Urology

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chapter 46 Urology

INTRODUCTION AND OVERVIEW

Symptoms suggesting urological pathology are common presentations in primary care. These include recurrent urinary tract infections, frequency and urgency of micturition, nocturia and urinary incontinence.

Acute presentations to general practitioners or hospital emergency departments often involve pain: acute loin pain, testicular pain and the pain of urinary retention. Some signs may be suspicious for malignancy (e.g. haematuria). In addition, lumps in the scrotum and testes are a frequent cause for patient concern. A systematic approach to these presentations is easily followed, and history and examination will provide the diagnosis in the majority of cases.

HISTORY AND EXAMINATION

History and examination of genitourinary presentations will necessarily differ between male and female patients.

ADULT MALE

History

History taking should include the presenting complaint and any associated symptoms that may not be volunteered (e.g. haematuria, haematospermia, urethral discharge). Enquire about erectile function and recent sexual activity.

Smoking and occupational history (increase risk of bladder cancer) should be obtained. It is important to obtain an assessment of both chronicity and severity as this will guide management, particularly in bladder outlet obstruction. Nocturia is a common symptom in middle age, in both men and women.

Current medications and allergies should be noted, as well as past surgical procedures.

Family history of prostate cancer will be potentially relevant to diagnosis and screening.

Various symptoms scores have been defined for assessing the severity of lower urinary tract symptoms (LUTS), the most notable being the International Prostate Symptom Score (IPSS). This can easily be remembered by the acronym FUNWISE: Frequency, Urgency, Nocturia, Weak stream, Intermittency, Straining, incomplete Emptying. It is scored from 0 to 5 based on the number of times the symptom has occurred in the past month, and the score is then totalled from 0 to 35. A score of 0–7 is defined as mildly symptomatic, 8–19 moderately symptomatic and 20–35 severely symptomatic. In addition there is a quality of life score from 0 (delighted) to 6 (terrible). These scores are useful for assessing severity and response to treatment, and are widely used.

Examination

Examination of a male presenting with a genitourinary problem will incorporate a general physical examination including an abdominal examination and examination of the penis, scrotum, testes and hernial orifices. Percuss for a palpable bladder and ballot for a palpable kidney. The examination of the prostate is regarded by some men as invasive and avoided by many doctors, but it is invaluable in the diagnosis and management of prostate diseases. Historical descriptions of the characteristics of benign and malignant prostate glands are largely erroneous (e.g. obliteration of the median sulcus); they are usually soft or hard, large or small. Nodules may be felt, and these are often suspicious for malignancy but may also represent intra-prostatic stones.

ADULT FEMALE

History

History will begin with the presenting complaint. Ask about frequency and urgency of micturition, nocturia and urinary incontinence, haematuria, loin pain and vaginal discharge. Ask about a history of past urinary tract infections, gynaecological conditions and procedures, menstruation pattern and bowel function. If appropriate, enquire about recent sexual activity.

Ask about current medications and allergies.

Examination

Examination of a female presenting with a genitourinary problem will incorporate a general physical examination including an abdominal and gynaecological examination. Specific gynaecological conditions should be sought, such as prolapse, fibroids or vaginal atrophy. Asking the woman to cough with a full bladder can give an indication as to the severity of stress incontinence.

BEDSIDE UROLOGICAL TESTS

Dipstick and/or microbiological examination of the urine is valuable for the diagnosis of urinary tract infection and microscopic haematuria. The collection of urine samples for microbiology should be done aseptically. The GP should instruct the patient in how to collect the sample. The patient should wash their hands and the urethra should be swabbed (from front to back in females) with saline-soaked gauze. In females, the labia should be parted and the initial part of the void should be then made into the toilet, the midstream should be voided into the specimen container and the remainder in the toilet. The specimen should then be labelled and note made of whether the patient is menstruating. The specimen should be placed in a specimen bag for transportation to the laboratory.

Urine examination is carried out at the bedside, usually using urine dipstick analysis or similar cellulose strips. These contain reagents sensitive to various substances in urine such as blood, leucocytes, protein, glucose, nitrite, bilirubin and urobilinogen. A diagnosis of urinary tract infection (UTI) can be made confidently in the presence of leucocytes, nitrites and protein. It is possible to treat on this basis alone but a midstream sample for culture should also be sent, to ensure that the correct antibiotic is used.

Urinary catheters

Urinary catheterisation is usually straightforward in the anatomically normal lower urinary tract. Adult urinary catheters used in urological surgery are sized from 12 French (Charriere or Ch) to 24 French and above. The gauge equates to the circumference in mm and is approximately three times the diameter in mm. Other catheters such as the Coudé tip catheter and the Tiemann’s are used to negotiate the prostatic urethra but these are uncommonly used and inhabit the realms of the specialist. For patients with acute retention of urine, a 12 Ch catheter is usually sufficient. Although these were traditionally made of rubber, silicone is now widely used. Silicone catheters have the advantage of softness without the risk of perishing and can be left in the bladder for up to 12 weeks.

Technique

Catheterisation should be carried out using aseptic technique, and consideration given to antibiotic prophylaxis in immunocompromised or unwell patients. Prepare with antiseptic and drape the area. Fenestrated drapes are usually included in catheterisation packs for this purpose. Use 1% lignocaine gel (e.g. Instillagel®) to anaesthetise and lubricate the urethra, and allow 5 minutes to achieve maximum effect. Use the smallest catheter to effect drainage (usually 12 or 14 Ch) and insert until urine is seen to drain. Only then can the balloon be inflated. Usually 10 mL of either normal saline or sterile water is used to fill the balloon. Connect the tubing to a proprietary urinary drainage bag.

If it not possible to perform urethral drainage, suprapubic drainage is sometimes required. A palpable bladder is a prerequisite for this. Seldinger kits are now available to aid avoidance of adjacent organs (bowel and large vessels), but the standard proprietary kits such as Add-a-Cath® are still commonly available. Fine-bore tubes designed for the draining of ascites are best avoided.

UROLITHIASIS

INCIDENCE

Stones are extremely common and have a significant economic impact on a largely working population. The lifetime risk of stone formation has been reported in the range of 12% for men and 5% for women. Approximately 50% of these patients will have a second episode in their lifetime. The peak incidence is 30–45 years of age and men are three times more likely to suffer than women.

AETIOLOGY

Theories of stone formation are by no means complete, partly due to the difficulties of mimicking in vivo disease with an in vitro model. What is clear, however, is that supersaturated urine is a prerequisite to stone formation. The nucleation theory suggests that stones originate from crystals in supersaturated urine, whereas the crystal inhibition theory suggests that it is an absence of urinary inhibitors that differentiates the stone former from the non-stone former. Some work has gone into examination of potential inhibitors, particularly magnesium and citrate. Types of stones are listed in Table 46.1.

TABLE 46.1 Types of stones

Type of stone Incidence (%)
Calcium oxalate/calcium phosphate 80–85
Urate 5–10
Struvite (magnesium, ammonium, phosphate) 5–10
Cystine ≈1–2
Xanthine ≈1–2

Risk factors for stone disease

• Genetic—there is a strong association between family history and incidence of stone disease, more than doubling the risk compared with the general population.
• Medications—certain drugs have been implicated in renal stone formation, particularly indinavir, an anti-retroviral drug now very uncommonly used.
• Chemotherapeutic drugs can cause hyperuricaemia as a side effect of protein breakdown of tumours.
• Soft drink consumption has been examined as a cause but the evidence is poor (relative risk for sucrose is 1.5).
• High protein/purine diet—high intake of animal proteins has been shown to change urinary pH, increase uric acid excretion, reduce urinary citrate and increase urinary calcium. Significant levels of purines are found in anchovies, asparagus, cauliflower, legumes, mushrooms, organ meats, poultry, sardines, spinach. By extension, a vegetarian diet appears to have a protective effect, although the effect is small.
• High sodium/salt intake—this causes increased urinary calcium excretion and has been shown to increase the risk of stones by approximately 1.3.
• Low fluid intake.

SIGNS AND SYMPTOMS

Urinary stone disease presents either acutely as renal colic or more insidiously with renal angle pain, haematuria or recurrent infections. Renal colic is a common emergency presentation, with very severe pain in the loin. The pain has been described as being more severe than labour, by patients who have endured both. Pain relief should be a priority for these patients when seen in an emergency setting. The pain is often described as a ‘colic’ but can be relentless. It often radiates to the groin or testicle, and testicular pain may be the predominant symptom. The differential diagnosis includes musculoskeletal pain and incipient herpes zoster. In the elderly, ruptured abdominal aortic aneurysm may mimic renal colic. In situations where immediate imaging is not available, this is a diagnosis to consider.

INVESTIGATIONS

Non-contrast CT of the kidneys (CTKUB) is the imaging of choice for kidney stone disease. It has largely replaced the classic intravenous pyelogram (IVP) because it gives better anatomical detail with similar radiation exposure. Measurement of serum creatinine and testing of urine for infection should be carried out.

THERAPEUTICS

Renal colic

The immediate priority is to relieve pain. Non-steroidal anti-inflammatory agents such as indomethacin or diclofenac are often used in this situation. Opiates such as morphine may be required in addition. Pethidine should be avoided as there is no evidence for superior efficacy and it has more potential as a drug of abuse. Many patients will be able to be discharged after a period of observation once a firm diagnosis has been made, as many small stones pass spontaneously.

Management of renal stones

Management of renal stones depends on many factors, including size and position, coexistent infection, renal failure and so on. Mandatory indications for immediate treatment include:

• obstructed infected kidney
• stone unlikely to pass spontaneously (e.g. > 1 cm in size)
• single kidney
• persistent pain.

