Robert M. Moldwin

Interstitial Cystitis/Painful Bladder Syndrome and Associated Medical Conditions With an Emphasis on Irritable Bowel Syndrome, Fibromyalgia and Chronic Fatigue Syndrome

PURPOSE We characterized and compared the impact of clinical phenotypic associations between interstitial cystitis/painful bladder syndrome and controls in relation to potentially related conditions, particularly irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. MATERIALS AND METHODS Female patients with interstitial cystitis/painful bladder syndrome and controls with no interstitial cystitis/painful bladder syndrome completed a biopsychosocial phenotyping questionnaire battery which included demographics/history form, self-reported history of associated conditions, and 10 validated questionnaires focused on symptoms, suffering/coping and behavioral/social factors. RESULTS Questionnaires were completed by 205 patients with interstitial cystitis/painful bladder syndrome and 117 controls matched for age. Prevalence of self-reported associated condition diagnosis in interstitial cystitis/painful bladder syndrome vs controls was irritable bowel syndrome 38.6% vs 5.2%, fibromyalgia 17.7% vs 2.6% and chronic fatigue syndrome 9.5% vs 1.7% (all p <0.001). In the interstitial cystitis/painful bladder syndrome cohort 50.3% reported no other associated condition, 24.4% had interstitial cystitis/painful bladder syndrome + irritable bowel syndrome only, 2.5% had interstitial cystitis/painful bladder syndrome + fibromyalgia only, 1.5% had interstitial cystitis/painful bladder syndrome + chronic fatigue syndrome only, while 20.2% had multiple associated conditions. As the number of associated conditions increased (ie localized, regional, systemic), pain, stress, depression and sleep disturbance increased while social support, sexual functioning and quality of life deteriorated. Anxiety and catastrophizing remained increased in all groups. Symptom duration was associated with this apparent phenotypic progression. CONCLUSIONS Irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome are more prevalent in patients with interstitial cystitis/painful bladder syndrome than in asymptomatic control subjects, and result in significant impact. There are at least 3 distinct clinical phenotypes based on identification of overlapping syndrome patterns. A suggestion that remains to be proven with longitudinal studies is that there may be progression over time from an organ centric to a regional and finally to a systemic pain syndrome with progression of symptom severity, and deterioration of cognitive and psychosocial parameters.

Proof of Concept Trial of Tanezumab for the Treatment of Symptoms Associated With Interstitial Cystitis

PURPOSE In this randomized, double-blind, placebo controlled phase 2 study we investigated tanezumab, a humanized monoclonal antibody that specifically inhibits nerve growth factor as a treatment for interstitial cystitis pain. MATERIALS AND METHODS Patients with interstitial cystitis received a single intravenous dose of 200 μg/kg tanezumab or placebo. Patients recorded daily pain scores (on an 11-point numerical rating scale) 7 days before attending study visits and completed a urinary symptom diary for 3 of those days. Patients also completed the Interstitial Cystitis Symptom Index questionnaire and a global response assessment. The primary end point was change in average daily numerical rating scale pain score from baseline to week 6. Secondary end points included global response assessment, Interstitial Cystitis Symptom Index score, micturition and urgency episode frequency per 24 hours, and mean voided volume per micturition. The incidence of adverse events was also assessed. RESULTS A total of 34 patients received tanezumab and 30 received placebo. At week 6 tanezumab produced a significant reduction from baseline in average daily pain score vs placebo (treatment difference [LS mean, 90% CI] was -1.4 [-2.2, -0.5]). A significantly higher proportion of patients on tanezumab responded as improved in the global response assessment and tanezumab also significantly reduced urgency episode frequency vs placebo. Tanezumab had no significant effect on Interstitial Cystitis Symptom Index score, micturition frequency or mean voided volume per micturition. The most common adverse events were headache (tanezumab 20.6%, placebo 16.7%) and paresthesia (tanezumab 17.6%, placebo 3.3%). CONCLUSIONS Tanezumab has shown preliminary efficacy in the treatment of pain associated with interstitial cystitis.

Psychosocial phenotyping in women with interstitial cystitis/painful bladder syndrome: a case control study.

