(collagen) following prostatectomy?

a.Prior radiation

b.Stricture

c.High-grade SUI

d.Low abdominal leak-point pressure (ALPP)

e.All of the above

.Which of the following statements about results of silicone microimplants (Macroplastique) for postprostatectomy incontinence are TRUE? (Select all that are true.)

a.Long-term deterioration of outcome is expected.

b.Noninferiority was demonstrated versus collagen.

c.Not as effective for more severe incontinence versus the artificial urinary sphincter (AUS).

d.Reinjections are not commonly required.

e.Patient satisfaction has been shown to be higher with the Macroplastique than Bulkamid

.Which of the following is a recognized adverse factor for ProACT (Uromedica, Düsseldorf, Germany) balloon success?

a.Slowly rising prostate-specific antigen (PSA)

b.Prior radiation

c.Failed artificial sphincter

d.Detrusor overactivity

e.Urinary tract infection

Answers

1.e. None of the above. The ideal injectable agent should be easily injectable and conserve its volume with time. It should also be biocompatible, nonantigenic, noncarcinogenic, nonmigratory, and cause little or no inflammatory reaction (Kershen and Atala, 1999)* or fibrotic ingrowth (Dmochowski and Appell, 2000). The components of the bulking agent should not separate or dissociate on injection, and if the agent contains microcrystalline or micropolymeric components, they should be reasonably uniform spheres of particle sizes greater than 110 μm that are nonfragile and adhere to host tissue (Dmochowski and Appell, 2000). If unsuccessful, it should not interfere with subsequent surgical intervention. To date, no substance has met all of these requirements.

2.b. Mechanism not yet defined. It is generally thought that these agents improve intrinsic sphincter function, although the exact mechanism has not been defined (Smith et al, 2009). Bulking agents such as collagen have been reported (McGuire and Appell, 1994; Monga et al, 1995) to augment urethral mucosa and improve coaptation and intrinsic sphincter function as evidenced by an increase in post-treatment abdominal leak pressure (Herschorn et al, 1992; Richardson et al, 1995; Winters and Appell, 1995). Bulking agents do not generally obstruct voiding after the initial post-treatment period (Monga et al, 1995).

3.d. Many studies have not confirmed the value of LPP in quantifying ISD.

Because injectable agents are indicated for the ISD component of SUI, can urodynamic studies assess ISD? Two measures of urethral function have been used: maximum urethral closure pressure (MUCP) and abdominal leak-point pressure (ALPP). A MUCP of ≤ 20 cm H2O has been suggested as an

indicator of clinically significant urethral weakness, but there is controversy regarding the diagnostic and predictive value of urethral pressure profilometry in characterizing ISD (Weber, 2001). Similarly, an ALPP of ≤ 60 cm H2O was identified as an indicator of severe ISD (McGuire et al, 1993), but many studies have not confirmed the test's value in quantifying the degree of ISD (Koelbl et al, 2009). Previously, ALPP measurements of initially ≤ 65 and then ≤ 100 cm H2O were used as indicators of ISD to justify the use of injectable agents (Appell and Winters, 2007). However, because ISD may be present in many patients with SUI with or without urethral hypermobility (Koelbl et al, 2009, 2013), the specific value of either the MUCP or ALPP may be of no importance in the clinical decision about the use of injectables. As with other patients with SUI who opt for interventional therapy, urodynamic studies may be helpful for the reasons mentioned earlier.

4.b. Adverse urethral factors such as scarring or diverticula can be assessed. Preinjection cystoscopy is helpful to make sure that there are no adverse factors or unexpected findings that may prevent or compromise the injection procedure, such as extensive urethral scarring from previous surgery, radiation, or trauma, foreign bodies, or urethral diverticula.

5.a. Both the periurethral and transurethral techniques have shown similar results. The periurethral and transurethral approaches for collagen were compared first by Faerber and colleagues (1998), who reported no significant difference in success rates and numbers of injections required in 24 patients

with transurethral treatment versus 21 with a periurethral approach. However, significantly more collagen was required for the periurethral approach. Schulz and coworkers (2004) reported similar findings in 40 women randomly assigned to either technique. There was no difference in short-term success rate, but the 20 women assigned to the periurethral approach required more collagen than those assigned to the transurethral approach. Furthermore, the Cochrane review concluded that there are insufficient data to determine whether transurethral is superior to periurethral and whether midurethral offers any benefit versus bladder neck injection (Kirchin et al, 2012). The transurethral approach is now more commonly reported than the periurethral approach.

6.a. Silicone microimplants (Macroplastique). Because of its high viscosity, Macroplastique injections require the use of a ratcheted injection gun. The injection needle is 7 Fr with a 10-mm 18-G needle tip.

7.c. A fluoroquinolone or trimethoprim-sulfamethoxazole for 24 hours or less can be recommended. Although randomized trials have not been done, prophylactic antibiotics with a fluoroquinolone or trimethoprimsulfamethoxazole (TMP-SMX) for 24 hours or less can be recommended (Wolf et al, 2008). An additional 2 to 3 days has also been suggested (Appell and Winters, 2007).

8.e. The minimum timing for reinjections is variable and depends on the agent. Although bovine glutaraldehyde cross-linked collagen (Contigen; C.R. Bard, Covington, GA) could be reinjected within 7 days, most clinicians waited 4 weeks or longer to assess response of the urethra and the need for reinjection (Appell and Winters, 2007). Silicone microimplant (Macroplastique) injections can be repeated after 12 weeks (Uroplasty). Carbon-coated zirconium beads (Durasphere) can be reinjected after a minimum of 7 days (Lightner et al, 2001) and calcium hydroxylapatite (Coaptite) after 1 month or less (Mayer et al, 2007). Polyacrylamide hydrogel (Bulkamid) has been reinjected at 1 to 2 months (Toozs-Hobson et al, 2012; Sokol et al, 2014).

