Efficacy and Safety of Treatment of Complex Idiopathic Fistula-in-Ano Using Autologous Centrifuged Adipose Tissue Containing Progenitor Cells: A Randomized Controlled Trial

BACKGROUND: Mesenchymal stem cells derived from adipose tissue have been successfully used to promote sphincter-saving anal fistula healing. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of the use of autologous centrifuged adipose tissue in the healing process of cryptoglandular complex anal fistulas. DESIGN: This is a randomized controlled trial. SETTINGS: This study was conducted at a single center. PATIENTS: Patients with complex perianal fistulas not associated with Crohn's disease were included. Rectovaginal fistulas were not included. INTERVENTIONS: Patients were randomly allocated to receive treatment with centrifuged adipose tissue injection (experimental group) and without injection (control group) in combination with fistula surgery. MAIN OUTCOME MEASURES: The primary outcome was defined as the proportion of patients with complete fistula closure at 4 weeks (short-term outcome) and 6 months after surgery (long-term outcome). Healing was defined as when the external opening was closed with no perianal discharge on clinical assessment. The secondary outcome was safety that was evaluated by the analysis of adverse events up to 3 months after surgery. Pelvic MRI was performed at 3 months to assure safety and the accuracy of the clinical determination of healing. Postoperative pain, return to work/daily activities, persistent closure at 6 months, fecal incontinence, and patient satisfaction were evaluated. RESULTS: Fifty-eight patients who received centrifuged adipose tissue injection and 58 patients who did not receive centrifuged adipose tissue injection were included in the safety and efficacy analysis. After 4 weeks, the healing rate was 63.8% in the experimental group compared with 15.5% in the control group (p < 0.001). No major adverse events were recorded. Postoperative anal pain was significantly lower in the injection group. Time taken to return to work/daily activities was significantly shorter in the experimental group (3 days) than in the control group (17 days). At 6 months, persistent closure was similar in the 2 groups (86.2% vs 81%). Fecal Incontinence Score at 6 months after surgery was identical to the preoperative score. Patient satisfaction was high in both groups. LIMITATIONS: The absence of blinding, the lack of correlation between stem cell content, and the clinical outcome were limitations of the study. CONCLUSIONS: Autologous centrifuged adipose tissue injection may represent a safe, efficacious, and inexpensive option for the treatment of complex fistula-in-ano. See Video Abstract at http://links.lww.com/DCR/B607.