“It’s really unknown whether [the cause] is a small microbial agent such as a bacterium or virus, cytokines or autoimmune factors, toxins in the urine or some kind of oxidative stress. But there’s evidence of all of these, particularly psychological and immunological [factors],” according to Dr. Mark Samuel Litwin of the University of California at Los Angeles. Dr. Litwin addressed an audience of urologists at the annual meeting of the American Urological Association in Atlanta last week.

Litwin pointed out that “there is a tremendous psychological burden associated with this chronic condition.” Prostatitis can affect men of any age, but is most common among those between 35 and 50.

In the past, men with prostatitis were usually treated with antibiotics because it was assumed that the condition was the result of an often-unidentified bacterial infection. But Litwin explained that most cases are not caused by infection although sometimes signs of bacteria can be found if a urologist looks hard enough.

Antibiotics are less likely to be prescribed today, says Litwin, and there are other treatment options: alpha-blockers (such as Cardura, used to treat benign prostatic hyperplasia (BPH) and high blood pressure), non-steroidal anti-inflammatory drugs (NSAIDs), finasteride (Proscar — used to treat BPH), microwave therapy and even the drug allopurinol, used to treat urinary stones and gout.

Current practice involves a more thorough evaluation at diagnosis to look for any source of infection, Litwin stated. A urologist will massage the prostate and take a sample of the milky fluid it produces, and it will be examined for bacteria and for white blood cells. If signs of infection are present, antibiotics are prescribed. In most cases, though, there’s no sign of infection, and patients are prescribed NSAIDs and/or alpha-blockers as well as counseling and stress management training.

Litwin also noted that current research is looking into the usefulness of the new COX-2 inhibitors and bioflavonoids in treating prostatitis. In addition, the National Institutes of Health has recently funded a large collaborative study at six North American centers that will focus on basic research to understand prostatitis as well as clinical research to evaluate treatments.

Diseases of the Prostate Gland

Prostatitis

2. Chronic Prostatitis

Chemotherapy has given a new hope in the treatment of chronic prostatitis, with the introduction of the sulf onamides and mandelic acid. Other useful drugs are salol and methenamine used with acid sodium phosphate. When prostatic pain is very severe, sedatives are often necessary. The barbiturates usually suffice, but occasionally it is necessary to give codeine, pantopon, or morphine. When there is pain in the region of the prostate, or during micturition, the patient should be given a soothing prescription, such as Kirwin’s mixture:

Spices and alcohol should be eliminated from the diet and constipation avoided. When there is marked vesical irritation, a restricted diet should be used, which limits meat, tea and coffee, and eliminates certain foods which are irritating to the bladder, such as asparagus, carrots, tomatoes, berries.

The application of heat to the inflamed prostate has definite therapeutic value. Relief may often be obtained by hot sitz baths, hot rectal irrigations, diathermy, or radiothermy. The Elliott treatment regulator, introduced through the rectum, is an effective method of applying dry heat directly to the prostate and adjacent structures.

Occasionally a prostate becomes so infected that no amount of treatment by these methods will effect a cure. Total prostatectomy is then indicated.

Diseases of the Prostate Gland

Prostatitis

2. Chronic Prostatitis

To secure uncontaminated prostatic secretion the patient is first asked to void his urine; the penis and meatus are cleansed with green soap and water; and the anterior urethra irrigated with rivanol dextrose, acriflavine, or other antiseptic solution. The patient kneels on the table and a small endoscopic tube is inserted to a point beyond the external sphincter into the prostatic urethra. He then bends over and rests on his hands or elbows. The prostate is massaged firmly but gently and finally the prostatic urethra emptied by vigorous strokes down the middle depression of the prostate. The uncontaminated prostatic fluid is received in a sterile test-tube which the assistant holds at the end of the endoscope.

Normal prostatic fluid is opalescent and viscid, and microscopically is seen to consist of corpora amylacea, lecithin globules, columnar epithelia, and occasional hyaline globules. In chronic prostatitis, the prostatic secretion is less opalescent than the normal fluid, and the normal elements are replaced by pus cells and degenerated epithelial cells. The degree of infection is measured by the amount of pus in relation to the lecithin. In well-developed chronic prostatitis much of the lecithin content will be replaced by pus cells, often in clumps. As the condition improves, the pus cells diminish and the normal elements reappear. Bacteria may be present in great numbers.

