text:
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.
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).
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.
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.
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 its utility.
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).
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 obtained after initial negative evaluation, and cystoscopy and upper tract imaging after a year.
In the absence of infection or other benign etiology, hematuria (either gross or microscopic) requires evaluation.
Daher Ede F et al. Renal tuberculosis in the modern era. Am J Trop Med Hyg. 2013 Jan;88(1):54–64. [PMID: 23303798]
Davis R et al. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline. J Urol. 2012 Dec;188(6 Suppl):2473–81. [PMID: 23098784]
Dick-Biascoechea MA et al. Asymptomatic microscopic hematuria. Curr Opin Obstet Gynecol. 2012 Oct;24(5):324–30. [PMID: 22954764]
Margulis V et al. Assessment of hematuria. Med Clin North Am. 2011 Jan;95(1):153–9. [PMID: 21095418]
Irritative voiding symptoms.
Patient usually afebrile.
Positive urine culture; blood cultures may also be positive.
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.
Irritative voiding symptoms (frequency, urgency, dysuria) and suprapubic discomfort are common. Women may 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.
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.
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.
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.
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.
Uncomplicated cystitis in women can be treated with short-term antimicrobial therapy, which consists of single-dose therapy or 1–9 days of therapy. Cephalexin, nitrofurantoin, and fluoroquinolones 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.
Table 23–1. Empiric therapy for urinary tract infections.
Infections typically respond rapidly to therapy, and failure to respond suggests resistance to the selected drug or anatomic abnormalities requiring further investigation.
• Suspicion or radiographic evidence of anatomic abnormality.
• Evidence of urolithiasis.
• Recurrent cystitis due to bacterial persistence.
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 Diseases Society of American and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103–20. [PMID: 21292654]
Marschall J et al. Antibiotic prophylaxis for urinary tract infections after removal of urinary catheter: meta-analysis. BMJ. 2013 Jun 11;346:f3147. Erratum in: BMJ. 2013;347:f5325. [PMID: 23757735]
Shepherd AK et al. Management of urinary tract infections in the era of increasing antimicrobial resistance. Med Clin North Am. 2013 Jul;97(4):737–57. [PMID: 23809723]
Tambyah PA et al. Catheter-associated urinary tract infection. Curr Opin Infect Dis. 2012 Aug;25(4):365–70. [PMID: 22691687]
Torpy JM et al. JAMA patient page. Urinary tract infection. JAMA. 2012 May 2;307(17):1877. [PMID: 22550203]
Flank pain.
Irritative voiding symptoms.
Positive urine culture.
Acute pyelonephritis is an infectious inflammatory disease involving the kidney parenchyma and renal pelvis. Gram-negative 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.
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.
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 organism, and blood culture may also be positive.
In complicated pyelonephritis, renal ultrasound may show hydronephrosis from a stone or other source of obstruction.
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 biochemical 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.
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.
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, a quinolone 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. However, a shorter 7-day course may be just as effective with fewer side effects, such as mucosal candidiasis. Follow-up urine cultures are mandatory following the completion of treatment.
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.
• Evidence of complicating factors (urolithiasis, obstruction).
• Absence of clinical improvement in 48 hours.
• Severe infections or complicating factors, evidence of sepsis or need for parenteral antibiotics.
• Need for radiographic imaging or drainage of urinary tract obstruction.
Colgan R et al. Diagnosis and treatment of acute uncomplicated cystitis. Am Fam Physician. 2011 Oct 1;84(7):771–6. [PMID: 22010614]
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]
Hooton TM et al. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med. 2013 Nov 14;369(20):1883–91. [PMID: 24224622]
Meng MV. Infection of the upper urinary tract. In: Wessells H (editor). Urological Emergencies: A Practical Guide. New York: Humana Press, 2012.
Sandberg T et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012 Aug 4;380(9840):484–90. [PMID: 22726802]
Irritative voiding symptoms.
Perineal or suprapubic pain; exquisite tenderness common on rectal examination.
Positive urine culture.
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.
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.
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).
Table 23–2. Clinical characteristics of prostatitis and prostatodynia syndromes.
Acute pyelonephritis or acute epididymitis should be distinguishable by the location of pain as well as by physical examination. Acute diverticulitis is occasionally confused 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.
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.
