Interventional Radiologic Management and Treatment of Enterocutaneous Fistulae

Interventional Radiologic Management and Treatment of Enterocutaneous Fistulae

REVIEW ARTICLE Interventional Radiologic Management and Treatment of Enterocutaneous Fistulae Feraz N. Rahman, MD, MS, and Joseph M. Stavas, MD, MPH ...

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Interventional Radiologic Management and Treatment of Enterocutaneous Fistulae Feraz N. Rahman, MD, MS, and Joseph M. Stavas, MD, MPH

ABSTRACT Enterocutaneous fistulae (ECFs) are abnormal sinus tract communications between the alimentary system and skin surface that can cause significant management problems and cost to the health care system. Interventional radiology can play an important role in diagnosis and treatment when conventional measures fail and additional surgery is difficult or poses a high risk. The management of patients with fistulae requires operator ingenuity and dedication, a multidisciplinary team approach, and an understanding of the pathophysiology. This article reviews the major issues in ECF management and the role of interventional radiology.

ABBREVIATIONS AFP = anal fistula plug, ECF = enterocutaneous fistula, ECM = extracellular matrix, IBD = inflammatory bowel disease, TPN = total parenteral nutrition, WV = wound vacuum

Enterocutaneous fistulae (ECFs) are feared sequelae of many medical conditions such as abdominal surgery, inflammatory bowel disease (IBD), and abscesses (1,2). ECFs can lead to malnutrition, sepsis, and even death. Even low-morbidity fistulae can impair quality of life and cause psychologic issues (3). The surgical definition of a fistula is an abnormal connection between two epithelialized surfaces. Fistulae are named by the direction of flow. For example, in gastrocutaneous fistulae, gastric contents drain to the skin surface directly through an abnormal tract. This review will focus on the management and treatment of ECFs between the stomach, small intestine, or colon and the skin surface (excluding etiologically disparate perirectal fistulae). Management of ECFs requires a multidisciplinary team communication between numerous health care providers including surgeons, gastroenterologists, radiologists, nutritionists, wound care specialists, enterostomal From the Division of Vascular and Interventional Radiology, University of North Carolina, 101 Manning Dr., CB 7510, Chapel Hill, NC 27599-7510. Received March 6, 2014; final revision received September 10, 2014; accepted September 13, 2014. Address correspondence to J.M.S.; E-mail: [email protected] J.M.S. is a paid clinical advisor for Excelerate Health Ventures (Durham, North Carolina) and a paid medical consultant for Cook (Bloomington, Indiana) and Tengion Inc (Winston-Salem, North Carolina). The other author has not identified a conflict of interest. & SIR, 2014 J Vasc Interv Radiol 2014; XX:]]]–]]]

therapists, and psychiatrists/psychotherapists. This article reviews the diagnosis and treatment of ECF and the role of interventional radiology with minimally invasive treatment methods. There is limited literature regarding percutaneous ECF closure methods, which allows ample opportunity and need for expanded research in this area.

BACKGROUND The mortality rate from ECFs is reported between 10% and 30% (4,5). ECFs allow enteric contents to contaminate sterile spaces and may cause infection and sepsis. Decreased flow through the distal digestive tract in highoutput fistulae can produce local inflammation, fluid depletion, electrolyte imbalance, and malnutrition, leading to catabolic conditions (6). This prevents healing of skin inflammation and necrosis caused by excess succus and bowel contents. Patients with ECFs have longer hospital stays, increased financial hardship, and decreased quality-of-life measures (7,8). The chronicity of ECF can lead to mental distress with resulting decreased self-esteem and depression (3). Although ECFs have many causes, the majority (as many as 85%) are iatrogenic/postoperative (9). This includes fistulae caused by unintended enterotomy and failure of surgical bowel anastomoses. Iatrogenic ECF has been reported following embolization for gastrointestinal bleeding, with ischemic bowel perforation, abscess, and fistula development (10). Fistulae have also been reported with palliative enteric stents (11) and traumatic penetrating bowel injuries (12). De novo


IR Management and Treatment of Enterocutaneous Fistulae

ECFs may result from underlying IBD or ulcerating tumors.

