Pain in Urology

Uronate peaks and urinary hyaluronic acid levels correlate with interstitial cystitis severity.
Lokeshwar VB, Selzer MG, Unwala DJ, Estrella V, Gomez MF, Golshani R, Kester RR, Klumpp DJ, Gousse AE
J Urol. 2006 Sep;176(3):1001-7.

PURPOSE: Levels of uronate, a basic component of urothelial glycosaminoglycans, are increased in urine specimens of patients with interstitial cystitis with severe symptoms. In this study we examined the urinary glycosaminoglycan profile and correlated the profile and urinary hyaluronic acid (a glycosaminoglycan) levels with symptom severity. MATERIALS AND METHODS: Urine specimens and completed O'Leary-Sant interstitial cystitis symptom and problem indexes questionnaires were obtained from 29 patients with interstitial cystitis, 14 normal individuals, and 14 patients with other benign pelvic and bladder conditions. Patients with interstitial cystitis were divided into group 1-1 or both indexes less than 50% maximum score, and group 2-both indexes 50% of maximum score or greater. All patients met the National Institutes of Diabetes and Digestive and Kidney Diseases criteria except regarding glomerulation. In a followup study 30 urine specimens were collected from 8 patients with interstitial cystitis and from 4 normal individuals during 12 months. The urinary glycosaminoglycan profile was determined by gel filtration chromatography. Glycosaminoglycan peaks were analyzed by polyacrylamide gel electrophoresis. Urinary hyaluronic acid levels were determined by the hyaluronic acid test. RESULTS: Group 2 urine specimens contained 3 uronate peaks, whereas urine specimens from normal individuals and patients in group 1 contained 1 or 2 peaks. Peak 1 consisted of macromolecular glycosaminoglycans whereas peaks 2 and 3 contained oligosaccharides. Urinary hyaluronic acid levels were 3 to 4-fold increased in group 2. Glycosaminoglycan profile and hyaluronic acid levels detected interstitial cystitis severity with 83% sensitivity, and 89.7% and 74.4% specificity, respectively. Interstitial cystitis urothelial cells/tissues also over expressed hyaluronic acid synthase 1 (which synthesizes hyaluronic acid) compared to normal urothelial cells/tissues. In the followup study urinary uronate levels, glycosaminoglycan profile and hyaluronic acid levels detected patients with severe symptoms with 73% sensitivity and 87% to 94% specificity. In both studies uronate, glycosaminoglycan profile and hyaluronic acid levels significantly correlated with interstitial cystitis severity (p <0.001). CONCLUSIONS: Urinary glycosaminoglycan profile, uronate content and hyaluronic acid levels are potentially useful markers for monitoring interstitial cystitis severity, and are likely to be involved in interstitial cystitis pathophysiology.

Safety and efficacy of hyperbaric oxygen therapy for the treatment of interstitial cystitis: a randomized, sham controlled, double-blind trial.
van Ophoven A, Rossbach G, Pajonk F, Hertle L
J Urol. 2006 Oct;176(4):1442-6.

PURPOSE: We conducted a double-blind, sham controlled study to evaluate the safety, efficacy and feasibility of hyperbaric oxygenation for interstitial cystitis. MATERIALS AND METHODS: A total of 21 patients with interstitial cystitis were randomized to 90 minutes treatment in a hyperbaric chamber pressurized with 100% O(2) to 2.4 atmosphere absolute for 30 treatments sessions or 1.3 atmosphere absolute, breathing normal air in the control group. Moderate or marked improvement in a global response assessment questionnaire was defined as treatment response (primary outcomes). Secondary measurements included changes of pain and urgency evaluated by visual analog scales, functional bladder capacity and frequency. Changes in the O'Leary-Sant Interstitial Cystitis Index and rating of overall satisfaction with the therapeutic outcome were also reported. RESULTS: There were 3 of 14 patients on verum and no control patients who were identified as responders (p <0.05). At 12-month followup 3 patients (21.4%) still reported treatment response. Hyperbaric oxygenation resulted in a decrease of baseline urgency intensity from 60.2 +/- 15.0 to 49.9 +/- 35.2 mm at 3 months and decrease of pain intensity from 43.1 +/- 20.5 to 31.2 +/- 19.8 mm, respectively (p <0.05). The Interstitial Cystitis Symptom Index score sum decreased from 25.7 to 19.9 points in patients on verum. Sham treatment did not result in improvement of the baseline parameters. CONCLUSIONS: A total of 30 treatment sessions of hyperbaric oxygenation appear to be a safe, effective and feasible therapeutic approach to interstitial cystitis. In the treatment responders application of hyperbaric oxygenation resulted in a sustained decrease of interstitial cystitis symptoms with a discordant profile regarding the peak amelioration of the various interstitial cystitis symptoms compared with a normobaric, normoxic sham treatment.

