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Urologic Disorders Maxwell V. Meng, MD, FACS Marshall L. Stoller, MD Thomas J. Walsh, MD, MS

Hematuria

``

Essentials of diagnosis

Both gross and microscopic hematuria require evaluation.

The upper urinary tract should be imaged, and cystoscopy should be performed if there is hematuria in the absence of infection.

``

``

``General Considerations An upper tract source (kidneys and ureters) can be identified in 10% of patients with gross or microscopic hematuria. For upper tract sources, stone disease accounts for 40%, medical kidney disease (medullary sponge kidney, glomerulonephritis, papillary necrosis) for 20%, renal cell carcinoma for 10%, and urothelial cell carcinoma of the ureter or renal pelvis for 5%. Drug ingestion and associated medical problems may provide diagnostic clues. Analgesic use (papillary necrosis), cyclophosphamide (chemical cystitis), antibiotics (interstitial nephritis), diabetes mellitus, sickle cell trait or disease (papillary necrosis), a history of stone disease, or malignancy should all be investigated. The lower tract source of gross hematuria (in the absence of infection) is most commonly from urothelial cell carcinoma of the bladder. Microscopic hematuria in the male is most commonly from benign prostatic hyperplasia. The presence of hematuria in patients receiving anticoagulation therapy cannot be ascribed to the anticoagulation; a complete evaluation is warranted consisting of upper tract imaging, cystoscopy, and urine cytology (see Chapter 39 for Bladder Cancer, Cancers of the Ureter and Renal Pelvis, Renal Cell Carcinoma, and Kidney and Testis Tumors).

``Clinical Findings A. Symptoms and Signs If gross hematuria occurs, a description of the timing (initial, terminal, total) may provide a clue to the localization

of disease. Associated symptoms (ie, renal colic, irritative voiding symptoms, constitutional symptoms) should be investigated. Physical examination should emphasize signs of systemic disease (fever, rash, lymphadenopathy, abdominal or pelvic masses) as well as signs of medical kidney disease (hypertension, volume overload). Urologic evaluation may demonstrate an enlarged prostate, flank mass, or urethral disease.

B. Laboratory Findings Initial laboratory investigations include a urinalysis and urine culture. Proteinuria and casts suggest renal origin.

Irritative voiding symptoms, bacteriuria, and a positive urine culture in the female suggest urinary tract infection, but follow-up urinalysis is important after treatment to ensure resolution of the hematuria.

Further evaluation may include urinary cytology to assist in the diagnosis of bladder neoplasm.

C. Imaging Upper tract imaging (usually abdominal and pelvic CT scanning without and with contrast) may identify neoplasms of the kidney or ureter as well as benign conditions such as urolithiasis, obstructive uropathy, papillary necrosis, medullary sponge kidney, or polycystic kidney disease. CT urography and MRI have replaced intravenous urography when imaging the upper tracts for sources of hematuria.

The role of ultrasonographic evaluation of the urinary tract for hematuria is unclear. Although it may provide adequate information for the kidney, its sensitivity in detecting ureteral disease is lower. In addition, its higher degree of operator dependence may further confound the issue.

D. Cystoscopy Cystoscopy can be used to assess for bladder or urethral neoplasm, benign prostatic enlargement, and radiation or chemical cystitis. For gross hematuria, cystoscopy is ideally performed while the patient is actively bleeding to allow better localization (ie, lateralize to one side of the upper tracts, bladder, or urethra).

Urologic Disorders

``Follow-up In patients with negative evaluations, repeat evaluations may be warranted to avoid a missed malignancy; however, the ideal frequency of such evaluations is not defined.

Urinary cytology can be repeated in 3–6 months, and cystoscopy and upper tract imaging after a year.

``When to Refer In the absence of infection, hematuria (either gross or microscopic) requires evaluation.

Grossfeld G et al. Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy—part I: definition, detection, prevalence, and etiology. Urology. 2001 Apr;57(4):599–603. [PMID: 11306356] Kelly JD et al. Assessment and management of non-visible haematuria in primary care. BMJ. 2009 Jan;16(338):a3021.

[PMID: 19151065] Margulis V et al. Assessment of hematuria. Med Clin North Am. 2011 Jan;95(1):153–9. [PMID: 21095418] Rao PK et al. How to evaluate “dipstick hematuria": what to do before you refer. Cleve Clin J Med. 2008 Mar;75(3):227–33.

[PMID: 18383931] Rodgers MA et al. Diagnostic tests used in the investigation of adult haematuria: A systematic review. BJU Int. 2006 Dec;98(6):1154–60. [PMID: 16879444]

Genitourinary Tract Infections 1. Acute Cystitis

``

Essentials of diagnosis

Irritative voiding symptoms.

Patient usually afebrile.

Positive urine culture; blood cultures may also be positive.

`` `` ``

``General Considerations Acute cystitis is an infection of the bladder most commonly due to the coliform bacteria (especially Escherichia coli) and occasionally gram-positive bacteria (enterococci).

The route of infection is typically ascending from the urethra. Viral cystitis due to adenovirus is sometimes seen in children but is rare in adults. Cystitis in men is rare and implies a pathologic process such as infected stones, prostatitis, or chronic urinary retention requiring further investigation.

``Clinical Findings A. Symptoms and Signs Irritative voiding symptoms (frequency, urgency, dysuria) and suprapubic discomfort are common. Women may

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experience gross hematuria, and symptoms may often appear following sexual intercourse. Physical examination may elicit suprapubic tenderness, but examination is often unremarkable. Systemic toxicity is absent.

B. Laboratory Findings Urinalysis shows pyuria and bacteriuria and varying degrees of hematuria. The degree of pyuria and bacteriuria does not necessarily correlate with the severity of symptoms. Urine culture is positive for the offending organism, but colony counts exceeding 105/mL are not essential for the diagnosis.

C. Imaging Because uncomplicated cystitis is rare in men, elucidation of the underlying problem with appropriate investigations, such as abdominal ultrasonography or cystoscopy (or both), is warranted. Follow-up imaging using CT scanning is warranted if pyelonephritis, recurrent infections, or anatomic abnormalities are suspected.

``Differential Diagnosis In women, infectious processes such as vulvovaginitis and pelvic inflammatory disease can usually be distinguished by pelvic examination and urinalysis. In men, urethritis and prostatitis may be distinguished by physical examination (urethral discharge or prostatic tenderness).

Noninfectious causes of cystitis-like symptoms include pelvic irradiation, chemotherapy (cyclophosphamide), bladder carcinoma, interstitial cystitis, voiding dysfunction disorders, and psychosomatic disorders.

``Prevention Women who have more than three episodes of cystitis per year are considered candidates for prophylactic antibiotic therapy to prevent recurrence after treatment of urinary tract infection. Prior to institution of therapy, a thorough urologic evaluation is warranted to exclude any anatomic abnormality (eg, stones, reflux, fistula).

The three most commonly used oral agents for prophylaxis are trimethoprim-sulfamethoxazole (40 mg/200 mg), nitrofurantoin (100 mg), and cephalexin (250 mg).

Single dosing at bedtime or at the time of intercourse is the recommended schedule.

The risk of acquiring a catheter-associated urinary tract infection in hospitalized patients can be minimized by using indwelling catheters only when necessary, implementing systems to ensure removal of catheters when no longer needed, using antimicrobial catheters in high-risk patients, using external collection devices in select men, identifying significant postvoid residuals by ultrasound, maintaining proper insertion techniques, and utilizing alternatives such as intermittent catheterization. The cost of treating a catheter-associated urinary tract infection acquired by a hospitalized patient is one of the complications that is not reimbursed by the Centers for Medicare & Medicaid Services.

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``Treatment

``When to Refer

Uncomplicated cystitis in women can be treated with short-term antimicrobial therapy, which consists of singledose therapy or 1–3 days of therapy. Fluoroquinolones and nitrofurantoin are the drugs of choice for uncomplicated cystitis (Table 23–1). Trimethoprim-sulfamethoxazole can be ineffective because of the emergence of resistant organisms. In men, uncomplicated urinary tract infection is rare, and thus, the duration of antibiotic therapy depends on the underlying etiology. Hot sitz baths or urinary analgesics (phenazopyridine, 200 mg orally three times daily) may provide symptomatic relief.

• Suspicion or radiographic evidence of anatomic ­abnormality.

• Evidence of urolithiasis.

• Recurrent cystitis due to bacterial persistence.

``Prognosis Infections typically respond rapidly to therapy, and failure to respond suggests resistance to the selected drug or anatomic abnormalities requiring further investigation.

Lo E et al. Strategies to prevent catheter-associated urinary tract infection in acute care hospitals. Infect Control Hosp Epidemiol. 2008 Oct;29(S1):S41–50. [PMID: 18840088] Norris DL 2nd et al. Urinary tract infections: diagnosis and management in the emergency department. 2008 May;26(2):413–30.

[PMID: 18406981] Saint S et al. Catheter-associated urinary tract infection and the Medicare rule changes. Ann Intern Med. 2009 Jun 16;150(12): 877–84. [PMID: 19528567] Saint S et al. Preventing hospital-acquired urinary tract infection in the United States: a national study. Clin Infect Dis. 2008 Jan 15;46(2):243–50. [PMID: 18171256]

Table 23–1. Empiric therapy for urinary tract infections.

Diagnosis Acute pyelonephritis

Antibiotic

Route

Duration

Cost per Duration Noted1

Ampicillin, 1 g every 6 hours, and gentamicin, 1 mg/kg every 8 hours

Intravenous

21 days

$567.00 not including intravenous supplies

Ciprofloxacin, 750 mg every 12 hours

Oral

21 days

$236.50

Ofloxacin, 200–300 mg every 12 hours

Oral

21 days

$239.00 (300 mg)

Trimethoprim-sulfamethoxazole, 160/800 mg every 12 hours2

Oral

21 days

$45.80

Chronic pyelonephritis

Same as for acute pyelonephritis, but duration of therapy is 3–6 months

Acute cystitis

Cephalexin, 250–500 mg every 6 hours

Oral

1–3 days

$16.60/3 days (500 mg)

Ciprofloxacin, 250–500 mg every 12 hours

Oral

1–3 days

$32.00/3 days (500 mg)

Nitrofurantoin (macrocrystals), 100 mg every 12 hours

Oral

7 days

$26.00

Norfloxacin, 400 mg every 12 hours

Oral

1–3 days

$26.40/3 days

Ofloxacin, 200 mg every 12 hours

Oral

1–3 days

$28.70/3 days

Trimethoprim-sulfamethoxazole, 160/800 mg, two tablets2

Oral

Single dose

$2.20

Acute bacterial prostatitis

Same as for acute pyelonephritis

21 days

Chronic bacterial prostatitis

Ciprofloxacin, 250–500 mg every 12 hours

Oral

1–3 months

$322.00/1 month (500 mg)

Ofloxacin, 200–400 mg every 12 hours

Oral

1–3 months

$360.00/1 month (400 mg)

Trimethoprim-sulfamethoxazole, 160/800 mg every 12 hours2

Oral

1–3 months

$65.40/1 month

Sexually transmitted

Ceftriaxone, 250 mg as single dose, plus Doxycycline, 100 mg every 12 hours

Intramuscular Oral

Once 10 days

$2.00/250 mg $10.40

Non-sexually transmitted

Same as for chronic bacterial prostatitis

Oral

3 weeks

Acute epididymitis

1 Average wholesale price, (AWP, for AB-rated generic when available) for quantity listed. Source: Red Book Online, 2012, Thomson Reuters (Healthcare) Inc. AWP may not accurately represent the actual pharmacy cost because wide contractual variations exist among institutions.

2 Increasing resistance noted (up to 20%).

Urologic Disorders

2. Acute Pyelonephritis

``

Essentials of diagnosis

Fever.

Flank pain.

Irritative voiding symptoms.

Positive urine culture.

`` `` `` ``

``General Considerations Acute pyelonephritis is an infectious inflammatory disease involving the kidney parenchyma and renal pelvis. Gramnegative bacteria are the most common causative agents including E coli, Proteus, Klebsiella, Enterobacter, and Pseudomonas. Gram-positive bacteria are less commonly seen but include Enterococcus faecalis and Staphylococcus aureus. The infection usually ascends from the lower urinary tract—with the exception of S aureus, which usually is spread by a hematogenous route.

``Clinical Findings A. Symptoms and Signs Symptoms include fever, flank pain, shaking chills, and irritative voiding symptoms (urgency, frequency, dysuria).

Associated nausea and vomiting, and diarrhea are common. Signs include fever and tachycardia. Costovertebral angle tenderness is usually pronounced.

B. Laboratory Findings Complete blood count shows leukocytosis and a left shift.

Urinalysis shows pyuria, bacteriuria, and varying degrees of hematuria. White cell casts may be seen. Urine culture demonstrates heavy growth of the offending agent, and blood culture may also be positive.

