AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Further Reading
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Further Reading
• Multimedia
• References

Hemorrhagic cystitis is defined as an infectious or noninfectious process that leads to gross hematuria originating in the urinary bladder. Infectious causes include bacterial and viral etiologies. The various noninfectious causes are the topic of this discussion.

Problem

Noninfectious hemorrhagic cystitis most commonly occurs in patients who have undergone pelvic radiation, chemotherapy, or both. Affected patients may develop microscopic hematuria without any symptoms or gross hematuria with clots, leading to urinary retention. Treatment depends on the etiology, severity of the bleeding, and symptoms.

Rarely, arteriovenous malformations, stones, metastatic tumors, and, more commonly, urothelial malignancies manifest as gross hematuria. These are differentiated from hemorrhagic cystitis with imaging and during endoscopic evaluation.

Frequency

Hemorrhagic cystitis occurs in up to 70% of patients exposed to high doses of cyclophosphamide or iphosphamide chemotherapy and up to 15% of patients who undergo pelvic irradiation to treat malignancy. However, over the last several years, newer irradiation techniques have decreased the incidence of hemorrhagic cystitis to approximately 10% of treated patients.

Etiology

Noninfectious hemorrhagic cystitis is an inflammation of the bladder associated with hematuria. Patients usually present with urgency, frequency, dysuria, and, in some cases, abdominal discomfort. 

Although the causes of noninfectious hemorrhagic cystitis vary, this condition most commonly develops as a complication of pelvic radiation or from toxicity related to the use of certain chemotherapeutic drugs (eg, cyclophosphamide, iphosphamide). Less commonly, exposure to certain industrial chemicals, such as aniline or toluidine derivatives, can cause hemorrhagic cystitis. Although rare, drugs such as penicillins or danazol can also precipitate hemorrhagic cystitis.

Other extremely rare reports include associations with food poisoning (Salmonella typhi) and prolonged high-altitude air travel (Boon disease). Regardless of the perceived circumstance, an infectious etiology should be sought as part of the initial assessment, even in the setting of radiation or chemical exposure, as infection may serve as an exacerbating factor. Bacterial, fungal, parasitic, and especially viral bladder infections in immunocompromised patients are often complicated by hemorrhagic cystitis.

Radiation-Induced Hemorrhagic Cystitis

Nearly one fourth of patients who undergo pelvic radiation develop bladder-related complications. Slightly less than 50% of these patients develop diffuse hematuria. These patients usually have undergone radiation therapy for cancer of the prostate, colon, cervix, or bladder. Urgency, frequency, dysuria, and stranguria may develop acutely during radiation, or these symptoms may begin months to years after completion of radiotherapy.

The symptoms of radiation cystitis are caused by a microscopic progressive obliterative endarteritis that leads to mucosal ischemia. The ischemic bladder mucosa then ulcerates and bleeding ensues. Neovascular ingrowth to the damaged area then occurs, causing the characteristic vascular blush on cystoscopic evaluation. The new vessels are more fragile and may leak with bladder distension, minor trauma or any mucosal irritation. Submucosal hemorrhage and overt hematuria may then begin precipitously. Acute episodes of radiation cystitis wane within 12-18 months in most patients following radiation therapy.

As expected, the higher the dose and the wider the field encompassed by the radiation exposure, the more likely the sequelae of radiation cystitis. Patients who have undergone pelvic radiation are at an increased risk for radiation cystitis if additional radiotherapy is performed because of the cumulative dose effect. Infection, bladder outlet obstruction, and instrumentation are all factors that can exacerbate radiation cystitis.

Drug-Induced Hemorrhagic Cystitis

Chemotherapeutic drugs

The oxazaphosphorine-alkylating agents cyclophosphamide and ifosfamide are chemotherapeutic drugs that are useful in the treatment of lymphoma, leukemia, and certain solid tumors. These drugs are also commonly administered as conditioners prior to bone marrow transplantation.

Unfortunately, the toxicity of these drugs is not insignificant, and many of the adverse effects are urologic. Both microscopic and gross hematuria can result from the use of cyclophosphamide. The incidence of urologic adverse effects varies from 2-40%, and the toxicity is dose-related.

Cyclophosphamide itself is not toxic; the drug's toxicity is due to its hepatic conversion to the metabolite acrolein, which is excreted in the urine and causes bladder edema and bladder hemorrhage. Over time, chronic bladder damage manifests as fibrosis with decreased capacity, trabeculations, and telangiectasias. The adverse effects of cyclophosphamide are more likely due to increased bladder exposure to acrolein. Thus, patients receiving cyclophosphamide should always receive good hydration, and a Foley catheter is often placed to ensure immediate drainage of the bladder. Continuous bladder irrigation is sometimes recommended to hasten the clearance acrolein from the bladder.

Penicillins

Rarely, penicillins have been known to cause hemorrhagic cystitis in certain patients. Case reports have implicated methicillin, carbenicillin, ticarcillin, piperacillin, and penicillin VK. Most cases of hemorrhagic cystitis in patients who took extended-spectrum penicillins have been reported in those with cystic fibrosis who had previously received penicillin antibiotics. Symptoms can take up to 2 weeks to develop after the drug is started; when symptoms occur, the best treatment is to discontinue the offending drug immediately. Hemorrhagic cystitis in patients taking penicillins is thought to be caused by an immune-mediated hypersensitivity. Examination of the urine frequently reveals eosinophils.

Danazol

Treatment with danazol, a semisynthetic anabolic steroid, has caused hemorrhagic cystitis in patients with hereditary angioedema. Interestingly, the advent of hemorrhagic cystitis in these patients followed years of symptom-free treatment with danazol. Hematuria developed after 30-77 months of treatment in one study. In almost all cases, the hematuria resolved after cessation of danazol. The dose of danazol did not correlate with the severity of hemorrhagic cystitis. The etiology of hemorrhagic cystitis in patients being treated with danazol is unclear.

Other medications

Other medications that have been implicated in the development of hemorrhagic cystitis in limited reports include busulfan, thiotepa, temozolomide, bleomycin, tiaprofenic acid, allopurinol, methaqualone, methenamine mandelate, gentian violate, nonoxynol-9 suppositories, and intravesical acetic acid.

