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What is the value of cystoscopy with hydrodistension for interstitial cystitis?

OBJECTIVES: To determine the utility of cystoscopy with hydrodistension for the diagnosis and therapy of interstitial cystitis. Cystoscopy with hydrodistension is the most commonly performed diagnostic test and procedure in patients with interstitial cystitis. METHODS: Eighty-four consecutive patients with interstitial cystitis (68 women and 16 men) were studied retrospectively. The patients underwent history and physical examination, urinalysis, and urine culture and filled in a voiding diary and pain urgency frequency questionnaire. Cystoscopy with hydrodistension was performed in 47 patients. Patients who had and had not undergone hydrodistension were compared. Patients who underwent hydrodistension were characterized and followed up for response. RESULTS: The mean patient age was 41 years, mean daily voided volume was 98 mL, mean number of nocturnal episodes was 3, and pain urgency frequency score was 21. Comparing patients undergoing versus not undergoing hydrodistension, pain was reported in 61% versus 25% (P = 0.03), vaginal pain in 62% versus 32% (P = 0.02), and dyspareunia or ejaculatory pain in 67% versus 29% (P < 0.01), respectively. All other parameters were statistically similar. Of the patients undergoing hydrodistension, 43 had follow-up and 24 (56%) reported improvement (mean duration of 2 months). Of the patients with and without improvement, no difference was found in mean age (40 versus 46 years, P = 0.20), duration of symptoms (7 versus 7 years, P = 0.92), anesthetic capacity (722 versus 721 mL, P = 0.99), or glomerulation grade (P = 0.61), respectively. CONCLUSIONS: Cystoscopy with hydrodistension provided little useful information above and beyond the history and physical examination findings. As therapy, 56% of patients reported improvement, but the duration was short lived.

Adolescent↗

Safety and efficacy of concurrent application of oral pentosan polysulfate and subcutaneous low-dose heparin for patients with interstitial cystitis.

OBJECTIVES: To conduct a prospective controlled study assessing the safety and efficacy of the additional administration of subcutaneous low-dose heparin in patients receiving oral pentosan polysulfate (PPS) medication for interstitial cystitis. METHODS: A total of 41 patients with interstitial cystitis who reported efficacy of oral PPS medication were divided into three groups (major, intermediate, and minor PPS response), according to their therapeutic response to PPS. Patients received 3 x 5000 IU/day heparin for 2 days, followed by 2 x 5000 IU/day for 12 days. The maintenance dose was 5000 IU/day heparin. We used 17 patients randomly taking PPS alone as the control group. The primary endpoint was a change in overall well-being. Secondary endpoints were changes in pain, urgency, frequency, functional bladder capacity, and the O'Leary-Sant index. RESULTS: Overall, 10 patients were identified as responders at 3 months (24.4%) and 9 patients at 6 months (21.9%) compared with no responders in the control group (P < or = 0.001). At 3 months, 7 (31.8%) of 22 patients in the minor response group reported a statistically significant overall improvement in their well-being compared with 1 (12.5%, P < or = 0.001) of 8 patients of the intermediate group and 2 (18.2%, P < or = 0.001) of 11 patients of the major response group. A significant amelioration of pain intensity was observed in the minor response group at 3 and 6 months. CONCLUSIONS: The concurrent administration of low-dose heparin and oral PPS appears to be a safe and efficacious treatment modality. The subcutaneous administration of heparin appeared to be predominantly of value for patients with interstitial cystitis and an initial minor response to PPS.

Administration, Oral↗

Prevalence, diagnosis, characterization, and treatment of prostatitis, interstitial cystitis, and epididymitis in outpatient urological practice: the Canadian PIE Study.