C. Imaging In complicated pyelonephritis, renal ultrasound may show hydronephrosis from a stone or other source of obstruction.

``Differential Diagnosis Acute intra-abdominal disease such as appendicitis, cholecystitis, pancreatitis, or diverticulitis must be distinguished from pyelonephritis. A normal urinalysis is usually seen in gastrointestinal disorders; however, on occasion, inflammation from adjacent bowel (appendicitis or diverticulitis) may result in hematuria or sterile pyuria. Abnormal liver function tests or elevated amylase levels may assist in the differentiation. Lower lobe pneumonia is distinguishable by the abnormal chest radiograph.

In males, the main differential diagnosis for acute pyelonephritis includes acute epididymitis, acute prostatitis, and acute cystitis. Physical examination and the location of the pain should permit this distinction.

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``Complications Sepsis with shock can occur with acute pyelonephritis. In diabetic patients, emphysematous pyelonephritis resulting from gas-producing organisms may be life threatening if not adequately treated. Healthy adults usually recover complete kidney function, yet if coexistent kidney disease is present, scarring or chronic pyelonephritis may result. Inadequate therapy could result in abscess formation.

``Treatment Urine and blood cultures are obtained to identify the causative agent and to determine antimicrobial sensitivity. In the inpatient setting, intravenous ampicillin and an aminoglycoside are initiated prior to obtaining sensitivity results (Table 23–1). In the outpatient setting, quinolones may be initiated (Table 23–1). Antibiotics are adjusted according to sensitivities. Fevers may persist for up to 72 hours; failure to respond warrants imaging (CT or ultrasound) to exclude complicating factors that may require intervention.

Catheter drainage may be necessary in the face of urinary retention and nephrostomy drainage if there is ureteral obstruction. In inpatients, intravenous antibiotics are continued for 24 hours after the fever resolves, and oral antibiotics are then given to complete a 14-day course of therapy.

Follow-up urine cultures are mandatory following the completion of treatment.

``Prognosis With prompt diagnosis and appropriate treatment, acute pyelonephritis carries a good prognosis. Complicating factors, underlying kidney disease, and increasing patient age may lead to a less favorable outcome.

``When to Refer • Evidence of complicating factors (urolithiasis, obstruction).

• Absence of clinical improvement in 48 hours.

``When to Admit • Severe infections or complicating factors, evidence of sepsis or need for parenteral antibiotics.

• Need for radiographic imaging or drainage of urinary tract obstruction.

Gupta K et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Disease Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103–20.

[PMID: 21292654] Meng MV. Infection of the upper urinary tract. In: Wessells H (editor). Urological Emergencies: A Practical Guide. New York: Humana Press, 2012.

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3. Acute Bacterial Prostatitis

``

with acute prostatitis; however, the history and urinalysis should permit clear distinction. Urinary retention from benign or malignant prostatic enlargement is distinguishable by initial or follow-up rectal examination.

Essentials of diagnosis

``Treatment

Fever.

Irritative voiding symptoms.

Perineal or suprapubic pain; exquisite tenderness common on rectal examination.

Positive urine culture.

`` `` ``

``

``General Considerations Acute bacterial prostatitis is usually caused by gram-­ negative rods, especially E coli and Pseudomonas species and less commonly by gram-positive organisms (eg, enterococci).

The most likely routes of infection include ascent up the urethra and reflux of infected urine into the prostatic ducts.

Lymphatic and hematogenous routes are probably rare.

Hospitalization may be required, and parenteral antibiotics (ampicillin and aminoglycoside) should be initiated until organism sensitivities are available (Table 23–1). After the patient is afebrile for 24–48 hours, oral antibiotics (eg, quinolones) are used to complete 4–6 weeks of therapy.

If urinary retention develops, urethral catheterization or instrumentation is contraindicated, and a percutaneous suprapubic tube is required. Follow-up urine culture and examination of prostatic secretions should be performed after the completion of therapy to ensure eradication.

``Prognosis With effective treatment, chronic bacterial prostatitis is rare.

``Clinical Findings

``When to Refer

A. Symptoms and Signs

• Evidence of urinary retention.

• Evidence of chronic prostatitis.

Perineal, sacral, or suprapubic pain, fever, and irritative voiding complaints are common. Varying degrees of obstructive symptoms may occur as the acutely inflamed prostate swells, which may lead to urinary retention. High fevers and a warm and often exquisitely tender prostate are detected on examination. Care should be taken to perform a gentle rectal examination, since vigorous manipulations may result in septicemia. Prostatic massage is contraindicated.

B. Laboratory Findings Complete blood count shows leukocytosis and a left shift.

Urinalysis shows pyuria, bacteriuria, and varying degrees of hematuria. Urine cultures will demonstrate the offending pathogen (Table 23–2).

``When to Admit • Signs of sepsis.

• Need for surgical drainage of bladder or prostatic abscess.

Benway BM et al. Bacterial prostatitis. Urol Clin North Am. 2008 Feb;35(1):23–32. [PMID: 18061021]

4. Chronic Bacterial Prostatitis

``

Essentials of diagnosis

Irritative voiding symptoms.

Perineal or suprapubic discomfort, often dull and poorly localized.

Positive expressed prostatic secretions and culture.

``

``Differential Diagnosis

``

Acute pyelonephritis or acute epididymitis should be distinguishable by the location of pain as well as by physical examination. Acute diverticulitis is occasionally confused

``

Table 23–2. Clinical characteristics of prostatitis and prostatodynia syndromes.

Acute Bacterial Prostatitis

Chronic Bacterial Prostatitis

Nonbacterial Prostatitis

Prostatodynia

Fever

+

−

−

−

Urinalysis

+

−

−

−

Contraindicated

+

+

−

+

+

−

−

Findings

Expressed prostate secretions Bacterial culture

Urologic Disorders

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``General Considerations

``Prognosis

Although chronic bacterial prostatitis may evolve from acute bacterial prostatitis, many men have no history of acute infection. Gram-negative rods are the most common etiologic agents, but only one gram-positive organism (Enterococcus) is associated with chronic infection. Routes of infection are the same as discussed for acute infection.

Chronic bacterial prostatitis is difficult to cure, but its symptoms and tendency to cause recurrent urinary tract infections can be controlled by suppressive antibiotic therapy.

``Clinical Findings A. Symptoms and Signs Clinical manifestations are variable. Some patients are asymptomatic, but most have varying degrees of irritative voiding symptoms. Low back and perineal pain are not uncommon. Many patients report a history of urinary tract infections. Physical examination is often unremarkable, although the prostate may feel normal, boggy, or indurated.

B. Laboratory Findings Urinalysis is normal unless a secondary cystitis is present.

Expressed prostatic secretions demonstrate increased numbers of leukocytes (>10 per high-power field), especially lipid-laden macrophages. However, this finding is consistent with inflammation and is not diagnostic of bacterial prostatitis (Table 23–2). Leukocyte and bacterial counts from expressed prostatic secretions do not correlate with severity of symptoms. Culture of the secretions or the postprostatic massage urine specimen is necessary to make the diagnosis.

C. Imaging Imaging tests are not necessary, although pelvic radiographs or transrectal ultrasound may demonstrate prostatic calculi.

``Differential Diagnosis Chronic urethritis may mimic chronic prostatitis, though cultures of the fractionated urine may localize the source of infection to the initial specimen, which would come from the urethra. Cystitis may be secondary to prostatitis, but urine samples after prostatic massage may localize the infection to the prostate. Anal disease may share some of the symptoms of prostatitis, but physical examination should permit a distinction between the two.

``Treatment Few antimicrobial agents attain therapeutic intraprostatic levels in the absence of acute inflammation. Trimethoprim does diffuse into the prostate, and trimethoprim-sulfamethoxazole is associated with the best cure rates (Table 23–1).

However, increasing resistance up to 20% has been noted.

Other effective agents include carbenicillin, erythromycin, cephalexin, and the quinolones. The optimal duration of therapy remains controversial, ranging from 6 to 12 weeks.

Symptomatic relief may be provided by anti-inflammatory agents (indomethacin, ibuprofen) and hot sitz baths.

``When to Refer • Persistent symptoms.

• Consideration of enrollment in clinical trials.

5. Nonbacterial Prostatitis

``

Essentials of diagnosis

Irritative voiding symptoms.

Perineal or suprapubic discomfort, similar to that of chronic bacterial prostatitis.

Positive expressed prostatic secretions, but culture is negative.

`` ``

``

``General Considerations Nonbacterial prostatitis is the most common of the prostatitis syndromes, and its cause is unknown. Speculation implicates chlamydiae, mycoplasmas, ureaplasmas, and viruses, but no substantial proof exists. In some cases, nonbacterial prostatitis may represent a noninfectious inflammatory or autoimmune disorder. Because the cause of nonbacterial prostatitis remains unknown, the diagnosis is usually one of exclusion.

``Clinical Findings A. Symptoms and Signs The clinical presentation is identical to that of chronic bacterial prostatitis; however, no history of urinary tract infections is present. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) (http:// www2.niddk.nih.gov/NR/rdonlyres/93B6388F-B4294603-9C3C-6765BDEB49A1/0/NIHCPSIEnglish.pdf) has been validated to quantify symptoms of chronic nonbacterial prostatitis or chronic pelvic pain syndrome.

B. Laboratory Findings Increased numbers of leukocytes are seen on expressed prostatic secretions, but all cultures are negative.

``Differential Diagnosis The major distinction is from chronic bacterial prostatitis. The absence of a history of urinary tract infection and of positive cultures makes the distinction (Table 23–2). In older men with irritative voiding symptoms and negative cultures, the possibility of bladder cancer must be excluded. Urinary cytologic examination and cystoscopy are warranted.

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``Treatment

``Treatment

Because of the uncertainty regarding the etiology of nonbacterial prostatitis, a trial of antimicrobial therapy directed against Ureaplasma, Mycoplasma, or Chlamydia is warranted. Erythromycin (250 mg orally four times daily) can be initiated for 14 days yet should be continued for 3–6 weeks only if a favorable clinical response ensues. Some symptomatic relief may be obtained with nonsteroidal anti-inflammatory agents or sitz baths. Dietary restrictions are not necessary unless the patient relates a history of symptom exacerbation by certain substances such as alcohol, caffeine, and perhaps certain foods.

Bladder neck and urethral spasms can be treated by α-blocking agents (terazosin, 1–10 mg orally once a day, or doxazosin, 1–8 mg orally once a day). Pelvic floor muscle dysfunction may respond to diazepam and biofeedback techniques. Sitz baths may contribute to symptomatic relief.

``Prognosis Annoying, recurrent symptoms are common, but serious sequelae have not been identified.

Dhar NB et al. New therapies in chronic prostatitis. 2007 Jul;8(4):313–8. [PMID: 18519016] Nickel JC et al. Phenotypic approach to the management of chronic prostatitis/chronic pelvic pain syndrome. Curr Urol Rep. 2009 Jul;10(4):307–12. [PMID: 19570493]

6. Prostatodynia Prostatodynia is a noninflammatory disorder that affects young and middle-aged men and has variable causes, including voiding dysfunction and pelvic floor musculature dysfunction. The term “prostatodynia” is a misnomer, as the prostate is actually normal.

``Prognosis Prognosis is variable depending on the specific cause.

Anothaisintawee T et al. Management of chronic prostatitis/ chronic pelvic pain syndrome: a systematic review and network meta-analysis. JAMA. 2011 Jan 5;305(1):78–86. [PMID: 21205969] Pontari MA. Chronic prostatitis/chronic pelvic pain syndrome.

Urol Clin North Am. 2008 Feb;35(1):81–9. [PMID: 18061026] Rodriguez MA et al. Evidence for overlap between urological and nonurological unexplained clinical conditions. J Urol. 2009 Nov;182(5):2123–31. [PMID: 19758633]

7. Acute Epididymitis

``

Essentials of diagnosis

Fever.

Irritative voiding symptoms.

Painful enlargement of epididymis.

`` `` ``

``Clinical Findings

``General Considerations

A. Symptoms and Signs

Most cases of acute epididymitis are infectious and can be divided into one of two categories that have different age distributions and etiologic agents. Sexually transmitted forms typically occur in men under age 40 years, are associated with urethritis, and result from Chlamydia tracho­ matis or Neisseria gonorrhoeae. Non-sexually transmitted forms typically occur in older men, are associated with urinary tract infections and prostatitis, and are caused by gram-negative rods. The route of infection is probably via the urethra to the ejaculatory duct and then down the vas deferens to the epididymis. Amiodarone has been associated with self-limited epididymitis, which is a dose-dependent phenomenon.

Symptoms are the same as those seen with chronic prostatitis, yet there is no history of urinary tract infection.

Additional symptoms may include hesitancy and interruption of flow. Patients may relate a lifelong history of voiding difficulty. Physical examination is unremarkable, but increased anal sphincter tone and periprostatic tenderness may be observed.

