Benign prostatic hyperplasia

• benign glandular and stromal hyperplasia of the transitional zone of the prostate

• BPH is a histological diagnosis. The term BPH is often used interchangeably with benign prostatic syndrome.

• lower urinary tract symptoms caused by benign hyperplasia of the transitional zone of the prostate

• any obstruction to urinary outflow from the bladder which presents with lower urinary tract symptoms and is confirmed on urodynamic testing

• BOO caused by BPH

• Prevalence of BPH increases with age (present in ∼ 50% of men > 50 years and more than 80% of men > 80 years).

• Hormonal factors

• Stem cell proliferation and longevity

• Genetic susceptibility

• Androgens

• Estrogens

• Androgen-estrogen imbalance

• Dihydrotestosterone (DHT) is a potent prostatic growth factor

• Gene amplification of androgen receptors (present in the glandular epithelial cells and stromal cells) → increased androgen receptor sensitivity to androgens → prostatic hyperplasia

• Estrogens (mainly estradiol) are potent stimulators of prostatic hyperplasia.

• In men, circulating estradiol is formed from aromatization of testosterone in fat and muscle, and ∼ 20% is secreted by the Leydig cells of the testes. Hence, obese men are at a higher risk of developing BPH.

• As men age, testosterone levels decline, but estrogen levels remain the same, which results in a higher estrogen/testosterone ratio.

• abnormal proliferation and longer prostatic stem cell life-span

• Genes involved in the development of BPH include growth factor genes, androgen-regulator genes, apoptosis genes, and androgen-regulated genes

• NO

• The prostate consists of zones and lobes

• The middle transition zone/the lateral and middle prostatic lobes (periurethral lobes) are involved in development of BPH.

• The outer peripheral zone is involved in development of prostate cancer.

• A combination of hormonal factors, stem cell proliferation and genetic susceptibility → glandular and stromal hyperplasia in the transition zone → formation of smooth, elastic, firm hyperplastic nodule → slit-like prostatic urethral compression → BOO → obstructive symptoms of BPH

• Detrusor overactivity (involuntary detrusor contractions during bladder filling) → irritative symptoms of BPH

• Weakening of the bladder wall → incomplete voiding → urinary stasis → predisposition to urinary tract infections, acute/chronic urinary retention, and formation of bladder stones

• Increased intracystic pressure while voiding → detrusor muscle hypertrophy → bladder trabeculation and pseudodiverticula formation

• The bladder mucosa protrude through the layers of the bladder wall due to the raised intracystic pressure. These protrusions are called pseudodiverticula.

Zones of the prostate

There are three main glandular zones of the prostate:

– The peripheral zone (6) is the largest zone, containing ∼ 75% of the glandular tissue of the prostate; prostate adenocarcinomas most commonly arise in this zone. The peripheral zone primarily lies in the inferolateral and posterior aspects of the prostate gland and is readily palpable on digital rectal examination.

– The central zone (5) lies posterior to the transition zone and surrounds the ejaculatory ducts. It contains ∼ 20% of glandular tissue and is an uncommon site of prostate adenocarcinoma.

– The transition zone (3) is the part of the prostate gland that surrounds the urethra. It contains < 5% of glandular tissue and is the region that is enlarged in benign prostatic hyperplasia.

A fourth zone known as the anterior zone (2) is located anterosuperiorly in the gland. It is primarily composed of fibromuscular tissue devoid of glands (anterior fibromuscular zone).

Externally, the prostate is surrounded by a condensation of the pelvic fascia, known as the false capsule (1).

Middle lobe hyperplasia in prostate hyperplasia

In this image, the structures can at best be presumed: The middle of the image may potentially show the middle lobe of the hypertrophic prostate that is obstructing the urethra. The lateral lobes of the prostate can be seen on the right and left, with the opened urinary bladder located cranially.

