**1. Introduction**

Mixed urinary incontinence (MUI) presents with characteristics of both stress urinary incontinence (SUI) and urge urinary incontinence (UUI). It has been generally assumed to respond less favourably to any type of interventional therapy, whether behavioural, pharmacologic, or surgical as compared with pure stress (effort) or urge urinary incontinence. These patients represent a therapeutic challenge: two pathologies coexist, and treatment of either condition may worsen the symptoms of the other. The result is likely to be a poor response to conservative or surgical interventions. (Chaliha & Khullar, 2004)

The development of midurethral sling (MUS) surgery has become the gold standard for surgical treatment of SUI. There is great variability in data regarding cure rate of MUI following mid urethral sling (MUS) surgery of both the stress and urge components. Moreover, the postoperative course of the urge component after surgery is unpredictable as it may resolve, persist or worsen. There are no consistent predictors for persistent worsening of urge components after sling surgery. While there have been various factors described in the literature to predict who will be more likely benefit, these have not been clearly defined. Further compounding the difficulty is the lack of appropriate tools in delineating the characteristics of a mixed presentation. The poor response to treatment in MUI patients have led investigators to attempt quantifying and comparing dominance of either spectrum to dictate a priority of treatment and quantitatively assess outcome.

Despite such limitations, advance of treatment has allowed more aggressive combined approach to MUI, necessitating the delineation of patient profiles appropriate for each treatment method. Here we will review the current investigations analysing the two distinct pathophysiologies of MUI, as well as the suggested factors determining the outcome following MUS treatment.

### **2. Prevalence of MUI**

MUI is the coexistence of stress and urgency urinary incontinence and is defined as involuntary loss of urine associated with the sensation of urgency and also associated with exertion, effort, sneezing or coughing.(Haylen et al., 2010) Mixed incontinence can also be

Preoperative Factors as Predictors of Outcome

correlated in less than 50% of the time.

diagnoses. (Chou et al., 2008)

presentation; however, this entity is yet to be defined.

seek medical attention for their problems (19.1% vs. 25.8%).

African American women (27%).

of Midurethral Sling in Women with Mixed Urinary Incontinence 209

Zimmern investigated 128 women reporting lower urinary tract symptoms and found that 26.6% had mixed incontinence, 20.3% had stress incontinence, 13.3% had urge incontinence, 14.1% had urgency and frequency symptoms, and 10.1% had vaginal prolapse. (Lemack & Zimmern, 1999) However, when symptoms were matched with urodynamic findings they

Urodynamic studies, which provide objective evidence of the type of urinary incontinence, have shown that between 8% and 56% of women with urinary disorders have proven mixed incontinence. Digesu et al. reported rates of DO in a population of stress predominant MUI was 11%. (Digesu et al., 2008) Dooley reported that the proportion of women diagnosed with MUI ranged from a low of 8.3% using only the urodynamic-based definition. (Dooley et al., 2008) Chou et al. suggested that patients may mistake the urge component for the "fear of leaking for urge", in explaining the discrepancy between subjective and objective

The absence of a universal definition of mixed incontinence has made it difficult to compare findings from studies. Whether it is defined urodynamically or symptomatically, incontinence associated with both stress and urge is considered mixed in nature. Ideally, a reproducible instrument that would clearly segregate stress versus urge symptoms and assess the magnitude of bother for a particular patient would best define the MUI

Another difficulty in estimating the population of MUI is the varying degrees of severity in what constitutes the urge component. In a recent, randomized study to investigate the treatment of mixed incontinence in women, Bump et al. found that 31% of patients had mixed urinary incontinence symptoms. (Bump et al., 2003) These women had more severe baseline urinary incontinence than did those with USI in terms of frequency of incontinence and impairment of quality of life. Surprisingly, the baseline severity of incontinence was less in women with urodynamically proven mixed incontinence than in those with USI. The authors performed a comprehensive nationwide survey in Korea and found 40.8% of patients aged 30-79 years reported urinary incontinence. (Choo et al., 2007) Pure stress incontinence only consisted about half of this population (22.8% overall), while the remainder reported mixed symptoms. Of note, patients with mixed symptoms reported a higher degree of impact on daily activities, social life and mental symptoms. More patients with mixed symptoms reported an insult on the overall quality of life (43.8%) compared to pure stress symptoms (28.3%). Furthermore, these patients reported a higher likelihood to