July

Churg-Strauss syndrome presenting with eosinophilic prostatitis.
Kiyokawa H, Koyama M, Kato H
Int J Urol. 2006 Jun;13(6):838-40.

We report a patient with eosinophilic prostatitis associated with Churg-Strauss syndrome. A 74-year-old man, who had been treated for asthma, underwent transurethral resection of the prostate. After the operation he had a high temperature of approximately 40 degrees C. The differential blood count revealed marked eosinophilia of 77.5%. The patient received 20-mg prednisolone and dramatically became afebrile. The pathological diagnosis was eosinophilic prostatitis. These findings strongly indicate Churg-Strauss syndrome.

Symphysitis following transrectal biopsy of the prostate.
Adam C, Graser A, Koch W, Trottmann M, Rohrmann K, Zaak D, Stief C
Int J Urol. 2006 Jun;13(6):832-3.

Transrectal ultrasound-guided needle biopsy of the prostate is a widely accepted technique to obtain prostatic tissue for histological examination. Severe complications are rarely seen. We report a case of symphysitis causing hospitalization and severe pain and discomfort of the patient. Possible etiologic factors are traumatic osseous lesions and transport of rectal bacteria to the periosseous region. Especially in small prostates, care should be taken to avoid this condition. Prolonged perioperative antibiotic prophylaxis is mandatory.

June

Prevalence of prostatitis-like symptoms in a managed care population.
Clemens JQ, Meenan RT, O'keeffe-Rosetti MC, Gao SY, Brown SO, Calhoun EA
J Urol. 2006 Aug;176(2):593-6.

PURPOSE: We calculated the prevalence of symptoms typically associated with chronic prostatitis/chronic pelvic pain syndrome in men in a managed care population in the Pacific Northwest. MATERIALS AND METHODS: A questionnaire mailing to 5,000 male enrollees 25 to 80 years old in the Kaiser Permanente Northwest (Portland, Oregon) health plan was performed. The questionnaires included screening questions about the presence, duration and severity of pelvic pain, and the National Institutes of Health Chronic Prostatitis Symptom Index. Chronic prostatitis/chronic pelvic pain syndrome symptoms were defined in 2 ways: 1) presence of any of the following for a duration of 3 or more months: pain in the perineum, testicles, tip of penis, pubic or bladder area, dysuria, ejaculatory pain; and 2) perineal and/or ejaculatory pain, and a National Institutes of Health Chronic Prostatitis Symptom Index total pain score of 4 or more. Prevalence estimates were age adjusted to the total Kaiser Permanente Northwest male population. RESULTS: A total of 1,550 questionnaires were returned. The prevalence of chronic prostatitis/chronic pelvic pain syndrome symptoms was 7.5% for definition 1 and 5.9% for definition 2. Mean National Institutes of Health Chronic Prostatitis Symptom Index scores were 17 for definitions 1 and 2. Of those with prostatitis-like symptoms, 30% met criteria for having both definitions present. The prevalence of prostatitis-like symptoms using either of the 2 diagnoses was 11.2%. CONCLUSIONS: This population based study indicates that approximately 1 in 9 men have prostatitis-like symptoms. Application of 2 different definitions for prostatitis-like symptoms identified unique groups of men, with limited overlap in the groups.

Neonatal urinary bladder inflammation produces adult bladder hypersensitivity.
Randich A, Uzzell T, Deberry JJ, Ness TJ
J Pain. 2006 Jul;7(7):469-79.

Inflammatory events experienced during early development may permanently alter sensory processing. Because urinary tract infections frequently occur during early development in females and painful bladder disorders have a high female prevalence, the present studies were undertaken to determine whether inflammation of the bladder in female rats could lead to altered sensory processing later in life. Female rat pups were anesthetized and treated as neonates (14th-16th days of life) or as adolescents (28th-30th days of life) with either intravesical zymosan (yeast cell wall component that produces robust inflammation), intravesical normal saline, or only with anesthesia. As adults, rats that had their bladders inflamed as neonates exhibited increased spontaneous micturition frequency and, after reinflammation of the bladder, increased cardiovascular and abdominal muscle contractile responses to urinary bladder distension when compared with controls. Similar effects were not observed in rats which did not experience inflammation of the bladder until adolescence. Evan's blue extravasation, a measure of the magnitude of inflammatory changes, was also greater in rats treated as neonates with intravesical zymosan. Thermal and mechanical hindpaw sensitivity was not altered by bladder inflammation. Altogether, this suggests that neonatal bladder inflammation increases bladder sensitivity and may be a cause of the hypersensitivity of painful bladder syndromes. PERSPECTIVE: The present study observed that bladder inflammation experienced in a neonatal rat led to accentuated responses to urinary bladder distension when tested as adults. This suggests that events experienced during development may permanently sensitize visceral sensory systems and so represent one of the causes of painful bladder disorders.

