Bladder 11

Technique

Conventional Cystography

Cystography is a well-established technique in evaluating the bladder lumen and providing access for biopsies. It is often used as a gold standard when evaluating other imaging proce- dures. Cystography as used here implies con- ventional cystography, which consists of lumen distention with a contrast agent introduced via a catheter and appropriate filming. Cystography is also feasible using computed tomography (CT), ultrasonography (US), magnetic reso- nance (MR), and radionuclide techniques.

Voiding cystourethrography continues to be the gold standard for imaging evaluation chil- dren with urinary tract infection, male urethra, functional bladder conditions and in detecting vesicoureteral reflux. Although radionuclide and contrast enhanced US cystography have a role in screening and follow-up of established conditions, most initial evaluation of function and anatomy appears best served by voiding cystourethrography.

Computed Tomography

A typical CT cystography technique consists of contiguous 5-mm axial scans after bladder dis- tention with a 4% iodinated solution as a posi- tive contrast agent. Air or carbon dioxide is

occasionally used for bladder distention, but a potential complication of air is air embolism.

Imaging in both the supine and prone positions is necessary when using gas to detect tumors otherwise covered with fluid.

Similar to CT colonoscopy, CT cystoscopy (also called virtual cystoscopy) is feasible with a contrast filled bladder. Computed tomography cystoscopy is an alternate procedure in patients with urethral strictures who cannot undergo conventional cystoscopy or cystography but indications are expanding and some enthusiasts believe it will replace a large part of conven- tional cystoscopy. Three-dimensional (3D) CT cystography using perspective volume render- ing and a shaded-surface 3D outline evaluates tumor size and shape and provides information about its relationship to adjoining mucosa. With current techniques, however, endoscopic cys- toscopy has better spatial resolution in detect- ing small bladder tumors; thus CT cystoscopy detected 90% of bladder tumors, with all unde- tected tumors being <5 mm in diameter (1);

transverse and virtual images are complemen- tary—some small tumors are identified only on virtual images but bladder wall thickening is more apparent on transverse images.

Flow of opacified urine into the bladder during contrast-enhanced CT results in intralu- minal artifacts due to incomplete mixing. If necessary, delayed bladder images should be obtained to eliminate these artifacts.

Bladder

685

Ultrasonography

Bladder US is performed using a transabdomi- nal, endorectal, endovaginal, or endourethral approach. Color Doppler US detects ureteral jets and with unilateral ureteral obstruction, Doppler US reveals asymmetry to these ureteral jets. The presence of normal ureteral jets excludes significant obstruction.

Intravesical instillation of an US contrast agent aids detection of certain abnormalities, such as vesicoureteral reflux. A galactose-based microbubble contrast agent, Levovist, is typi- cally employed. Contrast duration for this agent varies when mixed with normal saline. A high concentration of dissolved oxygen in normal saline appears to prevent diffusion of gas from the microbubbles into the solution and as a result contrast duration is longer than with use of a low oxygen concentration solution, such as is found in vacuum sealed containers (2).

Magnetic Resonance Imaging

On T1-weighted images urine is homo- geneously hypointense and blends into the bladder wall. On T2-weighted images urine is hyperintense while bladder wall muscle layers remain hypointense and the two can be differentiated from each other. Immediate postcontrast images reveal little or no urine enhancement, but with renal excretion urine becomes hyperintense on delayed images.

Bladder instillation of a superparamagnetic iron oxide contrast agent aids in evaluating intraluminal extension of bladder tumors.

High-resolution T2-weighted turbo spin echo (TSE) sequences detect tumors as small as 4 mm and estimate the depth of infiltration by identi- fying inner and outer bladder wall margins (3);

this technique, however, does not readily iden- tify different bladder wall layers.

Magnetic resonance (MR) cystoscopy is based on principles similar to CT cystoscopy.

After filling the bladder with a negative contrast agent and using a heavily T2-weighted sequence such as half-Fourier acquisition single-shot turbo spin echo (HASTE), axial and virtual cys- toscopic images achieved a sensitivity of about 90% in detecting tumors <1 cm and 100% for tumors 1 cm or larger (4), results not differing statistically from CT cystoscopy or conventional cystoscopy.

Virtual MR cystoscopy without bladder filling with contrast or use of IV contrast is also feasi- ble; tumors >1 cm are readily detected (5). The role of such a contrast-less MR study in screen- ing and diagnosis remains to be established.

Scintigraphy

Radionuclide cystography is less often per- formed than conventional cystography because of its poorer spatial resolution. Technetium- 99m (Tc-99m)–sulfur colloid is not absorbed from the bladder and is thus employed. Indi- rect radionuclide cystography using Tc-99m- mercaptoacetylglycilglycilglycine (MAG3) may be sufficient for some indications.

Congenital Abnormalities

Agenesis

Bladder agenesis is very rare and is usually associated with other major anomalies. Most affected neonates are stillborn.

Duplication

Bladder duplication is rare. With complete duplication each kidney and ureter drains into its separate bladder, which then drains by sepa- rate urethras. Some duplications are incomplete and the two bladders communicate through an isthmus. Some bladders only appear duplicated because of an internal septum. An “hourglass”

bladder or a large diverticulum arising from the dome of the bladder also mimics an incomplete duplication.

Cystography readily detects a bladder duplication.

A rare bladder duplication is associated with exstrophy, epispadias, and other abnormalities.

Cloacal Exstrophy

Various gradations in failure of fusion of the inferior abdominal wall range from an omphalocele, to cloacal (bladder) exstrophy, to epispadias. This condition is more common in males. In some, the anterior abdominal muscles and anterior bladder wall are absent.

Cloacal exstrophy is associated with an

omphalocele, imperforate anus, exstrophy of

two hemibladders, and an everted cecum between which lie the hemibladders. Epispadias is part of an exstrophy abnormality. Cryp- torchidism and an umbilical hernia are com- mon. Extensive bowel anomalies include a blind-ending hindgut and an omphalocele. The terminal ileum may prolapse out of the cecum.

Spinal anomalies are common and the spinal cord is tethered. An association exists between bladder exstrophy and subsequent development of a bladder malignancy.

Conventional radiographs reveal symphysis pubis widening. Such widening is not pathog- nomonic for cloacal exstrophy but is also found in cloacal malformation, epispadias, and other hindgut malformations. In exstrophy the iliac bones are rotated laterally.

Surgical treatment of these patients is complex and includes closure of an omphalo- cele, separation of the gastrointestinal tract from hemibladders, and creation of a single bladder. A bladder continence mechanism needs to be created. Lastly, if possible, a colon pull-through is performed.

Previous therapy for cloacal exstrophy was cystectomy and ureterosigmoidostomy. A num- ber of complications develop with this proce- dure, including urinary infections and renal damage, with the major long-term complication being development of rectosigmoid adenocarci- noma. The risk of carcinoma is much less after creation of a urinary colonic conduit than with a simple ureteral sigmoidostomy.

Serial renal US is worthwhile in these patients to assess renal status and check for development of hydronephrosis. Renal ectopia is common.

These patients are prone to reflux.

A cloacal malformation is a different entity, occurs only in girls, and is not related to cloacal exstrophy; it is discussed in Chapter 12.

Ureterocele

Clinical

A ureterocele is a congenital anomaly consisting of a dilated intramural ureteral segment. It is associated with urinary retention and infection.

Ureteroceles are mostly a pediatric diagnosis but they occasionally first manifest in adult- hood. They are classified into simple and ectopic, depending on the distal orifice. About 10% are bilateral. Some authors suggest that sib-

lings of children with ureteroceles be screened for urogenital abnormalities.

Ectopic ureteroceles are often part of a dupli- cated renal collecting systems, with most termi- nating a ureter draining the upper renal pole.

