Injections for Incontinence in Women and Men

In evaluating patients for the use of intraurethral injections as a treatment of urinary incontinence, it is essential to identify the cause(s) of incontinence in order to recommend appropriate therapy. Intraurethral injections benefit patients with incontinence occurring at the level of the bladder outlet. Incontinence occurring at this level may be caused by anatomic displacement of a normally functioning urethra (anatomic genuine stress urinary incontinence) in women or intrinsic incompetence of the urethral closure mechanism (intrinsic sphincteric dysfunction) in women or men. Patients with intrinsic sphincteric dysfunction (ISD) commonly have had a previous surgical procedure on or near the urethra, a sympathetic neurologic injury, or myelodysplasia. Female patients with genuine stress urinary incontinence have normal urethral function but hypermobility of the bladder neck and proximal urethra resulting from a deficiency in pelvic support. These patients benefit from bladder neck elevation and stabilization. Patients with ISD have poor urethral function and require procedures to increase outflow resistance. Patients with a fixed, well-supported urethra in association with ISD are excellent candidates for periurethral injection. In men this is most commonly encountered following radical prostatectomy, whereas in women the primary cause of ISD is a residual effect of multiple surgical resuspension procedures for genuine stress urinary incontinence.

DIAGNOSIS

Patients with ISD urodynamically display an open bladder outlet at rest in the absence of a detrusor contraction. However, standardization of a methodology to determine ISD has not yet been accepted. Because the incontinence of ISD is nonresistant (passive) urinary leakage, the goal of treatment should be only to coapt the urethra by passive occlusion. With respect to outlet function, maximum urethral closure pressure (UCPmax) obtained during urethral pressure profilometry has been the test used to determine the presence of ISD in women. Those women with UCPmax £ 20 cm H2O were said to have a “low-pressure urethra” or ISD, and these patients failed standard bladder neck suspension procedures.

One can infer that if urethral urinary loss can be induced by abdominal pressure, something must be wrong with the outlet. The abdominal leak-point pressure (LPPabd) is determined by direct measurement of the abdominal pressure required to overcome urethral resistance. This determination may be considered an indirect method of measuring the closure forces of the urethra during straining maneuvers. It is used primarily in women with stress urinary incontinence (SUI) to differentiate between anatomic displacement of a normal-functioning urethra (SUI caused by hypermobility) from poor outlet function (ISD). The leakage may be documented visually or fluoroscopically. At the point at which leakage occurs, LPPabd is recorded. Patients with ISD demonstrate minimal urethral resistance to straining, and therefore the urethral opening pressure is very low, whereas patients with an anatomic displacement of a normally functioning urethra have high urethral opening pressures, and therefore the LPPabd will be higher. However, no standardization of the technological methods to obtain LPPabd has been accepted. In summary, in evaluating leak-point pressures, until a universally accepted technique is established, a single mode with which the physician is comfortable should be used in the same manner on every patient whether for a preoperative evaluation or for the evaluation of a patient with an unsatisfactory result.

INDICATIONS FOR SURGERY

During the multicenter investigation of collagen in the treatment of ISD, the patients selected with anatomic (type II vesicourethral hypermobility) incontinence did not fare well. Therefore, the recommendation currently is to perform intraurethral or periurethral injections on patients with a poorly functioning urethra (ISD) and good anatomic support. However, recent data suggest that injectables may be used for selected female patients with anatomic stress urinary incontinence.

ALTERNATIVE THERAPY

The treatment of urinary incontinence related to the incompetent urethra has been a challenging problem and frequently involves surgical augmentation of intraurethral pressures by the use of slings made of autologous or synthetic materials, implantation of an artificial sphincter, or periurethral injection of bulk-enhancing agents.

SURGICAL TECHNIQUE

The technique of injection of material is not difficult; however, it is essential to perform precise placement of the material in order to ensure an optimal result. The equipment required for injection depends on the bulk-enhancing agent injected. The injection can be performed either suburothelially through a needle placed directly through a cystoscope (transurethral injection) or periurethrally with a needle inserted percutaneously and positioned in the urethral tissues in the suburothelial space, with the manipulation observed by cystourethroscopy. Men are injected predominantly by the transurethral approach, and women are injected by either technique. There is certainly a learning curve with any technique chosen, which ultimately results in using less injectable material to attain the desired result of continence. Injection techniques using glutaraldehyde-cross-linked collagen (Contigen) are presented, as this is currently the only injectable approved for incontinence.

