Anorectal Fistula

Etiology

A multitude of causes cause fistulas, but the well-known mnemonic "FRIEND" here aids memory. "F" for foreign body, "R" radiation, "I" infection or Inflammatory Bowel Disease, "E" epithelialization, "N" neoplasm, and "D" for distal obstruction (as is the case in the cryptoglandular theory). 

Foreign bodies in the rectum often are those placed intentionally, such as a seton to lower a fistula tract and make it more localized and aid healing. Radiation causing fistulas are well known and will be discussed briefly later on in this article. Infection is the most common cause of anorectal fistula and is thought to originate from a blockage of the anal glands and crypts. The two anal sphincters are divided by an avascular fatty areolar plane, which provides means for the spread and infiltration of an infection. Often an abscess will develop in this region, and it will find a way to drain via a fistula spontaneously.  Obstruction of the anal glands allows bacteria to proliferate and ultimately forms a perirectal or anorectal or perianal abscess. With or without surgical treatment of the anorectal abscess, there is a significant risk of fistula formation. In addition to an incision and drainage, a 5 to 10-day course of antibiotics has been shown to decrease the rate of fistula formation.[10]

A thorough understanding of anorectal anatomy is critical to understanding abscess-to-fistula development. The correct localization of the fistula relative to the sphincters is vital to correct operative management. The essential structures in the anorectal region include the rectum itself, anal glands, anal sphincters, the levator ani, which is comprised of the puborectalis, pubococcygeus, and iliococcygeus. The anal canal lining is composed of stratified squamous epithelium distally, which changes to squamocolumnar epithelium proximally past the dentate line. Proximal to the dentate line is where the columns of Morgagni appear, which are folds of columnar glandular epithelium.

Anal fistulas are rarely a presentation of anal tuberculosis and should be suspected in endemic regions or nonhealing recurrent fistulas. Utilizing the polymerase chain reaction of pus samples is more sensitive than histopathology in testing for tuberculosis.[11][12] Anal fistulas in a younger patient, particularly if they are complex fistulas or multiple, should raise suspicion for Crohn disease.

Sexually transmitted infections (STIs) of the anus and rectum, usually secondary to anal receptive intercourse, may predispose individuals to perianal abscess and fistula. These anorectal STIs are most commonly caused by gonorrhea, chlamydia as well as, syphilis (Treponema pallidum) and herpes simplex.[13]

Radiation proctitis is another cause of anal fistulas. Radiation proctitis requires surgical intervention in less than 10% of the cases with fistula tracks to the vagina, urethra, and bladder being a common complication. Impaired microvascular healing often requires multiple treatment modalities, including local excision, flap reconstruction, and diversion of stool or urine from the site.[14] Patients with human immunodeficiency virus, with or without AIDS, are predisposed to anorectal disease and anal fistulas. These fistulas may lack internal openings and are sometimes in the absence of an underlying abscess.[15] In one study, fistula-in-ano accounted for 6% anorectal pathologies in HIV patients and was irrespective of the utilization of antiretroviral therapy.[16]

Complicated vaginal deliveries with 3rd or 4th-degree tears or requirement of episiotomy may predispose to anal fistula; however, these fistulas often heal spontaneously. In nonhealing obstetric related anal fistulas, surgical therapy is dependent on the location of the fistula as well as vaginal involvement. When distal to the dentate line, a recto-vaginal fistula becomes an ano-rectovaginal fistula. Causes include obstetrical trauma typically associated with a traumatic vaginal birth. Patients who undergo episiotomy are at increased risk for sphincter injury and fecal incontinence.[17]

Although the majority of the resting anal tone is attributed to the involuntary internal sphincter, the external sphincter is vital to maintaining fecal continence and is comprised of striated voluntary muscle fibers. Three nerve branches innervate it; the external perineal nerve anteriorly, the inferior rectal nerve posteromedially, and in 31% of cases, an additional posterior branch arising from either S4 or the inferior rectal nerve.[18]

