INTRODUCTION
Fistula in ano (FIA), one of the most well-known colorectal diseases throughout history [1], may develop in accordance with the cryptoglandular theory. This theory posits that abscesses lead to chronic inflammation and epithelialization, forming a tract between the anal canal and the perianal skin [2]. Alternatively, in cases of inflammatory bowel disease, FIA can arise from chronic inflammation and abscess formation with subsequent drainage [3]. This condition reduces the patient’s quality of life by impairing anorectal function and causing pain [4]. Treatment options are multifaceted and often require a surgical approach, namely fistulotomy, use of an endorectal advancement flap (to preserve the sphincter), and seton placement. Furthermore, recurrence rates can be high [5], depending on the complexity of the anal fistula [1].
Intra-fistula surgery has potential benefits, such as reducing wound size and alleviating symptoms during the healing process. Techniques employed include fistula laser-assisted closure, insertion of fistula plugs or glue, and video-assisted anal fistula treatment (VAAFT) [6]. However, these methods have not consistently demonstrated high rates of success or reproducibility. One contributing factor to the observed ineffectiveness of these techniques is the induction of inflammation within and around the fistula tract, which perpetuates the chronic inflammatory process that first induced the FIA. Other surgical techniques that offer higher efficacy also carry the risk of postoperative complications. These include fecal incontinence due to disruption of the anal sphincter, anal canal stenosis resulting from perianal scarring, and perianal sepsis.
To address these challenges and offer an effective, minimally invasive approach, ovine forestomach-derived extracellular matrix (ECM) may be useful [7]. This decellularized ECM-based biomaterial is thought to possess anti-inflammatory properties, can serve as a chemotactic agent, and inhibits tissue proteases, including matrix metalloproteinases and neutrophil elastase [7, 8]. ECM-based dermal matrices have been used to reconstruct complex defects involving exposed vital structures, such as in cases of diabetic foot wounds or ulcers.
Our findings indicate that for both superficial transsphincteric and intersphincteric FIAs, surgical management with the insertion of ovine ECM into the fistulas preserves the structure and complexity of the natural ECM during healing. This approach also provides biological cues that facilitate tissue regeneration and promote angio-conduction. Postoperative healing was confirmed by endoanal ultrasound (EAUS), which showed minimal scarring associated with the intersphincteric fistulas.
TECHNIQUE
Fistulas are first examined under general anesthesia in the lithotomy position, with a perianal regional block applied using 20 mL of 2% bupivacaine. An example of FIAs, including one at the 6 o’clock position (transsphincteric) and another at 7 o’clock (intersphincteric) is shown in Fig. 1. Subsequently, the tracts are adequately curettaged with a thin strip of Raytec gauze (Smith & Nephew) (Fig. 1C). The tracts are then thoroughly flushed with chlorhexidine, ensuring adequate hemostasis. Myriad Matrix (AROA Biosurgery Ltd)—an ovine ECM product—can be rolled into a thin strip, secured at one end with Vicryl 3-0 (Ethicon Inc), and pulled through both the transsphincteric and intersphincteric tracts using an FIA probe (Fig. 1D, E). The internal opening can then be closed with Vicryl 3-0 in a figure-of-8 pattern, which also anchors the ECM at the internal opening. The external end of the Myriad Matrix, protruding from the external opening, is anchored to the skin with undyed Vicryl 3-0 using a single interrupted stitch. This is done without occluding the external opening, thus allowing for potential drainage during the healing process (Fig. 1F). Patients should receive instruction on how to maintain cleanliness of the area, such as by applying antiseptic spray (Betadine, 5% povidone-iodine; Alcon Laboratories Inc). In the present case, paracetamol was prescribed as the sole analgesic, and stool softeners were provided. Specifically, the patient received 1 sachet of phylum husk once a day and 10 mL of lactulose twice a day for 2 weeks.
To assess the postoperative healing of the tract, EAUS can be utilized 1 month after surgery. In our patient, EAUS revealed the resolution of the longer 7 o’clock intersphincteric tract without appreciable hyperechoic scarring, indicative of healing through regeneration of the surrounding native parenchyma. A small residual internal opening of the shorter 6 o’clock superficial transsphincteric tract likely corresponded to minor scarring where the internal stitch was placed for closure. The low-lying, shorter FIA of the 6 o’clock intersphincteric tract remained patent (Fig. 2).
Ethics statement
This study was approved by the Centralised Institutional Review Board of SingHealth (No. 2020-2525). Written informed consent for publication of the research details and clinical images has been obtained from the patient.