Prognostic Factors A useful interventional radiologic management algorithm is best developed by understanding ECF etiology and wound healing. Fistula location and anatomy can greatly affect prognosis and treatment as a result of widely variable physiologic function and location of bowel, underlying disease processes, and surgical interventions. These factors make fistula mapping a critical first step. Esophageal fistulae appear to have shorter spontaneous closure times without intervention than other types of ECFs (13). Gastric fistulae are less likely to close spontaneously secondary to acidic skin and tissue injury. High-flow ECFs involving the small bowel, particularly the duodenum (14) and ileum, are unlikely to close spontaneously and pose a higher risk of causing malnutrition. These may require more aggressive treatment attempts. Long, narrow fistulae heal more spontaneously than short fistulae of larger caliber (15). Fistulae with abdominal wall disruption as a result of complex open wounds or dehiscence are difficult to treat and require coordinated care with ostomy specialists. ECFs with established skin openings are relatively easier to treat. It is equally important to quantify the flow of digestive contents through ECFs. High-output fistulae drain greater than 500 mL over a period of 24 hours. These usually arise from small bowel, where large volumes of digestive material pass quickly. High-output fistulae cause significant nutritional morbidity from diversion of enteric contents and often require total parenteral nutrition (TPN) (16). Medium-output fistulae drain between 200 and 500 mL over a period of 24 hours, and low-output fistulae drain less than 200 mL over a period of 24 hours. These usually arise from large bowel. Patients with low-output fistulae often do well with oral nutrition alone. Color and odor of the drainage can foretell the small-bowel or large-bowel origin of the ECF. A number of additional factors contribute to ECF formation and affect closure rates. A useful mnemonic describing these is “FRIENDS”: Foreign bodies, Radiation treatment, Inflammatory bowel disease (Crohn disease and ulcerative colitis) and ischemia, Epithelialization (more commonly tissue granulation/fibrosis), Neoplasms, Distal obstruction, and Sepsis. Foreign bodies hinder healing and prevent spontaneous closure by causing inflammation and serving as a nidus for infection. Retained hernia mesh and suture material are often implicated, and the ECF may not heal without removal (17). Integrity of the bowel and surrounding tissue is important for closure of ECFs. Radiation can cause enteritis and damage of vasa recta. Ischemia and

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inflammation from radiation and other causes lead to mucosal inflammation, perforation, abscesses, and fistulae. IBD, most commonly Crohn disease, is another cause of gastrointestinal inflammation, ulceration, granulation, and fistula development. These ECFs may remain unhealed in active disease. Maturation of chronic fistulous tracts with granulation tissue prevents spontaneous closure. True epithelialization with metaplastic glandular or squamous tissue is rare except in perirectal fistulae because of the difference in mechanism. Most chronic tracts contain granulation or fibrous tissue. Metaplasia has also been implicated in the rare development of fistula-associated adenocarcinoma (18). A neoplasm at the fistulous origin will interrupt the normal mucosal surface and cause inflammation and tissue destruction that can lead to ECFs and prevent closure. Distal obstruction can impair closure by causing increased fistula output and pressure, and should be suspected in recurrence of a previously healed fistula. Sepsis prevents ECF closure by causing catabolism and decreased healing, and is discussed here later.

Approach to Management A mnemonic useful in approaching the management and treatment of ECF is the word “SNAP”: Sepsis control, Nutritional support, Anatomy definition, and Plan. Sepsis control is one of the most important determinants in ECF outcome (19). The catabolic state of sepsis decreases nutrition and immune response, significantly decreasing closure rates. Sepsis also limits many surgical and interventional radiologic closure procedures. Interventional radiologic drainage of fluid collections and abscesses is important to allow optimum healing, prevent sepsis, and reduce the risk of ECF formation. Nutritional status is extremely important for successful fistula closure. Similar to sepsis, malnutrition leads to a catabolic state and reduces healing (20,21). The role of correcting nutritional status with TPN is controversial. TPN has been shown to decrease fistula output, but not reduce closure times or improve mortality, and is associated with numerous risks (22). Enteric feeding promotes the immunologic, hormonal, and barrier functions of the gut and newer elemental formulations can reduce fistula output comparable to TPN (23). Fistuloclysis, the practice of inserting a tube through the fistula into the distal bowel for feeding, has been shown to be a viable nutritional substitute for TPN (24). This is more useful in proximal fistulae with increased digestive surface area distally but may prevent ECF closure from tract maturation. Anatomic mapping of the fistula source and characteristics yields prognostic information and helps plan an approach to treatment. Imaging performed to evaluate anatomy can also reveal the cause of the fistula (ie, anastomotic breakdown, neoplasm, or active IBD) and further guide management.

