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Abstract

Painful bladder syndrome/interstitial cystitis is a disabling disease of the urinary bladder that mainly affects women. It is of unknown etiology and can appear in all age groups. The main symptoms – bladder pain and urinary frequency – may completely govern the life of the unlucky person suffering from the disease. Treatment includes diet, behavioral modifications, medical treatments, inclusive specific-pain treatment and surgery, but it is unfortunately often insufficient. The disease is rare and lacks a specific definition as well as proper diagnostic criteria. Surgical treatments include neuromodulation, transurethral surgery, bladder augmentation and urinary diversion with or without cystectomy. This article examines the documentation, or lack of, for the often drastic surgical procedures performed to improve quality of life in patients with this disorder.

Keywords

cystectomy cystoplasty interstitial cystitis neuromodulation painful bladder syndrome surgery treatment urinary diversion

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a disease of the bladder characterized by pain in the bladder during filling, which is relieved by voiding, leading to frequent voiding day and night. Some patients have to void up to 50 times/day and night. It is easily understandable that voiding this often has a major impact on quality of life (QoL) for the unfortunate patient suffering from this disease. However, it differs among patients to what degree frequent voiding, pain or both are the most bothersome symptoms.

The diagnostic criteria for IC have been under heated debate during the last 5 years. From this discussion, it has become evident that it is not currently possible to define any useful diagnostic test for making the diagnosis of IC. At an International Consultation on Incontinence in 2005 (Monte Carlo, Monaco), the Committee on PBS (including IC) [1] therefore agreed to follow the definition of the International Continence Society [2], that PBS is the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms, such as increased daytime and night-time frequency, in the absence of proven infection or other obvious pathology. IC is a specific diagnosis and requires confirmation by typical cystoscopic and histological features.

This means that the diagnosis of PBS is clinical, based on symptoms and exclusion of other diseases by specific investigations for those diseases. The diagnosis of IC demands a diagnosis of PBS plus cystoscopic and/or morphological changes in the bladder consistent with the diagnosis.

It is evident that attempts to examine the prevalence of this disease have been hampered by the lack of a definition. In 1975, Oravisto reported a prevalence of 10/100,000 for both genders and 18/100,000 for women in Finland [3]. Held and colleagues reported a prevalence of 30/100,000 [4] and Jones and Nyberg a prevalence of 501/100,000 for both genders and 865/100,000 for women [5]. These differences mostly reflect differences in definition. A more recent questionnaire-based study found a prevalence of 450/100,000 in women in Finland [6], which might be a more precise estimate of the prevalence of PBS. Clemens and colleagues calculated the prevalence of physician-diagnosed IC to 197/100,000 women and 41/100,000 men [7].

The influence of PBS/IC on QoL has been evaluated by Koziol and colleagues, who demonstrated a significant negative effect on ability to travel, employment, leisure activities and sleep [8]. Michael and colleagues found that the QoL in females with IC was especially affected in the psychosocial dimensions, such as vitality and mental health [9].

Treatment

To find and document effective treatments of a relatively rare disease with no clear clinical definition is a difficult task. Many treatments are anecdotal or based on empiric data and proper prospective, randomized, controlled studies are the exception, not the rule. Treatment includes behavioral treatments, diets, oral medications, bladder dilatation and bladder irrigation directed against the frequent voiding and/or pain. Only when all these treatments have failed is surgery considered. Surgery includes surgery on the nervous system and the bladder.

Surgery on the nervous system

Old methods, such as sympathetic denervation [10], parasympathetic denervation [11] and cystolysis [12,13] have now been abandoned. In recent years, neuromodulation and especially sacral neuromodulation have gained some interest.