With effective treatment, chronic bacterial prostatitis is rare.
• Evidence of urinary retention.
• Evidence of chronic prostatitis.
• Signs of sepsis.
• Need for surgical drainage of bladder or prostatic abscess.
Campeggi A et al. Acute bacterial prostatitis after transrectal ultrasound-guided prostate biopsy: epidemiological, bacteria and treatment patterns from a 4-year prospective study. Int J Urol. 2014 Feb;21(2):152–5. [PMID: 23906113]
Dickson G. Prostatitis—diagnosis and treatment. Aust Fam Physician. 2013 Apr;42(4):216–9. [PMID: 23550248]
Nagy V et al. Acute bacterial prostatitis in humans: current microbiological spectrum, sensitivity to antibiotics and clinical findings. Urol Int. 2012;89(4):445–50. [PMID: 23095643]
Wagenlehner FM et al. Bacterial prostatitis. World J Urol. 2013 Aug;31(4):711–6. [PMID: 23519458]
Yoon BI et al. Clinical courses following acute bacterial prostatitis. Prostate Int. 2013;1(2):89–93. [PMID: 24223408]
Irritative voiding symptoms.
Perineal or suprapubic discomfort, often dull and poorly localized.
Positive expressed prostatic secretions and culture.
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.
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.
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.
Imaging tests are not necessary, although pelvic radiographs or transrectal ultrasound may demonstrate prostatic calculi.
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.
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 quinolones, cephalexin, erythromycin, and carbenicillin. 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.
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.
• Persistent symptoms.
• Consideration of enrollment in clinical trials.
Perletti G et al. Antimicrobial therapy for chronic bacterial prostatitis. Cochrane Database Syst Rev. 2013 Aug 12;8:CD009071. [PMID: 23934982]
Irritative voiding symptoms.
Perineal or suprapubic discomfort, similar to that of chronic bacterial prostatitis.
Positive expressed prostatic secretions, but negative culture.
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.
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) (www.prostatitisclinic.com/graphics/questionnaire2.pdf) has been validated to quantify symptoms of chronic nonbacterial prostatitis or chronic pelvic pain syndrome.
Increased numbers of leukocytes are seen on expressed prostatic secretions, but all cultures are negative.
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, bladder cancer must be excluded. Urinary cytologic examination and cystoscopy are warranted.
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.
Annoying, recurrent symptoms are common, but serious sequelae have not been identified.
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]
Cohen JM et al. Therapeutic intervention for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS): a systematic review and meta-analysis. PLoS One. 2012;7(8):e41941. [PMID: 22870266]
Chung SD et al. Association between chronic prostatitis/chronic pelvic pain syndrome and anxiety disorder: a population-based study. PLoS One. 2013 May 15;8(5):e64630. [PMID: 23691256]
Giannantoni A et al. The efficacy and safety of duloxetine in a multidrug regimen for chronic prostatitis/chronic pelvic pain syndrome. Urology. 2014 Feb;83(2):400–5. [PMID: 24231216]
Ismail M et al. Contemporary treatment options for chronic prostatitis/chronic pelvic pain syndrome. Drugs Today (Barc). 2013 Jul;49(7):457–62. [PMID: 23914354]
Lilienthal C. Chronic, non-bacterial prostatitis. Aust Fam Physician. 2013 Jun;42(6):362. [PMID: 23936942]
Nickel JC. Understanding chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). World J Urol. 2013 Aug;31(4):709–10. [PMID: 23812415]
Pontari M et al. New developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome. Curr Opin Urol. 2013 Nov;23(6):565–9. [PMID: 24080807]
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, since the prostate is actually normal.
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.
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 alpha-blockers or anticholinergics.
Normal urinalysis will distinguish it from acute infectious processes. Examination of expressed prostatic secretions will distinguish nonbacterial prostatitis from other prostatitis syndromes (Table 23–2).