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Planning a treatment course with input from all care team members is imperative. This includes appropriate imaging evaluation, nutritional support, sepsis treatment/prevention, and wound care. Based on the imaging and clinical characteristics of the fistula, an initial conservative approach can be attempted before surgical, endoscopic, or interventional radiologic interventions.

IMAGING EVALUATION OF ANATOMY Fluoroscopic Sinogram Evaluation Direct sinogram evaluation (also called fistulography) is performed with fluoroscopy after a simple skin preparation, and is the gold standard of ECF characterization (Fig 1). The study can be performed immediately before intervention. Local anesthesia may be required if there is skin tenderness or pain with catheter placement and manipulation in the tract. The skin wound may be temporarily sealed over at the time of the scheduled sinogram. The thin layer of epithelium can be punctured with a 16- or 18-gauge needle to access the subcutaneous tissue tract with a catheter. Otherwise, the patient can be rescheduled to be evaluated at a time when there is active fistula drainage. Any simple angled 5-F catheter can be used to cannulate the skin wound site and fistulous tract while injecting high-density iodinated contrast medium during fluoroscopic imaging. If there is too much resistance to contrast medium flow within the fistula from superficial reflux on the skin, a balloontipped catheter such as a pediatric Foley catheter can be used to gently occlude the fistula opening and prevent reflux. Fluoroscopy is intermittently used until contrast medium flows into the enteric lumen. The location of the enteric spill can be identified by the caliber and characteristic bowel folds. Fluoroscopic spot radiographs with anterior/posterior and oblique views are obtained to appropriately


characterize the length, diameter, number, and branching patterns of the fistulous tracts and appearance of the bowel mucosa. Observation of communicating fluid collections, cavities, and blind ending branches along the central tract is necessary because drainage is required before any closure treatment attempts are made. Distal colonic fistulous tracts can also be assessed by dilute contrast agent enema (Fig 2).

Cross-Sectional Imaging and Ultrasound Computed tomography (CT) is best used for early diagnostic evaluation of intraabdominal pathologic conditions and can identify certain developing fistulae but may not detect small ECF tracts. CT use in evaluating a known ECF is to determine cause and search for associated abnormalities such as abscess or bowel obstruction. Intravenous contrast medium is helpful to identify adjacent inflammation or neoplasm and the location of surrounding vascular structures in the event catheter drainage is necessary. Oral contrast medium better delineates bowel and may identify communication with surrounding structures and fluid collections. Secondary signs of ECF include extraluminal gas and inflammatory stranding tracking to the skin surface. Gee et al (25) showed magnetic resonance (MR) enterography to be an equal substitute for CT in evaluating IBD softtissue pathologic conditions and inflammation in a small series. In the same study (25), MR imaging differentiated inflammatory narrowing of bowel from chronic stenosis, which is helpful in planning treatment as active disease with ECF responds best to medical treatment. Ultrasound (US) was found inferior to MR enterography in the evaluation of fistula in IBD as a result of image degradation by bowel gas, obesity, pelvic bowel location, and wound dressings (26). However, US can often recognize bowel disease, hypoechoic fistulous tracts, and fluid collections. US evaluation

Figure 1. ECF sinogram evaluation (fistulography). (a) A 5-F angled or curved-tip catheter can be used. (b) The external orifice of the fistula is cannulated with the catheter. (c) Contrast agent is injected through the catheter under fluoroscopy to better characterize the course and anatomic origin. Kelly clamps are used to mark the skin orifice and better identify length, relative diameter, location of reflux, and external spillage. (Available in color online at


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Figure 2. Colocutaneous fistula imaging and repair. (a) An axial CT image through the pelvis in a patient with sigmoid resection secondary to diverticulitis and multiple previous bowel surgeries demonstrates a colocutaneous fistula with air and inflammation tracking to the anterior abdominal wall (white arrowheads) from the sigmoid colon (black arrowhead). (b) Barium enema demonstrates the fistula (black arrowheads) with free spill anteriorly. (c) Fistulography study demonstrates catheterization of the fistula. (d) Fluoroscopic image after percutaneous repair demonstrates T-tacks in position at the enteric opening of the fistula in the sigmoid colon (black arrowhead).

can be valuable in follow-up imaging of fluid collections as a result of its low cost, portability, and real-time capability. US sinography evaluates fistulous tracts with catheter injection of hydrogen peroxide, which creates highly echogenic gas bubbles. In a study examining patients with Crohn disease with known fistulae (27), H2O2enhanced US was superior to unenhanced US and plainfilm fistulography in fistula characterization and equal to CT in abscess detection. This technique may be beneficial for portable examinations or follow-up in pediatric patients to limit radiation.