Neuromodulation

The first report on neuromodulation came from Chai and colleagues in 2000 [14]. The implantation of the InterStim^© sacral nerve stimulator is a two-step procedure. First, a test electrode is placed at the spinal cord level SII (SIII or SIV might be used) and an external stimulator is connected. If test stimulation demonstrates sufficient effect, a permanent electrode and pacemaker are implanted. In the above study, six patients had a test electrode for 5 days. Urinary frequency, urgency and pelvic pain improved dramatically (Table 1). Interestingly, promising urinary markers for PBS/IC, such as heparin-binding epidermal growth factor and antiproliferative factor, also normalized considerably [14]. Maher and colleagues and Whitmore and colleagues found similar results (Tables 2 & 3) [15,16].

Table 1.

Results after sacral nerve stimulation test.

Parameter	Baseline	End point	p-value
Voiding frequency	23.1	10.6	0.0001
Pelvic pain (scale 0–10)	7.0	2.3	0.05
Urgency	6.0	1.8	0.02
Urine HB-EGF (ng/ml)	1.5	11.1	<0.005
APF	−76.1	−4.5	0.005

Results after SNS test stimulation in six patients with PBS/IC.

APF: Antiproliferative factor; HB-EGF: Heparin-binding epidermal growth factor; IC: Interstitial cystitis

PBS: Painful bladder syndrome; SNS: Sacral nerve stimulation.

Adapted from [14].

Table 2.

Results after sacral nerve stimulation test.

Parameter	Baseline	End point	p-value
Voiding frequency	20	11	0.012
Pelvic pain (scale 0–10)	8.9	2.4	<0.001
Urgency	2.4	0.9	0.013

Results after SNS test stimulation in 15 patients with PBS/IC.

IC: Interstitial cystitis; PBS: Painful bladder syndrome; SNS: Sacral nerve stimulation.

Adapted from [15].

Table 3.

Results after sacral nerve stimulation test.

Parameter	Baseline	End point	p-value
Voiding frequency	19.7	12.3	<0.05
Pelvic pain (scale 0–10)	2.2	1.6	<0.05
Urgency	1.8	1.6	0.09

Results after SNS test stimulation in 33 patients with PBS/IC.

IC: Interstitial cystitis; PBS: Painful bladder syndrome; SNS: Sacral nerve stimulation.

Adapted from [16].

In 2003, Comiter reported results after permanent implantation. A total of 17 of 25 patients passed the test period and had a permanent implant. Clinical results are shown in Table 4 [17].

Table 4.

Results of sacral nerve stimulation after permanent implantation.

Parameter	Baseline	End point	p-value
Voiding frequency	21.6	9.8	<0.01
Pelvic pain (scale 0–10)	5.8	1.6	<0.01
Interstitial cystitis symptom index	16.5	6.8	<0.01
Interstitial cystitis problem index	14.5	5.4	<0.01

Clinical results after permant sacral nerve stimulator implant in 17 patients with an average follow-up of 14 months. Adapted from [17].

Peters and Konstandt reported on the decrease in the use of narcotic drugs in patients with refractory IC treated with a permanent sacral stimulator [18]. After a mean follow-up of 15.4 months, 20 patients (95%) reported marked improvement in symptoms. Mean narcotic use decreased from 81.6 to 52 mg/day. Four skipped the use of narcotics completely.

Later results presented at the American Urological Association last year were not so promising. Vaze and colleagues reported on 27 patients with IC [19]. A total of 24 passed test stimulation. After a minimum of 3 months follow-up, the clinical success rate was only 48% (13/27). Peters and colleagues compared pudendal and sacral nerve stimulation and found pudendal nerve stimulation superior, so this might be a better approach in the future [20].

Transcutaneous tibial nerve stimulation has not shown any effect in a small study [21]. In this context, it is worth mentioning that suprapubic or pelvic floor stimulators, although scarcely reported, seem to have yielded better outcomes [22].

