pelvic floor. A cone-like excision of skin and perianal tis-ue was performed with the cone base in the perineum includinghe anal canal if affected, and the cone apex in the rectal wall wherehe fistula opened (Figs. 1 and 2).

Exposure of levator ani was needed to completely remove theffected tissue, including also rectal wall and anal sphincters ifnvolved.

The second step of this surgical approach was to recreate thenal canal. The rectal sleeve was prepared proximally to the inter-al opening of the rectum. We used Soave endorectal pull-through

Please cite this article in press as: Mattioli G, et al. Cone-like resectionthrough in paediatric Crohn’s disease with perianal complex fistula. D

ERPT), pulling the normal rectal mucosa to the anal skin and sutur-ng the sphincters to recreate anal ring normal shape. The perianalkin was always left open in order to reduce infection risks. No morehan two areas were treated simultaneously (Figs. 2 and 3).

ig. 2. The chronic Crohn’s granulation tissue involves skin, fatty tissue, anal sphincter anreatment, therefore the inflamed tissue should be completely removed before completereviously placed seton.

suprasphinteric fistula; R, rectum; RS, rectal sleeve; CLFR, cone-like fistulectomyresection.

2.3. Endpoints

The primary endpoint was clinical recurrence, defined symp-tomatic recurrence requiring surgical treatment.

, fistulectomy and mucosal rectal sleeve partial endorectal pull-ig Liver Dis (2015), http://dx.doi.org/10.1016/j.dld.2015.05.003

Secondary endpoints were definition of 30-day post-operativecomplication rate using Clavien-Dindo classification [11], assess-ment of post-operative faecal incontinence using Yamataka score

d rectal wall. In selected cases, when there is recurrence despite adequate medical destruction of sphincter activity due to risk of sepsis. The blue arrow indicates the

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Fig. 3. Cone-like resection includes removal of ano-rectal canal and perianal tis-sue (skin and subcutaneous) macroscopically involved by Crohn’s granulomatosisreaching the normal muscle of the perineum (levator ani, blue arrow). The secondstep includes restoration of normal continuity of the ano-rectal canal and sphincteractivity (yellow arrow). The proximal rectal mucosa is pulled down to the perianalskin. The anal ring is recreated by suturing the normal muscle. The skin is left open.Ts

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Table 1Overall patient population characteristics (n = 11).

Characteristic N (%)

Males 8 (72.7)Median age (years) 12 (range 5–19)Transsphincteric fistula 5 (45.4%)Intersphincteric fistula 4 (36.4%)Suprasphincteric fistula 2 (18.2%)Median PDAI 5 (range 3–12)Previous surgery

Seton 4 (36.4%)Abscess drainage 6 (54.5%)Fistulotomy 1 (9.1%)

Median operative time (min) 40 (range: 20–80)Median hospital stay (days) 4 (range: 3–7)Median FLACC score 0Median number of procedures 1 (range: 1–5)Complications 0

gical procedures.

he aspect of resection is cone-like, the apex is in the rectum and the base is thekin of the perineum.

12], and analysis of post-operative pain using Faces, Legs, Activity,ry, and Consolability (FLACC) score [13].

Follow-up was performed with clinical evaluation.

.4. Statistical analysis

Continuous variables are reported as means and standard devi-tion or median and range and were compared using Student’s tests; categorical variables are reported as n (%) and were comparedsing Chi-squared tests or Fisher’s test. Possible risk factors as aget presentation, type of previous surgical treatment, pre-operativer post-operative medical treatment were analyzed with statisticalignificance defined as p < 0.05.

. Results

From January 2009 to June 2014, 11 patients were treated (72.7%ales, median age at surgery 12 years, range: 5–19 years).In two patients perianal disease appeared after diagnosis of

rohn’s disease (after 1 and 8 years), during immunosuppres-ive therapy (azathioprine) and on mesalazine. In the other cases,rohn’s disease was diagnosed during the evaluation of perianalisease. Location was ileocaecal (n = 7), ileocolic (n = 3), and panen-eric (n = 1).