Other Causes of Noninfectious Hemorrhagic Cystitis

Environmental factors

Cases of hemorrhagic cystitis with no infectious etiology have been reported in patients whose occupation puts them in contact with certain urotoxic chemicals such as aniline (found in dyes, marking pens, and shoe polish) and toluidine (found in pesticides and shoe polish) derivatives. In these cases of hemorrhagic cystitis, the patient's exposure to the chemicals is usually work-related. Hemorrhagic cystitis due to these derivatives is self-limiting, and cessation of the exposure usually suffices for cure. Exposure to these chemicals also increases the risk of transitional cell carcinoma; thus, the workup for gross hematuria should reflect this possibility.

Chlordimeform

The pesticide chlordimeform is commonly used on cotton plants and fruit trees, and ingestion, inhalation, or skin contact with this chemical can cause hemorrhagic cystitis. The toxicity of chlordimeform is likely due to the fact that one of its metabolites, 2-methylaniline, is an aniline derivative. The hemorrhagic cystitis caused by chlordimeform is self-limiting, although whether these exposures increases the risk of bladder cancer is unknown.

Ether

Ether has been injected into the balloon ports of Foley catheters in an attempt to clear clogged ports and to deflate them, but this compound has an extremely toxic effect on the bladder. Balloons invariably rupture, and ether cystitis results in acute hematuria; long-term sequelae may include decreased capacity and irritative voiding symptoms.

Vaginal products

A chemical hemorrhagic cystitis can develop when vaginal products are inadvertently placed in the urethra. Gentian violet douching to treat candidiasis has resulted in hemorrhagic cystitis when the drug was misplaced in the urethra, but this hemorrhagic cystitis resolved spontaneously with cessation of treatment. Accidental urethral placement of contraceptive suppositories has also caused hemorrhagic cystitis in several patients. The bladder irritation was thought to be caused by contact of the acidic compound nonoxynol-9 (pH, 3.35) with the bladder. In the acute setting, the bladder can be copiously irrigated with alkalinized normal saline to minimize bladder irritation.

Viral causes of cystitis

Although hemorrhagic cystitis associated with posttransplantation/bone marrow transplantation is not technically noninfectious, a short discussion is in order for completeness. Patients undergoing therapy to suppress the immune system are at risk for hemorrhagic cystitis due to either the direct effects of chemotherapy or activation of dormant viruses in the kidney, ureter, or bladder.

Pathophysiology

See Etiology.

Clinical

Patients who present with hemorrhagic cystitis usually have a history of radiation or chemical exposure, and they are often inpatients or well known to their respective services. 

The presence or absence of clotted blood is not completely helpful in determining the etiology of hemorrhagic cystitis, but the presence of long stringy clots suggests an upper–urinary tract etiology. Symptoms include suprapubic discomfort, urinary frequency, and inability to empty the bladder due to the clots.

Upon examination, the patient often demonstrates suprapubic fullness and discomfort or pain to palpation, as well as costovertebral angle tenderness if the bladder obstruction is chronic.

Differential diagnoses

The differential diagnoses include the following:

• Active hemorrhage due to malignancy of the bladder, ureter, or kidney
• Acute effects of urinary tract infection
• Arteriovenous malformation
• Calculi at any point in the urinary system

In males, prostatic varices may also be an underlying etiology of gross hematuria.

INDICATIONS

Section 3 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Further Reading
• Multimedia
• References

Surgical intervention other than cystoscopy with cauterization is reserved for cases in which medical management fails. In extreme cases, when all other treatment options have failed, selective or superselective hypogastric branch artery embolization can be considered (see Surgical therapy).

RELEVANT ANATOMY

Section 4 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Further Reading
• Multimedia
• References

The bladder anatomy relevant to noninfectious hemorrhagic cystitis includes an appreciation of the layers from the lumen outward. The glycosaminoglycan (GAG) layer coats the inner surface over the transitional epithelium. Deep to this transitional epithelium, the bladder submucosa with its microvasculature overlies the detrusor muscle. A layer of fatty connective tissue surrounds most of the anterior and lateral bladder in the space of Retzius, while posteriorly, the peritoneal serosal surface separates it from the cul-de-sac and abdominal cavity contents. In cases of chronic cystitis, neovascularity in the submucosal area is often seen and is presumably the site of acute hemorrhage. Ischemic changes of endarteritis can lead to mucosal ulcerations and acute hemorrhage.

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Further Reading
• Multimedia
• References

Lab Studies

• Urine culture and sensitivity (C&S): Documentation of noninfectious hemorrhagic cystitis requires a negative urine C&S result. If even insignificant growth on an adequately collected specimen or any growth on a catheterized specimen is present, antibiotics should be initiated. Certain circumstances seem to predispose to urinary tract infections and cause signs and symptoms disproportionate to the amount of growth, especially hemorrhagic cystitis due to radiation treatment or chemotherapy.
• CBC count: The hematocrit level is rarely below the reference range during an initial occurrence of hemorrhagic cystitis; however, patients with chronic hemorrhagic cystitis may have a lower hematocrit level and prevailing signs of chronic anemia. The WBC count may be elevated because of a concurrent infection or because of the treatment (eg, chemotherapy) of the underlying malignancy.
• Basic metabolic profile (SMA-7): Findings are usually normal but may reflect sequelae due to treatment of the primary condition.
• Liver function test: Abnormalities related to the primary process may be found but are generally not related to the hemorrhagic cystitis.

Imaging Studies

In general, the evaluation of any patient with gross hematuria should include an assessment of the upper urinary tracts (in descending order of helpfulness, intravenous pyelography, CT scanning [without and with contrast], renal ultrasonography). When only renal ultrasonography or noncontrast CT scanning is performed, retrograde intravenous pyelography may be necessary to further evaluate the upper–urinary tract urothelium. Even if upper urinary tract lesions are identified, a bladder etiology for hematuria should be suspected and then checked with cystoscopy.

Diagnostic Procedures

Cystoscopy, with or without retrograde pyelography, is indicated in all cases of hemorrhagic cystitis. Often, cystoscopic clot evacuation is necessary to allow close inspection of the urothelium. Even in situations in which clots are initially removed with hematuria catheters, an endoscopic inspection is essential in planning treatment and in preventing future episodes.

Histologic Findings

Chronic inflammation is the most common finding on a bladder biopsy specimen.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Further Reading
• Multimedia
• References

Medical therapy

Regardless of the cause of noninfectious hemorrhagic cystitis, treatment follows the same course. Urine cultures should always be obtained to eliminate the possibility of bacterial cystitis. Elimination of the agent predisposing the patient to cystitis is paramount.

In the absence of clots and if the patient is voiding well, hydration with careful observation may be the only treatment required. If the patient demonstrates difficulty with urination, clots are likely occluding the bladder outlet. A large, stiff-walled hematuria catheter with wide holes is the best choice for initial clot evacuation.

