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PubMed1975

Cyclophosphamide-induced hemorrhagic cystitis in children with leukemia.

The records of 314 children with acute lymphocytic leukemia (ALL) were reviewed to determine the frequency, clinical and laboratory features; contributing factors; and prognosis of cyclophosphamide-induced hemorrhagic cystitis. Twenty-five well-documented cases of hemorrhagic cystitis were identified. While most of the affected children suffered a mild transient illness, 1 patient died as a result of bladder hemorrhage. The doses of cyclophosphamide received by these children ranged widely and did not correlate with the severity of the cystitis. The frequency of this complication did not differ significantly with sex, age or route of administration. However, cystitis was over twice as frequent in black children as in white. Nineteen of 25 cases occurred in the spring and summer months. The group of affected children did not differ significantly from a matched control group in terms of total drug dosage received, incidence of systemic toxicity, mean urine specific gravity, or overall survival.

Adolescent↗
PubMed1988

Cyclophosphamide-induced hemorrhagic cystitis. A review of 100 patients.

Cyclophosphamide is an alkylating agent used intravenously or orally in the treatment of both malignant and nonneoplastic diseases. A known adverse effect of such treatment is hemorrhagic cystitis. A series of 100 patients with hemorrhagic cystitis induced by cyclophosphamide was studied. Major symptoms were gross hematuria (78%) and irritative voiding symptoms (45%). Microhematuria developed in 93% of patients. Hemorrhagic cystitis developed at significantly lower doses and shorter durations of therapy in patients treated intravenously than in patients treated orally. Cystectomy was required in nine patients and bladder cancer developed in five. Urine cytologic study, urinalysis, and cystoscopy are important in the diagnosis of hemorrhagic cystitis, and these studies plus periodic excretory urography are important for surveillance. In addition, new methods of protecting against the urotoxicity are available.

Administration, Oral↗
PubMed2002

Non-surgical interventions for late radiation cystitis in patients who have received radical radiotherapy to the pelvis.

BACKGROUND: Chronic radiation cystitis occurs a minimum of three months after completion of pelvic radiotherapy and represents a range of clinical symptoms for which there is as yet no recommended standard management. OBJECTIVES: The aim of this review was to identify the various non-surgical treatment options for the management of late chronic radiation cystitis and evaluate the evidence. SEARCH STRATEGY: Synonyms for radiation therapy and for the spectrum of radiation toxicity to the bladder in both text and MeSH terms were combined and applied to a range of databases without restriction of year of publication, methodology or language. SELECTION CRITERIA: The inclusion criteria included studies of interventions for the non-surgical management of all grades of late radiation cystitis. DATA COLLECTION AND ANALYSIS: Out of 80 relevant studies, there were no RCTs that met the inclusion criteria, but there were three prospective case series and two non-randomised studies which assessed different interventions and were not comparable. MAIN RESULTS: Sixty-three reports met the stated inclusion criteria. The majority were predominantly retrospective case series with the exception of two trials which were unrandomised and unblinded studies with a control group for comparison of effect. Although these two trials, Micic 1988, (intravesical placental extract) and Milani 1988, (flavoxate) provided the strongest evidence they were not randomised and were essentially isolated controlled studies. REVIEWER'S CONCLUSIONS: In such a relatively rare condition there are obvious difficulties in identifying sufficient patients to participate in a randomised controlled trial. The number of published reports is a reflection of the degree of medical interest that exists in providing therapeutic solutions for late radiation cystitis. However, in spite of the two studies of level IIA evidence, the absence of randomised controlled trials makes it impossible to draw any firm conclusions.

Chronic Disease↗
PubMed1993

Hemorrhagic cystitis complicating untreated necrotizing vasculitis.

Although the genitourinary system is frequently affected in polyarteritis nodosa, involvement of the wall of the urinary bladder is extremely uncommon; moreover, when reported, it has been merely as an incidental finding late in the disease course. In contrast, hemorrhagic cystitis is a well-recognized complication of cyclophosphamide therapy for the systemic vasculitides, but has not previously been reported to complicate untreated vasculitis. Herein is described a patient who presented with non-treatment-related hemorrhagic cystitis which was found to be due to nongranulomatous necrotizing vasculitis of the wall of the urinary bladder. This represents both a novel presentation of polyarteritis and a previously unreported etiology of hemorrhagic cystitis. The differential diagnosis of apparently spontaneous hemorrhagic cystitis should therefore include active necrotizing vasculitis, independent of prior therapy.