Urethroscopic examination of the posterior urethra is advisable in cases where palpation of the prostate and vesicles, analysis of the voided urine, and microscopic examination of the secretions have proved inconclusive. The marked chronic inflammatory changes that may be revealed by such examination not infrequently are the only clue to a low-grade prostatitis and vesiculitis.

Prognosis. The patient suffering from long-standing prostatitis is not easily cured and it is advisable so to inform him at the outset of treatment. Relief of symptoms by some form of therapy, especially urethral dilatation, massage, rectal heat, and chemotherapy, is possible in most cases; but reversion to a normal prostatic fluid is more difficult to obtain and requires complete removal of infectious foci and restitution of prostatic drainage.

Treatment. In general, treatment consists of dilatation of the prostatic urethra, prostatic massage, urethrovesical irrigations and instillations, heat applied in the form of hot rectal irrigations, hot sitz baths, or diathermy, chemotherapy, and hyperpyrexia and vaccine therapy in selected cases.

The elimination of distant foci of infection, in the tonsils, teeth, sinuses, or colon, is of the greatest importance. In these cases, local measures are useful in relieving the symptoms, but are of little value in cure of the prostatitis, which is dependent upon removal of the primary focus.

The main problem in the treatment of chronic prostatitis is the restitution of free drainage, since retention favors infection. The most effective method of restoring the potency of prostatic and ejaculatory ducts is by a gradual, gentle, but thorough dilatation of the prostatic urethra to its maximal capacity. Urethral dilatation should precede massage of the partially or totally retentive gland since massage is beneficial only when drainage can take place through patent ducts. Active instrumentation is permissible in most cases at the time of the first consultation, the only clinical requirement being a clear first glass of urine. Dilatation is best carried out by means of sounds (passed upon a bladder partly filled with a mild antiseptic solution). Dilatation is carried on two or three times a week until the largest possible sound has been passed on at least three occasions and has remained tight, indicating that the maximal capacity of the urethra has been reached. The voided urine should be examined before each instrumentation, and treatment discontinued whenever the urine becomes cloudy. A mild urethritis may develop when the occluded ducts resume drainage and empty their infectious contents into the urethra. It may then be necessary to employ urinary antiseptics: sulfanilamide, mandelic acid, salol, or methenamine with acid sodium phosphate — their selection depending upon the nature of the infecting organism. Clinical proof of improved drainage can be obtained by a comparison of the amount and composition of the secretion before and after dilatation.

When satisfactory drainage of the diseased prostate has been restored, digital massage may be given once or twice a week upon a bladder partly filled with antiseptic solution. The aims of prostatic massage are: (1) the gentle expression of the accumulated secretion, (2) a stimulation of the contraction of smooth muscle fibers, and (3) the stretching and final removal of marginal adhesions. The technique, as well as the results obtained, vary widely with different operators. The patient may stand with the body bent forward, as over the back of a chair, or be placed in the Sims’ position, or he may rest upon his knees and elbows. The operator, with his gloved index finger in the rectum, exerts gentle pressure upon the lobes palpable from that position, using a downward stroking motion with the force directed toward the urethra, the object being to empty the prostatic acini of their purulent contents and to break up adhesions about the gland. Secretions later may be expressed from the ejaculatory ducts and the sinus pocularis by bringing the firmly pressing finger downward along the posterior urethra. Most patients with chronic prostatitis are benefited by intelligent application of prostatic massage; but too early, too vigorous, too frequent, or unduly prolonged massage may cause acute epididymitis or other unfavorable reactions. The degree of pressure is a matter of experience and is governed largely by the degree of inflammation present. As a rule, massage is carried out twice a week at first — the treatments tapering off, as the condition improves, until the patient is receiving massage once a week, then every ten days, semi-monthly, and finally once a month.