At preoperative endoscopy, rectal inflammation was presentnly in 2 cases (18.2%). One girl, previously followed for syndromiciarrhoea by home parenteral nutrition, presented with perianalectal Crohn’s-like disease involvement. Median Perineal Diseasectivity Index (PDAI) was 5 (range: 3–12).

Diagnosis and classification of perineal disease were made byhe surgeon with evaluation under anaesthesia with pelvic MRI.

Four subjects were initially treated at another hospital (3 withimple drainage and seton placement, 1 with fistulotomy). Oneatient presented a gluteus abscess and drainage with seton place-ent was performed along with prolonged antibiotic treatment.

Please cite this article in press as: Mattioli G, et al. Cone-like resectionthrough in paediatric Crohn’s disease with perianal complex fistula. D

fter abscess resolution, complex fistula persisted. The other patients underwent simple drainage before CLR (54.5%). In 2ases, patients were receiving medical treatment with biologics,

PDAI, Perineal Disease Activity Index; FLACC, Faces, Legs, Activity, Cry and Consola-bility score.

azathioprine and thalidomide (18.2%); in the other 9 cases onlyantibiotics were administered.

The locations of the fistulae are shown in Table 1; transsphinc-teric location was present in 5 patients (45%).

Median surgery duration was 40 min (range 20–80 min) andmedian hospital stay was 4 days (range 3–7 days; Table 1).

Anti-TNF therapy was started in all patients within 10 days post-operatively, for a minimum of 12 months. No significant adverseeffects were observed. Clinical and endoscopic follow-up was per-formed, post-operative MRI was performed in complex cases withmore than two recurrences requiring repeated surgery or to rule outabscess. Step down to thiopurines was performed only in patientswith sustained clinical and endoscopic remission. Median follow-up was 15 months (range 11–56 months).

A total of 20 CLRs with rectal sleeve were performed. In 6 casescomplete remission was obtained after the first operation (54.5%).The remaining 5 required subsequent surgeries for relapses or newlocalizations. Three patients needed a second intervention, one athird procedure. One patient needed five treatments (Supplemen-tary Table S1) and required colostomy for the recurrence of complexfistula, despite biological treatment. Colostomy was closed after 12months and the patient underwent clinical follow-up.

The median number of procedures to obtain fistula healing was1 (range: 1–5).

Evidence of wound healing by second intention was providedin the first month of follow-up (Fig. 4), and at the end of surgicaltreatment all eleven patients healed with complete restitutio adintegrum. No other minor recurrences were observed.

Age at surgery, absence of previous surgical treatments, type ofmedical treatment before surgical procedure were not statisticallyrelated with recurrence. Post-operative pain was easily controlledwith elastomeric pump (chirocaine plus clonidine) for the first twodays and with non-steroidal anti-inflammatory drugs on day threeevery 8 h. Daily FLACC score was 0 for all patients.

No major complications nor anal incontinence were observed(Table 1).

4. Discussion

Complex fistula is a debilitating condition for paediatricpatients. Several treatments have been proposed, however the riskof recurrence remains high with a long history of medical and sur-

, fistulectomy and mucosal rectal sleeve partial endorectal pull-ig Liver Dis (2015), http://dx.doi.org/10.1016/j.dld.2015.05.003

Very few studies on major surgical treatments for paediatriccomplex fistula are available in the literature. Current NASPHGANguidelines [6] recommend surgeons not to perform advancement

ARTICLE ING ModelYDLD-2884; No. of Pages 5

4 G. Mattioli et al. / Digestive and Live

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nd continence. The cosmetic aspect is not objectively evaluated but scar retractions limited and anal shape is normal.

aps or major surgery for high risk of failure, suggesting colostomyr ileostomy in case of severe or recurrent perianal Crohn’s dis-ase, especially in case of refractory infectious complications (suchs recurrent abscess). Fistulectomy and other major surgical pro-edures did not gain popularity in the treatment of complex fistulaor the risk of sphincter injury and incontinence.