Cystitis↗
PubMed2001

Boon's disease: hemorrhagic cystitis in conjunction with massive exfoliation of degenerated urothelial cells (apoptosis?) during intercontinental flights in an otherwise healthy person.

Hemorrhagic cystitis is a well-defined clinical emergency, usually occurring in the course of treatment with toxic agents such as cyclophosphamide. We present a case of hemorrhagic cystitis in an otherwise completely healthy female. The three documented attacks were severe and started during intercontinental flights. This type of hemorrhagic cystitis as a disease proved to be a boon, treatable by drinking large amounts of water, and was diagnosed by and in Dr. Boon; thus was the appellation Boon's disease coined. Cellular changes in the urine specimen taken after onset of the disease indicated massive exfoliation of degenerated urothelial cells with morphological features suggestive of apoptosis. It seems likely that this process can be initiated by any event which is associated with compromise of vitality of the urinary bladder lining, such as may occur in hypovolemia. This type of hemorrhagic cystitis is most probably not uncommon in susceptible individuals during intercontinental flights.

Aircraft↗
PubMed2002

Cytologic manifestations of cystitis follicularis in urine specimens.

Four cases of cystitis follicularis diagnosed by urine cytology are presented, and are the first reported in the cytologic literature. Cystitis follicularis (follicular cystitis) is characterized by formation of lymphoid follicles in the lamina propria of the trigonal region of the bladder, and is considered to be the result of repeated bouts of urinary tract infection, usually bacterial, with other pathologic processes contributing to the development and prolongation of the infection. Cytologically it differs from chronic cystitis with prominent lymphocytosis by the presence of cellular elements from the germinal centers of lymphoid follicles, reminiscent of the cytologic findings in follicular cervicitis, with possible additional epithelial cytologic atypias from the overlying urothelium, which frequently undergoes reactive changes (hyperplastic, metaplastic, and ulcerative). The practical aspect of recognition of this entity in cytologic specimens is avoiding diagnostic errors of possible malignancy (lymphoid or other), and also of other forms of inflammatory disease, such as granulomatous type, with a different clinical significance.

Aged↗
PubMed2007

The effect of tamoxifen on bladder functions and histology, and the role of estrogen receptor beta in a rat chemical cystitis model.

AIMS: The purpose of this study was to investigate the effect of tamoxifen citrate on bladder functions and histology, and also to investigate the role of estrogen receptor beta (ER beta) in a rat chemical cystitis model. METHODS: The study included 37 female Sprague-Dawley rats. Chemical cystitis was induced by intravesical instillation of hydrochloric acid in 32 rats, and the treatment group (n = 15) received daily 0.4 mg/kg of tamoxifen citrate with orogastric tube, and the control group (n = 17) received no treatment. The sham group consisted of five rats having no acid instillation and no treatment. Cystometric studies were performed in all rats at the beginning and end of the experiment. The rats were euthanized at 2 months. The bladders were removed and examined histologically for mast cells, inflammatory cells, and ER beta. RESULTS: The mean maximal bladder volume increased by 73.6% +/- 25.2 in the treatment group and decreased by 7.2% +/- 10.8 in the control group, revealing a significant difference (P = 0.007). The mean bladder compliance increased by 81.2% +/- 25.2 in the treatment group and decreased by 4.8% +/- 12.7 in the control group, revealing a significant difference between the two groups (P = 0.005). ER beta positive cells were significantly lower in the bladders with chronic cystitis than in the sham group (P = 0.038). CONCLUSIONS: Tamoxifen citrate may be an alternative choice, as easy, to other treatment options in the treatment of chronic inflammatory condition to improve deteriorated bladder function. In addition, ER beta may have a role on chronic bladder inflammation in a rat chemical cystitis model.

Animals↗
PubMed1994

Hemorrhagic cystitis following radiotherapy for stage Ib cancer of the cervix.