PURPOSE We characterized and compared psychosocial phenotypes in a female interstitial cystitis/painful bladder syndrome cohort and an age matched cohort without that diagnosis. MATERIALS AND METHODS Female patients with interstitial cystitis/painful bladder syndrome and controls without the condition completed a psychosocial phenotyping questionnaire battery, including a demographics/history form and validated questionnaires focused on a range of presenting symptoms, psychosocial parameters and quality of life. Specific measures included interstitial cystitis symptom and problem index, McGill Pain Questionnaire, Medical Outcomes Study Sleep Scale, Center for Epidemiological Studies Depression Scale, State-Trait Anxiety Inventory, Pain Catastrophizing Scale, Female Sexual Functioning Index and Multidimensional Scale of Perceived Social Support and Medical Outcomes Study Short Form-12 quality of life. Direct comparisons and correlations were made to establish group differences and the strength of associations for psychosocial parameters in patients with interstitial cystitis/painful bladder syndrome. RESULTS Questionnaires completed by 207 patients with interstitial cystitis/painful bladder syndrome were compared to those of 117 controls matched for age, partner status and education. Compared to controls patients reported significantly more pain (total, sensory and affective), worse physical quality of life, increased sleep dysfunction, depression, catastrophizing, anxiety, stress and moderately more sexual/social function problems. These suffering, coping and social parameters correlated with the degree of general pain but stress, anxiety, depression and catastrophizing further correlated with IC specific symptoms and strongly with decreased quality of life. Pain was strongly associated with physical quality of life, while depression, catastrophizing and stress, and to a lesser extent social support were associated with poor mental quality of life. CONCLUSIONS Patients with interstitial cystitis/painful bladder syndrome have significant cognitive and psychosocial alterations compared to controls.

Use of the neodymium: YAG laser for interstitial cystitis: a prospective study.

PURPOSE Interstitial cystitis is a disorder of the bladder characterized by urgency and frequency of urination, and pelvic pain. The classic type of interstitial cystitis is characterized by Hunners ulcers, which are focal regions of severe bladder inflammation. Patients with Hunners ulcers tend to have more severe symptoms and are often refractory to medical management. We present a prospective series of patients who underwent ablative therapy of Hunners ulcers using a neodymium (Nd):YAG laser. MATERIALS AND METHODS A total of 24 patients with interstitial cystitis underwent ablative therapy for Hunners ulcers. Medical therapy had failed in all cases. Using regional or general anesthesia the Nd:YAG laser under cystoscopic control was used to ablate the ulcers. The power setting was 15 W. with a firing duration of between 1 and 3 seconds. The procedure was performed on an outpatient basis. Symptoms were noted preoperatively and postoperatively. RESULTS All patients had symptom improvement within 2 to 3 days. The mean pain scores decreased from 9.1 to 1.2 (p <0.003), the mean urgency score decreased from 8.2 to 1.9 (p <0.003), the mean voiding interval increased from every 30 minutes to every 102 (p <0.0001) and nocturia decreased from a mean of 7.9 voids per night to 2.9 (p <0.0001). There were no complications. Mean followup was 23 months. However, relapse in 11 patients required 1 to 4 additional treatments. The re-treatment response was similar to the initial treatment. CONCLUSIONS Nd:YAG laser ablation of Hunners ulcers is an excellent, minimally invasive method of treating interstitial cystitis. While it is not a cure, it offers patients an opportunity to have decreased symptoms for an extended period and it may be repeated as necessary.

Minimally Invasive Treatment of Renal Abscess

PURPOSE We critically evaluated the most appropriate management of renal abscesses, and identified the set of patients that most benefits from conservative treatment. MATERIALS AND METHODS We retrospectively reviewed charts regarding discharge diagnoses, radiological studies, pathological specimens, epidemiology factors and outcomes. Statistical analysis was performed using loglinear and covariant analysis. RESULTS Nine years of experience (1984 to 1993) at 2 affiliated hospitals (1 public and 1 private) were reviewed. A total of 52 patients with renal abscesses was identified with a followup rate of 98%. In immunocompetent patients 100% of small abscesses (less than 3 cm.) managed by antibiotics and observation alone resolved. Of medium abscesses (3 to 5 cm.) treated with percutaneous abscess drainage alone 92% resolved. Large abscesses (greater than 5 cm.) often required more than 1 percutaneous drainage procedure (33%) or adjunct open surgical intervention (37%). Statistical analysis revealed that no single treatment modality yielded a superior resolution rate or shorter hospitalization for abscesses stratified by size, patient age or treatment instituted early (1984 to 1993) or late (1992 and 1993) in the study period. CONCLUSIONS Our series suggests that percutaneous drainage is as effective as open surgery for large and medium renal abscesses. Small abscesses may be effectively treated with a course of intravenous antibiotic therapy. A treatment algorithm is reported.

Diet and its role in interstitial cystitis/bladder pain syndrome (IC/BPS) and comorbid conditions

Whats known on the subject? and What does the study add?

