Interstitial Cystitis

Interstitial cystitis is a symptom complex comprised of chronic irritative voiding symptoms, sterile and cytologically negative urine, and bladder pain that is exacerbated by bladder filling but relieved, in many instances, by bladder emptying. This is predominantly a woman’s disease because they comprise more than 90% of all patients diagnosed with this disease. The low percentage of men reported in epidemiologic studies involving interstitial cystitis may in part reflect the difficulty in differentiating interstitial cystitis from chronic abacterial prostatitis because both conditions have similar overlapping symptoms. The exact etiology and pathogenesis of this debilitating disease are as yet unknown but may be related to an insufficient glycosaminoglycan layer, an abnormal inflammatory response to noxious urinary components, a primary sensory neuronal abnormality, and chronic infection with an as yet unidentified and/or fastidious organism, or a combination of these different etiologies.

DIAGNOSIS

The diagnosis of interstitial cystitis is based on the presence of irritative voiding symptoms, the absence of urinary organisms, and typical cystoscopic appearance. In 1988, an NIDDK-sponsored workshop was convened to propose inclusion and exclusion criteria to assist those investigating this disease.

Cystoscopic examination at the time of hydrodistention is mandatory in confirming the diagnosis of this disease as well as in ruling out other possible etiologies that could be responsible for bladder pain and irritative voiding symptoms. Hydrodistention is performed under regional or general anesthesia. The bladder is distended with either sterile water or normal saline irrigant at a pressure of 100 to 120 cm H2O and then emptied after 5 minutes. The presence of glomerulations or Hunner’s ulcers, which universally spare the trigone, are highly suggestive, though not pathognomonic, of interstitial cystitis. Some authors prefer to categorize those patients exhibiting Hunner’s ulcers separately from those patients exhibiting the much more common finding of glomerulation.

Pathologic features of interstitial cystitis include nonspecific chronic inflammatory infiltrate, edema, and vasodilation of the submucosa and detrusor layers. Bladder mastocytosis is often found on pathologic examination, but it is not pathognomonic, nor does its absence exclude the diagnosis of interstitial cystitis.

INDICATIONS FOR SURGERY

Other than hydrodistention and the intravesical instillation of certain agents, the primary treatment for interstitial cystitis is usually not surgical in nature. Most would agree that surgical treatment is appropriate only for a small and select group of patients with incapacitating and debilitating symptoms resistant to conventional medical and/or behavioral therapy.

ALTERNATIVE THERAPY

Alternatives to surgical treatment would include anticholinergics, anti-inflammatories, behavioral modification, and other methods of managing chronic pain, including TENS units and tricyclic antidepressants.

SURGICAL TECHNIQUE

Patient Selection

Once the diagnosis of interstitial cystitis is established, a reasonable attempt should be made to assess the impact of the disease on daily activities, work activities, leisure activities, and interpersonal relations. It is imperative that the patient be counseled extensively regarding the realistic goals and limitations of surgical therapy for this poorly defined disease. This is especially true in patients who are considering cystectomy with an incontinent or continent diversion. Instruction on the care involved in stoma care and use of a urinary appliance are certainly a vital part of patient teaching for those contemplating this type of surgical intervention. For those considered candidates for augmentation cystoplasty or continent diversion, assessment of manual dexterity and ability to perform self-catheterization is necessary before proceeding with surgery. A dedicated nurse or stomal therapist available to advise and instruct patients preoperatively is a crucial element in the preoperative preparation process.

Hydrodistention and Instillation of Vesical Agents

Hydrodilation of the bladder as a treatment for interstitial cystitis was first described nearly 65 years ago and remains the most common surgical treatment for the relief of bladder symptoms. Hydrodistention is an easy and relatively safe technique and is usually necessary as part of the diagnostic algorithm in patients with the symptom complex of irritative bladder symptoms in the face of sterile and cytologically negative urine. The therapeutic effect of hydrodistention appears to result from ischemia of the suburothelial nerve plexus with resultant sensory denervation secondary to bladder overdistention.

Before any endoscopic manipulation is done, the patient must have a sterile urine. Preoperative antibiotics are recommended. The patient then undergoes cystoscopy under general or regional anesthesia, which allows for adequate distention of the bladder. The bladder is distended with the irrigant bag (sterile water or saline) elevated to 100 to 120 cm above the bladder, which assures that distention up to at least 100 cm H2O occurs during filling. The bladder is inspected before and during filling. In the vast majority of patients, the bladder before distention is unremarkable. Bladder capacity is reached when the irrigant no longer flows in the drip chamber on the irrigant tubing. The bladder is distended for 3 to 5 minutes, drained, and the bladder volume measured. The presence of hematuria at the terminal portion of the drained fluid is very common in patients with interstitial cystitis. Reinspection of the bladder in patients with interstitial cystitis reveals diffuse glomerulations in most cases and, in some cases, Hunner’s ulcers. On rare occasions the lesions may be focal. Biopsies of the affected area(s) are necessary to rule out other possible pathologic conditions such as carcinoma in situ.