In addition, social factors sometimes supervene (e.g. incipient long-haul flight). People working in certain professions, such as pilots, are forbidden from working with a renal stone, and that may influence the timing of intervention.

There is good evidence that the use of alpha-blocking drugs and calcium antagonists can assist in the passage of small stones in the lower ureter, and these are often prescribed initially in combination with pain relief.

Methods of stone removal

Ureteric stones can be removed with the assistance of ureteroscopes, which can be either rigid (rod-lens), semi-rigid or flexible (fibre-optic). There have been considerable improvements in the technology of these techniques in recent years. A wide array of baskets is available and these can be used in combination with energy sources such as pneumatic lithotripsy or (holmium) laser. External shock wave lithotripsy (ESWL) is also commonly used, particularly for small stones in the kidney, and these techniques may need to be used in combination.

For larger stones in the kidney, staghorn calculi and so on, percutaneous access may be required to carry out stone surgery. It is unusual for open renal ureteric or renal surgery to be required.

PREVENTION

In order to identify risk of further stone formation, certain investigations are carried out in patients after their first episode of colic. Some authors suggest that metabolic evaluation should be carried out only on those patients with multiple or recurrent stones.

Measurement of serum calcium and urate will identify hypercalcaemic and hyperuricosuric patients. Identification of metabolic abnormalities associated with recurrent stone disease is usually carried out by analysis of 24-hour urine excretion (volume, pH, levels of calcium, phosphate and uric acid, oxalate, citrate, creatinine). Stone analysis may also assist following operative procedure or spontaneous passage.

The most common abnormality found is idiopathic hypercalciuria (with normal serum calcium). This is most easily treated with an increased fluid intake of 1.5–2 L per day.

Chemoprevention is a holy grail for stone disease. Urinary inhibitors such as potassium citrate, alone or in combination with a thiazide diuretic, can be used. Thiazide diuretics decrease hypercalciuria by increasing reabsorption of calcium from the distal tubule. Citric acid (as lemon juice) can be taken but large amounts (100–150 mL of pure lemon juice) are required to produce enough citrate in the urine.

Where possible, avoid medications likely to increase stone risk.

Diet

Dietary fact sheets containing sensible advice are invaluable in reducing further episodes of stone disease. The following points should be included:

• Increase water intake (1.5–2 L of water per day).
• Reduce consumption of soft drinks.
• Reduce high-purine foods in urate stone formers (alcohol, anchovy, asparagus, cauliflower, legumes, mushrooms, organ meats, poultry, sardines, spinach).
• Reduce salt intake.

Dietary restriction of calcium has a counterintuitive effect on the risk of subsequent stones, and is to be discouraged.

Supplements

• Calcium citrate is preferred for postmenopausal women with stone disease. The increase in urinary calcium is counteracted by the concomitant increase in urinary citrate.
• Magnesium reduces calcium oxalate risk.
• Vitamin B6 decreases oxalate production (foods rich in vitamin B6 include oily fish, whole grains, poultry, soybean, avocado, bananas, nuts). Dose: 50 mg/day.1

URINARY TRACT INFECTION

INCIDENCE

Urinary tract infection (UTI) is a common condition of young women, with an estimate of 10% of women aged between 16 and 65 years suffering from one UTI per year. It is predominantly a condition of women, but prostatic hypertrophy causes the incidence to increase in men over the age of 65 years. UTIs are classified as:

• uncomplicated lower UTI (cystitis)
• uncomplicated pyelonephritis
• complicated pyelonephritis
• urosepsis.

AETIOLOGY

UTIs can be acquired haematogenously but the vast majority arrive through ascending infection via the urethra. Bacteria vary in their virulence and this may vary depending on host factors such as obstruction, immunocompromise and so on. Most UTIs are caused by a single bacterial species. Escherichia coli is responsible for the vast majority, mostly of the O serotype. Less common pathogens include Proteus, Pseudomonas, Klebsiella and, rarely, Staphylococcus. The finding of persistent less common bacteria such as Proteus should prompt investigation for underlying pathology such as stone disease.

SIGNS AND SYMPTOMS

Simple cystitis in women usually gives a classic combination of symptoms: pain on micturition (dysuria), frequency, malaise and occasionally haematuria. In addition, patients may notice an odour associated with the urine. Pyelonephritis can cause significant morbidity, and patients may be pyrexial, with fevers, loin pain and potential sepsis. They frequently, but not always, have a preceding or coincident cystitis. Urinalysis will commonly demonstrate evidence of UTI (leucocytes, erythrocytes and nitrites), and culture of blood and urine will confirm infection with the same bacteria that lead to uncomplicated UTI.

INVESTIGATIONS

• Urinalysis—simple dipstick analysis of urine in the presence of symptoms will give the diagnosis in the majority of cases. In simple UTI, this may be sufficient, but a significant number of UTIs will not respond to empirical antibiotics, because of either resistance or lack of sensitivity. For this reason, urine culture is recommended. A culture result is usually available within a few days, such that prescribed antibiotics can be amended.
• Urine culture—the gold standard for identification of UTI is culture. Add a urine Chlamydia PCR if appropriate. Patients with dysuria and frequency may have false negative urine culture if organisms are fastidious or anaerobic.
• Upper tract investigation is not required for uncomplicated UTI. In patients with pyelonephritis, some upper tract imaging is required to rule out hydronephrosis and stone. An ultrasound of kidneys is usually sufficient. If there is evidence of complicated pyelonephritis (failure to settle, persistent pain), a contrast-enhanced CT scan may be required. It must be borne in mind that an abdominal CT carries a significant radiation dosage, with its attendant risk of malignancy.
• Cystoscopy is reserved for patients with recurrent UTI in whom no cause can be found. In young women, this is almost invariably normal. It is more common to find bladder outlet obstruction in elderly men, and a similar work-up to lower urinary tract symptoms is indicated.

THERAPEUTICS

• Antibiotics—the choice and duration of antibiotics is guided by local guidelines and antibiotic sensitivities. Trimethoprim or cephalexin have the advantage of being inexpensive and well tolerated, and are commonly used to treat uncomplicated UTI, although trimethoprim has limited sensitivity in Enterococcus and Pseudomonas species.
• Complicated UTIs are more commonly treated with quinolones (e.g. ciprofloxacin) or intravenous aminoglycosides. These are highly effective against gram-negative bacteria.
• Encourage fluid intake.
• Alkalinising urine (sodium citrotartrate) may help symptomatic dysuria.

PREVENTION

• Hygiene measures—many women will already be familiar with strategies to avoid UTI and these need to be taught to young girls from the age of toilet training. They include wiping from front to back after voiding, and avoidance of bath products, lubricants and synthetic underwear. In sexually active women, there may be a strong association between intercourse and UTI. Various measures such as voiding prior to, and after, intercourse or showering prior to intercourse can reduce the risk. Some authors advocate pre-coital antibiotics if the association is strong. (Often a single dose 4–6 hours beforehand is sufficient, or afterwards if not done so.)
• Cranberry juice—as either pure juice or as tablets, has been shown to reduce the incidence of UTI in women with recurrent cystitis by as much as half. Compliance with pure juice can be low but this is overcome by taking one tablet twice daily.
• Encourage fluids.
• Long-term low-dose antibiotics—this is rarely necessary and has been implicated in the emergence of resistant bacterial strains. Nevertheless, it is sometimes used, if only for a limited period (3–6 months). A prophylactic dose of trimethoprim or cephalexin can reduce the recurrence rate by as much as 95%. Self-start antibiotics can also be used in this way in patients with recurrent UTI, and the duration of antibiotic use may be less if employed in this way. For motivated patients, this is preferable. If antibiotics are used, they should be accompanied by a probiotic such as Lactobacillus acidophilus.

UTI IN CHILDREN

Incidence

UTI is a common bacterial infection causing illness in infants and children. It may lead to non-specific illness and the diagnosis is often more difficult to make than in adults. In this age group, a definitive microbiological diagnosis may not always be possible.

Aetiology

UTI in children may have no underlying cause, but the possibility of underlying congenital abnormality must be considered. This is discussed below.

SIGNS AND SYMPTOMS

In infants aged 3 months or less, fever and lethargy may predominate, with offensive urine and specific urinary symptoms being less common. In older infants, abdominal pain and tenderness may be more apparent, but failure to thrive and vague abdominal pain may predominate. In children above toddler age, dysuria and frequency may be more apparent than constitutional symptoms.

Investigations

Clean-catch urine is recommended. This takes patience and persistence. Urine collection pads may be used if this is not possible. Suprapubic aspiration may be required in the unwell infant prior to initiation of antibiotic treatment.

Therapeutics

Young children with UTI are mostly managed in hospital. Older children may be managed in the community but should be referred to a paediatrician. A 7–10 day course of antibiotics may be required.

Prevention and management

The investigation and management of UTI in children is a matter of debate and there has been criticism of over-investigation with invasive testing in the past. In general, the younger the infant, the greater the likelihood of underlying anatomical abnormality such as severe vesicoureteric reflux. For this reason, ultrasound is recommended as a first investigation, followed by micturating cyst-urethrography (MCUG). DMSA renography may be carried out under the care of a paediatrician in secondary care.

A diagnosis of reflux nephropathy is usually treated by prophylactic antibiotics, as most reflux will improve spontaneously over time. Circumcision has been shown to reduce the incidence of UTI in young boys with a congenital anomaly and should be considered. Severe reflux may need to be managed surgically with either endoscopic or open anti-reflux surgery.