Transurethral resection

In his first papers, Hunner described open resection of the bladder ulcer in the treatment of patients with IC [12,23]. He later abandoned this treatment owing to operative morbidity and recurrence of symptoms. Results of transurethral resection were originally reported by Greenberg and colleagues [24] and Fall [25]. The retrospective results of this treatment in a large samples of 116 patients with Hunner's lesion from Fall's clinic were later reported by Peeker and colleagues [26]. Hunner's lesion was first recognized by bladder distension during general anesthesia. All lesions were then resected including at least half of the underlying muscular coat. Large areas of the bladder might be treated to resect all diseased tissue. A total of 92 of the 116 patients experienced amelioration of their symptoms. The average duration of symptom alleviation was 23 months, ranging from 0–180 months. Up to 16 re-resections were performed if symptoms recurred. However, this is the only center that has reported larger clinical series of patients with IC treated in this manner. In 1987, Shanberg and Malloy reported on laser fulguration of 39 patients with IC [27]. A total of 19 had Hunner's lesion, while 20 did not. Of the 19 patients with Hunner's lesion, 17 reported good pain relief lasting between 6 and 18 months. In the 20 patients without Hunner's lesion, reddened areas in the bladder were photocoagulated with the Neodynium: Yag laser. A total of 13 patients experienced a marked improvement of symptoms, but time to possible recurrence was not reported. Small-bowel perforation in two patients was the most important complication in this series. Rofeim and colleagues reported on 24 patients, who all had good results after laser ablation of Hunner's lesion [28]. Pain score decreased from 9.1 to 1.2 and mean voiding interval increased from 30 to 102 min. Although widely referred to as a possible treatment, these are the only centers that have actually reported their results of resection or fulguration of bladder lesions in PBS/IC.

Cystoplasty & urinary diversion

If all other treatments have failed, major surgery may be necessary to relieve patients from their disabling symptoms. This includes bladder augmentation, urinary diversion and partial or total cystectomy. It is essential that a patient has been through an extensive work-up before irreversible surgery is undertaken.

Bladder augmentation

In a small proportion of patients, inflammatory processes in the bladder wall result in severe fibrosis and a contracted bladder with sometimes a very small capacity, even during general anesthesia. These patients often have the most severe frequency, but bladder pain becomes a smaller problem. These are the patients best suited for bladder augmentation, with or without resection of the patient's own bladder [29,30]. Most papers advocate resection of most of the bladder either supratrigonally [31] or including the trigone [32]. Nielsen and colleagues found bladder capacity during general anesthesia to be the best predictor of outcome [33]. Patients with small capacity (200 ml) had good outcomes, while patients with large capacity (525 ml) had poor outcomes. This was also the case in Peeker and colleagues' report, although they ascribed the difference in outcome to whether the patients had classic IC or not [30]. An excellent review by Hohenfellner and colleagues concluded that small bladder capacity during general anesthesia was the best predictor of good outcome after orthotopic bladder substitution [34]. Complications to bladder augmentation/substitution include the need for self catheterization, seen in a significant proportion of patients, especially after ileocystoplasty [31]. In PBS/IC, the need for intermittent catheterization is often an unacceptable outcome due to the hypersensitivity of the bladder base and urethra, making the procedure much too painful. In the chapter on PBS from the 3rd International Consultation on Incontinence, it was concluded that subtrigonal cystectomy with cystoplasty has no outcome advantage over supratrigonal cystectomy, but is associated with more complications and poorer functional bladder rehabilitation [1].

Urinary diversion

In a questionnaire to urologists in the USA, Gershbaum and Moldwin found urinary diversion to be the most common surgical treatment for PBS/IC [35]. It is therefore a little surprising that the literature on the subject is extremely sparse. It is often just mentioned in the text that this is the ultimate treatment to relieve patients from their symptoms and that diversion with or without cystectomy is often successful [33,36,37]. Using the bowel segment from a continent reservoir or an augmentation to create a conduit has been demonstrated successfully [38], the concern being the theoretical risk of continued pain in the converted ileal segment. It is still completely uncertain whether inflammation and fibrosis of the intestine, if observed at all, constitute the usual reaction to exposure to urine or a specific spread of IC [39]. At least six of seven patients with enteroplasty and the bladder remnant left in place in five became pain free [39]. This is interesting, as it has been a subject of discussion whether urinary diversion should be accompanied by simultaneous cystectomy or if cystectomy should be reserved for those patients having persistent pain or intolerable infectious problems from their bladder. The author and colleagues have recently reviewed their experience from the last 5 years. Of 11 patients with PBS/IC, ten became pain free and one had persistent, unchanged pain. This patient later had a cystectomy without any effect on the pain. One patient had a cystectomy due to pyocystos, with good results.