Using the International Continence Society's definition of painful bladder syndrome.
Warren JW, Meyer WA, Greenberg P, Horne L, Diggs C, Tracy JK
Urology. 2006 Jun;67(6):1138-42; discussion 1142-3.

OBJECTIVES: To determine what proportion of patients with recent-onset interstitial cystitis (IC)/painful bladder syndrome (PBS) met the International Continence Society (ICS) definition and how those who met the definition differed from those who did not. METHODS: We recruited women who had recent-onset IC/PBS for an ongoing case-control study to identify its risk factors and studied our first 138 eligible patients to identify those who met the ICS definition. We then compared those who met the definition with those who did not by variables acquired from interviews and medical records. RESULTS: The 138 participants had intensities of pain, urgency, frequency, and nocturia, as well as O'Leary-Sant Symptom Index scores, similar to those of previously reported patients with IC/PBS. Six percent of cystoscopies demonstrated Hunner's ulcers, and 89% of hydrodistensions under anesthesia revealed glomerulations. The most liberal interpretation of the ICS definition did not include 47 (34%) of our patients. Comparing these with the 91 (66%) who did meet the ICS criteria, we found that 96 of 97 clinical variables, including many generally thought to be characteristic of IC/PBS, were not significantly different between the two groups. CONCLUSIONS: The ICS definition identified only 91 (66%) of the 138 patients whom study investigators and caregivers diagnosed as having IC/PBS. Furthermore, those who met the ICS definition did not differ in important ways from those who did not. These observations taken together suggest that the ICS definition may not be sufficiently sensitive. Minor modifications of the definition appeared to increase its sensitivity. Validation of a case definition (ie, assessing its sensitivity and specificity) would require testing it in patients with IC/PBS, as well as in patients with other diseases with similar symptoms.

Is interstitial cystitis an allergic disorder?: A case of interstitial cystitis treated successfully with anti-IgE.
Lee J, Doggweiler-Wiygul R, Kim S, Hill BD, Yoo TJ
Int J Urol. 2006 May;13(5):631-4.

Interstitial cystitis (IC) is a chronic disorder diagnosed by symptomatology of pelvic pain and urinary frequency, which are extremely variable and unpredictable fluctuating among patients. IC has recently been found combined with some allergic disorders and histopathologic abnormalities resembling that of allergic disorders, including mast cell activation, histamine release and eosinophil infiltration. Therefore, it could be cautiously postulated that IC is one of the allergic disorders of the urogenital system. A 28-year-old Caucasian female patient, who was diagnosed with asthma and allergic rhinitis, suffered from bladder symptoms of frequency, urgency and pelvic pain for the past 3 years. The symptoms disturbed her every day and were intractable for treatment. Urologists concluded that she had interstitial cystitis. Specific immunotherapy (SIT) was recommended for her allergic symptoms. While taking specific immunotherapy, she had anaphylaxis. She still had the reaction even with the 1000-fold diluted shot of SIT. Omalizumab was used for her allergic symptoms and possible prevention of anaphylactic reaction to SIT. Interestingly, she reported that her urogenital symptoms had subsided since omalizumab had been started. According to the published literature, we postulate that interstitial cystitis might be one of the IgE mediated, mast cell driven allergic disorders of the urogenital system. Therefore, in this case, the patient's bladder symptoms are successfully controlled primarily by anti-IgE therapy and the improvement could be maintained by SIT. We report, for the first time, a case of interstitial cystitis with allergic rhinitis and asthma, successfully treated by anti-IgE therapy and specific immunotherapy.

May

[Bladder endometriosis. Case report and bibliographic review]
Canovas Ivorra JA, Castillo Gimeno JM, Michelena Barcena J, Alberto Ramirez D, Vera Roman J
Arch Esp Urol. 2006 Apr;59(3):290-2.