TREATMENT Medical Management Conservative management is the initial approach to fistula closure because as many as 30% of ECFs heal spontaneously without invasive therapy (28). Nonsurgical conservative therapy shows higher success rates of 60%–65% in other trials (Table) (1,5,13,29–34). The

decision to limit conservative therapy in lieu of intervention is considered in patients with high ECF output, short tract lengths, and unfavorable location (35). Spontaneous healing is unlikely when tract maturation has occurred, and further delay may lead to worsening skin breakdown and malnutrition. Medical management is a critical adjunct to maximize success by treating underlying inflammation or infection and improving nutritional status before interventional radiologic closure attempts. Wound care has a key role in ECF management and treatment. Fistula effluent (ie, drainage) can be acidic or alkaline and cause rapid skin breakdown (36). Advances have been made in ECF treatment with wound vacuum (WV) methods, particularly for larger open wounds and fistulae. These devices create a vacuum seal around the fistula opening with continuous negative pressure. Edematous fluid is eliminated while blood flow is increased to promote healing. Multiple case reports (37,38) have shown improved healing of ECFs with WV devices. Improved outcomes have been found when WV methods are used in conjunction with

No. of Fistula Study

Gastric (3), SB (46), LB (10)

Lynch et al (29)

(5), IBD (4), Cancer* (5) Postsurgical§ (26),

Surgery (40), conservative (43†; 23 failed) Surgery (202),

Rate) Surgery (80%), conservative (65%) Surgery (58%, one

LB (12),

diverticular (17), IBD (113),

catheter drain (3; 23

operation; 42%,

anastomosis (55)

cancer* (25), miscellaneous (24)

had initial abscess drainage catheter)

median 3 operations)

Complications Mortality, 6%; RR: surgery, 10%; conservative, 20% Mortality, 3.5%; RR, 20% at 3 mo


Gastric (8), SB (72),

Postsurgical (81), diverticular

Surgery (77),

Surgery (89%),

Mortality, 7%; cancer


LB (26) SB (2), LB (4; 3 HP)

(2), cancer|| Postsurgical (5), IBD (1)

nonoperative¶ (29) ECM-SIS

nonoperative (60%) 4 of 6 Primary closure

(4), sepsis (3) Footplate



Lyon et al (31)

Gastric (0), SB‡ (234),

Postsurgical (60), diverticular

Closure Method (no.)

Draus et al (5)


Fistula Etiology (no.)

Number X


Outcomes (Success Fistula Location (no.)

Taggarshe et al (1)


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Table . Studies of Comparative Enterocutaneous Fistula Closure Techniques (1,5,13,29–34)

displacement, 1 Lomis et al (34)


death MSF 1 death MSF

Gastric (1), NOS (6)

Gastric (1), IBD (2), NOS (4)

Bovine collagen

5 of 7 healed, 1 lost to

Esophageal (3), gastric (5), SB (11),

Postsurgical, low output, noncomplicated

Fibrin glue sealant

Closure time 12.5 d ⫾ 14.2 (P o .001)

Morbidity-related NS, 8.6%; 1 death to NS

LB (6)

All postsurgical: diverticular (2), cancer (4)

NBCA glue 1:5



Esophageal (3)

Cancer (8), diverticular (1),


Closure (86.6%),

Mortality, 13.5%; 1

follow-up Avalos-Gonzalez et al (13)


LB (4) Cambj Sapunar et al (30) Rabago et al (32)

6 15

gastric (1), LB (9), rectovaginal (1), rectovesical (1) Toussaint et al (33)


