We systematically reviewed literature examining predictors of fistula repair outcomes. Most studies were observational, and few conducted analyses that would permit assessment of independent effects of individual predictors. Patient and fistula characteristics were most frequently studied, with multiple studies of some predictors. Studies of peri-operative factors have been less frequently replicated.
Evidence in the published literature failed to demonstrate an independent role of patient characteristics in predicting repair outcome. The relationship between some patient characteristics and repair outcomes may be mediated by fistula characteristics. For instance age is related to pelvic size, and may thereby influence the degree of damage caused by the obstructed labor, in turn influencing the prognosis of the repair. The influence of patient comorbidities on repair outcomes has rarely been studied; further evaluation is warranted, as comorbidities may be addressed pre-operatively.
Unlike patient characteristics, the weight of evidence indicates that certain fistula characteristics, particularly scarring and urethral involvement, predict poor repair prognosis. These findings are biologically plausible. Urethral fistula repair is a complex procedure. It necessitates reconstruction of surviving tissues into a supple functional organ, which acts both as a passageway for urine, and as a “gatekeeper,” ensuring that passage of urine occurs at appropriate times.27
Reconstruction of the urethra may not necessarily re-establish normal physiology of urethral function and the urethral/bladder voiding reflex. Extensive scarring not only inhibits access to the fistula, but requires use of unhealthy tissue to close the defect.27
Vaginal scarring can also lead to incontinence, if it prevents normal urethral functioning.18
The relationship between other fistula characteristics and repair outcomes is less clear. While two large studies found that as fistula size increases, likelihood of continence following fistula closure decreases,6, 18
the samples of the two studies overlapped somewhat (personal communication A. Browning, July 2011). Nonetheless, these findings are not surprising. It has been suggested that more extensive dissection which may be required for larger fistulas can cause post-operative scarring around the urethra, holding the urethra open.18
The results of two studies showing an association between smaller bladder size and failure of fistula closure24
and incontinence following closure,18
are also biologically plausible. Loss of bladder tissue means the surgeon must close defects with limited remnants of (frequently damaged) bladder tissue; the small resulting bladder size may affect its capacity to retain urine. In addition, while no studies detected an independent association of prior repair and repair outcomes, prior repair has been correlated with degree of vaginal scarring.8
Thus, prior repair may be an indirect cause of negative repair outcomes, via vaginal scarring, which could explain the lack of an independent role of prior repair after adjusting for vaginal scarring seen in two studies.9, 18
Additional studies with large sample sizes are needed to study relatively rare exposures such as ureteric involvement.
Few studies have examined the role of peri-operative factors and all but three were observational designs. Results of the three RCTs 23-25
are difficult to interpret. The findings that prophylactic antibiotic use trended towards higher operative failure and more incontinence compared to no antibiotic use are surprising and counter-intuitive, given the expectation that reducing wound infections would promote fistula closure.23
A recent trial comparing single-dose versus extended antibiotic use demonstrate a marginally significant benefit in favor of single-dose antibiotics, though reasons for such a trend are unclear.24
However, the confidence intervals for both results were compatible with a chance result. The RCT comparing fibrin glue to Martius flap interpositioning was inconclusive, due to its small sample size.25
Observational studies examining medical interventions are subject to confounding by indication, or prognosis, whereby providers prescribe vigorous therapy when the outlook is poor.28
This applies to the observational studies examining peri-operative factors related to fistula surgery, reviewed here. For instance, Nardos et al.13
demonstrated that women catheterized for fewer days were significantly more likely to have fistula characteristics associated with a favorable repair prognosis. Similarly, while Kriplani and colleagues16
found a significantly higher proportion success among fistulas repaired vaginally, analyses did not account for the severity of the fistula, and it is possible that abdominal repairs were more difficult cases less likely to be successfully repaired. In addition, while Kirschner and coauthors found that use of relaxing incision was associated with poorer prognosis, analyses did not adjust for scarring and stenosis, factors that the authors acknowledge may have indicated use of relaxing incision.19
Several observational studies restricted their samples to women meeting specific criteria. Though preferable to no adjustment, this does not allow for adjustment of multiple confounding factors. For instance, while Browning11
found that a significantly higher proportion of women with a Martius flap experienced residual incontinence after repair, stratified analyses demonstrated that fistulas repaired with Martius flap may have been more difficult. Though differences persisted within select subgroups, the possibility of residual confounding by indication cannot be excluded.11
We have identified several research priorities. First, the endpoint “any incontinence,” does little to inform intervention efforts, since the causes of failure to close a fistula versus causes of residual incontinence cannot be teased out. Future studies should examine fistula closure and residual incontinence separately, in order to clarify the etiological importance of different characteristics and procedures being studied. Where possible, studies examining residual incontinence should employ urodynamic studies (UDS) to enable differentiation between types of incontinence, including stress, urge, overflow and mixed incontinence.
Secondly, post-hoc studies of the predictive value of an individual classification system cannot determine the sufficiency of the systems for predicting repair outcomes, or the superiority of one system over another. For instance, it is possible that patient or fistula characteristics not included in current classification systems are important in predicting repair outcomes. Similarly, the inability of any component of these systems to predict fistula closure may result from inadequate statistical power to detect small differences. In order to develop a single, standardized prognostic system for classifying fistulas, additional research confirming the prognostic value of parameters included in existing classification systems, as well as evaluating factors not included, is needed. It is also important to compare existing classification systems to assess their relative discriminatory value for predicting repair outcomes.
More research is also required to assess which peri-operative factors are associated with repair outcomes, independent of patient or fistula characteristics. In particular, further research is required on factors such as duration of catheterization and route of repair which may be associated with increased hospital stay and risk of health-care associated infection. A standardized system of classifying fistula prognosis will facilitate the conduct of such studies.
In summary, a small, albeit growing, number of empirical studies have examined the relationship between fistula repair outcomes and patient characteristics, fistula characteristics and peri-operative procedures used. Many of the studies we reviewed had relatively small sample sizes and did not use rigorous epidemiologic research methods. This, together with the range of predictors studied and variety of definitions of repair outcomes used, has resulted in lack of a unified evidence-base on most predictor-repair outcome relationships and thus little evidence on which to base clinical practice. Given the material and human resource shortages in the settings in which fistula surgery is often conducted, it is admirable that any data has been accumulated on this patient population. Nonetheless, further research is urgently needed to improve the care and treatment of this marginalized and neglected group of women.