Bladder neck and urethral spasms can be treated by alpha-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 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]
Chung SD et al. Association between chronic prostatitis/chronic pelvic pain syndrome and anxiety disorder: a population-based study. PLoS One. 2013 May 15;8(5):e64630. [PMID: 23691256]
Giannantoni A et al. The efficacy and safety of duloxetine in a multidrug regimen for chronic prostatitis/chronic pelvic pain syndrome. Urology. 2014 Feb;83(2):400–5. [PMID: 24231216]
Ismail M et al. Contemporary treatment options for chronic prostatitis/chronic pelvic pain syndrome. Drugs Today (Barc). 2013 Jul;49(7):457–62. [PMID: 23914354]
Nickel JC. Understanding chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). World J Urol. 2013 Aug;31(4):709–10. [PMID: 23812415]
Pontari M et al. New developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome. Curr Opin Urol. 2013 Nov;23(6):565–9. [PMID: 24080807]
Irritative voiding symptoms.
Painful enlargement of epididymis.
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 trachomatis 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 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 may appear as one enlarged, tender mass. The prostate may be tender on rectal examination.
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.
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.
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.
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.
Prompt treatment usually results in a favorable outcome. Delayed or inadequate treatment may result in epididymo-orchitis, decreased fertility, or abscess formation.
• Persistent symptoms and infection despite antibiotic therapy.
• Signs of sepsis or abscess formation.
Pilatz A et al. Acute epididymitis in ultrasound: results of a prospective study with baseline and follow-up investigations in 134 patients. Eur J Radiol. 2013 Dec;82(12):e762–8. [PMID: 24094645]
Srinath H. Acute scrotal pain. Aust Fam Physician. 2013 Nov;42(11):790–2. [PMID: 24217099]
Yagil Y et al. Role of Doppler ultrasonography in the triage of acute scrotum in the emergency department. J Ultrasound Med. 2010 Jan;29(1):11–21. [PMID: 20040771]
Pain with a full bladder or urinary urgency.
Submucosal petechiae or ulcers on cystoscopic examination.
Diagnosis of exclusion.
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 of these 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.
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.
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.
The bladder is distended with fluid (hydrodistention) to detect glomerulations (submucosal hemorrhage), which 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.
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.
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 first-line 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.
Persistent and bothersome symptoms in the absence of identifiable cause.
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]
Matsuoka PK et al. Intravesical treatment of painful bladder syndrome: a systematic review and meta-analysis. Int Urogynecol J. 2012 Sep;23(9):1147–53. [PMID: 22569686]
Quillin RB et al. Management of interstitial cystitis/bladder pain syndrome: a urology perspective. Urol Clin North Am. 2012 Aug;39(3):389–96. [PMID: 22877722]
Quillin RB et al. Practical use of the new American Urological Association interstitial cystitis guidelines. Curr Urol Rep. 2012 Oct;13(5):394–401. [PMID: 22828913]
Torpy JM et al. JAMA patient page. Interstitial cystitis. JAMA. 2012 May 23;307(20):2211. [PMID: 22618932]
Severe flank pain.
Nausea and vomiting.
Identification on noncontrast CT or ultrasonography.
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. While men are more frequently affected by urolithiasis than women, with a ratio of 2.5:1, the incidence in women appears to be rising over time. Initial presentation predominates between the third and fifth decade.
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 on plain abdominal radiographs. Uric acid stones frequently are composed of a combination of uric acid and calcium oxalate and thus are frequently radiopaque, though pure uric acid stones are radiolucent. Cystine stones frequently have a smooth-edged ground-glass appearance and are radiolucent.
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 with sedentary lifestyles have a higher incidence of stones and increasing evidence demonstrates that urinary stone disease may be a precursor to subsequent cardiovascular disease.
High protein and salt intake as well as inadequate hydration appear to be the most important factors in the development of urinary stones.
Genetic factors may contribute to urinary stone formation. While approximately 50% of calcium-based stones are thought to have a heritable component, other stone types are better characterized genetically. For example, cystinuria is an autosomal recessive disorder. Homozygous individuals have markedly increased excretion of cystine and frequently have numerous recurrent episodes of urinary stones. Distal renal tubular acidosis may be transmitted as a hereditary trait, and urolithiasis occurs in up to 75% of affected patients.
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, unremitting, 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 groin. If the stone becomes lodged at the uretero-vesicular 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.