INCONTINENCE

Urinary incontinence is the involuntary loss of urine. It is both a clinical sign and a symptom. The prevalence of incontinence increases with age and it is more common in women than men. Estimates are that 7–19% of adult women suffer from some form of urinary incontinence, with wide differences seen between different cultures and races.

Incontinence is not only a hygienic issue but it can negatively affect a patient’s quality of life, with social, psychological and sexual impairment.

Urinary incontinence may be classified as:

• stress incontinence (SUI)—loss of urine associated with abdominal effort, e.g. coughing, laughing, sneezing or straining
• urge incontinence (UUI)—urine loss that is preceded by the sudden uncontrollable desire to void
• mixed incontinence—a combination of both stress and urge incontinence
• continuous (total) incontinence—persistent loss of urine
• overflow incontinence—uncontrolled urine loss due to urinary retention
• nocturnal enuresis—loss of urine during sleep.

AETIOLOGY

(See Fig 46.1) Stress incontinence is more commonly seen with multiple vaginal deliveries and increasing age. Female continence is dependent on the supports of the bladder neck and urethra as well as the external sphincter located at the mid-urethral level. Tissue laxity and atrophy allow hypermobility with incomplete urethral closure. Male SUI is much less common and is usually due to traumatic sphincteric injury (e.g. prostatectomy for benign or malignant disease or pelvic fracture with urethral rupture).

image

FIGURE 46.1 Main types/causes of incontinence, and their management

Patients with UUI have increased urinary frequency and difficulty postponing voiding. They may report large-volume losses on the way to the toilet. Conditions that result in bladder irritation, such as infections, stones and tumours, may be causative and should be excluded. Detrusor overactivity is a common cause of UUI that is diagnosed with urodynamic studies. Detrusor overactivity is frequently idiopathic (overactive bladder) or it may be associated with longstanding bladder outlet obstruction or neurological disease (e.g. diabetic neuropathy, multiple sclerosis and spina bifida).

Continuous incontinence may be non-urethral and can occur with urinary fistulas and ectopic ureteric orifices.

Overflow incontinence is defined by urine leakage from a distended bladder. It results from bladder outlet obstruction or poor bladder contractility.

Signs and symptoms

A careful history should document the type, onset and severity of the incontinence. Associated urinary symptoms should be assessed as well as background fluid intake and voiding habits. The completion of a bladder diary may be beneficial in this regard. The presence of pain, haematuria or voiding difficulty may indicate complicated cases. Physical examination should include a neurological assessment including perineal sensation, anal sphincter tone and control of pelvic floor muscles.

Elderly patients may develop incontinence secondary to reversible conditions, which should be actively sought. These include: delirium, excess urine output, limited mobility, stool impaction and medications.

INVESTIGATIONS

Urinalysis and urine culture are routine. Imaging, such as with an ultrasound, is commonly done to assess the post-void residual and rule out pathology. Cystourethroscopy may be performed when indicated to evaluate the lower urinary tract anatomy.

Urodynamic studies with cystometry involve pressure/volume monitoring during artificial bladder filling. This is combined with fluoroscopy to define leakage. Information on bladder sensation, capacity, compliance and detrusor overactivity is provided. Urodynamics are indicated for patients with complicated or refractory incontinence, all those with neurological disease and prior to surgical therapy.

THERAPEUTICS

Stress incontinence

Conservative treatment involves fluid management, timed voiding and pelvic floor muscle exercises. Smoking cessation, elimination of constipation, oestrogen replacement and correction of obesity are also appropriate. Surgical therapy for female SUI involves bolstering the mid-urethral complex or bladder neck suspension. Colposuspension surgery involves elevation of the tissues surrounding the bladder neck behind the pubis, thus preventing mobility. Colposuspension has been largely replaced by urethral sling procedures. Autologous or synthetic slings are placed via the obturator foramen or retropubic space around the middle or proximal urethra to form a hammock for urethral support. The outcome data for synthetic slings (trans-vaginal tape, transobturator tape, etc) are now quite mature and they seem to remain effective at long-term follow-up.

Urge incontinence

Elimination of obvious bladder irritants, outlet obstruction and neurological disease will define overactive bladder (OAB). Anticholinergic medications (oxybutinin, toltoredine, solifenacin and darifenacin) are beneficial, along with bladder training. Anticholinergics may have significant side effects and should be used with caution in patients with glaucoma, obstructed voiding or cognitive impairment. Intravesical botulinum toxin injections are useful, but expensive, for refractory cases.

Complicated cases

Complicated cases may require more invasive therapy. Severe sphincteric deficiency such as that seen post prostatectomy or with lower motor neuron disease may be treated with an artificial urinary sphincter. An artificial sphincter involves the placement of a silicone cuff around the urethra, which is connected to a reservoir buried in the retropubic space. Fluid is cycled in and out of the cuff by a pump that is placed in the scrotum or labia. Debilitating UUI may require bladder augmentation surgery or a urinary diversion such as with an ileal conduit.

PREVENTION

Avoidance of exacerbating factors such as constipation, obesity, smoking and the treatment of asthma may prevent or reduce stress incontinence.

BENIGN PROSTATIC HYPERPLASIA

INCIDENCE

Benign prostatic hyperplasia (BPH) is a common clinical condition of the ageing man. Studies suggest that about 30% of men older than 65 years will suffer from clinical BPH. The definition of BPH is not standardised, and it may be used to refer to:

• histological features of stromoglandular proliferation
• benign prostatic enlargement
• clinical BPH—the most commonly used definition indicating the presence of lower urinary tract symptoms (LUTS) from bladder outlet obstruction by a non-cancerous prostate gland.

AETIOLOGY

BPH is an age-related process that is androgen dependent. Histological changes, prostate size and LUTS are all more prevalent with increasing age. BPH does have an inheritable component and severe forms may be hereditary.

SIGNS AND SYMPTOMS

The most common presentation of BPH is with LUTS due to bladder outlet obstruction. These symptoms can be assessed with validated scoring systems (e.g. IPSS, see above) and with a voiding diary. Occasionally, BPH-related complications such as recurrent urinary tract infections, recurrent haematuria, bladder calculi, bladder diverticula or urinary retention may lead to presentation.

History and physical examination aim to determine the impact of BPH and exclude differential diagnoses. Digital rectal examination is important to evaluate prostatic size and for possible cancer.

INVESTIGATIONS

There are a variety of investigations that may be used in the evaluation of patients with BPH. The more common tests are listed below.

• urine microscopy, culture and sensitivity—for all patients
• urine cytology, upper tract imaging and cystoscopy—if haematuria is present
• renal tract ultrasound—performed when information regarding renal anatomy and upper tract changes (e.g. hydronephrosis and stones), bladder anatomy, prostate size and post-void residual is sought
• flexible cystoscopy—not routinely indicated but may be done when urethral anatomy is questioned (e.g. stricture disease, previous prostatic surgery) or when bladder pathology needs to be excluded
• voiding flow rate with residual—a useful adjunct in assessing obstructive LUTS that may indicate aetiology by its pattern
• serum creatinine—may be measured when renal function may be compromised (e.g. urinary retention)
• prostate-specific antigen measurement—should be considered where the diagnosis of prostate cancer may alter the treatment plan
• urodynamic studies—indicated where confounding conditions may be responsible for LUTS (e.g. neurological disease or previous failed prostatic surgery).

INTEGRATED THERAPEUTICS

Many men with bladder outlet obstruction due to BPH are not significantly bothered by their symptoms and may be appropriate for watchful waiting. Many men will remain stable or have improvement with long-term observation. For men who are bothered by their symptoms, medical therapy should be considered.

• Regular physical exercise—most of the literature supports a clinically significant, independent and strong inverse relationship between exercise and the development of BPH/LUTS.2
• Supplements:

• quercetin 500 mg b.i.d. combined with bromelain
• beta sitosterol3
• saw palmetto4
• Pygeum africanum5 (50–100 mg extract daily) may be useful
• stinging nettle6
• pumpkin seed oil extracts standardised for fatty acid content—have been used in BPH studies in the amount of 160 mg t.i.d. with meals
• vitamin C 1000 mg daily
• zinc 60 mg daily
• omega-3 fatty acids 2000–4000 mg daily as anti-inflammatory.

Pharmaceutical

Alpha-blocking agents (e.g. tamsulosin or prazosin) provide rapid symptomatic improvement and improve urine flow. These are usually first-line pharmaceutical agents for BPH therapy. Inhibitors of 5-alpha reductase (e.g. finasteride and dutasteride) block the conversion of testosterone to dihydrotestosterone, the more potent androgen within the prostate. These agents result in a gradual decrease in prostatic size (20–30%), improve urinary symptoms and prevent disease progression. They are useful in men with significantly enlarged prostates and may be used alone or in combination with alpha-blockers. However, they may reduce PSA, altering the monitoring of prostate cancer.

Surgery

Surgical therapy is indicated for failed medical therapy and for BPH-related complications. Transurethral prostatic resection (TURP) remains the mainstay for surgical management of BPH. Possible complications include: haemorrhage, infection, stricture formation, retrograde ejaculation and, rarely, stress incontinence. The ‘TURP syndrome’ is a rare and potentially fatal complication that occurs from absorption of hypotonic irrigation solution. Erectile dysfunction has been reported post TURP; however, the rates appear to be similar to those of age-matched cohorts. Men with a very large prostate gland may require open surgical excision. Laser surgery may provide an alternative approach to TURP. Holmium laser enucleation of the prostate (HOLEP) provides similar results to traditional surgery and may be performed for large glands or in anticoagulated patients. Photoselective vaporisation with KTP (greenlight) laser is being increasingly used and may be performed as a day procedure. Less invasive measures such as radiofrequency needle ablation (TUNA) and microwave thermotherapy (TUMT) provide symptomatic benefit that in general is less than that seen with TURP, and are not widely performed.