B. Laboratory Findings Urinalysis is normal. Expressed prostatic secretions show normal numbers of leukocytes (Table 23–2). Urodynamic testing may show signs of dysfunctional voiding (detrusor contraction without urethral relaxation, high urethral pressures, spasms of the urinary sphincter) and is indicated in patients failing empiric trials of α-blockers or anticholinergics.

``Differential Diagnosis Normal urinalysis will distinguish it from acute infectious processes. Examination of expressed prostatic secretions will distinguish this entity from prostatitis syndromes (Table 23–2).

``Clinical Findings A. Symptoms and Signs Symptoms may follow acute physical strain (heavy lifting), trauma, or sexual activity. Associated symptoms of urethritis (pain at the tip of the penis and urethral discharge) or cystitis (irritative voiding symptoms) may occur. Pain develops in the scrotum and may radiate along the spermatic cord or to the flank. Fever and scrotal swelling are usually apparent. Early in the course, the epididymis may be distinguishable from the testis; however, later the two

Urologic Disorders may appear as one enlarged, tender mass. The prostate may be tender on rectal examination.

B. Laboratory Findings Complete blood count shows leukocytosis and a left shift. In the sexually transmitted variety, Gram staining of a smear of urethral discharge may be diagnostic of gram-negative intracellular diplococci (N gonorrhoeae). White cells without visible organisms on urethral smear represent nongonococcal urethritis, and C trachomatis is the most likely pathogen. In the non-sexually transmitted variety, urinalysis shows pyuria, bacteriuria, and varying degrees of hematuria. Urine cultures will demonstrate the offending pathogen.

C. Imaging Scrotal ultrasound may aid in the diagnosis if examination is difficult because of the presence of a large hydrocele or because questions exist regarding the diagnosis.

``Differential Diagnosis Tumors generally cause painless enlargement of the testis.

Urinalysis is negative, and examination reveals a normal epididymis. Scrotal ultrasound is helpful to define the pathology. Testicular torsion usually occurs in prepubertal males but is occasionally seen in young adults. Acute onset of symptoms and a negative urinalysis favor testicular torsion or torsion of one of the testicular or epididymal appendages. Prehn sign (elevation of the scrotum above the pubic symphysis improves pain from epididymitis) may be helpful but is not reliable.

``Treatment Bed rest with scrotal elevation is important in the acute phase. Treatment is directed toward the identified pathogen (Table 23–1). The sexually transmitted variety is treated with 10–21 days of antibiotics, and the sexual partner must be treated as well. Non-sexually transmitted forms are treated for 21–28 days with appropriate antibiotics, at which time evaluation of the urinary tract is warranted to identify underlying disease.

``Prognosis Prompt treatment usually results in a favorable outcome.

Delayed or inadequate treatment may result in epididymoorchitis, decreased fertility, or abscess formation.

``When to Refer • Persistent symptoms and infection despite antibiotic therapy.

• Signs of sepsis or abscess formation.

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Interstitial Cystitis

``

Essentials of diagnosis

Pain with a full bladder or urinary urgency.

Submucosal petechiae or ulcers on cystoscopic examination.

Diagnosis of exclusion.

`` ``

``

``General Considerations Interstitial cystitis (painful bladder syndrome) is characterized by pain with bladder filling that is relieved by emptying and is often associated with urgency and frequency.

This is a diagnosis of exclusion, and patients must have a negative urine culture and cytology and no other obvious cause such as radiation cystitis, chemical cystitis (cyclophosphamide), vaginitis, urethral diverticulum, or genital herpes. Up to 40% of patients referred to urologists for interstitial cystitis may actually be found to have a different diagnosis after careful evaluation.

Population-based studies have demonstrated a prevalence of between 18 and 40 per 100,000 people. Both sexes are involved, but most patients are women, with a mean age of 40 years at onset. Patients with interstitial cystitis are more likely to report bladder problems in childhood, and there appears to be a higher prevalence in women. Up to 50% of patients may experience spontaneous remission of symptoms, with a mean duration of 8 months without treatment.

The etiology of interstitial cystitis is unknown, and it is most likely not a single disease but rather several diseases with similar symptoms. Associated diseases include severe allergies, irritable bowel syndrome, or inflammatory bowel disease. Theories regarding the cause of interstitial cystitis include increased epithelial permeability, neurogenic causes (sensory nervous system abnormalities), and autoimmunity.

``Clinical Findings A. Symptoms and Signs Pain with bladder filling that is relieved with urination or urgency, frequency, and nocturia are the most common symptoms. Patients should be asked about exposure to pelvic radiation or treatment with cyclophosphamide.

Examination should exclude genital herpes, vaginitis, or a urethral diverticulum.

B. Laboratory Findings Urinalysis, urine culture, and urinary cytologies are obtained to examine for infectious causes and bladder malignancy. Urodynamic testing assesses bladder sensation and compliance and excludes detrusor instability.

C. Cystoscopy Tracy CR et al. Diagnosis and management of epididymitis. Urol Clin North Am. 2008 Feb;35(1):101–8. [PMID: 18061028]

The bladder is distended with fluid (hydrodistention) to detect glomerulations (submucosal hemorrhage), which

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may or may not be present. Biopsy should be performed to exclude other causes such as carcinoma, eosinophilic cystitis, and tuberculous cystitis. The presence of submucosal mast cells is not needed to make the diagnosis of interstitial cystitis.

Marinkovic SP et al. The management of interstitial cystitis or painful bladder syndrome in women. BMJ. 2009 Jul 31;339:b2707. [PMID: 19648180] Theoharides TC et al. Interstitial cystitis: bladder pain and beyond. Expert Opin Pharmacother. 2008 Dec;9(17):2979–94.

[PMID: 19006474]

``Differential Diagnosis Exposures to radiation or cyclophosphamide are obtained by the history. Bacterial cystitis, genital herpes, or vaginitis can be excluded by urinalysis, culture, and physical examination. A urethral diverticulum may be suspected if palpation of the urethra demonstrates an indurated mass that results in the expression of pus from the urethral meatus.

Urethral carcinoma presents as a firm mass on palpation.

``Treatment There is no cure for interstitial cystitis, but most patients achieve symptomatic relief from one of several approaches, including hydrodistention, which is usually done as part of the diagnostic evaluation. Approximately 20–30% of patients notice symptomatic improvement following this maneuver. Also of importance is the measurement of bladder capacity during hydrodistention, since patients with very small bladder capacities (< 200 mL) are unlikely to respond to medical therapy.

Amitriptyline (10–75 mg/d orally) is often used as firstline medical therapy in patients with interstitial cystitis. Both central and peripheral mechanisms may contribute to its activity. Nifedipine (30–60 mg/d orally) and other calcium channel blockers have also demonstrated some activity in patients with interstitial cystitis. Pentosan polysulfate sodium (Elmiron) is an oral synthetic sulfated polysaccharide that helps restore integrity to the epithelium of the bladder in a subset of patients and has been evaluated in a placebo-­ controlled trial. Other options include intravesical instillation of dimethyl sulfoxide (DMSO) and heparin. Intravesical bacillus Calmette-Guérin (BCG) is not beneficial.

Further treatment modalities include transcutaneous electric nerve stimulation (TENS) and acupuncture.

Surgical therapy for interstitial cystitis should be considered only as a last resort and may require cystourethrectomy with urinary diversion.

``When to Refer Persistent and bothersome symptoms in the absence of identifiable cause.

Bogart LM et al. Symptoms of interstitial cystitis, painful bladder syndrome and similar disease in women: a systematic review.

J Urol. 2007 Feb;177(2):450–6. [PMID: 17222607] Dawson TE et al. Intravesical treatment for painful bladder syndrome/interstitial cystitis. Cochrane Database Syst Rev. 2007 Oct;17(4):CD006113. [PMID: 17943887] Fall M et al. Treatment of bladder pain syndrome/interstitial cystitis 2008: can we make evidence-based decisions? Eur Urol. 2008 Jul;54(1):65–75. [PMID: 18403099] Hanno PM et al. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011 Jun;185(6):2162–70. [PMID: 21497847]

Urinary Stone Disease

``

Essentials of diagnosis

Severe flank pain.

Nausea and vomiting.

Identification on noncontrast CT or ultrasonography.

`` `` ``

``General Considerations Urinary stone disease is exceeded in frequency as a urinary tract disorder only by infections and prostatic disease and is estimated to afflict 240,000–720,000 Americans per year.

Men are more frequently affected by urolithiasis than women, with a ratio of 2.5:1. Initial presentation predominates in the third and fourth decades. The ratio of men to women approaches parity in the sixth and seventh decades.

Urinary calculi are polycrystalline aggregates composed of varying amounts of crystalloid and a small amount of organic matrix. Stone formation requires saturated urine that is dependent on pH, ionic strength, solute concentration, and complexation. There are five major types of urinary stones: calcium oxalate, calcium phosphate, struvite (magnesium ammonium phosphate), uric acid, and cystine. The most common types are composed of calcium, and for that reason most urinary stones (85%) are radiopaque (as seen on plain abdominal radiographs). Uric acid stones can be radiolucent yet frequently are composed of a combination of uric acid and calcium oxalate and thus are frequently radiopaque. Cystine stones frequently have a smooth-edged ground-glass appearance.

Geographic factors contribute to the development of stones. Areas of high humidity and elevated temperatures appear to be contributing factors, and the incidence of symptomatic ureteral stones is greatest during hot summer months. Persons in sedentary occupations have a higher incidence of stones than manual laborers. Increasing evidence is revealing that urinary stone disease may be a precursor to subsequent cardiovascular disease.

High protein and high salt intake may be important factors in the development of urinary stones while carbohydrates and fats have not been proven to have an impact on urinary stone disease.

Genetic factors may contribute to urinary stone formation. Cystinuria is an autosomal recessive disorder.

Homozygous individuals have markedly increased excretion of cystine and frequently have numerous recurrent episodes of urinary stones despite attempts to optimize medical treatment. Distal renal tubular acidosis may be

Urologic Disorders transmitted as a hereditary trait, and urolithiasis occurs in up to 75% of patients affected with this disorder.

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plain radiographs. Patients with calcium-based stones typically have a urinary pH between 5.5 and 6.8.

C. Metabolic Evaluation

``Clinical Findings A. Symptoms and Signs Obstructing urinary stones usually present with acute and severe colic. Pain usually occurs suddenly and may awaken patients from sleep. It is localized to the flank, is usually severe, and may be associated with nausea and vomiting.

Patients are constantly moving trying to find a comfortable position—in sharp contrast to those with an acute abdomen. The pain may occur episodically and may radiate anteriorly over the abdomen. As the stone progresses down the ureter, the pain may be referred into the ipsilateral testis or labium. If the stone becomes lodged at the ureterovesicular junction, patients will complain of marked urinary urgency and frequency and in men, pain may radiate to the tip of the penis. After the stone passes into the bladder, there typically is minimal pain with passage through the urethra. Stone size does not correlate with the severity of the symptoms.

B. Laboratory Findings Urinalysis usually reveals microscopic or gross hematuria (~90%). However, the absence of microhematuria does not exclude urinary stones. Infection must be excluded, because the combination of infection and urinary tract obstruction requires prompt intervention as described below. Urinary pH is a valuable clue to the cause of the possible stone.

Normal urine pH is 5.8–5.9. There is a normal postprandial urinary alkaline tide. Numerous dipstick measurements are valuable in the complete workup of a patient in whom urinary stones are suspected. Persistent urinary pH below 5.5 is suggestive of uric acid or cystine stones, both relatively radiolucent as seen on plain abdominal radiographs. In contrast, a persistent urinary pH > 7.2 is suggestive of a struvite infection stone, which is radiopaque on

Patients should strain their urine through cheesecloth or a urine strainer. Stone analysis should be performed on recovered stones. Controversy exists in deciding which patients need a thorough metabolic evaluation for stone disease. Patients with uncomplicated first-time stones should probably undergo blood screening for abnormalities of serum calcium, electrolytes, and uric acid as a baseline.

More extensive evaluation is required in patients who have recurrent stones or those with a family history of nephrolithiasis. Patients are encouraged to change their diet to reduce sodium intake, reduce their animal protein intake during individual meals, and to ingest adequate fluid intake to achieve a voided volume of 1.5–2.0 L of urine. After these dietary changes have been initiated, a 24-hour urine collection should be obtained to ascertain urinary volume, pH, calcium, uric acid, oxalate, phosphate, sodium, and citrate excretion. Serum parathyroid hormone (PTH) and calcium can be obtained if the 24-hour urine collection reveals hypercalciuria. Table 23–3 demonstrates the diagnostic criteria for the hypercalciuric states.

(See discussion below.)

