Noninfectious Hemorrhagic Cystitis

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Overview

Hemorrhagic cystitis is defined as an infectious or noninfectious process that leads to gross hematuria originating in the urinary bladder. Infectious causes of hemorrhagic cystitis include bacterial and viral etiologies. The various noninfectious causes are the topic of this discussion. Noninfectious hemorrhagic cystitis most commonly occurs in patients who have undergone pelvic radiation, chemotherapy, or both.[1] Affected patients may develop asymptomatic, microscopic hematuria or gross hematuria with clots, leading to urinary retention. Treatment depends on the etiology, severity of the bleeding, and symptoms.[2]

Rarely, arteriovenous malformations, stones, metastatic tumors, and, more commonly, urothelial malignancies manifest as gross hematuria. These are differentiated from hemorrhagic cystitis with imaging and endoscopic evaluation.[3]

Hemorrhagic cystitis occurs in up to 70% of patients exposed to high doses of cyclophosphamide or iphosphamide chemotherapy[4, 5, 6, 7] and up to 15% of patients who undergo pelvic irradiation to treat malignancy.[8, 9, 10] However, newer irradiation techniques have decreased the incidence of hemorrhagic cystitis to approximately 10% of treated patients.[11]

Anatomy

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 common and is presumably the site of acute hemorrhage. Ischemic changes of endarteritis can lead to mucosal ulcerations and acute hemorrhage.

Etiology and Pathophysiology

Noninfectious hemorrhagic cystitis is characterized by inflammation of the bladder associated with hematuria. Patients with this condition 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, causes 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)[12] and prolonged high-altitude air travel (Boon disease).[13] 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 have usually undergone radiation therapy for cancer of the prostate, colon, cervix, or bladder. Urgency, frequency, dysuria, and stranguria may develop acutely during radiation or may begin months to years after completion of radiotherapy. (See the image below.)


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Changes resulting from radiation cystitis following 7200cGy external beam radiation for localized prostate cancer.

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, as shown in the images below, 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.[8, 9, 10]


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Neovascularity associated with radiation cystitis. When distended, these weak-walled vessels often rupture, resulting in submucosal hemorrhage and gro....


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Bladder neck neovascularity after intensity-modulated radiation therapy (IMRT) for prostate cancer.

As expected, the higher the radiation dose and the wider the field encompassed by the radiation exposure, the more likely the sequelae of radiation cystitis will occur. 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.[14]

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.[15, 16, 17] Unfortunately, the toxicity of these drugs is not insignificant, and many of the adverse effects are urologic.

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. The onset of hematuria usually occurs within 48 hours of treatment.[18] Hemorrhagic cystitis due to ifosfamide therapy is generally worse than that caused by cyclophosphamide.[19] Ifosfamide causes the release of tumor necrosis factor-alpha and interleukin-1 beta, mediating the release of nitric oxide and leading to hemorrhagic cystitis.[20, 21]

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.[22] Patients receiving cyclophosphamide should always receive good hydration, and a Foley catheter is often placed to ensure immediate drainage of the bladder.[23] Continuous bladder irrigation is sometimes recommended to hasten acrolein clearance from the bladder.[24] Cyclophosphamide is also associated with bladder cancer, typically aggressive.[25, 26]

Penicillins

In rare cases, penicillins have been reported to cause hemorrhagic cystitis. Case reports have implicated methicillin, carbenicillin, ticarcillin, piperacillin, and penicillin VK. Most cases of hemorrhagic cystitis in patients taking 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.[27, 28, 27, 29]

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.[30]

Other medications

Other medications that have been implicated in the development of hemorrhagic cystitis, in limited reports, include the following:

Risperidone has been associated with hemorrhagic cystitis but is also used as treatment for hemorrhagic cystitis due to JC virus.[44]

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.[45]

Chlordimeform

The pesticide chlordimeform is commonly used on cotton plants and fruit trees; ingestion, inhalation, or skin contact with this chemical can cause hemorrhagic cystitis. The toxicity of chlordimeform is likely due to one of its metabolites, 2-methylaniline, an aniline derivative. Hemorrhagic cystitis caused by chlordimeform is self-limiting, although whether these exposures increase the risk of bladder cancer is unknown.[46, 47]

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.[48]

Vaginal products

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.[37, 38, 39, 40]

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.[41, 42]

Viral causes of hemorrhagic cystitis

Although hemorrhagic cystitis associated with post solid-organ transplantation, bone marrow transplantation, or cord blood 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.[49, 50, 51, 52, 53, 54, 55, 56, 57, 58]