Other than semantic aspects of this question, patients may also significantly vary in their pathophysiology. This is more evident in the diverse presentation of these components pertaining to age or race. Nygaard and Lemke reported that stress incontinence occurs in a higher degree in older women (i.e., 40%). (Nygaard & Lemke, 1996) In studies of Scandinavian women, the rates of SUI peaked at approximately 60% in patients who were in their fifth decade (40–49 years). Urge incontinence began to increase in the sixth decade of their life and peaked at approximately 20% between 80 and 89 years. Racial differences have in fact been reported in a few studies. Bump identified mixed incontinence in up to 17% of African American subjects compared with only 11% of whites. (Bump, 1993) A larger proportion of white women, however, were found to have USI (61%) compared with

defined urodynamically as the coexistence of urinary stress incontinence (USI) and detrusor over activity (DO). DO is characterized by involuntary detrusor contractions during the filling phase and is associated with urgency or incontinence. Urge urinary incontinence is the complaint of involuntary leakage accompanied by or immediately preceded by urgency. Investigators, however, often have grouped several different pathologies together under the category of ''mixed incontinence.''(Khullar et al., 2010) Further compounding the definition of MUI is an acknowledged fact that stress incontinence may also be misperceived as an urgency event. The presence of urine in the posterior urethra may actually induce urinary urgency and eventuate in a secondary episode of detrusor overactivity (stress-induced detrusor overactivity). Therefore, in some individuals, stress incontinence may actually masquerade as MUI due to the significant urgency component associated with spontaneous urinary loss. Urinary frequency is superimposed over this scenario as a behavioral response to the bothersome urinary symptoms. (Dmochowski & Staskin, 2005)

As previously noted, the difficulty in collating the results of different studies primarily lies with a confusion in definition. Epidemiologic studies also vary with reports based on symptoms to those based on urodynamic parameters. While the term ''mixed incontinence'' remains a clinically useful concept there is debate over the utility of its use for outcomes research. Dooley et al. investigated the discrepancy of prevalence between subjective and objective definitions of MUI. The study showed that in the population of women seeking surgical treatment for stress incontinence, the majority of women fell into the category of MUI when using subjective measures to define the condition. (Dooley et al., 2008) Prevalence rates ranged from 50% to 93% depending on the questions used and severity selected; however, when using objective measures only 8% were diagnosed as having MUI on urodynamics. These data illustrate how such wide variations in prevalence rates for MUI can occur. To date, the appropriate MUI definition has not been agreed upon for either research or clinical care.

Most clinical studies, however, generally approximate the prevalence of MUI as one-third of women with urinary incontinence. (Karram & Bhatia, 1989) Recent incidence data based on urinary symptoms were obtained through the National Overactive Bladder Evaluation (NOBLE) Program, which investigated urinary incontinence in 5,204 adults residing in the United States, 2,735 of who were women. When these survey data were applied to the 2000 US census, the total number of US women with incontinence was estimated to be 14.8 million. Urge, stress, and mixed incontinence each accounted for approximately one-third of cases. (Stewart et al., 2003) The study of medical, epidemiological, and social aspects of aging (MESA), conducted by Diokno et al. reported the prevalence of different types of urinary incontinence in senior citizens aged 60 years. (Diokno et al., 1986) Of the 1,150 randomly sampled non-institutionalized women included in the study, 716 were selfreported as continent and 434 as incontinent. The study found that 55.5% of the incontinent women had mixed stress and urge incontinence, 26.7% had stress incontinence alone, 9% had urge incontinence alone, and 8.8% had other diagnoses.

The limitations of comparing MUI in epidemiologic studies to MUI in clinical settings may also be due, in part, to the fact that they require purely symptom based assessments. Thus, one would expect that evaluations of MUI in clinical samples would be superior as they tend to employ a combination of subjective and objective evaluation. Unfortunately, the variation in prevalence rates for MUI in these settings is equally broad. Lemack and

defined urodynamically as the coexistence of urinary stress incontinence (USI) and detrusor over activity (DO). DO is characterized by involuntary detrusor contractions during the filling phase and is associated with urgency or incontinence. Urge urinary incontinence is the complaint of involuntary leakage accompanied by or immediately preceded by urgency. Investigators, however, often have grouped several different pathologies together under the category of ''mixed incontinence.''(Khullar et al., 2010) Further compounding the definition of MUI is an acknowledged fact that stress incontinence may also be misperceived as an urgency event. The presence of urine in the posterior urethra may actually induce urinary urgency and eventuate in a secondary episode of detrusor overactivity (stress-induced detrusor overactivity). Therefore, in some individuals, stress incontinence may actually masquerade as MUI due to the significant urgency component associated with spontaneous urinary loss. Urinary frequency is superimposed over this scenario as a behavioral response

