Porth's Essentials of Pathophysiology, 4e

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Kidney and Urinary Tract Function

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lined with neoplastic epithelium. Although these tumors may recur and rarely invade the underlying bladder wall, they are seldom life-threatening. 59,60 High-grade carcinomas can be papillary or flat; they tend to cover larger areas of the mucosal surface and carry a high risk of invasion into the detrusor muscle and surrounding tissues, and when associated with inva- sion, a significant metastatic potential. Bladder cancers are commonly staged according to the TNM classifica- tion (see Chapter 7) of the World Health Organization (WHO) with stage T3 carcinomas invading perivesical tissues and T4 carcinomas spreading to adjacent organs and distant metastases. 59–61 Etiology and Pathogenesis Although the cause of bladder cancer is unknown, evi- dence suggests that its origin is related to local influ- ences, such as carcinogens that are excreted in the urine and stored in the bladder. 57–62 Cigarette smoking is an important risk factor, with 30% to 50% of all bladder cancers among males who are current or past smok- ers. Other risk factors include the presence of arsenic in the drinking water and industrial exposure to the breakdown products of aromatic amines used in the dye industry and to chemicals used in the manufacture of rubber, textiles, paint, and petroleum products. 62 Both the heavy long-term use of cyclophosphamide, an immu- nosupressive agent, and prior exposure to bladder radi- ation, often administered for other pelvic malignancies, also increase the risk of bladder cancer. Bladder cancer also occurs more frequently among persons harboring Schistosoma haematobium , a parasite that is endemic in Egypt and Sudan, in their bladder. 59,61 Manifestations The most common sign of bladder cancer is painless hematuria. 58–61 Gross hematuria is a presenting sign in 75% of persons with the disease, and microscopic hema- turia is present in most others. Frequency, urgency, and dysuria occasionally accompany the hematuria. Because hematuria often is intermittent, the diagnosis may be delayed. Periodic urine cytology is recommended for all persons who are at high risk for the development of bladder cancer because of exposure to urinary tract carcinogens. Ureteral invasion leading to bacterial and obstructive renal disease and dissemination of the cancer are potential complications and ultimate causes of death. The prognosis depends on the histologic grade of the can- cer and the stage of the disease at the time of diagnosis. Diagnosis andTreatment Diagnostic methods include cytologic studies, excretory urography, cystoscopy, and biopsy. Ultrasonography, CT scans, and MRI are used as aids for staging the tumor. Cytologic studies performed on biopsy tissues or cells obtained from bladder washings may be used to detect the presence of malignant cells. 59

The treatment of bladder cancer depends on the type and extent of the lesion and the health of the patient. Endoscopic resection usually is done for diagnostic purposes and may be used as a treatment for superfi- cial lesions. For small papillary tumors that are not high grade, the initial diagnostic transurethral resection may be the only surgical procedure done. Segmental surgi- cal resection may be used for removing a large single lesion. When the tumor is invasive, a cystectomy with resection of the pelvic lymph nodes frequently is the treatment of choice. Cystectomy requires urinary diver- sion, an alternative reservoir, usually created from the ileum (e.g., an ileal loop), that is designed to collect the urine. External-beam radiation therapy is an alternative to radical cystectomy in some patients with deeply infil- trating bladder cancer. 59 Surgical treatment of superficial bladder cancer is often followed by intravesicular chemotherapy or immu- notherapy, a procedure in which the therapeutic agent is directly instilled into the bladder. One of the agents used for this purpose is an attenuated strain of the tubercu- losis bacillus, called bacillus Calmette-Guérin (BCG), which elicits an inflammatory response that destroys the tumor. Patients who are found to have regional inva- sion or distant metastasis are often treated with systemic chemotherapeutic agents. Therapy can be given before planned cystectomy (neoadjuvant) in an attempt to decrease recurrence or in some cases to allow for bladder preservation. Alternatively, adjuvant chemotherapy may administered after surgery to prevent tumor recurrence. ■■ Bladder cancers fall into two major groups: low-grade noninvasive tumors and high- grade invasive tumors that are associated with metastasis and a worse prognosis. ■■ Although the cause of cancer of the bladder is unknown, evidence suggests that carcinogens excreted in the urine may play a role. Cigarette smoking is an important risk factor. Other risk factors include the presence of arsenic in the drinking water and exposure to industrial chemicals. ■■ Microscopic and gross painless hematuria are the most frequent presenting signs of bladder cancer. The methods used in treatment of bladder cancer depend on the cytologic grade of the tumor and the lesion’s degree of invasiveness. ■■ Treatment methods include surgical removal of the tumor, radiation therapy, and chemotherapy. In many cases, chemotherapeutic or immuno­ therapeutic agents can be instilled directly into the bladder, thereby avoiding the side effects of systemic therapy. SUMMARY CONCEPTS