In the early 1990s, infection with polyomavirus or adenoviruses was implicated as the likely etiology of this condition. Polyomavirus is highly prevalent in the pediatric population and is thought to remain dormant and asymptomatic in the kidney and other organs after the initial infection. When the immune system is compromised, as in persons with human immunodeficiency virus (HIV) infection and those undergoing chemotherapy or chemical immunosuppression, the virus can be reactivated, leading to clinical nephritis, ureteritis, or cystitis.[59, 60, 61]

The BK polyomavirus[62, 63, 64, 65, 66, 67, 68, 69, 70] and adenovirus types 7, 11, 34, and 35[71, 72, 73, 74, 75, 76, 77, 78, 79] have been the most commonly described viruses in these cases. Cytomegalovirus,[80, 81] JC virus,[82] and herpesviruses[38, 83, 84] have also been identified as causative agents in these scenarios. BK virus has also been shown to be a causal transforming agent for bladder cancer.[85]

Prognosis

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

Conversely, radiation cystitis tends to recur for months or even years after completion of radiotherapy. Seemingly minor events, such as urinary tract infection or bladder distension, may trigger florid hemorrhage. Close follow-up with periodic urinalysis and urine C&S and aggressive management may prevent recurrences.

Complications are unusual in patients with chemical cystitis. 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.[86, 87]

History and Physical Examination

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 Diagnosis

The differential diagnoses of hemorrhagic cystitis include the following:

A history of trauma or recent manipulation of the urinary system (eg, catheterization, cystoscopy) suggests another etiology. In males, prostatic varices may be an underlying etiology of gross hematuria.

Lab Studies

Urine culture and sensitivity

Documentation of noninfectious hemorrhagic cystitis requires a negative urine culture and sensitivity (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.

Complete blood 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 white blood cell (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.

Biopsy

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

Radiologic and Endoscopic Studies

Radiology

In general, the evaluation of any patient with gross hematuria should include an assessment of the upper urinary tracts. The following imaging studies are listed in descending order of helpfulness:

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.[88, 89]

Cystoscopy

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.

Irrigation and Pharmacologic 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 to cystitis is paramount.

If there are no clots and 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 bladder irrigation 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 aid 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.[90] Alum and silver nitrate 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 intensive care unit (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 often difficult to manually evacuate through a catheter; thus, evacuation via cystoscopy or cystotomy in the operating room may be required.[91, 92]

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.[93, 94, 95, 96] 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. However, prostaglandin E1 and E2 are expensive, and their efficacy in bleeding reduction is marginal.[97]

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 excruciating.[98, 99, 100, 101] Placement via cutaneous vesicostomy has also been described.[102]

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.[103, 104]

Once radiation cystitis begins to develop, hyperbaric oxygen[14, 105, 106, 107, 108, 109, 110, 111] and conjugated estrogen therapies[112] have 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.

Intravenously administered WF10, currently in phase II trials, is a therapy used to treat patients with late-onset (>3mo following treatment) radiation-induced hemorrhagic cystitis. Studies have shown that WF10 may improve the degree of hematuria in these patients.[113, 114]

Chemotherapy-induced hemorrhagic cystitis

Cyclophosphamide toxicity can be minimized with the concurrent use of drugs such as N -acetylcysteine (Mucomyst), S-2-(3-aminopropylamino) ethyl phosphorothioic acid (amifostine),[104] pentosan polysulfate, and 2-mercaptoethanesulfonate (mesna).[115, 116, 117, 118, 119, 120, 121] 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 bleeding than it is at 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. The addition of dexamethasone with mesna may improve the results.[122]

Hyperbaric oxygen and conjugated estrogens have been used, with moderate success, in refractory hematuria due to cyclophosphamide chemotherapy.[112, 123, 124, 125] Intravesical epinephrine has been shown to be effective in rats with cyclophosphamide-induced hemorrhagic cystitis.[126]

Viral hemorrhagic cystitis

In immunosuppressed patients with viral hemorrhagic cystitis, decreased immunosuppression and the use of antiviral agents (cidofovir, vidarabine, ribavirin) administered orally, intravenously, intramuscularly, or intravesically is recommended.[72, 127, 128, 129, 130, 131, 132, 133, 134] Intravesical hyaluronate has been used to treat BK virus hemorrhagic cystitis, while risperidone has been used to treat hemorrhagic cystitis due to JC virus.[82, 135] Ciprofloxacin has been reported to decrease the BK viral load in these patients.[136] Continuous bladder irrigation during bone marrow transplant may prevent hemorrhagic cystitis.[137]

Treatment with continuous bladder irrigation and clot evacuation is implemented as in other cases of hematuria.