Technique of Injection in the Male Patient

The patient is positioned in the semilithotomy position and prepped and draped in the usual fashion, and 10 ml of a 2% lidocaine jelly is placed intraurethrally and left in place 10 minutes before instrumentation. Cystourethroscopy with a zero-degree lens is employed. The injectable material is then delivered suburothelially by way of a transcystoscopic injection needle under direct vision. The needle is advanced under the mucosa with the beveled portion of the needle facing the lumen of the urethra. This is performed in a circumferential matter, employing four quadrant needle placements. The material is injected until a mucosal bleb is created in each quadrant. Gradually, after the circumferential injections, the urethral mucosa meets in the midline, although additional needle placements may be required for completion.

In cases of ISD following a radical prostatectomy, a short segment of urethra remains above the external sphincter. If visualization of this segment of the urethra is difficult, the needle may be placed at the level of the external sphincter and advanced to ensure deposition of the material proximal to the external sphincter. To be effective, any injectable material must be injected in the urethra superior to the external sphincter, even if this means injecting into the actual bladder neck on the proximal side of the anastomosis. It is important to note that the material should not be injected directly into the external sphincter, as this can cause pudendal nerve irritation with resultant sphincter spasm and discomfort. The depth of injection is also critical. The materials must deform the urethral mucosa so that it closes the urethral lumen. Too deep an injection site is a waste of the material and is not effective.

Injection is more difficult in patients with post-radical-prostatectomy incontinence resulting from the short segment of urethra above the level of the external sphincter and extensive scarring, which usually occurs in this area following surgery. This problem can be circumvented by using an antegrade approach. The technique is performed by passing a cystoscope with a 5-Fr working port through a small suprapubic cystotomy tract. The vesical neck and proximal urethra are then visualized, and subepithelial injections are performed until the bladder outlet is coapted. Frequently there is less scar tissue in this location, which results in better tissue coaptation. In early clinical trials, this technique seems to facilitate more precise injection of material, generating improved results with the use of less material.4 In the authors’ opinion this technique represents an exciting new method of implantation in male patients and should be considered in any postprostatectomy man not achieving adequate success by way of the standard transurethral approach. Post-radical-prostatectomy urothelium covers scar, and there is migration of any injectable substance distally along the urethra. Once this stops, there is a “wall” to abut the freshly injected material at the bladder neck. Therefore, this additional technique is not recommended as the primary method for an initial injection.

A small subset of patients continue to have some degree of incontinence after the placement of a bulbous urethral artificial urinary sphincter. To date the only options to address this problem have been to place a more distal second (tandem) cuff around the bulbous urethra or to place a higher-pressure regulating balloon. Injectable agents have generally been avoided in this setting because of fear of damaging the sphincter cuff. The antegrade approach can be used for this situation without fear of damaging the cuff, although it remains important to know the location of the pressure-regulating balloon before performing the punch cystotomy.

In cases of ISD following prostatic resection, a short segment of urethra remains below the veru montanum and yet is still proximal to the external sphincter. The injections should be made in this position circumferentially until urethral coaptation is visible. Extrusion of material into the urethral lumen from the needle holes may occur but can be minimized by not traversing the injected area with the distal end of the cystoscope once the material has been injected. In other words, do not enter the bladder.

Technique of Injection in the Female Patient

Women may be injected by way of a transcystoscopic technique, as described for the male patient, or by a periurethral approach. The patient is placed in the lithotomy position and prepped and draped in the usual fashion. The introitus and vestibule are anesthetized with 20% topical benzocaine, and the urethra is anesthetized with 10 ml of 2% lidocaine jelly. Following this, a local injection of 1% plain lidocaine is performed periurethrally at the 3- and 9-o’clock positions using 2 to 4 ml on each side. Panendoscopy is performed with a 0- or 30-degree lens, and the needle is positioned periurethrally at the 4- or 8-o’clock position with the bevel of the needle directed toward the lumen. The needle is then advanced into the urethral muscle into the lamina propria in an entirely suburothelial plane. Once the needle is positioned in the lamina propria, it usually advances with very little force. The needle may also be introduced between the urethral fascia and vaginal epithelium at the 6-o’clock position, and, again, needle placement is fully observed endoscopically. Bulging of the tip of the needle against the mucosa of the urethra is observed during advancement of the needle to ensure its proper placement. When the needle tip is properly positioned 0.5 cm below the bladder neck, the material is injected until swelling is visible on each side, creating the appearance of occlusion of the urethral lumen. Once the urethra is approximately 50% occluded, the needle is removed and reinserted on the opposite side, and additional material is injected until the urethral mucosa coapts in the midline, creating the endoscopic appearance of two lateral prostatic lobes.