Interstitial cystitis: bladder pain and beyond

Background: Interstitial cystitis is characterized by over 6 months of chronic pain, pressure and discomfort felt in the lower pelvis or bladder. It is often relieved with voiding, along with daytime frequency and nocturia in the absence of a urinary tract infection. Interstitial cystitis occurs primarily in females including adolescents and its diagnosis is still one of exclusion. It is now recognized as a serious medical condition associated with significant disability. Objective: The aim of this paper was to review the pathogenesis and treatment of interstitial cystitis with emphasis on new pathogenetic trends and therapeutic modalities. Methods: About 713 mostly original papers were reviewed in Medline from 1990 to August. 2008. All authors independently reviewed the literature. Large, double-blind, placebo-controlled, clinical trials were few and the medical histories of the patients used varied considerably making conclusions difficult. Promising pilot trials turned out mostly negative on follow-up. Results: Increasing evidence of co-morbid diseases, neurogenic inflammation and the effect of stress are promising as new targets for pathophysiology. No new effective treatments have emerged. Oral pentosanpolysulfate, amitriptyline, hydroxyzine and quercetin, as well as intravesical heparin/bicarbonate/lidocaine solutions, are still used with variable success. Some pilot open-label trials presented encouraging findings. Conclusion: Interstitial cystitis contributes substantially to chronic pelvic pain and to poor quality of life. Oral or intravesical administration of solutions containing sodium hyaluronate, chondroitin sulfate and quercetin to both reduce bladder inflammation and ‘replenish’ the glycosaminoglycan layer should be tried. There is a clear need for therapeutic modalities. New potential translational research areas are suggested.

The Role of Cystoscopy in the Diagnosis of Hunner's Ulcer Disease

PURPOSE Interstitial cystitis can be classified into Hunners ulcer and nonulcer disease, which are easily distinguished by cystoscopic examination. Although therapeutic options may differ between these 2 groups, the diagnosis of interstitial cystitis is currently established by many clinicians in the absence of cystoscopy. We determined whether clinical parameters alone without cystoscopic evaluation could reliably distinguish the patient with Hunners ulcer vs nonHunners ulcer disease. MATERIALS AND METHODS Data were collected on 184 women and 39 men who met National Institute of Diabetes, Digestive and Kidney Diseases criteria for interstitial cystitis and who were evaluated at our institution between 1990 and 2005. A total of 86 patients with Hunners ulcer were consecutively identified. Of patients with nonHunners ulcer disease seen during that period a cohort of 137 who were consecutively identified were selected as a comparison group. Clinical data on each patient were collected. The groups were compared by the 2-sample t test, the Mann-Whitney test when appropriate and the chi-square test. RESULTS No significant differences in clinical parameters were found between women and men in either group. The female-to-male ratio was 6:1 and 3:1 in the nonHunners and Hunners ulcer groups, respectively. The mean age of patients with Hunners ulcer was significantly higher than that of patients with nonHunners ulcer disease (60 vs 47 years, t test p <0.001). No significant differences in symptom duration, history of gross hematuria, history of comorbid disease or visual analog pain scores were found between the 2 groups. Microscopic hematuria was present in 27 (31%) and 29 patients (21%) with Hunners ulcer and nonHunners ulcer disease, respectively (chi-square test p <0.086). CONCLUSIONS Although there have been recently published methods and markers by which to differentiate Hunners ulcer vs nonHunners ulcer interstitial cystitis, our data demonstrate that standard clinical evaluation cannot reliably distinguish these groups. These findings suggest that cystoscopy is needed to accurately identify patients with Hunners ulcer.

The management of overactive bladder syndrome

#### Summary points In 2010, the International Continence Society restated the definition of overactive bladder syndrome as a condition with characteristic symptoms of “urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of urinary tract infection or other obvious pathology.”1 In 2009, disease specific total expenditures for this syndrome exceeded

Etiology: where does prostatitis stop and interstitial cystitis begin?

24.9bn (£15.76bn; €19.01bn).2 However, overactive bladder syndrome remains underdiagnosed and undertreated, despite prevalence estimates in men and women of 17% in the United States (National Overactive Bladder Evaluation study) and 12-17% in six European nations.2 3 One population based prevalence study found that 60% of older or disabled patients seek treatment but only 27% receive it.4 The study also showed that overactive bladder syndrome is associated with worse quality of life scores than those in hypertension, depression, diabetes, and asthma. In fact, many patients are unaware that useful medical treatment is available.4 Retrospective observational studies have shown that the medical and surgical consequences of overactive bladder—particularly in older or disabled patients—include depression, falls, fractures, urinary …