Anal Fistula: From Diagnosis and Classification to Surgical Management

Abstract

In this chapter, we discuss the classification and diagnosis of anal fistulas and the surgical approaches for fistula repair. According to the Parks classification, there are four main fistula types based on the location of the fistula tract in relation to the external sphincter: intersphincteric, transsphincteric, suprasphincteric, and extrasphincteric. One of the conventional repair techniques for low transsphincteric fistulas involves cutting open the tract by lay open fistulotomy. Control of a complex fistula tract with a draining seton is used as the first of a two-stage repair or as definitive therapy in patients with contraindications to repair such as concomitant fecal incontinence or active Crohn’s disease. Sphincter-preserving techniques for high transsphincteric fistulas include ligation of the intersphincteric fistula tract (LIFT) and endorectal or anodermal advancement flap with largely equivalent expected results. Biologic adjuncts such as platelet-rich plasma (PRP), acellular matrix (AM) material, and mesenchymal stem cells (MSC) represent a promising area for possibly augmenting healing of complex fistulas. Additional novel treatment techniques being developed for complex fistulas including Video-Assisted Anal Fistula Treatment (VAAFT), Fistula Tract Laser Closure (FiLaC), and Over the Scope Clip (OTSC) are also described.

1. Introduction

Anal fistula is defined as a pathological, epithelial-lined tract connecting the perianal skin with the anal canal [1, 2]. The cryptoglandular theory dominates notions of anal fistula etiology, suggesting that obstruction of the glands within anal crypts by stool or debris and subsequent infection is the root cause. These crypts/glands exist within the base of the columns of Morgagni at the dentate line with an average of six glands per person (range 3–12) and are concentrated at the posterior anus [3]. Gland ducts penetrate the submucosa for a variable distance, with two thirds penetrating the internal sphincter muscle and the remaining glands terminating within the intersphincteric plane [3, 4]. This anorectal gland anatomy explains the predilection for anal fistulas to have posterior anal internal openings and the prevalence of intersphincteric fistulas as the most common subtype overall, since obstructed glands can form unmitigated abscesses within this space. Chronic infection and epithelialization of the abscess tract can result in fistula formation [1, 5, 6, 7]. The reported incidence varies in literature but up to 76% of patients with anorectal abscess are found to harbor or later develop anal fistula [8, 9]. Although the vast majority (90%) of fistulas are cryptoglandular in origin, they also are a hallmark of the fistulizing phenotypic subtype of Crohn disease (3%) or may develop as a result of postoperative/traumatic events (3%), tuberculosis (1%) or other rare causes such as radiation or malignancy [5].

The incidence of anal fistula ranges from 1.04 to 2.32 per 10,000 people per year while the prevalence ranges from 2.8 to 23.2 patients per 100,000 people [2, 10]. Significant variation in epidemiology worldwide exists, possibly influenced by the different health systems. Reported rates may also be underestimated from patient aversion to seeking care related to the sensitive nature of the symptoms and involved body area [7]. Patients presenting for evaluation and treatment of anal fistula have a mean age of 40 for both biological sexes and are uncommon in children. Men are affected more than women at a 2:1 male to female ratio [6, 7].

Anal fistulas have afflicted patients and physicians since antiquity, with little innovation in treatment for centuries until the last several decades. Hippocrates (460–375 BC) is credited as the first to treat anal fistula. He recognized the importance of timely drainage of anal abscesses to minimize the risk of fistula formation. He described the original seton, lint wrapped in horsehair, placed through the fistula tract and periodically tightened to act as a cutting seton and unroof the tract, as well as use of alum as a fistula plug [11, 12, 13]. In 1835, Frederick Salmon, a British surgeon who treated Charles Dickens for anal fistula, established the seven bed “Benevolent Dispensary for the Relief of the Poor Afflicted with Fistula and Other Diseases of the Rectum and Lower Intestines.” With increasing recognition in the field, the institution later moved to larger facilities in 1851 and renamed “St Mark’s Hospital for Fistula and other Diseases of the Rectum” [14, 15, 16]. Salmon discussed his recommendation for fistulotomy on the Lancet in 1844 and opined its low risk for hemorrhage from his nearly two decades of experience in proctology at the time [17]. Sir Lockhart-Mummery (1929) summarized the difficulties that surgeons encountered in treating anal fistula when he said, “Probably more reputations have been damaged by the unsuccessful treatment of cases of fistula than by excision of the rectum or gastro-enterostomy. Perhaps that is why the largest surgical fee in history was paid for the performance of an operation for fistula!” [18].

Perhaps the most famous case of anal fistula is that of the 17th century King Louis XIV, known as the Sun King, who developed a fistula after recurrent anal abscesses. The king’s physicians tried numerous treatments, including enemas, poultices, and bloodletting. Repeated barbaric treatments with a red-hot iron made the anal cavity larger. Plagued by pain and chronic drainage, Louis turned into an ill-tempered hermit, no longer participating in court and changing clothes three times a day. At that time, surgeons were viewed purely as technicians and inferior to physicians. However, given the failure of multiple treatments, the king obtained the opinion of the surgeon-barber and Surgeon of the Court, Charles-Francois Felix, for surgical repair. Felix worked hard to develop a long, silver probe known as a bistoury and practiced the operation on patients from Versailles hospitals, some reportedly dying and buried in secret in the early morning. His operation, a fistulotomy over the bistoury, took 3 hours but reportedly provided significant relief. The king ultimately required two additional debridements for “uneven healing” and another operation to achieve final success. Fame spread of his operation and reportedly courtiers lined up to have the same operation whether they had a fistula or not. This event changed how surgeons were viewed and sparked significant subsequent surgical advancement, including establishment of the first academy of surgery [19, 20, 21].

Like the distress experienced by King Louis XIV, patients with anal fistula have reported overall reduction in quality of life (QoL) compared to controls using the well-known short form 36 (SF-36) questionnaire on health status [22, 23]. Increased fistula complexity corresponded to worsened QoL. In a 2018 study of nearly 100 fistula patients to validate a new fistula-specific QoL tool, Anal Fistula Questionnaire (QoLAF-Q), moderately graded decreases in QoL were found, with significantly worse values in patients with recurrent disease vs. primary disease [24]. Such functional decrement has been mirrored anecdotally in our own practice but remains poorly defined. Despite advancement since the time of King Louis, these elements highlight the desperate need for further innovation for anal fistula repair. In this chapter, we will discuss current and novel treatments for anal fistula with a focus on cryptoglandular fistula.

2. Classification, diagnosis and the role of preoperative testing

2.1 Anal fistula classification

The easiest and most frequently discussed categorization of anal fistula is simple versus complex, with simple referring to a fistula treatable by fistulotomy without incurring incontinence and complex meaning the fistula requires an alternative technique for repair. Complex fistulas include: fistulas traversing >30% of anal sphincter mechanism, recurrent fistula after prior attempted repair, the presence of multiple branching tracts or a blind sinus tract, any anterior fistula in a female, horseshoe fistula, and any fistula in the presence of trauma, malignancy, inflammatory bowel disease, or history of pelvic radiation or immunosuppression. The formal classification of fistula-in-ano has evolved since it was first attempted in 1934 by Milligan and Morgan. This original classification system distinguished several types based on anatomic relation to the anorectal ring [25]. Parks et al. later amended this in 1976 in a published study of over 400 anal fistula cases [26]. This has become the most widely used classification system and characterizes fistulas based on the tract(s) course in Ref. to the external sphincter complex, given its crucial importance in choosing a treatment technique. The Parks system not only established a common nomenclature, but it dictated treatment based on the type of fistula encountered. The five types established by this system include superficial (subcutaneous), intersphincteric, transsphincteric, suprasphincteric, and extrasphincteric (Figure 1).