Hyperpyrexia and vaccines, serums, and injections of foreign proteins have a limited usefulness. Hyperpyrexia has been found highly beneficial in certain severe cases of gonorrhea and in the treatment of most gonococcal complications, but it is expensive, very uncomfortable, and attended with considerable risk. We have found vaccines very helpful in certain cases of arthritis where the infective focus was in the prostate, but in other cases their use has resulted in no appreciable benefit. Intraprostatic injections of antiseptic solutions have been recommended for recalcitrant pyogenic prostatitis; our experience has been that the benefits are not sufficient to offset the hazards of this method.

Diseases of the Prostate Gland

Prostatitis

2. Chronic Prostatitis

Symptoms. The signs and symptoms of chronic prostatitis vary greatly. The most frequent complaints are of pain, a urethral discharge, which may be profuse or merely the so-called “morning drop,” and some disturbance of sexual function, always accompanied by neurasthenia. The pain may be local or referred. Ordinarily, it is located in the perineum, and may be described by the patient simply as a “heaviness” in the rectum. With this type there is generally a history of the passage of prostatic fluid on defecation. The pain may be referred down the back or inner sides of the legs, or into the groins, penis, or sacrum; or it may simulate that produced by renal or ureteral stone. Frequent and painful urination, urgency, and difficulty are all common complaints, and result largely from involvement of the posterior urethra and bladder neck. If abscess occurs in the course of a chronic prostatitis, which is not uncommon with pyogenic infections, there is increased leukocytosis and pain, chills, and a rise in temperature.

Frequently the predominant symptoms are metastatic, with absence of local symptoms, so that the prostate is not suspected.

Diagnosis. The diagnosis of chronic prostatitis should be based on (1) rectal palpation, (2) repeated analyses of the voided urine, (3) microscopic examination of the prostatic secretion and ejaculate, and (4) urethroscopic examination of the posterior urethra and vesical neck. It is often wise to delay this last procedure until the most distressing symptoms have been allayed by treatment.

Rectal palpation, though of the greatest importance, is not of itself sufficient to establish the diagnosis of chronic prostatitis since, not infrequently, palpation of the chronically inflamed gland may reveal no gross changes, yet pus cells will be found in the prostatic strippings. Many a prostate that feels normal functions poorly and contains large amounts of pus and debris, and many microorganisms.

Often, however, careful rectal palpation will reveal changes in and about the gland. It will be hard and nodulated, and usually adhesions can be felt extending from its lateral borders to the seminal vesicles and adjacent pelvic tissues. Such a prostate is ordinarily, but not always, enlarged, and sometimes there are boggy spots between the areas of induration. Areas of normal gland are usually present.

Microscopic examination of the prostatic fluid, expressed by massage, is the only reliable method of demonstrating the presence of infection in the gland. Often the diagnosis must rest solely on microscopic evidence of pus in the expressed secretions. In treating a case of chronic prostatitis, frequent microscopic examinations of the unstained prostatic fluid should be made, as the conditions present in the gland can be ascertained in this way much more accurately than by palpation. Negative findings on one examination of prostatic secretion are, however, insufficient proof of the absence of prostatitis, since pus in some instances does not make its appearance until after the prostate has been massaged from two to five times. The secretion expressed from the first massage may be from normal portions of the gland, and two or more manipulations may be necessary to open a pathway into the urethra from a closed-off focus of infection. Massage for diagnostic purposes must, of course, be carried out firmly enough to express the secretions, but very gently and cautiously; otherwise, epididymitis may result. The prostatic fluid should be stained at least once to ascertain the presence or absence of bacteria, and their type. Bacteria are more readily identified on smear than in culture, but many of the more chronic cases fail to show bacteria either on smear or in culture.

Diseases of the Prostate Gland

Prostatitis

2. Chronic Prostatitis

Chronic inflammation of the prostate gland is a very common condition in adult males. In our series of 350 postmortem studies, a large number of the specimens showed evidence of inflammation of the prostate.

The chronically infected prostate is a common focus of infection, and urologists have repeatedly emphasized the importance of examining the gland and its secretion when searching for the source of obscure infectious conditions. We regard the prostate as second only to infected tonsils as a cause of arthritis. It may also be responsible for endocarditis, neuritis, iritis, and myositis.

