Stem Cell Injection for Complex Refractory Perianal Fistulas in Crohn's Disease: A Single Center Initial Experience

Abstract

From 30 to 70% of patients with Crohn's disease (CD) may develop perianal fistulas during their lifetime. The medical and surgical management of this complication is challenging, and its treatment still gives unsatisfactory results. However, recent studies on adipose-derived mesenchymal stem cells have proven their anti-inflammatory and immuno-modulatory potential, representing a new promising tool in the treatment of such stubborn disease. We report our initial experience with three patients who had recurrent perianal CD treated with local infiltration of stem cell darvadstrocel (Alofisel). All the patients had a long history of perianal disease refractory to multiple medical and surgical treatments. The preoperative workup included transperineal ultrasound (TP-US), pelvic MRI, and colonoscopy that ruled out active proctitis in all the patients. The post-treatment follow-up included clinical assessment at 1, 3, and 6 months with repeated MRI and TP-US at 6 months. At 6 months, 2 patients had a clinical response despite radiological persistence of fistula tracts, while one patient presented perianal fistula recurrence complicated by perianal abscess. Although our experience is limited to 3 patients and a short follow-up, our results confirm that darvadstrocel injection is a safe procedure, with a good clinical response in most of the patients, but that it apparently had no effect on the anatomical modification of the fistula tracts. Long-term results, with a rigorous assessment of anatomical lesions, are still needed to support the promising data of the literature.

Keywords: Crohn's disease; inflammatory bowel disease; mesenchymal; perianal abscess and fistula; postoperative outcomes; stem cells.

Figure 1

Surgical procedure. Panel (A) shows the fistula's internal orifice closure with a 2/0 absorbable stitch. Panel (B) shows the stem cell (Darvadstrocel) injection in the tissue around the internal orifice and through the external orifice into the fistula walls.

Figure 2

Case 1 imaging pre- and post-surgery. Panels (A, B) show preoperative pelvic magnetic resonance imaging and 3D reconstruction highlighting a complex branched perianal fistulising disease with trans-sphincteric fistulas joining in the posterior plane with two external orifices on the right and one on the left, with a 2-cm abscess in the left ischioanal fat. Panels (C, D) show 6-month MRI follow-up, with the persistence of fistula tracts, less signs of inflammation, less thickening, contrast enhancement, and no fluid collections.

Figure 3

Case 2 imaging pre- and post-surgery. Panels (A, B) show pre-operative pelvic magnetic resonance imaging and 3D reconstruction showing two active complex trans-sphincteric fistulas: on the left a trans-sphincteric fistula with a seton in place, and on the right a branched trans-sphincteric fistula with an abscessual cavity of 17 × 10 mm in the ischioanal space and a single external orifice in the posterior right perianal quadrant (h8). Panels (C, D) show 6-month MRI follow-up, with persistence of fistula tracts but with less thickness and no related collections.

Figure 4

Case 3 imaging pre- and post-surgery. Panels (A, B) show preoperative pelvic magnetic resonance imaging and 3D reconstruction showing a trans-sphincteric fistula starting from the left wall of the anal canal going forward up to the homolateral part of the vulva, with diffuse subcutaneous tissue imbibition but without abscesses, and a fistula in the posterior wall of the anal canal with an inter-sphincteric course. Panels (C, D) show 6-month MRI follow-up, with the persistence of the trans-sphincteric fistula toward the vulva but without signs of inflammation or collections.