DISCUSSION
Throughout history, the management of FIA has been technically challenging, with surgical techniques exhibiting varying levels of reproducibility and success [1, 5, 7, 9]. We observed that fistulas were replaced by innate tissue with no scar development visible on EAUS, a promising result that supports the recruitment of mesenchymal stem cells. In our case, involving FIA of likely cryptoglandular origin, we observed appropriate healing of the 7 o’clock FIA with the restoration of innate tissue following integration of the ECM after just a month from the procedure. The more superficial 6 o’clock FIA remained patent, likely due to the ECM dislodging from the shorter, relatively linear tract. These findings suggest that the use of ovine ECM may yield promising results in carefully selected cases of FIA, possibly by providing biological cues that allow key cell components to infiltrate the matrix, regenerate new parenchymal cells, and promote angio-conduction. The FIA tracts are thus replaced with innate tissue, which is more resistant to infection and breakdown, rather than forming a fibrous scar. Cases would require careful screening, as evidenced by the described failure involving short, superficial, and linear tracts. Another group has attempted this technique, with promising results; they attributed the success to the properties of the ECM, including anti-inflammatory effects, inhibition of key enzymes such as proteases, and promotion of stem cell migration [7]. Further studies and observations with a larger sample size are necessary to gather more data sets, as well as to follow up with patients and track their recovery over a longer period. Future research could include a larger case series, preferably conducted in a randomized controlled trial format to compare the efficacy of this technique with existing approaches.
Beyond the likely anti-inflammatory properties of ovine ECM, the described technique may also prove beneficial in treating complex FIA among patients with inflammatory bowel disease. This approach could reduce inflammation associated with the disease and promote the regeneration of innate mesenchymal stem cells within the tract. Consequently, it could offer an alternative in acute cases, including those with concomitant abscess, relative to the current standard practice of staging drainage with definitive surgery. While the use of ovine ECM in fistula management has no absolute contraindications, we would generally avoid employing this method with fistulas that are complex with multiple branching tracts, are short and narrow (which increases the risk of ECM displacement), or have wide internal openings (as suture closure of the internal opening may fail).
One limitation of the proposed technique is that the fistula tract must first be cannulated with a fistula probe to guide the Raytec gauze in using a suture. This technique is unsuitable for addressing secondary blind-ending tracts that cannot be cannulated or are overlooked during fistula probe cannulation, potentially resulting in the persistence of the tract. Additionally, our technique does not enable a thorough assessment of the completeness of curettage. Furthermore, any remaining epithelialized lining of the fistula tracts may compromise the efficacy of the ECM. Performing rigorous curettage until bleeding is observed helps ensure the de-epithelialization of the tract. Along with the use of ovine ECM, one might also consider incorporating VAAFT techniques to ensure complete curettage and to check for secondary tracts. Nevertheless, our technique demonstrates that, in carefully chosen cases and when the ECM is retained, this ECM effectively allows the tract to fully integrate with the surrounding native tissue and potentially restore the anal sphincter, thereby minimizing sphincter-related complications after fistula surgery. Thus, in select cases, ovine ECM presents promising results for aiding the healing of FIA with minimal scarring and may become the preferred approach in the management of FIA.
ARTICLE INFORMATION
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Conflict of interest
Frederick H. Koh is an editorial board member of this journal, but was not involved in the review or decision process for this manuscript. No other potential conflict of interest relevant to this article was reported.
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Funding
None.
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Author contributions
Conceptualization: FHK; Data curation: XC, FHK; Investigation: all authors; Methodology: all authors; Writing–original draft: XC, FHK; Writing–review & editing: all authors. All authors read and approved the final manuscript.
Fig. 1.Overview of the surgical technique. (A) The blue circle indicates the 6 o’clock external opening of the intersphincteric tract, located less than 0.5 cm from the anal verge. The yellow circle marks the 7 o’clock external opening of the transsphincteric tract, situated 0.5 cm from the anal verge. (B) Fistula probes were inserted into both 6 and 7 o’clock fistulas in ano. (C) The fistula tract was dilated and curetted with gauze. (D) The extracellular matrix (ECM) was rolled up and secured at one end with Vicryl 3-0 (Ethicon Inc). (E) The ECM was then pulled across the fistulas-in-ano tract. (F) The internal openings were closed with Vicryl 3-0. The ECM was trimmed and affixed to the skin at the external openings with Vicryl 3-0.
Fig. 2.Selected endoanal ultrasound images. Endoanal ultrasound evaluation at 1 month postoperatively revealed no scarring at the 7 o’clock position. (A) External opening (EO) at 6 o’clock. (B) Internal opening (IO) at 6 o’clock.
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