Etiology and Bacteriology. Chronic prostatitis may result from any cause which congests the gland, such as long-standing infection, sexual abuse, or instrumental or other trauma. Other possible etiological factors are prostatic calculosis, stricture of the urethra, and certain vitamin deficiencies and endocrine dyscrasias.

Chronic prostatitis is most frequently the sequel to an acute infection, which may be caused by either the gonococcus or other organisms. The incidence of acute prostatitis as a complication of gonorrheal urethritis has been variously estimated at from 50 to 90 per cent; and untreated acute gonorrheal prostatitis, or incompletely treated posterior urethritis, is undoubtedly the most important factor in the production of chronic prostatitis. Only immediately after the acute inflammation has subsided is the gonococcus to be found in the prostatic strippings.

Chronic inflammations are by no means always due to the gonococcus, however. Non-specific infection is common, and may be a direct extension from the urethra; or blood-borne from a focus in the tonsils, teeth, or sinuses; or the aftermath of an acute systemic infection. The most common organisms demonstrated are the colon bacillus and the staphylococcus, streptococcus and their subforms.

Pathology. Microscopically, there are usually to be observed regions of inflammatory reaction in and about the acini, characterized by an increase of the polymorphonuclear cells, lymphocytes, and plasma cells, with marked proliferation of connective tissue. In other cases, the micro-pathological changes consist in circumscribed areas of round cell or polymorphonuclear cell infiltration. Minute abscesses are sometimes observed.

In a large percentage of cases, cystoscopic examination will show pathological changes in the region of the bladder neck, trigone, or posterior urethra. There is usually more or less involvement of the seminal vesicles, which may be soft and atrophic, or enlarged and indurated.

Diseases of the Prostate Gland

Prostatitis

Prostatitis is a very common disease. It is usually associated with inflammation of the posterior urethra, seminal vesicles, vesical neck, trigone, or even the epididymes, and should, therefore, be studied in relation to both the urinary and genital tracts.

1. Acute Prostatitis

Etiology and Bacteriology. The most frequent cause of acute prostatitis is gonococcal infection. Non-specific acute infections are also common and have of late received much study. The organisms most often responsible are the Staphylococcus albus and aureus, Streptococcus pyogenes, and colon bacillus, but the Bacillus proteus, diphtheroid types, or other organisms may be present. Mixed infections are frequent Contributing causes of prostatitis are masturbation over a protracted period, excessive sexual excitation without gratification, excessive sexual intercourse, and coitus interruptus.

Infection may reach the prostate by direct extension from the posterior urethra up the prostatic ducts (the most common way); or it may be descending, and secondary to an acute infection of the kidney or bladder; or blood-borne, from a primary focus in the sinuses, teeth, or tonsils; or a complication of a systemic infection, such as influenza. A chronic prostatitis may be exacerbated into an acute condition by unwise instrumentation and manipulation in the treatment of chronic posterior urethritis and prostatitis.

Pathology. Three types of acute prostatitis are recognized:

(1) acute catarrhal inflammation, which is always present in acute posterior urethritis and is usually caused by direct migration of the organisms up the prostatic tubules;

(2) follicular prostatitis, which follows the first type and is characterized by many small abscesses and distention of the tubules with pus, which is not evacuated because of obstruction of the ducts;

(3) parenchymatous prostatitis, an intensification of the second stage, the suppurative foci involving a greater extent of the surrounding stroma.

The termination of acute prostatitis is resolution, the formation of a large prostatic abscess, or chronic prostatitis.

Symptoms. The onset of acute prostatitis may be mild, with few or no local symptoms; or it may be very severe. When of urethral origin, the initial symptoms are usually disturbances of urination: urgency, frequency, burning, pain during urination, dribbling. The prostate may enlarge to the point of causing complete retention, requiring catheterization. In acute prostatitis of hematogenous origin, the attack may be ushered in by a chill or fever, and there may or may not be urinary symptoms. Pain may vary from a sense of fulness in the perineum or rectum to acute pain — in the perineum, rectum, loins, penis, or above the pubes. There is leukocytosis.