D. Imaging A plain abdominal radiograph (KUB, kidney-ureter-­ bladder) and renal ultrasound examination will diagnose most stones. More than 60% of patients with acute renal colic will have with a stone in the distal 4 cm of the ureter; attention should be directed to that region when examining plain radiographs and abdominal ultrasonographic studies. Spiral CT is frequently the first-line tool in evaluating flank pain. Repeated CT scans should be avoided due to the substantial radiation exposure to these patients who have recurrent stones at a young age. CT scans should be obtained in the prone position to help differentiate distal

Table 23–3. Diagnostic criteria of different types of hypercalciuria.

Absorptive Type I

Absorptive Type II

Absorptive Type III

Resorptive

Renal

Calcium

N

N

N

↑

N

Phosphorus

N

N

↓

↓

N

PTH

N

N

N

↑

↑

Vitamin D

N

N

↑

↑

↑

Fasting

N

N

↑

↑

↑

Restricted

↑

N

↑

↑

↑

After calcium load

↑

↑

↑

↑

↑

Serum

Urinary calcium

PTH, parathyroid hormone; ↑, elevated; ↓, low; N, normal.

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ureterovesicular stones from those that have already passed into the urinary bladder. Stone density can be estimated with Hounsfield units (HU) on CT scans to help determine stone type. Stones with low HU (< 450) are typically composed of uric acid, while those with high HU (> 1200) are typically composed of calcium oxalate monohydrate. All stones whether radiopaque or radiolucent on plain abdominal radiographs will be visible on noncontrast CT except the rare calculi due to the protease inhibitor indinavir.

``Medical Treatment & Prevention To reduce the recurrence rate of urinary stones, one must attempt to achieve a stone-free status. Small stone fragments may serve as a nidus for future stone development.

Selected patients must be thoroughly evaluated to reduce stone recurrence rates. Patients who have formed uric acid stones may have recurrences within months if appropriate therapy is not initiated. If no medical treatment is provided after surgical stone removal, stones will generally recur in 50% of patients within 5 years. Of greatest importance in reducing stone recurrence is an increased fluid intake.

Absolute volumes are not established, but increasing fluid intake to ensure a voided volume of 1.5–2.0 L/d is recommended (average voided volume is 1.6 L/d). Patients are encouraged to ingest fluids during meals, 2 hours after each meal (when the body is most dehydrated), and prior to going to sleep in the evening—enough to awaken the patient to void—and to ingest additional fluids during the night. Increasing fluids only during daylight hours may not dilute a supersaturated urine overnight and thus initiate a new stone.

A. Diet Sodium intake should be restricted to keep urinary sodium levels < 150 mEq/d. Increased sodium intake will increase sodium and calcium excretion, increase monosodium urates (that can act as a nidus for stone growth), increase the relative saturation of calcium phosphate, and decrease urinary citrate excretion. All of these factors encourage stone growth. Animal protein intake should be spread out through the day and not consumed during any individual meal and is best limited to 1 g/kg/d. An increased protein load during an individual meal can also increase calcium, oxalate, and uric acid excretion and decrease urinary citrate excretion.

Bran can significantly decrease urinary calcium excretion by increasing bowel transit time and mechanically binding to calcium. Excess intake of oxalate and purines can increase the incidence of stones in predisposed individuals. Dietary calcium or calcium supplements should not be routinely decreased. In fact, decreased calcium consumption has been found to increase stone recurrence.

Only type II absorptive hypercalciuric patients (see below) benefit from a low calcium diet.

B. Calcium Nephrolithiasis 1. Hypercalciuric—Hypercalciuric calcium nephrolithiasis (>250 mg/24 h; >4 mg/kg/24 h) can be caused by absorptive, resorptive, and renal disorders.

Absorptive hypercalciuria is secondary to increased absorption of calcium at the level of the small bowel, predominantly in the jejunum, and can be further subdivided into types I, II, and III. Type I absorptive hypercalciuria is independent of calcium intake. There is increased urinary calcium on a regular or even a calcium-restricted diet.

Treatment is centered on decreasing bowel absorption of calcium. Cellulose phosphate, a chelating agent, is an effective form of therapy. An average dose is 10–15 g in three divided doses. It binds to the calcium and impedes small bowel absorption due to its increased bulk. Cellulose phosphate does not change the intestinal transport mechanism.

It should be given with meals so it will be available to bind to the dietary calcium. Taking this chelating agent prior to bedtime is ineffective. Postmenopausal women should be treated with caution. It is interesting, however, that there is no enhanced decline in bone density after long-term use.

Inappropriate use may result in a negative calcium balance and a secondary parathyroid stimulation. Long-term use without follow-up metabolic surveillance may result in hypomagnesuria and secondary hyperoxaluria and recurrent calculi. Routine follow-up every 6–8 months will help encourage medical compliance and permit adjustments in medical therapy based on repeat metabolic studies.

Thiazide therapy is more commonly used and is an alternative to cellulose phosphate in the treatment of type I absorptive hypercalciuria. Thiazides decrease renal calcium excretion but have no impact on intestinal absorption. This therapy results in increased bone density of approximately 1% per year. Thiazides have limited longterm utility (< 5 years) since they may lose their hypocalciuric effect with continued therapy.

Type II absorptive hypercalciuria is diet dependent and fortunately rare. Decreasing calcium intake by 50% (approximately 400 mg/d) will decrease the hypercalciuria to normal values (150–200 mg/24 h). There is no specific medical therapy.

Type III absorptive hypercalciuria is secondary to a renal phosphate leak. This results in increased vitamin D synthesis and secondarily increased small bowel absorption of calcium. This can be readily reversed by orthophosphates (250 mg orally three to four times per day), presently available without need for a prescription. Orthophosphates do not change intestinal absorption but rather inhibit vitamin D synthesis.

Resorptive hypercalciuria is secondary to hyperparathyroidism. Hypercalcemia, hypophosphatemia, hypercalciuria, and an elevated serum PTH value are found.

Appropriate surgical resection of the parathyroid adenoma cures the disease and recurrent urinary stones are decreased by > 90%. Medical management is invariably a failure.

Renal hypercalciuria occurs when the renal tubules are unable to efficiently reabsorb filtered calcium, and hypercalciuria results. Spilling calcium in the urine results in secondary hyperparathyroidism. Serum calcium typically is normal. Thiazides are effective long-term therapy in patients with this disorder.

2. Hyperuricosuric—Hyperuricosuric calcium nephrolithiasis is secondary to dietary purine excess or endogenous uric acid metabolic defects. Most cases (85%) can be

Urologic Disorders treated with purine dietary restrictions; those that are not reversed with dietary modification are successfully treated with allopurinol. In contrast to uric acid nephrolithiasis, patients with hyperuricosuric calcium stones typically maintain a urinary pH > 5.5. Monosodium urates absorb and adsorb inhibitors and promote heterogeneous nucleation. Hyperuricosuric calcium nephrolithiasis is initiated with epitaxy, or heterogeneous nucleation. In such situations, similar crystal structures (ie, uric acid and calcium oxalate) can grow together with the aid of a protein matrix infrastructure.

3. Hyperoxaluric—Hyperoxaluric calcium nephrolithiasis (> 40 mg oxalate/24h urine) is usually due to primary intestinal disorders. Patients usually have a history of chronic diarrhea frequently associated with inflammatory bowel disease. In these situations, increased bowel fat or bile (or both) combine with intraluminal calcium to form a soap-like product. Calcium is therefore unavailable to bind to oxalate, which is then freely and rapidly absorbed.

A small increase in oxalate absorption will significantly increase stone formation. If the diarrhea or steatorrhea cannot be effectively curtailed, oral calcium should be taken with meals; the calcium can be obtained by either ingesting milk products or taking calcium carbonate supplements (250–500 mg). Excess ascorbic acid (> 2 g/d) will substantially increase urinary oxalate levels. Rare enzymatic liver defects can lead to primary hyperoxaluria that is routinely fatal without a combined liver and kidney transplantation.

4. Hypocitraturic—Hypocitraturic calcium nephrolithiasis may be secondary to chronic diarrhea, type I (distal) renal tubular acidosis, chronic hydrochlorothiazide treatment, or in any other condition that results in a metabolic acidosis. The metabolic acidosis will encourage citrate transport into the proximal tubular cells and be consumed by the citric acid cycle in their mitochondria and result in hypocitraturia (< 450 mg/24h). Hypocitraturia is frequently associated with most forms of calcium stone formation. Urinary citrate binds to calcium in solution, thereby decreasing available calcium for precipitation and subsequent stone formation. Potassium citrate supplements are usually effective treatment in these situations.

Urinary citrate is decreased in acidosis and is increased during alkalosis. The potassium will supplement the frequently associated hypokalemic states, and citrate will help correct the acidosis. A typical dose is 20 mEq three times a day (available in 10-mEq waxed tablets or in solution), or 30 mEq of crystal formulations twice a day. Alternatively, oral lemonade has been shown to increase urinary citrate by about 150 mg/24h.

C. Uric Acid Calculi The average normal urinary pH is 5.8–5.9. Urinary pH is consistently < 5.5 in persons who form uric acid stones.

The pK of uric acid is 5.75, at which point half of the uric acid is ionized as a urate salt and is soluble, while the other half is insoluble. Increasing the urinary pH above 6.2 dramatically increases uric acid solubility and can effectively

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dissolve large calculi at a rate of 1 cm per month as seen on plain abdominal radiographs, and effectively prevents future uric acid stone formation. Urinary alkalinization is the key to stone dissolution and prophylaxis. Potassium citrate is the most frequently used medication to increase urinary pH. It can be given in liquid preparation, as crystals that need to be taken with fluids, or as tablets (10 mEq), two by mouth three or four times daily. Patients with uric acid calculi should be given nitrazine pH paper with which to monitor the effectiveness of their urinary alkalinization; the goal is a urinary pH > 6.2 and < 6.5 (to avoid calcium phosphate precipitation). Other contributing factors include hyperuricemia, myeloproliferative disorders, malignancy with increased uric acid production, abrupt and dramatic weight loss, and uricosuric medications. If hyperuricemia is present, allopurinol (300 mg/d orally) may be given. Although pure uric acid stones are relatively radiolucent, most have some calcium components and can be visualized on plain abdominal radiographs. Renal ultrasonography is a helpful adjunct for appropriate diagnosis and long-term management.

D. Struvite Calculi Struvite stones are synonymous with magnesium-­ ammonium-phosphate or infection stones. They are most commonly seen in women with recurrent urinary tract infections recalcitrant to appropriate antibiotics. They rarely present as ureteral stones with colic without prior upper tract endourologic intervention. Frequently, a struvite stone is discovered as a large staghorn configured calculus forming a cast of the renal collecting system.

Struvite stones are radiodense. Urinary pH is high, routinely above 7.2. These stones are formed secondary to urease-producing organisms, including Proteus, Pseudom­ onas, Providencia and, less commonly, Klebsiella, Staphylo­ coccus, and Mycoplasma. An E coli urinary tract infection is not consistent with an infectious reservoir originating from a struvite calculus. These frequently large stones are relatively soft and amenable to percutaneous nephrolithotomy. Appropriate perioperative antibiotics are required.

They can recur rapidly, and efforts should be taken to render the patient stone-free. Postoperative irrigation through nephrostomy tubes can eliminate small fragments.

Acetohydroxamic acid is an effective urease inhibitor, but it is poorly tolerated by most patients because of its gastrointestinal toxicity.

E. Cystine Calculi Cystine stones are a result of abnormal excretion of cystine, ornithine, lysine, and arginine. Cystine is the only amino acid that becomes insoluble in urine.

These stones are particularly difficult to manage medically. Prevention is centered around marked increased fluid intake during the day and evening to achieve a urinary volume of 3–4 L/d, urinary alkalinization with a urinary pH > 7.0 (monitored with Nitrazine pH paper), and disulfide inhibitors such as tiopronin (α-mercaptoproprionylglycine) or penicillamine. There are no known inhibitors of cystine calculi.

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``Surgical Treatment Forced intravenous fluids will not push stones down the ureter. Effective peristalsis directing a bolus of urine down the ureter requires opposing ureteral walls to approach each other and touch, which large dilated systems cannot do. In fact, forced diuresis is counterproductive and will exacerbate the pain; a euvolemic state should be achieved.

Associated fever may represent infection, a medical emergency requiring prompt drainage by a ureteral catheter or a percutaneous nephrostomy tube. Antibiotics alone are inadequate unless the obstruction is drained.

A. Ureteral Stones Impediment to urine flow by ureteral stones usually occurs at two sites: at the ureteropelvic junction and at the ureterovesicular junction as the ureter enters the bladder.