In our opinion, it is better to completely remove perianal chronicnflammatory tissue, obviously only in case of persistent, recurrentomplex disease not responding to medical treatment.

The purpose of this study was to use cone-like resection to reachomplete removal of granulation tissue (fistulectomy) and recreatehe ano-rectal canal. Sphincteric activity was restored using ERPTith rectal sleeve as main surgical technique in complex fistula

n order to reach primary healing, low recurrence rate, and mini-al risk of sphincter injury when sphincteric section was necessary

o remove all inflammatory tissue. ERPT allows the restoration ofearly normal perineal shape and limited scar retractions.

In our series of 11 patients with complex fistula, cone-likestulectomy with rectal sleeve was a safe and well-tolerated pro-edure. Fistula healing rate was 54.5% with no case of faecalncontinence after the first surgical procedure and 100% after max-mum 5 procedures.

In accordance to Arroyo et al. [14] our series confirms that fis-ulectomy with sphincteric surgery is a procedure with limited riskf faecal incontinence.

The role of faecal diversion for complex fistula remains unclearn the literature. In adult patients, the reported incidence is about1% [15], while in children the incidence of faecal diversion waseported in few articles, and in the largest series, 23% of cases hadefunctioning ileostomy with 38% of stoma-related complications7].

Though faecal diversion is an accepted major invasive treat-ent for complex fistula, in addition to stoma complications the

hild’s quality of life must also be considered. In adult patients sometudies on quality of life of have been published [16–18], to ournowledge, there is only one reported study on this topic in theaediatric population [19].

In our series, CLR was used as first major surgical procedurend faecal diversion was associated with fistulectomy only in oneatient (9%) with recurrent complex fistula and high risk of sepsis.

Please cite this article in press as: Mattioli G, et al. Cone-like resectionthrough in paediatric Crohn’s disease with perianal complex fistula. D

he introduction of biologic agents has dramatically changed theherapeutic strategy for IBD in children. The first evidence-basedractical guidelines on medical management in paediatric-onset

PRESSr Disease xxx (2015) xxx–xxx

Crohn’s disease have recently been published. Among the recom-mended biologics, anti-TNF agents are the treatment of choice inactive perianal fistulising disease in combination with appropriatesurgical intervention [20].

Combined anti-TNF therapy and surgery showed improvedhealing and lower recurrence of fistulae compared with surgeryalone in paediatric patients [21]. Combined treatment was also suc-cessful in adult patients with faster and prolonger fistula healing asdescribed by Sciaudone et al. [22].

Hukkinen reported a 70% healing rate in 13 patients and setonswere kept for 8 months [23]. In our series, all patients recov-ered from complex fistula and wounds healed by second intentionwithin one month.

NASPHGAN guidelines also suggested seton placement for treat-ment of paediatric complex fistula but as reported by Langer et al.[6,7], in some cases up to 7 placements with multiple anaesthe-sia procedures can be required. Furthermore, reported healing ratereported is low.

CLR is characterized by a low number of surgical interventionsand consequently of anaesthesia procedures in children. CLR alsoallows an easy post-operative pain management: morphine is notrequired and patients may be discharged only with non-steroidalanti-inflammatory drugs.

In our experience, CLR is a safe and well-tolerated techniquewith high primary healing and low recurrence rates, without risk ofsphincter injury and faecal incontinence when performed by expe-rienced surgeons. In some cases multiple procedures are required,and adequate medical treatment with biologics is needed to con-solidate remission. CLR could be considered as a primary majorsurgical technique in children with complex fistula, in associationwith biologics, reserving enterostomy only for very difficult non-responder cases.

However, as reported by Pellino et al. [24], other surgical treat-ments like fibrin glue or adipose tissue-derived stem cell injectionhave shown promising preliminary results and further studies arerequired to improve surgical outcomes for the treatment of com-plex fistula.

Conflict of interestNone declared.

Acknowledgements

We thank Anna Capurro for her help in revising the manuscript.

Appendix A. Supplementary data

Supplementary data associated with this article can be found, inthe online version, at http://dx.doi.org/10.1016/j.dld.2015.05.003

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