Initial irrigations may be performed manually with sterile water, which helps to lyse red blood cells and clots. Continuous bladder irrigation with normal saline is started after clots are cleared. If irrigation of the bladder to clear the clots is not possible, cystoscopy with clot evacuation under anesthesia and antibiotic coverage are necessary. Fulguration of bleeding sites and biopsies of suspicious areas may be performed at that time. Although continuous bladder irrigation with saline solution cannot replace manual irrigation for removal of the clots, it can be helpful in preventing further clotting.

Persistent hematuria may be treated with bladder irrigation with carboprost, 1-2% alum, or silver nitrate. Alum and silver nitrate, which are astringents, work by forming precipitates over the bleeding surfaces of the bladder wall. These agents are not significantly absorbed through an intact bladder wall but may enter the circulation under pressure through open veins. Rarely, alum irrigation causes encephalopathy and acidosis in patients with renal insufficiency, in whom serum aluminum level monitoring is advisable. Both agents are somewhat caustic to the bladder, and alum can cause bladder wall necrosis and even perforation.

Because alum and silver nitrate irrigations are not without risk, the importance of constant monitoring to ensure low-pressure bladder irrigation is paramount and may warrant an ICU setting. One drawback to alum irrigation is that it imparts a leathery consistency to any clot present in the bladder at the time of irrigation, thus precluding easy clot evacuation.

Epsilon aminocaproic acid (Amicar) can also be used, either orally or parenterally, to limit intravesical bleeding. This drug works by inhibiting clot lysis by urinary urokinase. Amicar is contraindicated in patients with upper–urinary tract bleeding because it can cause extremely dense clots, resulting in ureteral obstruction. These clots are also often difficult to manually evacuate through a catheter; thus, evacuation via cystoscopy or cystotomy in the operating room may be required.

Carboprost tromethamine (prostaglandin F2 [Hemabate], Pharmacia) is an FDA-approved medication for uterine bleeding and induction of second-trimester abortion. It induces smooth-muscle contraction in blood-vessel walls and has been used off-label for bladder irrigation in the treatment of hemorrhagic cystitis due to cyclophosphamide. The main advantages of carboprost are that it is easy to use and does not cause bladder pain with irrigation. Other prostaglandins have also been used intravesically or parenterally in the treatment of pain associated with hemorrhagic cystitis. Commonly used vasodilatory prostaglandins include prostaglandin E1 and prostaglandin E2. These agents cause vasodilation, which improves blood flow to the bladder wall, and presumably decrease pain because of their anti-inflammatory properties. These agents are expensive, and their efficacy in bleeding reduction is marginal.

In severe refractory cases of hemorrhagic cystitis, formalin can be instilled in the bladder. Formalin coagulates the bleeding bladder surface by hydrolyzing and cross-linking proteins. Prior to installation, reflux into the ureters must be assessed with cystography. Formalin must not reflux into the upper urinary tracts because this reflux can cause irreversible fibrosis, papillary necrosis, or ureteral obstruction. If present, reflux can be mitigated by placement of occlusive balloon catheters in the distal ureters prior to proceeding. A 2.5-4% formalin solution is instilled in the bladder and left for up to 30 minutes, after which the bladder is meticulously irrigated with continuous bladder irrigation. Intravesical formalin instillation must be performed with the patient under anesthesia because it is excruciatingly painful.

Radiation-induced hemorrhagic cystitis

Although radiation-induced hemorrhagic cystitis cannot be prevented at this time, encouraging research with sodium pentosan polysulfate is ongoing. This compound resembles heparin and may prove to be uroprotective.

Amifostine (Ethyol) has been used with mixed results in preventing radiation damage, and its use should still probably be limited to clinical trials. Amifostine is prodrug that is dephosphorylated by alkaline phosphatase to a pharmacologically active free thiol metabolite, which, in studies of head and neck cancer, is believed to be responsible for the reduced renal toxicity of cisplatin and reduced side effects of radiation on the normal oral tissues. The active thiol metabolite is thought to scavenge reactive oxygen species generated in irradiated cells. Amifostine is thought to protect the normal tissues since they have higher pH, higher alkaline phosphatase activity (and produce more active metabolite), and better vascularity than the tumor tissue. 

Once radiation cystitis begins to develop, hyperbaric oxygen and conjugated estrogen therapies have both demonstrated moderate effectiveness in treating the process. Hyperbaric oxygen is thought to promote granulation tissue and neovascularization and to cause vasoconstriction, which decreases hemorrhaging. Anticholinergic and antispasmodic drugs may also be helpful in limiting the discomfort and inconvenience of the frequency and urgency associated with radiation cystitis. Because these drugs are used to control irritative symptoms, any concurrent bladder outlet obstruction should be assessed and treated with alpha-blockade (eg, terazosin, doxazosin, tamsulosin, alfuzosin) alone or in combination with 5-alpha-reductase inhibitors (finasteride, dutasteride) and/or surgical intervention (eg, transurethral incision of the prostate [TUIP], transurethral resection of the prostate [TURP]) to prevent urinary retention.

Chemotherapy-induced hemorrhagic cystitis

Cyclophosphamide toxicity can be minimized with the concurrent use of drugs such as N-acetylcysteine (Mucomyst) and 2-mercaptoethane sulfonate (mesna). Both of these drugs bind to acrolein, creating stable thioester compounds with no bladder toxicity. Because it decreases the chemotherapeutic efficacy of cyclophosphamide, Mucomyst is less desirable than mesna, which is generally not reported to decrease the efficacy of cyclophosphamide.

Mesna can be given either orally or intravenously, and its routine concurrent administration has been recommended in the treatment of patients receiving cyclophosphamide and ifosfamide chemotherapy. In patients receiving cyclophosphamide who develop hemorrhagic cystitis, discontinuation of mesna is recommended. Unfortunately, mesna is much more successful at preventing than treating active bleeding. Even if hemorrhagic cystitis does not develop during the use of cyclophosphamide, the patient’s lifetime risk of developing bladder cancer is increased 9-fold after receiving the agent. Mesna administration may decrease this risk.

Viral cystitis

Surgical therapy

Intervention to eliminate the influence of urokinase on the clots in the bleeding bladder in the form of percutaneous nephrostomies or other supravesical diversions has been met with mixed success. Because as many as half of patients who undergo urinary diversion later require cystectomy, bladder removal at the time of diversion should be strongly considered.

