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The term cystitis cystica is a misnomer and reflects the unfortunate habit of labeling obscure bladder conditions as cystitis. Cystosis of the bladder would be a more correct term. Cystitis cystica is a derivative of the focal epithelial proliferation, the associated tumors tend to be non-infiltrating papillary and the prognosis is good.
Two patients were treated for interstitial cystitis after having had bladder biopsies that did not reveal tumor. However, in both cases an aggressive carcinoma of the bladder later proved to be present when simple cystectomy for the "benign" disease was done. The masquerade of carcinoma of the bladder as interstitial cystitis and the pitfalls inherent in making the correct diagnosis are emphasized. The possibility of underlying bladder carcinoma should be excluded in any patient who presents with symptoms of chronic cystitis. Urinary cytology is most helpful but repeated bladder biopsy with careful serial sectioning may be necessary to establish the diagnosis of malignancy. It is not known whether the carcinomas were primary or secondary developments in our cases. The term inflammatory carcinoma of the bladder is proposed to call the attention of clinicians and pathologists to this lethal imitator.
In a comparison of children with acute hemorrhagic cystitis it was noted that 51 per cent of those in Sendai, Japan and 23 per cent of those in Chicago, Illinois had adenoviruria during their illness. These 2 populations are the only ones in which the disease has been studied and reported. In both populations male outnumbered female patients, with a ratio of 3.4 to 1 in Japanese children and 2.3 to 1 in American children. Adenovirus type 11 was isolated exclusively in both studies, with the exception of 2 American children who had adenovirus type 21 in the urine. While the Japanese children experienced their illnesses for approximately 2 weeks American children had symptoms for only 4 to 5 days. Virus shedding continued throughout the illness in both populations. The adenovirus 11 strains from American children were antigenically similar to the prototype adenovirus type 11 strain as measured by cross hemagglutination-inhibition procedures. Adenovirus antigen was identified by immunofluorescence in exfoliated bladder epithelial cells from patients with acute hemorrhagic cystitis. Studies to date indicate that adenovirus type 11 is the etiologic agent in some but not all pediatric cases of acute hemorrhagic cystitis.
OBJECTIVE: To document the initial clinical diagnoses, determine the prevalence of urinary symptoms, and test for intravesical potassium sensitivity in gynecologic patients with chronic pelvic pain. METHODS: Gynecologists at three United States medical centers administered the Potassium Sensitivity Test to consecutive unselected pelvic pain patients. Before testing, each patient was given an initial clinical diagnosis based on the patient's chief symptomatic complaint(s) and surveyed for urologic symptoms. RESULTS: Of 134 patients, 114 (85%) had positive potassium sensitivity. Positive potassium sensitivity rates were similar across all three sites and all clinical diagnoses including endometriosis, vulvodynia (vulvar vestibulitis), and pelvic pain. A total of 75% of the subjects reported urologic symptoms, but only 2.9% received an initial diagnosis of interstitial cystitis. CONCLUSION: A significant majority of gynecologic patients presenting with pelvic pain have a positive Potassium Sensitivity Test, indicating their pain may have a bladder component (interstitial cystitis). Interstitial cystitis deserves greater consideration in the differential diagnosis of chronic pelvic pain.
In a retrospective analysis of hemorrhagic cystitis subsequent to allogeneic bone marrow transplantation, we focused on patients who underwent subtotal cystectomy with ileocystoplasty because stepwise use of conservative treatments had failed. Severe lasting hemorrhagic cystitis (more than 40 days) led to urinary tract obstruction and sepsis that required subtotal cystectomy in 3 of 1300 bone graft patients. Hematuria did not recur after surgery with a satisfactory functional result (follow-up 10 months to 17 years). Subtotal cystectomy with detubularized ileocystoplasty can be used to control life-threatening hemorrhagic cystitis.
We previously determined that the urine of interstitial cystitis (IC) patients specifically contains a factor (antiproliferative factor [APF]) that inhibits primary bladder epithelial cell proliferation, and that it has significantly decreased levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and increased levels of epidermal growth factor (EGF) compared with urine from asymptomatic controls and patients with bacterial cystitis. We sought to confirm the specificity of these findings for IC using a larger patient population, including control patients with a variety of urogenital disorders. Clean catch urine specimens were collected from 219 symptomatic IC patients, 113 asymptomatic controls without bladder disease, and 211 patients with various urogenital diseases including acute bacterial cystitis, vulvovaginitis, chronic nonbacterial prostatitis, overactive bladder, hematuria, stress incontinence, neurogenic bladder, benign prostatic hyperplasia, bladder or pelvic pain without voiding symptoms, bladder cancer, prostate cancer, or miscellaneous diagnoses including anatomic disorders. APF activity was determined by (3)H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and EGF levels were determined by enzyme-linked immunosorbent assay. APF activity was present significantly more often in IC than control urine specimens (P <0.005 for IC vs any control group; sensitivity = 94%, specificity = 95%, P <10(-82) for IC vs all controls). HB-EGF levels were also significantly lower and EGF levels significantly higher in IC urine than in specimens from controls (P <10(-84) and P <10(-36), respectively). These findings confirm the utility of APF, HB-EGF, and EGF as markers for IC. Understanding the reasons for altered levels of these markers may lead to understanding the pathogenesis of this disorder.