They are more common in girls and are a common cause of bladder obstruction in girls.

An extreme example consists of bilateral urete- roceles and bilateral duplex systems. An ectopic ureterocele does occur in patients with a single kidney or a horseshoe kidney.

An ectopic ureterocele can distort an adjacent normally located ureterovesical junction to the point of inducing reflux. A rare ureterocele pro- lapses and even strangulates. Or occasionally a simple ureterocele even prolapses into the urethra and leads to bladder outlet obstruction.

Bladder outlet obstruction can also be due to a simple ureterocele if it is large enough.

If necessary, a ureterocele is treated by endo- scopic ureterocele incision; the success rate is lower with ectopic ureteroceles. Vesicoureteral reflux develops after such endoscopic incision in about half the patients, with reflux being more common with an ectopic ureterocele.

Imaging

Intravenous urography of a simple ureterocele is usually diagnostic. A ureterocele is seen as a cyst-like dilation of the distal ureter protruding into the bladder lumen; the ureterocele wall appears as a thin radiolucent line, although infection or stasis results in thickening. The typical “cobra-head” appearance is familiar to most radiologists. At times urography simply reveals a large radiolucent tumor in the bladder in association with nonvisualization of the ipsilateral kidney upper pole.

A cystogram detects a ureterocele, provided instilled contrast does not efface or obscure it.

Serial visualization during bladder filling and voiding is helpful.

Computed tomography of a ureterocele reveals a well-marginated soft tissue tumor at the ureteral insertion (Fig. 11.1). A simple urete- rocele is seen on US as a thin-walled, fluid-filled structure at the trigone.

Occasionally a diminutive renal upper pole is

drained by a small duplicated ureter that ter-

minates in a relatively large ureterocele. This

condition, called ureterocele disproportion, is

difficult to diagnose with most imaging modalities.

Some ureteral duplications and ectopic urete- roceles are associated with ureteral obstruction, marked hydronephrosis, and dilation of the involved ureter to the point that adjacent nonobstructed collecting systems are displaced inferiorly. The reverse can also occur—occa- sionally an obstructed normal ureter mimics the appearance of a ureterocele.

Stones develop in some ureteroceles.

The term ureterocele eversion describes a ureterocele that everts or intussuscepts retrograde into the ureter during voiding cys- tourethrography. Radiographically, the out- pouching can appear similar to a paraureteral bladder diverticulum. At times fluoroscopy aids in detecting these eversions.

Urachal Abnormalities

The urachus, or median umbilical ligament, is a residual fibromuscular cord located in the

midline extending from the anterior superior bladder wall to the umbilicus. This embryonic communication normally closes before birth, but patency after birth results in luminal com- munication between the bladder and the umbilicus. Partial obliteration leads to a blind ending sinus at the umbilical end, or, with failure of the bladder end to close, a sinus com- municates with the bladder (vesicourachal

both the bladder and umbilical ends closed. In children with urachal abnormalities, urachal sinuses and cysts predominate, with a patent urachus and a urachal diverticulum being less common.

Ultrasonography identifies a midline mass between the rectus abdominis muscle and the superior-anterior bladder wall, representing a urachal remnant, in about one third of young adults. A majority of these urachal remnants are nodular, with a minority being tubular in shape. Their prevalence decreases with age, presumably due to involution. In most people a urachal remnant is a normal variant. Occa- sionally one manifests by hematuria and is resected.

Fistula and Sinus Tract

Urachal anomalies are more common in males.

The prevalence of vesicourachal fistulas is increased in the prune belly syndrome. A patent urachus is also associated with urethral obstruction, such as posterior urethral valves or urethral atresia.

The presence of a patent urachus is generally suspected in the neonate and is best established by direct contrast injection into the umbilical opening. A voiding cystourethrogram also detects patency, provided the images are obtained with the infant in a lateral projection.

At times an almost patent urachus is initially asymptomatic but manifests later in life when a bladder outlet obstruction develops.

A vesicourachal diverticulum is a midline outpouching extending from the superior- anterior bladder wall. Most are discovered inci- dentally. Occasionally stasis results in recurrent urinary tract infection and stone formation.

Cancer originating in a vesicourachal diverticu- lum is an uncommon occurrence developing in adults.

Figure 11.1. Ureterocele. Excretory phase three-dimensional (3D) computed tomography (CT) reconstruction identifies hydronephrosis, hydroureter, and a ureterocele (arrow). (Source:

Joffe SA, Servaes S, Okon S, Horowitz M. Multi-detector row CT urography in the evaluation of hematuria. RadioGraphics 2003;23(6):1441–1456, with permission from the Radiological Society of North America.)

A vesicourachal diverticulum can be sug- gested by CT, US, or MRI by detecting a bladder outpouching in the appropriate location.

Infection

Infection leads to a pyourachus, located in the midline, deep to the rectus abdominis muscle.

Imaging reveals a fluid-filled midline cavity close to the anterior bladder wall. When infected, the cyst in effect becomes an abscess and the cyst wall gradually thickens. A charac- teristic CT finding of a pyourachus is a conical- shaped structure extending from the umbilicus to the bladder dome. Inflammatory changes in adjacent subcutaneous tissues, the rectus abdo- minis muscle, and mesenteric fat surround the infected urachus. Chronic infection results in a thickened cyst wall.

An infected urachal cyst can be drained percutaneously, although this is generally a tem- porary measure because of an increased rein- fection rate. For these reasons most urachal cysts are resected. Also, if an infected urachal cyst is suspected in an adult, a necrotic (or infected) carcinoma should be in the differen- tial diagnosis.

Cyst/Neoplasm

Some urachal cysts remain asymptomatic, and others serve as a nidus for infection, while a neoplasm develops in an occasional one. Some urachal cysts gradually enlarge. In general, if US or other imaging shows a midline cystic struc- ture between the umbilicus and bladder not related to bowel, an urachal cyst should be suspected.

Occasionally dystrophic calcifications or osseous metaplasia develop in an urachal cyst wall. Metaplasia of urachal transitional epithe- lium can evolve into an adenoma and carci- noma. A majority of these carcinomas are adenocarcinomas, with an occasional transi- tional cell carcinoma, squamous cell carcinoma, sarcoma, or even a small cell carcinoma. In general, most carcinomas are detected late when the tumor has already spread. A not uncommon presentation is a suprapubic tumor, hematuria, mucusuria, pain, or discharge from the umbili- cus. An occasional urachal adenocarcinoma metastasizes (6); a urachal mucinous carcinoma

is a less common cause of pseudomyxoma peritonei.

Imaging reveals a tumor involving the bladder apex, mostly extravesical in location and often growing along the urachus. Primary bladder carcinomas tend not to have these findings. Some mucin-producing urachal ade- nocarcinomas develop psammomatous calcifi- cations, findings readily detected by CT. These mucinous adenocarcinomas can be solid, cystic, or mixed.

Ultrasonography should readily detect urachal cysts. If needed, CT confirms the diagnosis. Doppler US of an urachus adenocar- cinoma revealed neovascularity and a low resis- tive index in the tumor (7).

Trauma

Spontaneous bladder rupture in the absence of trauma is rare but has occurred in a setting of previous radiation therapy, surgery, infection, or is idiopathic. Contrast extravasation may occur during voiding cystourethrography performed in a patient with an unused bladder. Most of these extravasations are self-limiting.

The risk of bladder rupture increases with bladder distention. Perforation of an empty bladder is generally associated with a pene- trating injury, either extrinsic or a bone fragment.

After blunt pelvic trauma or in a setting of pelvic fractures, bladder or urethral injury is suggested by hematuria or inability to urinate.