OBJECTIVES: To determine the prevalence, diagnostic patterns, and management of prostatitis, interstitial cystitis, and epididymitis (PIE) in Canadian urology outpatient practice. METHODS: Representative urologists were randomly selected from the Canadian and Quebec Urological Associations. Each patient identified with a PIE diagnosis during a typical 2-consecutive-week period during April 2004 to July 2004 was requested to complete a corresponding Chronic Prostatitis Symptom Index (CPSI), O'Leary-Sant Symptom Index (OSSI), or a Chronic Epididymitis Symptom Index (CESI). Each day the participant urologist completed an outpatient log and a detailed programmed chart review to transcribe demographics, investigations, and treatments associated with each PIE patient. RESULTS: Sixty-five urologists were invited to participate. Fifty-seven (88%) agreed, and 48 (74%) completed the audit. Of the 8712 patients seen in outpatient practice (average 182 per urologist), 2675 were female and 6037 male. Prostatitis was identified in 2.7% of the men (n = 166; mean age 50 years; mean duration 3.1 years; mean CPSI score 19.7), interstitial cystitis in 2.8% of patients (n = 242; 211 women [7.9%], 26 men [0.4%]; mean age 50.2 years, mean duration 4.5 years, mean OSSI score 11.8), and epididymitis in 0.9% of men (n = 57; mean age 41.1 years, mean duration 2.5 years, mean CESI score 15.5). There was wide variance in investigations and treatments. CONCLUSIONS: This prospective audit indicates that prostatitis might not be as common as frequently believed and that interstitial cystitis is more common, and it represents the first estimate of the prevalence of epididymitis in urologic practice. The wide variance in investigations and treatments confirms the need for practice management guidelines.

Adolescent↗

Symptoms and cystoscopic findings in patients with untreated interstitial cystitis.

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.

Adult↗

Increased expression of growth-associated protein (GAP-43) in lower urinary tract pathways following cyclophosphamide (CYP)-induced cystitis.

Alterations in the expression of growth-associated protein 43 (GAP-43) were examined in lower urinary tract micturition reflex pathways in a chronic model of cyclophosphamide (CYP)-induced cystitis. In control animals, expression of GAP-43 was present in specific regions of the gray matter in the rostral lumbar and caudal lumbosacral spinal cord, including: (1) the dorsal commissure; (2) the dorsal horn and (3) the regions of the intermediolateral cell column (L1-L2) and the sacral parasympathetic nucleus (L6-S1) and (4) in the lateral collateral pathway of Lissauer in L6-S1 spinal segments. Densitometry analysis has demonstrated significant increases (p</=0.001; 1.5-4.0-fold increase) in GAP-43-immunoreactivity (IR) in these regions of the rostral lumbar (L1-L2) and caudal lumbosacral (L6-S1) spinal cord following CYP-induced urinary bladder inflammation. Changes in GAP-43-IR were restricted to those segmental levels examined (L1-L2 and L6-S1) that are involved in lower urinary tract reflexes. Changes in GAP-43-IR were not observed at the L5 segmental level. In contrast to significant increases in GAP-43-IR in specific regions of the rostral lumbar and caudal lumbosacral spinal cord, no changes in GAP-43-IR were observed in the L1, L2 or L6, S1 dorsal root ganglia (DRG). In control animals, virtually all retrogradely labeled (Fast Blue) bladder afferent cells in the L1, L2 and L6, S1 DRG expressed GAP-43-IR. This percentage (approximately 100%) of bladder afferent cells expressing GAP-43-IR was unchanged following CYP-induced urinary bladder inflammation. Alterations in GAP-43-IR following chronic cystitis may suggest a reorganization of bladder afferent projections and spinal elements involved in bladder reflexes consistent with alterations in bladder function observed in animal models of cystitis.

Animals↗

Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen: long-term followup.

PURPOSE: Hemorrhagic cystitis is a recognized possible side effect of therapeutic radiation administered for a variety of pelvic malignancies. Patients may experience pain, bleeding and clot retention. Various palliative treatments, including instillation of alum, silver nitrate and formalin, may be unsuccessful in alleviating patient symptoms. Hyperbaric oxygen therapy is often used to treat poorly healing wounds. We assess the long-term efficacy of hyperbaric oxygen therapy in treating the manifestations of radiation induced injury to the bladder. MATERIALS AND METHODS: A total of 11 patients with radiation induced hemorrhagic cystitis, confirmed by cystoscopy and biopsy, were treated with hyperbaric oxygen therapy. Symptoms included intractable hematuria in all 11 patients, and some also had other voiding symptoms, including persistent suprapubic pain and urinary urgency. In all patients most other types of management had failed and there was no evidence of active infection or recurrent malignancy. Patients received 100% oxygen in a hyperbaric chamber at 2.0 atmospheres for 90 minutes 5 days a week. Average number of treatments was 40 and median followup was 5.1 years. RESULTS: Of these 11 patients 3 (27%) experienced complete and durable resolution of symptoms, 3 had persistent symptoms despite hyperbaric treatments and required supravesical urinary diversion, and 5 initially responded to hyperbaric oxygen therapy but experienced long-term recurrent symptoms necessitating urinary diversion as definitive therapy. CONCLUSIONS: Hyperbaric oxygen offers a noninvasive therapeutic alternative in the management of radiation cystitis. It appears to produce good short-term benefits but it often does not produce definitive long-term cure of the disease process.

