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M. Obi and A. L. Lightner

complex perianal stulas in CD.MSCs are injected into the stula tract walls after curettage of the internal opening. After 24weeks, closure of all external opening without any additional collections was note in 51% of treated patients compared to 36% in the control group (p=0.021). Adverse events again remained fairly mild and similar to previously reported complications. At 54weeks follow-up, the efcacy and safety proles remained similar [114, 115]. Out of Mayo Clinic, the STOMP trial recently found that MSCs could effectively be utilized in a bioabsorbable matrix in the setting of simple stulas and another phase I study found that stula plugs coated with MSCs could also promote signicantly high healing rates [116,

117]. These phase I, II, and III trials have provided signicant promising results in

regards to expanding treatment options for patients who otherwise had limited to no other options for clinical improvement. While impactful, these early studies have largely excluded patients with active proctitis, 3 or more tracts, anal canal involvement, prior diversion, or vaginal or pouch. Recently submitted phase IB/IIA RCT data in this more severe patient population found at 1year, clinical and radiographic healing in 70% of perianal, 37.5% of rectovaginal, and 46.2% of ileal pouch stulas without any signicant treatment- related adverse effects [118]. As such, MSCs are continuing to demonstrate signicant effectiveness in the treatment of perianal stulizing CD.As more research continues to be done and cost- effectiveness continues to be examined, this treatment option is likely to become less investigational and more widely spread amongst medical practitioners (Fig.2.7).

Fig. 2.7 Injection of MSCs directly into the rectal mucosa around a stula opening as well as along the stula tract. (Adapted from Georgiev-Hristov etal. [119])

2 Surgical vs Medical Management of Symptomatic Anal Fistulas in Patients…

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Fistula Laser Closure (FiLaC™)

In 2006, Moy etal. described the rst use of a laser, specically a carbon dioxide laser, in the successful treatment of perianal stula in CD patients [120]. Subsequently in 2011, Wilhelm etal. described a new technique with a radial- emitting laser probe [Fistula-tract Laser Closure (FiLaC™), Biolitec AG, Jena, Germany] that works by destroying the epithelium of the stula tract despite lack of direct visualization of the pathway [121]. Closure of the internal opening with an endorectal advancement ap was also described. Initial studies demonstrated an overall healing rate of 64% of all stula patients and 69% in specically CD patients. This rate subsequently increased to 92% in the CD population after a second procedure [122]. FiLaC™ has the benet of a faster recovery, it preserves the sphincter, and it has a relatively short learning curve to incorporate into one’s practice. The cost though, can be prohibitive and because one is unable to visualize the tracts as they are treated, there is the potential for failure of treatment of secondary and more complex stulous tracts resulting in decreased healing rates. Ultimately, this technology is still relatively new and further studies are needed to describe its efcacy and benet related to other treatment techniques, however initial ndings in CD patients has been promising [123].

Video-Assisted Anal Fistula Treatment (VAAFT)

Video-assisted anal stula treatment (VAAFT) is a two stage procedure in which a “stuloscope” is rst inserted into the external opening of a stula tract in order to identify the internal opening as well as any secondary tracts. Once fully explored, a special electrode is placed and cautery is used to obliterate the tract under direct visualization followed by debridement of the tract and closure of the internal opening with suture, staples, or an advancement ap. The technique was initially described in by Meinero etal. in 2011in non-CD patients in which they described a 3month healing rate of 73% and 1year healing rate of 87% [124]. Subsequent studies in CD patients demonstrated consistent high healing rates. A prospective study in 13 CD patients who underwent VAAFT with and advancement ap closure demonstrated a success rate of 82% at 9months without any associated morbidity or incontinence [125]. A subsequent study in 25 CD patients who underwent VAAFT with seton placement instead of denitive closure, demonstrated improved self-reported pain and discharge in 84% of participants [126]. Unlike FiLaC™, VAAFT has the benet of direct visualization in addition to sphincter preservation but cost and longer learning curve are possible disadvantages. The VAAFT procedure remains a promising technique for the treatment of perianal stulas in CD patients but further studies and comparisons between other techniques are still needed (Fig.2.8).

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M. Obi and A. L. Lightner

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Fig. 2.8 Fistuloscope within the external opening of a stula tract (a). View from stuloscope of lumen of the stula tract and abscess cavity before (b) and after (c) cauterization. (Adapted from El-Barbary and Yusof etal. [127, 128])

Conclusion

Fistulizing perianal CD is a challenging phenotype of CD associated with substantial morbidity. Innovative surgical and medical approaches have enriched the therapeutic options available, but more work is needed to provide an algorithm for consistent ability to achieve remission. As such, a multidisciplinary approach continues to be required in order to maximize optimal patient outcomes.

Conict of Interest Amy Lightner: consultant for Takeda, Mesoblast, Ossium, Boomerang, Direct Biologics

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