Figure 1.

Parks classification of anal fistula. Superficial (1), Intersphincteric (2), Transsphincteric (3), Suprasphincteric (4), Extrasphincteric (5). Illustration used with permission from park, M. Y., et al. (2021).

Intersphincteric fistulas travel within the intersphincteric space and penetrate the anorectum without traversing the external sphincter. This has been reported as the most common fistula subtype, making up 20–45% of all anorectal fistula [27]. Parks further defined seven subsets of intersphincteric fistula based on the presence of a high tract and location of openings (simple intersphincteric, high blind tract, high tract with opening in the lower rectum, high tract with no rectal opening, high tract with no perineal opening, extra-rectal extension and secondary to pelvic disease). Treatment of intersphincteric fistulas ranges from fistulotomy to advancement flap depending on risk of incontinence.

Transsphincteric fistulas traverse the external anal sphincter (EAS) at some point below the level of the puborectalis muscle and through the ischiorectal fossa to exit the perianal skin. These are further classified based on where the tract crosses the EAS in Ref. to the puborectalis muscle and the presence or absence of a blind sinus tract. With the latter, care must be taken when exploring as the blind tract may take a high trajectory into the ischiorectal fossa or through the levator plate. Low transsphincteric fistula involve 30% or less of the sphincter complex and are generally considered likely safe for treatment by lay-open fistulotomy, especially in males with longer anal canals, but treatment must be personalized based on individuals’ risk for postoperative incontinence. High transsphincteric fistula are complex and require a more nuanced sphincter-sparing repair like ligation of intersphincteric fistula tract (LIFT) or advancement flap, discussed later in the text. Many clinicians have adopted verbiage referencing a third anatomic category of mid-height transsphincteric fistula, involving more than 30% of the sphincter complex but not abutting the puborectalis/levator plate at the internal opening. These similarly require a sphincter-sparing complex repair.

Suprasphincteric fistulas course over the top of the puborectalis muscle in the intersphincteric space and then down through the levator plate and ischiorectal fossa before exiting the perianal skin. Fistulas of this nature cannot simply be divided as this would cause incontinence. Given the location in the supralevator space, abscesses that form here might only be palpated on rectal exam. Progression of an infection here can result in a horseshoe abscess to form in the deep space around the rectum. The high curvilinear tract in these cases can be difficult to successfully cannulate for draining seton placement.

Extrasphincteric fistulas progress from the perineal skin through the ischiorectal fat and levator muscle into the rectum above the dentate line and anorectal ring, completely avoiding the external sphincteric complex. It is the least common type of fistula, with an incidence of 5% in the Parks study. These are further classified based on their etiology. They can form spontaneously, or secondary to trauma, retained foreign bodies, inflammatory bowel disease, malignancy or inflammation from the pelvis that tracks down through the levators to the perineum (such as in diverticulitis, ruptured appendicitis), or iatrogenically from aggressive probing of a blind tract in a transsphincteric fistula. Division of this fistula would lead to incontinence and their anatomy make repair by LIFT or flap often very difficult if not impossible, leaving alternative repair options of fistula plug or more recently, over-the-scope clip for an internal opening far enough above the anorectal ring. This is discussed in more detail later in this chapter.

With the advent of MRI, Morris et al. developed a system of classification that provides a more precise definition referred to as St. James Hospital University classification [28]. There are five grades increasing in complexity given the presence of multiple fistulous tracts or associated abscesses. Grades I and II are considered simple fistulas while Grade III–V are complex (III–IV are transsphincteric, and V is supralevator/extrasphincteric). More recently, Garg et al. proposed a new five-grade classification system based on a retrospective cohort study of 440 patients and their preoperative MRI and operative findings, comparing established classification systems [29]. This Garg classification was found to be more accurate than prior schemes in terms of appropriate treatment for the various grades but has not been widely adopted.

2.2 Diagnosis and imaging

It is estimated that up to 76% of patients who present with peri-rectal abscess either have an underlying fistula or will develop one [8, 9]. On rare occasions, an underlying anal fistula may be diagnosed on computed tomography (CT) imaging done to evaluate an acute abscess and a fraction of anal fistula are diagnosed at the time of surgical abscess drainage. A high-quality examination under anesthesia (EUA) is sufficient in most fistula cases and remains the surgical standard and it is the authors’ routine practice to always assess for fistula at the time of incision and drainage. With an anal retractor in place, the area of abscess is palpated, and purulent drainage within the anorectal lumen is the first clue to the presence of a fistula. To confirm, a diagnostic substance is instilled under pressure into the abscess cavity such as hydrogen peroxide, methylene blue dye, or even milk whilst directly viewing the distal anorectum by anoscopy. The presence of diagnostic fluid within the anorectal lumen signifies the presence of an underlying fistula tract. Gentle probing of the wound base can also be performed with a fistula probe, being careful not to create any false tracts. If a fistula is diagnosed by the methods above, the fistula probe is placed typically from external to internal opening, allowing assessment of the amount of sphincter muscle involved and either primary fistulotomy over the probe or placement of a draining seton as part of a 2-stage repair (discussed later). However, sometimes the acute soft tissue inflammation present with an acute abscess prevents an underlying fistula from being recognized. The fistula may heal or scar with adequate drainage alone, but more frequently reveals itself weeks to years later with the presence of recurrent peri-rectal abscess or a draining sinus with or without chronic granulation tissue at the external skin opening.

Fistula-specific factors that are higher risk for surgical failure and recurrence in a complex primary fistula include fistula height/length and the presence of multiple branching tracts or unrecognized blind-ending sinus. Thin-slice magnetic resonance imaging (MRI) is regarded as the most sensitive entity for soft tissue evaluation including characterization of anal fistula. However, the cost of MRI can be prohibitive and most clinicians including the authors will reserve cross-sectional evaluation with MRI judiciously for preoperative characterization only in diagnostic conundrums, very high-risk or otherwise difficult cases. Some examples include patients with blind sinus suggested by probing at the time of first-stage draining seton placement, those who suffer an early fistula recurrence, or those who demonstrate ongoing/recurrent signs of infection after seton placement like abscess, indurated soft tissues or heavy drainage. Preoperative evaluation by MRI prior to second stage fistula repair should be strongly considered in such cases. Endorectal ultrasound (ERUS) is also an effective diagnostic modality for the diagnosis and characterization of anal fistula but is especially operator-dependent and not commonly done for this purpose. Fistulography can be effective to diagnose and define fistula anatomy but may not be available at all locations and may require clinician assistance for performance, making it a rarely used diagnostic entity overall.

3. Surgical management

3.1 Fistulotomy and Seton

3.1.1 Overall treatment goals

The overarching goals of treatment of perianal fistulas are preventing systemic infection, closure of the fistula tract, maintain fecal continence by preserving sphincter function, and minimize recurrence [5]. To accomplish this goal, proper drainage of acute infection is crucial, followed by tailored surgical treatment that considers both fistula anatomy and patient-specific factors that risk postoperative functional decrement or recurrence, as no two fistulas are created equal.

