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Severe cyclophosphamide-induced hemorrhagic cystitis successfully treated by total cystectomy with ileal neobladder substitution: a case report.

A 45-year-old woman with intractable cyclophosphamide-induced hemorrhagic cystitis was successfully treated with total cystectomy and ileal neobladder substitution. To our knowledge this is the first reported reconstruction of the lower urinary tract in a patient with acute hemorrhagic cystitis using a neobladder. Neobladder substitution is contraindicated if the urethra or bladder neck is involved in the disease, although neither was involved in our patient. Whether these lesions are generally left intact has not been discussed previously. If a neobladder can be used, life threatening hemorrhagic cystitis should be treated with total cystectomy accompanied by immediate neobladder substitution.

Breast Neoplasms↗

Adenovirus-associated hemorrhagic cystitis treated with intravenous ribavirin.

Adenovirus hemorrhagic cystitis following bone marrow transplantation occurs in 2 to 16% of the patients. While usually self-limiting, this disease can cause significant morbidity and even mortality in the immunocompromised patient. Risk factors include graft versus host disease and pre-transplant seropositivity to adenovirus. Standard treatment of this disorder consists of hydration, diuresis and analgesics. Failure of these measures leads to multiple blood transfusions, severe patient morbidity and possible death. When conservative therapy is unsuccessful, there is no proved standard of care. We recently used ribavirin, a broad-spectrum antiviral agent against adenovirus infection in vitro, to treat refractory adenovirus hemorrhagic cystitis after bone marrow transplantation. The hematuria and urinary symptomatology resolved without demonstrable side effects. We present ribavirin as a therapeutic alternative when conservative treatment for adenovirus hemorrhagic cystitis fails.

Adenovirus Infections, Human↗

The bladder mucus (glycosaminoglycan) layer in interstitial cystitis.

The thin mucus or glycosaminoglycan layer of the bladder may be implicated in the pathogenesis of interstitial cystitis. We developed a specific anti-mucus, antisera stabilization technique to study the ultrastructural morphological appearance of the layer, and have used this technique to compare the surface morphology of 10 control and 10 interstitial cystitis patients. The electron micrographs demonstrate the ultrastructural characteristics of the pathological changes seen in interstitial cystitis but they did not show any significant difference in the morphological appearance of the mucus or glycosaminoglycan layer between the 2 groups.

Adult↗

Impaired bladder perfusion in interstitial cystitis: a study of blood supply using laser Doppler flowmetry.

Laser doppler flowmetry was used to study bladder blood flow in 16 patients with interstitial cystitis and in 18 control subjects. All studies were performed at cystoscopy under general anesthesia. Interstitial cystitis patients conformed to the diagnostic criteria of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Blood flow measurements were made at four specific sites in the bladder at a capacity of 100 ml. and at full capacity. The mean maximum capacity under anesthesia was 828 cc for the control group and 562 cc for the IC group. Blood flow at low capacity was similar in the two groups. When the bladder was filled to capacity, blood flow increased by a mean of 9.05 LDF units in the control group but only by 0.06 LDF units in the IC group (p = 0.007). Vault perfusion increased considerably more in the control group compared to the IC group (p = 0.002). The mean ratio of vault to trigonal perfusion was similar in both groups and was not affected by the overall blood flow changes which accompanied distension. Although the mean bladder capacity under anesthesia was greater in the control group, covariant analysis showed that the significant differences in perfusion between the two groups occurred independently of changes in capacity. It is concluded that bladder perfusion at capacity is significantly impaired in interstitial cystitis.

Cystitis↗

Percutaneous nephrostomy for treatment of intractable hemorrhagic cystitis.

Six patients with severe hemorrhagic cystitis unresponsive to traditional localized therapy were treated with percutaneous nephrostomy for diversion of urine. Bladder hemorrhage ceased in 3 patients, decreased in 2 and was unchanged in 1. In 1 patient with profound thrombocytopenia perirenal hematoma developed as a result of the nephrostomy placement but this complication was self-limited and did not require surgery. Our experience with these 6 patients indicates that nephrostomy diversion is safe and effective in most cases of hemorrhagic cystitis refractory to traditional, nonoperative therapy. Percutaneous urine diversion may obviate the need for surgical urinary diversion in patients who have intractable hemorrhagic cystitis.