In bone marrow recipients who develop hemorrhagic cystitis, presumably due to latent viral infections, infusions of factor VII, factor XII, epidermal growth factor, and carboprost have been described as efficacious.[93, 94, 138, 139, 140, 141]

Urinary Diversion and Cystectomy

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.

Intervention in the form of percutaneous nephrostomies or other supravesical diversions to eliminate the influence of urokinase on the clots in the bleeding bladder has been met with mixed success. Because up to half of the patients who undergo urinary diversion later require cystectomy, bladder removal at the time of diversion should be strongly considered.[142]

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.[143] Intravesical balloons to tamponade the vessels have resulted in some transient improvement; however, the therapy is not widely accepted.[144] In milder cases of radiation cystitis, hyperbaric oxygen treatments may offer some degree of palliation.

Urinary flow diversion via percutaneous nephrostomy tube placement is often successful, presumably because it 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[145, 146, 147, 148] or with use of the argon beam coagulator have been described as successful measures.[149]

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.[150, 151]

Neobladder creation and continent catheterizable pouches from uninvolved bowel segments, with or without removal of the bladder, are options in certain patients with severe refractory hemorrhagic cystitis.[142] Subtotal cystectomy with augmentation of the bladder with ileum is another option in these patients.[152]

Advances in the management of bleeding related to soft-tissue trauma, including argon beam coagulators,[149] activated thrombin and fibrin agents (eg, Evicel, FloSeal, Hemaseel),[153, 154, 155] and angiogenesis inhibitors (for cyclophosphamide cystitis),[156] may lead to new treatments that will lessen the need for cystectomy.

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.[86, 87]

Intraoperative details

Radical cystectomy to manage cancer usually involves anterior exenteration in 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.[157]

The choice of conduit material (eg, ileum, sigmoid colon, transverse colon) depends on the underlying etiology of the cystitis. In cases of radiation cystitis, a transverse colon conduit may be the best option, since it is generally out of the radiation field. The ureters must be taken well above the bladder to avoid implanting an ischemic, irradiated ureter in the conduit. The latter often requires the creation of a longer conduit than would otherwise be needed. This, in turn, may lead to metabolic consequences (eg, hyperchloremic metabolic acidosis) that must be considered postoperatively.[86, 87]

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.[86, 87]

Follow-up

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.[87]

Author

Joseph Basler, MD, PhD, Thomas P Ball Residency Education Professor, Urology Residency Program Director, Department of Urology, University of Texas Health Science Center at San Antonio; Chief, Section of Urology, Audie Murphy Veterans Affairs Hospital

Disclosure: Pfizer Stock ownership less than $5000 None

Coauthor(s)

Ryan Keith Miyamoto, MD, Staff Physician, Department of Urology, University of Texas Health Science Center at San Antonio

Disclosure: Nothing to disclose.

Chief Editor

Edward David Kim, MD, FACS, Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center

Disclosure: Lilly Consulting fee Advisor; Astellas Consulting fee Speaking and teaching; Watson Consulting fee Speaking and teaching; Allergan Consulting fee Speaking and teaching

Additional Contributors

Mark Jeffrey Noble, MD Consulting Staff, Urologic Institute, Cleveland Clinic Foundation

Mark Jeffrey Noble, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, Kansas Medical Society, Sigma Xi, Society of University Urologists, and Southwest Oncology Group

Disclosure: Nothing to disclose.

Bradley Fields Schwartz, DO, FACS Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine

Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoendoscopic Surgeons, and Society of University Urologists

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

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Changes resulting from radiation cystitis following 7200cGy external beam radiation for localized prostate cancer.

Neovascularity associated with radiation cystitis. When distended, these weak-walled vessels often rupture, resulting in submucosal hemorrhage and gross hematuria.

Bladder neck neovascularity after intensity-modulated radiation therapy (IMRT) for prostate cancer.

Changes resulting from radiation cystitis following 7200cGy external beam radiation for localized prostate cancer.

Neovascularity associated with radiation cystitis. When distended, these weak-walled vessels often rupture, resulting in submucosal hemorrhage and gross hematuria.

Bladder neck neovascularity after intensity-modulated radiation therapy (IMRT) for prostate cancer.