Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness.

PURPOSE: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated. RESULTS: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported. CONCLUSIONS: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.

Responsiveness of symptom scales for interstitial cystitis.

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.

A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis.

PURPOSE: This pilot study was designed to evaluate the feasibility of a multicenter, randomized, clinical trial in interstitial cystitis (IC). Secondary objectives were to evaluate the safety and efficacy of oral pentosan polysulfate sodium (PPS), hydroxyzine, and the combination to consider their use in a larger randomized clinical trial. MATERIALS AND METHODS: A 2 x 2 factorial study design was used to evaluate PPS and hydroxyzine. 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 for a minimum of 6 months before study entry. The primary end point was a patient reported global response assessment. Secondary end points included validated symptom indexes and patient reports of pain, urgency and frequency. The target sample size was 136 participants recruited during 10 months. RESULTS: A total of 121 (89% of goal) participants were randomized over 18 months and 79% provided complete followup data. The response rate for hydroxyzine was 31% for those treated and 20% for those not treated (p = 0.26). A nonsignificant trend was seen in the PPS treatment groups (34%) as compared to no PPS (18%, p = 0.064). There were no treatment differences for any of the secondary end points. Adverse events were mostly minor and similar to those in previous reports. CONCLUSIONS: The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC. This trial demonstrated the feasibility of conducting a multicenter randomized clinical trial in IC using uniform procedures and outcomes. However, slow recruitment underscored the difficulties of evaluating commonly available IC drugs.

Clinical highlights of the National Institute of Diabetes and Digestive and Kidney Diseases/Interstitial Cystitis Association scientific conference on interstitial cystitis.

In October 2000, the National Institute of Diabetes and Digestive and Kidney Diseases and the Interstitial Cystitis Association held a joint meeting in Minneapolis, Minnesota. Clinical highlights from this meeting are reviewed. The general state of interstitial cystitis from the vantage point of the clinician is discussed, as well as epidemiologic advances, new concepts in markers for interstitial cystitis, and new treatment strategies. Although there are no breakthroughs in finding a cure for this disorder, potential major changes in methods of diagnosis and new forms of therapy are in the offing.

Interstitial cystitis: current issues and controversies in diagnosis.

Current tests for the diagnosis of interstitial cystitis (IC) are reviewed, including clinical assessment, urodynamic testing, cystoscopy, bladder biopsy, and urinary markers. A MEDLINE search was performed of all studies dealing with the diagnosis of IC. These studies were critically reviewed with the goal of arriving at a utilitarian approach to IC diagnosis. IC is being diagnosed with increasing frequency. However, the diagnostic criteria are nonuniform and there is significant overlap between chronic pelvic pain syndromes in men and women and IC. Diagnosis of IC can be made clinically and by cystoscopy and hydrodistention. The sensitivity and specificity of urinary markers have not been prospectively studied. Individual practitioners continue to use the various diagnostic tests. There is a clear need for uniform diagnostic criteria for clinical diagnosis as well as epidemiologic and research studies.

Comparison of bladder blood flow in patients with and without interstitial cystitis.

PURPOSE: We compared bladder blood flow during filling and emptying in patients with and without interstitial cystitis, and correlated blood flow with symptoms in those with interstitial cystitis. MATERIALS AND METHODS: Bladder perfusion was measured using a dual channel endoscopic laser Doppler flow probe. Measurements were obtained in superficial and deeper vascular beds from the bladder mucosa at the trigone and back wall at baseline, at the volume of awake capacity, during 80 cm. water hydrodistention and after bladder drainage. American Urological Association symptom score was obtained preoperatively in interstitial cystitis patients. RESULTS: In all areas bladder perfusion decreased with filling in interstitial cystitis patients and increased in those without interstitial cystitis. There were no significant differences in response to emptying the bladder, as perfusion tended to increase in both groups. There was no correlation between bladder perfusion at baseline, or in response to filling or emptying with overall symptom score. CONCLUSIONS: Bladder perfusion decreases with bladder filling in patients with but increases in those without interstitial cystitis. The inability of the interstitial cystitis bladder to increase bladder blood flow with filling may be a reflection of other pathological processes in the bladder mucosa. The lack of correlation between blood flow and symptoms suggests that bladder ischemia alone cannot account for the symptoms in interstitial cystitis.