OBJECTIVE: To report a new case of bladder endometriosis and to perform a bibliographic review. METHODS: We report the case of a 34-year-old female with the diagnosis of bladder endometriosis treated by transurethral resection and subsequent hormonal therapy with good outcome one year after diagnosis. RESULTS: Treatment with analogs was started after TUR, in conjunction with the Gynecology Department, and maintained six months. The patient remained asymptomatic one year after diagnosis, with a negative cystoscopic study. CONCLUSIONS: We emphasize the need of early diagnosis due to the increased morbidity and health-care expenses; also the need of surgical treatment of all urological lesions before any hormonal therapy, mainly ureteral lesions. We finally emphasize that definitive treatment should be performed by the gynecologist.

Assessment of efficacy of transcutaneous electrical nerve stimulation for pain management during office-based flexible cystoscopy.
Hruby G, Ames C, Chen C, Yan Y, Sagar J, Baron P, Landman J
Urology. 2006 May;67( 5):914-7.

OBJECTIVES: To evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) for its effectiveness in eliminating or minimizing discomfort during office-based flexible cystoscopy. METHODS: A total of 148 patients were prospectively randomized into one of three groups: flexible cystoscopy with no analgesics, a placebo TENS, or an activated TENS. The patient data collected included patient parameters, number of previous flexible cystoscopies, visual analog pain scores during and after the procedure, surgeon's difficulty rating of procedure, and International Prostate Symptom Score before and 24 hours after the procedure. RESULTS: No statistically significant difference was found among the three groups regarding patient parameters. The visual analog pain scores were similar before and after the procedure. At 30 seconds, the mean visual analog scale score for the control group, placebo group, and TENS study group was 3.73, 3.65, and 3.52, respectively (control versus placebo, control versus active, and placebo versus active: P = 0.97, 0.29, and 0.53, respectively). At 1 and 5 minutes, the corresponding scores were 3.44, 4.37, and 3.50 (P = 0.88, P = 0.99, and P = 0.99) and 0.86, 1.23, and 0.88 (P = 0.97, P = 0.35, and P = 0.56), respectively. The surgeon's mean difficulty rating for the control procedures was 1.08 and for the placebo group was 2.30 (P = 0.02). CONCLUSIONS: All patients undergoing flexible cystoscopy in the office setting experienced discomfort. The TENS device provided no significant benefit for pain. The trend toward greater pain scores in the control group could be attributed to the greater degree of difficulty.

Increased prevalence of interstitial cystitis in women with detrusor overactivity refractory to anticholinergic therapy.
Wein AJ
J Urol. 2006 Jun;175(6):2209.

Is the potassium sensitivity test a valid and useful test for the diagnosis of interstitial cystitis?
Wein AJ
J Urol. 2006 Jun;175(6):2208-9.

Argument for the use of potassium sensitivity test in the diagnosis of interstitial cystitis.
Wein AJ
J Urol. 2006 Jun;175(6):2208-9.

Treatment of interstitial cystitis with Systistat: a hyaluronic acid product.
J Urol. 2006 Jun;175(6):2207-8.

Critical appraisal of dimethyl sulfoxide treatment for interstitial cystitis: discomfort, side-effects and treatment outcome.
Wein AJ
J Urol. 2006 Jun;175(6):2207-8.

How Does the Pre-Massage and Post-Massage 2-Glass Test Compare to the Meares-Stamey 4-Glass Test in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome?
Nickel JC, Shoskes D, Wang Y, Alexander RB, Fowler JE Jr, Zeitlin S, O'leary MP, Pontari MA, Schaeffer AJ, Landis JR, Nyberg L, Kusek JW, Propert KJ
J Urol. 2006 Jul;176(1):119-124.

PURPOSE: The Meares-Stamey 4-glass test is the standard method of assessing inflammation and the presence of bacteria in the lower urinary tract in men presenting with the chronic prostatitis syndrome. However, most urologists do not use it in daily practice because of the time and difficulty in performing it, as well as the additional expense. We evaluated a simpler test, the 2-glass pre-massage and post-massage test, and compared it with the Meares-Stamey 4-glass test to detect inflammation and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: The study population included 353 men enrolled in the National Institutes of Health Chronic Prostatitis Cohort study with baseline leukocyte counts and 2-day bacterial cultures on specimens obtained from a standard 4-glass test (VB1, VB2, expressed prostatic secretions, VB3). The chi-square test was performed to assess associations of white blood cell counts in expressed prostatic secretions and VB3. A receiver operating characteristic curve was constructed to determine the optimal cut point of white blood cells in VB3 in predicting white blood cells in expressed prostatic secretions. Sensitivity and specificity of VB3 cultures predicting expressed prostatic secretions and positive Meares-Stamey results were calculated from 2 x 2 contingency tables. RESULTS: Analysis of binary leukocyte outcomes (no white blood cells vs any white blood cells) suggests that white blood cells tend to be present in expressed prostatic secretions when there are any white blood cells in VB3, p <0.0001, the optimal cut point being white blood cell counts of 3 in VB3 (best predictive ability with area under ROC 0.771) to predict 5+ in expressed prostatic secretions with a sensitivity of 76% and specificity of 70%. The optimal cut point of white blood cells in VB3 to predict 10 white blood cells in expressed prostatic secretions was 4 (62% sensitivity and 75% specificity). Uropathogens localizing to expressed prostatic secretions or VB3 confirms a positive 4-glass Meares-Stamey localization test. The sensitivity and specificity of a VB3 localizing culture only in predicting a positive Meares-Stamey 4-glass test result for any uropathogen were 44% to 54% (depending on definition) and 100%, respectively. The pre-massage and post-massage test predicted a correct diagnosis in more than 96% of subjects. CONCLUSIONS: The value of localizing leukocytes and uropathogens to prostate specific specimens remains controversial in chronic heavily pretreated patients, but these data may help direct therapy (anti-inflammatory or antimicrobial) when obtained at first presentation. The pre-massage and post-massage test has strong concordance with the 4-glass test and is a reasonable alternative when expressed prostatic secretions are not obtained.