Prediction of spontaneous stone passage is difficult. Stones < 5–6 mm in diameter as seen on a plain abdominal radiograph usually passes spontaneously. Medical expulsive therapy with α-blockers (such as tamsulosin, 0.4 mg orally once daily) in combination with a nonsteroidal anti-­ inflammatory agent (such as ibuprofen 600 mg orally three times per day with a full stomach), with or without a short course of a low-dose oral corticosteroid dramatically increases the rate of spontaneous stone passage. Active medical expulsive therapy with appropriate pain medications is appropriate for the first few weeks. If stone passage fails, with or without medical expulsive therapy, or the patient has intolerable pain or persistent nausea or vomiting, therapeutic intervention is indicated. Distal ureteral stones are best managed with ureteroscopic stone extraction or in situ extracorporeal shock wave lithotripsy (SWL). Ureteroscopic stone extraction involves placement of a small endoscope through the urethra and into the ureter. Under direct vision, basket extraction or stone laser fragmentation followed by extraction is performed. Com­ plications during endoscopic retrieval increase as the duration of attempted medical expulsive therapy increases beyond 6 weeks. Indications for earlier intervention include severe pain unresponsive to medications, fever, persistent nausea and vomiting requiring intravenous hydration, social requirements requiring return to work, or anticipated travel. Most upper tract stones that enter the bladder can exit the urethra with minimal discomfort.

In situ SWL, an alternative, utilizes an external energy source that is focused on the stone. This focused energy is additive, resulting in minimal tissue insult except at the focus where the stone is positioned with the aid of fluoroscopy or ultrasonography. This can be performed under anesthesia as an outpatient procedure and has a high stone fragmentation rate. Most stone fragments will pass uneventfully within 2 weeks, but those that have not passed within 6 weeks are unlikely to pass without intervention.

Women of childbearing age are best not treated with SWL for a stone in the lower ureter because the impact on the ovary is unknown.

Proximal and midureteral stones—those above the inferior margin of the sacroiliac joint—can be treated with SWL or ureteroscopy. SWL is delivered directly to the stone

(in situ) without the need to push the stone back into the renal pelvis. To help ensure adequate drainage after SWL, a double J ureteral stent may be placed, but it does not ensure passage of stone fragments. Occasionally, stone fragments will obstruct the ureter after SWL. Conservative management will usually result in spontaneous resolution with eventual passage of the stone fragments. If this is unsuccessful, adequate proximal drainage through a percutaneous nephrostomy tube will facilitate passage. In rare instances, ureteroscopic extraction will be required.

B. Renal Calculi Patients with renal calculi presenting without pain, urinary tract infections, or obstruction need not be treated. They should be monitored with serial abdominal radiographs or renal ultrasonographic examinations. If calculi are growing or become symptomatic, intervention should be undertaken. Renal calculi < 1.5 cm in diameter are best treated with SWL. Calculi located in the inferior calix frequently result in suboptimal stone-free rates as measured at 3 months by x-ray. Such calculi and others of larger diameter are best treated via percutaneous nephrolithotomy.

Percutaneous nephrolithotomy is performed by inserting a needle into the appropriate renal calyx and dilating a tract large enough to allow a nephroscope to pass and inspect, fragment, and remove stone and stone fragments.

Perioperative antibiotic coverage should be given on the basis of preoperative urine cultures.

``When to Refer • • • •

Evidence of urinary obstruction.

Urinary stone with fever.

Anatomic abnormalities or solitary kidney.

Concomitant pyelonephritis.

``When to Admit • Intractable nausea and vomiting or pain.

• Fever.

Fink HA et al. Diet, fluid, or supplements for secondary prevention of nephrolithiasis: a systematic review and meta-analysis of randomized trials. Eur Urol. 2009 Jul;56(1):72–80. [PMID: 19321253] Nouvenne A et al. Effects of a low-salt diet on idiopathic hypercalciuria in calcium-oxalate stone formers: a 3-mo randomized controlled trial. Am J Clin Nutr. 2010 Mar;91(3):565–70.

[PMID: 20042524] Preminger GM et al; EAU/AUA Nephrolithiasis Guideline Panel.

2007 guideline for the management of ureteral calculi. J Urol.

2007 Dec;178(6):2418–34. [PMID: 17993340] Reiner AP et al. Kidney stones and subclinical atherosclerosis in young adults: the CARDIA study. J Urol. 2011 Mar;185(3): 920–5. [PMID: 21251678] Stoller ML et al. The primary stone event: a new hypothesis involving a vascular etiology. J Urol. 2004 May;171(5):1920–4.

[PMID: 15076312] Tracy CR et al. Update on the medical management of stone disease. Curr Opin Urol. 2009 Mar;19(2):200–4. [PMID: 19188774]

Urologic Disorders

Male Erectile Dysfunction & Sexual Dysfunction

``

Essentials of diagnosis

Erectile dysfunction can have organic and psychogenic etiologies.

Organic erectile dysfunction may be an early sign of cardiovascular disease and requires evaluation.

Peyronie disease is a common fibrotic disorder of the penile erectile bodies that causes penile deformity and sexual dysfunction.

``

``

``

``General Considerations Erectile dysfunction is the consistent inability to attain or maintain a sufficiently rigid penile erection for sexual performance. The condition affects nearly 30 million American men, and its incidence is age related. Approximately 52% of men aged 40–70 years experience erectile dysfunction.

Most cases of erectile dysfunction have an organic rather than a psychogenic cause. Normal male erection is a neurovascular event relying on an intact autonomic and somatic nerve supply to the penis, smooth and striated musculature of the corpora cavernosa and pelvic floor, and arterial blood flow supplied by the paired pudendal arteries. Erection is caused and maintained by an increase in arterial flow, active relaxation of the smooth muscle within the sinusoids of the paired corpora cavernosa of the penis, and an increase in venous resistance. Contraction of the bulbocavernosus and ischiocavernosus muscles results in further rigidity of the penis with intracavernosal pressures far exceeding systolic blood pressure. Nitric oxide is a pivotal neurotransmitter that initiates and sustains erections; however, other molecules contribute, including acetylcholine, prostaglandins, and vasoactive intestinal peptide.

Male sexual dysfunction may be manifested in a variety of ways, and patient history is critical to the proper classification and treatment. Androgens have a strong influence on the sexual desire of men. A loss of libido may indicate androgen deficiency on the basis of either hypothalamic, pituitary, or testicular disease. Loss of erections may result from arterial, venous, neurogenic, or psychogenic causes. Concurrent medical problems may damage one or more of the mechanisms. Of particular concern is endothelial dysfunction, defined as the decreased bioavailability of nitric oxide with subsequent impairment of arterial vasodilation. Erectile dysfunction may be an early manifestation of endothelial dysfunction, which precedes more severe, systemic atheroscle­rotic, cardiovascular disease. In addition, many medications, especially antihypertensive and antidepressant agents, are associated with erectile dysfunction. Peyronie disease is a fibrotic disorder of the tunica albuginea of the penis resulting in varying degrees of penile curvature or deformity and sexual dysfunction. Peyronie disease develops in approximately 5% of men older than 50 years, but this may be an underestimate related to embarrassment in seeking care. After onset of the disease, 10% of men improve

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spontaneously. If left untreated, the disease progresses in half of the remainder and the rest stabilize. Deformity of the penis can be severe enough to impair normal sexual function. The etiology of Peyronie disease is not fully understood and is likely multifactorial. The most promising hypothesis is that subtle penile trauma is followed by abnormal wound healing, although other potential disease modulators may include vascular disease and hypogonadism.

Priapism is the occurrence of penile erection unrelated to sexual stimulation, generally lasting longer than 4 hours, and potentially leading to irreversible damage to the erectile mechanisms. Priapism can be due to unregulated high blood flow, but more commonly, it is due to trapping of blood within the erectile bodies resulting in penile ischemia and infarction of the sinusoidal tissue. Priapism may be caused by any of the treatments for erectile dysfunction, drug use, and red blood cell dyscrasias.

Anejaculation is the loss of seminal emission and may result from androgen deficiency by decreasing prostate and seminal vesicle secretions as well as sympathetic denervation as a result of diabetes mellitus or pelvic or retroperitoneal surgery or radiation. Retrograde ejaculation may occur as a result of mechanical disruption of the bladder neck, especially following transurethral resection of the prostate, pelvic radiation, treatment with α-blockers, or due to sympathetic denervation. If libido and erection are intact, the loss of orgasm is usually of psychological origin.

Premature ejaculation is the persistent or recurrent ejaculation with minimal stimulation before a person desires (associated with distress) and may be primary or secondary. The former is usually psychogenic in origin and additional history may elucidate the presence of a new partner, unreasonable expectations about performance, or emotional disorders. The latter is caused by erectile dysfunction and may be corrected with erectile dysfunction treatment.

``Clinical Findings A. Symptoms and Signs Erectile dysfunction should be distinguished from problems of penile deformity, ejaculation, libido, and orgasm.

The severity of the dysfunction (maintaining vs attaining; chronic, occasional, or situational) as well as its timing should be noted. The history should include inquiries about dyslipidemia, hypertension, depression, neurologic disease, diabetes mellitus, chronic kidney disease, and endocrine disorders as well as cardiac or peripheral vascular disease. Pelvic trauma, surgery, or irradiation identifies patients at increased risk for erectile dysfunction. Penile deformity or curvature that prevents normal intercourse should be noted because this may indicate the presence of Peyronie disease, which may complicate treatment. The history should clarify the severity of curvature, loss of penile length, and other deformities that may prevent normal, painless sexual intercourse. It is important to determine whether the patient has any normal erections in the early morning or during sleep. If normal erections occur, an organic cause is less likely. The ability to attain but not maintain an erection may be the first sign of endothelial dysfunction, which is the decreased responsiveness of the

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penile vasculature to nitric oxide released from pelvic parasympathetic nerves. The gradual loss of erections over time is more suggestive of an organic cause with the exception of erectile dysfunction that immediately follows pelvic surgery or trauma. Medication use should be noted, since 25% of all cases of sexual dysfunction may be drug related.

The use of alcohol, tobacco, and recreational drugs should be recorded, since each is associated with an increased risk of sexual dysfunction.

During the physical examination, secondary sexual char­ acteristics should be assessed. Motor and sensory examination should be performed as well as palpation and quantification of lower extremity vascular pulsations. The genitalia should be examined, noting the presence of penile scarring or plaque formation (Peyronie disease) and any abnormalities in size or consistency of either testicle.

B. Laboratory Findings Laboratory evaluation should consist of a fasting lipid profile and glucose, testosterone, and prolactin. Patients with abnormalities of testosterone or prolactin require further evaluation with measurement of free testosterone and luteinizing hormone (LH) to distinguish hypothalamicpituitary dysfunction from testes failure.

C. Special Tests Further testing is based on the patient's history and is performed when etiology is unclear. Organic and psychogenic erectile dysfunction frequently occur in tandem, given that erectile dysfunction can contribute to emotional stress.

Erectile dysfunction that is primarily psychogenic can generally be differentiated by patient history, whereby men will describe normal nocturnal or morning erections, or situational erectile dysfunction. If the distinction remains unclear, clarity may be gained with the use of nocturnal penile tumescence testing, where the frequency and rigidity of erections are recorded by a tension meter attached to the penis before sleep.

Patients with psychogenic erectile dysfunction will have nocturnal erections of adequate frequency and rigidity.

Treatment of patients with oral medications (sildenafil, vardenafil, and tadalafil) provides insight into the etiology and severity of erectile dysfunction. Patients with inadequate response to oral medications may undergo further evaluation with direct injection of vasoactive medications into the penis. These medications (prostaglandin E1, papaverine, phentolamine or a combination of drugs) induce erections in men with intact vascular systems. Patients who respond with a rigid erection require no further vascular evaluation.

Additional vascular testing is indicated in select patients who do not achieve an erection after penile injection and who are candidates for vascular reconstructive surgery.

Duplex ultrasound, penile cavernosography, and pudendal arteriography can distinguish arterial from venous erectile dysfunction and help predict which patients may benefit from vascular surgery.

``Treatment Treatment of men suffering from sexual dysfunction should be patient centered and goal oriented, since the

disease is generally not life-threatening. Most men can be treated successfully with one of the approaches outlined below. Men who have psychogenic erectile dysfunction will probably benefit from behaviorally oriented sex therapy.

A. Hormonal Replacement Testosterone replacement therapy may be offered to men with documented biochemical hypogonadism who have undergone endocrinologic evaluation and in whom there is no evidence of prostate cancer or other contraindication to treatment. Restoration of normal testosterone levels may improve libido and effectiveness of oral erectile medications.

B. Vasoactive Therapy Sexual stimulation with subsequent nitric oxide release from the parasympathetic nerves and endothelium initiates penile erection. Nitric oxide enters smooth muscles cells, increases cyclic guanosine monophosphate (cGMP) production, which mediates calcium sequestration and cellular hyperpolarization. Phosphodiesterase-5 (PDE-5) degrades cGMP and fosters penile detumescence. Activation of pelvic sympathetic nerves causes ejaculation, contraction of the smooth muscle within the corpora cavernosa and complete penile detumescence.

1. Oral agents—Sildenafil, vardenafil, and tadalafil inhibit PDE-5, preventing the degradation of cGMP, thereby sustaining inflow of blood into the erect penis. The drugs are similarly effective; some patients who do not respond to one PDE-5 inhibitor may respond to one of the other agents.