Epidemiology

An anorectal fistula is relatively uncommon and has an incidence of 1-8 per 10,000 persons every year. In the western hemisphere, up to 25% of cases may be associated with Crohn disease.[19] It is two times more common in males than females and usually presents in the 3rd to 5th decade of life. Some risk factors for perirectal fistula include obesity, diabetes, hyperlipidemia, history of anorectal surgery, and even excess salt intake.[20] 

Smoking has also been associated with perianal abscess and fistula development and recurrent anal fistula in certain procedures.[21][22][23] Patients that are younger than age 40 or who have recurrent anal abscesses may be predisposed to the development of an anal fistula.[24]

Pathophysiology

An anal fistula, which is an epithelialized connection between the anal canal and external peri-anal area, is characterized by inflammatory tissue and granulation tissue. The distal obstruction prevents the fistula from healing. Because cells are continually being turned over, there is constant debris in the fistula tract, which causes obstruction and prevents healing. The use of a seton and how it allows fistulas to heal is evidence of this as setons allow constant drainage of the fistula and usually result in the fistula migrating and healing.

Histopathology

Histologic analysis of fistula tissue should be sent when an atypical etiology, such an infectious or malignant etiology, is suspected. In general, tissue from anal fistula surgery is not usually sent for pathologic analysis as it does not contribute to the management unless there is an occult process. A study of 84 patients treated for anal fistula evaluated the yield of histopathological analysis in the routine assessment of tissue from anal fistula surgery found a low positive for this tissue except in the setting of a recurrent fistula or when HIV, tuberculosis or Crohn disease was suspected.[25] The majority of fistula pathology simply demonstrates a fistula tract. In cases of Crohn disease, noncaseating granulomas may be seen, and if tuberculosis is present, then an acid-fast bacilli test is helpful to aid diagnosis.

History and Physical

A thorough history, complete review of systems, and physical exam are essential for determining the cause of fistula in patients who have not recently had a perirectal abscess drained. Patients with inflammatory bowel disease may be tender on an abdominal exam and provide a history of bloody diarrhea, abdominal pain, or systemic symptoms such as weight loss or fever. A complete sexual history is vital as lymphogranuloma venereum can, in some instances, cause a perianal fistula.[26]

A history of malignancy or radiation to the pelvis is essential as fistulas from radiation are well documented, and treatment should be coordinated with the patient’s cancer care.  A history of rash or multiple new sexual partners should prompt suspicion for syphilis. A patient with a chronic cough or a history of tuberculosis could present with the disease as an anorectal fistula, particularly if he or she is from an endemic region. Multiple draining fistulas, fistulas in abnormal locations, and fistulas that are chronic or recurrent should raise concern for a systemic process.

Typical complaints include itching, drainage, discomfort, and possible pain with defecation on presentation. Patients that had an abscess that was inadequately drained may present with a fistula and recurrent perianal abscess. The surgical and procedural history is vital as a history of anorectal procedures is associated with the development of an anorectal fistula.

A perianal exam and anoscopy in the office are necessary for the evaluation of concurrent abscess, assessing external fistulous opening and other anorectal diseases such as fissure or hemorrhoids. On inspection, a small opening outside the anus with or without visible drainage may be seen. The drainage may be serous, serosanguinous, bloody, purulent, or fecal matter depending on the location of the fistula. Around the opening, there may be hypertrophied tissue, which is suggestive of a developed tract; this is sometimes palpated on the digital rectal exam. The digital rectal exam is also essential to assess for any tenderness, which suggests occult abscess. 

Anoscopy may reveal the internal opening; however, usually, an exam under anesthesia is necessary to find the internal opening of the fistula. Cutaneous openings which lie anterior, or ventral, to transverse anal line typically are connected to the anal canal via a radial tract according to Goodsall’s rule. While his rule states openings posterior or dorsal to this transverse anal line will appear posteriorly internally. Perianal skin may have irritation from chronic drainage, and patients often complain of having to wear pads or change their underwear frequently during the day.

Evaluation

Imaging: An anorectal fistula is a clinical diagnosis, but imaging is beneficial in determining the course of a fistulous tract or determining its etiology. Imaging studies include endo-anal ultrasound, CT pelvis, CT-fistulography, and MRI of the pelvis.