The diagnosis of interstitial cystitis revisited: lessons learned from the National Institutes of Health Interstitial Cystitis Database study.

PURPOSE: The lack of a precise working definition of interstitial cystitis may have resulted in the de facto use of the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) "research" definition by clinicians. We evaluated these strict criteria in light of the broader inclusion criteria for patients evaluated in the Interstitial Cystitis Database study to determine their utility in clinical practice as a useful basis for the diagnosis of interstitial cystitis. MATERIALS AND METHODS: A total of 379 women who completed screening for the Interstitial Cystitis Database before January 1, 1996 met the basic criteria of urinary frequency, urgency or pain for at least 6 months in duration without a diagnosable etiology. Of these patients 148 underwent cystoscopy and hydrodistention of the bladder as a part of the evaluation. All patients were followed for a minimum of 1 year. Comparisons were made between patients judged to have a clinical diagnosis of interstitial cystitis and those who met the NIDDK research definition of the syndrome. RESULTS: Almost 90% of patients potentially meeting NIDDK criteria are believed by experienced clinicians to have interstitial cystitis, confirming the research value of these criteria in defining a homogeneous population for study. However, strict application of NIDDK criteria would have misdiagnosed more than 60% of patients regarded by researchers as definitely or likely to have interstitial cystitis. CONCLUSIONS: The NIDDK criteria are too restrictive to be used by clinicians as the diagnostic definition of interstitial cystitis.

Bulbocavernosus reflex studies and autonomic testing in the diagnosis of erectile dysfunction.

The electrophysiologic evaluation of patients with erectile dysfunction presents an important diagnostic challenge. The bulbocavernosus reflex (BCR) latency has been commonly used to evaluate these disorders. However, it is a measure of somatic penile innervation, whereas erection is primarily dependent on autonomic function. We evaluated 195 men with erectile dysfunction over a 3 year period. Each had electrophysiologic studies, nerve conduction studies and a BCR. BCR studies were abnormal in only 7%, of which most had diabetes or pelvic trauma. The BCR was the sole electrophysiologic abnormality in only 2%. Autonomic testing (AT) was additionally performed in 19 diabetic and 23 non-diabetic patients. This included sympathetic skin responses and measurement of the Valsalva ratio and heart rate variability with 6/min breathing. In the diabetic group, AT was positive in 63%, and most often was the sole abnormality. The bulbocavernosus reflex is relatively insensitive in the diagnosis of erectile dysfunction. Brief autonomic testing may provide valuable additional data, particularly in diabetics.

Lack of effect following repeated in vivo exposure of the rabbit urinary bladder to urine from interstitial cystitis patients at low infusion volumes.

We reported previously that substances in interstitial cystitis urine, when infused into the rabbit bladder, induce changes that resemble bladders of interstitial cystitis (IC) patients. Here we report our investigation of the effect of additional molecular weight subfractions of IC urine and lower infusion volume in this rabbit bladder bioassay. Urine was pooled from symptomatic IC patients, asymptomatic IC patients (in remission), and normal volunteers. Two fractions of 20x concentrated urine were obtained for each of the 3 groups: a 10-100-kD fraction and a fraction > 100 kD but <0.22 microm. Six rabbits per group were infused twice per week with 6 ml of 1 of these 6 urine fractions or saline as a control. After 6 weeks, each rabbit was cystoscoped before and after hydrodistension, bladder capacity and urea permeability were determined, and the bladder was removed for histologic examination. A questionnaire revealed a significant difference (P < 0.01) regarding voiding symptom severity between symptomatic IC patients and both normal volunteers and IC patients in remission. There was no statistically significant difference among groups of rabbits in cystoscopic bladder appearance, bladder capacity, urea permeability, or bladder histology. If a urine-borne factor is in part responsible for IC symptoms, the rabbit bladder must be filled with urine to near capacity to be able to detect a difference between IC and normal urine in this rabbit bladder bioassay.

The staging pelvic lymphadenectomy: implications as an adjunctive procedure for clinically localized prostate cancer.