Our purpose was to study the incidence, severity, timing, clinical management, and outcome for patients who developed hemorrhagic cystitis following pelvic radiotherapy for stage Ib cancer of the cervix. A total of 1784 patients with stage Ib cancer of the cervix were treated with pelvic radiotherapy at the University of Texas M. D. Anderson Cancer Center between 1960 and 1989. The majority received a combination of external-beam and intracavitary treatments. Patients with hemorrhagic cystitis were identified through retrospective review of their medical records, and a grade was assigned to each occurrence. A total of 116 (6.5%) patients with hemorrhagic cystitis were identified. The initial occurrence was grade 1 (minor occurrence) in 59%, grade 2 (repeated minor bleeding) in 23%, and grade 3 (hospitalization for medical management) in 18%. The median interval from the beginning of radiotherapy to the onset of hematuria was 35.5 months (mean 58 months). The median time to initial grade 3 occurrences was 37.5 months (mean 84 months). Actuarial life table analysis revealed that the risk of hematuria is 5.8% at 5 years, 7.4% at 10 years, and 9.6% at 20 years. The risk for a grade 3, 4 (requiring surgical intervention), or 5 (death) complication is 1.0, 1.4 and 2.3% at 5, 10, and 20 years, respectively. Approximately one-third of the patients with a grade 3 occurrence were rehospitalized for management of bladder complications a median of 3.5 months following the first grade 3 occurrence, although some of these readmissions occurred many years later. Associated urinary-tract infection was common. In no case did a cystoscopic bladder biopsy reveal recurrent tumor or a second primary tumor when visual inspection revealed typical radiation changes. The incidence of severe hemorrhagic cystitis following radiation for stage Ib cancer of the cervix is low and can occur many years following treatment. Minor episodes of hematuria are managed by empiric antibiotic therapy until the results of urine cultures are available. Cystoscopy is reserved for patients with persistent bleeding to rule out clot retention or the slight possibility of a second primary tumor or recurrent disease. Biopsy should be avoided if obvious radiation changes are present. Clot evacuation and continuous bladder irrigation remain the standard treatment for patients with heavy bleeding.

Cystitis↗
PubMed2000

Hemorrhagic pyelitis, ureteritis, and cystitis secondary to cyclophosphamide: case report and review of the literature.

OBJECTIVE: Hemorrhagic cystitis is a well-known complication of cyclophosphamide therapy but extensive involvement of the entire urinary tract is far less common. We report here a patient who developed severe hemorrhagic pyelitis, ureteritis, and cystitis after one cycle of cyclophosphamide-containing combination chemotherapy. METHOD: A patient with synchronous carcinoma of the ovary and the uterus developed severe hemorrhagic pyelitis, ureteritis, and cystitis leading to bilateral hydronephroses and acute renal failure after one cycle of combination chemotherapy containing cyclophosphamide. The blood clots in the upper urinary tract were aspirated endoscopically and bilateral internal ureteric stents were inserted. RESULT: She underwent a prolonged diuretic phase with several episodes of hypokalemia, hypomagnesemia, and hypocalcemia and required intensive fluid and electrolytes replacement. Subsequently, she recovered fully with the ureteric stents removed 26 days later. CONCLUSION: In contrast to previous reports, where 2.8 g of cyclophosphamide was estimated to be the minimum cumulative dose required to cause hemorrhagic cystitis, this case illustrates that severe hemorrhagic complication can occur even after a low dose of cyclophosphamide (600 mg/m(2), total dose of 846 mg). Prompt diagnosis and intervention may be life-saving.

Antineoplastic Agents, Alkylating↗
PubMed1995

Cyclophosphamide cystitis as a model of visceral pain in rats: model elaboration and spinal structures involved as revealed by the expression of c-Fos and Krox-24 proteins.

The evoked expression of the immediate early gene (IEG)-encoded proteins c-Fos and Krox-24 was used to monitor spinal visceronociceptive processing that results from cyclophosphamide cystitis in behaving rats. Animals received a single dose of 100 mg/kg i.p. of cyclophosphamide and survived for 30 min to 5 h. Longer survival times were not considered because of ethical considerations. Cyclophosphamide-injected animals developed characteristic behavioral signs in parallel with development of bladder lesions and spinal evoked expression of IEG-encoded proteins. Histological examination of the urinary bladder was used to evaluate the degree of cystitis and as a criterion for selection of groups of animals to be quantitatively analyzed. Controls consisted of freely behaving animals including control (un-injected), sham (saline-injected) or diuretic (furosemide-injected) animals. Behavioral modifications consisted of lacrimation, piloerection, assumption of a peculiar "rounded-back" posture, which was accompanied by head immobility and various brief "crises" (tail hyperextension, abdominal retractions, licking of the lower abdomen, backward withdrawal movements). Abnormal behaviors, which first appeared (lacrimation, piloerection) at the end of postinjection hour 1, progressively increased in severity (rounded-back posture) over the following 90 min to reach a plateau at about postinjection hour 2; the rounded-back posture was maintained up to time of death. Histological modifications of bladder tissue were assessed using a 4-grade scale in a blind setting. The 1st grade consisted of control or sham animals with no bladder lesion; 2nd grade, animals with simple chorionic edema; 3rd grade, animals with chorionic edema associated with mucosal abrasion, fibrin deposit, and onset of polymorphonuclear leukocyte infiltration; 4th grade, animals with complete cystitis corresponding to an increase in severity and spread of all the signs of cystitis described above plus petechial hemorrhage. Simple chorionic edema was observed from 30 min to 3 h postinjection, but with a progressive increase in severity over time. Edema accompanied by epithelial abrasion was observed for animals that survived 3-4 h postinjection; complete inflammation was observed in animals that survived 4-5 h postinjection. The study of c-Fos- and Krox-24-encoded protein expression demonstrated that few lumbosacral spinal areas were specifically involved in the processing of visceral inputs in response to bladder stimulation. These areas were the parasympathetic column (SPN), the dorsal gray commissure (DGC as the caudal extent of lamina X), and superficial layers of the dorsal horn.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1980