9.e. a, b, and c are correct. A number of pitfalls in reporting of injectable studies can lead to inflated success rate. Because injectable agents can be repeated if the initial treatment fails, authors should specify whether that time point is after all treatments have been completed or whether it is from baseline. If durability is reported after all injections are administered, then an accurate picture of duration of efficacy can be conveyed. A Kaplan-Meier

(Malizia et al, 1984).

.a. Urgency and retention. In the multicenter randomized trial of Durasphere versus collagen, the adverse event profiles were similar (Lightner et al, 2001). However, more women had significantly more post-treatment urgency and

acute retention with Durasphere versus collagen, 24.7% and 16.9% versus 11.9% and 3.4%, respectively.

.c. Macroplastique (silicone microimplant). Ghoniem and colleagues (2009) reported results of a North American multicenter randomized trial of Macroplastique versus collagen. After 1 year, 61.5% (75/122) with Macroplastique and 48% (60/125) with collagen had an improvement of at least 1 Stamey grade. This indicated that Macroplastique was noninferior to collagen (P < 0.001). The proportion of the patients who were dry was higher

in the Macroplastique group at 36.9% versus 24.8% (P < 0.05). However, there were no significant differences in pad weight testing, quality-of-life scale, or adverse events.

.b. Zuidex (hyaluronic acid dextranomer with Implacer). Lightner and colleagues (2009) reported 12-month outcomes of a North American prospective 2:1 randomized trial of Zuidex-Implacer versus collagen injected cystoscopically in 344 women. The study failed to demonstrate that Zuidex was noninferior to collagen. The proportion of women who achieved a 50% reduction in urinary leakage on provocation testing, the primary outcome, was achieved in 84% of collagen-treated women versus 65% of Zuidex-treated women. There was also a 15% incidence of pseudoabscess formation. This negative trial prompted the company to withdraw the Zuidex product.

.d. At 12 months there is almost no difference compared to no treatment.

Physiotherapy and pelvic floor rehabilitation have been shown to improve or enhance continence (decreased time to final continence level) in the

postoperative period in two randomized studies, but only if such measures are instituted before or immediately after catheter removal (Van Kampen et al, 2000; Parekh et al, 2003). Maximum difference between physiotherapy and no treatment is achieved at 3 months, with almost no difference at 12 months. A randomized study in which randomization occurred 6 weeks after surgery showed no difference in continence at 6 months (Wille et al, 2003).

.a. Multiple treatment sessions are usually required. Urethral bulking theoretically works by adding bulk and increasing coaptation at the level of the bladder neck and proximal urethra. Several agents have been used, including bovine collagen (Contigen), and silicone microparticles

(Macroplastique). All agents share similar problems, including the need for multiple injections, deterioration of effect over time, and low cure rates.

.e. Several authors have identified factors that negatively affect postprostatectomy incontinence treatment results, including extensive scarring or stricture formation, previous radiation, and high-grade stress incontinence and low ALPP (Aboseif et al, 1996; Sanchez-Ortiz et al,

1997; Smith et al, 1998; Cespedes et al, 1999).

.c. Not as effective for more severe incontinence versus the artificial urinary sphincter (AUS). Imamoglu and colleagues (2005) demonstrated no difference in success with AUS versus Macroplastique in men with mild incontinence. However, in patients with more severe incontinence, the AUS was superior, with minimal improvement seen following transurethral

Macroplastique.

.b. Prior radiation. Reported risk factors for failure and complications were prior external beam radiotherapy (Lebret et al, 2008; Gregori et al, 2010) and severe preoperative incontinence (Gregori et al, 2010). Kocjanic and colleagues (2007) reported a continence rate of 67% in nonradiated patients compared to 36% in radiated patients.

Chapter review

1.Injection therapy is thought to improve intrinsic sphincter function by improving mucosal coaptation.

2.Injectable agents are indicated for the ISD component of SUI.

3.Detrusor overactivity should be treated before injection therapy because it may compromise the results. Sphincter and bladder dysfunction may coexist in a third of patients.

4.A maximum urethral closure pressure less than or equal to 20 cm H2O or

an abdominal leak point pressure less than or equal to 60 cm H2O have been used to diagnose intrinsic sphincter deficiency; however, these parameters do not correlate with success after injection therapy.

5.The substance to be injected at the bladder neck or proximal urethra is injected immediately beneath the mucosa at the 3-and 9-o'clock position so as to coapt the mucosa.

6.The transurethral or paraurethral route of injection has similar results.

7.A catheter is not routinely used after injection except in patients who have retention; if that is the case, the catheter should be of small caliber.

8.Complications of injection therapy include urinary retention, urinary

infection, detrusor overactivity, hematuria, incontinence, vaginal discomfort, vaginal wall erosion, and urethral mucosa prolapse.

9.On average, approximately one third of patients are cured at 18 months.

10.Autologous materials that have been used for bulking agents include chondrocytes, fibroblasts, fat, and umbilical cord stem cells. The results have been mixed.

11.Postprostatectomy, sphincter and bladder dysfunction may coexist in one third of patients.

12.Injectable agents are not effective in a scarred membranous urethra.

13.Factors that negatively affect postprostatectomy incontinence treatment results include extensive scarring or stricture formation, previous radiation, high-grade stress incontinence, and low ALPP.

14.Injectables have been used in continent diversions with variable success. Vesicovaginal fistula has been reported as a complication in these patients.

* Sources referenced can be found in Campbell-Walsh Urology, 11th Edition, on the Expert Consult website.