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Introduction

Background & Objectives

Complex perianal fistulas in CD respond suboptimally to combined surgical/biologic therapy (healing ≤≈60%);
Autologous micro-fragmented adipose tissue (M-Fat) injection is minimally invasive and sphincter-sparing with encouraging pilot data

CD = Crohn’s disease; PCD = perianal Crohn’s disease; M-Fat = micro-fragmented autologous adipose tissue; MRI = magnetic resonance imaging; RCT = randomized controlled trial.

Laureti S, et al. UEGW 2025; Abstract [815].

Methods

Population: Italian multicentre, double-blind, randomized controlled trial (ATTIC) in adults with persistent complex fistulizing PCD refractory to a biosurgical approach/anti-TNF
Randomization (1:1):

Baseline pelvic MRI, surgical drainage with fistulectomy
M-Fat 15–20 cc (enzyme-free processed lipoaspirate) injected at the internal orifice and along tracts
Control: suture of internal orifice + 15 cc saline injection

Endpoints (W24): �Combined remission = clinical (no drainage on gentle compression) AND radiologic healing (no residual collections >3 mm). �Clinical remission = clinical healing of all external openings (without MRI confirmation).

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AUTOLOGOUS MICROFRAGMENTED ADIPOSE TISSUE (TAAM) INJECTION

*Absence of residual collections > 3mm

Laureti S, et al. UEGW 2025; Abstract [815].

Injection of microfractured adipose tissue overcomes these complex requirements.
Commercially available technology provides injectable autologous microfragmented adipose tissue without cell expansion or enzymatic processing in the same surgical session.

Pericytes become functional MSCs upon tissue damage, secreting bioactive molecules with immunomodulatory and anti-inflammatory properties, and promoting a regenerative micro-environment.

Pilot Study: Combined Surgical Drainage and MFat Injection

(Laureti et al. IBD, 2020)

15 pts with multi-refractory complex fistulizing PCD

Combined remission*: 66.7% (10/15 pts)

Clinical remission: 93.3% (14/15 pts)

2024 Long-Term Follow-Up Study (mean f.u. 6.7 yrs) �(Laureti et al. IBD, 2024)

Recurrence rate: 10% (6/6%)
1 delayed healing
Reoperation in 4 pts: (1 or 2 procedures) flap, flap + Lipogems
Final healing rate: 86.6%

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Methods

Laureti S, et al. UEGW 2025; Abstract [815].

Treatment Group: Surgical Drainage & MFat Transplant

Control Group: Sham Procedure

Phase 1: Adipose Tissue Harvesting

A board-certified plastic surgeon performed manual liposuction using a 13G cannula and a 20 mL VacLok syringe, yielding 60–100 mL of lipoaspirate.

Phase 2: Lipoaspirate Processing

Immediately, the adipose tissue was processed with the system to create minimally manipulated MFat, ready for transplantation.

Phase 3: Surgical Drainage & MFat Injection

Following EUA, a “cone-like” partial fistulectomy was performed carefully, preserving the sphincter plane.

Then, 15–20 mL of MFat were circumferentially injected into the submucosal tissue and along the fistula tract.

A 6-0 absorbable suture was applied to the skin of the thigh, and the skin was gently pinched to simulate the liposuction procedure.

Following EUA, a “cone-like” partial fistulectomy was performed carefully, preserving the sphincter plane.

The internal mucosal opening was closed using absorbable 2/0 polyglactin sutures, and the closure integrity was confirmed by injecting 10 mL of sterile saline through the external opening under pressure.

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Results (Primary Outcome)

Worse outcomes

Univariate logistic regression: �Age >45 years; low BMI

Multivariate logistic regression:

Age >45 years

Laureti S, et al. UEGW 2025; Abstract [815].

66 pts completed the study (33 per group) out of 80 pts randomized

Treatment

Control

Healed

Not Healed

81.8%

18.2%

42.4%

57.6%

p < 0.005

Combined Remission

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Results (Secondary Outcome)

Safety:

10% of 33 patients in the Treatment group and 8.1% of 33 in the Control group experienced AEs.
1 (3%) of patients in the Treatment group versus 2 (6%) in the Control group experienced serious adverse events.
2 patients (6%) in the Treatment group and 2 (6%) of 33 in the Control group withdrew from the study because of TAEs (unrelated to treatment).

Laureti S, et al. UEGW 2025; Abstract [815].

Treatment

Control

Remission

No Remission

81.8%

18.2%

42.4%

57.6%

p < 0.005

Clinical Remission

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Conclusions

M-fat injection following fistulectomy is a potentially safe, effective therapy for the management of complex refractory perianal disease.

Significance to clinical practice

Difficult to determine the additional benefit of M-Fat injection given that the surgical methods differed between the groups. While both groups underwent fistulectomy, there was no internal closure of the fistula tract in the M-FAT group.
Further studies are required to confirm these findings and to determine if the addtional of surgical closure of the internal opening with mFat injection would improve outcomes

Laureti S, et al. UEGW 2025; Abstract [815].

