Perianal injectable bulking agents as treatment for faecal incontinence
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The objective of this review is to determine if the injection of bulking agents is better than currently available existing or no treatment for faecal incontinence in adults in terms of effectiveness, complications, and quality of life. The following hypotheses will be tested:
1. The injection of bulking agents is better than no intervention or a placebo/sham injection;
2. The injection of bulking agent is better than any single or combination conservative treatment (biofeedback, diet, anal plug, anti‐diarrhoeal medication, pelvic floor exercise);
3. The injection of bulking agent is better than another minimally invasive or surgical intervention;
4. One type of bulking agent is better than another type;
5. One technique of administration of agent is better than another technique;
6. Larger volumes of agent are better than smaller volumes;
7. Injection of bulking agent is safer than another minimally invasive or surgical intervention (e.g. number of complications);
Some studies may address more than one hypothesis.
Background
Description of the condition
Faecal incontinence is defined as involuntary loss of solid or liquid faeces. Anal incontinence additionally includes the involuntary loss of flatus. It is a distressing condition with significant social and medical implications. The prevalence of faecal incontinence is reported from 1.4% to 20%, depending on the age and whether community‐dwelling or living in an institution (Chassagne 1999; Perry 2002). The symptom has a major impact on quality of life and activities of daily living, causing in many cases extreme embarrassment and discomfort.
Faecal incontinence has a diverse aetiology. The maintenance of continence is a complex mechanism which consists of the interaction of an intact and functional sphincter complex, consistency of faeces, adequate cognitive ability and physical mobility, and bowel motility. Any impairment of these elements can result in incontinence. The symptoms of incontinence have traditionally been divided into two symptom groups: urge and passive incontinence. Urge incontinence is loss of faeces following inability to hold the urge to defaecate for adequate time to reach toilet. Passive faecal incontinence is involuntary loss of faeces without the urge to defaecate and is predominantly associated with internal anal sphincter (IAS) dysfunction (Engel 1995). The multiple possible causes and contributing factors to faecal incontinence are reviewed elsewhere (NICE 2007). This review focuses specifically on passive faecal incontinence secondary to IAS problems.
The causes of IAS dysfunction can be classified into two main groups. One is a morphologically intact but functionally weak IAS and another is a structurally damaged IAS. A structurally intact but weak internal anal sphincter may be due to primary degeneration or systemic disease such as systemic sclerosis (Vaizey 1997) or local denervation. Radiotherapy can damage the myenteric plexus leading to diminished IAS function (Da Silva 2003). Destruction of or damage to the IAS can be caused by anal surgery such as anal dilatation, sphincterotomy, fistula surgery and haemorrhoidectomy (Lindsey 2004). Obstetric injury may extend to damage the IAS and direct anal trauma may disrupt IAS structure (Wheeler 2007). Symptoms are likely to be exacerbated by loose faeces or incomplete rectal evacuation. The exact cause of passive soiling for an individual patient is often unclear.
Currently the treatment for faecal incontinence associated with IAS dysfunction remains challenging. Medical management such as modifying faeces consistency by anti‐diarrhoeal agents or muscle training as in biofeedback is effective to a certain extent but is not found to be an ideal long‐term solution by many patients. The IAS is not amenable to surgical repair (Felt‐Bersma 1996; Leroi 1997; Morgan 1997) and major surgery such as implantation of artificial bowel sphincter or dynamic graciloplasty are associated with significant morbidities (Christiansen 1999; Wexner 1996) and so may be an intervention disproportionate to symptoms. Sacral nerve stimulation is an emerging treatment option for faecal incontinence with intact sphincters but has not yet proven to be effective for internal anal sphincter dysfunction. There is therefore a large gap between conservative and major surgical options for treating passive faecal incontinence. This review focuses specifically on one specific treatment that has been developed for the symptom of passive faecal incontinence secondary to IAS disruption or weakness. For further information on other interventions for faecal incontinence treatment, please refer to Cochrane reviews on surgery for faecal incontinence in adults (Brown 2007), sacral nerve stimulation for faecal incontinence and constipation in adults (Mowatt 2007), plugs for containing faecal incontinence (Deutekom 2005), electrical stimulation for faecal incontinence in adults (Hosker 2007), drug treatment for faecal incontinence in adults (Cheetham 2002), biofeedback and/or sphincter exercises for the treatment of faecal incontinence in adults (Norton 2006) and absorbent products for moderate‐heavy urinary and/or faecal incontinence in women and men (Fader 2008).