Diagnosis. Mild prostatitis is likely to escape observation during the course of acute gonorrhea. In severe cases, rectal palpation of a symmetrically enlarged, hot, tender gland is sufficient, with the symptoms and the findings of the two-glass urine test, to establish a diagnosis.

Treatment. Treatment of acute prostatitis is expectant, and consists in absolute rest in bed for all febrile cases; avoidance of physical strain and sexual excitation; avoidance of trauma to the gland; the application of heat in the form of hot sitz baths, hot rectal irrigations, or diathermy; sedatives and belladonna and opium suppositories for pain; alkalinization of the urine, and forced fluids if there is no urinary retention. With acute retention, catheterization may be necessary. Massage of the prostate and urethral instrumentation are contraindicated in the acute stage.

In addition to the above methods for symptomatic relief, chemotherapy has proved of great value in shortening the acute stage of prostatic infections. Sulfanilamide is a most useful drug in combating both gonococcal and non-specific infections. In bacillary infections, mandelic acid, and methenamine and sodium acid phosphate, are valuable.

Prostatitis is a broad term used to identify perianal and lower urinary tract symptoms in men. Prostatitis rarely occurs in males less than 30 years of age; however, it is a common problem in older males. Epidemiological data reveal that up to 50% of all males will develop an episode of prostatitis. Disorders involving inflammation of the prostate gland and its surrounding tissue may be classified into three distinct types: acute bacterial prostatitis, chronic bacterial prostatitis and nonbacterial prostatitis. Since the prostate is a privileged site (an area in which antimicrobial penetration is generally poor), the efficacy of antimicrobial agents is limited, a long duration of treatment is required, and failure rates are high (30%–40%). Furthermore, the diagnosis of prostatitis is both nebulous and controversial. As a result, the diagnosis and therapy of prostatitis remains a challenge. In this review we will discuss the pathophysiology, diagnosis and treatment of bacterial and nonbacterial prostatitis.

Pathophysiology of Prostatitis

Various physiological factors contribute to the development of prostatitis. Prostatic antibacterial factor (PAF) is a bactericidal fluid secreted from the normal prostate. Prostatic antibacterial factors antibacterial activity is dependent on adequate prostatic zinc concentrations. Both PAF and PAF zinc concentrations are diminished in patients with prostatitis. Normal prostatic secretions generally maintain a pH of approximately 6.6 to 7.6. With increasing age, the pH of prostatic secretions tends to rise. Patients with prostatitis have alkaline prostatic secretions ranging in pH from 7–9. Whether these physiological factors are a cause or effect of prostatitis is unknown. The introduction of bacteria into the prostate is multifactorial and includes an ascending urethral infection, reflux of infected urine into prostatic ducts which empty into the posterior urethra, invasion of rectal bacteria by direct extension into the prostate or by lymphatic spread, and hematogenous spread. It is postulated that intraprostatic urinary reflux, either with infected urine or sterile urine, may be the primary etiology of most bacterial and nonbacterial prostatitis cases.

The only antibiotic approved for chronic bacterial prostatitis is carbenicillin. Studies have not confirmed that this is the most appropriate drug for this disease. The new quinolones offer theoretical efficacy in that they do diffuse very freely into the prostatic secretion and are effective against most organisms that cause bacterial prostatitis. Preliminary clinical studies have, in fact, shown that chronic bacterial prostatitis can be successfully treated with the new-generation quinolones.

Acute prostatitis. The management of the different prostatitis syndromes is very different. Some men with acute bacterial prostatitis require hospitalization. The patient requires supportive care, including intravenous hydration. Acute urinary retention is not infrequent. Suprapubic urinary drainage by means of a percutaneous cystotomy is much preferable to a urethral catheter in acute prostatic inflammation. If hospitalization is required, parenteral antibiotic therapy should be instituted immediately after urine and blood have been taken for culture and sensitivity.