A small minority of patients with bladder rupture have only microscopic hematuria. A direct association exists between gross hema- turia and bladder perforation, most being extraperitoneal, less often intraperitoneal, and least common being both intra- and extraperi- toneal. Pelvic fractures are present in a majority of patients with bladder perforation.

A retrograde urethrogram is generally obtained to exclude urethral injury, followed by a cystogram. At times extraperitoneal contrast extravasation is only seen on postdrainage radiographs. A cystogram should detect not only bladder rupture but also determine whether the rupture is intra- or extraperitoneal (Fig. 11.2). During the cystogram an attempt should be made to identify a site of perforation.

Subtle intraperitoneal leaks are difficult to

detect; the diagnosis is generally made by seeing contrast outline the loops of the bowel.

Occasionally contrast absorbed from the peri- toneal cavity and excreted by kidneys provides a clue to an intraperitoneal leak and thus a radi- ograph over the kidneys after a cystogram is useful.

Intravenous urography is inadequate to eval- uate bladder trauma. Likewise, US is not a sub- stitute for a cystogram in a setting of trauma, although US may detect a hematoma or fluid in the peritoneal cavity. Magnetic resonance is generally precluded during the immediate post- trauma period by monitoring logistics in a strong magnetic field.

Many of these trauma patients undergo con- trast CT to evaluate for pelvic and abdominal trauma. The presence of pelvic fractures and pelvic fluid is associated with bladder rupture, but a bladder perforation cannot be excluded on this study without full bladder distension.

In some centers CT cystography, performed after retrograde instillation of contrast, has replaced conventional cystography. Another option is to clamp the patient’s Foley catheter prior to scanning and add a 5-minute or so delay after intravenous (IV) contrast injection to allow for bladder distention. Thin, contiguous slices through the bladder are necessary for this

study. Preliminary evidence suggests that CT cystography achieves similar accuracy to that of conventional cystography (8), but the practical choice between these two studies is not settled.

Also, extravasated contrast detected on a CT cystogram performed after IV contrast injec- tion does not necessarily represents bladder rupture—renal injury can lead to similar findings.

Whether children with pelvic trauma should first undergo a cystogram or CT is debatable, and the role of a CT cystogram in children is not clear.

Extraperitoneal urine and contrast extravasa- tion is into the prevesical space of Retzius; fluid can dissect along the tissue fascial planes and extend into the scrotum or dissect laterally into the hip, resulting in such curiosities as a hip arthrogram becaming evident due to extra- peritoneal bladder rupture and an acetabular fracture.

In general, extraperitoneal bladder rupture is managed by catheter drainage, while intraperitoneal rupture is explored surgically.

Most extraperitoneal bladder ruptures resolve without surgery. The key to successful manage- ment is continuous bladder drainage.

Shotgun pellets have passed spontaneously during voiding.

Figure 11.2. Bladder perforation. Early bladder filling (A) and after partial drainage (B) views during a cystogram indentify contrast extravasation from the bladder base (arrows).

A B

Wall Thickening

Infection/Inflammation

Cystitis

General Imaging Findings

Lower urinary tract infection is considerably more common in women than men. Most attacks clear with antibiotic therapy and recur only in a minority. Imaging is generally reserved for those women not responding to antibiotics, frequent reinfections, atypical presentation, or known risk factors, including hematuria, suspected upper urinary tract infection, past history of stones, infection, or reflux.

If imaging is deemed necessary for suspected upper tract involvement, IV urography is gen- erally the first preferred test. A minority of authors recommend a conventional radiograph combined with US. Some bladder abnormalities are detected on an IV urogram, although voiding cystography provides more informa- tion, including the presence of vesicoureteral reflux. Urethral diverticula are also detected with voiding cystography, although at times a specific double-balloon urethrogram and other studies are necessary for their detection (ure- thral diverticula are discussed in Chapter 12).

While mild cystitis has no abnormal radi- ographic findings, with progressively more severe involvement focal mural thickening evolves, intraluminal tumors may develop, and occasionally an irregular outline become evident. Initially bladder capacity tends to be normal, but with progressive inflammation the lumen contracts.

In adults, the presence of bladder wall thick- ening and irregularity can be secondary to either inflammation or neoplasm, and in many patients a biopsy is necessary to narrow the diagnosis. Not all bladder polyps are neoplastic;

occasionally cystitis results in inflammatory polyps. These inflammatory tumors can be dif- ferentiated from other spindle cell proliferations by immunohistochemical means.

Most so-called congenital hourglass bladders are found in adult males and are associated with bladder inflammation. Imaging simply reveals an hourglass outline.

T1-weighted MRI reveals two distinct layers in a cystitis-thickened bladder wall: a hyperin- tense inner and an isointense outer layer. T2-

weighted MRI reveals four distinct layers: (1) hypointense inner epithelium, (2) hyperintense lamina propria, (3) hypointense muscle layer, and (4) isointense outer layer representing muscle and connective tissue.

Interstitial Cystitis

Interstitial cystitis is more of a syndrome than a specific disease. Etiology is unknown but is often multifactorial in origin. Helicobacter

A relationship has been suggested between interstitial cystitis and collagenous colitis. The vast majority affected are women.

Interstitial cystitis is a severe and debilitating bladder disorder manifesting by pelvic pain and urinary frequency. No diagnostic test is avail- able for this condition and it is diagnosed by exclusion. Urodynamic studies, including a voiding cystourethrogram, are necessary to exclude other conditions. Thus in patients initially believed to have interstitial cystitis, urethral abnormalities such as periurethral fibrosis, urethral diverticula, and chronic ure- thritis are common; eventually only four of 23 patients in one study were believed to suffer from interstitial cystitis (9).

Therapy is difficult. Some women with intractable interstitial cystitis undergo entero- cystoplasty, but even some of these continue being symptomatic. Some require an ileal loop diversion. Of interest is that some subsequent ileal loop biopsies also show histologic changes of interstitial cystitis. Intravesical bacillus Calmette-Guérin (BCG) therapy has led to improvement in some patients (10).

An anterior vaginal hernia (enterocele) developed in 11% of women who underwent cystectomy and urethrectomy for intractable interstitial cystitis (11); clinically, these hernias mimic a midline cystocele except they contain bowel.

Hemorrhagic Cystitis

In some patients hemorrhagic cystitis and

interstitial nephritis are associated with the

use of nonsteroidal antiinflammatory drugs

(NSAIDs). Cyclophosphamide therapy is also

implicated, at times resulting in massive bleed-

ing. Radiation cystitis, secondary to pelvic radi-

ation therapy, also manifests as hemorrhagic

cystitis. Bladder wall edema and inflammation resolves in some patients, while in others it pro- gresses to a small, shrunken bladder. Of interest is that hyperbaric oxygen therapy appears helpful in radiation cystitis (12); hematuria sub- sides and symptoms improve.

The CT and MR appearance of hemorrhagic cystitis varies depending on timing (Fig. 11.3).

Active and very recent bleeding has T1- and T2-weighted imaging characteristics of fluid.

Slightly older blood becomes hyperintense on T1- and hypointense on T2-weighted images, findings reflecting intracellular methemoglobin due to subacute intramural hemorrhage.

Eosinophilic Cystitis

Eosinophilic cystitis is a histologic diagnosis characterized by massive eosinophilic infiltra- tion. Etiology in most patients is unknown, although remission in some patients undergo- ing steroid therapy suggests an allergic condi- tion. One should keep in mind, however, that occasionally a chronic infection results in eosinophilic cystitis. Partial cystectomy and a pseudoneoplastic condition or reaction to suture material can also lead to eosinophilic cystitis.

Eosinophilic cystitis can be subdivided into three clinical entities having different presenta- tions and treatments (13):

Group I consists of young adults and chil- dren with a background of atopy or

parasitic infestation who have micturition difficulties or hematuria. They respond to steroids.