3.1.2 Fistulotomy

As previously stated, simple fistulas are those amenable to treatment by primary lay-open fistulotomy, whereby the external and internal openings are connected by transecting the overlying soft tissues between them. These include subcutaneous fistulas, most low transsphincteric fistulas, and some intersphincteric fistulas. This class of fistula makes up a significant proportion of those encountered clinically, often estimated at 50% or more [5]. The primary concern when performing primary fistulotomy is iatrogenic functional complications of sphincter incompetence and fecal incontinence. The commonly reported absolute maximum amount of sphincter muscle that can be transected with a fistulotomy is 30%. This must be individualized to the patient and their baseline continence and sphincter function, as a history of prior traumatic vaginal birth can severely compromise sphincter tone and preclude safe treatment with fistulotomy. An informed digital rectal exam provides a quality initial assessment but when in doubt, anatomic sphincter defects can be defined using endorectal ultrasound and function characterized with anorectal manometry. At least one novel classification system uses MRI to predict amenability to fistulotomy. Patients with sizable deficits should be counseled extensively on the risk of proceeding or a sphincter-sparing approach should be employed like those described later in this text.

After cannulating the tract with a probe, the overlying tissues are transected sharply (Figure 2). Underlying granulation tissue and debris is removed with a bone curette and hemostasis obtained with electrocautery. Some clinicians prefer to marsupialize the exposed fistulotomy wound edges with absorbable suture to assure healing by secondary intention. Multiple randomized trials have demonstrated benefits of marsupialization, including decreased wound healing time, and decreased postoperative bleeding and [30, 31, 32, 33]. Patients should be counseled that fistulotomy wounds may take 8–12 weeks to fully heal. Fistulotomy is regarded as the preferred treatment option for fistula because of its low failure rate, commonly reported as 10% or less [34, 35]. In our practice, we commonly quote patients an expected success rate of 95% or more for fistulotomy treatment. Incontinence is the most feared complication of fistulotomy, but true incidence rates are difficult to reliably predict. Incidence of incontinence varies according to several factors including fistula complexity/height and surgeon experience and covers a wide range of severity from minor (e.g., temporary gas incontinence) to major incontinence as defined by a validated scoring system. A systematic review by Litta et al. of 66 studies and 4883 patients undergoing fistulotomy by some means found an overall weighted average healing rate of 93 and 12.7% incidence of any postoperative continence impairment, which directly correlated to self-reported decrement in quality of life [36]. Female sex, multiple prior abscess drainage procedures or other anorectal surgeries, high fistulas, and surgical fistulotomy versus cutting seton have been associated with incontinence [5].

Figure 2.

Seton and fistulotomy technique. (A) the candidate external opening or site of abscess drainage is injected with a diagnostic substance like hydrogen peroxide. Presence of the substance within the anorectum signifies presence of a fistula. (B) a probe is used to cannulate the tract and assess the degree of sphincter muscle involvement. (C) a loose, draining seton is brought through the tract and secured to itself. Large underlying abscess cavities may require counter-drainage as shown with a penrose style drain or another silastic seton. (D) Longstanding setons can act as a modified cutting seton over time to transpose the fistula to a lower position, which may convert a patient into a candidate for (E-F) second-stage fistulotomy and (G) marsupialization. Pictures care of Jeff Van Eps, MD, and Mark Pidala, MD, UT physicians colon & rectal clinic.

3.1.3 Seton

Fistulas that are too complex for single-stage treatment by fistulotomy because of fistula-specific factors like involvement of over 30% of the sphincter or patient-specific factors like active Crohn-related proctitis require control of the tract with a drain to prevent recurrent abscess and potential further complex evolution of the fistula with branching. This involves placement of some material through the tract and secured to itself as a draining seton. Materials used range from a simple silk suture tie, penrose-style rubber drain, pediatric feeding tube or most commonly, a silastic vessel loop. With the patient in either prone jackknife or lithotomy position depending on surgeon preference and anatomic location, a diagnostic substance is instilled under pressure into the suspected external opening to identify the internal fistula opening with a retractor in the anus (Figure 2). Various substances have been utilized, including hydrogen peroxide (H₂O₂), methylene blue, or even milk. Chronic tracts often have granulation tissue externally and the corresponding internal anal pit may be identified as a depression with or without active drainage with abscess compression. Cannulation with a fistula probe and a guiding finger in the anus may be used as an alternative or in addition to solution, but care must be taken not to create an iatrogenic false passage. Patience is paramount and probing should never be forced. Once the tract is defined, a seton is pulled through the tract and its ends secured together with silk ties. Seton placement is frequently combined with a partial fistulotomy, whereby the tract is opened over a probe from the external opening up to the edge of the external sphincter muscle. This effectively shortens the tract for second-stage repair, which has been shown to improve outcomes [37, 38].

Setons may be either the loose, non-cutting or cutting type. A cutting seton is purposely applied snugly and is often tightened sequentially over time, with a purpose of using pressure and tension necrosis to slowly work its way through the overlying tissues to unroof a fistula essentially as a slow fistulotomy. Cutting setons have been shown to have essentially equivalent outcomes to surgical fistulotomy regarding healing and incontinence rates [39, 40]. Non-cutting setons maintain drainage of the fistula to prevent recurrent abscess as fibrosis occurs. For Crohn-associated fistulas, seton placement may be the definitive, permanent treatment or used as a bridge until medical control of underlying proctitis can be achieved to make the patient a candidate for fistula repair, albeit with counseling on the increased risk of surgical failure. Seton drains can also be useful for complex fistulas in the presence of other perianal pathology and/or complex perineal soft tissue disease, such as necrotizing soft tissue infection (NSTI), hidradenitis, or pilonidal disease (Figure 3).

Figure 3.

Fistulotomy and seton special conditions and circumstances. A fistula in conjunction with (A) anal fissure may mandate treatment by fistulotomy, treating both conditions well. Complex perineal infections from (B) necrotizing soft tissue infection (NSTI) and (C) hidradenitis suppurativa can present with complex fistulizing networks involving the soft tissues and the anorectum. (D) Multiple setons may be placed within the same tract when encountering one particularly long or difficult to successfully cannulate, but more than two setons is unnecessary. Multiple drains were removed in this case to simplify. Non-Crohn cryptoglandular fistulas may present as (E) multifocal, complex locations requiring multiple draining setons, or as (F) branching tracts with multiple external or, more rarely, multiple internal openings like this patient with both types. Pilonidal cysts may rarely present as part of a complex anal fistula and should be treated by (G) excision/unroofing with or without (H) marsupialization and possibly negative pressure wound therapy prior to second-stage treatment. Pictures care of Jeff Van Eps, MD, UT physicians colon & rectal clinic.

3.2 Ligation of intersphincteric fistula tract (LIFT)

3.2.1 Background and indications

The ligation of intersphincteric fistula tract (LIFT) procedure is designed to treat complex perianal fistula while simultaneously sparing as much of the anal sphincter complex as possible to decrease the likelihood of postoperative incontinence. The procedure was first pioneered in Thailand in 2007 by Rojanasakul and colleagues [41]. This section will discuss indications for the LIFT procedure, operative details of the procedure, and outcomes compared to flap repair.