Description of the intervention
Injection of bulking agents has emerged as a new treatment for faecal incontinence following on reported success in treating urinary incontinence. The concept is to inject a biocompatible material into the submucosa of the anal canal or the space between the anal sphincters in order to bulk out the tissue around anal canal and approximate the anal mucosa, thereby closing down the anal canal or raising intra‐anal pressure to avoid faecal incontinence. This may be performed under local, regional or general anaesthetic and has been reported as used as a “minimally invasive” treatment option in an outpatient clinic setting. There have been reports on eight different materials (autologous fat, bovine glutaraldehyde cross‐linked collagen, carbon‐coated zirconium beads, polydimethylsiloxane elastomer, dextranomer/non‐animal stabilised hyaluronic acid, hydrogel cross‐linked with polyacrylamide, porcine dermal collagen) used for injection, either via the perianal skin or via the anal mucosa to date.
Why it is important to do this review
The treatment is becoming widespread following the results of observational studies as it is potentially attractive in its simplicity and minimal invasiveness. However, it is not clear if this intervention is effective, cost effective and if any effect persists in the long term. There is no consensus regarding the indications for the treatment nor the choice of optimum material. There is little information on possible adverse events (either acute such as infection or chronic such as new difficulties with evacuation). We aim to systematically review the studies published to date and combine best evidence currently available on which to base recommendations for clinical practice.
Objectives
The objective of this review is to determine if the injection of bulking agents is better than currently available existing or no treatment for faecal incontinence in adults in terms of effectiveness, complications, and quality of life. The following hypotheses will be tested:
1. The injection of bulking agents is better than no intervention or a placebo/sham injection;
2. The injection of bulking agent is better than any single or combination conservative treatment (biofeedback, diet, anal plug, anti‐diarrhoeal medication, pelvic floor exercise);
3. The injection of bulking agent is better than another minimally invasive or surgical intervention;
4. One type of bulking agent is better than another type;
5. One technique of administration of agent is better than another technique;
6. Larger volumes of agent are better than smaller volumes;
7. Injection of bulking agent is safer than another minimally invasive or surgical intervention (e.g. number of complications);
Some studies may address more than one hypothesis.
Methods
Criteria for considering studies for this review
Types of studies
All randomised or quasi‐randomised controlled trials comparing use of injectable bulking agents for faecal incontinence with any alternative treatments or placebo will be reviewed to evaluate the therapeutic effects. Case‐control and cohort studies will be also reviewed to assess risks and complications associated with the treatment.
Types of participants
All adults with faecal incontinence of any severity and any cause. Children will be excluded as the aetiology of incontinence is more diverse and complex (eg congenital disorders).
Types of interventions
Injection of bulking agents (biomaterials and autologous tissues) into the anal submucosa or inter‐sphincteric space, either via the anal mucosa or peri‐anally as a treatment for faecal incontinence. This will include injection of autologous fat, bovine glutaraldehyde cross‐linked collagen, carbon‐coated zirconium beads, polydimethylsiloxane elastomer, dextranomer/non‐animal stabilised hyaluronic acid, hydrogel cross‐linked with polyacrylamide, porcine dermal collagen and any other materials found in the literature search. Comparison intervention could include no treatment or placebo/sham treatment, another bulking agent, conservative treatment (biofeedback, anal plug, diet, anti‐diarrhoeal medication, pelvic floor exercise), minimally invasive treatment (sacral nerve stimulation, radio‐frequency ablation) and surgical intervention. Different injection techniques will also be compared to determine whether one technique is superior to another.
Types of outcome measures
Primary outcomes
Change in incontinence scores (eg Wexner or St Mark’s incontinence score).