Prevention

No preventative strategies exist.

PROSTATITIS

Chronic prostatitis is a difficult condition to manage, and has been calculated to be responsible for two million outpatient visits in the United States in 2009. The majority of these patients fulfill the criteria for chronic pelvic pain syndrome and most do not respond to antibiotics. It is characterised by diagnostic uncertainty and unsatisfactory outcomes.

Acute prostatitis is a serious but uncommon infection, often requiring inpatient treatment. Parenteral quinolone and aminoglycoside antibiotics may be required. In less severe cases, long courses of oral quinolones (e.g. 3 weeks) may be sufficient. It may rarely be complicated by prostatic abscesses, which may require surgical intervention.

Bacterial prostatitis is usually divided into acute and chronic, depending on the duration of symptoms. The National Institutes of Health classification is frequently used and is outlined in Box 46.1.

BOX 46.1 NIH classification of prostatitis

I Acute bacterial prostatitis
II Chronic bacterial prostatitis
III Chronic abacterial prostatitis—chronic pelvic pain syndrome

• A—Inflammatory chronic pelvic pain syndrome (white cells in semen/expressed prostatic secretions)
• B—Non-inflammatory chronic pelvic pain syndrome (no white cells in semen/expressed prostatic secretions)

IV Asymptomatic inflammatory prostatitis (histological prostatitis)

AETIOLOGY

The aetiology of acute and chronic prostatitis is unclear. It is assumed that acute prostatitis begins with a cystitis or a urethritis, which then spreads to involve the gland along the prostatic ducts. There is a strong association between chronic prostatitis and bladder outlet obstruction, but true chronic pelvic pain syndrome may exist without any pre-existing urinary pathology.

SIGNS AND SYMPTOMS

Acute prostatitis is associated with severe urinary symptoms, fever and possible signs of sepsis. Chronic prostatitis/chronic pelvic pain syndrome is a constellation of symptoms. Testicular, perineal, rectal or penile pain may predominate. In addition, frequency of micturition and dysuria are common. The pain may be debilitating, with many of the characteristics associated with chronic pain elsewhere.

INVESTIGATIONS

The investigations for chronic prostatitis should include:

• urinalysis and urine culture
• exclusion of sexually transmitted disease using urine PCR for chlamydia
• assessment of lower urinary tract dysfunction using a flow rate and voiding chart
• an attempt to culture a prostatic pathogen for either urine or expressed prostatic secretions (EPS). This can be achieved by using the ‘Stamey three glass test’ where the patient voids 15–20 mL of urine into the first glass (voided bladder (VB) urine 1), then performs an MSU as described above (VB2). The prostate is then massaged by the doctor and the prostatic secretions expressed (expressed prostatic secretions (EPS)). The patient then voids 10–15 mL into a third container (VB3). In essence, bacteria or white cells in VB1 suggests urethritis, in VB2 cystitis and in EPS prostatitis.

THERAPEUTICS

Standard medical treatment for acute prostatitis usually involves antibiotics for 4–12 weeks (with probiotics), combined with anti-inflammatory medication (NSAIDs). Usually, quinolones (e.g. ofloxacin), trimethoprim or tetracyclines are used. Alpha-blockers may help if there is trouble with micturition, and are usually tried in addition. However, there is a lack of proven efficacy for conventional medical treatment of chronic abacterial prostatitis/chronic pelvic pain syndrome.

Where symptoms are chronic or refractory to treatment, the condition may represent non-bacterial prostatitis. Standard medical treatment is usually unhelpful for this condition.

The following combination can be trialled:7

• cernilton, a flower pollen extract (500–1000 mg 2–3 times/day)8
• quercetin 500 mg b.d. combined with bromelain
• beta sitosterol
• saw palmetto3 inhibits 5-alpha-reductase, dose 320 mg/day
• stinging nettle
• vitamin C 1000 mg daily
• zinc 60 mg daily
• omega-3 fatty acids 2000–4000 mg daily
• avoid alcohol and caffeine.

URINARY RETENTION

INCIDENCE

Various longitudinal community studies have attempted to measure the risk of acute retention in men with benign prostatic hyperplasia (BPH). A recent study identified men with BPH and randomised them into receiving placebo, or treatment with alpha-blockers and/or 5-alpha reductase inhibitors. The placebo arm represented untreated BPH and 2% of those men developed acute retention in 5 years. A similar study estimated the risk of retention in untreated men with BPH was 23% after 20 years.

AETIOLOGY

Urinary retention can be either acute (commonly) or chronic (rare). Acute retention is often caused by obstruction to the outflow tract in elderly men, due to BPH or, less commonly, malignant disease. Less common causes include urethral stricture disease and spinal cord injury.

Acute urinary retention in hospital commonly follows surgery, particularly to the groin, anus or hip. In these cases, pain and anti-cholinergic side effects of anaesthetic agents often conspire to inhibit voluntary voiding. In the community, alcohol, anticholinergics and tricyclic antidepressants are sometimes implicated.

Chronic retention of urine is an insidious condition seen in elderly men. They often describe a painless swelling of the abdomen associated with nocturia and incontinence, caused by overflow of urine from a distended bladder. Most of these are low pressure, and renal function is preserved, but there may be bilateral hydronephrosis if the pressure within the bladder is high. This is an emergency and has to be relieved by catheterisation. In cases of acute renal failure, catheterisation can lead to a large diuresis and profound fluid shifts, and requires careful management. A regimen of replacing hourly losses with normal saline may be required. Daily weights may assist the fluid management in these cases. Bladder outlet surgery is mandatory in these patients as a removal of the catheter will result in further episodes of renal failure. This should be delayed for at least 6 weeks to allow glomerular and tubular function to recover.

INVESTIGATIONS

The investigation of patients with retention of urine is similar to those with lower urinary tract symptoms (LUTS). At the time of catheterisation, a sample of urine is sent for culture and sensitivity. Blood tests for creatinine and full blood count are checked. PSA measurement at the time of retention is a controversial topic but is probably best avoided. Significant increases in PSA can be seen in cases of retention and this will require at least a further PSA after an interval to ensure that it has returned to normal. In contrast, some authors suggest that a normal PSA is reassuring and a very high PSA associated with metastatic prostate cancer can speed diagnosis. Clinical examination of the prostate is required to assess for size and possible malignancy.

THERAPEUTICS

Simple measures can be tried, to assist voiding. Sitting in a warm bath, pain relief or simply sitting out of bed for the hospitalised patient can be useful manoeuvres. If catheterisation is required, the patient should be catheterised as described above. Some units prefer suprapubic catheterisation as a routine. The ability to carry out a trial of voiding without removing the catheter must be weighed against the additional morbidity associated with suprapubic catheterisation. There is good evidence that the addition of an alpha-blocker (e.g. tamsulosin 400 mcg OD) can improve the percentage of men who void following removal of the catheter. This is normally started on admission and requires at least two doses. Approximately half of men will void following a first episode of retention. In patients who have an obvious precipitant and minimal LUTS prior, this is more likely to succeed. In men who have had worsening symptoms over a long period culminating in an episode of retention, it is less likely and they are best managed with prostate surgery in the first instance.

RENAL DISEASE

Diseases of the kidney are important in general practice for a range of reasons. First, when severe they cause considerable morbidity and mortality. Secondly, they are common, particularly in some sections of the community, such as the elderly and indigenous peoples, and they are regularly co-managed by GPs. Thirdly, their management can be complex and includes not just managing the illness itself but also the symptoms commonly associated with kidney diseases. Fourthly, many of the symptoms and signs associated with chronic kidney disease can come on slowly and are both ill-defined and common, so as to mimic other illnesses, thereby causing diagnostic problems.

Kidney disease is mentioned in a number of other chapters in the context of its association with other illnesses and risk factors. For example, it is discussed in the chapter on diabetes (Ch 26) in the context of complications and monitoring, and in the chapter on cardiovascular disease (Ch 25) due to its role in hypertension. This section of the chapter will therefore focus on kidney failure.

KIDNEY FAILURE

Kidney failure is defined as acute or chronic, depending on whether the decline in renal function has occurred for days/weeks or longer.

Acute kidney failure

Acute kidney failure (AKF) is a sudden and significant decrease in renal function, which leads to a number of sequelae. These include oliguria (less than 400 mL/day in adults or 0.5–1.0 mL/kg/h in children and infants, or nil in the case of ureteric obstruction) and electrolyte imbalance.

Aetiology

AKF can arise from a variety of causes, including:

• pre-renal—causes of kidney hypoperfusion such as severe dehydration, blood loss or major and prolonged drop in blood pressure
• intrinsic—causes of kidney diseases such as glomerulonephritis or toxic overload (as with certain drugs, such as chemotherapy)
• post-renal—causes such as prostate enlargement or ureteric obstruction due to renal calculi.

Polypharmacy, particularly with commonly prescribed medications for the elderly, such as anti-inflammatory medications, diuretics and ACE inhibitors, is a very common cause of AKF. Other medications can exacerbate complications of kidney failure, such as hyperkalaemia. Drugs that can do this include diuretics such as aldactone and Moduretic®, ACE inhibitors, anti-inflammatory medications and AIIR antagonists. It is also worth bearing in mind that medications that are excreted through the kidney may have a substantially longer half-life in the elderly, due to poorer excretion.

Investigations

Tests for AKF will include :

• estimated glomerular filtration rate (eGFR)
• serum creatinine, and urea and electrolytes
• identifying the underlying cause (e.g. plain abdominal X-ray in the presence of renal colic).