An aminoglycoside-ampicillin combination is recommended to cover both the Gram-negative bacteria and the enterococci. Clinical experience indicates that these drugs do diffuse into the prostate at adequate levels during the acute inflammatory stage. Perhaps the physiologic barriers to diffusion of most antibiotic agents in the prostatic fluid are disrupted by such acute inflammation.

Response to treatment is usually rapid, and oral antibiotic therapy can be instituted in several days. If the patient is not severely ill, outpatient treatment with oral antibiotics can be initiated at the first presentation. If fever and pain persist, further investigation, such as intravenous pyelography and ultrasonography, should be done to rule out stones, obstruction, and abscess. While the optimal duration for antimicrobial therapy is unknown, one must always be aware that inadequately treated acute bacterial prostatitis could evolve into difficult-to-treat chronic bacterial prostatitis. Therefore, one further month of oral antibiotic therapy with either trimethoprim or a trimethoprim-sulphamethoxazole combination or one of the newer quinolones is recommended.

Chronic bacterial prostatitis. Chronic bacterial prostatitis is much more difficult to treat. Once the bacteriologic diagnosis is obtained, the goal of treatment is, of course, to cure the patient: to completely eradicate the focus of infection in the prostate and to eliminate the cause of persistent bacteria within the gland. There is, however, a high failure rate and a very high relapse rate with antibiotic therapy in this disease, and sometimes suppression is all that can be achieved. As previously discussed, the diffusion of antibiotics in the prostate gland in chronic bacterial prostatitis is perhaps the single most important factor in choosing an antibiotic. Trimethoprim and the newer quinolones appear to be the drugs of choice. Of course, the selection of antibiotics must be modified according to the sensitivity of the bacteria obtained on culture. A minimum of 6 weeks’ treatment is recommended; however, most experts find that it usually takes 3 months of continuous antibiotic therapy to cure the disease. The cure rate, with these medications, ranges from 40% to 70%.’ While full-dose antibiotic therapy is generally well tolerated, about 15% of patients experience adverse side effects.

When the disease cannot be cured, the physician must consider low-dose, suppressive therapy. The drugs used most often are low-dose trimethoprim at 50 mg/d, low-dose trimethoprim-sulphamethoxazole at half a tablet per day, or nitrofurantoin at 50 mg/d. These are remarkably effective in suppressing the symptoms and eradicating the bacteriuria, but once they are discontinued, the disease can recur because of bacteria persisting within the prostate gland.

Recently there has been some interest in intraprostatic antimicrobial injection. This is thought to produce antimicrobial concentrations in the parenchyma and ducts of the prostate that greatly exceed those achievable with systemic administration. Certainly this technique deserves further clinical exploration, but at present it is not a practical consideration.

Surgery is really the treatment of last resort. Complete total prostatectomy, including complete excision of the prostate and seminal vesicles, should constitute a predictable cure for chronic bacterial prostatitis; however, its application is limited by the anticipated and certainly the potential morbidity. Impotence and incontinence are both possible results.

Radical transurethral resection has been suggested as an alternate surgical approach. This is only rarely successful, because the inflammation associated with chronic bacterial prostatitis is largely confined to the periphery rather than to the central portion of the prostate gland. Some investigators, however, report reasonably good results, and long-term antibiotic therapy can be considered. Patients with prostatic calculi that have become secondarily infected by bacteria will rarely be cured by antibiotic therapy alone. Transurethral resection to remove all the stones is a reasonable approach, and it is appropriate to have an intraoperative radiographic assessment of the prostate gland to ensure complete removal of the calculi.

Non-bacterial prostatitis. Non-bacterial prostatitis is difficult to treat because the cause is unknown. It could be a manifestation of a variety of different inflammatory processes, or it could be secondary to infection with such bacteria as coagulase-negative staphylococcus or such organisms as chlamydia or mycoplasma. Our approach in patients with a definite prostatic inflammation but no bacteriologic localization is to use tetracycline or doxycycline for 2 weeks and then assess the results of therapy. Erythromycin and, to a lesser extent, tiimethoprim-sulphamethoxazole are also active against these agents.

