The ideal procedure for treatment of PF has been elusive because the invasive closure techniques that have higher efficacy incur higher risk, and minimally invasive techniques with lower risk generally have poor success. PAFI with OFM is a minimally invasive technique that is simple to learn and perform, and in this pilot retrospective cases series resulted in a 64% (n = 9/14) healing rate at 8 weeks and 78% (n = 11/14) were healed over the study period. There was one recurrent PF (patient #14) in the healed cohort at last follow-up and there were no significant complications in any of the study patients. These findings demonstrate the potential for PAFI with OFM to offer high efficacy with low risk in definitive treatment of PFs.

The use of biologic implants in treating PFs has been described by others previously. dECM and collagen-based implants, termed “fistula plugs”, were first proposed as a minimally invasive alternative to more invasive surgical procedures based on the application of these technologies across a range of soft tissue defects [7]. However, first-generation dECM fistula plugs used in this application had relatively low clinical efficacy compared to invasive surgical procedures. For example, Bondi et al. [1] compared the clinical effectiveness of a porcine small intestine submucosa fistula plug (Surgisis®, Cook Surgical, Bloomington, Indiana, USA) to a mucosal flap procedure, and reported 12-month recurrence rates of 66% and 38%, respectively. These results were consistent with a previous study comparing a dECM fistula plug and an endorectal anal flap (ERAF) procedure, with 12-month recurrence rates of 80% and 12.5%, respectively [8].

It is interesting to speculate on the unique properties of OFM that may contribute to its success in this pilot. Previous studies on OFM have characterized its anti-inflammatory components [9] and in vitro testing has demonstrated its inhibition of tissue proteases [10], key contributors to chronic tissue inflammation [5]. More recently, OFM has been shown to recruit stem cells [9], drawing parallels to the deployment of stem cells in treatment of PF diseases [4]. In addition to the OFM implant being a different source tissue to existing fistula plugs, the OFM implant used in this series was fashioned during the operation, rather than being pre-formed as a plug, and the material can be cut to size. This approach allows for a tailored implant that can be fashioned to fit the dimensions of the patient’s PF, as measured in real time by the operating surgeon. While PF included in the current case series had a length of approx. 4 cm, the approach would also be applicable to shorter PF tracts, though fistula tracts smaller than 2 cm would likely be best treated with a fistulotomy procedure with little to no morbidity. An additional advantage of the method described in this series is the low potential for local tissue disruption compared to other surgical techniques. Techniques that rely upon tissue mobilization and surgical dissection generate fibrosis within the natural tissue planes. In cases of recurrence, this scarring can make subsequent repairs more challenging and may even be prohibitive. In contrast, PAFI carries minimal risk for local scarring and does not compromise or limit subsequent surgical options. As an example from this series, two patients (#5 and #12, Table 3) who failed to heal, underwent a repeat PAFI that resulted in complete healing within 4 weeks of the second procedure. This highlights the relative ease with which the PAFI technique can be deployed, and even in the event of initial failed healing subsequent application may still lead to a successful outcome. This is consistent with wounds of various etiologies which may require multiple applications of extracellular matrix material to achieve healing.

As a retrospective pilot study, there are several limitations to this study. Most importantly, the results are based on a relatively small cohort of patients that were retrospectively reviewed and the follow-up was relatively short. However, on the basis of these initial results, further prospective studies are warranted to validate the results herein. For example, a randomized controlled trial comparing OFM-based PAFI treatment to invasive surgical intervention (e.g., LIFT) or traditional fistula plugs may be considered. Another limitation of the current case series was the absence of MRI characterization of the fistula tracts prior to treatment. Future studies would include MRI evaluations of the PF to aid in diagnosis and evaluation the extent of fistula tracts. The authors are considering prospective study designs to validate and expand the results of this study such as a randomized controlled trials comparing to OFM-based PAFI treatment with standard-of-care or existing PF treatment options such as traditional fistula plugs.