Management

AKF is potentially life-threatening and requires urgent diagnosis and admission to hospital. The underlying cause needs to then be identified and treated, such as restoration of fluids or blood, or passing of the calculus.

Recovery from AKF tends to be good, provided the underlying cause can be alleviated, although there is a risk of chronic kidney failure in the future. Sometimes dialysis may be required in the short term until normal kidney function returns.

Chronic kidney failure

Chronic kidney failure (CKF) is defined as a measured or estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 and/or evidence of kidney damage for three or more months, such as proteinuria (ratio of > 30 mg albumin to 1 g creatinine on untimed (spot) urine testing), abnormal renal function tests or abnormalities in imaging tests (scarring or polycystic kidneys).

The majority of patients will be managed in general practice.

Like other organ systems, the kidney has a significant functional reserve of approximately 75–80%. This means that 75% of renal function can be lost without any significant electrolyte or metabolic results or symptoms. Beyond that point (less than 20% of renal function), the effects of diminishing renal function can be measured and symptoms become noticeable. At less than 10% of renal function, the mortality rate rises sharply without dialysis or kidney transplant.

Aetiology

CKF can arise from diseases that primarily originate in the kidney itself, or from other illnesses that affect the kidney (Box 46.2). Many of these illnesses, such as type 2 diabetes, hypertension and vascular disease, are lifestyle related and are therefore preventable.

BOX 46.2 Common causes of chronic kidney failure

• Diabetes mellitus
• Hypertension
• Glomerulonephritis
• Renal artery stenosis
• Polycystic kidney disease
• Toxins and pharmaceuticals—e.g. aspirin, anti-inflammatory medications such as ibuprofen and the COX-2 inhibitors, codeine, antibiotics including gentamicin, vancomicin and tetracyclines, ACE inhibitors and lithium
• Reflux nephropathy
• Outflow obstruction of the bladder
• Connective tissue disorders, e.g. SLE
• Amyloidosis
• Gout

CKF can be diagnosed on investigating indicative symptoms and signs, but as the early stages are usually asymptomatic, often diagnosis will depend on clinical suspicion resulting in testing of at-risk groups, or on the results of blood tests or screening done for other reasons.

Signs and symptoms

Early CKF is commonly asymptomatic. The most common early symptoms are generally non-specific and related to uraemia, such as malaise, nausea, vomiting, weight loss and anorexia and lethargy. As the kidney disease progresses, further symptoms and signs are caused by the complications.

The symptoms associated with CKF are largely due to effects on fluids and electrolytes, homeostasis and erythropoietin. Symptoms (e.g. pruritis), signs (e.g. unexplained hypertension, fatigue or anaemia) and laboratory findings (e.g. proteinuria, uraemia) should raise the clinical suspicion of CKF. Box 46.3 outlines the main symptoms and signs of CKF.

BOX 46.3 Signs and symptoms of chronic kidney failure

Symptoms

• Symptoms associated with uraemia:

• nausea, vomiting, weight loss, anorexia, diarrhoea, bad taste in mouth and bad breath

• Electrolyte imbalance:

• phosphate—itching, bone pain
• potassium—arrhythmias, muscle weakness
• calcium—muscle cramps
• acidosis

• Fluid balance:

• swelling of ankles and legs, shortness of breath and aggravation of heart failure

• Inadequate erythropoetin

• tiredness, malaise, dizziness, drowsiness

• Skin pigmentation—yellowish
• Easy bruising and epistaxis
• Polyuria and nocturia

Signs

• General appearance—pale, weight loss
• Skin—dry, scratch marks, yellowish pigmentation, bruising, purpura
• Fluid balance—peripheral oedema, signs of congestive cardiac failure (CCF)
• Anaemia—pallor, pale conjunctiva
• Nails—leuconychia
• Urine—haematuria, proteinuria, polyuria
• Cardiovascular—hypertension, signs of CCF
• Neurological—from drowsiness to confusion, seizures and coma in severe cases
• Muscular—weakness and muscle spasm
• Respiratory—tachypnoea
• Prostate—potential prostatic enlargement in cases of obstructed outflow
• Eyes—retinopathy secondary to diabetes or hypertension
• Abdomen—renal enlargement, particularly with polycystic kidneys, or small scarred kidneys with chronic kidney damage
• Signs of underlying illness contributing to CKF, e.g. diabetes

When confirmed upon measurement of the eGFR, serum creatinine and urea, further tests should also be directed at determining the underlying cause of the CKF, such as diabetes.

Investigations

When a clinical suspicion of CKF is aroused, it needs to be confirmed on investigations and the severity of various complications determined. The following tests should be considered by the GP, although a range of others may also be performed by a renal specialist.

• Urine tests:

• Test for glucose, blood, protein and albuminuria (initially with a dipstick). The albumin:creatinine ratio (ACR) is now used to help establish the severity of CKF. ACR on a random spot urine sample is carried out to further quantify proteinuria (albuminuria). Where this is abnormal, repeat specimen a few weeks later to determine whether it is persistent. If positive, two further tests for ACR are done in the next 2 months. Albuminuria is stratified according to International Diabetes Federation guidelines9 as shown in Table 46.2.
• Haematuria—exclude non-glomerular haematuria such as menstruation, urinary tract infection, urinary neoplasm, calculus, prostatic disease. Glomerular haematuria is related to kidney disease. Persistent haematuria or haematuria with other indicators of kidney damage requires investigation.

• Electrolytes:

• sodium, chloride, potassium, calcium, phosphate, bicarbonate.

• Renal function tests:

• urea, creatinine, creatinine clearance
• eGFR.

• Full blood examination.
• Blood pressure assessment.
• Ultrasound imaging of the kidney and urinary tract
• Further tests as indicated, such as looking for the cause of the CKF or assessing general wellbeing—blood glucose, urate, lipids, ECG, lupus serology, iron studies.
• Further tests generally ordered by a nephrologist—could include kidney biopsy, immunological tests.

TABLE 46.2 International Diabetes Federation guidelines8 on albuminuria

  Urinary ACR (mg/mmol)
  Women Men
Normoalbuminuria < 3.5 < 2.5
Microalbuminuria 3.5–35 2.5–25
Macroalbuminuria > 35 > 25

Kidney function is measured by the eGFR, measured in mL/min. Creatinine is the most commonly used compound used to calculate the eGFR. The formula used to calculate eGFR is:

image

The eGFR varies with age, gender and size, and so what would be considered normal kidney function needs to be interpreted in light of these parameters.

CKF is divided into five stages according to the eGFR:

1. > 90: normal
2. 60–90: mild
3. 30–60: moderate
4. 15–30: severe
5. < 15: end-stage.

Patients with moderate levels of kidney failure or above should be referred to a renal specialist (Box 46.4) for advice and co-management.

BOX 46.4 Indications for referral to a nephrologist

• eGFR < 30 mL/min/1.73 m2
• Unexplained decline in renal function (> 15% reduction in eGFR in 3 months)
• Proteinuria > 1 g/24 h
• Glomerular haematuria (particularly if proteinuria is present)
• CKD and hypertension unable to achieve or maintain at target
• Unexplained anaemia (Hb < 100 g/L) with eGFR

Integrative management

The management of CKF can be complex and prolonged, and needs specialist referral, close monitoring and review by a multidisciplinary team. The following are some of the key principles of managing CKF.

• Treat underlying conditions that may be contributing to or exacerbating the CKF—these commonly include hypertension, diabetic control or the cessation of some medications.
• Assess and manage cardiovascular risk factors such as hypertension, cholesterol, smoking and diabetes. Optimal management of these risk factors slows the progression of CKF (Box 46.5 lists treatment targets).
• Control blood pressure—ACE inhibitors are first-line for management of hypertension, and multiple medications may be required to achieve optimal blood pressure control. If hypertension is resistant to medication, consider renal artery stenosis.
• For eGFR 30–59, an ACE inhibitor or ARB agent used singly or in combination reduces proteinuria/albuminuria significantly and is associated with improved outcomes.
• Electrolyte balance—particularly phosphate and potassium. Calcium carbonate can be used for patients with high phosphate levels because it binds to phosphate. Avoid potassium-sparing diuretics.
• Fluid balance is important, being careful to avoid dehydration, which can further impair kidney function, and over-hydration, which can exacerbate oedema and CCF.
• Manage intercurrent illnesses and risk factors, particularly urinary tract infections, cardiovascular disease and diabetes.
• Nutrition can be a significant concern and care should be taken to have a low-protein diet and avoid excess intake of electrolytes such as potassium and sodium—advise low-sodium foods and no added salt. Referral to an accredited practising dietician with experience in renal disease is appropriate.
• Avoid hydrogenated vegetable oils, because they are high in trans-fatty acids.
• Manage anaemia with adequate iron and erythropoetin.
• Manage symptoms, especially nausea.
• Prescribe medications with caution, because of the potential for many drugs to exacerbate CKF, such as those mentioned previously, or to accumulate due to a longer half-life. Some examples of drugs that do accumulate in those with CKF are provided below, but it is always advisable to check drug information sheets before prescribing any medications to patients with significant levels of CKF. A lower dose of these medications would generally be recommended if a decision is made to prescribe them, taking care to monitor the patient closely for side effects. Examples:

• antibiotics—penicillin, co-trimoxazole, flagyl, quinolones
• cardiovascular drugs—atenolol, sotalol, digoxin
• diabetic medications—insulin, sufonylureas, metformin
• lithium
• codeine
• methotrexate.