In patients with either symptomatic or asymptomatic kidney stones, urinalysis usually reveals microscopic or gross hematuria (~90%). However, the absence of microhematuria does not exclude urinary stones. Urinary pH is a valuable clue to the cause of the possible stone. Normal urine pH is 5.8–5.9. Numerous dipstick measurements are valuable in the complete work-up of a patient in whom urinary stones are suspected. Persistent urinary pH below 5.5 is suggestive of uric acid or cystine stones. In contrast, a persistent urinary pH > 7.2 is suggestive of a struvite infection stone or calcium phosphate stone (when above 7.5). Patients with calcium oxalate–based stones typically have a urinary pH between 5.5 and 6.8.
Patients should strain their urine through cheesecloth or a urine strainer during a symptomatic episode. This facilitates stone analysis on recovered stones. Controversy exists in deciding which patients need a thorough metabolic evaluation for stone disease. Patients with uncomplicated first-time stones should all undergo dietary counseling as outlined below and can be offered metabolic evaluation.
Complete metabolic 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/d 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), calcium, uric acid, electrolytes (including bicarbonate), and creatinine and BUN should also be obtained. Table 23–3 demonstrates the diagnostic criteria for the hypercalciuric states.
Table 23–3. Diagnostic criteria of different types of hypercalciuria.
A plain abdominal radiograph (KUB, kidneys-ureters-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 given its increased sensitivity and specificity over other tests. CT scans should be obtained in the prone position to help differentiate distal ureterovesicular stones from those that have already passed into the urinary bladder. Repeated CT scans should be avoided due to the substantial radiation exposure to these patients with recurrent stones. 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 protease inhibitors (classically indinavir).
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. Metabolic evaluation often identifies a modifiable risk factor that can reduce stone recurrence rates. If no medical treatment is provided after surgical stone removal, stones will generally recur in 50% of patients within 5 years. Some stone types (eg, uric acid, cystine) are more prone to rapid recurrence than others. 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 (normal average voided volume is 1.6 L/d).
Sodium intake should be restricted to keep urinary sodium levels < 150 mEq/d. Increased sodium intake will increase renal sodium and calcium excretion, increase urinary 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.
Excessive 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 and Table 23–3) benefit from a low calcium diet.
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 one 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. Inappropriate use may result in a negative calcium balance and a secondary parathyroid stimulation and consequent bone reabsorption. However, there is generally no enhanced decline in bone density with long-term use. 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 long-term 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, although recurrent urinary stones can still occur in 10% of patients after parathyroidectomy. Medical management invariably fails.
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 an 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 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 often 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 in the gut, 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, either by ingesting milk products or taking calcium carbonate supplements (250–500 mg). This helps to bind dietary oxalate in the gut and oxalate movement into the kidneys. 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 condition that results in a metabolic acidosis. The metabolic acidosis enhances citrate transport into the proximal tubular cells where it is consumed by the citric acid cycle in their mitochondria, resulting in hypocitraturia (< 450 mg/24h). Hypocitraturia is frequently associated with 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. A typical dose is 60 mEq total daily intake, divided either into three times daily as tablets or twice daily as the crystal formulations dissolved in water (it is also available as a solution). Alternatively, oral lemonade has been shown to increase urinary citrate by about 150 mg/24h.
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, can effectively dissolve large calculi at a rate of 1 cm per month, and effectively prevents future uric acid stone formation. Urinary alkalinization with potassium citrate or an equivalent agent is the key to stone dissolution and prophylaxis. The goal is a urinary pH > 6.2 and < 6.5 (to avoid calcium phosphate precipitation). Other precipitating 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.
Struvite stones are radiodense magnesium-ammonium-phosphate stones. They are most common in women with recurrent urinary tract infections with urease-producing organisms, including Proteus, Pseudomonas, Providencia and, less commonly, Klebsiella, Staphylococcus, and Mycoplasma (but not E coli). They rarely present as ureteral stones with colic without prior upper tract endourologicintervention. Frequently, a struvite stone is discovered as a large staghorn calculus forming a cast of the renal collecting system. Urinary pH is high, routinely above 7.2. Struvite stones are relatively soft and amenable to percutaneous removal. Appropriate perioperative antibiotics are required. They can recur rapidly, and efforts should be taken to render the patient stone-free. Acetohydroxamic acid is an effective urease inhibitor that can dissolve and prevent struvite stones, but it is poorly tolerated by most patients because of gastrointestinal side effects.