Secondary outcomes
Patient reported:
Subjective assessment of change by the patient (improved, no change, or deterioration in incontinence). Symptoms, generic and condition‐specific change in quality of life score, ability to conduct activities of daily living, measures of psychological well‐being, satisfaction/dissatisfaction with treatment, need for additional therapy (need to wear absorbent products for incontinence, drugs, dietary changes, repeat procedure, evidence of differential response in different patient sub‐groups (by diagnosis, cause of faecal incontinence, sphincter integrity, comorbidity, gender or any other characteristic).
Clinician observation:
Physiological measures (maximum resting anal pressure, maximum squeeze pressure, mucosal electrosensitivity), evidence of migration of material, length of hospital stay, costs.
Further surgical intervention for faecal incontinence (including formation of colostomy), post‐operative complications (e.g. bleeding, infection, injection site/anal pain or discomfort, new evacuation difficulty).
Search methods for identification of studies
Electronic searches
Relevant trials will be identified from the Incontinence Group Specialised Register of controlled trials which is described under the Incontinence Group’s details in The Cochrane Library (For more details please see the ‘Specialized Register’ section of the Group’s module in The Cochrane Library). The register contains trials identified from MEDLINE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL). The search will be conducted using appropriate free text and MeSH terms by adapting terms drawn from the existing search strategies for the Incontinence Review Group to meet the objectives of this review. Additional trials will be sought from the UK National Research Register, Controlled Clinical Trials and ZETOC database of conference abstracts (searching specifically the American, European and UK societies of colorectal surgeons’ meetings abstracts for the past 10 years).
Searching other resources
The reviewers will also search all the reference lists of relevant articles, and will consider handsearching particularly when abstracts and the conference proceeding of associated meetings are not available electronically. We will not impose any language or other limits on the searches. Where there is insufficient information in a published paper an attempt will be made to contact primary authors for clarification or additional information.
Data collection and analysis
Selection of studies
The titles and abstracts of all studies identified from the above search strategy will be assessed for potential eligibility by two independent reviewers and the full paper will be obtained for all studies considered eligible. Any disagreements will be resolved by consultation with a third reviewer. RCTs and quasi‐randomised RCTs only will be included for the efficacy review.
All other study designs (eg case series of any design, and any length of follow up and sample size) will be reviewed for reports of adverse events and complications. This review for adverse events will form a separate section of the review and specifically alert the reader to the different search method employed.
Data extraction and management
Data extraction from the included trial will be undertaken independently by the two review authors (YM, CN). Data from RCTs and quasi‐randomised RCTs will be processed as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008). Data will be analysed using the RevMan Analyses statistical programme in Review Manager. Data on adverse events and complications will be extracted and entered onto an Excel spreadsheet for review and analysis by all three review authors. Where data are unclear or missing an attempt will be made to contact primary authors for clarification.
Assessment of risk of bias in included studies
Methodological quality of all included RCT and quasi‐randomised RCT trials in the efficacy review will be evaluated by two reviewers using the criteria recommended by the Cochrane Incontinence Review Group to assess risk of bias. In particular, trials will be assessed for randomisation procedure, blinding, adequacy of allocation concealment and intention‐to‐treat analysis. Where this is unclear an attempt will be made to contact primary authors for clarification.
Measures of treatment effect
We shall report odds ratio (OR), risk ratio (RR) or risk difference (RD) for dichotomous data and weighted mean differences (WMD) for continuous data, accompanied by 95% confidence intervals (CI).
Assessment of heterogeneity
On visual inspection of the forest plot together with the chi‐squared test for heterogeneity at the 10% level and the I‐squared statistic if there is evidence of heterogeneity between the trials a reason will be sought by considering the populations, interventions, outcomes and settings of the individual trials. If heterogeneity persists implications will be explored further using random effects models and sensitivity analyses.
Subgroup analysis and investigation of heterogeneity
If data allow, sub‐group analyses will also be undertaken according to cause of incontinence, sphincter integrity, sex of participants, and injection techniques.
Sensitivity analysis
Similarly, if the data allow, sensitivity analysis may be performed to assess the quality of the study data.
