List of Abbreviations
European Crohn’s and Colitis Organisation
Exam under anesthesia
Magnetic resonance imaging
Tumor necrosis factor
Perianal disease is one of the most disabling aspects of Crohn’s disease. It affects 17%–43% of the patients, especially those with proctitis. Perianal Crohn’s disease affects both the pelvic floor muscles as well as the gastrointestinal tract. The anal canal contains epithelial lining, subepithelium, supporting tissues, as well as musculature of the pelvic floor and anal sphincter complex ( Fig. 17.1 ). The upper anal canal is composed of transitional and columnar epithelium which changes to squamous anal epithelium at the dentate line that contains anal columns and crypts. Perianal fistulas may develop in this region, and the risk of development increases with those who have more distal involvement. In one natural history study, 92% of the patients with rectal disease developed perianal fistulas. Several theories have been proposed for the development of fistulas. One theory proposes that deep penetrating ulcers in the anus or rectum are extended over time into fistulous tracts as feces are forced into the ulcer with the pressure of defecation. Another theory holds that Crohn’s perianal fistulas may result from an infection or abscess of the anal glands, themselves.
Classification systems for describing fistula anatomy allow gastroenterologists, endoscopists, and surgeons to speak a common language when describing fistula anatomy. There are multiple classification systems to describe the extent of perianal fistulas. One system classifies fistulas as either “high” or “low” relative to their presence above or below the dentate line. Fistulas that open into the rectum above the dentate line are considered high fistulas, while those that open below the dentate line are considered low fistulas. Park’s classification system, developed in 1976, uses the external anal sphincter to identify five main groups of fistulae: intersphinteric, transsphincteric, suprasphincteric, extrasphincteric, and superficial ( Fig. 17.2A ). Intersphincteric fistulas do not involve the external anal sphincter. These could also be described as “low” fistulas. Transsphincteric fistulas pass through the external anal sphincter. Suprasphincteric fistulas pass over the external anal sphincter and through the pelvic floor muscles. Extrasphincteric fistulas are outside the external sphincter complex and pass through the rectal wall, pelvic floor muscles, and ischiorectal fossa. Finally, superficial fistulas do not involve the internal or external sphincter. A third classification system was established in 2003 by the American Gastroenterological Association technical review of perianal fistulas which combines physical exam as well as endoscopic evaluation to define fistulas as either simple or complex ( Fig. 17.2B ). A simple fistula occurs low in the anal canal with a single external opening and no evidence of abscess, rectovaginal fistula, or anorectal stricture. A complex fistula occurs above the dentate line, involving a significant portion of the external anal sphincter and may have multiple external openings, pain, evidence of abscess, rectovaginal fistula, stricture, and may have active rectal disease as visualized by endoscopy. With these newer classification systems of perianal Crohn’s disease, an advanced imaging modality is crucial in characterizing fistula anatomy. Endoscopic ultrasound (EUS) can help demonstrate fistula extension, sphincter complex involvement, and distinguish fistulas and abscesses from other causes of perineal pain as well as provide information about the anatomic extent of the fistulas. It can also be used to assess the degree of inflammation present and also to monitor response to the eventual treatment utilized.
Endoscopic evaluation is normally done with either a flexible sigmoidoscopy or colonoscopy to assess disease activity, identify if a rectal mass is present, and evaluate the adequacy of preparation. The presence of proctitis is one of the key determinates in deciding the best medical and surgical options to utilize for an individual patient. This is normally followed by a rectal EUS to determine fistulas anatomy. As such, both assessments can be performed very quickly during the same session. Previously, the gold standard for diagnosis of perianal fistulas had been exam under anesthesia (EUA) as performed by a surgeon. Given the degree of inflammation and scarring that is often present in patients with perianal Crohn’s disease, this can be very inaccurate. Previous accuracy estimates of a digital rectal exam to define fistulas were rated at only 62%.