The LIFT procedure is considered an appropriate surgical treatment of complex fistulas of mid- and high height (see “Classification” Section 2) for which traditional fistulotomy would result in an unacceptable risk of post-operative incontinence. While no absolute contraindications to the procedure have been identified in the literature, certain factors have been found to increase the risk of surgical failure. These include patient factors such as obesity, smoking, and diabetes mellitus which may impair wound healing and characteristics that increase the complexity of the fistula and the resulting operation (i.e. previous operations, active infection/perianal collections, increased length of the fistula tract) [42, 43]. Fistula with a particularly deep course within the intersphincteric plane such as suprasphincteric fistulas should be approached with caution for LIFT repair as a much larger incision may be required and a high-quality ligation can be particularly difficult. While prior attempted repair of a fistula by LIFT is not an absolute contraindication, scarred tissues within the intersphincteric space may increase the difficulty or risk of injury with the operation and an alternative approach like advancement flap should be considered. The senior author specifically finds a LIFT approach ideal to repair radial fistulas that have the external and internal openings both lateral to the anatomic midline.

3.2.2 LIFT operative technique

As with any complex fistula repair, the LIFT procedure should be approached in a staged fashion. The first stage addresses the acute infectious/inflammatory process with drainage of any local fluid collections and seton placement [44]. This allows for the initial infection and local inflammation to abate and meanwhile facilitates tract maturation to make it not only more easily identifiable during dissection, but also robust enough to tolerate suture ligation.

To begin the operation, the patient is positioned in accordance with fistula location. Anterior fistulas are treated in the prone, jack-knife position whereas posterior fistulas are treated with the patient in lithotomy position. A lacrimal probe is then inserted through the fistula to use as a visual/tactile aid and confirm that the tract depth is amenable to repair by LIFT. The intersphincteric groove is palpated and a 3-4 cm curvilinear incision is made following this landmark with the incision centered on the fistula tract (Figure 4). Using a combination of blunt dissection and electrocautery, the tract is isolated within the intersphincteric space where it is suture ligated.

Figure 4.

LIFT operative technique schematic. Illustration used with permission from Abcarian, AM, et al. (2012). (A) the intersphincteric groove is identified and dissected with a probe through the tract to assist with (B) circumferential dissection of the tract in that space. (C-D) the medial and lateral exposed intersphincteric margins of the tract are suture ligated, and (E) the intervening portion can be excised along with fistulectomy of the external opening before (F) closing the incision with suture.

It is crucial to remain within the intersphincteric plane during this phase of the operation. Deviation can cause injury to the internal or external sphincters, increasing the risk of post-operative incontinence. Using the lacrimal probe as a guide, overlying soft tissue is transected and the fistula tract is isolated as it traverses the intersphincteric plane with a window created immediately underneath. A right-angle clamp is helpful during this portion of the dissection and to pull suture ties into place for ligation. After excising anorectal mucosa immediately around the internal fistula opening, it is closed at the level of the internal sphincter muscle using absorbable suture. The adequacy of closure is confirmed by injecting hydrogen peroxide under pressure into the external opening(s) without bubbling at the anorectum and additional sutures can be placed as needed. The adjacent anorectal mucosa/submucosa can be closed over the closure site for reinforcement. The previously placed suture ties are used to ligate the fistula medially and laterally, close to the respective sphincters. It is not uncommon for one of the ties to be inadvertently cut when transecting the ligated tract with a scalpel, so it is the senior author’s practice to err well medially toward the internal sphincter with the initial ligation. Any remaining opening defect in the external sphincter can be easily identified by placing the fistula probe from the external skin opening and ligating around the probe. Some authors have reported reinforcing this ligation with a biologic matrix (discussed later in the text, Figure 5). Finally, the intersphincteric site is closed in layers with interrupted absorbable suture and the previous external opening can be excised by fistulectomy to promote drainage if so desired.

Figure 5.

LIFT repair operative technique. After seton removal and tract debridement the intersphincteric groove is identified and dissected sharply (A). The primary internal opening is closed with suture (not pictured). The mature fistula tract is encircled circumferentially within the intersphincteric space (B) and isolated with suture for ligation(C). In special cases or within a clinical trial, tract ligation can be reinforced by placement of an acellular scaffold as a bio-LIFT procedure, (D, matrix denoted by green arrows). The intersphincteric space is closed in layers (E), followed by the anoderm with possible fistulectomy of the external fistula opening to promote external drainage (F). Pictures care of Jeff Van Eps, MD, UT physicians colon & rectal clinic.

3.2.3 LIFT outcomes

A recent updated meta-analysis of 26 studies by Emile et al. found pooled LIFT success rates of 76% and identified specific factors associated with surgical failure including horseshoe fistulas, Crohn-associated fistulas, and recurrent fistulas after prior repair attempt [45]. As previously stated, both the LIFT procedure and endorectal or anodermal advancement flap are acceptable procedures for the treatment of complex perianal fistula. There have been conflicting results in the literature regarding outcomes of the two procedures. In a randomized control trial by Kumar et al., LIFT was compared to endorectal advancement flap in the treatment of high anal fistula. LIFT was found to have significantly higher healing rate (76.2 vs. 54.7%) and lower operative time (46 vs. 90 minutes), but the authors’ reported healing rate for endorectal advancement flap was lower than the average reported elsewhere [46, 47]. In comparison, Tan et al. found in a retrospective review that endorectal advancement flap had a significantly higher success rate compared to LIFT (93.5 vs. 62.5%) [48]. Others have not been able to consistently demonstrate a significant difference in success rate between the two procedures [49, 50]. A 2019 meta-analysis of 30 studies found no statistically reliable difference between the two procedures for surgical success or recurrence, but LIFT was found to have slightly higher postoperative incontinence rates (7.8 vs. 1.6%) [51]. No direct comparison has been specifically made of anodermal advancement flap to LIFT. Various modifications to the classic LIFT procedure have been developed including but not limited to: LIFT with fistula plug, LIFT with advancement flap, LIFT with bioprosthetic mesh, etc. There is a general paucity of literature directly comparing any of these procedural variations and more data is needed but this is discussed in more detail in subsequent sections regarding biologic augmentation [52].

3.3 Advancement flap

3.3.1 Background and theory

It is thought that failure to control the internal fistula opening at the anorectal lumen is the primary cause of surgical failure and fistula recurrence. This dynamic area with at times questionable tissue viability experiences mechanical and pressure forces that risk reopening after simple suture closure. Repair of complex fistula by local tissue advancement flap prevents ongoing contamination by reinforcing this deep suture closure of the internal fistula opening with a well-vascularized adjacent tissue transfer. There are two general types of advancement flap—endorectal flaps (also termed anorectal, transanal, etc.) whereby the proximal anorectal tissue is moved downward/caudally or “up to down,” and anodermal flaps whereby adjacent anodermal soft tissue is moved upward/cranially or “out to in” to cover the internal opening. Specific techniques described in literature vary widely regarding the depth of tissue layers incorporated, flap size and configuration, and preparation of the recipient site prior to securing the flap. This section will describe the indications/contraindications for advancement flaps, provide some expansion on technical details of the procedure, and compare flap repair to the ligation of intersphincteric fistula tract (LIFT) procedure.