In extreme cases, when all other treatment options have failed, selective hypogastric branch artery embolization can be considered. This surgical procedure is associated with a low success rate because most cases are associated with diffuse venous bleeding that cannot be controlled with embolization. Intravesical balloons to tamponade the vessels have resulted in some transient improvement; however, the therapy is not widely accepted. In milder cases of irradiation cystitis, hyperbaric oxygen treatments may offer some degree of palliation.

Urinary flow diversion via percutaneous nephrostomy tube placement is often successful, presumably because this decreases the exposure of the nascent clots to urokinase, a potent clotting inhibitor in urine. Often, permanent urinary diversion (ie, ileal conduit, colon conduit, cutaneous ureterostomy) is necessary to prevent future hemorrhagic episodes. Cystostomy for vesical installation and cystotomy with temporary packing of the bladder or with use of the argon beam coagulator have been described as successful measures. Cystectomy may be necessary to control pain but may be avoided in some patients once the urine stream is diverted. Cystectomy poses a significant risk because the patient is usually compromised from chemotherapy or radiation therapy.

Neobladder creation and continent catheterizable pouches from uninvolved bowel segments are options in certain patients but are not generally considered in patients who have undergone radiation therapy or in whom renal insufficiency is an issue. Complications are discussed below.

Preoperative details

Prior to urinary diversion and cystectomy, culture-directed antibiotics or preoperative second-generation cephalosporins are usually administered after a mechanical bowel preparation. The latter is accomplished with oral sodium phosphate (Fleets Phosphosoda) or a polyethylene glycol electrolyte solution (GoLYTELY, NuLYTELY) with enemas on the evening prior to surgery. Oral erythromycin base and neomycin are also administered upon completion of the mechanical bowel preparation to minimize peritoneal contamination when the bowel is entered for creation of the conduit or substitute.

Intraoperative details

Radical cystectomy to manage cancer usually involves anterior exenteration female patients and cystoprostatectomy in male patients. However, for benign causes (eg, hemorrhagic cystitis), a more conservative approach can be used. The so-called simple cystectomy is accomplished in the standard fashion, but the removal of the ovaries, fallopian tubes, uterus, and anterior vagina in female patients can be avoided if desired. Similarly, prostatectomy in male patients may be avoided if indicated by anatomical concerns or a desire for cavernosal nerve sparing (erectile nerve preservation) or neobladder creation.

Postoperative details

Stabilization of hematocrit levels is the rule. Electrolyte abnormalities may supervene if preoperative renal insufficiency was present. Postoperative care is similar to that in other patients who have undergone cystectomy.

Follow-up

As noted, longer conduits and bladder substitutions require close follow-up and monitoring for sequelae of metabolic acidosis that may accompany these diversions. Vitamin B-12 deficiency and steatorrhea have been reported in patients in whom the distal ileum and ileocecal valve were used for diversion.

COMPLICATIONS

Section 7 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Further Reading
• Multimedia
• References

Complications are unusual for patients with chemical cystitis, but wound problems, urinary anastomotic strictures and leaks, and bowel anastomosis problems are more common in patients who have undergone a urinary diversion procedure after radiation therapy.

OUTCOME AND PROGNOSIS

Section 8 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Further Reading
• Multimedia
• References

In general, cystitis due to chemical exposure can be expected to resolve after discontinuation of the agent and irrigation/fulguration.

FUTURE AND CONTROVERSIES

Section 9 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Further Reading
• Multimedia
• References

Recent advances in the management of bleeding related to soft-tissue trauma, including argon beam coagulators, activated thrombin agents (eg, Evicel, FloSeal, Hemaseal), and angiogenesis inhibitors (for irradiation cystitis), may lead to new treatments that will hopefully lessen the need for cystectomy.

FURTHER READING

Section 10 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Further Reading
• Multimedia
• References

Recent review: Rastinehad A, Kavoussi L, Noble M. Hemorrhagic Cystitis. AUA Update Series. 2007;26(Lesson 7):66-75.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Further Reading
• Multimedia
• References

Media file 1:  Irradiation cystitis changes after 7200 cGy external beam radiation for localized prostate cancer.
	View Full Size Image
Media type:  Photo

Media file 2:  Neovascularity associated with irradiation cystitis. When distended, these weak-walled vessels often rupture, resulting in submucosal hemorrhage and gross hematuria.
	View Full Size Image
Media type:  Photo

Media file 3:  Bladder neck neovascularity after radiation therapy (IMRT) for prostate cancer.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Further Reading
• Multimedia
• References