OBJECTIVES: To evaluate the utility of staging pelvic lymphadenectomy and to identify factors associated with nodal metastases in which a node dissection would be of clinical benefit. PATIENTS AND METHODS: A retrospective analysis (1989-1993) was performed on 303 consecutive patients who underwent staging bilateral modified pelvic lymph node dissection for clinically localized prostate cancer. Multivariate logistic regression analysis was used to evaluate age, race, clinical stage, prostate-specific antigen (PSA) level and Gleason score for predicting nodal metastases. RESULTS: Twenty-eight patients had nodal metastases, giving an overall prevalence of 9.2%. PSA and Gleason score (both P < 0.001) were significantly predictive of nodal involvement when combined or as independent variables. Relative to PSA and Gleason score, the patients' age, race and clinical stage were less relevant. Sensitivity analysis determined that combining a PSA of > or = 20 ng/mL (normal 0-4) and a Gleason score of > or = 8 gave a negative predictive value of 92% with a specificity of 99%, a positive predictive value of 67% and an overall accuracy of 91% for predicting nodal metastases. CONCLUSION: From this data, lymph node metastases are unlikely in patients with clinically localized prostate cancer who have a PSA of < 20 ng/mL and a Gleason score < 8, and that a pelvic lymph node dissection as an adjunctive procedure should be avoided in such individuals.

Interstitial cystitis: unexplained associations with other chronic disease and pain syndromes.

OBJECTIVE: To determine the prevalence of concomitant disease in individuals with interstitial cystitis and to compare these results to the general population. METHODS: We used a questionnaire-based study evaluating 12 disease processes and a survey of interstitial cystitis characteristics. The population was 2,405 individuals with interstitial cystitis who responded to the initial survey and an additional 277 individuals who were randomly selected and individually contacted. RESULTS: Allergies, irritable bowel syndrome, and sensitive skin were the most common diseases in the interstitial cystitis population. In comparison to the general population, individuals with interstitial cystitis are 100 times more likely to have inflammatory bowel disease and 30 times more likely to have systemic lupus erythematosus. In addition, allergies, irritable bowel syndrome, sensitive skin, and fibromyalgia have an increased association with interstitial cystitis. CONCLUSIONS: Interstitial cystitis has, as yet, an unexplained association with certain other chronic disease and pain syndromes.

Analysis of long-term Elmiron therapy for interstitial cystitis.

OBJECTIVES: The long-term efficacy and safety of Elmiron (oral pentosan polysulfate sodium) in relieving recurring symptoms of interstitial cystitis (IC) were investigated in a long-term, open-label physician's usage study. METHODS: Patients with diagnosed interstitial cystitis who met the study entry criteria received shipments of Elmiron for 3 months at a dose of 100 mg 3 times a day and for the consecutive 3-month periods, provided they completed and returned questionnaires about their disease symptoms, reported any adverse events, and had laboratory data collected before each new shipment. Patients were required to purchase the medication. Responses to questionnaires provided the data reported here. Several symptomatic parameters of the disease (overall improvement, overall improvement in pain and urgency, urinary frequency, and nocturia) were recorded in this way and used to evaluate efficacy. RESULTS: Elmiron usage was correlated with improvements in some symptoms, and these improvements increased with duration of treatment. Some symptoms were improved within 5 months, although most continued to show improvements in both severity rating and in percentage of positive responders over 1 to 2 years. Populations of patients receiving extended treatment, some for > 90 months, showed no further improvement or worsening in symptom values. Forty-six percent of patients dropped out of the study within the first 3 months of Elmiron treatment. The frequency of adverse events was < 4%. The most notable adverse events were reversible alopecia, diarrhea, nausea, headache, and rash. CONCLUSIONS: Elmiron appears to be an efficacious long-term treatment for reducing a constellation of debilitating symptoms associated with interstitial cystitis in some patients. Patients with a positive response to Elmiron appear to maintain this response over time.

Logical and systematic approach to the evaluation and management of patients suspected of having interstitial cystitis.