Gastric sleeve (3), gastrojejunal (2)

gastroplasty (1), abscess (1), actinic stricture (1)

fibrin glue

mean 2.5 sessions per patient


postpyloroplasty Bariatric sleeve gastrectomy and RYGBP

fistula reopened on follow-up 2 mo to

Endoscopic rendezvous-

Closure 80%

Mortality 0%

assisted SurgiSIS** ECM-SIS ¼ extracellular matrix small intestinal submucosa, HP ¼ Hartmann pouch, IBD ¼ inflammatory bowel disease, LB ¼ large bowel, MSF ¼ multisystem failure, NBCA ¼ n-butyl2-cyanoacrylate, NOS ¼ not otherwise specified, NS ¼ nutritional support, RR ¼ recurrence rate, RYGBP ¼ Roux-en-Y gastric bypass, SB ¼ small bowel. *Includes carcinoma and postradiation. † Conservative treatment included total parenteral nutrition and octreotide. ‡ Multiple SD sites of fistulae in cohort. § Includes mesh repair and laparoscopy. || Radiation only. ¶ Conservative treatment included octreotide, vacuum-assisted closure, and fibrin glue. # Prospective case-controlled trial. nn Combined interventional radiologic/gastrointestinal procedure with percutaneous and endoscopic fistula access.



IR Management and Treatment of Enterocutaneous Fistulae

medication to lower intestinal pressure. Modified vacuum ostomy bags have also been used in the treatment of ECFs (19). Vacuum devices can be used in conjunction with image-guided interventions and drains to improve outcomes. Promising research in abdominal wound care includes the use of electric nerve stimulation (39), hyperbaric oxygen chambers, and local ozone insufflation (40). Pharmacotherapy is important in ECF treatment. Sepsis is treated aggressively with antibiotic agents, with vigilance for associated opportunistic infection and electrolyte imbalances. Underlying IBD can be addressed with tumor necrosis factor–α inhibitors and other medications (41). Steroids treat inflammation, but decrease healing and suppress the immune system (42). Octreotide somatostatin analogues decrease enteric motility, inhibit the release of numerous hormones, and decrease mucosal secretions (43,44) to lessen fistula output and loss of fluid and electrolytes. Octreotide has been shown to decrease fistula output and spontaneous fistula closure time, but not to increase closure rates (45). Psychosocial support to the patient with an ECF may also be necessary. Patients with fistulae can be managed as outpatients but are reported to have longer hospital stays and spend twice as much on medical care, in addition to lost workdays and workplace limitations (8). Fistulae can cause lifestyle alterations, limitation of activity, and embarrassment. It is important to recognize the patients’ issues and signs of depression and offer assistance when needed.

INTERVENTION Surgery The definitive treatment recommended for ECF repair is resection and primary anastomosis (29). Surgical fistula resection has shown success rates ranging between 58% and 89%, with 15%–29% improvement compared with conservative methods but with recurrence rates as high as 20% and mortality rates as high as 7% (Table). Surgical resection is not tolerated by many patients with ECFs because of multiple previous surgeries or malnourishment. Resections cause bowel shortening and potential for obstructing adhesions with risk of fistula recurrence. Alternative surgical procedures have been reported for fistula blockade without bowel resection with muscle flaps and patching, but outcomes are uncertain (46). Surgery is unavoidable when complications of underlying IBD or malignancy must be addressed. Surgery may also be required to repair abdominal wall defects even with successful interventional radiologic fistula closure. Because of the recurrent nature of fistulae and considerable morbidity associated with complex repeated surgery, patients often have limited options. Interventional radiology can offer potential solutions for ECF closure or symptom reduction.

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INTERVENTIONAL RADIOLOGY Catheter Drainage An important first role for interventional radiology in ECF management is percutaneous drainage of adjacent fluid, abscesses, and the fistula itself (1). Fluid collections greatly increase the risk of sepsis and often prevent ECF closure with abscess formation in as many as 44% of fistulae (47). The window of approach into the fluid collection should be through the healthiest-appearing tissue to avoid further skin and tissue damage. Catheter drainage of the fistula can be performed soon after development when repeat surgery may be harmful to the patient (48). Catheter insertion with bulb suction and sequential downsizing and advancement can lead to decrease in size and length of the tract and even fistula closure by draining bowel effluent and allowing surrounding tissues to heal. Although fistulae drainage can become more manageable, the drainage catheter within the ECF may promote tract maturation. An initial sinogram assessment is performed to delineate the fistula tract and enteric origin with continued ECF drainage. A straight or angled-tipped catheter is inserted through the external fistula wound orifice and advanced under fluoroscopic guidance, with the tip placed in the proximal aspect of the fistula tract adjacent to the mouth of the fistula at the gut entrance. If the catheter cannot be advanced easily, a smaller caliber catheter or hydrophilic guide wire can be used. Guide wires should be used carefully and followed with fluoroscopy along the expected path of the fistula to prevent tissue injury and tract dissection. Follow up sinograms at 2–4-week intervals are performed to assess ECF closure and the need to downsize, reposition, or place additional drains. Persistent lack of healing requires a search for underlying cause and consultation with the care team.