Endoanal Ultrasound

Endorectal ultrasound is also a useful modality to assess for an abscess with similar sensitivity but less specificity than MRI.[27] The introduction of hydrogen peroxide into the external fistulous opening canal improves the accuracy of endoanal ultrasound in identifying both fistulous tracts and occult abscesses and may be equivalent to anal MRI in the diagnosis of fistulous tracts.[28][29][30][31] It is a less expensive modality than MRI and may be done in the office, facilitating its use for patients with chronic fistula such as Crohn disease patients who require long term follow up.

CT scan and CT Fistulogram

Computerized tomography is useful for identifying abscesses and drainable fluid collections, as is quick and readily accessible in the majority of clinical scenarios. Although it is not as sensitive or specific as pelvic MRI for classification of anal fistulas.[32] In the clinical setting where an acute infection of an anal fistula or an underlying abscess is suspected, and timely diagnosis is needed, a CT scan may be the most appropriate imaging to expedite diagnosis and treatment for a patient.[33]

In the outpatient setting, CT-fistulography is a useful and efficient modality for identifying fistula tracts preoperatively.[34] However, it requires expert radiologists to read the images as well as a skilled surgeon being available to inject the contrast for the exam. It may be a cost-saving when compared to MRI. It should be considered in complex anal fistula preoperative planning when trying to save costs or in patients who are reluctant or unable to undergo an MRI. Multidetector CT has been utilized with similar efficiency in identifying fistulous tracts as well as underlying abscesses.[35]

Magnetic Resonance Imaging (MRI)

MRI of pelvis assists in the identification of fistulous tracts and occult abscesses as well as characterizing proximity of tracts to the internal and external sphincters to coordinate effective planning. Although CT pelvis is useful for the evaluation of underlying abscess, it is less sensitive than MR in identifying fistulous tracts.[36] MRI has been shown in different studies to aid operative planning and reduce fistula recurrence or need for various operations as it allows the surgeon to identify occult fistulous tracts and plan for a more extensive procedure when necessary. 

MRI is a compelling preoperative tool, particularly in complex fistulas and those with an external opening greater than 2 cm from the anus.[37] MRI is very sensitive and specific in diagnosing fistulous tracts and characterizing their internal and external openings.[38][39][40][41][42] In a study by Garg et al. of 229 patients, the use of MRI changed the preoperative diagnosis in half of simple and over a third of complex fistulas.[43]

It is efficacious in identifying post-operative complications such as an abscess or recurrent fistula, particularly at or after 12 weeks postoperatively.[44] In complex fistulas, the utilization of a balloon rectal channel catheter improves the accurate identification of internal openings.[45] Buchanan & colleagues found the usage of MRI to plan surgery was associated with decreased recurrence of fistulas by facilitating a complete initial operation.[46] In a case-controlled study of 41 patients comparing CT-fistulography to MR preoperatively, internal openings were more readily identified by MRI than CT-fistulography (85.3% vs. 68.2%); the combination of both imaging modality findings in patients was most consistent with operative findings.[32]

Laboratory Findings

Basic laboratory panels should be obtained in patients, including complete blood count and comprehensive metabolic panel. Low hemoglobin may reveal underlying anemia, which could be secondary to an inflammatory bowel disease or gastrointestinal malignancy. Leukocytosis may reveal an underlying infectious process or occult abscess, as well as an elevated C reactive protein. Other blood tests for inflammatory bowel disease, rapid plasma reagin, and others.

Treatment / Management

Current Management Options for Anorectal Fistula

Treatment Options for Anorectal Fistula

The treatment for a fistula depends on etiology. Still, in general, an exam under anesthesia is typically indicated to identify the fistulous tract using a lacrimal probe and methylene blue or hydrogen peroxide. When the fistulous tract is detected if the cause is known to be an abscess or otherwise, there have been excellent results with a fistulotomy on the initial operation, which is shown to decrease the need for additional procedures.