OBJECTIVES: To outline a systematic approach to the evaluation, diagnosis and treatment of interstitial cystitis (IC). METHODS: A review of the literature as well as of our experience. RESULTS: The exclusion criteria for the research definition of IC can be used as guides when obtaining the history, physical examination, laboratory workup, and finally urodynamics and cystoscopy/hydrodistension under anesthesia. Once the diagnosis is established, patients who are still symptomatic after hydrodistension are treated initially with oral medications. Those who do not respond to oral therapy are given intravesical therapy. Patients whose symptoms are refractory to both routes can be considered for a TENS unit, experimental oral therapies, chronic pain control with opioids, or, as a last resort, surgery to create a urinary diversion. CONCLUSION: As IC is a diagnosis of exclusion, the evaluation remains one of ruling out other disorders that produce similar symptoms in patients whose history suggests IC. Until the etiology and pathogenesis of IC are identified, specific therapy is not possible. However, symptomatic treatments are helpful in the majority of patients.

Factitious renal colic.

OBJECTIVES: We reviewed our experience with patients with factitious disorders who presented with renal colic to identify their common characteristics and to quantify the cost burden placed on the health care system as a result. METHODS: We retrospectively reviewed the medical records of two Philadelphia area hospitals from 1989 to 1995 to find patients with factitious disorders who presented with renal colic. A control group of patients with nephroureterolithiasis was also identified. RESULTS: We identified 12 patients who presented with renal colic and had a final diagnosis of Munchausen's syndrome or malingering. The incidence of factitious renal colic was 0.6%. Eighty-three percent of these 12 patients were men, had an average age of 32 years, and made a total of 18 hospital visits. Ninety-two percent claimed an intravenous contrast allergy, 25% claimed an allergy to a specific narcotic, and 39% of the hospital visits ended with the patient voluntarily discharged against medical advice. Thirty-three percent were treated elsewhere for similar complaints. Only the number of intravenous contrast allergies and the number of patients leaving against medical advice were statistically different from the control group. The total cost for all factitious visits was $52,452, with a mean cost per visit of $2914. The average bill of those patients who received retrograde pyelograms was $3046 greater than for those who did not. CONCLUSIONS: Factitious disorders should be considered when evaluating patients with an intravenous contrast allergy and renal colic. These patients are likely to leave against medical advice and place a significant cost burden on hospitals.

External genitalia gunshot wounds: a ten-year experience with fifty-six cases.

OBJECTIVE: To determine the appropriate methods for the diagnosis and management of gunshot injuries to the external genitalia. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Fifty-six patients with gunshot wounds (GSWs) to the external genitalia were seen over the last 10 years. All patients underwent physical examination, radiographic staging, and surgical exploration, according to protocol. RESULTS: There were 25 testicular, 19 scrotal soft tissue, 14 penile, 4 epididymal, 4 urethral, 4 vasal, and 3 superficial scrotal skin injuries. When possible, all injuries, except for the vasal and 1 urethral injury, were primarily repaired with excellent long-term results. Orchiectomy was required in half of testes struck by gunshots. Associated injuries with single GSWs were mostly to the proximity soft tissue and were amenable to conservative management. Major associated injuries were present in patients with multiple GSWs. In the absence of a suspected major associated injury, genital GSWs required only two diagnostic studies, a retrograde urethrogram for suspected urethral injury and a routine abdominal radiograph. Gunshot injuries to the penis or perineum, blood at the penile meatus, or gross hematuria were highly suggestive of urethral injury. CONCLUSIONS: Successful management of genital GSWs is dependent upon prompt surgical exploration, conservative debridement, and primary repair.

Adult acute idiopathic scrotal edema.

We report here a rare case of adult acute idiopathic scrotal edema (AISE). Its characteristics and management are the same for adults as for prepubertal boys. AISE typically affects prepubertal boys, with an acute onset of a relatively painless scrotal erythema and subcutaneous edema, which resolves spontaneously, without sequela, in 1 to 3 days. The erythema and swelling can also extend to the perineum, abdomen, or penis. Its diagnosis is primarily made by exclusion. Vital signs, urinalysis, urine and tissue culture, and white blood cell count are normal. Palpably normal scrotal contents on physical examination and thickened scrotal wall and normal testis arterial flow on scrotal ultrasound with color flow Doppler further confirm the diagnosis. Differentiating AISE from a scrotal surgical emergency is essential in order to avoid unnecessary exploration.