Group II consists mostly of middle-aged women with chronic, recurrent cystopathy.

They respond poorly to therapy.

Group III consists of elderly patients with chronic bladder irritation or other type of injury. They usually do not require therapy.

Some of these patients have eosinophilia and eosinophiluria. A minority progress to fibrosis and a small, retracted bladder, similar to that seen with interstitial or tuberculous cystitis.

Ureteral involvement and hydronephrosis necessitate surgery.

Imaging findings in eosinophilic cystitis are nonspecific. Some patients develop an intralu- minal tumor. Spontaneous bladder rupture is a rare complication of eosinophilic cystitis.

Emphysematous Cystitis

Emphysematous cystitis almost always implies infection, with the most common infection being due to Escherichia coli. Many of these patients are diabetics. Occasionally emphyse- matous pyelonephritis coexists with emphyse- matous cystitis. Some of these patients have gas in the bladder and develop pneumaturia, thus suggesting an enterovesical fistula. Untreated, the condition evolves into bladder gangrene.

Cystoscopy reveals bladder mucosal vesicles.

Computed tomography readily detects emphysematous cystitis or emphysematous pyelonephritis. Conventional radiographs may miss small amounts of intraluminal air unless films with a horizontal x-ray beam are obtained.

Ultrasonography reveals a thickened hyper- echoic bladder wall and acoustic shadowing within the lumen.

Fungal Cystitis

Fungal infection of the lower urinary tract is seen in patients with a neurogenic bladder, pro- longed antibiotic therapy, or prolonged use of an indwelling catheter. Occasionally the condi- tion evolves into emphysematous cystitis, espe- cially in diabetics.

When extensive, Candida cystitis results in a

“fungus ball,” which on rare occasion can result in bladder outlet obstruction.

Figure 11.3. Hemorrhagic cystitis due to Cytoxan therapy.Com- puted tomography reveals a thick-walled bladder containing blood clots, debris, and gas. (Courtesy of Patrick Fultz, M.D., Uni- versity of Rochester.)

Tuberculous Cystitis

Bladder tuberculosis is usually associated with renal involvement. This chronic infection results in an interstitial cystitis and an eventual spastic, small capacity, thick-walled bladder. Clinical presentation tends to mimic interstitial cystitis.

A rare tuberculous cystitis results in a sponta- neous bladder perforation.

Cystography reveals a polypoid bladder outline, ulcerations, and infiltration of the ureterovesical junctions, with the latter evolving into ureteral obstruction or vesicoureteral reflux. Calcifications develop in some bladders but are not commonly detected with conven- tional radiography. Any intraluminal septations are best seen with either CT or US. Extensive granulomas result in a polypoid appearance.

The overall appearance mimics a malignancy (Fig. 11.4).

Schistosomal Cystitis

Schistosomiasis (bilharziasis) is endemic in Africa and western Asia, and infection occurs by contact with water containing cercariae emitted from snails. Schistosoma haematobium develops in portal veins and migrates against the blood flow in the portal vein, the inferior mesenteric vein, and probably from hemorrhoidal veins

into bladder veins, where adults deposit eggs.

The eggs then pass through the bladder wall and are eliminated in urine.

Initially involved are bladder trigone and adjacent ureteral segments, distinguishing schistosomiasis from tuberculosis; the kidneys are primarily involved with the latter, and the ureters are secondarily affected.

Hematuria is a typical and often the only clin- ical presentation. Neither urinary tract infec- tions nor urinary stones are more common than in the general population.

The bladder wall gradually assumes an irre- gular outline and hydroureters develop. At times a biopsy yields eosinophilic cystitis. Some patients develop granulomatous bladder polyps.

Fibrosis and hyperplastic changes evolve into squamous metaplasia, predisposing these patients to subsequent carcinoma. An early onset of chromosomal aberration is found even in histologically benign-appearing mucosa. Car- cinomas in bilharziasis are common and occur at a relatively early age. Tumors range from nodular to infiltrating.

A classic conventional radiographic finding of bladder schistosomiasis is bladder wall calcification, and in endemic areas in the appro- priate clinical setting, little else is in the differ- ential diagnosis. These calcifications are better defined with CT. They range from being barely visible, to those having a thin, rim-like appear- ance, to marked calcification of the entire bladder wall. Ureteral calcifications appear as distal ureteral linear, parallel lines mimicking vascular calcifications.

Urography reveals thickened folds and a shrunken bladder lumen. An enlarged prostate elevating the bladder base is common. In some countries the ready availability of US has made this modality the imaging choice in following these patients.

Actinomycosal Cystitis

Bladder actinomycosis is uncommon. Infected individuals tend to develop extensive fistulas and fibrosis; at times the appearance mimics that of a bladder tumor.

Granulomatous Cystitis

A granulomatous cystitis, often seen in children, is part of eosinophilic cystitis and is often

renal tuberculosis. Computed tomography shows a thick walled shrunken bladder and a nodule projecting from the wall (arrows). The ureters are dilated. (Courtesy of Egle Jonaitiene, M.D., Kaunas Medical University, Kaunas, Lithuania.)

considered to be an immunologic disorder, although a number of these children probably suffer from chronic granulomatous disease, an inherited disease characterized by recurrent bacterial or fungal infections. These children present with hematuria, urgency, and dysuria.

They develop chronic bladder tumors mimick- ing neoplasms.

Crohn’s Disease

Cystitis in Crohn’s patients most often is sec- ondary to an adjacent phlegmon or an enterovesical fistula. A rare patient presents with gross hematuria.

Malacoplakia

Malacoplakia is a granulomatous inflammatory reaction characterized by bladder wall thicken- ing, at times involving adjacent structures.

Pathogenesis is unknown, although many of these patients have other underlying systemic disorders.

Infection by urea splitting organisms results in deposition of inorganic salts and an alkaline encrusted cystitis. These encrustations are asso- ciated with malacoplakia, although the relation- ship between alkaline encrusted cystitis and malacoplakia is incompletely understood. Both malacoplakia and primary squamous cell carci- noma have developed in chronic cystitis.

Imaging reveals one or more intraluminal sessile nodules varying in size, occasionally leading to vesicoureteral junction stenosis and hydronephrosis.

If diffuse, cystitis cystica is in the imaging differential diagnosis.

Ischemia

Bladder overdistention can lead to ischemia and eventual gangrene. The mucosa is most sen- sitive to ischemia and occasionally a necrotic mucosa will slough; eventually the mucosa will regenerate.

Bladder infarction develops with bladder strangulated in an inguinal hernia.

Behçet’s Syndrome

Urinary tract involvement in Behçet’s syndrome can lead to recurrent cystitis, urethritis, or epi- didymitis. Extensive fistulas are not common;

if present, actinomycosis or Crohn’s disease is more likely.

Radiation

Acute radiation cystitis starts 4 to 6 weeks after therapy and presents as a hemorrhagic cystitis.

Imaging reveals edema and a nodular outline.

Postcontrast MRI reveals an enhancing bladder wall; the appearance is similar to that of other causes of cystitis and to some neoplastic infiltrations.

Chronic cystitis develops months or years later and results in a scarred, fibrotic bladder wall with a small shrunken lumen. In general, imaging during the chronic stage is nonspecific.

Radiation cystitis is one cause of a nonfunc- tioning hypertonic bladder.

Occasionally a vesical fistula develops sec- ondary to radiation therapy.

Amyloidosis

Primary bladder amyloidosis is rare; more often encountered is secondary bladder amyloidosis, both presenting with hematuria. The diagnosis is made by histologic examination. Once detected, systemic amyloidosis or a malignant lymphoproliferative disorder should be excluded.