3.3.2 Indications and contraindications

Advancement flaps are generally considered a ‘sphincter-sparing’ approach and are indicated to treat fistulas in which traditional fistulotomy would be associated with an unacceptably high risk of post-operative incontinence. As previously defined in the section on fistula classification, a ‘high’ anal fistula is defined as involving greater than one-third of the internal anal sphincter. Simple fistulotomy in such patients is associated with unacceptably high rates of incontinence (2–63%) and require a more nuanced approach [53]. Other fistula subtypes or special situations that might call for flap repair include a high or mid-height intersphincteric fistula in a patient with tenuous continence or sphincter function (e.g., women with history of traumatic vaginal birth). These are not candidates for LIFT repair and are ideal candidates for anodermal flap repair. In reality, however, calling advancement flaps sphincter-sparing is a misnomer. No modality of complex fistula repair can avoid all muscular injury, even if it includes just a portion of the subcutaneous portion of external sphincter.

Bleeding diatheses and active infection at the site of the fistula (heavy purulent drainage, indurated local tissues) are contraindications to any fistula repair. Contraindications specific to advancement flap repair follow similar constraints as tissue transfer at other anatomic sites. Active smoking status, history of pelvic/perineal radiation, and severe, poorly controlled diabetes can all cause microvascular disease that threatens flap viability through mechanisms such as local ischemia and would be considered by some to be contraindications to flap repair—particularly by anodermal advancement, which is a true pedicled flap. For modifiable risks such as smoking and glucose control, it is important to optimize patients during prolonged seton drainage prior to any attempt at fistula repair.

It can often be difficult to determine the best approach for fistula repair using in-office examination alone in a conscious patient with a flexible seton drain in place, as full muscular relaxation under anesthesia is often required to determine tract depth and the level of the internal opening in Ref. to the dentate line, as it can transpose distally after prolonged seton drainage. It is the practice of the senior author to prepare these patients for repair by LIFT versus flap to be determined when under anesthesia. In our practice broadly speaking, advancement flaps are preferred for fistula with tracts coursing deeply within the intersphincteric plane or those with midline internal openings, particularly anterior midline fistulas in females, as the anterior sphincter mechanism is known to be anatomically variable and may be incompletely developed even if nulliparous [54, 55]. When deciding between an endorectal or anodermal approach, surgeon preference usually dominates, but the height of the internal opening is also very important. Anodermal flaps can work well to cover internal openings at or below the lower border of the dentate line, particularly in females who tend to have shorter anal canals by rule compared to males. However, in patients with a long anal canal or a primary opening just above the dentate, this can place an anodermal flap at risk for failure from flap retraction or necrosis secondary to undue tension and is better suited for endorectal flap coverage from above. Conversely, low to mid-height fistula repaired by endorectal flap from above risk complications of mucosal ectropion and increased urgency or incontinence secondary to muscular injury with flap harvest.

3.3.3 Staged repair of perianal fistula and preparation of flap site

Patients with perianal fistula undergoing advancement flap repair are typically treated via a two-stage approach. The first stage typically addresses the acute septic foci with incisional drainage of any perianal abscess and placement of a non-cutting seton through the fistula tract to prevent abscess reaccumulation and promote tract maturation. Having ensured adequate drainage, the fistula tract is allowed to ‘cool-down’ for a minimum period of 6–8 weeks. It is our practice to allow first-stage seton drainage for a minimum of 12 weeks prior to final repair or until physical exam confirms a mature tract and uninfected perineum with softened, pliable tissues and drainage that is more fibrinous than purulent. Rare patients with refractory inflamed tissues and/or heavy purulence despite appropriate seton drainage may require cross-sectional imaging to rule out occult blind-ending sinus and possible preoperative oral antibiotic treatment. In a retrospective review specifically evaluating endorectal advancement flap repair of high transsphincteric fistula, Van Onkelen et al. found that pre-operative seton drainage did not significantly affect outcomes [56]. However, most clinicians would have significant concerns for flap failure if performing a local advancement flap in the setting of an acute infectious process and this should be approached with caution.

3.3.4 Flap technique: positioning and preparation of flap site

Once the acute infectious process has resolved and the tract has matured, the patient may undergo second stage repair. The patient is positioned in accordance with the location of the fistula. Posterior fistulas are best approached with the patient in lithotomy positioning. Anterior fistulas are best approached with the patient in a prone jack-knife position. A fistula probe is passed through the fistula tract following the course of the pre-existing seton and the seton is removed. The tract is de-epithelialized and cleared of granulation and debris using a curette or umbilical tape and flushed with hydrogen peroxide or saline. Electrocautery is used to circumferentially core out denuded mucosa immediately surrounding the tract internal opening down to the internal sphincter muscle to ensure that healthy mucosa will be incorporated into the final repair. The internal opening is then closed primarily with interrupted absorbable suture, confirmed by instilling hydrogen peroxide under pressure at the external opening with adequate closure signaled by a lack of bubbling at the closure site.

3.3.5 Flap technique: endorectal advancement flap

Having prepared the fistula site for flap coverage, the next step involves selecting an appropriate flap technique. Literature surrounding advancement flaps in the treatment of perianal fistula focuses primarily on endorectal advancement flaps. With this technique, a ‘U’ shaped flap is raised from the rectal wall with the tip distal to the internal opening of the fistula. Dissection is continued 4–6 cm proximally taking care to leave the base wider than the tip of the flap (Figure 6). Care should be taken to raise a flap with a base twice as wide as the tip as a rough measurement to prevent flap ischemia. Regarding flap thickness, multiple studies have demonstrated superiority of both full-thickness flaps (the entire rectal wall) and partial-thickness flaps (mucosa, submucosa, and a portion of the internal sphincter) compared to mucosal flaps (mucosa and submucosa only) [57, 58]. The apical area of the flap with poor quality mucosal and submucosal tissues that previously surrounded the fistula is transected and excised back to healthy, bleeding tissue. After a sufficient flap is raised to allow for tension-free closure, the flap is then re-approximated to the distal edge of mucosa using intermittent absorbable sutures. Retrospective study has shown durable healing rates several years of about 72% after repair without significant impact on fecal continence and failed patients were able to undergo repeat reparative attempt(s) with variable success without serious quality of life decrement [59].

Figure 6.

Endorectal advancement flap. Illustration used with permission from Wexner et al. [10]. (A) Fistula probe passing through internal opening. (B) a partial-thickness rectal flap is raised. (C) Suture ligation of internal opening. (D) Excision of non-viable tissue from around internal opening. (E) Approximation of flap over tissue defect with interrupted sutures. An operative example of endorectal flap repair for low rectovaginal fistula is shown with (F) early flap mobilization and suture closure of primary opening, (G) partial-thickness flap containing some muscle partially secured with suture before (H) fully secured, care of Jeff Van Eps, MD, UT physicians colon & rectal clinic.