As previously noted, the difficulty in collating the results of different studies primarily lies with a confusion in definition. Epidemiologic studies also vary with reports based on symptoms to those based on urodynamic parameters. While the term ''mixed incontinence'' remains a clinically useful concept there is debate over the utility of its use for outcomes research. Dooley et al. investigated the discrepancy of prevalence between subjective and objective definitions of MUI. The study showed that in the population of women seeking surgical treatment for stress incontinence, the majority of women fell into the category of MUI when using subjective measures to define the condition. (Dooley et al., 2008) Prevalence rates ranged from 50% to 93% depending on the questions used and severity selected; however, when using objective measures only 8% were diagnosed as having MUI on urodynamics. These data illustrate how such wide variations in prevalence rates for MUI can occur. To date, the appropriate MUI definition has not been agreed upon for either

Most clinical studies, however, generally approximate the prevalence of MUI as one-third of women with urinary incontinence. (Karram & Bhatia, 1989) Recent incidence data based on urinary symptoms were obtained through the National Overactive Bladder Evaluation (NOBLE) Program, which investigated urinary incontinence in 5,204 adults residing in the United States, 2,735 of who were women. When these survey data were applied to the 2000 US census, the total number of US women with incontinence was estimated to be 14.8 million. Urge, stress, and mixed incontinence each accounted for approximately one-third of cases. (Stewart et al., 2003) The study of medical, epidemiological, and social aspects of aging (MESA), conducted by Diokno et al. reported the prevalence of different types of urinary incontinence in senior citizens aged 60 years. (Diokno et al., 1986) Of the 1,150 randomly sampled non-institutionalized women included in the study, 716 were selfreported as continent and 434 as incontinent. The study found that 55.5% of the incontinent women had mixed stress and urge incontinence, 26.7% had stress incontinence alone, 9%

The limitations of comparing MUI in epidemiologic studies to MUI in clinical settings may also be due, in part, to the fact that they require purely symptom based assessments. Thus, one would expect that evaluations of MUI in clinical samples would be superior as they tend to employ a combination of subjective and objective evaluation. Unfortunately, the variation in prevalence rates for MUI in these settings is equally broad. Lemack and

to the bothersome urinary symptoms. (Dmochowski & Staskin, 2005)

had urge incontinence alone, and 8.8% had other diagnoses.

research or clinical care.

Zimmern investigated 128 women reporting lower urinary tract symptoms and found that 26.6% had mixed incontinence, 20.3% had stress incontinence, 13.3% had urge incontinence, 14.1% had urgency and frequency symptoms, and 10.1% had vaginal prolapse. (Lemack & Zimmern, 1999) However, when symptoms were matched with urodynamic findings they correlated in less than 50% of the time.

Urodynamic studies, which provide objective evidence of the type of urinary incontinence, have shown that between 8% and 56% of women with urinary disorders have proven mixed incontinence. Digesu et al. reported rates of DO in a population of stress predominant MUI was 11%. (Digesu et al., 2008) Dooley reported that the proportion of women diagnosed with MUI ranged from a low of 8.3% using only the urodynamic-based definition. (Dooley et al., 2008) Chou et al. suggested that patients may mistake the urge component for the "fear of leaking for urge", in explaining the discrepancy between subjective and objective diagnoses. (Chou et al., 2008)

The absence of a universal definition of mixed incontinence has made it difficult to compare findings from studies. Whether it is defined urodynamically or symptomatically, incontinence associated with both stress and urge is considered mixed in nature. Ideally, a reproducible instrument that would clearly segregate stress versus urge symptoms and assess the magnitude of bother for a particular patient would best define the MUI presentation; however, this entity is yet to be defined.

Another difficulty in estimating the population of MUI is the varying degrees of severity in what constitutes the urge component. In a recent, randomized study to investigate the treatment of mixed incontinence in women, Bump et al. found that 31% of patients had mixed urinary incontinence symptoms. (Bump et al., 2003) These women had more severe baseline urinary incontinence than did those with USI in terms of frequency of incontinence and impairment of quality of life. Surprisingly, the baseline severity of incontinence was less in women with urodynamically proven mixed incontinence than in those with USI. The authors performed a comprehensive nationwide survey in Korea and found 40.8% of patients aged 30-79 years reported urinary incontinence. (Choo et al., 2007) Pure stress incontinence only consisted about half of this population (22.8% overall), while the remainder reported mixed symptoms. Of note, patients with mixed symptoms reported a higher degree of impact on daily activities, social life and mental symptoms. More patients with mixed symptoms reported an insult on the overall quality of life (43.8%) compared to pure stress symptoms (28.3%). Furthermore, these patients reported a higher likelihood to seek medical attention for their problems (19.1% vs. 25.8%).