Virulence of Escherichia coli in acute pyelonephritis, acute cystitis and asymptomatic bacteriuria.

E. coli strains were isolated from urine specimens of hospitalised patients with acute pyelonephritis, acute cystitis or asymptomatic bacteriuria (ABU), and tested for virulence in an experimental mouse model. Of 12 pyelonephritis-strains 11 were shown to be virulent and 1 avirulent; of 12 cystitis-strains 4 were virulent and 8 avirulent; of 12 ABU-strains 5 were virulent and 7 avirulent. It is concluded that, while no difference in virulence was found between cystitis- and ABU-strains, pyelonephritis-strains were more often virulent than cystitis- and ABU-strains. No associations could be shown between virulence of the isolated strains and the presence of antibody-coated bacteria in the urine. Common urinary O types were not more often virulent than other O types. No relationship was seen between virulence and the presence of K antigen or the presence of particular K types.

Acute Disease↗
PubMed1997

[Chronic interstitial cystitis (Hunner) associated verrucous carcinoma of the urinary bladder].

A verrucous carcinoma of the urinary bladder (pT4N0M0, G1) developed in a 66-year-old woman who had been suffering from interstitial cystitis with Hunner's ulcer for 10 years. Up to now, only 7 cases of verrucous carcinoma of the urinary bladder unassociated with bilharzial cystitis have been reported. Although the development of a verrucous carcinoma as a complication of interstitial cystitis has not been reported so far, the authors regard the chronic irritation of the bladder to be the most important etiologic factor for the malignant transformation. After conservative management had failed, a radical cystectomy with supravesical urinary diversion was performed. The characteristics of interstitial cystitis, verrucous carcinoma and surgical management are discussed.

Aged↗
PubMed2005

Contribution of flavonoid antioxidants to the preventive effect of mesna in cyclophosphamide-induced cystitis in rats.

Cyclophosphamide (CP) is widely used, alone or in combination with other chemotherapeutic agents, for treatment of neoplastic diseases. Its urotoxicity may cause dose-limiting side-effects, for example hemorrhagic cystitis. The agent most often used to prevent this side-effect is mesna (2-mercaptoethane sulfonate). Overproduction of reactive oxygen species during inflammation is one reason for possible urothelial injury. The aim of this study was to evaluate whether combinations of quercetin and epigallocatechin 3-gallate (EGCG), flavonoid antioxidants and mesna could prevent cystitis induced by cyclophosphamide, better than mesna alone. A total of 38 male Sprague-Dawley rats were divided into five groups. Four groups received single dose of CP (100 mg kg(-1)) intraperitoneally at the same time. Group 2 received CP only, group 3 received mesna (3 x 21.5 mg kg(-1)), group 4 received a single dose of mesna+EGCG (2 x 20 mg kg(-1)), and group 5 received a single dose of mesna+quercetin (2 x 20 mg kg(-1)), before and after CP injection. Group 1 (not treated) served as control. CP injection alone resulted in severe cystitis. Mesna resulted in some, but not full, protection against CP toxicity. Quercetin and catechine, together with mesna, resulted in full protection against CP toxicity, on the basis of histopathology of the urinary bladder. It was concluded that oxidants might be important in the pathogenesis of CP-induced cystitis, and that flavonoid antioxidants, used in addition to mesna, may help to ameliorate bladder damage.

Animals↗
PubMed1978

Interstitial cystitis: early diagnosis, pathology, and treatment.