• Alkan I, Jeschke S, Leeb K, Albquami N, Janetschek G. Treatment of radiation-induced hemorrhagic cystitis with laparoscopic cystoprostatectomy. Urol Int. 2006;77(2):190-2. [Medline].
• Andriole GL, Brickman C, Lack EE, et al. Danazol-induced cystitis: an undescribed source of hematuria in patients with hereditary angioneurotic edema. J Urol. Jan 1986;135(1):44-6. [Medline].
• Andriole GL, Yuan JJ, Catalona WJ. Cystotomy, temporary urinary diversion and bladder packing in the management of severe cyclophosphamide-induced hemorrhagic cystitis. J Urol. May 1990;143(5):1006-7. [Medline].
• Arad E, Naschitz J, Yeshurun D. [Hemorrhagic cystitis as a presenting symptom of acute infection with Salmonella typhi]. Harefuah. Jun 16 1996;130(12):815-6. [Medline].
• Ashrani AA, Gabriel DA, Gajewski JL, Jacobs DR Jr, Weisdorf DJ, Key NS. Pilot study to test the efficacy and safety of activated recombinant factor VII (NovoSeven) in the treatment of refractory hemorrhagic cystitis following high-dose chemotherapy. Bone Marrow Transplant. Dec 2006;38(12):825-8. [Medline].
• Assreuy AM, Martins GJ, Moreira ME, Brito GA, Cavada BS, Ribeiro RA. Prevention of cyclophosphamide-induced hemorrhagic cystitis by glucose-mannose binding plant lectins. J Urol. Jun 1999;161(6):1988-93. [Medline].
• Avidor Y, Nadu A, Matzkin H. Clinical significance of gross hematuria and its evaluation in patients receiving anticoagulant and aspirin treatment. Urology. Jan 2000;55(1):22-4. [Medline].
• Azzi A, Ciappi S, De Santis R, Fanci R, Leoni F, Colli S. Hemorrhagic cystitis associated with BKV in patients with refractory acute lymphoblastic leukemia. Am J Hematol. Jun 1996;52(2):121-2. [Medline].
• Azzi A, Fanci R, Bosi A, Ciappi S, Zakrzewska K, de Santis R. Monitoring of polyomavirus BK viruria in bone marrow transplantation patients by DNA hybridization assay and by polymerase chain reaction: an approach to assess the relationship between BK viruria and hemorrhagic cystitis. Bone Marrow Transplant. Aug 1994;14(2):235-40. [Medline].
• Ballen KK, Becker P, Levebvre K, Emmons R, Lee K, Levy W. Safety and cost of hyperhydration for the prevention of hemorrhagic cystitis in bone marrow transplant recipients. Oncology. Nov 1999;57(4):287-92. [Medline].
• Baronciani D, Angelucci E, Erer B, Fabrizi G, Galimberti M, Giardini C. Suprapubic cystotomy as treatment for severe hemorrhagic cystitis after bone marrow transplantation. Bone Marrow Transplant. Aug 1995;16(2):267-70. [Medline].
• Barouch DH, Faquin WC, Chen Y, Koralnik IJ, Robbins GK, Davis BT. BK virus-associated hemorrhagic cystitis in a Human Immunodeficiency Virus-infected patient. Clin Infect Dis. Aug 1 2002;35(3):326-9. [Medline].
• Batista CK, Mota JM, Souza ML, Leitão BT, Souza MH, Brito GA. Amifostine and glutathione prevent ifosfamide- and acrolein-induced hemorrhagic cystitis. Cancer Chemother Pharmacol. Jan 2007;59(1):71-7. [Medline].
• Bedi A, Miller CB, Hanson JL, Goodman S, Ambinder RF, Charache P. Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation. J Clin Oncol. May 1995;13(5):1103-9. [Medline].
• Blatt J, Gold SH, Wiley JM, Monahan PE, Cooper HC, Harvey D. Off-label use of recombinant factor VIIa in patients following bone marrow transplantation. Bone Marrow Transplant. Aug 2001;28(4):405-7. [Medline].
• Boeckh M, Erard V, Zerr D, Englund J. Emerging viral infections after hematopoietic cell transplantation. Pediatr Transplant. Dec 2005;9 Suppl 7:48-54. [Medline].
• Bogdanovic G, Priftakis P, Giraud G, Kuzniar M, Ferraldeschi R, Kokhaei P. Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation. J Clin Microbiol. Nov 2004;42(11):5394-6. [Medline].
• Boldorini R, Veggiani C, Barco D, Monga G. Kidney and urinary tract polyomavirus infection and distribution: molecular biology investigation of 10 consecutive autopsies. Arch Pathol Lab Med. Jan 2005;129(1):69-73. [Medline].
• Boubenider S, Hiesse C, Marchand S, Hafi A, Kriaa F, Charpentier B. Post-transplantation polyomavirus infections. J Nephrol. Jan-Feb 1999;12(1):24-9. [Medline].
• Bracis R, Sanders CV, Gilbert DN. Methicillin hemorrhagic cystitis. Antimicrob Agents Chemother. Sep 1977;12(3):438-9. [Medline].
• Bramble FJ, Morley R. Cystitis associated with allopurinol. Br J Urol. May 1997;79(5):817. [Medline].
• Bratsas KS, Stephanides AA, Spyropoulos E, Zachariades BP, Androulakakis PA. Hyperbaric oxygen therapy for cyclophosphamide induced refractory hemorrhagic cystitis in a child. J Urol. Aug 2004;172(2):679. [Medline].
• Bridges B, Donegan S, Badros A. Cidofovir bladder instillation for the treatment of BK hemorrhagic cystitis after allogeneic stem cell transplantation. Am J Hematol. Jul 2006;81(7):535-7. [Medline].
• Cannon J, Linke CA, Cos LR. Cyclophosphamide-associated carcinoma of urothelium: modalities for prevention. Urology. Nov 1991;38(5):413-6. [Medline].
• Chong KT, Hampson NB, Corman JM. Early hyperbaric oxygen therapy improves outcome for radiation-induced hemorrhagic cystitis. Urology. Apr 2005;65(4):649-53. [Medline].
• Chow YC, Yang S, Huang CJ, Tzen CY, Huang PL, Su YH. Epinephrine promotes hemostasis in rats with cyclophosphamide-induced hemorrhagic cystitis. Urology. Mar 2006;67(3):636-41. [Medline].
• Christmas TJ, Chapple CR, Payne SD, Milroy EJ, Warwick RT. Bonney's blue cystitis: a warning. Br J Urol. Mar 1989;63(3):281-3. [Medline].
• Corman JM, McClure D, Pritchett R, Kozlowski P, Hampson NB. Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen. J Urol. Jun 2003;169(6):2200-2. [Medline].
• Crawford ML, Waller PC, Wood SM. Severe cystitis associated with tiaprofenic acid. Br J Urol. Apr 1997;79(4):578-84. [Medline].
