Pathophysiology of prostate cancer

Benign prostatic hyperplasia (BPH) is a condition that affects many men. Treatment of this condition includes medical, noninvasive, and surgical approaches. Transurethral resection of the prostate (TURP) has been used successfully to treat BPH since 1930;1 however, the TURP procedure uses an irrigating solution that has the potential to cause transurethral resection (TUR) syndrome.

A new technology now is available for performing TURP that uses saline irrigation, eliminating the risk of TUR syndrome. In addition, until recently, the use of monopolar current was the only method available for electrosurgery in urology procedures. The bipolar TURP, however, uses bipolar electrosurgery, which does not travel through the body and creates less risk of electrical shock.

ANATOMY OF THE PROSTATE

The prostate is a glandular, fibromuscular organ that lies at the base of the bladder and surrounds the urethra. It is the size of a large chestnut (ie, approximately 4 cm x 3 cm x 2 cm) and is divided into the right and left lateral lobes and the median lobe (Figure 1). (2) The ejaculatory ducts from the seminal vesicles enter the prostate and continue to the prostatic portion of the urethra. The prostate produces a milky, thin, alkaline fluid. During coitus, the prostate gland contracts and promotes the expulsion of semen during ejaculation. (3)

[FIGURE 1 OMITTED]

The section of the urethra that traverses the prostate gland is called the prostatic urethra. This area is lined with a thin, smooth muscle layer that is continuous with the lining of the bladder wall. This smooth muscle is the involuntary sphincter of the posterior urethra in the male. The small mucosal, intermediate submucosal, and large main prostatic secretory glands are arranged concentrically around the prostatic urethra. The enlargement of the small mucosal glands causes BPH. (4) This occurs in the area of the prostate that surrounds the urethra, so urinary obstruction can result.

BENIGN PROSTATIC HYPERPLASIA

Benign prostatic hyperplasia is a nonmalignant enlargement of the mucosal glands of the prostate. It is age related with increased incidence as a man ages. Fifty percent of men age 60 and older are affected by BPH, and 80% to 90% of men age 80 years and older are affected. (5) Although BPH is not a life-threatening disorder, it does interfere with quality of life. Daytime frequency of urination may limit activities, and nocturia prevents restful sleep.

Pathophysiology of BPH. Circulating androgens that are produced primarily in the testes are responsible for the proper functioning of the prostate gland. The prostate binds circulating testosterone and converts it to the hormone dihydrotestosterone. The enzyme 5-reductase, which is produced in the prostatic stroma, must be present for this process to take place. The dihydrotestosterone binds to androgen receptors in the prostatic epithelium, and cellular reproduction takes place. During the aging process, the amount of circulating and bound testosterone decreases. This should reduce the potential for BPH, but the amount of androgen receptors increases so that overgrowth of the prostate still can occur. (6)

Benign prostatic hyperplasia creates bladder outlet obstruction in two ways. The enlarging lobes of the prostate create a compressive obstruction of the urethra, resulting in decreased force and caliber of the urinary stream. The process of micturition requires the smooth muscle of the urethral sphincter to relax and distend so urine can flow freely. In men with BPH, this smooth muscle in the prostatic urethra is hypertrophied. This hyperplasia prevents the relaxation of the sphincter, and the outflow of urine is impeded. (7)

Symptoms associated with BPH are both irritative and obstructive and include

* decreased urinary stream force;

* hesitancy;

* increased daytime frequency (ie, voids at least every two hours);

* nocturia (ie, waking with an urge to void);

* post-void dribble, and

* urinary retention (ie, feeling that the bladder is not emptying completely).

Urinary retention can result in urinary tract infections, bladder stones, hematuria, and renal insufficiency. (8)

Patient evaluation. Although BPH is a nonmalignant condition, a diagnostic workup should be conducted to rule out prostatic cancer. The symptoms of BPH interfere with quality of life, and treatment should be approached with this in mind. The Agency for Health Care Policy and Research developed guidelines for the management of BPH in 1994. The key components in the evaluation include history, physical examination, digital rectal examination to assess size and presence of masses in the prostate, urinalysis, blood testing for serum creatinine to evaluate kidney function, and prostate-specific antigen (PSA) to screen for prostate cancer. (9) A patient with a PSA level higher than 4.0 mg per dL is a candidate for further prostate cancer testing. (10)

The American Urological Association developed the international prostate symptom score to assist in the assessment of BPH and its effects on the patient. (11) This tool includes questions about bladder emptying, frequency, urgency, nocturia, and urinary stream. The scores range from zero (ie, mild) to 35 (ie, severe). A watch and wait attitude may be taken for patients who do not feel their symptoms are significant. Patients with severe symptoms require some form of treatment for BPH.

Current treatment for BPH is based on symptom relief and can range from medical to noninvasive to surgical. Table 1 presents alternative treatments for symptoms of BPH. Heat therapy treatments are considered noninvasive and are performed under local anesthesia in a urologist's office. (12)

SURGICAL TREATMENT OF BPH

Transurethral resection of the prostate is the gold standard for treatment of BPH. This procedure results in the best improvement of symptoms and urine flow rates. (13) Until recently, the TURP procedure was the only surgical treatment alternative to open prostatectomy. (14) Although new minimally invasive techniques are available, patient satisfaction is high and postoperative complaints are fewer with the TURP procedure. (15)

Transurethral resection of the prostate is performed to remove the hyperplastic tissue in the prostatic urethra. (16) A resectoscope with a wire loop electrode is inserted into the urethra. This wire loop electrode is passed along the prostatic tissue and cuts away the tissue to remove the obstruction in the urethra. (17)

Monopolar TURP. Typically, TURP is performed using monopolar electric current and a wire loop electrode. Prostatic tissue is cut away using the cutting current of the electrosurgical unit (ESU). Bleeding is controlled using the coagulation current. (18) When using monopolar energy, the current flows from the active electrode (ie, the wire loop) to a ground? The electrical energy that is not absorbed by tissue travels through the patient to an ESU grounding pad. To avoid conduction of this electrical energy to surrounding tissues, a nonconductive irrigating solution is used. The most commonly used irrigating fluid is glycine because it is electrically inert and provides a clear visual field. (20) In addition, glycine is metabolized to ammonia in the liver. (21)

Transurethral resection syndrome. Monopolar TURP has some limitations, including the size of the prostate gland and procedure time. These limitations are set to avoid the potential risk of TUR syndrome. The risk of developing TUR syndrome increases with a gland larger than 45 g or resection time greater than 90 minutes. (22) Two percent of prostate resections are estimated to result in TUR syndrome. (23)

Transurethral resection syndrome is caused by the absorption of fluids, which results in dilutional hyponatremia and water intoxication. (24) During a TURP procedure, irrigating fluid is used to aid in visualization. As tissue is cut, bleeding occurs. The fluid flow must be enough to clear the surgical site of bleeding, so the pressure of the fluid must be greater than or equal to the pressure of the blood coming from the tissue. The open capillaries in the cut tissue provide access for the irrigating fluid to enter the bloodstream, (25) which results in a hypervolemic state with dilutional hyponatremia. (26) When using glycine, this absorption also can include hyperammonemia and lead to cerebral edema and seizures. (27)