Fistulotomy Versus Fistulectomy

 A fistulotomy is the gold standard for an acute anal fistula and entails first identifying the tract of the fistula using a probe. The patient is placed in a lithotomy or prone jackknife position. Deep sedation or general anesthesia is used. The anus and perianal area are prepped with betadine. A local anesthetic is injected at the start of the procedure, which helps decrease postoperative pain and may help separate tissue planes. A digital rectal exam is performed. A Lonestar retractor or a Park's retractor is placed. The fistula tract is identified by probing the external opening using a lacrimal probe. Then an injection of methylene blue and or hydrogen peroxide into the external opening using a small angio-catheter will reveal the internal opening and if there are multiple internal openings. Keeping the probe through the external and internal openings, the sphincters are carefully identified, and their involvement is assessed. If the external sphincter is not involved, a fistulotomy is performed. Division of the external sphincter should be avoided at best to preserve continence; however, if a necessary division of the lower segment is associated with acceptable postoperative continence rates.[47]

Being careful to avoid the external sphincter and simply splaying open the fistulous tract using a Bovie cautery or sharply. Electrocautery is then used to obliterate the epithelialized tract as much as possible, and the wound is left open to heal. Fistulotomy healing rates have been reported as high as 94% in some series.[48](B2)

A newer procedure that is utilized for high transphincteric or supra-sphincteric fistula is fistulectomy with sphincter reconstruction. In this procedure, the sphincter is divided where the fistula tract is, and after excision of the fistula tract, the sphincter is re-approximated with absorbable sutures. Recent studies have shown promising results with this technique for high and complex fistulas with healing rates approaching 90% and incontinence of 2%.[49] Further utilization of this technique and studies on outcomes is necessary to expand its usage.

When compared to other operations, fistulotomy is associated with higher healing rates and less need for additional surgeries. Fistolotomy has been historically known as the gold standard as therapy for a fistula; however, its utilization varies. It has excellent first time healing rates.[50] Results of fistulotomy versus fistulectomy are variable with some studies favoring fistulotomy over fistulectomy because of faster healing time but similar complication rates.[51] Fistuolotomy with marsupialization has been associated with shorter duration of wound discharge and decreased healing time as compared to fistulectomy by significantly decreasing wound size. It also may decrease bleeding rates.[52] A study utilizing endoanal ultrasound to assess internal and external sphincter lengths postoperatively found the injury to the sphincter mechanism occurred more often during fistulectomy versus fistulotomy.[53](A1)

A meta-analysis of six randomized controlled trials comparing the two showed no significant difference in healing rates or postoperative complications.[7] In patients undergoing fistulotomy, a sphincter sparing approach may yield improved functional outcomes.[54] Recurrence of fistula-in-ano after a fistulotomy is performed usually seen within 12 months after the index operation.[55] Patients who are at high risk for postoperative incontinence, such as females, patients with prior history of anorectal procedures, pre-existing poor sphincter control, should be considered for a sphincter sparing procedure. Complex fistulas, while amenable to fistulotomy and fistulectomy, may be associated with poorer outcomes as for a trans-sphincteric fistula division of the sphincter is necessary for an adequate fistulotomy or fistulectomy. Performing preoperative anal manometry is a useful tool for predicting postoperative functional outcomes as well as guiding the type of fistula surgery to minimize sphincter related complications.[56] In an international survey of surgeons who treat anal fistula, 80% considered fistulotomy as the gold standard.[57](A1)

Seton-Primary Drainage of the Fistula

Seton placement works by the simple concept of allowing a fistula to adequately drain so that healing by secondary intention, from internal to external, may occur. A seton may be placed in the operating room once both the internal and external openings of a fistulous tract are known, and the tract is probed with a lacrimal probe. By allowing the tract to drain and having the seton in place continuously, the tract will slowly migrate from a deeper or higher space to a more superficial location. There are various kinds of setons, mainly simple setons, which may be a small vessel loop that is placed loosely. Setons may be used as the primary treatment for a fistula or as a staged procedure, and the patient return to the operating room for a fistulotomy after their high fistula has converted to a low fistula.