• General support for the patient and the family, including psychological support and, commonly, assistance with issues such as finances and employment.
• A healthy lifestyle should be encouraged in as much as it is possible. This will assist with maintaining wellbeing as well as slowing decline in kidney function.
• Dialysis or kidney transplant are the last resort for patients with end-stage kidney failure. When more conservative measures have failed and kidney function continues to decline, leading to a level of symptoms that is having a significant impact on the patient’s life, these options should be discussed and an assessment made by the specialist team as to the appropriateness of the various options available. Although they are not without their complications, risks and expense, when successful they can often lead to a rapid and significant improvement in quality of life.

BOX 46.5 Treatment targets

• Maintain blood pressure < 130/80 mmHg. Maintain BP <125/75 if proteinuria > 1 g/24 h or diabetes present.
• Proteinuria will usually halve with blockade of angiotensin and this has a reno-protective effect, so ACE inhibitor or ARB are first-line medications.
• Maintain total cholesterol < 4.0 mmol/L, LDL < 2.5 mmol/L.
• Pre-prandial blood glucose 4.4–6.7 mmol/L, HbA1c < 7.0% with lifestyle management, oral hypoglycaemics, insulin (see Ch 26, Diabetes).

Prevention

• Cease and avoid smoking.
• Maintain healthy BMI.
• Maintain blood pressure in normal range.
• Prevent diabetes or manage existing diabetes.
• Maintain waist circumference < 94 cm for males, < 80 cm for females.
• Encourage at least 30 minutes exercise daily.
• Limit dietary salt intake.
• Moderate alcohol consumption.
• Immunise against influenza and pneumococcal disease if diabetes or end-stage kidney disease present.
• Avoid NSAIDs and COX-2 inhibitors.

BLADDER CANCER

INCIDENCE

Bladder cancer is the second most common urological cancer. Incidence rates vary worldwide and are highest in Egypt, North America and Western Europe. Bladder tumours are three times more common in men and are most often diagnosed after age 55.

AETIOLOGY

Transitional cell carcinoma (TCC) is the most common type of bladder cancer (> 90%). The most important risk factors associated with bladder cancer are cigarette smoking and occupational exposure to urothelial carcinogens (e.g. aromatic amines, polycyclic hydrocarbons) such as in the textile and dye industries. Other possible causes include analgesic abuse, cyclophosphamide exposure and previous radiation. The bladder is the most common site of TCC occurrence, but it is important to note that the entire urothelium is at risk of neoplastic changes.

Squamous cell carcinomas of the bladder are rare (5%) and are associated with chronic inflammation, such as with stones or schistosomiasis. Adenocarcinomas are even rarer (1%) and may be associated with persistent urachal remnants.

SIGNS AND SYMPTOMS

The most common presentation is painless haematuria, which is typically gross. Other urinary symptoms such as frequency, urgency and dysuria are less common, and if present indicate associated in-situ carcinoma or muscle-invasive disease.

INVESTIGATIONS

Endoscopic examination of the lower urinary tract (cystoscopy) is the diagnostic standard for bladder cancer, and is combined with urinary studies and radiological imaging. Urinary cytology has only moderate sensitivity but good specificity for the detection of urothelial cancers, and is more useful in post-therapy surveillance.

Radiological studies including ultrasound, intravenous urography (IVU) and CT urography may detect the presence of a tumour but cannot replace cystoscopy. Their utility is in the staging of disease extent and assessing for upper urinary tract pathology.

THERAPEUTICS

Transurethral resection of bladder tumour (TURBT) in combination with bimanual palpation provides local disease staging and in many cases is therapeutic. Bladder cancer may be classified according to appearance (papillary or sessile) or whether it is superficial or muscle-invasive.

TURBT is essential in determining the grade (low or high) and local stage of the tumour (TNM classification), which are used in deciding on prognosis and treatment. TNM stages are as follows:

• Ta papillary, urothelial confined
• Tis carcinoma in-situ
• T1 lamina propria invasion
• T2 muscle wall invasion
• T3 extension through bladder wall
• T4 invasion of surrounding organs.

Non-muscle-invasive tumours are treated with complete TURBT. This is followed by periodic surveillance cystoscopy and urinary cytology for life. Tumours that are at higher risk of disease progression (i.e. high tumour grade, T1 or associated with Tis) should be considered for Bacillus Calmette-Guérin (BCG) intravesical therapy. BCG therapy is effective in reducing recurrence rate and disease progression.

Muscle invasive disease is treated by radical cystectomy and urinary diversion with an ileal conduit or a neo-bladder in select patients. Radiation therapy is an option for patients desiring bladder preservation, poor surgical candidates and those with unresectable disease. Patients with unresectable disease or metastases are treated with chemotherapy.

PREVENTION

Smoking cessation reduces the risk of developing bladder cancer, with a greater than 30% risk reduction in 1–4 years, and 60% after 25 years. The risk, however, never decreases to that of non-smokers.

RENAL CELL CANCER

INCIDENCE

Renal cell carcinomas are adenocarcinomas of renal tubular cells. They represent 2–3% of all adult malignancies and are the most lethal urological cancer.

AETIOLOGY

Renal cell carcinomas (RCC) are more common after middle age and in men. There is some association with cigarette smoking. There are a number of familial syndromes associated with increased risk of RCC, most notably Von Hippel Lindau’s disease (up to 50% develop RCC).

SIGNS AND SYMPTOMS

The ‘classic’ presentation of RCC, with flank pain, haematuria and a palpable abdominal mass, is no longer common. These features herald advanced disease. The majority of renal tumours are now incidental discoveries on abdominal imaging carried out for other reasons. Less commonly, patients may present with a paraneoplastic syndrome, such as hypertension, anaemia, pyrexia of unknown origin (PUO), abnormal liver function tests, hypercalcaemia or erythrocytosis. These result from tumour endocrine activity with the production of renin, parathyroid-like peptides, erythropoietin and so on. The plethora of possible presentations has resulted in the coining of the term the ‘internist’s tumour’.

INVESTIGATIONS

High-quality triple phase CT scan of the abdomen and pelvis is the imaging modality of choice for renal tumours. The presence of a solid enhancing renal parenchymal lesion is considered an RCC until proved otherwise. Imaging should also exclude nodal disease and bony, liver, adrenal or venous involvement. The presence of a normal contralateral kidney without synchronous lesion is also assessed. Chest imaging with X-rays or CT should be done to assess lung metastases. Baseline blood studies including FBC, renal function tests, LFTs and calcium should be drawn. Renal tumour biopsy is rarely indicated but may be used to assess atypical lesions, such as with suspected renal lymphoma.

Cystic lesions are treated according to their level of complexity; this is determined by the presence of septations, calcification and solid components. Simple cysts are uniformly benign and require no therapy unless symptomatic. Complex cysts will require either surveillance with follow-up imaging or resection, depending on the level of complexity.

THERAPEUTICS

Radical nephrectomy is the standard treatment for RCC. Partial nephrectomy is an option for smaller (< 4 cm) exophytic tumours and may be mandatory where radical nephrectomy will result in renal insufficiency, such as in a solitary kidney. Cancer-specific survival rates for partial nephrectomy are equivalent to radical nephrectomy for treating small renal tumours. Both radical and partial nephrectomy can be accomplished open or laparoscopically. Unfortunately, up to a third of patients present with metastatic disease.

Organ-confined tumours of < 7 cm carry a good long-term prognosis. Solitary metastatic deposits can be resected along with nephrectomy, with reasonable outcome. Locally invasive tumours or those with nodal or metastatic deposits are associated with very poor survival rates. In situations where a single metastatic deposit is present, nephrectomy may be combined with resection of the metastasis, with reasonable outcome. Venous extension is not such a poor prognostic factor and even when extensive can be excised at nephrectomy. Renal cell carcinomas are resistant to radiotherapy and chemotherapy. For patients with advanced disease at diagnosis, tyrosine kinase inhibitors (sunitinib and sorafenib) have resulted in disease stabilisation or even regression, but are not curative.

PREVENTION

No preventative measures currently exist.

TESTICULAR CANCER

INCIDENCE

Testicular cancer represents 1–1.5% of male tumours and 5% of urological tumours in general. The vast majority are germ cell tumours (GCTs) and can be classified histologically as pure seminomas or non-seminomas (NSGCT). Presentation is most common in the third or fourth decade of life.

AETIOLOGY

Risk factors for the development of testicular cancer include undescended testes (cryptorchidism), familial history, Klinefelter’s syndrome, infertility and the presence of tumour in the contralateral testicle. Testicular cancer is more common in men of Scandinavian descent.

SIGNS AND SYMPTOMS

The most common presentation is the casual discovery of a unilateral testicular mass. Pain is reported in only 20–25% of cases. Occasionally scrotal trauma leads to the detection of a mass. Rarely, diagnosis is made during the work-up of secondary gynaecomastia or abdominal discomfort from retroperitoneal nodal involvement.

Physical examination should aim to characterise the scrotal mass as well as look for distant disease (abdominal masses, supraclavicular nodes).

INVESTIGATIONS

Scrotal ultrasound is invaluable in evaluating a testicular mass. It has excellent diagnostic accuracy for testis tumours and can exclude possible differentials (i.e. epididymitis and hernia).

The tumour markers human chorionic gonadotrophin (HCG), alpha-fetoprotein (aFP) and lactate dehydrogenase (LDH) are useful for the diagnosis, staging and prognosis of testicular GCTs. These markers are also used in post-treatment surveillance and may aid therapeutic decisions.

Imaging is critical in the staging of GCTs. Testicular GCTs spread in an ordered manner to the retroperitoneal nodes adjacent to the great vessels, with distant nodal or haematogenous dissemination occurring thereafter. Contrast CT scan should be done to assess for involvement of the retroperitoneum, mediastinum or visceral organs. PET scans are not indicated for the initial diagnosis but may be useful in assessing treatment response.