Amyloid infiltration results in a thickened, somewhat irregular bladder wall, and the imaging appearance mimics that of an infiltrat- ing neoplasm. Magnetic resonance imaging reveals amyloid infiltration as a hypointense region on T2-weighted images (compared to a normal bladder wall).

Systemic Sclerosis

Lower urinary tract involvement with systemic sclerosis is not common. Bladder involvement results in varying degrees of wall fibrosis. While autonomic dysfunction is common, urody- namic abnormalities are not.

Tumors

Nonneoplastic Tumors Interureteric Ridge Edema

Interureteric ridge edema is related to trauma

or acute distal ureteral obstruction. It is best

identified with the bladder either partially filled or almost empty.

Cystitis Cystica (Cystitis Glandularis) A condition of unknown etiology, cystitis cystica is associated with chronic urinary tract infection. Histology reveals marked mucosal thickening, lymphatic obstruction, bladder wall edema, and intramural cysts.

Cystitis glandularis is probably a more severe form of cystitis cystica. Pathologically, con- siderable difficulty can be encountered in distinguishing cystitis glandularis from an ade- nocarcinoma, and anecdotal reports describe partial cystectomy performed because of an erroneous diagnosis of adenocarcinoma. Con- fusing the picture further is the occasional patient with cystitis glandularis who subse- quently develops an adenocarcinoma, presum- ably due to the persistence of chronic irritation.

At times cystitis glandularis and pelvic lipo- matosis coexist.

A cystogram reveals large nodules or even a single confluent infiltrating tumor, often at the bladder base; the imaging appearance is very similar to that of a neoplasm, although the presence of several smooth bladder base nodules should suggest cystitis cystica. Both CT and US show irregular regions of bladder wall thickening in association with intraluminal tumors. Trigone involvement leads to ureter obstruction.

Hemangioma

Bladder hemangiomas are not common. They occur in all age groups but are more prevalent in children and young adults. Especially in chil- dren, they manifest with hematuria.

Hemangiomas range from a focal, sessile tumor to a diffuse intramural infiltration. Some are multiple. Similar to hemangiomas at other sites, MR shows them to be hypointense on T1- and hyperintense on T2-weighted images.

The role of selective arterial embolization is not well established for these rare tumors.

Pseudosarcoma

A fibroblastic proliferation of unknown etiol- ogy, called a pseudosarcomatous myofibroblastic

mor, develops in a number of organs, including

the bladder. This tumor has some characteris- tics of a desmoid tumor; indeed, whether these are all the same entity is conjecture. It occurs in both children and adults. It is not associated with prior trauma. Some patients present with hematuria or progressive anemia. Associated pain suggests a hematoma or even intraperi- toneal hemorrhage.

The bladder wall and, at times, surrounding tissues are infiltrated by a tumor superficially resembling a sarcoma. These are highly vascu- lar myxoid stroma tumors showing both early and delayed CT contrast enhancement. In children, both clinically and radiologically this tumor has been mistaken for an embryonal rhabdomyosarcoma or some other type of sarcoma. The diagnosis is established by histol- ogy; no cytologic atypia or increase in number of mitoses should be evident. Immunohisto- chemistry reveals myofibroblast proliferation.

Immunoreactivity with vimentin is positive in some patients.

Condyloma

A bladder condyloma is rare. These tumors are induced by human papilloma virus infection, result in a proliferation of squamous epithe- lium, and are associated with an increased risk of malignancy.

A cystogram reveals one or more intralumi- nal tumor. Imaging identifies an irregular bladder wall thickening and, in fact, a large condyloma mimics a neoplasm.

Endometriosis

Bladder endometriosis is rare. Most often it is contiguous with an extrinsic endometrioma and presents as an infiltrating tumor at the bladder dome. Several reports describe mali- gnant transformation in bladder endome- triosis; most often these are clear cell adenocarcinomas.

Some women with bladder endometriosis develop dysuria and hypogastric pain. Bladder and ureteral endometriosis was associated with recurrent acute pyelonephritis (14).

Computed tomography or MR should define

the often present extrinsic soft tissue com-

ponent (Fig. 11.5). Nevertheless, a neoplasm

cannot be excluded from the imaging

appearance.

Benign Neoplasms Papilloma

A papilloma consists of a fibrovascular bundle covered by either transitional or squamous cells. As discussed in Chapter 10, papilloma eti- ology is unknown and their histopathologic diagnosis difficult.

A type of transitional cell papilloma is the inverted papilloma, found throughout the urothelial tract, but most often in the bladder.

An initial diagnosis of an inverted papilloma should be made with care; papillomas mimic and are readily misdiagnosed as transitional cell carcinomas. These tumors are believed to be related to human papillomavirus type 18 infec- tion, chronic irritation, and subsequent meta- plasia. An occasional one is associated with a more proximal urothelial carcinoma or a superficial bladder tumor.

A typical papilloma appearance is that of an isolated, endophytic tumor. On immediate post- contrast MRI papillomas appear as enhancing polyps arising from a less enhancing bladder wall and surrounded by intraluminal signal- void urine.

Leiomyoma

Bladder leiomyomas are the most common benign bladder neoplasm but still represent less than 1% of all bladder tumors. They are detected in a younger patient age group than are carcinomas.

Many of these patients are asymptomatic, and these tumors are detected incidentally. Some manifest with hematuria, and less often bladder outlet obstruction or ureteral obstruction.

Intraluminal growth is most common; a minority grow extravesically, while a dumbbell appearance is relatively rare. Some extravesical leiomyomas reach a large size before being detected.

A cystogram reveals leiomyomas as smooth, sessile tumors. Magnetic resonance typically identifies a well-marginated tumor having an intermediate signal intensity on T1- and inter- mediate-to-hypointense signal on T2-weighted images. Leiomyomas exhibit variable MR con- trast enhancement. Tumor degeneration leads to a varied appearance.

An imaging-guided suprapubic biopsy can often establish the diagnosis, although most of these tumors are resected.

Nephrogenic Metaplasia/Adenoma

Nephrogenic metaplasia is a rare condition occurring throughout the urothelium but most often involving the bladder. The pathogenesis is unknown, but prior stone disease or some type of trauma appears to be the predisposing factor. Whether the occasionally reported nephrogenic adenoma simply represents fur- ther cell differentiation or is the same entity is speculation.

Nephrogenic adenomas occur in the bladder, bulbar urethra, urethral diverticula, and prosta- tic urethra. Most are discovered incidentally. A history of prior instrumentation or inflamma- tion is not uncommon; these adenomas pro- bably represent a metaplastic response to prior urothelial trauma. Select examples include a 4-year-old girl with a bladder nephrogenic adenoma (15); she had a ureterocele resection and bilateral ureter reimplantations at 3 months of age. Cystoscopy in a 76-year-old man revealed a papillary nephrogenic adenoma (16); he had received intravesical BCG therapy for recurrent bladder transitional cell carcinoma.

Most of these adenomas are polypoid, and imaging simply reveals a sessile tumor, although some are flat.

Recurrence is common after resection, but most authors agree that little risk of malignant transformation exists; nevertheless, some

identifies an irregular intramural tumor posterior and to the left of the bladder (arrow). The appearance mimics a neoplasm.

(Courtesy of Patrick Fultz, M.D., University of Rochester.)

nephrogenic metaplasias and adenomas are associated with bladder cancer. A rare report describes a bladder villous adenoma, at times with foci of adenocarcinoma.

Malignant Neoplasms Transitional Cell Carcinoma Clinical Aspects

Primary bladder cancer is three times more common in men than women and more common in whites than blacks. In the West, most bladder cancers are transitional cell carci- nomas. They range from carcinoma in situ to diffuse infiltration and metastasis. Adenocarci- noma and squamous cell carcinoma are consid- erably less common and tend to occur in certain settings, discussed later.