Cystitis↗

Mast cell infiltration in intestine used for bladder augmentation in interstitial cystitis.

Two patients with histologically confirmed interstitial cystitis underwent bladder augmentation procedures (clam cystoplasty and Mainz pouch cystoplasty) because of therapy resistant low abdominal pain and decreased functional bladder capacity. However, symptoms of low abdominal pain and urinary retention (1 patient) persisted, and cystectomy was performed in both patients after 14 and 20 months, respectively. Histological examination of the specimens showed changes in the intestinal areas of the augmented bladder, resembling interstitial cystitis. The etiology of this phenomenon and the possible role of intestinal interstitial cystitis in augmentation failures are discussed.

Adult↗

Failure of combined supratrigonal cystectomy and Mainz ileocecocystoplasty in intractable interstitial cystitis: is histology and mast cell count a reliable predictor for the outcome of surgery?

Eight women with severe intractable interstitial cystitis were treated with supratrigonal cystectomy and Mainz ileocecocystoplasty. The preoperative evaluation consisted of symptom analysis, cystometry, cystoscopy and bladder pathological findings. Seven patients had increased mast cell density. Median followup was 10 months. The symptoms resolved in 2 patients but recurred in 6 shortly after the operation. Voiding could not be established in 4 patients. Self-catheterization was difficult and painful. Ultimately, cystectomy and urinary diversion were performed in 5 patients and is scheduled in 1. The 2 cured patients had a small contracted bladder preoperatively while they were under anesthesia, while all 6 failed cases had a large bladder capacity. Postoperative biopsies from the trigone showed no difference in the amount of fibrosis, the degree of degenerative changes in the muscle and mast cell density between the 2 cured patients and the 6 who failed to improve. The mast cell density and the histological status of the trigone cannot be used as predictors of the outcome of supratrigonal cystectomy. The role of the mast cells in interstitial cystitis is reviewed. Combination of supratrigonal cystectomy and a Mainz augmentation cystoplasty cannot be recommended in patients with intractable interstitial cystitis and a large bladder capacity.

Cecum↗

Time-course of alterations of bladder function following acetone-induced cystitis.

Although chemical cystitis is known clinically to cause decreased bladder function, there are few experimental studies on the progression of, and recovery from chemical cystitis. Mature male rabbits underwent intravesical instillation of 50% acetone solution through a urethral catheter. Micturition profiles showed a marked decrease of the mean and maximal micturition volume and an increase in number of micturitions as early as one day after treatment. The micturition profile gradually normalized between four and eight weeks after instillation. In vivo cystometry showed a very small bladder capacity and low compliance during the first week following instillation, and gradually recovered to control levels by four weeks. Functional studies using the in vitro whole bladder model showed a significant decrease in the ability of the bladder to generate pressure and to empty at three days after instillation. These parameters recovered partially by two weeks, and completely by four weeks. Chemical cystitis induced by intravesical acetone instillation resulted in a severe decrease in the bladder function, i.e. contracted bladder with low compliance and poor ability to generate pressure and empty. However, these changes were reversible within the two month period of study.

Acetone↗

The use of prostaglandin F2 alpha for the prophylaxis of cyclophosphamide induced cystitis in rats.

It is well-established that cystitis is a significant cause of morbidity after cyclophosphamide administration in clinical populations. We induced hemorrhagic cystitis in rats using cyclophosphamide and compared controls to those pretreated with prostaglandin F2 alpha. Rats were then evaluated for differences in bladder weights, gross edema, gross bleeding, and histologic changes. The weights of the bladders which had been treated with cyclophosphamide were 94% greater than the controls. The weights of the bladders which were pretreated with prostaglandin F2 alpha before cyclophosphamide were only 19% greater than controls. Significant differences were found between cyclophosphamide controls and prostaglandin F2 alpha pretreated groups for gross weight (p less than .0005), gross edema (p less than .0005), and histology (.0005 less than p less than .005). We conclude that prostaglandin F2 alpha may be helpful in preventing cyclophosphamide induced cystitis.

Animals↗

Clinical features and spectrum of light microscopic changes in interstitial cystitis.