Correlation between ultrasound alterations of the preprostatic sphincter and symptoms in patients with chronic prostatitis-chronic pelvic pain syndrome.
Dellabella M, Milanese G, Muzzonigro G
J Urol. 2006 Jul;176(1):112-8.

PURPOSE: We investigated ultrasound alterations of the preprostatic sphincter in patients with chronic prostatitis-chronic pelvic pain syndrome. We evaluated the frequency of these alterations, standardized their ultrasound measurement and correlated them with symptoms in patients with chronic prostatitis-chronic pelvic pain syndrome. MATERIALS AND METHODS: In 37 patients with chronic prostatitis-chronic pelvic pain syndrome and 23 healthy volunteers certain parameters were measured by transrectal ultrasound, including prostate volume, hypoechoic periurethral zone volume, posterior prostate lip thickness, bladder neck thickness, detrusor thickness and the degree of echogenicity of the anterior fibromuscular stroma. All patients were evaluated with the International Prostate Symptom Score and National Institutes of Health Chronic Prostatitis Symptom Index. Urinary flow rate and post-void residual urine volume were also considered in each patient. All assessments were done independently and consecutively by 3 operators. RESULTS: A hypoechoic periurethral zone volume was found in 36 of 37 patients with chronic prostatitis-chronic pelvic pain syndrome. No significant intra-observer and interobserver differences were found in ultrasound parameter measurements. In the chronic prostatitis-chronic pelvic pain syndrome group ultrasound findings showed greater post-void residual urine volume, detrusor thickness and hypoechoic periurethral zone volume, increased posterior prostate lip thickness and bladder neck thickness, and greater anterior fibromuscular stroma hyperechogenicity. On multivariate analysis hypoechoic periurethral zone volume was an independent predictive factor for worse National Institutes of Health Chronic Prostatitis Symptom Index pain, urinary and total scores. Posterior prostate lip thickness was the only factor predictive of a worse International Prostate Symptom Score in patients with chronic prostatitis-chronic pelvic pain syndrome. A hypoechoic periurethral zone volume, posterior prostate lip thickness and bladder neck thickness with calculated threshold values revealed fair to excellent accuracy for identifying a patient with chronic prostatitis-chronic pelvic pain syndrome. CONCLUSIONS: Ultrasound evaluation of the bladder neck-posterior urethra in patients with chronic prostatitis-chronic pelvic pain syndrome led us to identify a set of lesions that cannot be found in healthy subjects. The measurement of hypoechoic periurethral zone volume, posterior prostate lip thickness and bladder neck thickness could be useful for following patients with chronic prostatitis-chronic pelvic pain syndrome and maybe for better understanding the complicated pathophysiological mechanisms of chronic nonbacterial prostatitis.

Heat/burning sensation induced by topical application of capsaicin on perineal cutaneous area: new approach in diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome?
Turini D, Beneforti P, Spinelli M, Malagutti S, Lazzeri M
Urology. 2006 May;67(5):910-3.