THERAPEUTICS

Radical/inguinal orchidectomy, which involves the excision of the testicle within its tunical coverings, is the initial treatment for localised testicular cancer. Surgery provides local staging and histological classification, which determines further treatment.

Post orchidectomy, patients with locally confined (Stage I) seminoma may be managed with single-agent chemotherapy (carboplatin), radiotherapy to the retroperitoneum or surveillance. Surveillance is best suited for those without adverse risk factors on pathological assessment (i.e. tumour size > 4 cm or Rete testis involvement). Seminomas with small-volume retroperitoneal disease can be treated with either combination chemotherapy (bleomycin, etoposide and cisplatin (BEP)) or radiation. Bulky nodes or distant disease is treated with chemotherapy (BEP).

Patients with locally confined NSGCT are usually treated with adjuvant chemotherapy (BEP) or retroperitoneal lymph node dissection (RPLND); those without adverse histological features may be selected for surveillance. Retroperitoneal nodal involvement is treated with chemotherapy and RPLND for residual disease post chemotherapy.

Most patients with GCTs enjoy a favourable prognosis. Non-pulmonary visceral metastases and persistently elevated tumour markers post orchidectomy are poor prognostic factors.

PREVENTION

• Correction of undescended testes in children.
• The excision of undescended testes in post-pubertal men is recommended, to prevent the subsequent development of testicular cancers.

ADRENAL DISEASES

Paired adrenal glands lie adjacent to the upper aspect of each kidney. These glands are composed of an outer cortex (mesodermal origin) and inner medulla (neuroectodermal origin). Adrenal cortical function involves the production of aldosterone, cortisol and adrenal androgens as part of normal homeostasis. The adrenal medulla is composed of chromaffin cells, which produce the catecholamines epinephrine and norepinephrine.

The adrenal gland may be the site of a variety of benign and malignant diseases (Table 46.3).

TABLE 46.3 Causes of adrenal diseases

Non-neoplastic Neoplastic
Adrenal cyst Adrenal adenoma
Adrenocortical hyperplasia Adrenal carcinoma
Haematoma/abscess Phaeochromocytoma
Myelolipoma Metastatic deposit

INCIDENCE

Most adrenal tumours are now discovered incidentally on abdominal imaging. Estimates are that 1–5% of abdominal CT scans will detect an adrenal mass. When an adrenal lesion is detected in a patient with a history of malignancy, 75% of these lesions prove to be metastatic deposits, and two-thirds of lesions found in patients without a cancer history are benign.

AETIOLOGY

While the majority of adrenal lesions are of unknown aetiology, there are a few genetic syndromes associated with the development of adrenal tumours. For example, phaeochromocytomas may be associated with von Hippel Lindau disease, MEN 2 or neurofibromatosis.

SIGNS AND SYMPTOMS

Functional tumours may present with symptoms associated with hormone production. Cortisol excess produces Cushing’s syndrome, with obesity, hypertension, muscle weakness, cutaneous striae and glucose intolerance. Conn’s syndrome results from aldosterone excess, with hypertension, hypokalaemia, polydipsia and polyuria. Phaeochromocytoma is a rare cause of hypertension that may be paroxysmal and associated with headaches, palpitations, sweating, anxiety and chest pain.

Adrenal carcinomas are rare aggressive tumours commonly presenting with pain and constitutional symptoms. They typically secrete multiple compounds and may present with virilisation or feminisation.

INVESTIGATIONS

Imaging with CT or MRI defines the size and character of the adrenal lesion. Adenomas tend to have low signal intensity due to their high lipid content. Myelolipomas and cysts are usually easily identified on routine imaging. Adrenal carcinomas tend to be heterogenous with calcification and they have high signal intensity on T2-weighted MRI.

Following the diagnosis of an adrenal lesion, functional studies are indicated to detect secretory activity. Cortisol production is assessed with 24-hour urine samples. Elevated urinary levels of the catecholamine metabolites metanephrines and vanillyl mandelic acid (VMA) are found with phaeochromocytoma. Aldosterone excess results in HTN with hypokalaemia and an abnormal renin:aldosterone ratio. Dexamethasone suppression testing may be required to differentiate pituitary pathology (Cushing’s disease), adrenal hyperplasia or adenoma.

THERAPEUTICS

All biochemically active lesions require surgical excision. Special attention should be paid to preoperative alpha-adrenergic blockade for phaeochromocytomas, to avoid hypertensive emergencies, and steroid replacement in Cushing’s syndrome, to limit adrenal insufficiency.

The majority of asymptomatic non-functional lesions are benign; however, larger adenomas share imaging features with carcinomas. It has been shown that more than 90% of adrenal carcinomas are larger than 6 cm at diagnosis and adrenal tumours less than 4 cm have a 2% chance of being malignant. Tumours that are larger than 5 cm at diagnosis and those with suspicious features on T2-weighted MRI are possibly carcinomas and should be excised. Other tumours may be observed.

Adrenal tumours may be resected via open or laparoscopic approach. Suspected adrenocortical carcinomas are best dealt with open due to their tendency for local invasion, which may require en-bloc resection of surrounding organs.

PREVENTION

No preventative strategies exist.

PENILE DISORDERS

Penile disorders may be classified anatomically and functionally as:

• disorders affecting the prepuce
• disorders affecting the urethral meatus
• disorders affecting the glans
• disorders affecting the penile shaft
• sexually transmitted infections
• sexual and functional disorders.

DISORDERS OF THE PREPUCE

Phimosis is stenosis of the preputial orifice that prevents retraction of the foreskin over the glans. This may be considered primary (childhood) or secondary (previously retractible). Congenital adhesions between the glans and prepuce are present at birth and tend to loosen with age; about 90% of boys have a retractible foreskin by the age of 3 years. Inability to retract the foreskin persists in 1% of pubertal males. Pathological phimosis occurs from trauma or infection, with a resultant fibrotic ring. Recurrent infections of the glans and preputial sac (balanoposthitis) may cause and result from phimosis. Infections may result from poor foreskin hygiene (failure to retract the foreskin and clean underlying smegma daily) and are more common in diabetics.

Treatment may be initially conservative, with the application of steroid creams. Circumcision is indicated where adult phimosis prevents normal hygiene.

Paraphimosis is the inability to replace a retracted foreskin. This may occur after forcible retraction of a phimotic prepuce or where the prepuce has been left retracted (e.g. post catheterisation). The resultant constricting band can result in a vicious cycle of congestion and oedema of the glans and prepuce, with the potential for necrosis when severe. Treatment is by prompt replacement of the foreskin. This usually requires manual decompression of the oedema and occasionally a dorsal slit under local anaesthetic.

A short frenulum results in ventral deviation of the glans when the prepuce is retracted. This may result in tears during cleaning or intercourse. Treatment is usually by circumcision, although frenuloplasty may be sufficient.

Circumcision is the surgical excision of the prepuce. It is most commonly performed on male neonates for social or religious reasons. Circumcision may be medically indicated for recurrent balanoposthitis, recurrent UTIs associated with abnormal anatomy and in secondary phimosis. Although the procedural risks are low, there is an increased risk of meatal stenosis, concealed penis and the potential for excessive skin removal or damage to the glans. Potential benefits include some protection against sexually transmitted diseases and penile cancer as well as cosmetic considerations. Circumcision is contraindicated in the presence of congenital penile anomalies (e.g. hypospadias), as the prepuce may be required for reconstructive surgery.

DISORDERS AFFECTING THE URETHRAL MEATUS

The external urethral meatus is a sagittal slit that is the narrowest point of the urethra. The urethra just proximal to the meatus is dilated and this configuration produces rotational streaming and focuses the issuing urinary stream.

Hypospadias is malpositioning of the urethral meatus to the undersurface of the penis. Congenital hypospadias are most commonly distal (glandular or coronal). More proximal (severe) hypospadias may be penile or perineal. This disorder is associated with an incomplete foreskin and a ventral band connecting the meatus to its normal position, with a resulting ventral chordee.

Epispadias, the reverse disorder, is much less common and is usually associated with gross defects of fusion of the anterior bladder and urethra and of the pelvic girdle (extroversion).

Meatal strictures may be congenital or acquired. A meatal ulcer is a common problem in infancy and is virtually confined to circumcised infants. Meatal strictures can follow ammoniacal dermatitis (nappy rash) in babies. Any urethral discharge should be noted, its character observed and a bacteriological swab taken for smear and culture. Meatal strictures may be treated with simple dilation or meatoplasty.

DISORDERS AFFECTING THE GLANS

Discharge from the prepuce with inflammatory skin changes suggests an underlying disorder. The glans is examined after gently retracting the prepuce fully.

Balanitis and balanoposthitis are often non-specific but may be due to a number of specific venereal infections or secondary to malignant or premalignant conditions. Treatment with antibiotic or antifungal creams may hasten resolution. Recurrent episodes should prompt urological consultation.

Penile carcinoma is an uncommon condition that is largely preventable with adequate penile hygiene.

Premalignant lesions of the glans include:

• leukoplakia—an area of whitish, painless indurated epithelium secondary to chronic balanitis
• erythroplasia of Queyrat (or Paget’s disease)—an indurated plaque of epithelium of similar origin with a violaceous hue, which is similar to Bowen’s disease of the skin elsewhere and indicates carcinoma-in-situ of the glans, prepuce or shaft.