Interventional Radiologic Closure Procedures Interventional ECF closure procedures have similar methodologies. After sinogram evaluation of the ECF, the tract is prepared by tissue debridement along the tract surface to promote healing and sanitization to prevent infection. Various materials are then placed along the length of the tract to promote healing. Before fistula closure attempts, intravenous antibiotics covering gram-negative gastrointestinal flora should be administered. Small case series show the effectiveness of percutaneous ECF closure (Table), but reported closure rates as high as 100% may be inflated by patient selection (30). Interventional radiologic closure methods of complex and chronic ECFs often fail (Fig 3). Patients must be informed of the limited available options, the high failure rates, and the possibility of repeat procedures. Additional attempts can use different materials or

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techniques, but it may be advisable to seek consultation or referral to centers with comprehensive and multidisciplinary ECF management experience.

Tract Preparation ECFs referred to interventional radiology are typically chronic, having undergone failed conservative management, and lined by granulation or fibrous tissue that prevents spontaneous closure. Debridement of the ECF wall improves closure success and can be performed by “flossing” the tract with abrasive tools to disrupt the surface (49) (Fig 4). The anal fistula plug (AFP; Cook, Bloomington, Indiana), described later, includes a brush


to traverse and score the tract. This brush or highfriction wires are used when there is proximal and distal tract access. Other tools to abrade the fistula walls can be used with only cutaneous access. The tip of a vascular access sheath can be cut into a crown shape to create a more abrasive cutting surface and be rapidly advanced and withdrawn within the tract. Trerotola thrombolysis devices (Arrow, Reading, Pennsylvania), endoscopic biopsy brushes, and biopsy forceps are used on an offlabel basis in a similar manner. Minor bleeding may occur during tract preparation. After abrasion, sanitation of the tract surface is performed by H2O2 irrigation. Fistulous effluent is nonsterile and can infect any inserted foreign body and the

Figure 3. ECF with associated abscess. (a) An axial CT image through the pelvis in this postcolectomy case demonstrates multiple fluid/gas collections with enhancing walls representing abscesses (black arrowheads) associated with a small-bowel ECF (white arrowheads). (b) Sinogram of the fistula does not demonstrate the complexity of the associated abscesses.

Figure 4. ECF tract preparation. (a) With access to the cutaneous tract and the enteric lumen such as with a distal colocutaneous fistula, the granulation tissue lining can be reduced by flossing with a stiff wire. (b) A Trerotola thrombectomy device can be used on an off-label basis for tract abrasion when enteric access is not available. (c) Hydrogen peroxide is injected throughout the tract for sanitization and seen at the skin surface as foamy material. (Available in color online at


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Figure 5. ECF repair tools. (a) The Biodesign enterocutaneous fistula plug consists of an ECF plug with collapsible enteric anchor (1), deployment pusher (2), sheath (3), and external cutaneous anchor (4). (b) Schematic illustration demonstrating use of the Cook enterocutaneous fistula plug in colocutaneous fistula closure. (c) TISSEEL bioadhesive closure syringe.

tract walls. A single case report (50) raised the risk of air embolism with hydrogen peroxide instillation as a result of venous intravasation of gas. To avoid this risk, it is important to identify venous intravasation of contrast medium during sinography.

Closure Materials Bioadhesives. Fibrin glue or sealant has been used since the 1970s in surgical procedures for hemostasis and fistula closure (51). Fibrin sealant was first mixed with barium and observed fluoroscopically during endoscopic and percutaneous treatment of fistulae in the mid-1990s. Use of bioadhesives in the fistulous tracts theoretically increases the risk of sepsis given the placement of foreign material, but this has not been well studied. Fibrin glues consist of separate solutions of fibrinogen and thrombin that instantly coagulate when mixed together. TISSEEL (Baxter, Deerfield, Illinois) is available as a preloaded dual-injection syringe that also contains