3.3.6 Flap technique: anodermal advancement flap

Anodermal advancement flap is better studied in the treatment of anal stenosis and anal fissure but may provide certain advantages in select patients with perianal fistula. Unlike endorectal advancement flap, this technique represents a true pedicled tissue flap. The internal fistula opening site is prepared and closed in identical fashion as previously described. With this technique, a tissue island is raised in diamond or house-shaped configuration from the cranial tip immediately adjacent to the internal fistula opening down to the base, which extends caudally distal to the anal verge onto and including the perianal skin (Figure 7). The flap is dissected through all layers of superficial tissue down to the underlying sphincter muscle and into deep perianal subcutaneous fat. It is vitally important not to bevel this dissection underneath the harvested flap and to take care when dissecting the caudal flap base not to compromise the feeding vasculature at this site. Failure to follow these principles can lead to a thin, ischemic flap and treatment failure. Zimmerman et al. found that anodermal advancement flaps were successful in 78% of patients who had no or only one previous attempt at repair [60]. Results deteriorated significantly in patients who had 2 or more previous attempts at repair. This technique may facilitate repair for patients in whom an endorectal advancement flap is challenging such as those with large body habitus or anatomically narrow anal canal, or as a fresh alternative in patients who have failed prior repair at the same site.

Figure 7.

Anodermal advancement flap. (A) Diamond and (B) house shaped anodermal advancement flap. Illustration demonstrates technique for purposes of anal fissure repair, used with permission from Shawki and Costedio [8]. An example is shown of anodermal advancement flap repair for anterior anal fistula and adjacent anal fissure. After anal seton removal and tract cleaning and closure of the internal opening, (C) the remaining internal defect is measured and (D) a diamond-shaped piece of adjacent anodermal skin is marked and mobilized by sharp dissection before (E) securing it with suture over the internal defect and (F) closure of the flap harvest site and possible external opening fistulectomy. Pictures care of Jeff Van Eps, MD, UT physicians colon & rectal clinic.

3.4 Biologic augmentation

3.4.1 Background and need

Given the propensity for failure of complex fistula repair as previously stated, any adjuncts that provide improved surgical success could theoretically translate to profound impacts on patients’ health-related quality of life (HRQoL) and healthcare spending. Biologic additives that have been investigated for augmented fistula repair with promising potential include injection of platelet-rich plasma (PRP), stem cells, or implanted acellular matrix (AM) material.

3.4.2 Platelet-rich plasma (PRP)

The biologic milieu within alpha granules and the provisional matrix provided by PRP provide an optimal environment for soft tissue wound regeneration and have demonstrated anti-bacterial and anti-inflammatory effects to decrease infection and postoperative pain [51, 61, 62]. Platelets assist in the healing of complex fistula tracts by initiating the immune cascade through interaction with neutrophils and leukocytes via surface toll-like receptors and P-selectins [61, 63, 64]. This activation causes alpha granules to release their contents, flooding the nearby area with bioactive factors and chemokines that culminate in neovascularization, type II macrophage phenotypic polarization, and stem cell and fibroblast recruitment/retention [61, 65, 66]. Some studies have demonstrated enhanced healing of chronic wounds and anti-bacterial effects both in vitro and in vivo including randomized trials of sternal and skin closure after major vascular operations [61, 67, 68].

There is a dearth of high-quality data for the use of PRP in anal fistula repair, with most studies performed as prospective cohort studies with insufficient power or controls and often employed in non-traditional techniques rather than an augmenting agent to standard repairs. Of the available evidence however, one prospective cohort study evaluated flap repair augmented by PRP in 25 patients noted an 83% success rate at a mean follow-up beyond 2 years [69]. A separate study evaluating augmented flap repair using adipose-derived stromal vascular fraction with PRP in 45 patients witnessed an 84% success rate (38/45 patients) [70]. At the time of this writing, only a single RCT exists with greater than 10 patients, which evaluated LIFT surgical repair augmented with PRP compared to LIFT alone. This demonstrated significant improvement in overall fistula healing at 1 year in the LIFT + PRP group (42/49 vs. 32/49 patients, p = 0.03) [71]. There is some evidence that the anti-inflammatory effects of PRP can diminish postoperative pain [71] but whether this can translate to improved postoperative QoL for augmented anal fistula repair remains undefined.

3.4.3 Mesenchymal stem cells (MSC)

Although the exact mechanism by which mesenchymal stem cells (MSC) exert therapeutic effects for anal fistula repair is unknown, it is likely mediated via a local immunomodulatory and regenerative response [72, 73]. The application of MSC is primarily reserved for patients with perianal fistulizing Crohn disease (PFCD) who fail to respond to other medical therapies. Most studies utilize adipose-derived MSC and include direct injection both at the muscular level during simple suture closure of the internal opening as well as into the soft tissues surrounding the tract walls. Alternative sources of MSC such as bone marrow-derived mesenchymal stem cells (bm-MSC) have also demonstrated efficacious results in smaller studies [72, 74, 75]. The largest trial evaluating MSC effects in Crohn disease was the ADMIRE-CD (Adipose-Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn’s Disease) trial [72, 76]. This was a randomized, double-blind, placebo-controlled study comparing injection of Cx601 (a solution of 120 million adipose-derived MSC) into the fistula versus a placebo saline solution in a 1:1 fashion [72, 76]. Treatment success at 1 year, defined as closure of external opening(s) and absence of internal collections >2 cm on MRI imaging, occurred in 58/103 (56.3%) patients in the MSC treatment arm compared to 39/101 (38.6%) in the control arm (p = 0.010) [77]. A similar trial, ADMIRE-CD-II, is ongoing in the U.S. and a European registry has been established to follow the safety and efficacy of an MSC product being used for fistula commercially [72].

A systematic review by Ciccocioppo et al. of 23 studies including 4 RCT found 64% fistula closure in MSC treated patients versus 37% in control (OR 1.54) without significant safety events [78]. Two other systematic reviews by Cheng and Huang et al. evaluated 7 and 13 trials respectively and found similarly consistent improvement in fistula healing for PFCD patients without increased adverse events. In the first review, patients receiving MSC were twice as likely to heal in pooled results (OR 2.05) overall compared to control while also noting that the source of MSC is important, with autologous stem cells outperforming allogeneic (79% healing vs. 57%) [79]. Their second review examined over 730 patients from 7 RCT and found a similar pooled overall increase in healing with MSC treatment (OR 2.03) that differed depending on individual study definitions of fistula healing, with a range of OR 1.77–5.92 [79]. Included in this review is one of the rare trials of MSC treatment for non-Crohn cryptoglandular fistula, which demonstrated improved healing as well with OR 2.98 compared to control. Also, an interesting subset of MSC application with fibrin glue displayed improved healing with an odds ratio of 3.27, suggesting there may be a role for combining MSC with different biologic matrices or carriers to enhance their regenerative effect. Additional studies are warranted to address optimal dosing and treatment protocols; however the use of MSC is likely to remain an important adjunct once widely available [72]. As the process and cost of MSC isolation is streamlined, there is exciting potential for well-designed trials of MSC application to augment repair of non-Crohn cryptoglandular fistula as well.

3.4.4 Acellular matrix scaffold

Another alternative therapeutic adjunct is biologic acellular matrix (AM), which act as scaffolding for recruited cells and regenerative tissue to build upon. Evidence suggests that AM also induce anti-inflammatory, pro-regenerative effects at the molecular level [80]. Use of AM has increased in popularity since their introduction in 1994, stemming from widespread use in breast surgery beginning in 2001, and their indications continue to expand. A variety of different brands, decellularization processes, and tissue sources (animal-derived vs. cadaveric, dermis vs. small intestine vs. urinary bladder) are now commercially available for use in a multitude of operations ranging from burn and breast surgery to abdominal wall reconstruction [81, 82]. These AM have traditionally only been available as a solid implantable sheet, but more recently micronized powder formulations have been introduced, capable of lining a wound bed or even direct tissue injection after reconstitution. The concept of utilizing biocompatible material to fill fistulous tracts was first investigated using fibrin glue in gynecologic literature in 1982 [83]. Within the realm of anorectal surgery, AM have been used as a biologic ‘plug’ to fill the fistula tract or as an additional barrier augmenting the LIFT procedure, with varying degrees of success. Most commonly, this matrix plug is secured with suture at the primary internal opening using an internal cuff and customizable tail(s) trimmed to fit the individual tract length at the secondary external opening thereby filling in the previous tract (Figure 8).