Epithelial origin bladder neoplasms are uncommon in the second decade of life and rare in the first. Most bladder neoplasms at these ages are of mesodermal origin. Some studies suggest that patients under 40 years of age with bladder transitional cell carcinoma have a lower recurrence rate and a better prognosis com- pared to older patients, but other studies con- clude that the prognosis depends primarily on tumor stage and is not correlated with age. In children, transitional cell carcinomas tend to be low grade and have a low recurrence rate.

The most common clinical presentation is painless hematuria, ranging from gross to microscopic and often intermittent. Ureteral obstruction due to an adjacent cancer is often silent. Spontaneous perforation of a bladder carcinoma is a curiosity. An occasional bladder cancer manifests first via spread to other struc- tures, at times to unusual sites.

The Leser-Trelat sign consists of an associa- tion of multiple seborrheic keratoses with an internal malignancy. It occurs with transitional cell bladder carcinomas.

Etiology

A familial form of bladder transitional cell car- cinoma exists, with two genetic patterns: a minor autosomal-dominant pattern and a more common multifactorial pattern involving both genetic and environmental factors. Some papil- lary and invasive tumors harbor a chromosome 9 allelic loss, while others contain a p53 gene

mutation without alterations of chromosome 9.

Immunohistochemical study of bladder tumors in patients younger than 30 years reveals p53 gene product overexpression in a majority (17);

aneuploidy of chromosome 17 is common. The

grade, high-stage urothelial cancers, and these gene mutations suggest a monoclonal origin for multicentric cancers. An extremely early age at onset, in particular, should suggest a genetic factor.

Infection, the presence of stones, smoking, various direct-acting chemicals, and a number of environmental factors are associated with these cancers. Carcinogenic chemicals impli- cated include benzidine and 4-aminobiphenyl;

cyclophosphamide also appears to increase the risk of bladder cancer. Some affected indivi- duals are infected with human type 18 papillo- mavirus.

Bladder carcinoma is the most common malignancy in those parts of the Middle East and Africa where schistosomiasis is endemic.

The specific relationship is not clear, but N- nitrosamine compounds appear involved because urine levels of these compounds are increased in patients with schistosomiasis- associated bladder cancer.

Associated Conditions

In patients with renal pelvis and ureteral tran- sitional cell carcinomas, almost half have syn- chronous or will develop metachronous bladder tumors, and these patients should undergo regular cytologic evaluation and radiologic screening for a prolonged time period in order to detect these associated bladder carcinomas.

On the other hand, only in a small minority does

a bladder tumor antedate an upper tract tumor,

and in these patients the primary bladder tumor

tends to be multifocal. Whether patients with a

bladder cancer should undergo regular upper

urinary tract follow-up is not clear from the

literature, although among patients with stages

Ta, T1, and Tis bladder tumors entered in a

prospective trial of BCG therapy and followed

for 15 years or longer, 21% developed upper

tract tumors (18); some of these tumors

occurred between 10 and 15 years later, and thus

these patients need lifelong follow-up. Intra-

venous urography is useful for screening upper

urinary tracts; retrograde pyelography provides

alternate visualization if IV urography is incon- clusive. Some investigators, on the other hand, believe that IV urography at the initial diagno- sis of bladder cancer is unnecessary because of a low upper urinary tract tumor detection rate with urography.

In patients with a prostate or bladder cancer, the risk of having or developing the other cancer is considerably greater than expected. Patients with a bladder carcinoma are also at increased risk for renal cell carcinomas and bronchopul- monary carcinoma.

Pathology

Histologically, a diagnosis of transitional cell carcinoma is not always straightforward.

Mimicry by benign cystitis glandularis has already been mentioned. The reverse is also true; even an invasive bladder transitional car- cinoma can be composed of cells and glands having relatively bland cytologic features sug- gesting a benign condition.

Metaplastic changes, at times extensive, are often observed in a setting of a bladder cancer.

Epithelial dysplasia is found in most resected bladders with a bladder cancer. Incidental car- cinoma in situ is also common, and up to one third of cancers are multifocal. An occasional bladder carcinoma exhibits osseous or carti- laginous metaplasia or osteoclast-like giant cells.

The World Health Organization grading system for transitional cell carcinomas consists of grade I lesions, which are low grade (well- differentiated), and grade III lesions, which are poorly differentiated. Grade II lesions are inter- mediate. Grade I tumors rarely invade, and the vast majority of invasive tumors are grade III.

Detection

Urinary cytology detects low-grade bladder cancers with about 50% sensitivity, although currently the diagnosis is generally established by cystoscopy and biopsy. Bladder wash cytol- ogy at the time of cystoscopy also aids in diagnosis.

Proposed tests to detect urothelial neoplasms include tumor antigen, fibrin/fibrinogen degra- dation products, and nuclear matrix protein (NMP-22); these require further study to estab- lish their place in cancer detection.

Bladder transitional cell carcinomas range from exophytic (papillary) to infiltrating or a combination of both. Exophytic tumors are either polypoid or frond-like. Demonstration of intraluminal extension, although helpful in localizing a tumor, does not aid tumor staging.

A carcinoma can originate in a bladder diverticulum.

Computed tomography identifies a soft tissue tumor arising from the bladder wall (Fig. 11.6).

Depending on growth, these tumors range from a sessile polyp to bladder wall thickening. The least common is a pedunculated polyp. Tumors at the bladder dome or trigone are poorly imaged with CT, the limitation being the axial slices used. Because of partial volume averaging, these lesions tend to blend into the bladder wall and surrounding structures. Likewise, tumors at the bladder base tend to blend into the prostate.

In general, CT misses lesions smaller than about 1 to 2 cm in diameter. Computed tomography also cannot distinguish adherent blood clots from a tumor. Coronal views are often helpful.

Contrast enhanced multidetector CT reveals bladder cancers enhancing more than the sur- rounding bladder wall, best seen on 60–80 sec delayed scans (19); tumors <4 cm in diameter tend to have homogeneous enhancement, larger ones become more heterogeneous. A urine dis- tended bladder aids tumor detection.

Computer tomography cystoscopy, with the bladder opacified with contrast, can also detect

Figure 11.6. Bladder transitional cell carcinoma. Excretory phase CT identifies a right bladder tumor (arrow). The bladder base tumor (arrowheads) is due to prostatic enlargement.

(Source: Joffe SA, Servaes S, Okon S, Horowitz M. Multi-detector row CT urography in the evaluation of hematuria. RadioGraph- ics 2003;23(6):1441–1456, with permission from the Radiologi- cal Society of North America.)

bladder cancer, with undetected tumors gener- ally being <5 mm in diameter. One study, however, identified 88% of tumors <5 mm (20).

Transverse and virtual cystoscopy images are complimentary—some small tumors are identified only on virtual images but bladder wall thickening is more apparent on transverse images. Computer tomography 3D cystography using perspective volume rendering and a shaded-surface 3D outline evaluates tumor size and shape and provides information about its relationship to adjoining mucosa. With current techniques, however, endoscopic cystoscopy has better spatial resolution in detecting small bladder tumors.

A typical US appearance of a transitional cell carcinoma is that of a hypoechoic tumor. The findings are nonspecific. Bladder tumors can be evaluated with endourethral US. The major lim- itation of intravesical US is the inability to dif- ferentiate among neoplasms, inflammation, and bladder wall hypertrophy due to other factors.

Likewise, intravesical US is limited in evaluating deep invasion.

These carcinomas have a T1-weighted signal intensity similar to that of muscle (Fig. 11.7).

T2-weighted images reveal a higher signal intensity than normal bladder wall or fibrosis.