aprotinin, a substance that prevents breakdown of the formed fibrin clot and is rarely associated with anaphylaxis (Fig 5c). A similar fibrin sealant, EVICEL (Ethicon, Somerville, New Jersey), does not contain aprotinin and is provided as separate fibrin and thrombin solution vials. These products are available with dual-chamber applicator attachments of various lengths to ensure that coagulation occurs at the target site. Some sealants are provided in frozen prefilled syringes that require thawing to room temperature. When access to the ECF has been obtained, the applicator can be inserted until the tip is at the fistula mouth. The fibrin and thrombin are then slowly simultaneously injected as the catheter or applicator is pulled distally to seal the length of the tract. A recent study examining percutaneous fibrin closure procedures with endoscopic monitoring (13) showed statistically significant improvement in fistula closure times for esophageal, gastric, and small-bowel cutaneous fistulae, with a trend for decreased colocutaneous fistula closure time that did not reach statistical significance.

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Other bioadhesives have been used in fistula closure. BioGlue (CryoLife, Kennesaw, Georgia) consists of bovine serum albumin and glutaraldehyde. BioGlue provides increased cohesive strength (52), but may pose a higher risk of sepsis (53). Synthetic glues such as Nbutyl-2-cyanoacrylate have been used in treatment of colocutaneous fistulae, with a 100% success rate in six patients (30). Extracellular Matrix Material. Extracellular matrix (ECM) material is a biologic scaffold of proteoglycan and nonproteoglycan components that provide cellular support and contain growth factors. The ECM provides a flexible framework for tissue segregation and stem cell support. SurgiSIS (Cook) is an ECM material consisting of freeze-dried decellularized porcine small intestine. ECM has been shaped into various forms and devices and used for hernia repair, vascular surgery, dural closure, and wound care. Of particular interest to interventional radiology is the Biodesign fistula plug line of products (Cook), which is available in various forms for repair of anal, enterocutaneous, and rectovaginal fistulae. The simplest form of the Cook AFP device consists of a tapered ECM cone. For perianal fistula repair, the proximal end of a single plug is anchored within the rectal lumen by suture or plastic button and the trailing end is sutured at the skin. ECF tracts may be longer in interventional radiologic procedures, and the luminal end of the plug is deep in the bowel and cannot be


sutured in place. In our experience, multiple AFP devices can be sutured together to form plugs of varying lengths (Fig 6). One method of anchor to the bowel mucosa is to affix multiple T-fasteners to the luminal end of the plug. The plugs are prepared by soaking in sterile saline solution for a maximum of 2 minutes or until the desired flexibility is obtained. If there is bidirectional access to the fistulous tract, the plug can be deployed by using a “pull” method with an 0-silk suture or a snare attached to the cutaneous end of the plug that can be passed through the ECF tract and used to pull the plug into appropriate position. Alternatively, a “push” method can be used in which the entire device is preloaded into a 12–14-F sheath. After the tract is prepared as described earlier, the loaded catheter is inserted through the fistula tract under fluoroscopic guidance. When the tip is in the enteric lumen, an inner dilator blunted by trimming the tip can be used to push the plug out and deploy the T-fasteners within the bowel. Slight tension is applied to ensure the T-fasteners remain open against the luminal wall and the plug will not migrate distally. The external portion of the plug can then be secured to the anterior abdominal wall with absorbable sutures (Fig 7). Modification of the original AFP material for other types of ECFs allows easier placement than the solution described earlier. The SurgiSIS enterocutaneous fistula plug device (Cook) consists of a collapsible phalange that can be loaded into the catheter and provides the same function as the T-fasteners described earlier (Fig 5).

Figure 6. ECF repair customized plug assembly and preparation. (a) Biodesign AFP consisting of ECM material. (b) Two AFP devices are sutured together to assemble a longer ECM plug to fit the fistula length. (c) T-tack attachment for enteric-side anchor. (d) Soaking plug in sterile saline solution allows increased malleability and interface with tissue walls for potential stem cell attachment. (e) Sheathing of the entire device to prepare for deployment by the push method.


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Figure 7. ECF plug insertion. (a,b) With access to the cutaneous tract and the enteric lumen such as in this perianal abscess, the fistula plug can be pulled through without the use of a sheath. (c) In a different patient without bidirectional access, the plug is firmly anchored within the lumen by using T-tacks and a sheath. Gentle outward pressure is applied to ensure apposition to the enteric defect and prevent fistula recurrence. (d) The plug can then be cut to the appropriate length and sutured in place.