In a retrospective review, 52 patients with interstitial cystitis have been studied. Patients with persistent lower tract irritative symptoms, repeatedly sterile urine, and negative urine cytology must be suspected of having interstitial cystitis, and a diagnosis of urethral syndrome in such patients is highly questionable until cystoscopy under anesthesia has been performed. We believe that the finding of multiple petechia-like hemorrhages (glomerulations) on the second distention of the bladder is the hallmark of interstitial cystitis, and that a reduced bladder capacity and a Hunner's ulcer represent a different (classic) stage of this disease. In all stages, the characteristic histologic finidng is submucosal edema and vasodilation. The presence of eosinophils and mast cells is variable, and even in the classic disease the muscularis often appears to be normal. Immuno fluorescent studies and laboratory tests, including the fluorescent antinuclear antibody test (FANA), have not helped us to diagnose (or investigate) interstitial cystitis. Bladder instillations with a 0.4 per cent solution of oxychlorosene sodium (Clorpactin WCS-90) have provided remarkable relief for many patients with this disease, particulary those with the classic form.

Adult↗
PubMed1991

Eosinophilic cystitis in children.

Eosinophilic cystitis is an uncommon inflammatory disorder of the urinary bladder which causes irritative voiding symptoms and may mimic rhabdomyosarcoma radiographically. In children, eosinophilic cystitis has been previously reported to be self-limiting and requires no specific therapy. Reported herein is a case of a nine-year-old girl in whom eosinophilic cystitis recurred following antireflux surgery, raising the question of an association of eosinophilic cystitis with local trauma such as bladder surgery. Consideration should be given to pretreatment with steroids and antihistamines prior to surgery in these patients.

Child↗
PubMed1992

Eosinophilic cystitis in children.

A case of eosinophilic cystitis in a child is presented and the pediatric literature reviewed. The etiology of this condition is still unknown. Mean age of children with eosinophilic cystitis is 5.9 years. Black children appear to be more affected than white children, with a male preponderance. Hematuria and dysuria are the most common symptoms. The diagnosis of eosinophilic cystitis is made by cystoscopy with biopsy. The disease appears self-limited with its course unaltered by antibiotics. Recurrence of eosinophilic cystitis is possible.

Adolescent↗
PubMed2004

Oral glucosamine and the management of feline idiopathic cystitis.

Oral glucosamine was compared to a placebo for the management of cats with feline idiopathic cystitis (FIC) in a randomised, double-blinded, placebo-controlled, study. Forty cats with a history of recurrent cystitis due to FIC were divided into two groups and treated daily per os with either 125 mg N-acetyl glucosamine or a placebo for six months. Owners graded their cats' clinical signs at the beginning and end of the study, and kept daily diaries documenting signs of cystitis using visual analogue scales. Further episodes of cystitis were seen in 26 (65%) of the cats during the study. Affected cats experienced a mean of five recurrences (range 1-19) with each recurrence lasting a mean of four days (range 1-64 days). There were no significant differences between the two groups when considering the owners assessments of the mean health score (P>0.5), the average monthly clinical score (P=0.22) or the average number of days with clinical signs (P=0.28). Two cats suffered from such severe recurrent urethral obstruction that they were euthanased; they were both in the placebo group. Compared to the start of the study the majority of cats in both groups improved significantly (P<0.001) (mean health score of each group at the start was 0.5+/-SD 0.5, compared to glucosamine 4.4+/-0.7 and placebo 3.9+/-1.6 at the end). This is believed to have occurred because the owners of 36 of the 40 cats (90%) started feeding more canned cat food. The urine specific gravity at the start of the trial was significantly higher (mean 1.050+/-SD 1.007) than when reassessed one month later (1.036+/-1.010, P<0.01).

Administration, Oral↗
PubMed2004

Eosinophilic cystitis after bladder instillation with dimethyl sulfoxide.

Eosinophilic cystitis is a rare and poorly understood disorder. We report the first case of an acute flare of eosinophilic cystitis in a 51-year-old woman after bladder instillation with dimethyl sulfoxide (DMSO) for presumed interstitial cystitis. The patient presented with severe bladder pain, fever, and eosinophilia several hours after instillation. These symptoms were unresponsive to conventional analgesic and antibiotic treatments. Cystoscopy revealed erythema and exudate at the bladder walls, along with edema of both ureteral orifices. Bladder biopsies demonstrated massive eosinophilic infiltration of the bladder, confirming the diagnosis of eosinophilic cystitis. Urologists should bear in mind this clinical entity, particularly when DMSO is administered to patients with multiple drug allergies.

Abdominal Pain↗