Ascentx Medical

F125 Injectable Bulking Agent for Fecal Incontinence

Fecal Incontinence (FI), also referred to as bowel or anal incontinence, is the inability to control the passage of fecal contents through the anus. Normal continence results from an integrated activity of the anal sphincters (internal and external), pelvic floor muscles, and adequate neural input. It is also influenced by stool consistency, rectal capacity and compliance, the anorectal sampling reflex, normal resting tone, and normal anorectal sensation. Failure of any of those factors may result in FI.

Fecal Incontinence is a life-altering 'taboo subject', an extremely debilitating and embarrassing medical condition that has enormous consequences on the patient's psychologic, emotional and social well-being. As a result of social stigma and poor self-esteem, many patients are reluctant to seek medical attention and isolate themselves socially.

There are varying grades of Fecal Incontinence, ranging from incontinence of flatus to severe incontinence of solid stool. In general, Fecal Incontinence can be classified into three categories:

1. Fecal seepage, which is the conscious leakage of stool after normal bowel action or with activity
2. Passive incontinence, in which the patient is unaware of stool leakage
3. Urge incontinence, whereby the patient is unable to actively defer a bowel movement

Because of the lack of standardization, the true prevalence of fecal incontinence is difficult to determine. The reluctance of patients to discuss their condition with physicians adds to the inaccuracy of estimates of true prevalence. Studies have described a range of 2.2%- 20.7%. In a telephone survey performed in the U.S., the reported prevalence of FI was 2.2% and 63% of the respondents were female. In two population-based surveys of females in Washington and Minnesota, the prevalence was reported as 7.2% and 10%, respectively. A more recent meta-analysis reported significantly higher rates ranging from 11%-15% of the population or 40-50 million Americans. Most clinical studies tend to have a preponderance of female patients, whereas epidemiologic studies show that there is no gender difference.

Compared with the general population, the prevalence of fecal incontinence is much higher in the geriatric and institutionalized population where reported rates are approximately 50%. FI is the second leading cause of nursing home placement.

Fecal Incontinence is usually a multi-factorial disorder and Rao and Patel (1997) reported in a prospective study that 80% of patients had more than one abnormality. FI is commonly an acquired disorder and only a small percentage of cases are the result of congenital disorders such as rectal agenesis or myelomeningocele. In adult females, the most common acquired cause is obstetric trauma or episiotomy. After vaginal delivery, up to 35% of primiparas have been reported to have sphincter injuries, although some females remain asymptomatic.

Other factors such as anorectal surgical procedures (e.g. hemorrhoidectomy) can also lead to sphincter damage and incontinence. Trauma to the pelvis or perineum can result in pelvic fractures, which can cause nerve damage or direct sphincter injury. Neuromuscular disease can affect neural and muscular function. Furthermore, diabetes mellitus, stroke, multiple sclerosis and other neurological and muscular disorders can lead to fecal incontinence.

Treatment Options

Fecal Incontinence can be caused by defects of the external anal sphincter (EAS) or the internal anal sphincter (IAS), or both. Disruption of the EAS results in urge related FI and disruptions to the IAS can decrease the resting anal tone leading to 'passive FI'.

When planning a treatment regimen, it is extremely important to make the subjective complaints and symptoms of FI somewhat more objective. To accomplish this goal, several scoring systems have been designed and validated. The Cleveland Clinic Florida FI (CCF-FI; Wexner) score has evolved into the most popular and widely cited. This scale measures the frequency of incontinence to gas, liquid, and solid stool (0=total control, 20=complete incontinence) and the degree of alteration in lifestyle, and the use of protective devices. In one of several validation studies of this scoring system, it has been demonstrated that a score of greater than 9 is associated with significant alteration in quality of life and can be used as an indication for surgical therapy.

Based on the etiology and severity of FI, treatment options range from medical therapy (non-operative measures such as dietary and lifestyle modifications) to anti-diarrheal agents (e.g. loperamide), biofeedback, sacral nerve stimulation, anal plugs (e.g. patients with spina bifida), minimal invasive procedures (bulking agents, radio-frequency), to invasive surgical procedures (sphincteroplasty, artificial bowel sphincter (ABS), colostomy).

There are many treatment modalities for FI due to EAS dysfunction, but few effective options for 'passive FI' due to internal sphincter impairment. The decision of which surgical modality should be undertaken is usually straightforward, depending on the condition of the anal sphincters. Patients who have obvious sphincter defects normally should undergo an overlapping sphincteroplasty; conversely, other modalities should be pursued in patients who have intact sphincters.

Surgical sphincter repair is indicated ONLY for localized injuries of the external anal sphincter (e.g. after traumatic injury or childbirth). Of these, obstetric injury is the most common cause. Results after surgical repair deteriorate long-term and it was shown that only 40-62% of patients remain continent after 3 years. The etiology of poor longer-term function after sphincter repair is unclear and it seems that the long-term results of a repeat sphincteroplasty are only modest and are similar to the initial repair.

Internal sphincter dysfunction requires alternative treatments such as Injectable Bulking Agents or radio-frequency (Secca procedure), and there are only few effective options.

Injectable Bulking Agents for Fecal Incontinence

The use of injectable bulking agents for the treatment of Fecal Incontinence was first described in 1993 by Shafik, who injected a Teflon^® paste (Polytef^®) into the submucosa of the anus to re-establish the anal 'seal'. Injectable bulking agents offer the possibility of a minimally invasive, cost-effective and simple outpatient procedure to treat internal sphincter dysfunction.

At rest, the Internal Anal Sphincter (IAS) provides most of the 'resting anal tone' with anal mucosal folds and anal vascular cushions providing the 'anal seal'. Disruptions to the IAS can decrease the resting anal tone leading to passive FI. The use of Injectable Bulking Agents for passive FI stems from the reported success of their use by urologists for the treatment of Stress Urinary Incontinence (SUI). It has been proposed that by mechanically 'bulking' the IAS, the same success can be achieved for passive FI.

There are wide variations in the method of application of bulking agents. These include different materials, injection methods, variable volumes and different methods of assessing FI and study design. Initial studies reported good results and based on these results, the use of Injectable Bulking Agents is now widespread.

Currently there is only one injectable bulking agent approved by the U.S. Food and Drug Administration (FDA) for the treatment of FI: Solesta^® (Dextranomer particles suspended in stabilized hyaluronic acid) by Oceana Therapeutics was approved in May 2011 for the treatment of Fecal Incontinence in patients 18 years and older who have failed conservative therapy.