Ureteral injuries from penetrating trauma.

Twelve patients with ureteral injuries from stab or gunshot wounds were evaluated. All 12 underwent surgical exploration on admission. None of the injuries were diagnosed preoperatively. Eleven of 12 injuries were diagnosed during surgical exploration. Diagnosis was delayed in one patient, until 2 weeks after injury, when a CT scan revealed a urinoma. High-dose intravenous urograms (IVUs) were nondiagnostic in nine of nine patients. Hematuria was absent in 45% of patients (5 of 11). Repair of ureteral injury was successfully performed on the proximal and middle portions of the ureter (nine patients) with stented ureteroureterostomy. Three patients sustained distal ureteral injuries. Two underwent ureteroneocystostomy and psoas hitch, and one a primary repair. Mean follow-up time after repair was 4 months in nine patients, and only two minor complications were noted. Currently available preoperative methods, including urinalysis and high-dose IVU, are not reliable for detecting penetrating ureteral injury. In addition, 1 of 12 ureteral injuries was not initially identified, despite routine surgical exploration, urinalysis, and high-dose IVU. A high index of suspicion is required to diagnose ureteral injury.

Primary treatment of radiation-induced hemorrhagic cystitis with hyperbaric oxygen: 10-year experience.

Radiation-induced hemorrhagic cystitis continues to cause frustration for patients and urologists alike. Virtually all present modes of treatment tend to yield short-term benefits and entail potentially devastating risk by virtue of the tissue destructive nature. We report our 10-year experience in the treatment of hemorrhagic radiation cystitis with hyperbaric oxygen therapy, a tissue-reparative method, in followup of our prior reports. A total of 13 patients who previously underwent radiation therapy for various pelvic malignancies had endoscopically or biopsy proved hemorrhagic cystitis. All but 1 patient experienced durable cessation of hematuria with minimal side effects following hyperbaric oxygen therapy. These results suggest hyperbaric oxygen therapy to be a significant weapon in the armamentarium for treatment of hematuria secondary to radiation-induced injury to the bladder.

Bladder permeability in interstitial cystitis is similar to that of normal volunteers: direct measurement by transvesical absorption of 99mtechnetium-diethylenetriaminepentaacetic acid.

Bladder permeability was directly measured with the radionuclide used clinically for detecting vesicoureteral reflux (99mtechnetium-diethylenetriaminepentaacetic acid, 99mTc-DTPA) in 10 interstitial cystitis patients diagnosed according to National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criterion and compared to 9 sex matched, symptom-free, normal volunteers. After functional bladder capacity was determined (capacity at which the patient demands fluid inflow to stop), the bladder was emptied and 5 mCi. 99mTc-DTPA in 10 ml. of saline were infused followed by normal saline to 80% of functional capacity. This was done to normalize the patients to the same low bladder pressure, since previous studies of rabbits indicated that bladder permeability is low and not significantly different at 20% and 60% of anesthetized bladder capacity (defined as the volume producing an intravesical pressure of 20 cm. water). Radioactivity of 1 ml. serum specimens taken at 0, 2, 15 and 30 minutes after radionuclide infusion was determined in a gamma counter, corrected for radioactive decay and converted to per cent of instilled dose per whole body based on blood volume estimated from body weight for each individual. There was considerable interindividual variability in the absorption between the patients and the volunteers. Analysis of variance of these data showed no statistically significant difference between the patients and controls at any time sampled. These results indicate that while some interstitial cystitis patients have a more permeable bladder than others, the same is true for normal, symptom-free volunteers. Thus, the concept of increased bladder permeability in interstitial cystitis is not supported by this direct measurement of bladder permeability.

Current findings and future research avenues in the study of interstitial cystitis.

This article reports the progress made in the last several years of investigations into possible pathogenic processes that lead to the development of interstitial cystitis. The evidence presented here asserts that bladder mucin is functionally intact in interstitial cystitis and that the permeability of the afflicted patient's bladder is not greater than normal.