Aged↗

Anterior enterocele following cystectomy for intractable interstitial cystitis.

PURPOSE: We clinically define the development of an anterior vaginal wall hernia following cystectomy for the management of intractable interstitial cystitis and establish surgical technique for its correction. MATERIALS AND METHODS: Of 27 women who underwent simple cystectomy and urethrectomy for intractable interstitial cystitis an anterior vaginal wall hernia developed in 3 (71, 56 and 61 years old) at 8, 14 and 16 months, respectively, postoperatively. Clinical appearance was similar to a midline cystocele but it contained bowel contents in the form of an anterior enterocele. Anterior enterocele was associated with vaginal vault prolapse in 1 patient who was treated with transvaginal sacro-spinous colpopexy. Patients with isolated anterior enterocele required a transabdominal approach with mobilization of the intestinal hernia contents and obliteration of the intervaginal abdominal wall space. RESULTS: At 12, 19 and 33 months following reconstruction prolapse has not recurred, and sexual function was restored in 1 patient. CONCLUSIONS: These cases suggest that an extended simple cystectomy performed on women with intractable interstitial cystitis may result in a weakening of the anterior vaginal wall with resultant anterior enterocele formation. When it is associated with vaginal vault prolapse a transvaginal technique may be considered but we prefer a transabdominal approach for an isolated anterior enterocele. Prevention of this entity may be warranted at the time of cystectomy.

Aged↗

Treatment of interstitial cystitis: comparison of subtrigonal and supratrigonal cystectomy combined with orthotopic bladder substitution.

PURPOSE: We retrospectively evaluate the outcome of interstitial cystitis treated with subtrigonal or supratrigonal cystectomy and orthotopic bladder substitution. MATERIALS AND METHODS: Of 22 women and 1 man a mean of 51 years old with interstitial cystitis refractory to conservative therapy 17 were treated with subtrigonal cystectomy and ureteral reimplantation (group 1), and 6 were treated with supratrigonal cystectomy directly above the ureteral orifices (group 2). Both groups underwent orthotopic bladder substitution with an ileocecal pouch (Mainz pouch I). RESULTS: Postoperatively functional capacity significantly increased from a mean plus or minus standard error of mean 46 +/- 5 to 346 +/- 57 ml. in group 1 and 34 +/- 61 to 319 +/- 29 ml. in group 2 (p < 0.001). Daytime and nighttime urinary frequency significantly decreased from 24 +/- 2 to 8 +/- 1 and 7 +/- 1 to 2 +/- 1 ml., respectively, in group 1 and 28 +/- 2 to 6 +/- 1 and 6 +/- 1 to 1 +/- 1 ml., respectively, in group 2 (p < 0.001). At a mean followup of 93.9 months 14 patients in group 1 (82%) are completely symptom-free, and 1 has tolerable residual urinary urgency and suprapubic pain. At a mean followup of 31.5 months all group 2 patients are symptom-free and void spontaneously, whereas 41% of the group 1 patients require self-catheterization after subtrigonal cystectomy. CONCLUSIONS: For interstitial cystitis refractory to conservative treatment subtotal cystectomy with orthotopic bladder substitution with the ileocecal pouch (Mainz pouch I) is a valid therapeutic option. In this series supratrigonal and subtrigonal cystectomy resulted in similar relief of symptoms but the former appears to provide better functional bladder rehabilitation.

Adult↗

Interstitial cystitis in The Netherlands: prevalence, diagnostic criteria and therapeutic preferences.