Pelvic lipomatosis is a rare disorder of benign mature adipose tissue proliferation around the bladder and rectum. Most cases are associated with proliferative cystitis, in particular, cystitis glandularis. The etiology of pelvic lipomatosis and its association with proliferative cystitis are not well understood. This is the first reported case of familial pelvic lipomatosis. The pathogenesis and the possibility that this disorder could be secondary to genetic abnormalities of the HMG-IC (high mobility group) gene on chromosome 12 are discussed.
OBJECTIVES: To study the clinical effect of diagnostic overdistension plus hyaluronic acid (HA) instillations in interstitial cystitis and the association of the clinical response with the intensity of intercellular adhesion molecule (ICAM)-1 expression. HA is an important component in the urothelium. It inhibits adherence of immune complexes to polymorphonuclear cells, leukocyte migration, and aggregation. HA binds to lymphocytes and endothelial cells expressing ICAM-1. METHODS: Eleven patients with interstitial cystitis who fulfilled the diagnostic criteria of the National Institutes of Health were selected for the trial. The bladder was distended for 1 minute with a pressure of 80 cm H2O and biopsies were taken from the petechial areas. The patients were treated with four weekly intravesical HA instillations (40 mg/50 mL NaCl solution). Biopsies were repeated 2 weeks after the instillations. The ICAM-1 intensity was blindly determined in the lymphocytes and endothelial cells of the vessels from the histologic biopsies. A semiquantitative scoring index was used to measure the inflammatory effect of ICAM-1 receptors. RESULTS: In the long-term responders (2 women and 1 man) and short-term responders (5 women), the pretreatment ICAM-1 index was 3.7 (range 3 to 4); it was 1.8 (range 1.5 to 2) in the nonresponders. Two weeks after the final instillation, the index was 3.5 (range 3 to 4) in the long-term responders and 3.4 (range 3 to 4) in the short-term responders; in the nonresponders, it had increased to 2.8 (range 2.5 to 3.5). CONCLUSIONS: Increased ICAM-1 intensity was found in patients with interstitial cystitis; it was higher in those who responded to overdistension plus HA instillations. By blocking the ICAM-1 receptors, HA presumably alleviates the inflammatory processes, but repeated instillations are needed to maintain the response.
OBJECTIVES: To determine the microcirculatory disturbances in a rat model of ischemia-reperfusion-induced cystitis using intravital fluorescence videomicroscopy. METHODS: Twenty male Sprague-Dawley rats were used for the experiments. In 10 animals, warm ischemia of the bladder was induced for 60 minutes. After 30 minutes of reperfusion, microvascular macromolecular leakage, leukocyte-endothelial cell interactions, venular red blood cell velocity, functional capillary density, and the arteriolar and venular diameters were determined by intravital videomicroscopy. In addition, the intravesical pressure and macrohemodynamic parameters were assessed during the experiments. Sham-operated animals served as the controls (n = 10). RESULTS: After ischemia-reperfusion, the numbers of rolling and firmly adherent leukocytes in the postcapillary venules were significantly increased. Venular red blood cell velocity and functional capillary density, as well as the arteriolar and venular diameters, were significantly decreased. The macromolecular leakage had increased in both arterioles and venules. CONCLUSIONS: After ischemia-reperfusion, inflammatory reactions and microcirculatory failure were observed in the urinary bladder. This study targeted the microcirculatory consequences of cystitis using intravital videomicroscopy. Because the parameters investigated are relevant not only for ischemia-reperfusion of the urinary bladder but also for cystitis caused by other stimuli, this model represents a novel tool in the field of inflammation research in urology.
OBJECTIVE: To determine whether or not patients with refractory interstitial cystitis who had failed conservative therapy might benefit from intravesical bacillus Calmette-Guérin (BCG) immunotherapy. METHOD: Five patients with refractory interstitial cystitis who had failed conservative therapy underwent six weekly treatments with intravesical BCG. All 5 patients were evaluated before therapy and quarterly thereafter by water cystometry and symptom questionnaire. RESULTS: The average number of medications used daily per patient decreased from 3.2 to 1.2 after therapy. Average volumes of both first desire to void and cystometric capacity doubled after BCG. Improvement in cystometric capacity, average daytime urinary frequency, nocturia, and global pain/discomfort were statistically significant (P = 0.0277, P = 0.0131, P = 0.0199, and P = 0.0317, respectively). Three patients experienced near total relief of their symptoms with six to twelve months' follow-up (average follow-up equals 33.6 weeks). CONCLUSIONS: Although the mechanism of action of BCG in interstitial cystitis is unknown, we recommend a double-blind placebo controlled trial to confirm these results and determine an optimal dosage and treatment schedule.