For a cutting seton, a suture is placed and is tied snugly to encourage the migration of the tract. As the wound migrates, the seton becomes loose, and it is then tied again more snugly in the office at intervals. A loose seton, typically a vessel loop, the patient may regularly turn to assist the healing, and these are effectively similar to cutting setons.[58] Setons are an effective definitive therapy for high trans-sphincteric fistulas with complete healing rates up to 98%.[59][60][61][62][61] They can also be used as effectively as a staged procedure. Setons are highly effective in Crohn disease patients as well.[63](B2)

In an extensive study of 372 patients in Saudi Arabia with high anal fistula, the combination of cutting seton, an 0-silk suture-0, placed after a partial fistulotomy had exceptional healing rates of 97% with no fecal incontinence and a low recurrence 2.4%.[64] In a study of high trans-sphincteric fistulas in the US, the daily rotation of a silk suture seton by the patient was an effective means for treating the high fistulas with zero patients having incontinence of stool.[65] Of patients with high trans-sphincteric fistulas treated with setons, recurrent fistula, supra-levator extension, or the presence of horseshoe fistula have a higher propensity for recurrence.[66] Setons have also been shown to be successful in supra and extra-sphincteric fistulas.[67] Advantages are the preservation of the sphincter, the ability to treat high or complex fistulas with a simple technique. Preserving the internal sphincter intraoperatively may further decrease rates of incontinence postoperatively.[68] Setons have been shown to have significantly higher healing rates than treatment with fibrin glue.[69](A1)

Some disadvantages of setons are that they require frequent follow-up, are cumbersome for the patient, might be uncomfortable for patients, and have long healing times, which can be up to 6 months or, in some cases, longer. In a study of 55 patients who failed seton therapy for their fistula, an endorectal advancement flap had superior short term results than a LIFT.[70](B2)

Ligation of Intersphincteric Fistula Tract (LIFT)

Description: 

The LIFT procedure was first described by Rojanasakul & colleagues in 2007, in which 18 patients with intersphincteric fistulas were successfully treated using this novel technique. The method involves identifying the intersphincteric groove (ISG), identifying the internal and external openings of the fistula, followed by careful dissection of the portion of the fistula tract within the intersphincteric groove. The dissection can be carried out using cautery and or small scissors. Once the tract is dissected and is clamped with a right angle clamp, it can be safely suture ligated within the ISG close to the internal sphincter while preserving the integrity of both the internal and external sphincter musculature. It is then ligated with an absorbable suture. Distal to its ligation the tract is sharply divided, and this is confirmed with an injection of saline or hydrogen peroxide through the external opening. Any remnant of the intersphincteric tract is carefully removed, and finally, a small incision on the external opening is made to facilitate drainage. The wound over the ISG is precisely approximated with a few simple absorbable sutures.[71] The LIFT procedure can also be safely performed using a lateral approach with acceptable outcomes of up to 75% healing rates.[72](A1)

This technique is specific for trans-sphincteric fistula tracts. Still, it can also be utilized for other complex fistulas that have a tract through the ISG, such as horseshoe or supra-sphincteric fistulas.

LIFT is an effective surgical modality for high and complex anal fistulas with healing rates ranging from 40-100%  and very low or absent sphincter dysfunction with larger cohorts demonstrating first time healing around 75% of the time.[73] Failures of the operation are usually attributed to incorrect identification of the intersphincteric portion of the fistula tract. In a systemic review and meta-analysis of which included 1295 patients comparing LIFT to anal advancement flap, there was no significant difference in cure rates in both cryptoglandular and Crohn disease-associated fistulas; however, the LIFT had better continence preservation.[74] Both groups had acceptable cure rates in 61% of Advancement flap patients and 53% of LIFT patients.(A1)

Some cons of the LIFT is the potentially high recurrence rates reported in studies approaching 40%.[75]

Benefits of the LIFT procedure are the ability to operate on patients with previous fistula surgeries, preservation of continence, small incision, and scar, and the method is compatible with re-operation if needed. Patients with a history of multiple fistula surgeries, a longer fistula tract, smokers, or those with obesity are at higher risk for failure of the operation.[76]