Because of differences in receptor binding affinity and pharmacokinetics, the drugs have variable durations of activity and side effects. Each drug should be initiated at the lowest dose and titrated to effect. There is no effect on libido, and priapism is exceedingly rare. The additive effect of nitrate medications may lead to exaggerated cardiac preload reduction and hypotension; therefore, these drugs are contraindicated in patients taking nitroglycerin or nitrates. The greatest risk for this effect is within the first hour after taking sildenafil but this risk period may be longer for tadalafil due to increased drug half-life. All patients being evaluated for acute chest pain should be asked if they are taking a PDE-5 inhibitor before administering nitroglycerin and close monitoring of blood pressure is warranted if there is concern regarding drug overlap. Fixed atherosclerotic disease in the aortoiliac system is associated with diminished efficacy.

The combination of PDE-5 inhibitors and α-receptor blockers (which may be prescribed for lower urinary tract symptoms) may cause a larger reduction in systemic blood pressure than when PDE-5 inhibitors are used alone.

However, these two classes of medication may be safely used in combination if they are started in a stepwise fashion, with escalation of dose when there is no evidence of syncope. In select men, combined treatment with PDE-5 inhibitors and testosterone replacement may be warranted, since adequate androgen levels may be required for the penile vasculature to be fully responsive to vasoactive drugs.

2. Injectable agents—Direct injection of vasoactive prostaglandins with or without papaverine or phentolamine into the penis is an acceptable form of treatment for many men

Urologic Disorders with erectile dysfunction. Injections are performed using a tuberculin syringe or a metered-dose injection device. The base and lateral aspect of the penis is used as the injection site to avoid injury to the superficial blood supply located anteriorly. Complications are rare and include bruising, dizziness, local pain, fibrosis, priapism, and infection. Vasoactive prostaglandins (alprostadil) can also be delivered via a urethral suppository with slightly less effectiveness.

The presence of a prolonged erection (priapism) requires immediate medical attention to prevent erectile dysfunction and fibrosis of the cavernosal tissues. Initial management may include aspiration of blood from the penis or injection of sympathomimetic drugs (epinephrine or phenylephrine); if these maneuvers fail, surgical shunts may need to be performed to drain blood from the corpora cavernosa.

C. Vacuum Erection Device The vacuum erection device causes erection by creating a vacuum chamber around the penis, whereby blood is drawn into the corpora cavernosa. Once adequate tumescence has been achieved, an elastic constriction band is placed around the proximal penile shaft to prevent loss of erection, and the vacuum cylinder is removed. Such devices are highly effective, regardless of the cause of erectile dysfunction; however, the devices are cumbersome with a high rate of discontinued use. Complications are rare.

D. Penile Prostheses Prosthetic devices may be implanted directly into the paired corporal bodies. Penile prostheses may be semirigid (malleable) or inflatable. Each is manufactured in a variety of sizes and is custom-fit to the individual. Even for men with normal erectile function, the penis is flaccid 90% of time; therefore, inflatable devices may result in a more natural appearance and better functionality. Complications are rare but include mechanical failure, infection, and injury to adjacent anatomic structures during surgery. For men who elect this treatment, personal and partner satisfaction rates exceed 90%.

E. Vascular Reconstruction Patients with disorders of the arterial system are candidates for various forms of arterial reconstruction, including endarterectomy and balloon dilation for proximal arterial occlusion and arterial bypass procedures utilizing arterial (epigastric) or venous (deep dorsal vein) segments for distal occlusion. Patients with venous disorders may be managed with ligation of certain veins (deep dorsal or emissary veins) or the crura of the corpora cavernosa. Experience with vascular reconstructive procedures is limited, and many patients so treated still fail to achieve a rigid erection.

F. Medical and Surgical Therapy for Peyronie Disease A wide range of medical and surgical treatments have been used to treat the disorder. There are no oral therapies for Peyronie disease that are approved by the FDA; however, evidence from randomized controlled trials supports the use of pentoxifylline, coenzyme Q10, colchicine, potassium

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aminobenzoate (Potaba), and L-carnitine. The intraplaque injection of verapamil or interferon improves penile deformity in some patients. Surgical treatment is an alternative for men with compromised sexual function due to severe curvature or lesions causing penile instability. The choice of corrective procedure should be tailored to each patient after a detailed evaluation of disease severity and sexual function.

``When to Refer • Patients with inadequate response to oral medications or who are unable to tolerate side effects.

• Patients with Peyronie disease (penile curvature) or other penile deformity.

• Patients with a history of pelvic or perineal trauma, surgery, or radiation.

• Young patients or those with lifelong erectile dysfunction.

• Ischemic priapism is a medical emergency and requires immediate referral to a urologist or the emergency department for intervention to allow restoration of penile blood perfusion.

Corona G et al. Phosphodiesterase type 5 (PDE5) inhibitors in erectile dysfunction: the proper drug for the proper patient. J Sex Med. 2011 Dec;8(12):3418–32. [PMID: 21995676] McVary KT. Clinical practice. Erectile dysfunction. N Engl J Med. 2007 Dec 13;357(24):2472–81. [PMID: 18077811] Meuleman EJ et al. Diagnostic tests for male erectile dysfunction revisited. Committee Consensus Report of the International Consultation in Sexual Medicine. J Sex Med. 2010 Jul; 7(7):2375–81. [PMID: 20487240] Porst H. An overview of pharmacotherapy in premature ejaculation. J Sex Med. 2011 Oct;8(Suppl 4):335–41. [PMID: 21967395] Shin D et al. Erectile dysfunction: a disease marker for cardiovascular disease. Cardiol Rev. 2011 Jan–Feb;19(1):5–11. [PMID: 21135596] Smith JF et al. Peyronie's disease: a critical appraisal of current diagnosis and treatment. Int J Impot Res. 2008 Sep–Oct;20(5): 445–59. [PMID: 18650828] Tsertsvadze A et al. Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction: a systematic review and meta-analysis. Ann Intern Med. 2009 Nov 3;151(9):650–61. [PMID: 19884626]

Male Infertility ``

Couple infertility is related to the male partner in 50% of cases.

Causes include decreased or absent sperm production or function, or obstruction of the male genital tract.

Detailed history, physical examination, and repeated semen analysis are the cornerstones of diagnosis and treatment.

In select men, abnormal semen quality may indicate poor somatic health and increased risk for certain health conditions.

``

``

``

``

Essentials of diagnosis

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``General Considerations Infertility, the inability of a couple to conceive a child after 1 year of sexual intercourse without contraceptive use, affects 15–20% of US couples. Approximately one-third of cases result from male factors, one-third from female factors, and one-third from combined factors; therefore, evaluation of both partners is critical. Clinical evaluation is warranted following 6 months of unprotected intercourse in select couples.

Following a detailed history and physical examination, a semen analysis is essential for diagnosis and should be performed at least twice, on two separate occasions (Figure 23–1).

Because spermatogenesis takes approximately 74 days, it is important to review events from the past 3 months. Some types of male infertility put men at higher risk for the later development of testicular germ cell cancer; thus, they should be counseled appropriately and taught self testicular exam.

``Clinical Findings A. Symptoms and Signs The history should include prior testicular insults (torsion, cryptorchidism, trauma), infections (mumps orchitis,

epididymitis), environmental factors (excessive heat, radiation, chemotherapy, prolonged pesticide exposure), medications (anabolic steroids, cimetidine, and spironolactone may affect spermatogenesis; phenytoin may lower FSH; sulfasalazine and nitrofurantoin affect sperm motility), and drugs (alcohol, tobacco, marijuana). Sexual habits, frequency and timing of intercourse, use of lubricants, and each partner's previous fertility experiences are important.

Loss of libido and headaches, visual disturbances, or galactorrhea may indicate a pituitary tumor. The past medical or surgical history may reveal thyroid or liver disease (abnormalities of spermatogenesis), diabetic neuropathy (retrograde or anejaculation), radical pelvic or retroperitoneal surgery (absent seminal emission secondary to sympathetic nerve injury), or hernia repair (damage to the vas deferens or testicular blood supply).

Physical examination should pay particular attention to features of hypogonadism: underdeveloped secondary sexual characteristics, diminished male pattern hair distribution (axillary, body, facial, pubic), body habitus, and gynecomastia. The scrotal contents should be carefully evaluated. Testicular size should be noted (normal size approximately 4.5 × 2.5 cm, volume 18 mL). Varicoceles

Infertility

Male evaluation

History Physical examination

Complete, simultaneous evaluation

Female evaluation

Address modifiable factors, eliminate gonadotoxins or exogenous androgens

Semen analysis × 2

Abnormal

Hormonal evaluation

Correct gonadotropin deficiency

Normal

Low volume

Oligozoospermia, asthenozoospermia, teratozoospermia

Azoospermia

Advanced sperm function testing

Post ejaculate urinalysis (for presence of sperm)

Correct reversible factors such as gonadotoxin exposure or varicocele

Testicular biopsy, FNA, or sperm retrieval

Couple based treatment approach: correct specific etiologies, consider assisted reproductive technology, sperm donation, or adoption

s Figure 23–1. Couple based approach to evaluation and treatment of male factor infertility. FNA, fine-needle aspiration.

Urologic Disorders are abnormally dilated and refluxing veins of the pampiniform plexus that can be identified in the standing position by gentle palpation of the spermatic cord and, on occasion, may only be appreciated with the Valsalva maneuver. The vas deferens, epididymis, and prostate should be palpated (absence of all or part of the vas deferens may indicate the presence a cystic fibrosis variant, congenital bilateral or unilateral absence of the vas deferens).

B. Laboratory Findings Semen analysis should be performed after 2 to 3 days of ejaculatory abstinence. The specimen should be analyzed within 1 hour after collection. Abnormal sperm concentrations are <15 million/mL (oligozoospermia is the presence of <15 million sperm/mL in the ejaculate; azoospermia is the absence of sperm). Normal semen volumes range between 1.5 mL and 5 mL (volumes <1.5 mL may result in inadequate buffering of the vaginal acidity and may be due to retrograde ejaculation, ejaculatory duct obstruction, or androgen insufficiency). Normal sperm motility and morphology demonstrate >45% motile cells and >4% normal morphology (World Health Organization). Abnormal motility may result from varicocele, antisperm antibodies, infection, abnormalities of the sperm flagella, or partial ejaculatory duct obstruction.

Abnormal morphology may result from a varicocele, infection, or exposure to gonadotoxins (eg, tobacco smoke).

Endocrine evaluation is warranted if sperm counts are low (< 15 million/mL) or if there is a basis from the history and physical examination for suspecting an endocrinologic origin. Initial testing should include serum FSH and testosterone. Specific abnormalities in these hormones should prompt additional testing, including LH and prolactin.

Elevated FSH and LH levels and low testosterone levels (hypergonadotropic hypogonadism) are associated with primary testicular failure. Low FSH and LH associated with low testosterone occur in secondary testicular failure (hypogonadotropic hypogonadism) and may be of hypothalamic or pituitary origin. Elevation of serum prolactin may indicate the presence of pituitary prolactinoma.

C. Genetic Testing Men with sperm concentrations <10 million/mL should undergo testing for Y chromosome microdeletions and karyotypic abnormalities. Gene deletions from the long arm of the Y chromosome may cause azoospermia or oligozoospermia with age-related decline in spermatogenesis that is transmissible to male offspring. Karyotyping may reveal Klinefelter syndrome. Partial or complete absence of the vas deferens should prompt testing for cystic fibrosis mutations.

D. Imaging Scrotal ultrasound may detect a subclinical varicocele.

Vasography may be required in patients with suspected genital duct obstruction. Men with low ejaculate volume and no evidence of retrograde ejaculation should undergo transrectal ultrasound to evaluate the prostate and seminal vesicles. MRI of the sella turcica should be performed in

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men with markedly elevated prolactin or hypogonadotropic hypogonadism to evaluate the anterior pituitary gland.

MRI of the pelvis and scrotum should be considered in men for whom the testes cannot be identified in the scrotum by physical examination or ultrasound.

E. Special Tests Patients with low volume ejaculate should have post-­ ejaculation urine samples centrifuged and analyzed for sperm to evaluate for retrograde ejaculation. In cases of disproportionately low motility, sperm vitality and the presence of autoantibodies should be assessed. Rounds cells in concentrations > 1 million/mL should prompt leukocyte esterase or peroxidase staining (immature germ cells are found normally, but inflammatory cells may require treatment).

``Treatment A. General Measures Education about the proper timing for intercourse in relation to the woman's ovulatory cycle as well as the avoidance of spermicidal lubricants should be discussed. In cases of gonadotoxic exposure or medication-related factors, the offending agent should be removed. Patients with active genitourinary tract infections should be treated with appropriate antibiotics. Healthy lifestyle habits, including healthy diet, moderate exercise, and avoidance of gonadotoxins (such as tobacco smoke) should be reinforced.