OBJECTIVES: To investigate the feasibility, safety, and efficacy of perineal cutaneous application of capsaicin as a test for the diagnosis, as well as a potential therapeutic tool, in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: We recruited 22 patients (mean age 34.5 years, range 19 to 56), who had been diagnosed with CP/CPPS according to the National Institutes of Health criteria, and 6 healthy control subjects. Both groups received a topical application of 5 mL capsaicin at a concentration of 10(-5) M to the perineal body skin. The patients were asked to mark on a visual analogue scale the intensity of any heat or burning sensation. All the patients had completed a National Institutes of Health Chronic Prostatitis Symptom Index before and 1 week after the test. The scores of the two groups were compared using the Mann-Whitney U test. RESULTS: The patients with CP/CPPS reported a heat/burning sensation intensity that was statistically greater than that of the healthy controls (7.5 versus 4.3, P <0.001) and a shorter time to heat sensation onset and maximal intensity (1.5 versus 3.4 minutes, P <0.001, and 2.5 versus 7 minutes, P <0.001, respectively). Of the 22 patients, 16 reported an improvement of symptoms after 7 days and the mean National Institutes of Health Chronic Prostatitis Symptom Index score decreased from 27 to 16 (P <0.01). CONCLUSIONS: We found a statistically significant difference in the pain visual analogue scale and interval between topical application and the onset of the heat/burning sensation between patients with CP/CPPS and healthy controls. The small sample size strongly suggests the need for additional larger and more controlled studies.

April

[Bladder endometriosis. Report of two cases and bibliographic review, with special focus on Spanish articles]
Pastor Navarro H, Donate Moreno MJ, Gimenez Bachs JM, Pastor Guzman JM, Polo Ruiz L, Atienzar Tobarra M, Salinas Sanchez A, Virseda Rodriguez JA

Arch Esp Urol. 2006 Mar;59(2):111-22.
OBJECTIVES: To study and review the etiopathogenic hypothesis for endometriosis and the clinical features, diagnosis and treatment of bladder endometriosis. METHODS/RESULTS: We report two cases and review the international bibliography, collecting the cases published by Spanish authors. CONCLUSIONS: Bladder endometriosis is a rare pathological entity, but its diagnosis should be considered in fertile women with urinary tract symptoms during menstruation. Diagnosis is obtained by various imaging tests (ultrasound, CT scan, MRI), and is confirmed with cystoscopy and biopsy. The treatment may be surgical (TUR, partial cystectomy) and/or medical (hormonal).

Multimodal therapy for painful bladder syndrome/interstitial cystitis.
Dell JR, Butrick CW
J Reprod Med. 2006 Mar;51(3 Suppl):253-60.

Most patients who suffer from PBS/IC can now be simply and effectively treated. The first step to successful management is accurate and timely diagnosis, which has become easier with available and validated screening and diagnostic tools such as PUF and PST. Once PBS/IC is correctly diagnosed, prompt treatment should address the main components of the disease, a dysfunctional urothelium, mast cell activation and neural upregulation. Multimodal treatment that has shown benefit includes oral PPS plus an antihistamine, such as hydroxyzine, and a TCA, such as amitriptyline. Behavioral interventions and intravesical instillation therapy are adjunctive measures that will promote symptom relief. Intravesical "rescue" solutions using lidocaine and heparin or PPS (dissolved in water or in the instillation solution [off-label use of PPS]) can provide immediate relief while patients develop a response to oral PPS. Patient education and support are critical in managing this complex but treatable disorder.

Current issues in the diagnosis of painful bladder syndrome/interstitial cystitis.
Evans RJ, Stanford EJ
J Reprod Med. 2006 Mar;51(3 Suppl):241-52.

PBS/IC, which was traditionally thought to be a rare condition, is increasingly thought to be a frequent cause of CPP. Failure to consider the bladder as a component of this pain is common, primarily because of the similarity in symptoms to other urogynecologic conditions. The diagnosis of PBS/IC has been one of exclusion; as a result, PBS/IC is frequently misdiagnosed as urogenital infection, OAB or endometriosis, among other conditions with similar symptomatology. Such misdiagnosis results in unnecessary and ineffective pharmacologic or even surgical interventions. Diagnosis of PBS/IC and appropriate management early in the disease process afford women a better outcome and a better quality of life. Making PBS/IC a diagnosis of inclusion is necessary to attain this goal. Two additions to the diagnostic armamentarium, the PUF Patient Symptom Scale and the PST, can help to identify women whose presenting complaints of CPP might have a bladder component. The high correlation between these 2 tools allows clinicians to administer the noninvasive PUF questionnaire as an initial screening device to identify women suspected of having IC. If PBS/IC is diagnosed early in the disease process, it can be treated successfully in most patients.

Proposed pathogenesis of painful bladder syndrome/interstitial cystitis.
Sand PK
J Reprod Med. 2006 Mar;51(3 Suppl):234-40.

Chronic pelvic pain in women: Focus on painful bladder syndrome/lnterstitial cystitis.
Mishell DR Jr
J Reprod Med. 2006 Mar;51(3 Suppl):225-6; quiz 261-2.

