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.