Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

bladder cancer, with undetected tumors generally being <5mm in diameter. One study, however, identified 88% of tumors <5mm (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 limitation of intravesical US is the inability to differentiate 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 contrast 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 curvilinear calcifications identified by CT, and chemisorption of urinary Tc-99m-HMDP excretion probably accounted for the uptake.

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

Staging

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

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

Primary tumor:

Distant metastasis:

Mx Distant metastases cannot be assessed M0 No distant metastasis

M1 Distant metastasis

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

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mucosa (22). In patients with a bladder cancer, the presence or absence of accompanying carcinoma 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 superior 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 carcinoma in situ through tumors invading deep muscle. Because no definite fat planes exist between bladder and adjacent posterior structures, 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 obliteration between the seminal vesicle anterior surface and posterior bladder wall implies tumor invasion. Computed tomography is more accurate with more advanced tumors. Computed tomography does evaluate for metastases. Overall CT staging accuracy is only 30% to 40% and CT changes management in only few patients.

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

Figure 11.8. Invasive bladder carcinoma. Computed tomography 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.)

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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, especially 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 potential 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 visualization of the bladder base and dorsal structures but are of limited use for the rest of the bladder. T1-weighted images provide good contrast 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. T2weighted images evaluate bladder wall infiltration 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 differentiating between superficial tumors and those invading 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 dependent, and the results obtained with a specific technique do not apply to all MR scanners and techniques. Lymph nodes have longer T1 relaxation 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 T2weighted 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

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 procedure of choice.

Resection: Resection ranges from local excision, to segmental resection, to radical cystectomy. The surgical therapy adopted depends on the extent of tumor and varies for superficial disease and muscle-invasive disease. Noninvasive, 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 recurrence even with these tumors, additional therapy is often instituted; surveillance cystoscopy 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, recurrence eventually develops in almost half of these patients and the surgeon is faced with a dilemma in these patients between focal resection and a cystectomy.

In the United States, therapy for stage T2 to T4 bladder cancer is generally a total cystoprostatectomy. 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-

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mittent catheterization (Kock pouch). The ureters are anastomosed to the neobladder. In some countries radiotherapy is preferred initially. 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 hyperchloremic 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 survival 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 transitional cell carcinoma, the risk of a subsequent tumor is decreased by adding either intravesical adjuvant chemotherapy or BCG immunotherapy. 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 carcinoma; 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. Intravesical 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

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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 responding 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 complications develop. In addition to the sequelae of tuberculous infection, tuberculous lymphadenitis leads to tumor overstaging. Bacillus Calmette-Guérin therapy for superficial bladder tumor led to epididymitis and epididymal abscess requiring an orchidectomy (28). Tuberculous 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 cystography commonly identifies bladder wall thickening at a tumor site after radiotherapy and chemotherapy due to a granulomatous reaction even without tumor recurrence. Magnetic resonance 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 transitional 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 occasionally 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 carcinoma 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 cystoprostatectomy 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