Continent urinary diversion using an intestinal reservoir has become the treatment of choice in patients having a cystectomy due to bladder cancer. It has therefore also been tried in patients with PBS/IC, due to the better QoL with an internal urinary reservoir. However, experience has shown that this is often complicated by the reoccurrence of pain in the intestinal reservoir. Again, the literature on the subject is sparse [40], although chronic inflammatory changes have been observed in the cystoplasty pouch, resembling IC [41,42]. The persistent pain after major irreversible surgery is an enigma and often causes patients to defer surgery for many years. However, in this discussion it must be remembered that two symptoms are the major causes of the poor QoL in these patients: pain and frequency. At least it can always be promised that frequency is alleviated by a urinary diversion, making daily life much easier and making it possible to have a full night's sleep. The author's latest results also seem to demonstrate a very good chance of pain relief [J. Nordling and colleagues, unpublished data].

Conclusion

Currently, the surgical treatment of PBS/IC involves neuromodulation, transurethral resection/fulguration, urinary bladder augmentation and urinary diversion. The literature on these subjects is very scarce and often of limited value, owing to retrospective, uncontrolled studies. Neuromodulation might prove to be beneficial, but results are contradictory and treatment is expensive. Neuromodulation must still be considered experimental. Transurethral resection/fulguration is only reported from a few centers and the effect is temporary, but treatment can be repeated many times. These treatment modalities seem to deserve more attention. Urinary bladder augmentation should be reserved for the burnt-out IC patient with a contracted bladder and urinary frequency as the main problem, while pain is not a significant symptom. Urinary diversion is reserved for the patient whose QoL is more or less destroyed owing to pain and urinary frequency, and who has demonstrated an unsatisfactory response to less invasive treatments. Continent urinary diversion should only be considered in patients with a successful urinary diversion for more than 1–2 years.

Future perspective

The focus on PBS/IC has increased dramatically during the last 3 years, resulting in a variety of new approaches to etiology, pathophysiology and treatment. Promising medical treatment modalities are being tested, as well as neuromodulation and bladder installations. This will lead to better diagnosis and treatments.

Patients with PBS/IC are chronic pain patients, and physicians' awareness of this, as well as better pain treatments already available today, give promise for improving the QoL of these often severely disabled patients. In cases where conservative treatment fails, major surgery should be considered earlier, both to relieve patients' symptoms and to prevent centralization of the pain.

It is probably most important that a better understanding of the disease will lead to an earlier diagnosis, relieving many patients from the frustration of suffering from severe symptoms without being readily believed to have a somatic disease.

Executive summary

Painful bladder syndrome/interstitial cystitis is a chronic, often severely disabling, disease of the urinary bladder.

Treatment

Treatments involve behavioral treatment, diet, oral medications, bladder distension, bladder irrigation and surgery.

Surgery on the nervous system

Old surgical treatments, such as sympathetic denervation, parasympathetic denervation and cystolysis are now abandoned.

Sacral neuromodulation is still under investigation and posterior tibial nerve stimulation has been disappointing in small studies.

Transurethral resection

Transurethral resection or laser fulguration of Hunner's lesions, if present, might be a useful therapeutic option.

Cytoplasty & urinary diversion

Cystoplasty should be performed supratrigonally, but is mainly indicated in end-stage disease (contracted bladder and little pain).

Urinary diversion resolves the problem of frequency and, in a majority of patients, also of pain. Cystectomy is only indicated due to pyocystos or persistent pain.