Cystine stones are a result of abnormal excretion of cystine excretion. 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 (alpha-mercaptoproprionylglycine) or penicillamine. There are no known inhibitors of cystine calculi.
In the acute setting, forced intravenous fluids will not push stones down the ureter. Forced diuresis can be counterproductive and exacerbate the pain; instead, a euvolemic state should be achieved. Signs of infection, including associated fever, tachycardia, or elevated white blood cell count may indicate a urinary tract infection behind the obstructing stone. Any obstructing stone with associated infection is a medical emergency requiring prompt drainage by a ureteral catheter or a percutaneous nephrostomy tube. Antibiotics alone are inadequate unless the obstruction is drained.
Impediment to urine flow by ureteral stones usually occurs at three sites: the ureteropelvic junction, the crossing of the ureter over the iliac artery, or the ureterovesicular junction. Prediction of spontaneous stone passage is difficult. Stones < 5–6 mm in diameter on a plain abdominal radiograph usually pass spontaneously. Medical expulsive therapy with alpha-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 (such as prednisone 10 mg orally daily for 3–5 days) dramatically increases the rate of spontaneous stone passage. Medical expulsive therapy with appropriate pain medications is appropriate for the first few weeks. If the stone fails to pass within 4 weeks, the patient has fever, intolerable pain or persistent nausea or vomiting, or the patient must return to work or anticipates travel, then therapeutic intervention is indicated.
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. Complications during endoscopic retrieval increase if medical expulsive therapy has been attempted for > 6 weeks.
In situ SWL utilizes an external energy source focused on the stone with the aid of fluoroscopy or ultrasonography. SWL can be performed under anesthesia as an outpatient procedure and results in a high rate of stone fragmentation. Most stone fragments then pass uneventfully within 2 weeks, but those that have not passed within 6 weeks are unlikely to do so without intervention. Decreased SWL success rates are associated with lower pole and distal stone location, as well as larger stone burden. Women of childbearing age with a stone in the lower ureter are best not treated with SWL because its impact on the ovary is unknown.
Proximal and midureteral stones—those above the inferior margin of the sacroiliac joint—as well as intrarenal stones can be treated with SWL or ureteroscopy. SWL is delivered directly to the stone in situ. To help ensure adequate urinary 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. In rare instances, ureteroscopic extraction will be required.
Patients with renal calculi but without pain, urinary tract infection, or obstruction may not warrant surgical treatment. If surveillance is elected, 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 or ureteroscopic extraction. Calculi located in the inferior calix and 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 directly into the kidney. In this fashion, larger and more complex renal stones can be inspected, fragmented, and removed. Perioperative antibiotic coverage for any stone procedure should be given, ideally based on preoperative urine culture.
• Evidence of urinary obstruction.
• Urinary stone with associated flank pain.
• Anatomic abnormalities or solitary kidney.
• Concomitant pyelonephritis or recurrent infection.
• Intractable nausea and vomiting or pain.
• Obstructing stone with signs of infection.
Bagga HS et al. New insights into the pathogenesis of renal calculi. Urol Clin North Am. 2013 Feb;40(1):1–12. [PMID: 23177630]
Fink HA et al. Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline. Ann Intern Med. 2013 Apr 2;158(7):535–43. [PMID: 23546565]
Goldfarb DS et al. Metabolic evaluation of first-time and recurrent stone formers. Urol Clin North Am. 2013 Feb;40(1):13–20. [PMID: 23177631]
Matlaga BR et al. Treatment of ureteral and renal stones: a systematic review and meta-analysis of randomized, controlled trials. J Urol. 2012 Jul;188(1):130–7. [PMID: 22591962]
Punnoose AR et al. JAMA patient page. Kidney stones. JAMA. 2012 Jun 20;307(23):2557. [PMID: 22797461]
Erectile dysfunction can have organic and psychogenic etiologies, and the two frequently overlap.
Organic erectile dysfunction may be an early sign of cardiovascular disease and requires evaluation.
Peyronie disease is a common fibrotic disorder of the corpora cavernosa of the penis that causes pain, penile deformity, and sexual dysfunction.