Additional intravesical agents such as dimethylsulfoxide (DMSO), silver nitrate, heparin sulfate, and chlorpactin WCS 9 can be instilled at the same time as the hydrodistention. Fifty milliliters of 50% aqueous solution of DMSO with or without steroids (i.e., 100 mg hydrocortisone or 50 mg methylprednisolone) are left indwelling for 20 to 30 minutes. Intravesical heparin in a dose of 10,000 IU can also be instilled and left indwelling much the same manner as DMSO. Silver nitrate in concentrations of 0.5% to 2% can also be instilled and left to dwell for 5 to 7 minutes. At the end of the dwell time, the silver nitrate solution is irrigated with copious amounts of saline solution. A white precipitate of silver chloride is formed, and saline irrigation should continue (usually 1 to 2 liters) until the irrigant is clear. It is best to avoid using silver nitrate at the same time as biopsy or in patients with vesicoureteral reflux. Chlorpactin at 0.4% is instilled in a similar manner as DMSO. However, the same precautions should be observed with chlorpactin instillation as with silver nitrate in that it should not be administered if vesicoureteral reflux is present or if bladder biopsies were performed.

Endoscopic Resection or Fulguration

Endoscopic resection or fulguration of lesions can also be performed in those select few patients who have Hunner’s ulcers or localized disease. Resection can be carried out with the loop resectoscope in which the continuous-flow resectoscope is very helpful because it allows a constant bladder volume during the resection, minimizing the risk of inadvertent bladder rupture. Fulguration of discrete areas of glomerulation can be performed with electrocautery, using either the Bugbee or rollerball electrode, or with the neodymium:YAG laser. With the laser set at 25 watts continuous and the tip set 1 to 2 mm from the bladder wall, the entire lesion is treated including a 2- to 3-mm margin of normal mucosa. Retreatment can be repeated at 4 to 6 weeks.

Cystolysis

Bladder denervation procedures have been reported in the treatment of patients with intractable bladder pain and urinary frequency and urgency. Division of the posterior sacral roots, posterior rhizotomy, or division of the inferior vesical neurovascular pedicle has resulted in temporary improvement in urinary frequency, urgency, and pain. However, the return of symptoms and the development of poorly compliant bladders over the long term have resulted in the abandonment of these procedures as a viable surgical treatment for interstitial cystitis.

Ingelmann-Sundberg has recently described a more selective denervation in which a transvaginal approach is used to resect the inferior hypogastric plexus, whereby both the sympathetic and parasympathetic fibers to the bladder are divided4. Candidates for transvaginal denervation are selected by first performing a subtrigonal injection with bupivacaine. Patients amenable to denervation should experience a period of complete or significant relief from their irritative symptoms.

To perform the denervation, place the patient in a lithotomy position and determine the bladder neck and trigone by palpation of the Foley catheter balloon. Ureteral stents should be placed before the vaginal dissection is done to avoid inadvertent injury to the ureters during the vaginal dissection. A posterior-based U incision is made in the anterior vagina, and the vaginal epithelium is sharply dissected off the underlying proximal urethra, bladder neck, and distal trigone. The vaginal epithelium is then reapproximated using a running suture of 2-0 or 3-0 chromic catgut. The ureteral stents are removed, and the Foley catheter is left indwelling for 24 hours.

Urinary Diversion

Urinary diversion without removal of the diseased bladder usually is not sufficient to relieve symptoms secondary to interstitial cystitis. Most patients will continue to be symptomatic, and therefore, urinary diversion alone is not an adequate or appropriate method of treatment.

Augmentation Cystoplasty

Simple augmentation of the bladder without excision of the diseased bladder has been described as a method of treating patients with intractable interstitial cystitis who are found to have small-capacity bladders (<400 cc under general anesthesia). Both small and large bowel segments can be used. Concern remains regarding the relative wisdom of leaving a significant portion of affected bladder behind in interstitial cystitis patients when performing simple augmentation. Intuitively, removal of as much diseased or affected bladder would be preferred in patients with interstitial cystitis, and therefore, partial or subtotal cystectomy with substitution cystoplasty would appear to be a better surgical choice.

Partial Cystectomy and Substitution Cystoplasty

Supratrigonal cystectomy with enterocystoplasty is the preferred surgical choice for patients with small-capacity bladders (<400 cc under general anesthesia) and urinary frequency and urgency related to this small bladder capacity. Patients who have a predominant pain component, especially if it is unrelated to bladder fullness, are not good candidates for partial cystectomy and substitution cystoplasty because they are unlikely to experience symptomatic relief. Patients undergoing partial cystectomy and cystoplasty should also be able to perform intermittent catheterization in order to achieve complete bladder emptying as well as to perform bladder irrigation of the mucus secreted by the bowel segment used.