March

Primary evaluation of patients suspected of having interstitial cystitis (IC).
Wein AJ
J Urol. 2004 Dec;172(6 Pt 1):2494-5.

Hyperbaric oxygen for the treatment of interstitial cystitis: long-term results of a prospective pilot study.
Wein AJ
J Urol. 2004 Dec;172(6 Pt 1):2496.

Caecocystoplasty for intractable interstitial cystitis: long-term results.
Wein AJ
J Urol. 2004 Dec;172(6 Pt 1):2495-6.

What is the pain of interstitial cystitis like?
FitzGerald MP, Brensinger C, Brubaker L, Propert K
Int Urogynecol J Pelvic Floor Dysfunct. 2006 Jan;17(1):69-72. Epub 2005 Jul 2.

To describe the characteristics of pain experienced by patients with interstitial cystitis (IC) in terms of pain site, severity, and character, we performed a secondary analysis of data from the IC database (ICDB), which was a prospective, longitudinal, cohort study of IC patients. We analyzed the cross-sectional baseline data from 629 patients who had a completed baseline symptom questionnaire. Patients answered questions about whether they had pain or discomfort associated with urinary symptoms over the past 4 weeks and if so, about the location, characteristics, intensity, and frequency of their pain. Logistic regression examined associations between pain location and the presence of urinary symptoms. Analyses were performed using SAS version 8.2 (SAS Institute, Cary, NC, USA) and considered significant at the 5% level. Five hundred and eighty-nine (94%) patients with a mean age of 45 years (SD 14 years) reported baseline pain or discomfort associated with their urinary symptoms. The most common baseline pain site was lower abdominal (80%), with urethral (74%) and low back pain (65%) also commonly reported. The majority of patients described their pain as intermittent, regardless of the pain site. Most patients reported moderate pain intensity, across all pain sites. There was a statistically significant link between pain in the urethra, lower back, and lower abdomen, and urinary symptoms. Patients with IC report pain at several sites other than the bladder, possibly arising from the previously well-described myofascial abnormalities of pelvic floor and abdominal wall present in patients with IC and other chronic pelvic pain syndromes.

Risk factors for painful bladder syndrome in women seeking gynecologic care.
Kennedy CM, Bradley CS, Galask RP, Nygaard IE
Int Urogynecol J Pelvic Floor Dysfunct. 2006 Jan;17(1):73-8. Epub 2005 Jul 2.

The aim of this cross-sectional study was to report risk factors for painful bladder syndrome in women. We surveyed 645 women presenting for care to general gynecology clinics and a vulvar specialty clinic using a standardized questionnaire and validated outcome measures. We used two definitions for painful bladder syndrome, based on the O'Leary-Sant interstitial cystitis symptom and problem indices. Of those women surveyed, 29.5% met broader criteria and 8.5% met more restrictive criteria for painful bladder syndrome. After adjusting for confounders, bladder pain was significantly associated with current smoking, irritable bowel syndrome, and a generalized pain disorder. Tobacco use, the only modifiable association noted on multivariate analysis, has not been previously identified to our knowledge.

January

Symptoms and cystoscopic findings in patients with untreated interstitial cystitis.
Lamale LM, Lutgendorf SK, Hoffman AN, Kreder KJ
Urology. 2006 Jan 24;.

OBJECTIVES: To examine the relationships between symptoms and cystoscopic findings in women newly diagnosed with interstitial cystitis who had not previously received treatment. METHODS: Twelve newly diagnosed and not previously treated women with interstitial cystitis completed a bladder symptom questionnaire the day before undergoing cystoscopy, hydrodistension, and biopsy. The daily voiding frequency was reported. Cystoscopic findings were converted to a numerical scale, and the data were analyzed using Pearson correlations. RESULTS: Pain symptoms had consistent positive correlations with the cystoscopic findings. An increase in pain with bladder filling was associated with inflammation (P = 0.011), ulceration, and smaller bladder capacity. Pain relief after voiding correlated with smaller bladder capacity (P = 0.019), hematuria, and total cystoscopic score. Pain intensity in the urethra was related to ulceration and hematuria, and pain in the lower abdomen was related to a smaller bladder capacity (P = 0.047), glomerulations, and a larger total cystoscopic score. Daytime frequency correlated negatively with most cystoscopic findings, and nocturnal frequency had a positive relationship with most cystoscopic findings and was significantly associated with a smaller bladder capacity (P = 0.010). Urgency showed no strong associations with any cystoscopic findings. CONCLUSIONS: In patients with untreated interstitial cystitis, a strong correlation between pain and cystoscopic findings was observed. The differences between our results and those of previous studies that found no relationship between symptom reports and cystoscopic findings suggest possible effects of treatment on pain perception and therapeutic influence on cystoscopic findings.