Figure 8.

Anal fistula plug repair. (A) Ex vivo picture of the Gore®️ bio-a®️ fistula plug prior to implantation. (B) after seton removal, the fistula tract is cannulated and cleaned of debris. (C) Control of plug using suture through tails. (D) Suture used to pull customized plug through fistula tract. (E) Plug pulled snugly within tract. (F) Plug cuff secured with suture at the internal opening at the anal sphincter. Pictures care of Michael Snyder, MD, UTHealth, UT physicians colon & rectal clinic (CRC).

Success of this method occurs approximately 40–50% per utilization, with limitations including plug extrusion and fistula recurrence [84, 85, 86]. The primary advantage of using a plug repair is a low-risk potential high-reward opportunity for healing with minimal risk of incontinence or further morbidity given a lack of tissue disruption. Indications for the use of a matrix plug may include patients with impaired fecal continence at baseline, or the presence of a long, high extrasphincteric fistula tract. When assessing the available literature as a whole, fibrin glue and fistula plugs are generally regarded as relatively ineffective treatment modalities.

The first reported study detailing the use of AM for anal fistula completed by Champagne and colleagues applied a porcine small intestinal submucosa (Surgisis®) ‘plug’ to fill the fistula tract [87]. They reported an 83% healing rate after follow up of 6–24 months [87]. Subsequent efforts to replicate these results have been unsuccessful, and the combination of non-reproducible results coupled with unclear clinical indications for the optimal type of anal fistula to benefit from a biologic ‘plug’ have led the technique to largely fall out of favor among clinicians [88, 89, 90, 91]. However, subsequent prospective cohort studies have reported promising outcomes when combining standard repairs with AM. Notably, Ellis et al. utilized a Bio-LIFT procedure whereby a biologic matrix was secured within the intersphincteric space after fistula tract ligation with a 94% success rate (29/31 patients) at one-year follow up [92]. This was corroborated by Han and colleagues who also witnessed excellent success rates, (95% success, 20/21 patients) by modified bio-LIFT procedure with a biologic fistula plug placed within the external sphincter portion of the fistula tract following proximal intersphincteric ligation [93].

3.4.5 Future considerations

The overall optimistic but inconclusive results from using biologic agents in the limited number of studies available provide a glimmer of hope for improving the historically unacceptable failure rates of complex anal fistula repair. With the added cost of applying biologic adjuncts, defining their cost utility with consideration for patient-centered impacts on HRQoL will be crucial. Looking to the future, well-designed and adequately powered randomized clinical trials comparing biologic augmentation to standard technique are required to define the indications, if any, for their routine use in complex fistula repair. Our research group is currently trying to address that need with a factorial, randomized controlled clinical trial [94].

4. New and alternative fistula treatments

4.1 Background and clinical need

High recurrence rates of 25–30% or more with advancement flap and LIFT repair and difficult cases like extrasphincteric fistula that preclude standard repair with these approaches have prompted ongoing efforts to develop novel sphincter-sparing approaches. These alternative techniques are in different stages of development and availability but are important tools to keep in mind as anal fistula surgery continues to evolve.

4.2 Video-assisted anal fistula treatment (VAAFT)

Accurate diagnosis and characterization of an anal fistula is crucial, as undetected additional tracts contribute to recurrence. However, complex cross-sectional imaging such as pelvic MRI is an expensive diagnostic modality that is not indicated for most anal fistula. Motivated by these principles, Meinero and Mori introduced the idea of direct fistula visualization through VAAFT [95]. First described in 2006, this sphincter sparing technique involves two phases—diagnostic and operative. In the diagnostic phase, a fistuloscope is inserted through the external opening with continuous glycine-mannitol irrigation and advanced slowly to the internal opening with the assistance of an obturator to straighten the tract (Figure 9). Stay sutures are placed in the internal opening illuminated by the fistuloscope but not tied. The goal is to reliably identify the internal opening as well as any secondary tracts or abscess cavities. In the operative phase, the tract is destroyed internally with an electrode under direct visualization working toward the internal opening, removing debris with a brush. The internal opening is then closed either with suture alone, circular stapler, or with a local advancement flap. Meinero and Mori report reinforcing this site of closure using 0.5 mL of cyanoacrylate in the soft tissue just deep to the internal opening applied using a small catheter, leaving the remainder of the treated tract to drain. Their initial series of 136 cases yielded a success rate of 74% at 3 months and 87% at 1 year, but less than half of patients followed up for this duration. Although not measured with a validated scoring tool no patients reported new or worsened fecal incontinence.

Figure 9.

Video-assisted anal fistula treatment (VAAFT). (A) Standard rigid fistuloscope. (B) Schematic of the VAAFT procedure with cauterization of the fistula tract by the VAAFT electrode. Reused with permissions from Meinero et al. [95].

According to multiple systematic reviews, VAAFT demonstrates success rates between 76 and 86% [96, 97] with the most recent study reporting a weighted mean success rate of 83% on pooled analysis. Some important differences exist in the likelihood of treatment success according to the method of internal opening closure and fistula type. Zelic evaluated recurrence rates according to closure method and reports recurrence rates of 21% with staple closure, 19% with suture closure, and 24% with advancement flap [98]. Regarding fistula type, Stazi showed short term success rates at 77 and 64% for simple (n = 52) and complex fistulas (n = 172) respectively [99]. Romaniszyn reports long-term success rates (mean of 31 months) by fistula type with 80% (n = 30) of simple transsphincteric fistulas healing, while only 39% (n = 38) of complex fistulas healed [100].

VAAFT has several purported strengths. It is a sphincter sparing procedure with relatively rare and minor complications (creation of false tract, scrotal edema, bleeding, prolonged discharge, itching, allergic reaction, cellulitis, and problems related to spinal anesthesia) [95, 101]. Procedure time is relatively short at an average of 42 to 52 minutes [96, 101], patients report less postoperative pain compared to traditional fistulotomy [96, 102], and quick recovery to baseline function of three to 5 days [103, 104]. Its diagnostic capabilities are emphasized, both with the ability to identify and treat secondary tracts/cavities and identification of a primary internal opening in 79–98% of cases [95, 96, 101].

Reported drawbacks include variable success depending on fistula pathology, rigid construction, and wide diameter of the fistuloscope, and difficulty adequately ablating wide fistula tracts [95, 100]. The rigid nature of the fistuloscope makes traversal of angulated fistula tracts particularly difficult. Prior anal surgery or treatment of a recurrent fistula is associated with treatment failure after VAAFT [101, 105]. Lastly, VAAFT is not currently widely available in the U.S. as it has not been FDA approved at the time of this writing, making our evaluation of its potential utility reliant upon non-randomized international studies often insufficiently controlled or powered.