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.
OBJECTIVES: To provide a brief overview of intravesical dimethly sulfoxide (DMSO) therapy for interstitial cystitis and offer a practical approach to patient treatment. METHODS: A review of the literature and a summation of the experience with treatment of > 300 patients with DMSO at the Interstitial Cystitis Clinic, New England Medical Center. RESULTS: DMSO is helpful in a significant number of patients and it has acceptable morbidity and an excellent safety profile. CONCLUSIONS: Intravesical DMSO (singly or in combination) is one of the mainstays in the pharmacologic treatment of interstitial cystitis.
OBJECTIVES: To establish that conventional protocols often do not provide an adequate framework for managing interstitial cystitis, and to describe the special role of the urologic caregiver in developing a collaborative relationship with interstitial cystitis (IC) patients that can allay fears and provide hope that this devastating disease can be managed effectively. METHODS: Epidemiologic studies and a decade of experience of IC patients and their physicians are utilized in developing a rationale for a collaborative relationship between urologic caregivers and IC patients. RESULTS: The symptoms of interstitial cystitis-pain, urgency, and urinary frequency-can have a profoundly disruptive effect on patients' lives and present unique challenges to physicians as urologic caregivers. The impact of IC on patients' lives needs to be accounted for empathetically, and appropriate referrals for depression, sexuality, or relationship problems should be made. Pain should be managed aggressively, and patients who have had delayed diagnosis or who have not responded to the traditional treatments should be educated about the array of medical, complementary/alternative, and self-help modalities available. CONCLUSIONS: A successful treatment paradigm requires that physicians and patients be knowledgeable about the array of medical and complementary/alternative therapies and that these be applied in a systematic but creative way. Through empathic support, information, and a flexible treatment protocol, patients will learn to trust the medical process and take an active part in the management of IC.
OBJECTIVE: To develop and evaluate a diagnostic algorithm based on the alteration of mast cell and nerve fiber observed in bladder tissue of patients with interstitial cystitis (IC). MATERIALS AND METHODS: Non-IC samples from 6 control groups (N = 10, 10, 13, 2, 11, and 3, respectively) and nonclassic interstitial cystitis (NC-IC, N = 20) were stained with Giemsa stain in order to calculate the detrusor to mucosa mast cell ratio (DMMCR) using quantitative image analysis and morphometry (QIAM). Immunohistochemical staining for S-100 protein was also performed to quantify nerve fiber proliferation in the detrusor muscle of the bladder. RESULTS: The average DMMCR of NC-IC was 1.19. Bacille Calmette-Guérin (BCG) cystitis was 0.84 and microscopically normal bladder tissue from patients with bladder or prostate cancer was 0.45. No case of IC that we examined had a DMMCR < 0.5. The number and percentage area of nerve fibers in the detrusor in IC were increased compared to controls and BCG (IC, 2.01%; BCG, 0.95%; control, 1.3%). CONCLUSION: A diagnostic algorithm is proposed for IC based on the findings that indicate that: 1) if the DMMCR > 0.75, then IC is present; 2) if the DMMCR < 0.5, then IC is negative; and 3) if the DMMCR is between 0.5 and 0.75, a quantitative S-100 protein staining analysis can be employed to evaluate nerve fiber proliferation to detect those marginal cases of NC-IC. The findings of the study also suggest that a neuroimmune process or mediation may be involved in the pathogenesis of IC.
OBJECTIVES: To develop 2 brief self-administered indices for measuring lower urinary tract symptoms and their impact in patients with interstitial cystitis (IC). METHODS: An initial set of questions was developed and evaluated in focus groups. The index was revised, shortened, and validated with patients diagnosed in 3 large urologic practices with experience in interstitial cystitis (N = 45). Controls were recruited from a group of healthy volunteers in a gynecology clinic (N = 67). Internal consistency, construct validity, and test-retest reliability were evaluated. RESULTS: The IC symptom index and the IC problem index measure urinary and pain symptoms and assesses how problematic symptoms are for patients with interstitial cystitis. Psychometric performance of both instruments is good, with the symptom index demonstrating excellent ability to discriminate characteristics between patients and controls. CONCLUSION: Both indices should be useful in the evaluation and management of patients with IC and should be particularly useful in clinical trials of new therapies for this condition, where reliable, validated, and reproducible outcome measures are critically important.