If the patient is responding, we will continue for another 4 weeks. Chronic antibacterial therapy should, however, be avoided, especially if it is not working. Treatments that occasionally help include hot sitz baths, avoidance of alcohol and foods that aggravate the problem, a trial of anticholinergic and anti-inflammatory agents, and possibly a trial of anxiolytic medications. Oral zinc treatment, which is advocated by some, has never been proved effective.

Prostatodynia. The patient with prostatodynia does not have inflammation and will not benefit from a trial of antibiotics. An important component of management is to clinically eliminate all extraprostatic causes for the symptoms, such as interstitial cystitis, carcinoma of the bladder, and other conditions that could give pelvic pain. If urodynamic investigation reveals vesical sphincter dyssynergia, pharmacologic management with OC-blockers, such as prazosin, can help. Agents such as diazepam and oxybutynin can also help in selected cases.

Bladder neck incision has been used with variable success. Biofeedback technology has demonstrated some improvement in symptoms. We find that the best treatment is reassurance and counseling by the family physician, the urologist, and if necessary, psychologists or psychiatrists. The physician’s common sense, compassion, and concern for the patient’s very real frustrations are the keys to successful management of prostatodynia. Usually this chronic disorder remains undefined despite repeated investigations and treatment.

Conclusion

Prostatitis has been called a "wastebasket of clinical ignorance." If this situation is to change, family physicians must develop an awareness of the importance of proper classification based on an understanding of the etiology of these syndromes. A rigorous systematic diagnostic plan, especially at first presentation, is essential to understanding and treating the whole spectrum of specific and undefined prostatic disorders. ■

The absolute key to diagnosis of chronic prostatitis is investigation of expressed prostatic secretion or, if this cannot be obtained, of seminal fluid. (If acute infection of the prostate gland is suspected, expressed prostatic secretions should not be obtained, as the patient could become septic.) Microscopic examination of the expressed prostatic secretion is extremely helpful. Excessive leukocytes (more than 10 per high-power field in an unspun specimen) and macrophages containing fat or oval fat bodies indicate prostatic inflammation. However, other genitourinary conditions, such as urethritis, urethral condylomata, and strictures, can also cause excessive leukocytosis in the expressed prostatic secretion.

Microscopic examination of seminal fluid, which usually can be collected more easily and certainly in larger volumes than the expressed prostatic secretion (EPS), can be misleading because of the difficulty of determining leukocytosis in the specimen. Immature sperm cells in unstained or conventionally stained samples look very much like leukocytes and limit the practical value of microscopic analysis. Moreover, the impact of prostatic inflammation on seminal fluid leukocyte density is really unknown.

The most accurate way to diagnose bacterial pathogenesis is to employ specific cultures. These simultaneous, quantitative bacterial cultures of urethral urine, bladder urine, and expressed prostatic secretion (Figure 2) are extremely important, especially on the first presentation. Physicians need a working understanding of the rationale and interpretation of this method to manage chronic prostatitis syndromes. Because prostatic fluid is subject to contamination by bacteria that colonize the urethra, one must determine the origin of the prostatic fluid isolates.

Figure 2. Segmented Cultures of the Lower Urinary Tract in Men

The first 5 to 10 mL of urine collected after retracting the foreskin and thoroughly cleaning the glans penis is labelled as VB1, or voided bladder 1. The second collection is similar to a midstream urine sample (MSSU) and is labelled VB2. The physician then massages the prostate gland while collecting or having the patient collect the drops of expressed prostatic secretion emitting from the urethral meatus. After the EPS has been collected, the residual drop along the urethra is used to prepare a slide for microscopic examination as previously described. The patient is then asked to void again, and the VB3 is collected in the same manner as VB1. While a high bacterial count in the EPS strongly suggests chronic bacterial prostatitis, the definitive diagnosis is confirmed when a quantitative count demonstrates a significantly higher number of bacteria per mL in the prostatic fluid than in VB1 or in the midstream VB2 specimen (Figure 3). If EPS is impossible to obtain, a significantly higher bacterial count in the VB3, which should contain some prostatic expressate, may be suggestive.