Erectile dysfunction is the consistent inability to attain or maintain a sufficiently rigid penile erection for sexual performance. More than half of men aged 40–70 years experience erectile dysfunction and its incidence is age-related. 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 exceeding systolic blood pressure. Nitric oxide is a key 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. A loss of libido may indicate androgen deficiency. Loss of erections may result from arterial, venous, neurogenic, hormonal, or psychogenic causes. Concurrent medical problems may damage one or more of the mechanisms. Endothelial dysfunction is 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 atherosclerotic cardiovascular disease. Many medications, especially antihypertensive, antidepressant, and opioid 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. Peyronie disease develops in approximately 5–10% of men older than 50 years. While 10% of men improve spontaneously, 50% will stabilize and the remainder will progress if left untreated. Penile deformity can impair normal sexual function and impact self-esteem. The cause of Peyronie disease is not fully understood.
Priapism is the occurrence of penile erection unrelated to sexual stimulation lasting longer than 4 hours that potentially causes ischemic injury of the corpora cavernosa and erectile dysfunction (low flow or "ischemic" priapism). Ischemic priapism may be caused by red blood cell dyscrasias, drug use, and any of the treatments for erectile dysfunction.
Anejaculation is the loss of seminal emission and may result from androgen deficiency by decreasing prostate and seminal vesicle secretions, or by 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, due to transurethral resection of the prostate, pelvic radiation, sympathetic denervation, or treatment with alpha-blockers. Premature ejaculation is the persistent or recurrent ejaculation with minimal stimulation before a person desires (associated with distress). It may be primary or secondary to erectile dysfunction. The former is common and may be treated with behavioral modification, sexual health counseling, local anesthetic agents, and systemic medications. The latter will often correct with treatment of erectile dysfunction.
Erectile dysfunction should be distinguished from problems of penile deformity, ejaculation, libido, and orgasm. The severity of erectile dysfunction (maintaining vs attaining; chronic, occasional, or situational) and its timing should be noted. The history should include inquiries about dyslipidemia, hypertension, depression, neurologic disease, diabetes mellitus, chronic kidney disease, endocrine disorders, and cardiac or peripheral vascular disease. Pelvic trauma, surgery, or irradiation puts patients at increased risk for erectile dysfunction. A history of penile deformity or curvature that prevents normal intercourse indicates Peyronie disease, which may complicate treatment. The history should clarify the severity of curvature, loss of penile length, and other problems that may prevent normal, painless sexual intercourse. The ability to attain but not maintain an erection may be the first sign of endothelial dysfunction and further cardiovascular risk stratification is warranted. The gradual loss of erections over time is more suggestive of an organic cause. Erectile dysfunction may immediately follow pelvic surgery or trauma. Medication use should be reviewed, since 25% of all cases of sexual dysfunction may be drug related. Alcohol, tobacco, and recreational drug use are associated with an increased risk of sexual dysfunction.
During the physical examination, vital signs and secondary sexual characteristics should be assessed. Thorough cardiovascular examination should be performed with auscultation of the heart as well as palpation and quantification of lower extremity arterial pulsations. Motor and sensory examination should be performed. 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.
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 hypothalamic-pituitary dysfunction from primary testicular failure.
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 and decreased quality of life. 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) 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 of men suffering from sexual dysfunction should be patient centered and goal oriented. Men who have a significant psychogenic component to their erectile dysfunction will benefit from behaviorally oriented sex therapy or counseling. Lifestyle modification and reduction of cardiovascular risk factors are important components to any treatment plan. This should potentially include smoking cessation; reduction of alcohol intake; diet; exercise; and close monitoring and treatment of diabetes, dyslipidemia, and hypertension.
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 (eg, erythrocytosis). Restoration of normal testosterone levels may improve libido and effectiveness of oral erectile medications.
1. Oral agents—Sildenafil, vardenafil, tadalafil, and avanafil inhibit phosphodiesterase-5 (PDE-5), preventing the degradation of cGMP, thereby sustaining inflow of blood into the erect penis. These drugs are similarly effective, but 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. When taken with nitrate medications, there may be exaggerated cardiac preload reduction and hypotension; therefore, these drugs are contraindicated in patients taking nitroglycerin or nitrates. 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.
The combination of PDE-5 inhibitors and alpha-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 hypotension or syncope. In select men, combined treatment with PDE-5 inhibitors and testosterone replacement may be warranted, since adequate androgen levels appear to support normal penile structure and function.