PURPOSE: We determine the prevalence of interstitial cystitis in The Netherlands, and analyze the most common diagnostic and therapeutic approaches among Dutch urologists. MATERIALS AND METHODS: A questionnaire was completed by urologists and analyzed with the help of a statistical computer program. RESULTS: The prevalence of interstitial cystitis was calculated to be 8 to 16/100,000 female patients. Pathology of bladder biopsies and the presence of mast cells were the main diagnostic criteria. Dimethyl sulfoxide instillations, bladder hydrodistension and surgery were the most frequently applied therapies. CONCLUSIONS: The prevalence of interstitial cystitis in The Netherlands is in line with that of other reports from Europe but low compared to the United States findings. The importance of pathology and the presence of mast cells in the diagnosis, as well as less awareness might contribute to this difference.

Cystitis, Interstitial↗

Detection of eubacteria in interstitial cystitis by 16S rDNA amplification.

OBJECTIVE: To determine what role non-culturable microorganisms play in the etiology of interstitial cystitis (IC). MATERIALS AND METHODS: Thirty patients fulfilling NIH criteria for the diagnosis of interstitial cystitis and sixteen control patients with culture negative urine gave written informed consent and underwent bladder biopsy. Polymerase chain reaction (PCR) using two sets of universal primers for bacterial 16S rDNA was performed on urine from the cystoscope and on a cold cup bladder biopsy specimen. Of the PCR positive bladder biopsies, three patients with interstitial cystitis and three controls were randomly selected and cloned. Ten clones from each were sequenced and putative taxonomic assignments made. RESULTS: 12/26 (46%) IC and 5/12 (42%) control urine specimens and 16/30 (53%) and 9/15 (60%) bladder biopsies were PCR positive, respectively. The bacterial populations in the two patient groups tested appeared to be different based upon analysis of the 16S rRNA sequences. CONCLUSIONS: Both IC and control patients had non-culturable bacteria in their bladders. A random sampling of the two populations revealed that the bacterial populations are different, suggesting a possible link between one or more bacterial species and IC.

Bacteria↗

Comparison of the uroprotective efficacy of mesna and HBO treatments in cyclophosphamide-induced hemorrhagic cystitis.

The aim of this research was to compare the protective effects of mesna, hyperbaric oxygenation (HBO), and their combination in cyclophosphamide-induced hemorrhagic cystitis in guinea pigs. Following one dose of i.p. 21.5 mg./kg. mesna administration 20 minutes before i.p. 68.1 mg./kg. cyclophosphamide, 3 additional doses of mesna were given every three hours. A total of 8 HBO exposures, 5 of which were applied prophylactically before cyclophosphamide, were performed at 2.8 ATA for 90 minutes 2 times a day. Although mesna or HBO provided significant protection for cyclophosphamide-cystitis in animal bladders, there was also significant damage compared with controls. The combination of mesna and HBO, which act through independent mechanisms, resulted in complete protection, since mean histological scores and hematuria levels in this group were not different from controls (p >0.05). Therefore, this combination may be a useful tool in the prophylaxis and treatment of cyclophosphamide-induced hemorrhagic cystitis.

Animals↗

Long-term results of trigone-preserving orthotopic substitution enterocystoplasty for interstitial cystitis.

PURPOSE: Interstitial cystitis is a chronic debilitating condition mainly affecting women. Conservative treatment often produces unsatisfactory results and the identification of the best surgical treatment modality is difficult. We evaluate retrospectively the long-term results of trigone-preserving cystectomy followed by orthotopic substitution enteroplasty for women suffering from interstitial cystitis. MATERIALS AND METHODS: The study comprised 18 women with a mean age of 55.9 years. All surgical interventions were performed by 1 surgeon. All patients completed a voiding log and were interviewed about symptoms. Renal ultrasonography was done to evaluate the upper urinary tract. Followup data also comprised blood chemistry studies, including vitamin B12 blood levels and blood gas analysis. Pain and lower urinary tract problems were measured using a validated self-assessment symptom index. RESULTS: Ileocoecal augmentation was performed in 10 women and ileal substitute was done in 8. After a mean followup of 57 months 14 patients are completely pain-free, 12 void spontaneously and 15 report complete resolution of dysuria. Three patients perform intermittent self-catheterization and 1 woman prefers a suprapubic catheter for control of urinary hypercontinence. These 4 patients underwent ileoplasty. Surgery failed to relieve symptoms in 2 of the 18 patients. Surgery achieved a statistically highly significant improvement of diurnal and nocturnal voiding frequencies, functional bladder capacity and symptom index score. CONCLUSIONS: Substitution enterocystoplasty is a valuable and safe therapeutic option for patients with intractable interstitial cystitis resistant to conservative therapy. In our series use of the ileocecal bowel segment showed better functional results.