Introduction: Complex perianal fistulas represent one of the most challenging manifestations of Crohn’s disease. Combined surgical and medical therapy with biologic drugs represents today the first-line treatment option, but its efficacy does not exceed 60% in terms of healing. Recently, new therapeutic approaches, such as autologous microfragmented adipose tissue (M-Fat) injection, have shown promising results. Indeed, a recent non-profit prospective pilot study on 15 patients has demonstrated that the local injection of M-Fat is a safe and promising “rescue therapy” for patients with multiresistant complex fistulizing Crohn’s disease (PCD), with a 66.7% rate of combined remission in such difficult patients. It has to be highlighted that the M-Fat injection is minimally invasive, with less risk of sphincteric damage and can be carried out in day-surgery setting.

Aims & Methods: The primary aim of this multicentre double-blind randomized controlled trial (ATTIC) is to evaluate the efficacy of the infiltration of M-Fat in the healing of perianal complex fistulas not-responding to treatment with biologics. Consecutive patients referring to the 6 investigation Centers for surgical treatment of persistent complex fistulizing PCD refractory to biosurgical approach were assessed for eligibility. After baseline pelvic magnetic resonance imaging, those included were submitted to surgical drainage with “cone-like” fistulectomy, and then randomized to receive a 15 to 20 cc local injection, at the internal orifice level and along fistula tracts, of M-Fat obtained by a lipoaspiration and processed with an enzyme-free technology (treatment group), or a suture placement and injection of 15 cc of saline solution at the internal orifice (control group). Clinical follow-up were conducted at 2, 4, 8, 12, and 24 weeks; at 24 weeks after surgery, pelvic magnetic resonance was obtained. Success was defined as “combined remission”, combination of clinical (absence of drainage upon gentle finger compression) and radiological healing (absence of residual collections > 3 mm). Clinical remission was defined as clinical healing of all external openings not confirmed at radiological assessment.

Results: An overall 92 patients were screened, and 66 (33 per group) completed the 24-week follow-up. A statistically significant difference in favour of the treatment group in terms of combined remission emerged at the primary endpoint at 24-week follow-up (control group, 18.18%; treatment group: 57.58%; p = 0.0020). No significant differences in clinical outcome measures were encountered at any of the other follow-up points. No significant differences emerged between the groups in terms of recurrence rate, complication rate, and number of adverse events. Clinical remission was 63.64% in the treatment group compared to 51.52% in the control group with no statistically significant difference (p > 0.05).

Conclusion: This multicentre double-blind randomized controlled trial demonstrates that the intraoperative injection of M-Fat, associated with surgical complete drainage of perianal sepsis, is safe, effective, and reproducible in healing complex multirefractory perianal Crohn's disease, while improving the quality of life and significantly reducing the risk of definitive oostomy.

Nothing to disclose: Yes

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Traitement des fistules périanales complexes de la maladie de Crohn par tissu adipeux autologue micro-fragmenté (M-Fat) : essai contrôlé randomisé ATTIC

Silvio Laureti; Luca Sofo; Andrea Cappelli; Federico Colombo; Giacomo Luglio; Simone Scaringi; Chiara Isopi; Federico Sacchetti; Giacomo Clerico; Paolo Danelli; Marco Cricrì; Francesco Ficari; Lorenzo Gentilini; Anisha Menon; Paolo Gionchetti; Gianluca Poggioli; Antonino Spinelli

Slides compiled by Dr. Cynthia Seow

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Introduction

Contexte et objectifs

Les fistules périanales complexes dans la MC répondent de façon sous-optimale au traitement combiné chirurgical/biologique (guérison ≤≈60 %)
L’injection de tissu adipeux autologue micro-fragmenté (M-Fat) est une approche peu invasive et épargnant le sphincter, appuyée par des données préliminaires encourageantes

MC = maladie de Crohn; MCP = maladie de Crohn périanale; M-Fat = tissu adipeux autologue micro-fragmenté; IRM = imagerie par résonance magnétique; ECR = essai contrôlé randomisé.

Laureti S, et al. UEGW 2025; Abstract [815].

Méthodes

Population : essai contrôlé randomisé italien multicentrique, à double insu (ATTIC), chez des adultes présentant une MCP fistulisante complexe persistante, réfractaire à une approche biosurgicale/anti-TNF
Randomisation (1:1) :

IRM pelvienne de base, drainage chirurgical avec fistulectomie
M-Fat 15–20 cc (lipoaspirat traité sans enzymes) injecté à l’orifice interne et le long des trajets fistuleux
Témoin : suture de l’orifice interne + injection de 15 cc de solution saline

Endpoints (Semaine 24): �Rémission combinée = clinique (absence d’écoulement à la compression douce) ET guérison radiologique (absence de collection résiduelle >3 mm).�Rémission Clinique = guérison clinique de tous les orifices externes (sans confirmation par IRM).