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 with erectile dysfunction. Injections are performed using a tuberculin-type 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 and nerve 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 ischemia 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 arteriovenous shunts may be performed to allow detumescence.
The vacuum erection device creates a vacuum chamber around the penis and draws blood into the corpora cavernosa. Once adequate tumescence is 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 effective, regardless of the cause of erectile dysfunction; however, the devices are cumbersome and may cause penile discomfort leading to a high rate of disuse. Serious complications are rare.
Penile prostheses are implanted directly into the paired corporal bodies. Penile prostheses may be semi-rigid (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 are very high due to enhanced spontaneity and reliability of erections.
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.
A wide range of medical and surgical treatments have been used to treat the disorder. No oral therapies for Peyronie disease are approved by the FDA; however, evidence from randomized controlled trials supports the use of pentoxifylline and coenzyme Q10. The intraplaque injection of verapamil or interferon improves penile deformity in some patients. Clostridial collagenase is the only FDA-approved medication for the treatment of Peyronie disease. Collagenase is administered to the central portion of the penile plaque by needle injection; it causes enzymatic digestion of the lesion with subsequent correction of penile curvature. 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.
• Patients with inadequate response to oral medications, who are unable to tolerate side effects or who are dissatisfied with their current treatment.
• Patients with Peyronie disease or other penile deformity.
• Patients with a history of pelvic or perineal trauma, surgery, or radiation.
• 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]
Gandaglia G et al. A systematic review of the association between erectile dysfunction and cardiovascular disease. Eur Urol. 2014 May;65(5):968–78. [PMID: 24011423]
McCabe MP et al. A systematic review of the psychosocial outcomes associated with erectile dysfunction: does the impact of erectile dysfunction extend beyond a man's inability to have sex? J Sex Med. 2014 Feb;11(2):347–63. [PMID: 24251371]
Porst H. An overview of pharmacotherapy in premature ejaculation. J Sex Med. 2011 Oct;8(Suppl 4):335–41. [PMID: 21967395]
The male partner contributes to 50% of infertility 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 important for diagnosis and treatment.
Abnormal semen quality may indicate poor health or increased risk of certain health conditions.
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-half of cases result from male factors; therefore, evaluation of both partners is critical. 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 health events and gonadotoxic exposures from the preceding 3 months. Male infertility is associated with a higher risk for the later development of testicular germ cell cancer; thus, these men should be counseled appropriately and taught testicular self-examination.
Figure 23–1. Couple based approach to evaluation and treatment of male factor infertility. FNA, fine-needle aspiration.
The history should include prior testicular insults (torsion, cryptorchidism, trauma), infections (mumps orchitis, epididymitis, sexually transmitted infections), environmental factors (excessive heat, radiation, chemotherapy, prolonged pesticide exposure), medications (testosterone, finasteride, cimetidine, selective serotonin reuptake inhibitors, and spironolactone may affect spermatogenesis; phenytoin may lower FSH; sulfasalazine and nitrofurantoin affect sperm motility; tamsulosin causes retrograde ejaculation), and other drugs (alcohol, tobacco, marijuana). Sexual function, frequency and timing of intercourse, use of lubricants, and each partner's previous fertility are important. Loss of libido, headaches, visual disturbances, or galactorrhea may indicate a pituitary tumor. The past medical or surgical history may reveal chronic disease, including thyroid or liver disease (abnormalities of spermatogenesis), diabetes mellitus (retrograde or anejaculation), or radical pelvic or retroperitoneal surgery (absent seminal emission secondary to sympathetic nerve injury).
Physical examination should pay particular attention to features of hypogonadism: underdeveloped sexual characteristics, diminished male pattern hair distribution (axillary, body, facial, pubic), body habitus, gynecomastia, and obesity. The scrotal contents should be carefully evaluated. Testicular size should be noted (normal size approximately 4.5 × 2.5 cm, volume 18 mL). Varicoceles 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).
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, congenital bilateral absence of the vasa deferentia, 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 the history and physical examination suggest an endocrinologic origin. Initial testing should include serum testosterone and FSH. Specific abnormalities in these hormones should prompt additional testing, including serum LH, prolactin, and estradiol levels. 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. Elevation of estradiol may impair normal gonadotropin production and impact normal spermatogenesis.