If EPS is impossible to obtain, a culture of the ejaculate, which does contain prostatic secretions, may be performed. Because the ejaculate must pass through the urethra and can be contaminated by urethral organisms, a concomitant study of urethral (VB1) and bladder (VB2) specimens is required. Comparisons of the three specimens must show an excessive bacterial count in the seminal fluid.

When non-bacterial prostatitis is suggested by leukocytosis in a sterile prostatic secretion, one can obtain specific cultures for chlamydia and mycoplasma. This is not routinely done at present and remains a research tool. Unfortunately most patients have not undergone such a rigorous work-up before therapy. It is very frustrating to attempt to properly diagnose and treat patients after they have been on a number of antibiotics for various durations. It is a good idea with such a patient to discontinue antibiotics for at least 6 weeks and repeat the segmented cultures as described. If this procedure does not localize the bacterial pathogen, and previous history or previous cultures still make the physician suspect chronic bacterial prostatitis, I would recommend proceeding (with the patient’s consent) to an ultrasound-guided percutaneous aspiration biopsy of the prostate gland. Because infection is likely very focal, sampling errors are inevitable, and this does not present an ideal diagnostic test.

When other causes are excluded.If all these investigations have failed to disclose a pathogen and the patient has failed to respond to a trial course of antibiotics for either bacterial or non-bacterial organisms, the disorder is categorized as non-bacterial prostatitis (if inflammation is present) or prostatodynia (if it is not).

It cannot be overemphasized that a rigorous diagnostic routine, as described in this section, is mandatory for the prostatitis syndromes, especially at first presentation. Proper diagnosis will reduce frustration for both patient and physician and lead to a more rewarding outcome.

History and physical examination. A detailed analysis of the type and duration of symptoms, the results of prior investigations, and the response to previous treatments are critical components of the history. Physical examination should not be limited to the external genitalia and the prostate, but should be complete. Sometimes neglected aspects of patient evaluations disclose an alternate explanation for the apparent prostatic symptoms (neurologic, diabetic, malignant, etc).

Patients with acute prostatitis have sudden onset of urinary frequency, urgency, nocturia, and dysuria associated with fever and chills, low back and perineal pain, generalized malaise, and varying degrees of bladder outlet obstruction. On examination the patient usually has an exquisitely tender, boggy, and warm prostate gland.

Chronic bacterial prostatitis can develop from acute bacterial prostatitis, sometimes from inadequately treated acute prostatitis or from subacute prostatitis that did not give rise to acute clinical symptoms. Symptoms are variable and include dysuria, frequency, nocturia, ejaculatory pain, and discomfort in any area of the perineum or external genitalia. The prostate is usually tender to some degree. Patients usually have a history of recurrent urinary tract infections with the same organism.

Non-bacterial prostatitis, perhaps the most common of the prostatitis syndromes, has clinical symptoms and physical findings similar to those of chronic bacterial prostatitis. However, the patient does not have a history of recurrent urinary tract infections.

Patients with prostatodynia usually present with pelvic, perineal, suprapubic, and even penile or urethral pain. These patients do not have a history of recurrent urinary tract infections. Irritative voiding symptoms are uncommon, but many patients with prostatodynia complain of varying degrees of obstructive symptoms, such as hesitancy and a weak or intermittent stream. Palpation of the prostate usually demonstrates a normal gland, although there can be a degree of anal sphincter spasm.

One point that should be made is that palpation of the prostate does not always provide insight into the disease process. The consistency of the prostate and the degree of discomfort accompanying digital rectal examination does not always indicate whether the cause is bacterial.

Perhaps the most important clue to the cause of chronic prostatic symptoms is a history of urinary tract infections. Chronic bacterial prostatitis is the most common cause of recurrent urinary tract infections in males; it follows that a patient with recurrent UTI and inflammation of the prostate is likely to have chronic bacterial prostatitis. Response to antibiotic treatment also provides an important clue. Most men with chronic bacterial prostatitis will achieve some significant symptomatic relief while receiving antimicrobial therapy. This benefit may result from sterilization of the urine and can be independent of the bacteriologic response of the prostatic infection. If the treatment is not curative, the symptoms characteristically recur.