• Dall'Era MA, Hampson NB, Hsi RA, Madsen B, Corman JM. Hyperbaric oxygen therapy for radiation induced proctopathy in men treated for prostate cancer. J Urol. Jul 2006;176(1):87-90. [Medline].
• Del Pizzo JJ, Chew BH, Jacobs SC, Sklar GN. Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen: long-term followup. J Urol. Sep 1998;160(3 Pt 1):731-3. [Medline].
• Demesmay K, Tissot E, Bulabois CE, Bertrand MA, Racadot E, Woronoff-Lemsi MC. Factor XIII replacement in stem-cell transplant recipients with severe hemorrhagic cystitis: a report of four cases. Transplantation. Oct 27 2002;74(8):1190-2. [Medline].
• deVries CR, Freiha FS. Hemorrhagic cystitis: a review. J Urol. Jan 1990;143(1):1-9. [Medline].
• Donahue LA, Frank IN. Intravesical formalin for hemorrhagic cystitis: analysis of therapy. J Urol. Apr 1989;141(4):809-12. [Medline].
• Dorticós E, Pavón V, Jaime JC, Reboredo M, López Saura P, Berlanga J. Successful application of epidermal growth factor for treatment of hemorrhagic cystitis after bone marrow transplantation. Bone Marrow Transplant. Apr 2003;31(7):615-6. [Medline].
• Efros M, Ahmed T, Choudhury M. Cyclophosphamide-induced hemorrhagic pyelitis and ureteritis associated with cystitis in marrow transplantation. J Urol. Nov 1990;144(5):1231-2. [Medline].
• Ehrlich RM, Freedman A, Goldsobel AB, Stiehm ER. The use of sodium 2-mercaptoethane sulfonate to prevent cyclophosphamide cystitis. J Urol. May 1984;131(5):960-2. [Medline].
• El-Zimaity M, Saliba R, Chan K, Shahjahan M, Carrasco A, Khorshid O. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters. Blood. Jun 15 2004;103(12):4674-80. [Medline].
• Erard V, Kim HW, Corey L, Limaye A, Huang ML, Myerson D. BK DNA viral load in plasma: evidence for an association with hemorrhagic cystitis in allogeneic hematopoietic cell transplant recipients. Blood. Aug 1 2005;106(3):1130-2. [Medline].
• Erard V, Storer B, Corey L, Nollkamper J, Huang ML, Limaye A. BK virus infection in hematopoietic stem cell transplant recipients: frequency, risk factors, and association with postengraftment hemorrhagic cystitis. Clin Infect Dis. Dec 15 2004;39(12):1861-5. [Medline].
• Fairchild WV, Spence CR, Solomon HD, Gangai MP. The incidence of bladder cancer after cyclophosphamide therapy. J Urol. Aug 1979;122(2):163-4. [Medline].
• Fanourgiakis P, Georgala A, Vekemans M, Triffet A, De Bruyn JM, Duchateau V. Intravesical instillation of cidofovir in the treatment of hemorrhagic cystitis caused by adenovirus type 11 in a bone marrow transplant recipient. Clin Infect Dis. Jan 1 2005;40(1):199-201. [Medline].
• Fazili T, Bhat TR, Masood S, Palmer JH, Mufti GR. Fate of the leftover bladder after supravesical urinary diversion for benign disease. J Urol. Aug 2006;176(2):620-1. [Medline].
• Fernandes ET, Manivel JC, Reddy PK, Ercole CJ. Cyclophosphamide associated bladder cancer--a highly aggressive disease: analysis of 12 cases. J Urol. Dec 1996;156(6):1931-3. [Medline].
• Focosi D, Kast RE. Hyaluronate and risperidone for hemorrhagic cystitis. Bone Marrow Transplant. Jan 2007;39(1):57. [Medline].
• Folland DS, Kimbrough RD, Cline RE, et al. Acute hemorrhagic cystitis. Industrial exposure to the pesticide chlordimeform. JAMA. Mar 13 1978;239(11):1052-5. [Medline].
• Fu LW, Chen WP, Wang HH, Lin AT, Lin CY. Formalin treatment of refractory hemorrhagic cystitis in systemic lupus erythematosus. Pediatr Nephrol. Nov 1998;12(9):788-9. [Medline].
• Furness PD 3rd, Palmer LS, Palmer JS, Capelli-Schellpfeffer M, Cheng EY. Hyperbaric oxygen therapy for pediatric hemorrhagic cystitis. J Urol. May 1999;161(5):1596-7. [Medline].
• Geetha D, Tong BC, Racusen L, Markowitz JS, Westra WH. Bladder carcinoma in a transplant recipient: evidence to implicate the BK human polyomavirus as a causal transforming agent. Transplantation. Jun 27 2002;73(12):1933-6. [Medline].
• Giné E, Rovira M, Real I, Burrel M, Montaña J, Carreras E. Successful treatment of severe hemorrhagic cystitis after hemopoietic cell transplantation by selective embolization of the vesical arteries. Bone Marrow Transplant. May 2003;31(10):923-5. [Medline].
• Giraud G, Bogdanovic G, Priftakis P, Remberger M, Svahn BM, Barkholt L. The incidence of hemorrhagic cystitis and BK-viruria in allogeneic hematopoietic stem cell recipients according to intensity of the conditioning regimen. Haematologica. Mar 2006;91(3):401-4. [Medline].
• Goldfarb M, Finelli R. Necrotizing cystitis. Secondary to "bootleg" methaqualone. Urology. Jan 1974;3(1):54-5. [Medline].
• Gomes TN, Santos CC, Souza-Filho MV, Cunha FQ, Ribeiro RA. Participation of TNF-alpha and IL-1 in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis. Braz J Med Biol Res. Oct 1995;28(10):1103-8. [Medline].
• Gorczynska E, Turkiewicz D, Rybka K, Toporski J, Kalwak K, Dyla A. Incidence, clinical outcome, and management of virus-induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. Oct 2005;11(10):797-804. [Medline].
• Goren MP, McKenna LM, Goodman TL. Combined intravenous and oral mesna in outpatients treated with ifosfamide. Cancer Chemother Pharmacol. 1997;40(5):371-5. [Medline].
• Habs MR, Schmähl D. Prevention of urinary bladder tumors in cyclophosphamide-treated rats by additional medication with the uroprotectors sodium 2-mercaptoethane sulfonate (mesna) and disodium 2,2'-dithio-bis-ethane sulfonate (dimesna). Cancer. Feb 15 1983;51(4):606-9. [Medline].
• Hatakeyama N, Suzuki N, Kudoh T, Hori T, Mizue N, Tsutsumi H. Successful cidofovir treatment of adenovirus-associated hemorrhagic cystitis and renal dysfunction after allogenic bone marrow transplant. Pediatr Infect Dis J. Oct 2003;22(10):928-9. [Medline].
• Hatakeyama N, Suzuki N, Yamamoto M, Kuroiwa Y, Hori T, Mizue N. Detection of BK virus and adenovirus in the urine from children after allogeneic stem cell transplantation. Pediatr Infect Dis J. Jan 2006;25(1):84-5. [Medline].