4.3 Fistula tract laser closure (FiLaC)

Persistent fistula epithelium or granulating tissue contributes to fistula persistence or recurrence [106]. In the pilot study of FiLaC [107], Wilhelm sought to improve success rates of the advancement flap technique by following internal closure of the internal opening by flap with subsequent ablation of the epithelial layer of the fistula using a radial emitting laser probe to shrink and seal the tract by denaturation (Figure 10). Since then the FiLaC procedure has been described both independently as the laser ablative portion and in conjunction with the closure of the internal opening (e.g., via advancement flap, staple, suture closure).

Figure 10.

FiLAC procedure schematic. Source: Biolitec®, used with permissions.

Primary healing rates of this technique are 63–67% based on pooled calculations from two systematic reviews performed to date [108, 109]. Elfeki et al. reported a 67% healing rate but 117 of the 454 patients were treated with additional closure of the internal opening (mainly by advancement flaps) compared to the rest that underwent FiLaC alone. The 117 patients were from Wilhelm’s study which reported a 64% healing rate [110].

Interestingly, FiLaC has similar treatment success for Crohn’s fistula. A systemic review of studies that employed FiLaC to fistulizing Crohn’s disease reports a pooled primary healing rate of 68% [111]. Wilhelm found that intersphincteric fistulas showed superior success rates compared to transsphincteric, suprasphincteric, and extrasphincteric fistulas [106].

The nature of failure after FiLaC in most cases is one of persistence rather than recurrence [108]. Patients who fail treatment will have persistent drainage that does not resolve in the acute period [112]. Repeat FiLaC does not portend lower chances of success in subsequent attempts, meaning it can be repeated liberally without apparent significant morbidity [110, 111, 112, 113].

Proponents of pre-procedural seton placement argue that it allows the fistula tract to mature, allowing homogenous formation of granulation tissue for consistent FiLaC treatment [111]. Giamundo et al. reported a trend toward greater success after seton drainage, however, it was not a significant difference [112]. It is not clear whether fistula length is a predictor of success as discrepant opinions exist. Giamundo claims anecdotally that longer fistulas (>4 cm) produce the best results and shorter tracts (<2 cm) should not be candidates for FiLaC [112]. Conversely, Lauretta et al. found in their small retrospective study (n = 30) that fistulas <3 cm actually had superior outcomes compared to longer fistulas with healing rates 58 vs. 16% [114]. These results should be taken with a modicum of skepticism given their low overall success rate of 33% compared to figures reported in the literature.

There are several strengths to FiLaC. It has comparable efficacy whether the fistula is of Crohn’s or cryptoglandular etiology. FiLaC is repeatable without accumulation of negative effects or morbidities and complications are rare with a pooled rate of 4% [108] and usually minor in nature (e.g., minor soiling, temporary postoperative pain, abscess, bleeding) [106, 108]. The average reported procedure is 20 minutes [108, 110] with an average learning curve of only five procedures [115]. Patients report minimal postop pain and early return to work [116].

The disadvantage of FiLaC is that it is a blind procedure which could lead to missed identification of secondary tracts. The laser fiber is also not FDA approved in the United States at the time of writing.

4.4 Over the scope clip (OTSC)

OTSC is an endoscopic technique developed in 2008 to enhance efficient control of gastrointestinal bleeding and iatrogenic perforations, as it utilizes a clip much larger than is allowable by the endoscope working channel [117, 118]. Indications expanded to include usage for anastomotic leaks and fistulas, particularly anal fistulas with the OTSC Proctology device (Ovesco Endoscopy GmbH, Tübingen, Germany) (Figure 11). This technique involves curetting the fistulous tract with a wire brush followed by irrigation and dissection of a circumferential area of anoderm from around the internal opening to expose the internal sphincter muscle. Two U-stitches are placed through or adjacent to the internal opening for clip applier guidance over the sutures to allow positioning at the base of the internal opening. The clip—made of biocompatible nitinol—is deployed, and the external opening is widened to ensure easy drainage of the fistula tract. There is no evidence-based data regarding how long the clip should remain in place and it is frequently left in place indefinitely unless the patient experiences symptoms.

Figure 11.

Over the scope clip (OTSC) equipment. (a) Representation of the “bear claw” clip that is deployed and (b) the OTSC proctology device. Reused from Prosst et al. [119] with permissions from Taylor and Francis.

The largest current study is a series of 100 procedures by Prosst et al. with the vast majority indicated for cryptoglandular fistula and 11 associated with IBD [120]. The median length of procedure was 32 minutes with a length of stay between three and 4 days [120]. They report an overall success rate of 65% with differential outcomes based on indication. Treatment for an initial fistula showed a 79% healing rate compared to the dismal 26% in those treated for recurrence, and 45% for the 11 IBD patients. The same group reported the most comprehensive review to date summarizing the ten available published studies [119] and a total of 236 procedures. Apart from Prosst’s largest study (n = 100), the studies have very small sample sizes ranging from single case reports to case series of 35 procedures. Predictors of failure included application on a recurrent fistula, early clip detachment prior to 4 weeks, and IBD [119].

OTSC treatment of anal fistulas seems to be safe and painless. Multiple studies report the surprisingly high level of patient tolerance with application despite the full thickness force of the clip [119, 120, 121]. Proponents of this technique emphasize the clip’s ability to apply constant pressure in between its jaws despite the dynamic changes in the tissue throughout the healing process. This is especially pronounced when compared to the static nature of a simple suture [117, 120, 121].

Many questions remain to be answered as robust data is currently lacking for OTSC. IBD fistulas seem to have inferior outcomes, but larger studies are needed [119, 120]. Management the clip postoperatively also needs to be clarified. Prosst was able to identify clips in 15 patients postoperatively at 6 months and they were not removed [120]. The risks should be considered as there is no long-term data on the effect of clips remaining in situ.

5. Conclusion

Anorectal fistulas represent a difficult and complex spectrum of disease that continues to plague surgical patients and clinicians alike with impacts on quality of life and high rates of surgical failure. Successful surgical treatment aims to control infection while maximizing healing and safeguarding anorectal function. This requires an intimate knowledge of anorectal anatomy and fistula classification, along with experience in management of simple and complex fistulas, and an ever-growing armamentarium of tools and techniques to promote successful outcomes through individualized treatment. Surgical dogma of fistulotomy for simple, low fistulas and two-stage sphincter-sparing approaches for complex, high fistulas remain the rule. A truly skilled fistula specialist is comfortable with a variety of treatments ranging from seton placement to LIFT, to advancement flap and more importantly, discerns when each is appropriate. However, the surgical landscape is ever-changing, and the future is bright for fistula surgery, with the promise of improved outcomes potentially coming with the advent of new biologic augmentations, fistula-specific instruments, and minimally-invasive techniques as outlined in this text.

Conflict of interest

Dr. Van Eps is the primary investigator on the BIO RAMP clinical trial currently underway to investigate biologic augmentation of complex fistula repair, which is supported by ACell (Integra) with donated biologic matrix material only.

Notes/thanks/other declarations

Thanks to our partners and colleagues within the UT Health Colon & Rectal Clinic (CRC) for supporting this effort and specifically to Mark Pidala, MD, Scott McKnight, MD, and Michael Snyder, MD for contributing operative images used in our figures.