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Injection de tissu adipeux autologue micro-fragmenté (TAAM)

*Absence de collections résiduelles > 3 mm

Laureti S, et al. UEGW 2025; Abstract [815].

L’injection de tissu adipeux micro-fragmenté permet de répondre à ces exigences complexes.
Une technologie commerciale disponible fournit un tissu adipeux autologue micro-fragmenté injectable, sans expansion cellulaire ni traitement enzymatique, au cours d’une même intervention chirurgicale.

Les péricytes deviennent des CSM fonctionnelles lors d’une lésion tissulaire, sécrétant des molécules bioactives aux propriétés immunomodulatrices et anti-inflammatoires et favorisant un micro-environnement régénératif.

Étude pilote : drainage chirurgical combiné et injection de M-Fat (Laureti et al. IBD, 2020)

15 patients présentant une MCP fistulisante

complexe multi-réfractaire

Rémission combinée* : 66,7% (10/15 pts)

Rémission Clinique : 93,3% (14/15 pts)

Étude de suivi à long terme 2024 (f.u. moyen 6,7 ans)�(Laureti et al. IBD, 2024)

Taux de récidive : 10 % (6/6 %)
1 guérison retardée
Réintervention chez 4 patients : (1 ou 2 interventions) lambeau, lambeau + Lipogems
Taux de guérison finale : 86,6%

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Méthodes

Laureti S, et al. UEGW 2025; Abstract [815].

Groupe de traitement : drainage chirurgical et greffe de M-Fat

Groupe témoin : procédure factice

Phase 1: prélèvement de tissu adipeux

Un chirurgien plasticien certifié a réalisé une liposuccion manuelle à l’aide d’une canule 13G et d’une seringue VacLok de 20 mL, produisant 60–100 mL de lipoaspirat.

Phase 2: traitement du lipoaspirate

Immédiatement, le tissu adipeux a été traité au moyen du système afin d’obtenir un M-Fat minimalement manipulé, prêt pour la transplantation.

Phase 3: drainage chirurgical et injection de M-Fat

Après un examen sous anesthésie (EUA), une fistulectomie partielle « en cône » a été réalisée avec précaution, en préservant le plan sphinctérien.

Ensuite, 15–20 mL de M-Fat ont été injectés de façon circonférentielle dans le tissu sous-muqueux et le long du trajet fistuleux.

Un fil résorbable 6-0 a été appliqué sur la peau de la cuisse, et la peau a été pincée délicatement afin de simuler la procédure de liposuccion.

Après l’EUA, une fistulectomie partielle « en cône » a été réalisée avec précaution, en préservant le plan sphinctérien.

L’orifice muqueux interne a été fermé au moyen de sutures résorbables en polyglactine 2/0, et l’intégrité de la fermeture a été confirmée par l’injection de 10 mL de solution saline stérile à travers l’orifice externe sous pression.

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Résultats (critère principal)

Moins bons résultats

Régression logistique univariée : �âge >45 ans; IMC faible

Régression logistique multivariée :

âge >45 ans

Laureti S, et al. UEGW 2025; Abstract [815].

66 patients ont terminé l’étude (33 par groupe) sur 80 patients randomisés

Traitement

Témoin

Guérison

Non guéri

81,8%

18,2%

42,4%

57,6%

p < 0,005

Rémission combinée

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Résultats (critère principal)

Sécurité :

10 % des 33 patients du groupe Traitement et 8,1 % des 33 patients du groupe Témoin ont présenté des événements indésirables (EI).
1 patient (3 %) dans le groupe Traitement versus 2 (6 %) dans le groupe Témoin ont présenté des événements indésirables graves.
2 patients (6 %) dans le groupe Traitement et 2 (6 %) des 33 patients dans le groupe Témoin se sont retirés de l’étude en raison d’EI liés au traitement (TAE), non liés au traitement étudié.

Laureti S, et al. UEGW 2025; Abstract [815].

Rémission

Absence de rémission

81,8%

18,2%

42,4%

57,6%

p < 0,005

Rémission clinique

Traitement

Témoin

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Conclusions

L’injection de M-Fat après fistulectomie est un traitement potentiellement sûr et efficace pour la prise en charge de la maladie périanale complexe réfractaire

Incidences sur la pratique clinique

Il est difficile de déterminer le bénéfice additionnel de l’injection de M-Fat puisque les techniques chirurgicales différaient entre les groupes. Bien que les deux groupes aient subi une fistulectomie, il n’y avait pas de fermeture interne du trajet fistuleux dans le groupe M-FAT
Des études supplémentaires sont nécessaires pour confirmer ces résultats et déterminer si l’ajout d’une fermeture chirurgicale de l’orifice interne associée à l’injection de M-Fat permettrait d’améliorer les résultats cliniques

Laureti S, et al. UEGW 2025; Abstract [815].