Tumor detection is superior with postcontrast images, although one should keep in mind that both cystitis and tumors exhibit early MR con- trast enhancement.

Superficial tumor calcifications are usually secondary to calcium salt deposition. More central calcifications develop secondary to tumor necrosis, although such calcifications are also seen in carcinosarcomas containing osseous metaplasia or an osteosarcoma component.

One bladder transitional cell carcinoma showed intense uptake of Tc-99m–hydrox- ymethylene diphosphonate (HMDP) during bone scintigraphy (21); uptake corresponded to a bladder tumor containing punctate and cur- vilinear calcifications identified by CT, and chemisorption of urinary Tc-99m-HMDP excre- tion probably accounted for the uptake.

A biopsy is necessary to establish the diagno- sis; both benign and malignant tumors and some nonneoplastic conditions overlap in their imaging appearance. Cystoscopic tumor detec- tion specificity and sensitivity are improved by using laser-induced autofluorescence spectra for guidance of suspicious lesions that are oth- erwise difficult to detect.

Staging

The Union Internationale Contre le Cancer (UICC) and American Joint Committee on Cancer (AJCC) both use the tumor, node, metas- tasis (TNM) staging system for bladder cancers (Table 11.1). This system differentiates superficial from infiltrating tumors. The TNM

A

B

system is used for both pretherapy staging and postresection staging (pathologic staging).

Tumor stage is the most important predictive prognosis factor. The presence of bilateral ureteral obstruction affects the prognosis. Over 90% of patients with bilateral obstruction have extravesical extension of their cancer, but among those with unilateral obstruction a third have disease confined to the bladder, at times with the cancer even limited to the bladder

mucosa (22). In patients with a bladder cancer, the presence or absence of accompanying carci- noma in situ or epithelial dysplasia does not seem to influence survival significantly.

Recent cystoscopic biopsy leads to confusion because of edema and interferes with accurate tumor staging, and it is reasonable to delay a staging imaging study for several weeks after biopsy.

For superficial bladder tumors clinical staging (cystoscopy and biopsy) appears supe- rior to MRI, but MRI is better than clinical staging for more infiltrating tumors.

Currently CT is not sufficiently accurate in staging bladder tumors ranging from carci- noma in situ through tumors invading deep muscle. Because no definite fat planes exist between bladder and adjacent posterior struc- tures, CT cannot readily define the invasion of these structures (Figs. 11.8 and 11.9). Seminal vesicles have a CT soft tissue density whether invaded or not; an exception is the seminal vesicle anterior surfaces, where fat angle oblit- eration between the seminal vesicle anterior surface and posterior bladder wall implies tumor invasion. Computed tomography is more accurate with more advanced tumors. Com- puted tomography does evaluate for metastases.

Overall CT staging accuracy is only 30% to 40%

and CT changes management in only few patients.

Table 11.1. Tumor, node, metastasis (TNM) staging of bladder cancer

Primary tumor:

Tx Primary tumor cannot be assessed T0 No evidence of primary tumor Ta Non-invasive papillary carcinoma Tis Carcinoma in situ

T1 Tumor invades subepithelial connective tissue T2a Tumor invades superficial muscle

T2b Tumor invades deep muscle T3 Tumor invades perivesical tissue T4a Tumor invades prostate, uterus, vagina T4b Tumor invades pelvic wall, abdominal wall Lymph nodes:

Nx Regional nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis to single lymph node 2 cm or less

in greatest dimension

N2 Metastasis to single lymph node larger than 2 cm but not more than 3 cm

N3 Metastasis in a lymph node more than 3 cm in greatest dimension

Distant metastasis:

Mx Distant metastases cannot be assessed M0 No distant metastasis

M1 Distant metastasis Tumor stages:

Stage 0a Ta N0 M0

Stage 0is Tis N0 M0

Stage I T1 N0 M0

Stage II T2a N0 M0

T2b N0 M0

Stage III T3 N0 M0

T4a N0 M0

Stage IV T4b N0 M0

any T N1 M0

any T N2 M0

any T N3 M0

any T any N M1

Source: From the AJCC Cancer Staging Manual, 6^thedition (2002), published by Springer-Verlag, New York, NY, used with permission of the American Joint Committee on Cancer (AJCC), Chicago, IL.

Figure 11.8. Invasive bladder carcinoma. Computed tomogra- phy identifies an infiltrating tumor in the left posterior bladder wall. It was inseparable from the uterus and sigmoid colon but invasion could not be determined. (Courtesy of Patrick Fultz, M.D., University of Rochester.)

Transabdominal US is seldom used to stage bladder cancers, having been replaced by more accurate imaging modalities. Endorectal US also has a low accuracy, but endourethral US shows promise in local staging of these tumors, espe- cially for those limited to the bladder wall.

Endourethral US is useful in detecting tumors in bladder diverticula.

Although color Doppler US detects some vascularity in transitional cell carcinomas, the Doppler findings are not helpful in evaluating tumor grade or stage, although in general, larger and higher-grade tumors tend to be more vascular.

Magnetic resonance imaging has the poten- tial for accurate bladder tumor staging, although both CT and MR tend to overstage more often than understage. The use of surface coils leads to better image quality than does the use of body coils. Endorectal coils improve visu- alization of the bladder base and dorsal struc- tures but are of limited use for the rest of the bladder. T1-weighted images provide good con- trast between hyperintense perivesical fat and isointense bladder wall, and detects perivesical fat invasion, spread to lymph nodes, and bone marrow metastases; the latter are identified against the hyperintense normal marrow. T2- weighted images evaluate bladder wall infil- tration and prostatic and adjacent structure invasion, although differentiation between tumor and edema is difficult. Using early-phase contrast enhancement, MRI achieves relatively

high staging accuracy, especially in differentiat- ing between superficial tumors and those invad- ing muscle. Magnetic resonance appears especially useful in evaluating depth of bladder wall invasion. It thus appears reasonable to perform MRI before resection. Postcontrast MR reveals early tumor enhancement and appears more sensitive and specific than precontrast imaging. Bladder cancers begin to enhance several seconds after the start of arterial enhancement, which is earlier than most other structures.

When staging for lymph node involvement, CT and conventional MRI appear comparable.

The accuracy of MRI is very technique depend- ent, and the results obtained with a specific technique do not apply to all MR scanners and techniques. Lymph nodes have longer T1 relax- ation times than fat and thus T1-weighted images are useful in distinguishing nodes from adjacent pelvic fat, although subtle findings are better defined with postcontrast fat-suppressed images. Separating adjacent skeletal muscle from nodes, on the other hand, is easier on T2- weighted images, and thus several sequences are usually employed. In either case, CT and MRI simply detect whether a lymph node is enlarged or not but cannot detect whether it is infiltrated by tumor or enlarged secondary to a benign cause.

Bladder cancers spread to the lungs; chest radiography is a simple screening test, at times supplemented by chest CT. Bone scintigraphy is

Figure 11.9. Invasive bladder carcinoma. More superior (A) and inferior (B) transverse pelvic CT images show marked right-sided bladder wall thickening (arrows). Reflux into the right ureter is evident. The cancer is extending almost to the anterior abdominal wall. (Courtesy of Egle Jonaitiene, M.D., Kaunas Medical University, Kaunas, Lithuania.)

A B

not commonly obtained at initial staging unless symptoms suggest bone metastases.

Attempts have been made to evaluate bladder cancers with positron emission tomography (PET) using both 2-[18F]-fluoro-deoxy-D- glucose (FDG) and other compounds, but the results for local tumor spread are not superior to those of more traditional imaging. Urinary excretion of FDG limits tumor identification from the surrounding activity. For detecting lymph node involvement, however, PET-FDG in patients with bladder neck carcinoma achieved a 67% sensitivity and 86% specificity (23); these results appear superior to those obtained with CT or MRI studies.