Advancement Flap for Anal Fistula

Advancement flap for anal fistula is one of the earlier techniques for treating complex anal sphincters that has remained an important surgical option through the years despite many variations in technique and combinations of this technique with others. Rectal advancement flap or mucosal advancement flap, this procedure is commonly performed using rectal mucosa coverage of the internal opening of the fistula after coring out of the fistula tract. Usually, the external opening is left open to drain. It has been shown to have acceptable healing rates with low recurrence in <10% of patients and is a viable option for patients who have had prior fistula surgeries.[77] The shape of the endorectal flap, which can be elliptical or rhomboid, does not appear to affect outcomes.[78] For higher or more proximal fistulas, a trans-anal approach, or TAMIS (transanal minimally invasive surgery), can be utilized successfully to allow easier and more extensive mobilization of a long rectal flap.[79] Compared to seton placement, RAF may have a lower recurrence and wound infection rates.[80] Partial or full thickness flaps are superior to mucosa only flaps in some studies with lower failure rates. This is generally attributed to the improved blood supply of the flap as the underlying circular smooth muscle contains significant vasculature.[81][82](A1)

Despite usually high rates of fistula recurrence in Crohn disease patients, RAF is another treatment option for these patients, provided there is adequate drainage before the flap procedure.[83] Crohn disease patients treated with immunologic seems to have improved outcomes with this operation.[84] Smoking is associated with failure of advancement flap repairs, and with recurrence of the fistula, horseshoe fistula is associated with failure.[85] There are multiple variations of advancement flaps published in the literature with the type necessary determined by the type of fistula present. For instance, rectal advancement flap, in combination with sphincteroplasty, has been effectively utilized for the treatment of rectovaginal fistulas secondary to obstetric procedures.[86](A1)

Anal Fistula Plug: 

An anal fistula plug is another sphincter sparing procedure which can be utilized in patients with a high risk of incontinence or complex fistulas. Plugs can be made of fibrin, porcine, or other biologic absorbable materials. Adequate drainage of the fistula must take place before placing any foreign body to minimize the risk of anal sepsis. For the fistula plug surgery, the internal and external opening of the fistula is first identified, and a probe is placed through them. This is sometimes followed by a mini-debridement of the track using a "fistula brush" or curette. A suture is easily pulled through the track, and the plug threaded through it.

The plug is sutured in place in the internal opening to the mucosa and the internal anal sphincter such that mucosa covers it entirely. In contrast, the external fistula opening is left open to drain. Anal fistula plugs have been widely controversial, with studies being inconsistent in outcomes. A large randomized control trial of fistula plug versus surgeon preference for transphincteric fistula in the United Kingdom found similar healing rates but with higher cost in the anal plug group, with no difference in the fecal incontinence, quality of life scores between the two groups.[87] Healing rates for complex fistulas treated with anal fistula plug as a primary therapy range 13-60%, with most studies quoting around 55%.[88][89][90][91] They tend to have higher recurrence rates of fistula than other surgeries for anal fistula as well. In a randomized controlled trial comparison of fistula plug versus mucosal advancement flap, the fistula plug had recurrence rates 66%.[92] Besides lower healing rates, absorbable fistula plugs have been associated with postoperative anal sepsis.[93] Studies in favor of anal fistula plugs have shown cost-effectiveness when compared to endoanal advancement flap repair but in a small sample.[94] In a randomized controlled trial of 104 patients with Crohn disease, anal fistula plug was not superior to the removal of seton.[95] Because the results of studies have varied widely, it is still recommended in some international guidelines for the treatment of Crohn disease anal fistulas and recognized as a treatment option for these patients by the ASCRS guidelines.(A1)

Video-Assisted Anal Fistula Treatment (VAAFT)