B. Varicocele Varicocelectomy is performed by stopping retrograde blood flow in spermatic cord veins. Surgical ligation may be accomplished via subinguinal, inguinal, retroperitoneal, or laparoscopic approaches. Percutaneous venographic embolization of varicoceles is feasible but may have a higher recurrence rate.

C. Endocrine Therapy Hypogonadotropic hypogonadism may be treated with chorionic gonadotropin once primary pituitary disease has been excluded or treated. Dosage is usually 2000 international units intramuscularly three times a week. If sperm counts fail to rise after 12 months, FSH therapy should be initiated.

D. Ejaculatory Dysfunction Therapy Patients with retrograde ejaculation may benefit from Îą-adrenergic agonists (pseudoephedrine, 60 mg orally three times a day) or imipramine (25 mg orally three times a day). Medical failures may require the collection of post-ejaculation urine for intrauterine insemination.

Anejaculation can be treated with vibratory stimulation or electroejaculation in select cases.

E. Ductal Obstruction Obstruction of the ejaculatory ducts may be corrected by transurethral resection of the ducts in the prostatic urethra.

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If obstruction of the vas deferens or epididymis is suspected, the level of obstruction must be determined via a vasogram prior to operative treatment, with the exception of prior vasectomy. Obstruction of the vas deferens is best managed by microsurgical vasovasostomy or vasoepididymostomy.

F. Assisted Reproductive Techniques Intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection (ICSI) are alternatives for patients in whom other means of treating reduced sperm concentration, motility, or functionality has failed. With the use of ICSI, azoospermic men can father their genetic progeny by surgical retrieval of sperm from the testicle, epididymis, or vas deferens.

``When to Refer • Couples with clinical infertility or concern about fertility potential.

• Men with known genital insults, genetic diagnoses, or syndromes that preclude natural fertility.

• Reproductive-aged men with newly diagnosed cancer or other disease that may require cytotoxic therapies with interest in fertility preservation.

Lopushnyan NA et al. Surgical techniques for the management of male infertility. Asian J Androl. 2012 Jan;14(1):94–102.

[PMID: 22120932] Patel ZP et al. Male factor assessment in infertility. Med Clin North Am. 2011 Jan;95(1):223–34. [PMID: 21095425] Practice Committee of American Society for Reproductive Medicine in collaboration with Society for Male Reproduction and Urology. Evaluation of the azoospermic male. Fertil Steril. 2008 Nov;90(5 Suppl):S74–7. [PMID: 19007652] Walsh TJ et al. Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med. 2009 Feb 23;169(4): 351–6. [PMID: 19237718] Walsh TJ et al. The genetics of male infertility. Semin Reprod Med. 2009 Mar;27(2):124–36. [PMID: 19247914]

Benign Prostatic Hyperplasia

``

Essentials of diagnosis

Obstructive or irritative voiding symptoms.

May have enlarged prostate on rectal examination.

Absence of urinary tract infection, neurologic disorder, stricture disease, prostatic or bladder malignancy.

`` `` ``

``General Considerations Benign prostatic hyperplasia is the most common benign tumor in men, and its incidence is age related. The prevalence of histologic benign prostatic hyperplasia in autopsy studies rises from approximately 20% in men aged 41–50 years, to 50% in men aged 51–60, and to over 90% in men

over 80 years of age. Although clinical evidence of disease occurs less commonly, symptoms of prostatic obstruction are also age related. At age 55 years, approximately 25% of men report obstructive voiding symptoms. At age 75 years, 50% of men report a decrease in the force and caliber of the urinary stream.

Risk factors for the development of benign prostatic hyperplasia are poorly understood. Some studies have suggested a genetic predisposition and some have noted racial differences. Approximately 50% of men under age 60 years who undergo surgery for benign prostatic hyperplasia may have a heritable form of the disease. This form is most likely an autosomal dominant trait, and first-degree male relatives of such patients carry an increased relative risk of approximately fourfold.

``Clinical Findings A. Symptoms The symptoms of benign prostatic hyperplasia can be divided into obstructive and irritative complaints. Obstruc­ tive symptoms include hesitancy, decreased force and caliber of the stream, sensation of incomplete bladder emptying, double voiding (urinating a second time within 2 hours), straining to urinate, and postvoid dribbling. Irritative symptoms include urgency, frequency, and nocturia.

The American Urological Association (AUA) symptom index (Table 23–4) is perhaps the single most important tool used in the evaluation of patients with this disorder and should be calculated for all patients before starting therapy. The answers to seven questions quantitate the severity of obstructive or irritative complaints on a scale of 0–5. Thus, the score can range from 0 to 35, in increasing severity of symptoms.

A detailed history focusing on the urinary tract should be obtained to exclude other possible causes of symptoms such as prostate cancer or disorders unrelated to the prostate such as urinary tract infection, neurogenic bladder, or urethral stricture.

B. Signs A physical examination, digital rectal examination (DRE), and a focused neurologic examination should be performed on all patients. The size and consistency of the prostate should be noted, but prostate size does not correlate with the severity of symptoms or the degree of obstruction. Benign prostatic hyperplasia usually results in a smooth, firm, elastic enlargement of the prostate.

Induration, if detected, must alert the clinician to the possibility of cancer, and further evaluation is needed (ie, prostate-specific antigen [PSA] testing, transrectal ultrasound, and biopsy). Examination of the lower abdomen should be performed to assess for a distended bladder.

C. Laboratory Findings Urinalysis should be performed to exclude infection or hematuria. A serum PSA is considered optional, yet most clinicians will include it in the initial evaluation, particularly if life expectancy is > 10 years. PSA certainly increases

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Table 23–4. American Urological Association symptom index for benign prostatic hyperplasia.1 Not at All

Less Than One Time in Five

Less Than Half the Time

About Half the Time

More Than Half the Time

Almost Always

1. Over the past month, how often have you had a sensation of not emptying your bladder completely after you finish urinating?

0

1

2

3

4

5

2. Over the past month, how often have you had to urinate again less than 2 hours after you finished urinating?

0

1

2

3

4

5

3. Over the past month, how often have you found you stopped and started again several times when you urinated?

0

1

2

3

4

5

4. Over the past month, how often have you found it difficult to postpone urination?

0

1

2

3

4

5

5. Over the past month, how often have you had a weak urinary stream?

0

1

2

3

4

5

6. Over the past month, how often have you had to push or strain to begin urination?

0

1

2

3

4

5

7. Over the past month, how many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning?

0

1

2

3

4

5

Questions to Be Answered

1 Sum of seven circled numbers equals the symptom score. See text for explanation.

Reproduced, with permission, from Barry MJ et al. The American Urological Association symptom index for benign prostatic hyperplasia.

J Urol. 1992 Nov;148(5):1549–57.

the ability to detect prostate cancer over DRE alone; however, because there is much overlap between levels seen in benign prostatic hyperplasia and prostate cancer, its use remains controversial (see below in the section on screening for prostate cancer).

D. Imaging Upper tract imaging (CT or renal ultrasound) is recommended only in the presence of concomitant urinary tract disease or complications from benign prostatic hyperplasia (ie, hematuria, urinary tract infection, chronic kidney disease, history of stone disease).

E. Cystoscopy Cystoscopy is not recommended to determine the need for treatment but may assist in determining the surgical approach in patients opting for invasive therapy.

F. Additional Tests Cystometrograms and urodynamic profiles should be reserved for patients with suspected neurologic disease or those who have failed prostate surgery. Flow rates, postvoid residual urine determination, and pressure-flow studies are considered optional.

``Differential Diagnosis A history of prior urethral instrumentation, urethritis, or trauma should be elucidated to exclude urethral stricture or bladder neck contracture. Hematuria and pain are

commonly associated with bladder stones. Carcinoma of the prostate may be detected by abnormalities on the DRE or an elevated PSA (see Chapter 39 for Prostate Cancer). A urinary tract infection can mimic the irritative symptoms of benign prostatic hyperplasia and can be readily identified by urinalysis and culture; however, a urinary tract infection can also be a complication of benign prostatic hyperplasia. Carcinoma of the bladder, especially carcinoma in situ, may also present with irritative voiding complaints; however, urinalysis usually shows evidence of hematuria (see Chapter 39 for Bladder Cancer). Patients with a neurogenic bladder may also have many of the same symptoms and signs as those with benign prostatic hyperplasia; however, a history of neurologic disease, stroke, diabetes mellitus, or back injury may be obtained, and diminished perineal or lower extremity sensation or alterations in rectal sphincter tone or the bulbocavernosus reflex might be observed on examination. Simultaneous alterations in bowel function (constipation) might also suggest the possibility of a neurologic disorder.

``Treatment Clinical practice guidelines exist for the evaluation and treatment of patients with benign prostatic hyperplasia (Figure 23–2). Following evaluation as outlined above, patients should be offered various forms of therapy for benign prostatic hyperplasia. Patients are advised to consult with their primary care clinicians and make an educated decision on the basis of the relative efficacy and side effects of the treatment options (Table 23–5).

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Initial evaluation 2

• History • Physical examination and DRE • Urinalysis • Creatinine • PSA (optional)

3

Presence of Refractory retention Any of the following, clearly secondary to BPH: • Recurrent urinary tract infection • Recurrent or persistent gross hematuria • Bladder stones • Kidney disease

Quantitative symptom assessment

Surgery 4

5

Mild

7

Moderate to severe

6

Optional diagnostic tests based on clinician and patient preference

Offer treatment alternatives

8 Watchful waiting

Surgery: TUIP, TURP, open

• Flow rate • Residual urine • Pressure flow

Medical therapy Yes

9

Compatible with obstruction?

No

Option for urethrocystoscopy or sonography if important in planning operative approach Non-BPH problems identified and treated

s Figure 23–2. Benign prostatic hyperplasia decision diagram. DRE, digital rectal examination; PSA, prostate-specific antigen; BPH, benign prostatic hyperplasia; TUIP, transurethral incision of the prostate; TURP, transurethral resection of the prostate.

Table 23–5. Summary of benign prostatic hyperplasia treatment outcomes.1 Outcome

TUIP

TURP

α-Blockers

Watchful Waiting

Finasteride2

Chance for improvement1

78–83%

94–99.8%

75–96%

31–55%

59–86%

54–78%

Degree of symptom improvement (% reduction in symptom score)

73%

79%

85%

Unknown

51%

31%

Morbidity and complications1

2.2–33.3%

7–42.7%

5.2–30.7%

1–5%

2.9–43.3%

13.6–8.8%

Death within 30–90 days

0.2–1.5%

1–4.6%

0.5–3.3%

0.8%

0.8%

0.8%

Total incontinence1

0.1–1.1%

0.3–0.7%

0.7–1.4%

2%

2%

2%

Need for operative treatment for surgical complications1

1.3–2.7%

0.6–14.1%

0.7–10.1%

0

0

0

Erectile dysfunction1

3.9–24.5%

4.7–39.2%

3.3–34.8%

3%

3%

2.5–5.3%

Retrograde ejaculation

6–55%

36–95%

25–99%

0

4–11%

0

Loss of work in days

7–21

21–28

7–21

1

3.5

1.5%

Hospital stay in days

1–3

5–10

3–5

0

0

0

1

1

Open Surgery

90% confidence interval.

Most of the data reviewed for finasteride are derived from three trials that have required an enlarged prostate for entry. The chance of improvement in men with symptoms yet minimally enlarged prostates may be much less, as noted from the VA Cooperative Trial.

TUIP, transurethral incision of the prostate; TURP, transurethral resection of the prostate.

2

Urologic Disorders Patients with mild symptoms (AUA scores 0–7) should be managed by watchful waiting only. Absolute surgical indications are refractory urinary retention (failing at least one attempt at catheter removal), large bladder diverticula, or any of the following sequelae of benign prostatic hyperplasia: recurrent urinary tract infection, recurrent gross hematuria, bladder stones, or chronic kidney disease.

A. Watchful Waiting The risk of progression or complications is uncertain.

However, in men with symptomatic disease, it is clear that progression is not inevitable and that some men undergo spontaneous improvement or resolution of their symptoms.

Retrospective studies on the natural history of benign prostatic hyperplasia are inherently subject to bias, relating in part to patient selection and also to the type and extent of follow-up. Very few prospective studies addressing the natural history have been reported. One small series demonstrated that approximately 10% of symptomatic men may progress to urinary retention while 50% of patients demonstrate marked improvement or resolution of symptoms. A large randomized study compared finasteride with placebo in men with moderate to severely symptomatic disease and enlarged prostates on DRE. Patients in the placebo arm demonstrated a 7% risk of developing urinary retention over 4 years.

Men with moderate or severe symptoms can also be observed if they so choose. The optimal interval for follow-up is not defined, nor are the specific end points for intervention.

B. Medical Therapy 1. `-Blockers—α-Blockers can be classified according to their receptor selectivity as well as their half-life (Table 23–6).