• Heath JA, Mishra S, Mitchell S, Waters KD, Tiedemann K. Estrogen as treatment of hemorrhagic cystitis in children and adolescents undergoing bone marrow transplantation. Bone Marrow Transplant. Mar 2006;37(5):523-6. [Medline].
• Held TK, Biel SS, Nitsche A, Kurth A, Chen S, Gelderblom HR. Treatment of BK virus-associated hemorrhagic cystitis and simultaneous CMV reactivation with cidofovir. Bone Marrow Transplant. Aug 2000;26(3):347-50. [Medline].
• Hirsch HH. BK virus: opportunity makes a pathogen. Clin Infect Dis. Aug 1 2005;41(3):354-60. [Medline].
• Hoffman JA, Shah AJ, Ross LA, Kapoor N. Adenoviral infections and a prospective trial of cidofovir in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2001;7(7):388-94. [Medline].
• Hofland CA, Eron LJ, Washecka RM. Hemorrhagic adenovirus cystitis after renal transplantation. Transplant Proc. Dec 2004;36(10):3025-7. [Medline].
• Hudson RG, Cain MP. Risperidone associated hemorrhagic cystitis. J Urol. Jul 1998;160(1):159. [Medline].
• Iavazzo C, Athanasiou S, Pitsouni E, Falagas ME. Hyaluronic Acid: an effective alternative treatment of interstitial cystitis, recurrent urinary tract infections, and hemorrhagic cystitis?. Eur Urol. Jun 2007;51(6):1534-41. [Medline].
• Ippoliti C, Przepiorka D, Mehra R, Neumann J, Wood J, Claxton D. Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation. Urology. Dec 1995;46(6):811-5. [Medline].
• Islam R, Isaacson BJ, Zickerman PM, Ratanawong C, Tipping SJ. Hemorrhagic cystitis as an unexpected adverse reaction to temozolomide: case report. Am J Clin Oncol. Oct 2002;25(5):513-4. [Medline].
• Ison MG. Adenovirus infections in transplant recipients. Clin Infect Dis. Aug 1 2006;43(3):331-9. [Medline].
• Jurincic C, Horlbeck R, Metz K, Klippel KF. [Acute hemorrhagic cystitis following chlordimeform poisoning ]. Dtsch Med Wochenschr. May 24 1991;116(21):816-8. [Medline].
• Kanat O, Kurt E, Yalcinkaya U, Evrensel T, Manavoglu O. Comparison of uroprotective efficacy of mesna and amifostine in Cyclophosphamide- induced hemorrhagic cystitis in rats. Indian J Cancer. Jan-Mar 2006;43(1):12-5. [Medline].
• Kapelushnik J, Verstandig A, Or R, Meretyk S, Drakos P, Naparstek E. Hydronephrosis in children after bone marrow transplantation: case reports. Bone Marrow Transplant. May 1996;17(5):873-5. [Medline].
• Kausman JY, Somers GR, Francis DM, Jones CL. Association of renal adenocarcinoma and BK virus nephropathy post transplantation. Pediatr Nephrol. Apr 2004;19(4):459-62. [Medline].
• Khojasteh NH, Zakerinia M, Ramzi M, Haghshenas M. A new regimen of MESNA (2-mercaptoethanesulfonate) effectively prevents cyclophosphamide-induced hemorrhagic cystitis in bone marrow transplant recipients. Transplant Proc. May 2000;32(3):596. [Medline].
• Kim SJ, Koh DH, Park JS, Ahn HS, Choi JB, Kim YS. Hemorrhagic cystitis due to intravesical instillation of gentian violet completely recovered with conservative therapy. Yonsei Med J. Feb 2003;44(1):163-5. [Medline].
• Kim YJ, Kim DW, Lee DG, Park ST, Park YH, Min CK. Human herpesvirus-6 as a possible cause of encephalitis and hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Leukemia. May 2002;16(5):958-9. [Medline].
• Kitabayashi A, Hirokawa M, Kuroki J, Nishinari T, Niitsu H, Miura AB. Successful vidarabine therapy for adenovirus type 11-associated acute hemorrhagic cystitis after allogeneic bone marrow transplantation. Bone Marrow Transplant. Nov 1994;14(5):853-4. [Medline].
• Klastersky J. Side effects of ifosfamide. Oncology. 2003;65 Suppl 2:7-10. [Medline].
• Koc S, Hagglund H, Ireton RC, Perez-Simon JA, Collins SJ, Appelbaum FR. Successful treatment of severe hemorrhagic cystitis with cystectomy following matched donor allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. Oct 2000;26(8):899-901. [Medline].
• Koga S, Shindo K, Matsuya F, et al. Acute hemorrhagic cystitis caused by adenovirus following renal transplantation: review of the literature. J Urol. Apr 1993;149(4):838-9. [Medline].
• Koga S, Shindo K, Matsuya F, Hori T, Kanda S, Kanetake H. Acute hemorrhagic cystitis caused by adenovirus following renal transplantation: review of the literature. J Urol. Apr 1993;149(4):838-9. [Medline].
• Kok LP. Boon's disease: hemorrhagic cystitis in conjunction with massive exfoliation of degenerated urothelial cells (apoptosis?) during intercontinental flights in an otherwise healthy person. Diagn Cytopathol. Dec 2001;25(6):361-4. [Medline].
• Komiya I, Nojiri M, Kuriya S, Saito Y. Hemorrhagic cystitis caused by bleomycin treatment. Jpn J Med. Jul-Aug 1991;30(4):392. [Medline].
• Kopterides P, Theodorakopoulou M, Mentzelopoulos S, Armaganidis A. Cyclophosphamide-induced hemorrhagic cystitis successfully treated with conjugated estrogens. Am J Hematol. Oct 2005;80(2):166-7. [Medline].
• Lakhani A, Raptis A, Frame D, et al. Intravesicular instillation of E-aminocaproic acid for patients with adenovirus-induced hemorrhagic cystitis. Bone Marrow Transplant. Dec 1999;24(11):1259-60. [Medline].
• Lakhani A, Raptis A, Frame D, Simpson D, Berkahn L, Mellon-Reppen S. Intravesicular instillation of E-aminocaproic acid for patients with adenovirus-induced hemorrhagic cystitis. Bone Marrow Transplant. Dec 1999;24(11):1259-60. [Medline].
• Laszlo D, Bosi A, Guidi S, Saccardi R, Vannucchi AM, Lombardini L. Prostaglandin E2 bladder instillation for the treatment of hemorrhagic cystitis after allogeneic bone marrow transplantation. Haematologica. Sep-Oct 1995;80(5):421-5. [Medline].
• Lee HJ, Pyo JW, Choi EH, Ha IS, Cheong HI, Choi Y. Isolation of adenovirus type 7 from the urine of children with acute hemorrhagic cystitis. Pediatr Infect Dis J. Jul 1996;15(7):633-4. [Medline].