Therapy

Therapy of a bleeding, nonresectable bladder cancer is difficult. One approach is intraarterial chemoperfusion with mitoxantrone, which in one study controlled hemorrhage in 14 of 15 patients (24). In patients with life-threatening bleeding, intraarterial embolization is the pro- cedure of choice.

Resection: Resection ranges from local exci-

sion, to segmental resection, to radical cystec- tomy. The surgical therapy adopted depends on the extent of tumor and varies for superficial disease and muscle-invasive disease. Noninva- sive, low-grade cancers are often fulgurated. The 5-year survival for patients with treated bladder carcinoma-in-situ is about 90%. Stage Ta and some T1 cancers are resected transurethrally.

Nevertheless, because of a high rate of recur- rence even with these tumors, additional therapy is often instituted; surveillance cys- toscopy results in an excellent 5-year survival.

Dysplasia or a multicentric cancer requires resection. T1 disease, by definition, signifies lamina propria invasion but is still considered superficial; if treated by focal resection, recur- rence eventually develops in almost half of these patients and the surgeon is faced with a dilemma in these patients between focal resec- tion and a cystectomy.

In the United States, therapy for stage T2 to T4 bladder cancer is generally a total cysto- prostatectomy. Two types of ileal conduits are constructed after bladder resection: a stomal noncontinent ileal diversion or a continent urinary reservoir anastomosed to either the urethra or a cutaneous stoma requiring inter-

mittent catheterization (Kock pouch). The ureters are anastomosed to the neobladder. In some countries radiotherapy is preferred ini- tially. Some stage pT2 bladder transitional cell carcinomas are treated by conservative surgery and iridium-192 brachytherapy.

Urinary tract diversion into the sigmoid colon was the initial anastomosis performed after a cystectomy until this operation was superseded by the use of various ileal conduits.

A ureterosigmoidostomy is still encountered in the follow-up of previously operated patients.

The complications of such diversion includes septic reflux, anastomotic stenosis, and hyper- chloremic metabolic acidosis.

A study of patients undergoing cystectomy for bladder cancer found the 5-year survival for those with tumors confined to the bladder (<T3) to be 79%, but in patients with tumor spread beyond the bladder (>T3) survival was only 28%

(25); from a lymph node viewpoint, 5-year sur- vival for those with N0, N1, and N2–3 nodes was 64%, 48% and 14%, respectively.

Cystectomy is generally not considered for tumors extending beyond the bladder wall.

Prostatic involvement is common with invasive transitional cell bladder cancers. Transitional cell carcinoma has a tendency to invade the prostatic urethra, and such invasion has a poor prognosis. Also, intravesical chemotherapy is ineffective in the prostatic urethra.

Bacillus Calmette-Guérin: Besides surgery,

chemotherapy and immunotherapy with BCG are used to treat superficial bladder cancer.

After the initial resection of a superficial transi- tional cell carcinoma, the risk of a subsequent tumor is decreased by adding either intravesical adjuvant chemotherapy or BCG immuno- therapy. Some long-term studies of intravesical chemotherapy, however, reveal a limited decrease in tumor recurrence, and the use of routine prophylactic intravesical chemotherapy is questioned. BCG, on the other hand, is an effective intravesical agent in the prophylaxis and therapy of superficial transitional cell car- cinoma; nevertheless, the use of BCG for Ta and T1 cancers varies considerably.

Bacillus Calmette-Guérin is a potent immune

stimulant and exerts a direct toxic effect. Intrav-

esical instillation leads to an inflammatory and

immune cell infiltration into bladder lamina

propria. The use of BCG prophylaxis results in

less tumor recurrence than with surgical tumor

resection. Therapy with BCG in patients with primary bladder carcinoma-in-situ leads to complete response in a majority of patients. It appears to delay progression and the need for cystectomy in high-risk patients—those with dysplasia, carcinoma in situ, and multiple primary tumors. Low-dose BCG therapy in high-risk patients with stage T1, grade 3 bladder tumors combined with transurethral tumor resection resulted in 80% of patients respond- ing to BCG instillation (26).

Among patients with pTa or pT1 bladder tumors treated by transurethral resection and intravesical BCG with 2 years of maintenance therapy, 62% of patients were recurrence-free at 48 months (27); a similar group of patients treated by transurethral resection alone and a group treated with transurethral resection and mitomycin C achieved recurrence-free results in 18% and 38% of patients, respectively. At 42 months, 11% of pT1 tumors treated with BCG had progressed to invasive carcinoma, compared to 25% of those treated by transurethral resection alone and 21% of those treated with transurethral resection and mitomycin C (27).

In a minority of patients BCG instillation results in toxicity, and a number of complica- tions develop. In addition to the sequelae of tuberculous infection, tuberculous lymph- adenitis leads to tumor overstaging. Bacillus Calmette-Guérin therapy for superficial bladder tumor led to epididymitis and epididymal abscess requiring an orchidectomy (28). Tuber- culous enteritis (29) and mycotic aneurysms (30) have developed. In France, BCG Pasteur strain was used previously, more recently being supplanted by the Connaught (Toronto) strain.

Toxicity appears similar for the two strains (31).

Ultrasonography after BCG therapy reveals hypoechoic foci in the prostate transition zone, representing necrotizing granulomas; confusing the issue is that bladder carcinoma invading the prostate also appears hypoechoic, and thus biopsies of these lesions are indicated.

Other Therapy: Some advanced bladder

cancers are treated with radiotherapy and chemotherapy. Computed tomographic cystog- raphy commonly identifies bladder wall thick- ening at a tumor site after radiotherapy and chemotherapy due to a granulomatous reaction even without tumor recurrence. Magnetic reso- nance angiography (MRA) appears useful in

evaluating the chemotherapy response in patients with advanced bladder cancer. Using persisting early contrast enhancement as a criterion, MRA achieves high sensitivity and specificity in distinguishing responders from nonresponders.

Superficial bladder tumors have been treated cystoscopically by injecting ethanol through a needle into the tumor base. Photodynamic therapy for small papillary bladder cancers achieves a response.

Interferon-a appears useful in carcinoma in situ and primary and recurrent papillary tran- sitional cell carcinomas, although the response and relapse rates are inferior to those of BCG.

Intravesical recombinant interferon-a therapy also appears useful in patients not responding or refractory to BCG therapy. Interleukin-2 is a potential agent in bladder cancer therapy. Even garlic appears to inhibit cancer cell growth and protects against suppression of immunity by chemotherapy (32).

Microwave-induced hyperthermia is occa- sionally mentioned for recurrent superficial bladder tumors not amenable to transurethral resection.

Metastasis/Recurrence

Clinical: After resection of one tumor, whether

a new bladder tumor represents a recurrence or a new metachronous tumor is often unclear.

Findings of distinct foci of synchronous carci- noma or carcinoma in situ argue for separate tumors. On the other hand, the increased risk for subsequent bladder cancers after an upper tract transitional cell carcinoma and lower risk of upper tract tumors after an initial bladder cancers argues for tumor dissemination.

Most recurrence of bladder carcinoma is detected within several years of initial surgery, with risk gradually tapering thereafter, although occasional metastases are detected a decade or longer after cystectomy. Most bladder cancers spread locally. Urethral recurrence after cysto- prostatectomy occurs in about 5% of patients.

Following cystectomy, recurrence within an

ileal conduit is uncommon. Some tumors

recur in regional lymph nodes, and distant

metastases eventually develop in up to one

third. Distal metastases are most common to the

lungs, and then to the lymph nodes, bone, and

liver. Rarer sites include malignant pericardial