Computed tomography (CT) scan has been implemented to assess perianal Crohn’s disease but has been unreliable in evaluation due to the difficulties in differentiating inflammation and fistulous tracts. A study conducted by Schratter-Sehn of 25 patients, 17 of which had fistulas, CT scan was only able to classify 24% of the areas as fistulas. However, endoscopic evaluation can evaluate for active inflammation and affect possible surgical options.
MRI has been useful to demonstrate fistula extension, involvement of the sphincter complex, and delineate perianal fistulas from other causes of perineal infection. A study conducted by Beets-Tan et al. showed that after initial EUA, MRI findings led to a change in surgery in 12 (21%) of 56 patients. MRI has been compared to EUA, and the specificity of MRI in identifying the fistula and its path ranges from 76% to 100%. A prospective study comparing pelvic MRI, EUS, and EUA showed that the pelvic MRI correctly classified 26 of 30 (87%) patients as compared to the consensus gold standard. MRI provides an additional imaging modality to accurately diagnose perianal Crohn’s disease.
Endoscopic Ultrasound Evaluation
Rectal EUS for the purpose of assessing perianal fistulas is normally conducted utilizing a radially scanning echoendoscope. The scope is advanced to the rectosigmoid junction and imaging is then performed upon withdrawal. Special attention is paid to the puborectalis, the internal, and external anal sphincter. Fistulas normally appear as dark or hypoechoic tracts with beads of hyperechoic foci noted within. This corresponds to air (hyperechoic foci) present within an inflammatory fistula (hypoechoic track). ( Fig. 17.3 ) As the fistula heals, the fistula becomes less hypoechoic and more heterogeneous in appearance, and the width of the hypoechoic appearance shrinks in size ( Fig. 17.3B ). EUS can assist in the classification of fistula tracts, identify abscess cavities, and assess the degree of active inflammation surrounding a fistula tract which can in turn guide decisions regarding medical and surgical therapy. It is extremely important to properly and accurately characterize a perianal process due to risk of incomplete healing, recurrent fistula, or even iatrogenic sphincter injury if the evaluated anatomy is not correct.
Use of endoscopic ultrasound has been shown to assist in delineating the anatomy of the fistula track to complement both clinical assessment and examination under anesthesia to guide treatment by either excision of the fistulous track, seton drainage, or combination with medical therapy. A study of 18 patients over a 16-month period employed anal endosonography to assist in finding the site of the internal opening, level of the fistula track, relation to the anal sphincters (intersphincteric, transsphincteric, or extrasphincteric), and establish site of fluid collections. This study identified 14 complex fistulas with two or more fistulous tracks present and showed complications such as a horseshoe shape that may not have been identified solely by examination under anesthesia.
A study by Lindsey et al. showed that anal endosonography performed preoperatively influenced operative management in 38% cases toward a more conservative treatment. The utility of endoscopic ultrasound was studied in a pediatric population identifying 25 children who underwent seton placement or EUS between 2002 and 2007 in a large academic center. In this population, 42 total endoscopic ultrasounds were performed. In total 28 EUS were used to evaluate suspected perianal disease, 15 (54%) identified complex fistulizing perianal disease requiring seton placement. Fourteen EUS were used to monitor continued healing, and 7 (50%) cases found persistent inflammation despite seton placement and the setons were left in place. These patients were more likely to have a biologic initiated in 57% versus 0% who did not have follow-up EUS. The conclusion of this study demonstrated that endoscopic ultrasound is a viable option for guiding therapy and providing accurate evaluation of persistence of perianal disease.
Endoscopic Ultrasound Evaluation Compared to Other Imaging Modalities
EUS as compared to CT is highly superior in diagnosing fistulas as evidenced by Schratter-Sehn’s evaluation. Their study investigated 25 patients with clinical symptoms of perianal Crohn’s disease as defined by endoscopically active rectal disease, perianorectal pain, visible perianal inflammation, fistula opening visible externally or endoscopically. Their results showed fistula diagnosed in 17 of 25 patients with EUS detecting fistulas in 14 (82%) patients compared to 4 (24%) patients detected by CT scan. Fistulas and perianal disease are seen as branching hypoechoic structures that may contain either fluid or air on endoscopic ultrasound. CT scan evaluation of perianal disease can only identify areas as a dense linear streak if it receives contrast medium or air, which is not always the case. Endoscopic ultrasound has become the primary method for diagnosing perianal disease in Crohn’s disease with the advantage of avoiding radiation and can aid in localizing fistulas when selecting if a possible surgical procedure is necessary. Endoscopic ultrasound can also employ injection of either methylene blue or hydrogen peroxide to aid in the sonographic detection by causing bubbles to be produced that can aid in localizing the fistulous area.