Although urologists and urogynecologists are more familiar with transurethral than periurethral techniques, we prefer the periurethral approach, as this minimizes intraurethral bleeding and extravasation of the injectable substance. A useful “trick” described by Neal et al. is to add methylene blue to the injectable lidocaine to aid in the location of the needle tip before injecting the bulking agent.8 Once the needle is located at the bladder neck position, the syringe of anesthetic/methylene blue is removed, and the syringe containing the bulking agent is engaged. When the desired appearance of the coapted mucosa is attained, have the patient stand and cough to see if there is any leakage, and, if there is, reposition the patient and reinject.

Perioperative antibiotic coverage is continued for up to 3 days following the procedure. Most patients are able to void without difficulty following the procedure; however, if retention does develop, clean intermittent catheterization is begun with a 10- to 14-Fr catheter. An indwelling urethral catheter is to be avoided in patients, as this promotes molding of the material around the catheter. Although it is usually unnecessary, if longer-term catheterization is needed, suprapubic cystotomy should be performed in these patients.

Patients are contacted 2 weeks postprocedure in order to determine their continence status. Repeat injections are scheduled as necessary and at a time interval appropriate for the injectable substance.

OUTCOMES

Complications

The perioperative complications associated with periurethral injections are uncommon. In the multicenter clinical trial using Contigen injections, transient retention developed in approximately 15% of patients, but only 1% of patients experienced irritative voiding symptoms, and 5% developed a urinary tract infection. Hypersensitivity responses with Contigen are not a problem, as the possibility is assessed by skin testing (wheal and flare) with the more immunogenic and sensitizing non-cross-linked collagen prior to treatment. Those with a positive skin test are excluded from treatment. Regardless of the material, the use of periurethral injections has proven to be safe, eliciting only minor complications. All complications resolve rapidly, and a serious long-term complication from the use of periurethral injections has yet to be reported.

Results

There are no controlled, long-term reports available on any injectable. In fact, it is difficult to glean information in any group reported as to etiology of the incontinence. For example, in women results of injectables are reported without differentiating among patients with hypermobility, those with ISD, and those with both; and men with prostatic resection for benign disease are not separated from those having had a radical prostatectomy. Thus, results have been a combination of anecdotal reporting mixed with conjecture, speculation, and the hope that the truth is involved. Having stated this, it appears that injectables are helpful for some incontinent patients, especially selected women. There are two major disadvantages to the use of injectables: (a) the inability to determine the quantity of material needed for an individual patient and (b) the safety of nonautologous products for injection with respect to migration, foreign body reaction, and immunologic effects. At this point in time only Contigen has been approved as an injectable for incontinence in the United States, and results presented are confined to this approved substance.

Results of the North American Contigen Study Group of 134 postprostatectomy patients (17 postresection; 117 post-radical-prostatectomy) and 17 postradiation incontinent men demonstrated that only 22 men (16.5%) regained continence following injections of collagen, but 78.7% were dry or significantly improved at 1 year of follow-up, and 67% at 2 years following injections.2,7 Use of the antegrade injection technique in men failing the standard retrograde, cystoscopic approach increased the “cured” rate at 1 year by another 37.5%.

Results of the North American Contigen Study Group of 127 women demonstrated 46% dry and 34% socially continent (patients requiring a single minipad/day) with 77% remaining dry once continence had been attained. Worldwide independent studies have supported these findings. Patients with no anatomic hypermobility and ISD appear to be the most satisfactory candidates for intraurethral injections. In selected elderly and less mobile female patients with anatomic incontinence, recent data suggest that collagen may also be useful in this patient population.

Injectables are still in the developmental stages and their roles in the management of incontinence still need to be defined more precisely. Because the methods are less invasive and generally performed on an outpatient basis, medical costs should be reduced, and there should also be a more rapid return to the patient’s normal activities. The ideal material is still sought and should combine ease of administration with minimal tissue reaction, lack of migration, and persistence over time. The physician considering injectables for his or her patient should consider that there is a learning curve in patient selection as well as method of delivery of the bulking agents to attain optimal results.

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