Video-Assisted Anal Fistula Treatment of VAAFT is an emerging modality for the treatment of anal fistulas. It involves placing a tiny endoscope, a "fistuloscope," through the external opening of the fistula tract and the tract is explored for its internal opening. Any contiguous tracts or abscesses are identified. Diathermy is used to obliterate the tract under direct visualization, and, similar to plug therapy, the tract is debrided with a brush. The internal opening, once localized, and after debridement, is closed with sutures. In one study of 73 patients treated for complex cryptoglandular fistulas, VAAFT was associated with decreased pain, length of stay, and wound secretion and was able to be repeated safely for patients who failed initial VAAFT.[96] Further studies will provide more insight into this novel technique. (B2)

Anal Fistula in Crohn Disease

Fistulizing disease in Crohn patients is a severe disease to treat, but early recognition and diagnosis are critical to effective therapy. These patients should be referred to a gastroenterologist and receive anti-TNF alpha therapy as their primary treatment for fistula disease. After medical treatment, if the fistula persists, setons are the most commonly used primary surgical option in these patients with reasonable healing rates after anti-TNF alpha therapy.[97] Crohn disease patients often are misdiagnosed and have delays in care and also may experience prolonged waiting periods to obtain their medications; thus, a comprehensive care team may be more effective in the management of these patients.[97] Infliximab is the primary treatment for these patients.  In patients receiving infliximab therapy, higher blood levels of the drug have been associated with improved healing rates.[98][99] Patients with Chron disease are likely to have concomitant proctitis, which is revealed by preoperative imaging. A study of 126 patients with anal fistulas who underwent preoperative MRI found that MRI findings of concomitant rectal inflammation were more closely associated with Crohn disease.[100]

The International Organisation for Inflammatory Bowel Diseases (IOIBD) global consensus guidelines emphasize the importance of evaluation of the rectum in these patients as their disease may often affect the rectal mucosa and anorectal area simultaneously. In a study of 36 pediatric and adult patients with fistulizing Crohn disease, a cutoff of 2.5 cm seen on MRI predicted patients who responded to infliximab therapy and those with the persistence of illness.[101] A few studies have shown effective healing rates around 67-90% of combined seton and anti-TNF alpha therapy in Crohn disease patients that were retrospective in nature.[102][103] A large meta-analysis comparing healing of primary seton versus infliximab failed to determine which was superior as the studies varied in outcomes.[104](A1)

Differential Diagnosis

The differential diagnosis for anal fistula includes firstly all of the common anorectal conditions seen in a primary care providers office or that of a general or colorectal surgeon.

• Anal fissure
• Anal warts
• Condyloma acuminate
• Hemorrhoids
• Perianal abscess
• Solitary rectal ulcer syndrome

In addition to these, there are infectious, benign, and malignant processes which may present as or appear as an anal fistula such as

• Crohn disease
• Hidradenitis suppurativa
• Anal cancer
• Atypical presentation of anal sexually transmitted diseases can mimic anorectal fistula. Anorectal sexually transmitted infections include syphilis, herpes, gonorrhea, or chlamydia [105], as well as granuloma inguinal caused by Calymmatobacterium granulomatosis.[26]
• In HIV positive patients presenting with symptoms of anal fistula, the diagnosis of potential Kaposi sarcoma,[106] as well as lymphoma.[107]

Prognosis

Prognosis of the anorectal fistula is variable depending on etiology. In anal fistulas of cryptoglandular origin healing rates for simple fistulas approach 80%, and that of complex fistulas are around 60% for sphincter preserving operation. Setons have been used with much success up to 80 to 90% healing rates, but these are healing rates measured after six months. In general, a fistula that is treated with a fistulotomy or fistulectomy, depending on the wound size, should be entirely healed by 12 weeks. If drainage is increased or persistent up the twelfth week that the fistula recurred or did not close completely. Causes for failure of surgical therapy include incomplete division of the fistula in a fistulotomy or incomplete resection or obliteration of tract in a fistulectomy. In the LIFT procedure, leaving a long fistula tract behind and incomplete ligation of the fistula tract are possible causes of failure. In anal-cutaneous or rectal mucosal advancement flap techniques, if the flap fails, the fistula will either not heal or will recur. Smoking is a risk factor for failure of treatment with flap, as well as Crohn disease.[108] This is often secondary to the inadequate blood supply of the flap, as evidenced by improved healing rates when the muscular layer is used in the flap. 