This allows percutaneous placement of an anchor similar to the plastic button option of the AFP. The device is available in 4-mm and 7-mm diameters delivered through 18-F and 22-F sheaths, respectively. The plug can be cut to match the fistula dimensions. Early results in six patients treated with the Cook enterocutaneous fistula plug (31) show a 100% closure rate at 2 weeks and recurrence in only one of those patients as a result of device failure. ECM closure has mostly been studied in relation to perirectal fistulae. AFP use in high transsphincteric anocutaneous fistulae had a 59% success rate, versus 39% for fibrin glue (54). The same study (54) found that this was equivalent to surgical success rates (60%), although surgery carries a higher risk of morbidity, specifically sphincter damage and incontinence. Other studies have shown much lower success rates of 14%– 32% (55,56), possibly because of variability in technique and patient selection. Other ECM products are available but not studied extensively in ECF closure. Some of the earliest percutaneous ECM fistula closures were performed with collagen-only plugs such as VasoSeal plugs (DataScope, Montvale, New Jersey). AlloDerm (LifeCell, Bridgewater, New Jersey), an ECM material made from

decellularized human dermis, has not been studied in fistula closure but is available in a liquid form (Cymetra Micronized AlloDerm) and may be useful in the future. Gelatin Sponge. Gelatin sponge such as Gelfoam (Pfizer, New York, New York) is a low-cost, easily available bioabsorbable material mostly known as an embolic agent to stop hemorrhage. Gelfoam embolization of ECFs has been described (57) but is rarely used as a result of availability of the newer agents described earlier.

Endoscopy Endoscopic treatment of ECFs is an evolving minimally invasive alternative to surgical repair. A few small case series of endoscopic fibrin glue injection (32,58,59) show closure rates as high as 90% (Table). Newer endoscopic technologies developed to combat hemorrhage are also being applied to fistula closure. The recently released over-the-scope clip system (Ovesco, Tubingen, Germany) can manually clip the internal orifice of a fistula. Banding procedures, ENDOLOOP (Olympus America Inc, Center Valley, Pennsylvania) ligature products (60), and endoscopic suturing (61) have also been used successfully. In addition, removable silicone and palliative self-expanding

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metallic stents are available to endoscopically divert enteric contents beyond the fistula ostium and allow healing (62–64). Endoscopic identification of the internal fistula orifice is difficult and limits the role of endoscopy. In addition to incomplete visualization, the endoscopist is limited by ECF location, as more distal small bowel visualization may require single- or double-balloon enteroscopy. Endoscopy is a valuable tool in evaluation and treatment of the intraluminal aspect of the ECF, and interventional radiology can assist in fistula localization by injecting methylene blue dye or by placing a small catheter, guide wire, or ECM plug (33) (Fig 8). Direct endoscopic evaluation of the fistula itself has been reported via insertion of a small-caliber flexible endoscope into the external orifice. Limited surgical


studies that used an external endoscopic approach report favorable results (65,66). Direct visualization allows detection and removal of foreign bodies such as suture material and better targeting of closure material administration.

CONCLUSIONS ECFs can be a debilitating chronic condition with high costs to health care and impact on quality of life. ECF treatment is challenging, and success rates are suboptimal even with meticulous use of the numerous methods described here. Treatment measures range from traditional surgery and basic catheter drainage to more innovative procedures across multiple disciplines. Improved success in ECF closures requires continuance

Figure 8. Combined procedure with endoscopy using the over-the-scope clip in the same colocutaneous fistula patient as Figure 2 after failure of initial plug placement. (a) Image of the closed clip. Note the teeth used to close the tissue defect. (b) Schematic illustrating clip deployment over a focus of active hemorrhage. (c) Endoscopic image of the sigmoid colon demonstrates interventional radiologically placed wire and fistula plug entering through the bowel defect (arrowhead). (d) The over-the-scope clip device has been loaded onto the endoscope and advanced atop the enteric defect. The wire has been removed. The loaded clip can be seen ready to be deployed (arrowhead). (e) After deployment and trimming of the fistula plug (arrowhead), the closed clip can be seen surrounding the enteric defect. (f) Two-month follow-up contrast agent enema demonstrates a small residual sinus tract (arrowhead) but healing of the previously seen cutaneous fistula allowing ostomy takedown (compare to Fig 2b).


IR Management and Treatment of Enterocutaneous Fistulae

of medical specialist collaboration, expansion of clinical management and procedure skills, and promotion of investigational research.

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