EUS and MRI for the evaluation of Crohn’s perianal fistulas have been compared in several studies. A study of 34 patients comparing endoscopic ultrasound, MRI, and EUA for evaluation of perianal Crohn’s disease found similar accuracies of EUS 91%, MRI 87%, and EUA 91% as compared to the consensus diagnosis . When these modalities are combined the accuracy can increase to up to 100%.
The advantages of MRI imaging for recurrent fistulas include the views of fistulas in both coronal and sagittal planes to better delineate landmarks and to predict location of disease. The disadvantages of endoscopic ultrasound include poor visualization beyond the external sphincter and difficulty in imaging in the coronal plane as compared to MRI.
Endoscopic/Endoscopic Ultrasound–Guided Therapy
The use of imaging to guide multimodality treatment (combination medical and surgical therapy) during the initiation of treatment has been shown to improve the initial outcomes for patients and is now incorporated into the many of treatment guidelines that have been published recently. The 2016 European Crohn’s and Colitis Organisation (ECCO) guidelines state that pelvic MRI is the initial procedure for assessment of perianal fistulizing Crohn’s disease with EUS as an alternative with increased specificity when these modalities are combined with EUA. As per the guidelines, anal endosonography in combination with clinical assessment is recommended to guide response to medical or surgical treatment. The use of imaging to improve long-term fistula healing is just starting to be incorporated into clinical practice. Several studies have shown that fistulas stop draining well before they are completely healed. Relying on physical examination (i.e., cessation of drainage) alone to make important treatment decisions such as seton removal or alteration in medical therapy can lead to suboptimal results.
Endoscopy and endoscopic ultrasound have become essential in monitoring medical therapy and stratifying appropriate treatment. Endoscopic ultrasound may demonstrate persistent inflammation even if drainage has ceased after seton placement leading to longer times prior to the removal of seton with improved outcomes or medication changes. Schwartz et al. demonstrated in 21 patients with active perianal disease that using EUS to tailor therapy for Crohn’s perianal fistulas with infliximab, an immunosuppressive, and antibiotics is associated with a high short- and long-term fistula response rate and can identify patients who may discontinue infliximab without recurrence of fistula drainage. Initial assessment was made by endoscopic ultrasound followed by EUA to determine whether incision and drainage and seton placement was needed. In this study, most patients had incision and drainage performed surgically or setons placed, although seven patients with simple fistulas were treated solely with medical therapy. All patients were treated with induction regimen of infliximab followed by maintenance infliximab infusion with endoscopic ultrasound monitoring every 8 weeks to guide treatment decisions. Setons were not removed unless the fistula appeared inactive by endoscopic ultrasound, which is shown when the hypoechoic texture of the tract becomes more heterogeneous and closely approximates the seton. Endoscopic ultrasound may show persistent fistula activity at the time of drainage cessation with median time to inactivity at 21 weeks compared to drainage cessation at 12 weeks.
A recent randomized prospective study compared endoscopic ultrasound guidance of fistula treatment to the standard of care for perianal Crohn’s disease. The study contained nine patients who underwent EUS-guided therapy and 11 control patients whose treatment management was based on exam and patients symptoms. The initial results showed a higher rate of drainage cessation in the EUS-guided treatment cohort versus control group at week 24 (78% vs. 27%), which disappeared by the primary endpoint of week 48. These results demonstrated that patients receiving serial rectal EUS examinations to guide therapy had more rapid improvement in fistula drainage as compared to the standard of practice. These results are promising that serial monitoring may allow for faster healing times of perianal fistulas to improve patient’s quality of life.