Transurethral resection material from a series of 64 patients with classical (ulcer) interstitial cystitis (60 women and 4 men, with a mean age of 64 years), 44 with nonulcer interstitial cystitis (40 women and 4 men, with a mean age of 39 years) and 20 control women (mean age 49 years) were studied by light microscopy. Patients with classical disease had mucosal ulceration and hemorrhage, granulation tissue, intense inflammatory infiltrate, elevated mast cell counts and perineural infiltrates. Patients with nonulcer disease, despite the same severe symptoms, had a relatively unaltered mucosa with a sparse inflammatory response, the main feature being multiple, small, mucosal ruptures and suburothelial hemorrhages that were noted in a high proportion of the patients. It is suggested that these features are characteristic, specific and prevalent enough to allow for morphological differentiation of the 2 clinical subtypes of interstitial cystitis.

Adult↗

Intravesical formalin for hemorrhagic cystitis: analysis of therapy.

In an extensive search of the literature 235 cases of intractable hemorrhagic cystitis treated with intravesical formalin were identified. Effectiveness of therapy, rate of recurrence of hematuria, morbidity and mortality were analyzed with respect to concentration of formalin and to the etiology of hematuria. Increasing concentrations of formalin slightly improved effectiveness of therapy and reduced the rate of recurrence of hematuria. However, this often resulted in an increase in morbidity. When patients were categorized according to the etiology of intractable hematuria it was noted that lower concentrations of formalin were effective in controlling hematuria caused by either cyclophosphamide cystitis or unresectable carcinoma of the bladder. In contrast, higher formalin concentrations were required to control bleeding due to radiation cystitis.

Administration, Intravesical↗

A prospective double-blind clinically controlled multicenter trial of sodium pentosanpolysulfate in the treatment of interstitial cystitis and related painful bladder disease.

Painful bladder disease, sensory bladder disease, chronic abacterial cystitis and interstitial cystitis are ill-defined conditions of unknown etiology and pathogenesis, and, therefore, they are without any rational therapy. Pathogenetic theories concerning defects in the epithelium and/or mucous surface coat (including glycosaminoglycans) of the bladder, and theories concerning immunological disturbances predominate. Sodium pentosanpolysulfate (Elmiron) acts by substituting a defective glycosaminoglycan layer and inhibits complement reactions in inflammatory processes. We compared sodium pentosanpolysulfate versus placebo in a prospective double-blind, clinically controlled multicenter trial of 115 patients with painful bladder disease. Two protocols were used. Protocol A included 43 patients with clinically and pathologically anatomically verified interstitial cystitis (28 or more mast cells per mm.2), and protocol B included 72 patients with a painful bladder and unspecific histological findings. The patients were randomized to receive either sodium pentosanpolysulfate (200 mg. twice daily) or placebo capsules for 4 months. Before and after the trial the patients were evaluated with symptom grading, urodynamics and cystoscopy with distension and deep bladder biopsies. The results showed no difference between the pre-trial and post-trial values in the sodium pentosanpolysulfate and placebo groups in both protocols in regard to symptoms, urodynamic parameters, cystoscopic appearance and mast cell counts. A significant increase in the cystoscopically determined bladder capacity in the sodium pentosanpolysulfate group in protocol A was found. We conclude that no statistically or clinically significant effect of sodium pentosanpolysulfate was found compared to placebo in patients with painful bladder disease.

Adult↗

Treatment of ulcer and nonulcer interstitial cystitis with sodium pentosanpolysulfate: a multicenter trial.

The effect of sodium pentosanpolysulfate (Elmiron) in the treatment of interstitial cystitis was observed in an open controlled multicenter trial. We studied 87 patients with symptoms for more than 2 years at 17 centers in Finland and Sweden. Patient selection was based on the typical chronic symptomatology but the material subsequently was stratified according to objective cystoscopic findings. The medication (400 mg. daily in 2 oral doses) was discontinued after 6 months. The response was evaluated every 4 weeks during treatment and every 3 months thereafter. Most patients responded favorably, many with diminution of pain within only 4 weeks from the start of treatment. The frequency of micturition decreased significantly and the mean volume per void per 24 hours increased in the patients without bladder ulceration but such changes were not found in the patients with ulcer. The bladder capacity was smaller in the ulcer group. In these patients the pre-treatment intensity of pain was somewhat greater than in those without bladder ulcer but the pain was alleviated in both groups and this effect was stable at the 3-month followup. The differences in responses in the 2 groups indicate a probable fundamental difference between ulcerative and nonulcerative interstitial cystitis. Side effects of the drug were few, slight and transient. Therefore, the study indicates that a significant number of patients with interstitial cystitis can be expected to benefit from treatment with sodium pentosanpolysulfate.