Responsiveness of symptom scales for interstitial cystitis.
Propert KJ, Mayer RD, Wang Y, Sant GR, Hanno PM, Peters KM, Kusek JW
Urology. 2006 Jan;67(1):55-9.

OBJECTIVES: To evaluate the responsiveness of composite scales to change over time in a clinical trial of patients with interstitial cystitis (IC). The measurement of symptoms in IC includes the O'Leary-Sant Symptom and Problem Indexes and the University of Wisconsin Interstitial Cystitis Inventory and scales that measure the individual symptom domains of pain/discomfort, urgency, and voiding frequency. METHODS: The data were derived from a randomized clinical trial conducted by the Interstitial Cystitis Clinical Trials Group. Participants met the National Institutes of Health-National Institute for Diabetes, and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency. The primary endpoint was a patient-reported global response assessment (GRA) at 24 weeks. Secondary endpoints included the three composite indexes, pain/discomfort and urgency, and 24-hour frequency. Responsiveness was assessed by comparing symptom score changes against response categories defined by the GRA. RESULTS: Of the 121 subjects in the original trial, 94 with complete data were included. All three composite indexes were sensitive to subject improvement over time as measured by the GRA. A 1.2-point change in the O'Leary-Sant indexes and a 3.1-point change in the Wisconsin IC inventory corresponded to a one-category change in the GRA. Individual symptoms were also responsive. The correlation was high among the changes in the six outcome measures. CONCLUSIONS: The three composite symptom scales are responsive to change over time in patients with IC. These indexes provide important insight into symptom changes and are recommended as secondary endpoints in future clinical trials of IC. Additional endpoints addressing individual symptom domains should also be considered to aid in the evaluation of effect mechanisms.

Interstitial cystitis versus detrusor overactivity: a comparative, randomized, controlled study of cystometry using saline and 0.3 M potassium chloride.
Philip J, Willmott S, Irwin P
J Urol. 2006 Feb;175(2):566-70; discussion 570-1.

PURPOSE: We compared cystometric findings in interstitial cystitis and detrusor overactivity using 0.3 M KCl and 0.9% normal saline. MATERIALS AND METHODS: Female patients with established diagnoses of IC (7 patients according to NIDDK criteria) and urodynamically proven DO (10 patients) underwent consecutive cystometrograms using 0.9% normal saline and 0.3 M KCl, the order of which was randomized for each patient. Individual CMGs were performed by separate investigators, and patients and investigators were blinded to the order in which the solutions were used and to the results of the other CMG. The results were analyzed on a comparative basis using a 2-tailed t test for comparison of the means and a Kolmogorov-Smirnov z test was used for group comparison. A ROC curve was used to plot sensitivity to the false-positive rate. RESULTS: Irrespective of the diagnosis or the type of infusion used, the volume at FDV was slightly lower with the first CMG compared to the second (mean 76.1 vs 94.2 ml) but did not reach statistical significance (p = 0.20). However, Cmax was similar for first and second CMGs (mean 214 vs 213.2 ml, p = 0.98). Although lower with KCl, there was no significant difference in FDVs obtained with either solution (mean 78.2 vs 92.2 ml for KCl and NS, respectively, p = 0.33). However, KCl produced a significant reduction in Cmax across the whole group (mean 244.5 vs 182.7 ml, p = 0.008). This was most marked in the DO group in which there was a 23% reduction in Cmax with KCl compared to NS, while the IC group showed only a 15% reduction in mean Cmax. The ROC curve, comparing Cmax values for NS with KCl cutoff values of 15% and 30%, resulted in poor positive predictive values (51% and 66%, respectively) for comparative cystometry in distinguishing IC from DO. CONCLUSIONS: The 0.3 M KCl reduces Cmax in IC and DO, the effect being more pronounced in DO. Urothelial hyperpermeability is not specific to IC. Comparative cystometry using NS and 0.3 M KCl does not help to differentiate IC from DO.

Is the potassium sensitivity test a valid and useful test for the diagnosis of interstitial cystitis? Against.
Hanno P
Int Urogynecol J Pelvic Floor Dysfunct. 2005 Nov-Dec;16(6):428-9. Epub 2005 Apr 15.

Argument for the use of the potassium sensitivity test in the diagnosis of interstitial cystitis. For.
Parsons CL
Int Urogynecol J Pelvic Floor Dysfunct. 2005 Nov-Dec;16(6):430-1. Epub 2005 Jun 2.

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