• Lower urinary tract symptoms (LUTS)

• Often gross hematuria

• the irritative and obstructive symptoms of BPH, grouped together

• Urinary frequency

• Urinary urgency and urge incontinence

• Nocturia

• Occasionally dysuria

• Hesitancy --> Difficulty to initiate micturition → delayed onset of urination

• Straining to urinate --> The patient strains (contracts his abdominal muscles) to initiate, maintain, and improve the urinary stream

• Poor and/or intermittent stream (not continuous)

• Prolonged terminal dribbling

• Sensation of incomplete voiding

• The vascularity of the prostate gland is increased due to the hyperplastic process. These vessels are friable and easily disrupted on physical activity, which can result in recurrent hematuria.

• symmetrically enlarged, smooth (no nodules), firm, nontender prostate with rubbery or elastic texture

• Presence of nodules or a hard consistency of the prostate is suggestive of prostate cancer. Tenderness on palpation is suggestive of prostatitis.

• a scoring system based on the presence and severity of seven BPH symptoms in the past 30 days

• The symptoms scored are frequency, nocturia, urgency, weak stream, straining, intermittency, and sensation of incomplete voiding. Scores range from 0 (for absence of particular symptom) to 5 (for persistent symptoms) which adversely affects the patient's quality of life.

• 0–7 points: mild symptoms

• 8–19 points: moderate symptoms

• 20–35 points: severe symptoms

• IPSS is also useful as a prognostic marker of disease progression and response to treatment.

To remember the symptoms of BPH, think “FUNWISE”: Frequency, Urgency, Nocturia, Weak stream /hesitancy, Intermittent stream, Straining to urinate, and Emptying (not emptying completely, terminal dribbling).

• mainly used to assess complications and rule out accompanying or differential diagnoses

• Prostate specific antigen levels (PSA)

• Renal parameters

• Urinalysis and urine culture

• Serum PSA levels may be elevated in BPH patients with acute urinary retention. The level normalizes within 2 weeks. Hence, PSA should be tested only > 2 weeks in these patients. Unlike previously thought, serum PSA can be tested immediately after DRE. This is because DRE only mildly and transiently increases the serum PSA levels.

• Indicated in men with ≥ 10 year life expectancy to identify co-existent prostate cancer, if present

• Men with a < 10 year life-expectancy may harbor prostate cancer which may not progress/metastasize during the person's life-time. Surgery in these patients, with its accompanying risks and complications, is not recommended. BPH, however, is not a risk factor for the development of prostate cancer.

• ↑ Free PSA levels

• In contrast, prostate cancer is characterized by ↓ free PSA and ↑ total PSA. Suspect malignancy if PSA levels > 4 ng/ml.

• blood urea nitrogen, creatinine, electrolyte levels

• indicated in men with high post-void residual volumes

• In these patients, the risk of chronic renal insufficiency secondary to bladder outlet obstruction is high.

• to rule out urinary tract infection and hematuria

• Symptoms of urinary tract infection (urgency, frequency) can mimic the irritative symptoms of BPH. Patients with BPH can also have concomitant UTI.

• Abdominal ultrasound

• Transrectal ultrasound

• Intravenous pyelogram (IVP)

• MRI

• Increased total prostate volume --> Total prostate volume is a useful marker to measure disease progression and response to medication.

• Elevated post-void residual volume (> 100 ml) --> The first scan is done when the patient's bladder is full. The patient is then asked to micturate and the scan is repeated. Normal post-void residual volume is < 15 ml.

• Bladder wall thickening

• Hydronephrosis

• indicated only if prostate cancer is suspected (e.g., abnormal DRE, elevated serum PSA)

• Elevation of the bladder floor

• Fishhook appearance of the distal ureters

• Allows for the lobar classification and preprocedural assessment of prostatic tissue

• Can be used to differentiate BPH from prostate cancer

• > 15 mL/sec

• Maximal flow rates < 15 mL/sec: bladder outlet obstruction

• Maximal flow rates < 10 mL/sec (due to BPH): indication for surgery

• Performed if there is a high suspicion of postatic cancer

• Differentiated prostatic cells

• ossible corpora amylacea

• Prostate cancer

• Prostatitis

• Prostatic abscess

• Recurrent UTI --> BPH → incomplete voiding → urinary stasis → predisposition to urinary tract infections

• Urinary retention with bladder distension and bladder wall thickening (hypertrophy)

• Bladder calculi

• Hydronephrosis

• Chronic kidney disease