References

Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

Hanno

Baranowski

Fall

: Painful bladder syndrome (including interstitial cystitis). In: Incontinence. Abrams

Cardozo

Khoury

Wein

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Abrams

Cardozo

Fall

: The standardisation of terminology of lower urinary tract function: report from the standardisation sub-committee of the international continence society Neurourol. Urodyn. 21, 167–178 (2002).

Comprehensive recent review of painful bladder syndrome/interstitial cystitis (PBS/IC)

Oravisto

: Epidemiology of interstitial cystitis. Ann. Chir. Gynaecol. Fenn. 64(2), 75–77 (1975).

Held

Hanno

Wein

: Epidemiology of interstitial cystitis: 2. In: Interstitial Cystitis. Hanno

Staskin

Krane

Wein

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Nyberg

: Prevalence of interstitial cystitis in the United States. J. Urol. 151, 423A (1994) (Abstract).

Leppilahti

Tammela

Huhtala

Auvinen

: Prevalence of symptoms related to interstitial cystitis in women: a population based study in Finland. J. Urol. 168(1), 139–143 (2002).

Clemens

Meenan

Rosetti

Gao

Calhoun

: Prevalence and incidence of interstitial cystitis in a managed care population. J. Urol. 173, 98–102 (2005).

10.

Koziol

Clark

Gittes

Tan

: The natural history of interstitial cystitis: a survey of 374 patients. J. Urol. 149(3), 465–469 (1993).

11.

Michael

Kawachi

Stampfer

Colditz

Curhan

: Quality of life among women with interstitial cystitis. J. Urol. 164(2), 423–427 (2000).

12.

Douglass

: Excision of the superior hypogastric plexus in the treatment of intractable interstitial cystitis. Am. J. Surg. 25, 249–257 (1934).

13.

Moulder

Meirowsky

: The management of Hunner's ulcer by differential sacral neurotomy: preliminary report. J. Urol. 75, 261–262 (1956).

14.

Hunner

: A rare type of bladder ulcer in women; report of cases. Boston Med. Surg. J. 172, 660–664 (1915).

15.

Worth

: The treatment of interstitial cystitis by cystolysis with observations on cystoplasty. A review after 7 years. Br. J. Urol. 52(3), 232 (1980).

16.

Chai

Zhang

Warren

Keay

: Percutaneous sacral third nerve root neurostimulation improves symptoms and normalizes urinary HB-EGF levels and antiproliferative activity in patients with interstitial cystitis. Urology 55(5), 643–646 (2000).

17.

Documents changes in IC markers during sacral nerve stimulation treatment

18.

Maher

Carey

Dwyer

Schluter

: Percutaneous sacral nerve root neuromodulation for intractable interstitial cystitis. J. Urol. 165(3), 884–886 (2001).

19.

Whitmore

Payne

Diokno

Lukban

: Sacral neuromodulation in patients with interstitial cystitis: a multicenter clinical trial. Int. Urogynecol. J. Pelvic Floor Dysfunct. 14(5), 305–308

20.

Comiter

: Sacral neuromodulation for the symptomatic treatment of refractory interstitial cystitis: a prospective study J. Urol. 169(4), 1369–1373 (2003).

21.

Peters

Konstandt

: Sacral neuromodulation decreases narcotic requirements in refractory interstitial cystitis. BJU Int. 93(6), 777–779 (2004).

22.

Vaze

Rackley

Murphy

Hijaz

Daneshgari

Goldman

HVS

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23.

Peters

Konstandt

Huynh

Feber

: Sacral vs. pudendal nerve stimulation for the treatment of interstitial cystitis: a prospective, single blinded, randomized, crossover trial. J. Urol. 173(4), 81 (2005) (Abstract).

24.

Zhao

Nordling

: Posterior tibial nerve stimulation in patients with intractable interstitial cystitis. BJU Int. 94(1), 101–104 (2004).

25.

