Tissue-Engineered Treatment

16 September 2007 (Last Updated September 16th, 2007 18:30)

The long-term treatment of anal fistulas is often unsuccessful, with patients left suffering from chronic conditions. But a new tissue-engineered product could be the solution to repair and recovery, as the Georgia Colon and Rectal Surgical Clinic’s David Armstrong investigates.

In recent years, the clinical management of anal fistulas associated with inflammatory bowel disease, Crohn's, colitis and other conditions has evolved toward a new treatment paradigm. Traditional means of repairing fistulas have included fistulotomy, endorectal/anal sliding flaps, fibrin glue and setons.

A fistula is an abnormal channel that develops between body organs. The most common fistulas occur from the anorectal region to an opening in the skin. The presence of a fistula can be painful and can seriously impact on a patient's quality of life. Unfortunately, current treatments involving either an extensive surgical procedure or use of fibrin glue do not always yield satisfactory results, leaving the patient with a chronic, debilitating problem. Current data indicates that between 40,000 and 60,000 anal fistula surgeries are performed annually in the EU. It is estimated that more than 125,000 surgeries to repair fistulas are performed each year in the US.

The oldest and best-studied anal fistula treatment is fistulotomy, considered the best option for superficial fistulas. Despite its clinical efficacy in certain cases, recent data presented by Bradford Sklow, MD, assistant professor of University of Utah School of Medicine, Colon and Rectal Surgery, suggests it is poorly suited to more severe fistula cases.

According to the data, fistulotomy is suboptimal for deep transphincteric and suprasphincteric fistulas because of an increased risk for fecal incontinence. Patient distress over this outcome is a leading source for litigation in colorectal surgery.

The seton, where a loop of flexible material is placed along the fistula tract to maintain drainage for a period of time, has been an accepted fistula management practice for years in some patient groups. One team reported a 78% healing rate in 37 patients for whom setons were used alone.

But subsequent studies have shown a 36–50% incidence of fecal incontinence with stand-alone seton drainage. The seton is also often associated with pain and inconvenience for the patient. For that reason, this technique is recommended most often today as a bridge solution until a terminal procedure can be implemented.

When used as part of a staged approach to complex anal fistulas, the endorectal/anal sliding advancement flap has been shown to have a potential success rate of 75%. However, this is an invasive procedure known to be difficult to perform posteriorly, making it less popular.

Fibrin glue, first introduced in the 1990s, was at first hailed as a possible "Holy Grail" for repairing fistulas due to its simple, non-invasive placement. After numerous studies, however, success rates have been unimpressive. Today, in most cases, fibrin glue is reserved for first-line treatment in anal fistulas.

"Fibrin glue was at first hailed as a "Holy Grail" due to its simple, non-invasive placement. However, success rates have been unimpressive."

Herand Abcarian, Turi Josefsen professor and chairman of the Department of Surgery, University of Illinois College of Medicine in Chicago, says: "[Fibrin glue] has its place in the surgeon's armamentarium. It is definitely ineffective in rectovaginal fistulas. But it is much more effective in long, complex tracts and may be used in Crohn's disease.

"You have nothing to lose if you use it as a first-line treatment. If it fails, repeat it once; if it fails again or the fistula recurs, move to endorectal advancement flap, dermal-island flap anuloplasty, seton drainage, or the anal fistula plug."

Fibrin glue can be considered to have some negative effects. As much as 50% of the time, patients may have extruded the glue out of the fistula tract before they even get in the car to drive home following the procedure.

A BIOMATERIAL SOLUTION

These and other difficulties in effectively treating this persistent and debilitating condition have led to the development of an innovative approach using a new acellular bio-engineered tissue called Surgisis®. This three-dimensional biomatrix supports the body's natural healing process and is eventually resorbed following the ingrowth of native tissues.

The Surgisis AFP Plug from Cook Surgery received CE Marking approval in May 2006 as the first surgical device for the repair of anal fistulas. Surgisis AFP provides an innovative, yet simple treatment for a notoriously difficult condition, which has traditionally required surgical intervention. The plug is well-tolerated by patients and early clinical results are showing significant improvement over conventional therapies.

Early reports indicate a rate of fistula closure above 80%. Easy to place, this minimally invasive solution results in reduced pain and fewer complications. As a suturable material, Surgisis offers more staying power than fibrin glue options. The biological-derived collagen matrix also supports native tissue healing for complete fistula closure.

TESTING AND RESEARCH

A prospective study was performed to compare fibrin glue with fistula plug use. Patients with anorectal fistulas were prospectively enrolled. Patients with Crohn's disease were excluded. Age, gender, number of fistula tracts and number of prior fistula surgeries were compared between groups. All patients underwent conventional bowel prop, with enteric antibiotics (Flagyl 2 gm po). Under general anaesthesia, patients underwent thorough debridement and irrigation of the fistula tract in a prone jack-knife position.

In the collagen plug patients, a conical plug constructed from lyophilised porcine small intestinal submucosa was pulled into the primary opening, using a 2-0 chromic catgut thread inserted through the fistula tract and sutured into the primary opening.

In the fibrin glue patients, 5cc of Tisseal was infused into the secondary opening(s) and all primary and secondary openings were sutured closed. Median follow-up was three months in both groups. Fistula closure rate at 90 days was compared between groups using Fisher's Exact test.

Twenty-five patients were prospectively enrolled. Ten patients underwent fibrin glue closure, while the remaining 15 received the fistula plug. Patients' age, gender, number of fistula tracts and number of prior closure attempts were similar in both groups.

"The deeper and longer the fistula tract is, the better candidate it becomes for the plug, which has no septic complications."

RESULTS AND TREATMENT OPTIONS

In the fibrin glue group, six patients (60%) had persistence of one or more fistulas at three months, compared to two patients (13%) in the collagen plug test group. The majority of collagen plug and fibrin glue failures both occurred less than four weeks postoperatively.

The implantation of the Surgisis AFP plug is easily performed, non-invasive and associated with few complications, the study noted. Placement may also be repeated if it fails initially, which could make it the gold standard for reoperative complex fistulas.

Superficial anal fistulas are not good candidates for the Surgisis AFP plug, since these can be treated effectively with a simple fistulotomy. The deeper and longer the fistula tract is, the better candidate it becomes for the plug, which has no septic complications and thus, no risk of incontinence.

Closure of the primary opening of a fistula tract using a suturable biodegradable collagen-based plug is an effective method of treating anorectal fistulas. This method appears to be more effective than fibrin glue closure, demonstrating initial results of 87% closure using the collagen plug, versus 40% closure for fibrin glue.

The greater efficiency of the biodegradable plug may be due to the ability to suture the plug in the primary opening, thus closing the primary opening more effectively. This contrasts with the liquid consistency of the fibrin glue, which tends to leak from the fistula tract.

The Surgisis AFP Plug is gaining favour for complex fistulas and repeat surgeries. Proper insertion procedures must be followed to ensure optimal outcomes, but surgeons employing this new procedure can have considerable success in treating demanding fistula patients.