Porth's Essentials of Pathophysiology, 4e

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Genitourinary and Reproductive Function

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factors such as dietary fat reduction and supplemen- tation with vitamins D and E and selenium. 50 Dietary intake of soy, green tea, and tomato-rich products (lyco- pene) may also be important. Vitamin D is not techni- cally a vitamin, but a steroid hormone that has a variety of antiproliferative and proapoptotic effects in prostatic as well as other cancer cell lines. Vitamin E, selenium, and lycopene are all antioxidants, thought to play an important role in cellular defenses to oxidative stress. The low incidence of prostate cancer in Asia has led to an interest in the study of soy and green tea, which are highly consumed in these nations. In terms of hormonal influence, androgens are believed to play a role in the pathogenesis of prostate cancer. 14 Evidence favoring a hormonal influence includes the presence of steroid receptors in the prostate, the require- ment of sex hormones for normal growth and develop- ment of the prostate, and the fact that prostate cancer almost never develops in men who have been castrated. The response of prostate cancer to estrogen administra- tion or androgen deprivation further supports a correla- tion between the disease and testosterone levels. 14 Clinical Features. Prostatic adenocarcinomas, which account for most primary prostate cancers, are com- monly multicentric and located in the peripheral zones of the prostate 14,15 (see Fig. 39-12). The high frequency of invasion of the prostatic capsule by adenocarcinoma relates to its subcapsular location. Invasion of the uri- nary bladder is less frequent and occurs later in the clinical course. Metastasis to the lung reflects lymphatic spread through the thoracic duct and dissemination from the prostatic venous plexus to the inferior vena cava. Bony metastases, particularly to the vertebral col- umn, ribs, and pelvis, produce pain that often presents as a first sign of the disease. Most men with early-stage prostate cancer are asymptomatic. 51 The presence of symptoms often sug- gests locally advanced or metastatic disease. Depending on the size and location in the prostate of the cancer at the time of diagnosis, there may be changes associated with the voiding pattern similar to those found in BPH. These include urgency, frequency, nocturia, hesitancy, dysuria, hematuria, or blood in the ejaculate. 44 On digi- tal rectal examination, the prostate can be nodular and fixed. Bone metastasis often is characterized by low back pain. Pathologic fractures can occur at the site of metastasis. Men with metastatic disease may experience weight loss, anemia, or shortness of breath. Screening. Whether screening for prostate cancer results in a decrease in prostate cancer deaths is a sub- ject of much debate. 52,53 The screening tests currently available are digital rectal examination, PSA testing, and transrectal ultrasonography. Depending on the pop- ulation studied, detection using digital rectal examina- tion varies from 1.5% to 7%, with most cancers being far advanced when they are detected. 53 Prostate-specific antigen is a glycoprotein secreted into the cytoplasm of benign and malignant prostatic cells that is not found in other normal tissues or tumors. However, a positive

unclear. Standardization of these products is also worri- some (as with all herbal therapies). The surgical removal of an enlarged prostate can be accomplished by the transurethral, suprapubic, or perineal approach. 44–46 Currently, transurethral prosta- tectomy (TURP) is the most commonly used technique. With this approach, an instrument is introduced through the urethra, and prostate tissue is removed using a resectoscope and electrocautery. Late complications of TURP include sexual dysfunction, incontinence, and bladder neck constriction. Many new and experimen- tal techniques have also been used to treat BPH includ- ing transurethral incision of the prostate, laser surgery, transurethral vaporization, transurethral microwave therapy, and transurethral needle ablation. For men who have heart or lung disease or a condition that precludes major surgery, a stent may be used to widen and main- tain the patency of the urethra. A stent is a device made of tubular mesh that is inserted under local or regional anesthesia. Within several months, the lining of the ure- thra grows to cover the inside of the stent. Cancer of the Prostate Globally, prostate cancer is the second most frequently diagnosed cancer in men. An estimated 900,000 new cases were projected to occur in 2008. Nearly three quarters of these cases were expected to be diagnosed in developed countries, with the highest rates being recorded in the United States (233,000 cases in 2014). 47 The increase in diagnosed cases is thought to reflect ear- lier diagnosis because of widespread use of PSA testing since the early 1990s. African American men have the highest reported incidence rate for prostate cancer at all ages, and the cancer also tends to be diagnosed at a later stage. 47,48 Asians and Native American men have the lowest rate. Prostate cancer also is a disease of aging. The incidence increases rapidly after 50 years of age; more than 85% of all prostate cancers are diagnosed in men older than 65 years of age. 48 Etiology and Pathogenesis. The precise cause of pros- tate cancer is unclear. As with other cancers, it appears that the development of prostate cancer is a multistep process involving genes that control cell differentiation and growth. The incidence of prostate cancer appears to be higher in relatives of men with prostate cancer. It has been estimated that men who have an affected first-degree relative (e.g., father, brother) and an affected second-degree relative (e.g., grandfather, uncle) have an eightfold increase in risk. 14,15,49 It has been suggested that dietary patterns, including increased dietary fats, may alter the production of sex hormones and growth fac- tors and increase the risk of prostate cancer. Supporting the role of dietary fats as a risk factor for prostate can- cer has been the observation that the diet of Japanese men, who have a low rate of prostate cancer, is much lower in fat content than that of U.S. men, who have a much higher incidence. Several factors appear to be protective against the development of prostate cancer. These include dietary