Fall

Lindstrom

: Transcutaneous electrical nerve stimulation in classic and nonulcer interstitial cystitis. Urol. Clin. North Am. 21(1), 131–139 (1994).

26.

Rarely used treatment with seemingly good long-term results

27.

Hunner

: A rare type of bladder ulcer. Further notes, with a report of eighteen cases. JAMA 70(4), 203–212 (1918).

28.

Greenberg

Barnes

Stewart

Furnish

: Transurethral resection of Hunner's ulcer. J. Urol. 111(6), 764–766 (1974).

29.

Describes transurethral resection of Hunner's ulcer

30.

Fall

: Conservative management of chronic interstitial cystitis: transcutaneous electrical nerve stimulation and transurethral resection. J. Urol. 133(5), 774–778 (1985).

31.

Peeker

Aldenborg

Fall

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32.

Shanberg

Malloy

: Treatment of interstitial cystitis with neodymium: YAG laser. Urology 29(Suppl. 4), 31–33 (1987).

33.

Rofeim

Hom

Freid

Moldwin

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34.

Describes laser treatment of IC

35.

Webster

Maggio

: The management of chronic interstitial cystitis by substitution cystoplasty. J. Urol. 141(2), 287–291 (1989).

36.

Classic paper confirming bladder augmentation is for the contracted bladder

37.

Peeker

Aldenborg

Fall

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38.

van Ophoven

Oberpenning

Hertle

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39.

Nurse

Parry

Mundy

: Problems in the surgical treatment of interstitial cystitis. Br. J. Urol. 68(2), 153–154 (1991).

40.

Nielsen

Kromann-Andersen

Steven

Hald

: Failure of combined supratrigonal cystectomy and Mainz ileocecocystoplasty in intractable interstitial cystitis: is histology and mast cell count a reliable predictor for the outcome of surgery? J. Urol. 144(2 Pt 1), 255–258 (1990).

41.

Hohenfellner

Black

Linn

Dahms

Thuroff

: Surgical treatment of interstitial cystitis in women. Int. Urogynecol. J. Pelvic Floor Dysfunct. 11(2), 113–119 (2000).

42.

Excellent review on surgery for IC

43.

Gershbaum

Moldwin

: Practice trends for the management of interstitial cystitis. Urology 57(6 Suppl. 1), 119 (2001).

44.

Messing

Stamey

: Interstitial cystitis: early diagnosis, pathology, and treatment. Urology 12(4), 381–392 (1978).

45.

Webster

Galloway

: Surgical treatment of interstitial cystitis. Indications, techniques, and results. Urology 29(Suppl. 4), 34–39 (1987).

46.

Elzawahri

Bissada

Herchorn

: Urinary conduit formation using a retubularized bowel from continent urinary diversion or intestinal augmentations: II. Does it have a role in patients with interstitial cystitis? J. Urol. 171, 1559–1562 (2004).

47.

Confirms IC as a disease of the bladder

48.

van Ophoven

: Urinary conduit formation using a retubularized bowel from continent urinary diversion or intestinal augmentations: does it have a role in patients with interstitial cystitis? J. Urol. 173, 1435 (2005).

49.

Yong

Dublin

Pickard

Cody

Neal

N'Dow

: Urinary diversion and bladder reconstruction/replacement using intestinal segments for intractable incontinence or following cystectomy. Cochrane Database Syst. Rev. (1), CD003306 (2003).

50.

Kisman

Nijeholt

van Krieken

: Mast cell infiltration in intestine used for bladder augmentation in interstitial cystitis. J. Urol. 146(4), 1113–1114 (1991).

51.

Baskin

Tanagho

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Surgical Treatment of Painful Bladder Syndrome/Interstitial Cystitis

Abstract

Keywords

Treatment

Surgery on the nervous system

Neuromodulation

Transurethral resection

Cystoplasty & urinary diversion

Bladder augmentation

Urinary diversion

Conclusion

Future perspective

References