Men with sperm concentrations < 10 million/mL should consider 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.
Scrotal ultrasound can aid in characterizing the testes and may detect a subclinical varicocele. 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 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. Men with unilateral absence of the vas deferens should have abdominal ultrasound or CT to exclude absence of the ipsilateral kidney, given the association of these two conditions.
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. Round 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).
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 whenever feasible. 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, excessive alcohol, and marijuana) should be reinforced.
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.
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.
Patients with retrograde ejaculation may benefit from alpha-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.
Obstruction of the ejaculatory ducts may be corrected by transurethral resection of the ducts in the prostatic urethra. 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.
Intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection are alternatives for patients in whom other means of treating reduced sperm concentration, motility, or functionality has failed. Intrauterine insemination should only be performed when adequate numbers of motile sperm are noted on an ejaculate sample. With the use of intracytoplasmic sperm injection, azoospermic men can father their genetic progeny by surgical retrieval of sperm from the testicle, epididymis, or vas deferens.
• 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.
Eisenberg ML et al. The relationship between male BMI and waist circumference on semen quality: data from the LIFE study. Hum Reprod. 2014 Feb;29(2):193–200. [PMID: 24306102]
Lopushnyan NA et al. Surgical techniques for the management of male infertility. Asian J Androl. 2012 Jan;14(1):94–102. [PMID: 22120932]
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]
Winters BR et al. The epidemiology of male infertility. Urol Clin North Am. 2014 Feb;41(1):195–204. [PMID: 24286777]
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.
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.
The symptoms of benign prostatic hyperplasia can be divided into obstructive and irritative complaints. Obstructive 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.
Table 23–4. American Urological Association symptom index for benign prostatic hyperplasia.1
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.
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.
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 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 Chapter 39).
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).
Cystoscopy is not recommended to determine the need for treatment but may assist in determining the surgical approach in patients opting for invasive therapy.
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.
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). 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). 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.
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).
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
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.
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.
1. Alpha-blockers— Alpha-blockers can be classified according to their receptor selectivity as well as their half-life (Table 23–6).
Table 23–6. Alpha-blockade for benign prostatic hyperplasia.
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.
Long-acting alpha-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.
Alpha-1a-receptors are localized to the prostate and bladder neck. Selective blockade of these receptors results in fewer systemic side effects than alpha-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. Alfuzosin is a long-acting alpha-1a-blocker; its dose is 10 mg orally once daily with food and does not require titration. 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 alpha-blockers and alpha-1a-blockers.
2. 5-alpha-Reductase inhibitors—Finasteride is a 5-alpha-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 5-alpha-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 5-alpha-reductase inhibitors in reducing the risk of prostate 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 5-alpha-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, double-blind, 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 was 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 patient-driven 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.
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.
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, rarity of transurethral resection syndrome, ability to treat patients during anticoagulant therapy, and outpatient surgery. Disadvantages are the lack of tissue for pathologic examination, longer postoperative catheterization time, more frequent irritative voiding complaints, and expense of laser fibers and generators.
Large multicenter, randomized studies with long-term follow-up are needed to compare 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 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.
5. Implant to open prostatic urethra—In 2013, the FDA approved an implant placed in a minimally invasive fashion to retract the enlarged lobes of the prostate in symptomatic men 50 years and older with an enlarged prostate. Data from trials suggest that the technique improved symptoms and voiding flow while having minimal impact on ejaculation.
• Progression to urinary retention.
• Patient dissatisfaction with medical therapy.
• Need for surgical intervention or further evaluation (cystoscopy).
Juliao AA et al. American Urological Association and European Association of Urology guidelines in the management of benign prostatic hypertrophy: revisited. Curr Opin Urol. 2012 Jan;22(1):34–9. [PMID: 22123290]
McNicholas TA et al. Minimally invasive prostatic urethral lift: surgical technique and multinational experience. Eur Urol. 2013 Aug;64(2):292–9. [PMID: 23357348]
McVary KT et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011 May;185(5): 1793–803. [PMID: 21420124]
Toren P et al. Effect of dutasteride on clinical progression of benign prostatic hyperplasia in asymptomatic men with enlarged prostate: a post hoc analysis of the REDUCE study. BMJ. 2013 Apr 15;346:f2109. [PMID: 23587564]