Penile carcinoma usually starts as a warty or nodular growth on the glans, coronal sulcus or the inner aspect of the prepuce. It may resemble genital warts. Progressive growth is associated with purulent and bloody discharge. The lesion eventually develops the typical appearance of a squamous cell cancer, with elevation, induration and fungative ulceration. Associated groin nodes may be inflammatory or malignant.

Treatment is by surgical excision with an adequate margin, usually a partial penectomy. Palpable nodes may also need excision based on the stage and grade of the primary lesion or their persistence after antibiotic therapy.

DISORDERS AFFECTING THE PENILE SHAFT

Subcutaneous induration of the shaft with a firm, non-tender plaque of fibrous tissue in the fascia surrounding the corpus cavernosum on one or both sides is due to Peyronie’s disease, a condition of unknown cause akin to Dupuytren’s disease and which results in irreversible damage of the tunica albuginea of the corpora cavernosa. Peyronie’s disease is one of the causes of chordee during erection. The natural history of the disease is an active and painful phase of plaque development and then a quiescent phase. The active phase is treated symptomatically and no further treatment of the quiescent phase is required unless chordee that limits voiding in the upright position or sexual penetration results from the plaque.

A fractured penis defines rupture of the corpora cavernosa due to forcible bending. This occurs exclusively with an erect penis and may involve one or both corpora and in severe cases the urethra as well. It is most commonly the result of intercourse but may occur with self-manipulation. The typical history is that of trauma with an audible ‘cracking’ sound followed by immediate loss of erection and the onset of penile bruising and swelling. The diagnosis is made clinically. Surgical repair of the corporal rent is undertaken to prevent penile angulation, pain and erectile dysfunction.

SEXUALLY TRANSMITTED INFECTIONS

The management of sexually transmitted infections (STIs) requires up-to-date knowledge of diagnostic and treatment practices, awareness of contact tracing and compassionate, non-judgmental care. An increasing number of patients with STIs have human immunodeficiency virus (HIV) infection, with either overt disease or positive antibody titre. All patients who present with a suspected STI should be screened for HIV and hepatitis B and C.

As a general rule it should be assumed that an ulcer on the glans penis is a syphilitic ulcer until proved otherwise. Care to prevent cross-infection should be taken. Syphilitic ulcers take about 4 weeks to appear from the time of contact. The chancre is usually painless. The lesion first appears as a firm reddened macule, usually in the coronal sulcus which, in most cases, undergoes ulceration and eventually regresses. The inguinal lymph nodes are invariably enlarged and are firm, discrete and mobile. Patients are not toxic at the time of penile ulceration but become so during the secondary stage of the disease (about 6–8 weeks after the appearance of the penile lesion). The causal organism, Treponema pallidum, is recognised by dark-field examination of exudate obtained from the lesion. The diagnosis may also be made by positive serology. Pain during micturition with a purulent discharge is commonly due to gonococcal urethritis. The causative organism is Neisseria gonorrhoeae. Infection often also involves the epididymis, seminal vesicles, prostate and bladder. Urethral stricture is a late complication.

Ulceration, particularly if painful, may be due to herpes simplex infection. This viral infection starts as a patch of erythema on the inner surface of the prepuce or on the glans, which develops vesicles and pustules that, on abrasion, form small ulcers. The diagnosis is made cytologically by finding the characteristic ‘ground glass’ inclusion in giant cells from the involved epithelium. The common venereal viral warts (condylomata acuminata) occasionally ulcerate. Rare causes of ulceration include chancroid (soft chancre). Chancroid is an acute ulcerative lesion with lymphadenopathy caused by Haemophilus ducreyi. Other diseases diagnosed by smear and culture are lymphogranuloma venereum (Chlamydia) and granuloma inguinale (Donovan bacillus). These infections are more common in tropical countries. Penile candidiasis presents as an itchy balanitis with white plaques.

Sexually transmitted infections usually respond to antibiotics. Syphilis is treated with penicillin. Azithromycin 1 g orally in a single dose or doxycycline 100 mg orally twice a day for 7 days is the treatment of choice for non-gonococcal urethritis in men or other infection with Chlamydia trachomatis. Uncomplicated gonococcal infections are treated with ceftriaxone. Herpes genitalis is treated with aciclovir. Chancroid is treated with sulfonamides, granuloma venereum and inguinale with tetracycline, and venereal warts with topical anti-viral cream or local diathermy excision. Treatment of the patient’s partner is important in preventing recurrence.

SEXUAL AND FUNCTIONAL DISORDERS

Impotence is a common problem and is defined as failure to obtain or maintain an erection strong enough for satisfactory sexual activity. Organic causes can be grouped by aetiology and are most commonly:

• vasculogenic—associated with and having the same risk factors as generalised vascular disease
• traumatic—particularly to the pelvic nerves and vasculature (including surgery for prostate cancer)
• neurogenic—including spinal cord injury and multiple sclerosis
• endocrine—including diabetes, where the autonomic neuropathy and vascular insufficiency result in loss of erections
• any debilitating disease (anaemia, carcinoma)
• old age.

Many drugs (alcohol, opiates, hypotensives, phenothiazines and sedatives) are thought to be contributory, although the association is often poorly understood. Functional causes associated with psychogenic factors are not as common as a primary cause; these are usually diagnoses of exclusion once organic causes have been excluded.

Management of impotence has been revolutionised by the development of phosphodiesterase type-5 (PDE5) enzyme inhibitors. These drugs act in the breakdown of cyclic guanosine monophosphate (cGMP), which causes smooth muscle relaxation in the arterioles of the corpora cavernosa, hence increasing intracavernosal blood flow and invoking erection. These drugs (sildenafil, tadalafil and vardenafil) can be taken by most patients, except where there is concomitant nitrate use for the management of angina. There is a small incidence of minor side effects such as headache and facial flushing. Initial management of impotence may therefore take place in the primary care setting where, after careful history and examination to exclude organic pathologies that should otherwise be treated, a trial of PDE5 inhibitors may take place. Local intracavernosal injections of a vasodilator, such as alprostadil or a papaverine-based mixture, can be used in patients who do not respond to PDE5 drugs. Long-term compliance with this treatment is poor. Implanting an inflatable penile prosthetic device, which has high satisfaction and efficacy rates, is suitable for men who want a long-term ‘cure’ of erectile dysfunction.

Priapism is a persistent erection, not associated with sexual stimulation, lasting more than 4 hours. It may be divided into veno-occlusive (low-flow) and arterial (high-flow) states. The corpora cavernosa are stiff and distended and painful; the corpus spongiosum and glans are flaccid. Low-flow priapism occurs where there is venous stasis, which can be due to multiple causes, including persistent spasm of the venous smooth muscle sphincters that maintain erection, after use of intracavernosal injection for impotence, conditions causing hyper-coagulable states such as sickle cell anaemia, multiple myeloma or leukaemia, other malignancy, and other drugs including anticoagulants, phenothiazine, fluoxetine and cocaine. High-flow priapism results from an arteriovenous anomaly after pelvic, perineal or penile trauma and, unlike low-flow, is generally not painful early on. If prolonged, priapism of either cause will lead to thrombosis of the veins draining erectile tissue. Subsequently, even though priapism is relieved, there may be permanent impotence.

If initial treatment with cold showers and oral pseudoephedrine fails, then intracavernosal injections with vasoactive agents such as phenylephrine (with cardiac monitoring) should be attempted. If these measures fail, a shunt between one of the corpora cavernosa and the corpus spongiosum or between corpus cavernosum and saphenous vein should be carried out within 6 hours. Prompt therapy is required, to reduce permanent erectile dysfunction.

RESOURCES

emedicine, urology articles (an online resource for patients and doctors). http://emedicine.medscape.com/urology.

European Association of Urology, urological guidelines (authoritative and much used). http://www.uroweb.org/guidelines/online-guidelines/.

Kidney Health Australia, Chronic kidney disease management in general practice. http://www.kidney.org.au/LinkClick.aspx?fileticket=dSUlcQgPd6o%3d&tabid=635&mid=1584.

Society for Chronic Pelvic Pain and Interstitial Cystitis. http://ucpps.org/.

REFERENCES

1 Goldfarb DS, Coe FL. Prevention of recurrent nephrolithiasis. American Family Physician 2009; 15 November. Online. Available: http://www.aafp.org/afp/991115ap/2269.html.

2 Sea J, Poon KS, McVary KT. Review of exercise and the risk of benign prostatic hyperplasia. Phys Sportsmed. 2009;37(4):75-83.

3 Wilt TJ, MacDonald R, Ishani A. Beta-sitosterol for the treatment of benign prostatic hyperplasia: a systematic review. BJU Int. 1999;83(9):976-983.

4 Kaplan SA, Volpe MA, Te AE. A prospective, 1-year trial using saw palmetto versus finasteride in the treatment of category III prostatitis/chronic pelvic pain syndrome. J Urol. 2004;171:284-288.

5 Wilt T, Ishani A, MacDonald R, et al. Pygeum africanum for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2002;1:CD001044.

6 Konrad L, Müller HH, Lenz C, et al. Antiproliferative effect on human prostate cancer cells by a stinging nettle root (Urtica dioica) extract. Planta Med. 2000;66(1):44-47.

7 Shoskes DA, Kannan Manickam AE. Herbal and complementary medicine in chronic prostatitis. World J Urol. 2003;21:109-113.

8 Elist J. Effects of pollen extract preparation Prostat/Poltit on lower urinary tract symptoms in patients with chronic nonbacterial prostatitis/chronic pelvic pain syndrome: a randomized, double-blind, placebo-controlled study. Urology. 2006;67:60-63.

9 International Diabetes Federation. Clinical Guidelines Task Force. Global guideline for type 2 diabetes. Brussels: IDF, 2005.

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