Adult↗

The bladder acellular matrix graft in a rat chemical cystitis model: functional and histologic evaluation.

PURPOSE: We investigated the feasibility of augmentation in a diseased bladder with a bladder acellular matrix graft. MATERIALS AND METHODS: In 50 female Sprague-Dawley rats chemical cystitis was induced by intravesical instillation of HCl repeated monthly to maintain chronic inflammation. Urodynamic studies were performed in all rats 1 week after the induction of chemical cystitis and repeated at sacrifice. The 29 rats in the experimental group underwent partial cystectomy (50% or greater), followed by bladder acellular matrix graft augmentation, while the 21 controls underwent monthly HCl instillation only. The rats were sacrificed at 2 weeks, 1, 2 and 3 months, respectively. The bladder was removed and examined for histological changes. RESULTS: Urodynamic studies showed that bladder capacity and compliance were significantly higher in the grafted than in the control group (p = 0.008 and 0.006, respectively, at 3 months). Histological studies revealed urothelial and smooth muscle regeneration within the bladder acellular matrix graft at 1 month and nerve regeneration at 3. The number of mast cells was significantly lower in the grafted region than in the host bladder of all grafted rats (p <0.001). CONCLUSIONS: In this rat chemical cystitis model bladder augmentation with a bladder acellular matrix graft led to functional and histological improvement over diseased host bladder.

Animals↗

Interleukin-6 and interstitial cystitis.

We analyzed the presence of the cytokine interleukin-6 in urine samples from interstitial cystitis patients. Interleukin-6 was significantly elevated in patients with interstitial cystitis (169.29 +/- 90.81 pg./ml. versus 34.8 +/- 6.35 pg./ml. in controls). Representative urine samples were analyzed with specific antibody to interleukin-6 and greater than 80% of the biological activity was neutralized. These cytokine measurements were then compared with clinical parameters and interleukin-6 levels correlated positively with the pain scores. Studies on the potential cellular origin of interleukin-6 showed increased levels in spontaneously voided urine but not in ureteral urine, which was collected during cystoscopy, suggesting that interleukin-6 is the product of activated cells in the bladder. This finding is supported by in situ hybridization analyses, which showed that interleukin-6 messenger ribonucleic acid expressing cells are located in the interstitium and epithelial layer, and within blood vessels. The implications of these findings for interstitial cystitis pathogenesis are discussed.

Base Sequence↗

Hemorrhagic cystitis associated with herpes simplex virus.

A 45-year-old man presented with hemorrhagic cystitis and was found to have herpes simplex infection of the bladder by biopsy, immunohistochemistry and in situ hybridization. The patient had no clinical evidence of immunosuppression or disseminated infection. Although viral etiologies of hemorrhagic cystitis are recognized, to our knowledge only 4 cases of hemorrhagic cystitis due to herpes simplex virus have been reported.

Biopsy↗

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.

Adult↗

Autoantibodies in interstitial cystitis.

We have identified and partially characterized autoantibodies from the sera of patients with interstitial cystitis. Our characterization included initial screening by antinuclear antibody testing on human HEp-2 cell substrate and mouse kidney/stomach tissue substrate, titering and subtyping of positive sera, and Western blotting to identify target autoantigens. Of 96 interstitial cystitis patients 35 (36%) were positive for antinuclear antibodies at titers of 1/40 or greater. Among the antinuclear antibody patterns observed 24 were dense fine nuclear speckles, 7 were nucleolar, 3 were mitochondrial and 1 was coarse nuclear speckles. All but 4 of the antinuclear antibody positive sera were exclusively of the IgG class. As determined by unique antinuclear antibody staining patterns and by specificities on Western blots, interstitial cystitis autoantibodies appear to recognize novel autoantigens not previously described in patients with systemic autoimmune diseases, such as lupus, scleroderma and Sjögren's syndrome.

Adult↗

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.

Adult↗