Adult↗

The effects of chronic cystitis on vesicoureteral reflux in an animal model.

The purpose of this study was to determine if chronic cystitis interferes with maturation of the ureterovesical junction, thus prolonging vesicoureteral reflux in infant rhesus monkeys (Macaca mulatta). Serial implantations of a Proteus-infested silastic pellet into the bladder wall ensured continued infection as demonstrated by urine culture. Chronic cystitis as evidenced by pathological findings at surgery and sacrifice was created in a group of infant monkeys who had initial spontaneous vesicoureteral reflux. There was no evidence of pyelonephritis. Four animals represent a short term study since they were followed from four months to one year of age. Three animals were long term studies and were evaluated for at least 21/2 years. In no animals did chronic cystitis delay the normal disappearance of vesicoureteral reflux that is commonly seen in these animals as the ureterovesical junction matures, as demonstrated by serial cystograms. In two animals reflux (after initial clearing) reappeared when a bladder calculus formed in these chronically infected animals. Renal damage occurred only in these animals. In conclusion, this animal model failed to demonstrate interference with normal vesicoureteral junction maturation in the face of a chronic bladder infection.

Aging↗

Scanning electron microscopy of polypoid cystitis--a reversible lesion of the human bladder.

Scanning electron microscopy was performed on forceps biopsies from 13 patients with catheter-associated polypoid cystitis. Pleomorphic microvilli, which varied considerably in appearance, were found on surface cells of all cases with polypoid cystitis. Practically all of the characteristics of pleomorphic microvilli assigned earlier to bladder tumor cells in humans were identified on specimens from patients with polypoid cystitis. Pleomorphic microvilli were not observed in the bladder biopsies from control patients. The appearance of pleomorphic microvilli was consistent with reversible lesions of the human bladder and they are not specific markers of pre-neoplastic hyperplasia or malignancy.

Aged↗

Busulfan-induced hemorrhagic cystitis.

We report a case of severe hemorrhagic cystitis induced by prolonged busulfan therapy. The clinical course and pathological results were similar to irradiation and cyclophosphamide cystitis. Only 1 such case has been described previously. Although hemorrhagic cystitis induced by busulfan is a rare complication it should be considered in the differential diagnosis and busulfan should be discontinued immediately.

Adult↗

Cystitis follicularis in children with primary vesicoureteral reflux.

In an attempt to determine whether cystitis follicularis affects the spontaneous resolution of primary vesicoureteral reflux we reviewed the records of 65 children with reflux and cystitis follicularis. A group of children with primary vesicoureteral reflux but without cystitis follicularis was included as controls. The data did not reveal a statistically significant difference in either the rate of spontaneous resolution of reflux or the need for surgical correction between these 2 groups of children.

Child↗

The prevalence and significance of Brunn's nests, cystitis cystica and squamous metaplasia in normal bladders.

The frequency of Brunn's nests, cystitis cystica and squamous metaplasia was studied by multiple histologic sections in 100 grossly normal bladders obtained at postmortem examination. Of the 100 bladders 93 per cent had at least 1 of the 3 proliferative changes. Brunn's nests and cystitis cystica were seen in 89 and 60 per cent of the bladders, respectively, most often at the bladder neck and trigone. Non-keratinizing squamous metaplasia of the vaginal type was seen almost exclusively on the trigone and bladder neck in 46 per cent of the premenopausal and postmenopausal women but in only 7 per cent of the men. There was no satisfactory evidence that inflammation was casually associated with these changes. These findings suggest that Brunn's nests, cystitis cystica and squamous metaplasia of the vaginal type in women are normal variants of bladder urothelium and have no precancerous potential.

Adolescent↗