The patient is given a bowel prep and adequate hydration before surgery and is placed in a supine position. A Foley catheter is placed sterilely in the bladder and connected to a three-way irrigation. The peritoneal cavity is entered through a vertical midline incision, and an appropriate segment of either large or small bowel with a mesentery long enough to reach down to the bladder is selected. The preferred bowel segments are the cecum, sigmoid colon, or ileum. The bladder is filled with irrigant via the three-way irrigation and is then divided in a clam-shell technique, exposing the trigone. Ureteral catheters are placed before resection of the bladder to avoid inadvertent injury to the ureters. Using electrocautery, supratrigonal cystectomy is performed, resecting all but a 1- to 2-cm cuff of bladder that includes the trigone and bladder neck. Hemostasis during the resection is controlled by placement of Allis clamps on the edges of the remaining bladder. The vesicoenteric anastomosis is completed using a two-layer running closure of 3-0 chromic on the mucosa and 2-0 chromic on the muscularis layer. In addition to the Foley, a 22-Fr Malecot suprapubic catheter is left indwelling via a separate “cystotomy” to provide adequate postoperative drainage.

Starting on postoperative day 2, gentle irrigation of the suprapubic tube and Foley catheter is done to prevent obstruction secondary to mucus production from the bowel segment. Patients are usually discharged on postoperative day 7 to 10 when normal bowel function returns. Before discharge, the Foley catheter is removed, and patients are taught how to irrigate via the suprapubic tube. At 3 to 4 weeks postoperatively, a cystogram is performed, and the suprapubic tube is removed if no leakage is noted. Patients are instructed to perform intermittent catheterization to ensure adequate bladder emptying as well as to ensure irrigation of mucus.

An alternative to the supratrigonal cystectomy is a total cystectomy and orthotopic urinary diversion, which has been described in both men and women after cystectomy for bladder cancer . This type of diversion may be a viable alternative to partial cystectomy because less of the affected bladder is left behind.

Total Cystectomy with Urinary Diversion

Total cystectomy with urinary diversion is the treatment option for patients who have failed to respond to all previous conservative treatments or who have failed partial cystectomy and enterocystoplasty. Patients with a significant component of urethral pain are probably better candidates for complete cystectomy and urinary diversion rather than partial cystectomy. The choice of performing a continent versus an incontinent diversion is based mainly on patient preference. As continent diversions have become more popular in recent years, the majority of my patients have preferred this type of urinary diversion. To be considered a candidate for a continent diversion, patients must show a proficiency in performing intermittent catheterization and be highly motivated. The technique of cystectomy and urinary diversion, including complications.

OUTCOMES

Complications

The most serious complication is bladder rupture, but fortunately, this is very uncommon, occurring in fewer than 0.1% of more than 1,500 hydrodistentions performed for the treatment of interstitial cystitis at our institution over the past 8 years. No return of irrigant fluid after distention, or the sudden return of irrigant fluid at the end of bladder filling, or severe suprapubic and/or abdominal pain should alert one to the possibility of a spontaneous bladder rupture. Immediate cystogram should be performed. Prolonged Foley catheter drainage is probably all that is necessary to allow the rupture to heal spontaneously. Any bladder rupture that occurs following instillation of agents such as chlorpactin or silver nitrate probably warrants open exploration with copious irrigation of the site of extravasation because of the severe caustic properties of these agents.

Bladder perforation is more likely to occur following fulguration or excision of interstitial cystitis lesions because the bladder wall is normally quite thin. In addition, bowel injury can occur following aggressive loop resection or injudicious use of laser energy.

Persistence of symptoms is probably the most common and disheartening for both patient and surgeon.

Results

Hydrodistention alone without the addition of intravesical agents relieves the symptoms in up to 30% of patients. The addition of DMSO with or without steroids has been shown to relieve symptoms in about 50% of patients. Similar clinical responses are also seen with chlorpactin and heparin. Interestingly, after intravesical therapy, symptoms may improve, but the cystoscopic appearance of the bladder, regardless of the agent used, typically remains unchanged. The choice of intravesical agent used, and in which order, is not critical to how a patient may respond clinically. It is common for patients to become resistant to one treatment and respond favorably to another treatment. The advantage to DMSO and heparin is that these agents can be administered in the office under topical anesthesia, whereas silver nitrate and chlorpactin almost universally require general or regional anesthesia.

Resection or fulguration in select patients results in clinical improvement in 33% to 80% of patients, with those with Hunner’s ulcers responding more favorably than those patients with focal glomerulations.

The more aggressive, open surgical approaches have shown good results in selected patients. Relief of symptoms in a highly select group of patients undergoing supratrigonal cystectomy and enterocystoplasty has been reported to range between 60% and 90%.6,8 The results of total cystectomy for the treatment of incapacitating interstitial cystitis are varied. Although a significant percentage of this highly select group of patients who undergo cystectomy will experience significant relief, there are reports of patients having persistent pelvic pain despite having undergone complete cystectomy and urethrectomy.

Interstitial cystitis is a difficult disease to treat in a surgical manner aside from hydrodistention and intravesical instillation therapy. Fortunately, the vast majority of patients with interstitial cystitis do not ever have symptoms so severe or incapacitating as to warrant any further invasive surgical intervention aside from hydrodistention. In those few patients who continue to have significant symptoms and who are interested in further surgical intervention, a thorough discussion of treatment options between physician and patient is critical to ensure a satisfactory outcome. Suffice it to say that our basic understanding of this poorly understood disease is still in its infancy, and therefore, proper therapy including surgery is as yet poorly delineated.

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