• Leung AY, Chan MT, Yuen KY, Cheng VC, Chan KH, Wong CL. Ciprofloxacin decreased polyoma BK virus load in patients who underwent allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. Feb 15 2005;40(4):528-37. [Medline].
• Levenback C, Eifel PJ, Burke TW, Morris M, Gershenson DM. Hemorrhagic cystitis following radiotherapy for stage Ib cancer of the cervix. Gynecol Oncol. Nov 1994;55(2):206-10. [Medline].
• Levine LA, Jarrard DF. Treatment of cyclophosphamide-induced hemorrhagic cystitis with intravesical carboprost tromethamine. J Urol. Apr 1993;149(4):719-23. [Medline].
• Levine LA, Kranc DM. Evaluation of carboprost tromethamine in the treatment of cyclophosphamide-induced hemorrhagic cystitis. Cancer. Jul 15 1990;66(2):242-5. [Medline].
• Lima MV, Ferreira FV, Macedo FY, de Castro Brito GA, Ribeiro RA. Histological changes in bladders of patients submitted to ifosfamide chemotherapy even with mesna prophylaxis. Cancer Chemother Pharmacol. Apr 2007;59(5):643-50. [Medline].
• Liu YK, Harty JI, Steinbock GS, et al. Treatment of radiation or cyclophosphamide induced hemorrhagic cystitis using conjugated estrogen. J Urol. Jul 1990;144(1):41-3. [Medline].
• Liu YK, Harty JI, Steinbock GS, Holt HA Jr, Goldstein DH, Amin M. Treatment of radiation or cyclophosphamide induced hemorrhagic cystitis using conjugated estrogen. J Urol. Jul 1990;144(1):41-3. [Medline].
• Marx CM, Alpert SE. Ticarcillin-induced cystitis. Cross-reactivity with related penicillins. Am J Dis Child. Jul 1984;138(7):670-2. [Medline].
• Mathews R, Rajan N, Josefson L, et al. Hyperbaric oxygen therapy for radiation induced hemorrhagic cystitis. J Urol. Feb 1999;161(2):435-7. [Medline].
• Mayersak JS, Viviano CJ. Severe chemical cystitis from the transurethral intravesical insertion of a vaginal contraceptive suppository: a report of 3 cases and proposed method of management. J Urol. Apr 1993;149(4):835-7. [Medline].
• McCarville MB, Hoffer FA, Gingrich JR, Jenkins JJ 3rd. Imaging findings of hemorrhagic cystitis in pediatric oncology patients. Pediatr Radiol. Mar 2000;30(3):131-8. [Medline].
• McClanahan C, Grimes MM, Callaghan E, Stewart J. Hemorrhagic cystitis associated with herpes simplex virus. J Urol. Jan 1994;151(1):152-3. [Medline].
• Morais MM, Belarmino-Filho JN, Brito GA, Ribeiro RA. Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis - comparison of the effects of dexamethasone and Mesna. Braz J Med Biol Res. Oct 1999;32(10):1211-5. [Medline].
• Mori T, Aisa Y, Shimizu T, Ikeda Y, Okamoto S, Okada K. Hemorrhagic cystitis caused by adenovirus type 34 after allogeneic bone marrow transplantation. Transplantation. Mar 15 2005;79(5):624. [Medline].
• Mylonakis E, Goes N, Rubin RH, Cosimi AB, Colvin RB, Fishman JA. BK virus in solid organ transplant recipients: an emerging syndrome. Transplantation. Nov 27 2001;72(10):1587-92. [Medline].
• Nagafuji K, Aoki K, Henzan H, Kato K, Miyamoto T, Eto T. Cidofovir for treating adenoviral hemorrhagic cystitis in hematopoietic stem cell transplant recipients. Bone Marrow Transplant. Nov 2004;34(10):909-14. [Medline].
• Nellans RE, Ellis LR, Kenny GM. Ether cystitis. JAMA. Jul 26 1985;254(4):530. [Medline].
• Nguyen ML, Borochovitz D, Thomas G, McClure T, Ruben FL. Hemorrhagic cystitis with herpes simplex virus type 2 in the bladder mucosa. Clin Infect Dis. Mar 1992;14(3):767-8. [Medline].
• Nielsen FT, Hornstrup MK. [Antibiotic-induced hemorrhagic cystitis]. Ugeskr Laeger. Nov 24 1997;159(48):7150-1. [Medline].
• Okaneya T, Kontani K, Komiyama I, Takezaki T. Severe cyclophosphamide-induced hemorrhagic cystitis successfully treated by total cystectomy with ileal neobladder substitution: a case report. J Urol. Dec 1993;150(6):1909-10. [Medline].
• Osorio AV, Simckes AM, Hellerstein S. Hemorrhagic cystitis caused by acetic acid instillation. J Urol. Feb 1996;155(2):685. [Medline].
• Ouwenga MK, Langston MD, Campbell SC. Use of fibrin sealant in recalcitrant hemorrhagic cystitis. J Urol. Oct 2004;172(4 Pt 1):1348. [Medline].
• Palandri F, Bonifazi F, Rossi C, Falcioni S, Arpinati M, Giannini MB. Successful treatment of severe hemorrhagic cystitis with selective vesical artery embolization. Bone Marrow Transplant. Mar 2005;35(5):529-30. [Medline].
• Pedersen-Bjergaard J, Ersbøll J, Hansen VL, Sørensen BL, Christoffersen K, Hou-Jensen K. Carcinoma of the urinary bladder after treatment with cyclophosphamide for non-Hodgkin's lymphoma. N Engl J Med. Apr 21 1988;318(16):1028-32. [Medline].
• Perazella M, Brown E. Acute aluminum toxicity and alum bladder irrigation in patients with renal failure. Am J Kidney Dis. Jan 1993;21(1):44-6. [Medline].
• Pliskin MJ, Dresner ML. Inadvertent urethral insertion of a contraceptive suppository. J Urol. May 1988;139(5):1049-50. [Medline].
• Priftakis P, Bogdanovic G, Kokhaei P, Mellstedt H, Dalianis T. BK virus (BKV) quantification in urine samples of bone marrow transplanted patients is helpful for diagnosis of hemorrhagic cystitis, although wide individual variations exist. J Clin Virol. Jan 2003;26(1):71-7. [Medline].
• Purves JT, Graham ML, Ramakumar S. Application of fibrin glue to damaged bladder mucosa in a case of BK viral hemorrhagic cystitis. Urology. Sep 2005;66(3):641-3. [Medline].
• Quinlan DM, Naslund MJ, Brendler CB. Application of argon beam coagulation in urological surgery. J Urol. Feb 1992;147(2):410-2. [Medline].
• Ratliff TR, Williams RD. Hemorrhagic cystitis, chemotherapy, and bladder toxicity. J Urol. Mar 1998;159(3):1044. [Medline].
• Redman JF, Kletzel M. Cutaneous vesicostomy with direct intravesical application of formalin: management of severe vesical hemorrhage resulting from high dose cyclophosphamide in boys. J Urol. Apr 1994;151(4):1048-50.