Prazosin is effective; however, it requires dose titration and twice daily dosing. Typical side effects include orthostatic hypotension, dizziness, tiredness, retrograde ejaculation, rhinitis, and headache.

Table 23–6. α-Blockade for benign prostatic hyperplasia.

Agent

Action

Oral Dose

Alfuzosin

α1-Blockade

10 mg daily

Doxazosin

α1-Blockade

1–8 mg daily

Phenoxybenzamine

α1- and α2-Blockade

5–10 mg twice daily

Prazosin

α1-Blockade

1–5 mg twice daily

Silodosin

α1a-Blockade

4 or 8 mg daily

Tadalafil

Phosphodiesterase type 5 inhibitor

5 mg daily

Tamsulosin

α1a-Blockade

0.4 or 0.8 mg daily

Terazosin

α1-Blockade

1–10 mg daily

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Long-acting α-blockers allow for once-a-day dosing, but dose titration is still necessary because side effects similar to those seen with prazosin may occur. Terazosin improves symptoms and in numerous studies is superior to placebo or finasteride. Terazosin is started at a dosage of 1 mg orally daily for 3 days, increased to 2 mg orally daily for 11 days, then 5 mg orally daily. Additional dose escalation to 10 mg orally daily can be performed if necessary.

Doxazosin is started at a dosage of 1 mg orally daily for 7 days, increased to 2 mg orally daily for 7 days, then 4 mg orally daily. Additional dose escalation to 8 mg orally daily can be performed if necessary. Alfuzosin is a long-acting α-blocker; its dose is 10 mg orally once daily and does not require titration. α1a-Receptors are localized to the prostate and bladder neck. Selective blockade of these receptors results in fewer systemic side effects than α-blocker therapy (orthostatic hypotension, dizziness, tiredness, rhinitis, and headache), thus obviating the need for dose titration. The typical dose of tamsulosin is 0.4 mg orally daily taken 30 minutes after a meal. Several randomized, double-blind, placebo-controlled trials have been performed comparing terazosin, doxazosin, tamsulosin, and alfuzosin with placebo. All agents have demonstrated safety and efficacy. However, floppy eye syndrome, a complication of cataract surgery, can occur in patients taking α-blockers and α1a-blockers.

2. 5`-Reductase inhibitors—Finasteride is a 5α-reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone. This drug impacts upon the epithelial component of the prostate, resulting in reduction in size of the gland and improvement in symptoms. Six months of therapy is required for maximum effects on prostate size (20% reduction) and symptomatic improvement.

Several randomized, double-blind, placebo-controlled trials have been performed comparing finasteride with placebo. Efficacy, safety, and durability are well established.

However, symptomatic improvement is seen only in men with enlarged prostates (> 40 mL by ultrasonographic examination). Side effects include decreased libido, decrease in volume of ejaculate, and erectile dysfunction. Serum PSA is reduced by approximately 50% in patients receiving finasteride therapy. Therefore, in order to compare with pre-finasteride levels, the serum PSA of a patient taking finasteride should be doubled.

A report suggests that finasteride therapy may decrease the incidence of urinary retention and the need for operative treatment in men with enlarged prostates and moderate to severe symptoms. The larger the prostate over 40 mL, the greater the relative-risk reduction.

However, optimal identification of appropriate patients for prophylactic therapy remains to be determined.

Dutasteride is a dual 5α-reductase inhibitor that appears to be similar to finasteride in its effectiveness; its dose is 0.5 mg orally daily.

Both finasteride and dutasteride have been shown to be effective chemopreventive agents for prostate cancer in large, randomized clinical trials. The 25% risk reduction was observed in men with both low and high risk for prostate cancer. However, despite the strength of the evidence for 5α-reductase inhibitors in reducing the risk of prostate

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Chapter 23

cancer, an FDA advisory committee recommended against labeling these agents for prostate cancer chemoprevention, citing the potential increased risk of high-grade tumors in these studies, isolated risk reduction in low-grade tumors, and inability to apply the findings to the general population. Moreover, the FDA has included the increased risk of being diagnosed with high-grade prostate cancer in the labels of all 5α-reductase inhibitors.

3. Phosphodiesterase-5 inhibitor—The FDA approved the use of tadalafil to treat the signs and symptoms of benign prostatic hyperplasia in 2011; it is also approved for use in men with both urinary symptoms and erectile dysfunction. The data from two randomized, doubleblind, placebo-controlled trials demonstrated significant improve­ments in standardized measurements of urinary function between 2 and 4 weeks after initiating treatment at 5 mg, with minimal adverse effects.

4. Combination therapy—The four-arm Veterans Administration Cooperative Trial compared placebo, finasteride alone, terazosin alone, and combination of finasteride and terazosin. Over 1200 patients participated, and significant decreases in symptom scores and increases in urinary flow rates were seen only in the arms containing terazosin.

However, enlarged prostates were not an entry criterion; in fact, prostate size in this study was much smaller than in previous controlled trials using finasteride (32 versus 52 mL). Other randomized, placebo-controlled trials comparing finasteride with placebo in men with lower urinary tract symptoms and large prostates showed finasteride to be beneficial for reducing symptoms, increasing urinary flow rate, and reducing the risk of complications due to benign prostatic hyperplasia as well as reducing the number of men who required surgery for benign prostatic hyperplasia. The Medical Therapy of Prostatic Symptoms (MTOPs) trial is a large, randomized, placebo-controlled trial comparing finasteride, doxazosin, the combination of the two, and placebo in 3047 men observed for a mean of 4.5 years.

Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.

Combination therapy had the risks of additional side effects and the cost of two medications.

5. Phytotherapy—Phytotherapy is the use of plants or plant extracts for medicinal purposes. Its use in benign prostatic hyperplasia has been popularized by patientdriven enthusiasm. Several plant extracts have been popularized, including the saw palmetto berry, the bark of Pygeum africanum, the roots of Echinacea purpurea and Hypoxis rooperi, pollen extract, and the leaves of the trembling poplar. The mechanisms of action of these agents are unknown. A 2006 prospective, randomized, double-blind, placebo-controlled trial revealed no improvement in symptoms, urinary flow rate, or quality of life for men with benign prostatic hyperplasia with saw palmetto treatment compared with placebo.

C. Conventional Surgical Therapy 1. Transurethral resection of the prostate (TURP)— Ninety-five percent of simple prostatectomies can be performed endoscopically (TURP). Most of these procedures are performed under a spinal anesthetic and require a 1- to 2-day hospital stay. Symptom scores and flow rate improvement are superior following TURP relative to any minimally invasive therapy; however, the length of the hospital stay is greater. Much controversy revolves around possible higher rates of morbidity and mortality associated with TURP in comparison with open surgery, but the higher rates observed in one study probably related to more significant comorbidities in the TURP patients compared with the patients who received open surgical treatment. Several other studies could not confirm the difference in mortality when controlling for age and comorbidities. The risks of TURP include retrograde ejaculation (75%), erectile dysfunction (5–10%), and urinary incontinence (< 1%). Complications include bleeding, urethral stricture or bladder neck contracture, perforation of the prostate capsule with extravasation, and, if severe, transurethral resection syndrome, a hypervolemic, hyponatremic state resulting from absorption of the hypotonic irrigating solution. Clinical manifestations of the syndrome include nausea, vomiting, confusion, hypertension, bradycardia, and visual disturbances. The risk of transurethral resection syndrome increases with resection times over 90 minutes. Treatment includes diuresis and, in severe cases, hypertonic saline administration (see Hyponatremia, Chapter 21).

2. Transurethral incision of the prostate (TUIP)—Men with moderate to severe symptoms and small prostates often have posterior commissure hyperplasia or an “elevated bladder neck.” These patients will often benefit from incision of the prostate. The procedure is more rapid and less morbid than TURP. Outcomes in well-selected patients are comparable, though a lower rate of retrograde ejaculation has been reported (25%).

3. Open simple prostatectomy—When the prostate is too large to remove endoscopically, open enucleation is necessary. What size is “too large” depends upon the surgeon's experience with TURP. Glands over 100 g are usually considered for open enucleation. In addition to size, other relative indications for open prostatectomy include concomitant bladder diverticulum or bladder stone and whether dorsal lithotomy positioning is or is not possible.

Open prostatectomies can be performed with either a suprapubic or retropubic approach. Simple suprapubic prostatectomy is performed transvesically and is the operation of choice if there is concomitant bladder pathology.

After the adenoma is removed, both a urethral and a suprapubic catheter are inserted prior to closure.

In simple retropubic prostatectomy, the bladder is not entered but rather a transverse incision is made in the surgical capsule of the prostate and the adenoma is enucleated as described above; only a urethral catheter is needed at the end of the case.

Urologic Disorders D. Minimally Invasive Therapy 1. Laser therapy—Several coagulation necrosis techniques have been utilized. Transurethral laser-induced prostatectomy (TULIP) is performed under transrectal ultrasound guidance. The instrument is placed in the urethra and transrectal ultrasound is used to direct the device as it is slowly pulled from the bladder neck to the apex. The depth of treatment is monitored with ultrasound.

Most urologists prefer to use visually directed laser techniques. Visual coagulative necrosis is performed under cystoscopic control, and the laser fiber is pulled through the prostate at several designated areas depending upon the size and configuration of the gland. Four-quadrant and sextant approaches have been described for lateral lobes, with additional treatments directed at enlarged median lobes. Coagulative techniques do not create an immediate visual defect in the prostatic urethra—tissue is sloughed over the course of several weeks up to 3 months following the procedure.

Visual contact ablative techniques take longer in the operating room because the fiber is placed in direct contact with the prostate tissue, which is vaporized.

Photovaporization of the prostate (PVP), an alternative laser technique, uses a high-power KTP laser. An immediate defect is obtained in the prostatic urethra, similar to that seen during TURP. Interstitial laser therapy places fibers directly into the prostate, usually under cystoscopic control. Irritative voiding symptoms may be less in these patients as the urethral mucosa is spared and prostate tissue is resorbed by the body rather than sloughed.

Advantages to laser surgery include minimal blood loss, rare occurrence of transurethral resection syndrome, the ability to treat patients while on anticoagulation therapy, and outpatient surgery. Disadvantages are the lack of tissue for pathologic examination, the longer postoperative catheterization time, the more frequent irritative voiding complaints, and the expense of laser fibers and generators.

Large multicenter, randomized studies with long-term follow-up are needed in comparing laser prostate surgery with TURP and other forms of minimally invasive surgery.

2. Transurethral needle ablation of the prostate (TUNA)—This procedure uses a specially designed urethral catheter that is passed into the urethra. Interstitial radiofrequency needles are then deployed from the tip of the catheter, piercing the mucosa of the prostatic urethra.

Radiofrequencies are then used to heat the tissue, resulting in coagulative necrosis. Bladder neck and median lobe enlargement are not well treated by TUNA. Subjective and

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objective improvement in voiding occurs. In randomized trials comparing TUNA to TURP, similar improvement was seen when comparing life scores, peak urinary flow rates, and postvoid residual urine.

3. Transurethral electrovaporization of the prostate— This technique uses the standard resectoscope. High current densities result in heat vaporization of tissue, creating a cavity in the prostatic urethra. Because the device requires slower sweeping speeds over the prostatic urethra and the depth of vaporization is approximately one-third of a standard loop, this procedure usually takes longer than a standard TURP. Long-term comparative data are needed.

4. Hyperthermia—Microwave hyperthermia is most commonly delivered with a transurethral catheter. Some devices cool the urethral mucosa to decrease the risk of injury.

However, if temperatures do not go above 45 °C, cooling is unnecessary. Symptom score and flow rate improvement are obtained, but (as with laser surgery) large randomized studies with long-term follow-up are needed to assess durability and cost-effectiveness.

``When to Refer • Progression to urinary retention.

• Patient dissatisfaction with medical therapy.

• Need for surgical intervention or further evaluation (cystoscopy).

Andriole GL et al; REDUCE Study Group. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010 Apr 1;362(13):1192–202. [PMID: 20357281] Kaplan SA. Update on the American urological association guidelines for the treatment of benign prostatic hyperplasia.

Rev Urol. 2006;8(Suppl 4):S10–7. [PMID: 17215996] McConnell JD et al; Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003 Dec 18;349(25):2387–98. [PMID: 14681504] McVary KT et al. American Urological Association Guideline: Management of Benign Prostatic Hyperplasia (BPH). http:// www.auanet.org/content/clinical-practice-guidelines/ clinical-­guidelines.cfm?sub=bph Roehrborn CG. BPH progression: concept and key learning from MTOPS, ALTESS, COMBAT, and ALF-ONCE. BJU Int. 2008 Mar;101(Suppl 3):17–21. [PMID: 18307681] Selius BA et al. Urinary retention in adults: diagnosis and initial management. Am Fam Physician. 2008 Mar 1;77(5):643–50.

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