Other than semantic aspects of this question, patients may also significantly vary in their pathophysiology. This is more evident in the diverse presentation of these components pertaining to age or race. Nygaard and Lemke reported that stress incontinence occurs in a higher degree in older women (i.e., 40%). (Nygaard & Lemke, 1996) In studies of Scandinavian women, the rates of SUI peaked at approximately 60% in patients who were in their fifth decade (40–49 years). Urge incontinence began to increase in the sixth decade of their life and peaked at approximately 20% between 80 and 89 years. Racial differences have in fact been reported in a few studies. Bump identified mixed incontinence in up to 17% of African American subjects compared with only 11% of whites. (Bump, 1993) A larger proportion of white women, however, were found to have USI (61%) compared with African American women (27%).

Preoperative Factors as Predictors of Outcome

of Midurethral Sling in Women with Mixed Urinary Incontinence 211

**4. Outcome of midurethral sling in resolution of mixed urinary incontinence**  The presenting symptoms of patients may be a guide to the approach to MUI. In those cases where either the stress or urge symptoms predominate, the most bothersome symptom should be approached first to potentially lessen the impact of the secondary symptom. Older surgical literature implies that patients with significant stress symptoms preoperatively, even if detrusor over activity is present, have a greater likelihood of success than those patients with a significant preoperative urge. The use of history (inclusive of symptomatic appraisal) associated with physical examination demonstrating (or not) stress incontinence may be very helpful in assessing the relative contributions of stress and urgency symptoms as well as the other potential insensate urinary loss that some patients experience.(Dmochowski & Staskin, 2005) Once the patient's initial response to the primary intervention is determined, further therapies can be recommended for persistent symptoms or for secondary symptoms, should those symptoms remain problematic. For instance, patients with mixed symptoms with a strong urge component and definable but less severe stress component could undergo therapy specially defined to ameliorate the urgency symptoms including anticholinergic use followed by neuromodulation (and/or botulinum toxin) and a secondary intervention for the bladder outlet, should persistent stress symptoms remain bothersome. Similarly, patients with predominant stress symptoms could undergo intervention for SUI with secondary interventions for UUI depending upon the results of the primary intervention and persistence of bothersome urinary symptoms. Therefore, the approach to MUI should be based on symptomatic segregation, with therapy promulgated on the basis of the most bothersome symptom and secondary interventions reserved for either persistence of the primary symptom or bother arising from the less prominent initial symptom. In those individuals with relatively equal bother, or who are unable to segregate their symptoms, the initial guideline to therapy may become apparent only after beginning more intensive evaluation (such as urodynamic studies). Alternatively, conservative or minimally invasive intervention may be initiated to establish response, followed by more intensive intervention for nonresponse. Ideally, patients should be informed about which symptoms may persist or become problematic post-intervention.

The role of surgery in the treatment of mixed incontinence had been historically considered highly controversial due to a high failure rate, from symptomatic or asymptomatic DO. (Stanton et al., 1978) More recently, several studies have concluded that an effective pubovaginal sling can cure stress incontinence and may also have benefit for urge symptoms. Langer et al. reported the results of a study of 30 women with mixed incontinence who underwent Burch colposuspension. (Langer, 1988) The proportion of patients with symptoms of DO decreased significantly from 73.3% before to 33.3%after surgery. In all, 50% of patients had marked improvement in clinical symptoms of DO. Normal cystometric findings were present postoperatively in 60% of patients, and only 40% had evidence of DO on postoperative urodynamic assessments. Ulmsten et al. evaluated the effect of TVT in 80 women suffering from MUI. (Ulmsten et al., 1996) They demonstrated that at a mean of 4 years, both SUI and UUI were cured in 85% of patients, significantly improved in 4%, and unchanged or worse in 11%. They concluded that TVT could be used to treat women patients with MUI. This study excluded patients with significant detrusor overactivity; therefore, the population was somewhat selected. Anger and Rodriguez reported that surgical intervention for patients with mixed incontinence resulted in