OBJECTIVES: Interstitial cystitis is a symptom complex characterized by pelvic pain, urinary urgency, urinary frequency, and nocturia. Patients with these symptoms, at the 5 clinical centers participating in the National Interstitial Cystitis Data Base (ICDB) Study, have been evaluated with history and physical exams, questionnaires, and urodynamic studies. METHODS: Of the 388 female subjects entered in the study as of December 31, 1995, 150 women have undergone cystoscopy with hydrodistension. The data from the endoscopic procedures and the urodynamic studies were analyzed. The associations among cystoscopic and urodynamic findings were reviewed. RESULTS: Patient demographics of this subgroup show a predominance of Caucasians 139/150 (92.7%), with the average age being 43 (+/-13.2) years. Of the total, 17 patients (11.3%) had a Hunner's patch (HP). The prevalence by center varied from a low of 2/38 (5.3%) to a high of 3/9 (33.3%). Bloody effluent following hydrodistension was present in 113/150 (75.3%). Glomerulations appeared in varying degrees (mild, moderate, severe) in 91.3% of the 150 patients. There was a strong inverse relationship (P < 0.001) between bladder capacity under anesthesia and the presence of a HP (mean of 845 cc with HP absent versus a mean of 531 cc when present). The incidence of HP varied from 67.6% among women with a bladder capacity at hydrodistension of < 400 cc to 3.8% for those with a bladder capacity of at least 800 cc. The presence and increasing severity of glomerulations was positively associated (P < 0.003) with the presence of HP, ranging from 0/13 (0%) when glomerulations were not present to 6/31 (19.4%) when glomerulations were graded as severe. Of the patients with HP, 17/17 (100%) had glomerulations after hydrodistension. HP is more closely associated with the moderate to severe range of glomerulations (P < 0.01). Nearly half of the patients with HP or 8/17 (47.1%) had "moderate" glomerulations, while 6/17 (35.3%) had "severe" glomerulations. The volume at first sensation to void on urodynamics (mean 87 cc without HP versus 34.7 cc with HP) was highly inversely associated (P = 0.002) with the presence of HP, but not with any of the other cystoscopic findings. Of patients with HP, 94% had a volume at first sensation to void of < or = 50 cc where only 36% of patients without HP had a volume at first sensation to void of < or = 50 cc. The volume at maximum capacity on urodynamics was positively associated with the volume at hydrodistension (P < 0.001). CONCLUSIONS: Overall, patients with HP had lower bladder capacities, lower volumes at first sensation to void, and more severe glomerulations. Thus, the presence of HP would imply a more severe case of interstitial cystitis. Logically, a higher bladder capacity on cystometrogram is associated with a higher volume at the time of hydrodistension, and bloody effluent is associated with more severe glomerulations.
OBJECTIVES: To determine the minimal active dose and extent of activity of intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation. METHODS: Twenty-four adults with grade 3 or 4 hemorrhagic cystitis were treated. All but 2 had failed other local therapy. Treatment was initiated at a median of 32 days post-transplant. Eleven patients received carboprost intravesicularly at 0.2 mg/dL for 60 minutes every 6 hours, and the dose was escalated every 24 hours until a dose of 1.0 mg/dL was reached unless a response was achieved. Thirteen additional patients were treated at an initial dose of 0.8 mg/dL, with escalation to 1.0 mg/dL after four doses in the absence of a response. RESULTS: Overall, 15 of the 24 patients responded. In the dose-escalation setting, 0.8 mg/dL was the minimal active dose. The total response rate was 62% with doses at or above 0.8 mg/dL and 18% at lower doses. All but one response occurred with 7 or fewer days of therapy, and 9 patients relapsed later. Four additional patients were salvaged following cystoscopy with clot evacuation with or without alum or formalin instillation. In all but 1 patient, bladder spasms developed during treatment with carboprost, but were not sufficiently severe to discontinue therapy. CONCLUSIONS: Intravesicular carboprost at 1.0 mg/dL every 6 hours for no more than 7 days should be considered for a randomized study for treatment of refractory hemorrhagic cystitis. Cystoscopic examination and evacuation of clots prior to therapy may be required to achieve the full benefit of this treatment.
OBJECTIVE: To evaluate supratrigonal cystectomy and enterocystoplasty in patients with interstitial cystitis. METHODS: We reviewed four women with interstitial cystitis with infructuos conservative treatment and performed supratrigonal cystectomy and enterocystoplasty. All the patients fulfilled the NHI criteria with increased voiding frequency by night (mean 7.3 times). In 3 cases urodynamic study was available. We used is the four patients ileon as segment for the enterocystoplasty. RESULTS: Mean postoperative follow up was 60 months. In all cases the suprapubic pain disappeared and night voiding frequency reduced (mean 2.2 times). We don't have mayor complications. One patient needs self catheterism 3 years after surgery. CONCLUSION: In patients with interstitial cystitis to be operated supratrigonal cystectomy and enterocystoplasty is the most effective method.