Failure of anal fistula plugs to allow fistulas to heal can be attributed to multiple reasons including, not completely covering the plug internally, incomplete debridement of the fistula tract, and premature dislodgement of the fistula plug. Setons that are removed too early may lead to the fistula not healing if the tract has not migrated sufficiently to allow the fistula to heal. Some setons may lead to a lower fistula that then requires a fistulotomy for complete healing to occur. 

Depending on the initial procedure performed, additional procedures are used to treat recurrence fistula. When a fistula recurs, an MRI is helpful to determine its course, and an exam under anesthesia should be performed to characterize the fistula tract. Treatment is based on the type of fistula present, which may be different on recurrence than on complex fistula. Because the risk of incontinence is increased with repeated anorectal surgeries, a sphincter preserving approach is best utilized in the treatment of recurrent fistula, mainly if a fistulotomy or fistulectomy was the primary treatment. LIFT procedure is an option for recurrent fistulas. A failed LIFT procedure may be followed by a repeat LIFT procedure or an advancement flap procedure or seton. One study which evaluated outcomes of 53 patients who failed LIFT procedure and went on to undergo an endorectal advancement flap or fistulotomy staged with seton showed a 50% healing rate.[109] Of patients with a high transphincteric fistula, those with a horseshoe extension of the fistula may have improved success with anal advancement flap repair.[85]

Setons used as the primary treatment should be considered a staged procedure and followed by a fistulotomy. Anal fistula plug procedure that has failed may be followed by a seton, advancement flap, LIFT, or even fistulotomy depending on the location of the fistula. A failed flap may be repeated using tissue from a different site. VAAFT is a safe treatment option when repeated for failed initial VAAFT with increased healing rates on the repeat procedure.[110]

Complications

Complications of anal fistula surgery are

• Recurrence of fistula
• Incontinence to flatus or stool
• Chronic draining wound
• Anal stricture

A large meta-analysis examined risk factors for recurrence of anal fistula after fistula surgery included a high transanal fistula, horseshoe extensions, and multiple fistula tracts as well as the patient having a history of anal procedures or not identifying the internal opening of the fistula intraoperatively.[111] In a study of 251 patients who had high transphincteric fistulas and were treated with loose setons history of fistula surgery, horseshoe fistula, and anterior fistula were risk factors of recurrence.[66]

Risk Factors for fecal incontinence after fistula surgery include a history of anorectal procedures, female gender, complex fistulas, and preoperative incontinence. Fistulotomy should be avoided in fistulas, which are grades 3 or 4 as complex fistulas are associated with higher rates of postoperative incontinence.[112] Performing anal manometry can be helpful preoperatively in determining which patients should undergo a sphincter sparing approach as patients that exhibit signs of incontinence before surgery are more likely to have worsened function postoperatively.[113] A history of incisions and drainage or multiple fistula surgery is associated with a higher risk of worsened postoperative sphincter function as well as the type of operation performed, a fistulotomy, or a sphincter sparing procedures.[114]

Female sex is a risk factor for postoperative incontinence. Treatment of incontinence to flatus and stool involves biofeedback therapy, sacral nerve stimulation. A systematic approach to fecal incontinence has been proposed with initial treatment consisting of bulking agents for stool and increasing dietary fiber followed by training of the pelvic floor muscles with biofeedback therapy. If these are not effective, then more invasive options, including surgical sphincteroplasty, magnetic anal sphincter, or implantation of an artificial anal sphincter may be considered. Only in patients that have exhausted all non-invasive and invasive options is a colostomy offered for recalcitrant fecal incontinence.[115]

The best remedy for any complication is prevention. One way to prevent incontinence is by minimizing the number of procedures a patient requires for his or her fistula and tailoring therapy for high-risk patients. Counseling patients preoperatively on the risks of fecal incontinence and obtained preoperative anal manometry are all useful for stratifying patients preoperatively. Obtaining preoperative imaging to classify fistulas before surgery more accurately should be considered as well.