Embryology

From the primitive urethra as a series of solid epithelial buds which in a matter of weeks become canalised

     Surrounding mesenchyme forms the muscular and connective tissue of the gland and has a major role in differentiation (stromal epithelium interactions)

Skene’s tubules opening on either side of the female urethra are the homologue of the prostate

Surgical anatomy

The contemporary classification of the prostate into different zones was based on the work of McNeal (Fig. 66.1). He showed that it is divided into: the peripheral zone (PZ) which lies mainly posteriorly and from which most carcinomas arise, and a central zone (CZ) which lies posterior to the urethral lumen and above the ejaculatory ducts as they pass through the prostate; the two zones are rather like an egg in its egg-cup. There is a also periurethral transitional zone (TZ) from which most benign prostatic hyperplasia (BPH) arises. Smooth muscle cells are found throughout the prostate, but in the upper part of the prostate and bladder neck, there is a separate sphincter muscle that sub serves a sexual function, closing during ejaculation. Resection of this tissue during prostatectomy is responsible for retrograde ejaculation. The distal striated urethral sphincter muscle is found at the junction of the prostate and the membranous urethra, it is horse-shoe shaped with the bulk lying anteriorly; it is quite distinct from the muscle of the pelvic floor (Fig. 65.1).

The glands of the peripheral zone (Fig. 66.2), lined by columnar epithelium, lie in the fibromuscular stroma and their ducts which are long and branched open into posterolateral grooves on either side of the verumontanum. The glands of the CZ and TZ are shorter and un­ branched. All of these ducts, the common ejaculatory ducts and the prostatic utricle open into the prostatic urethra. No wonder that infection of the prostatic urethra is difficult to eradicate!

Benign prostatic hyperplasia (BPH) starts in the periurethral tran­sitional zone and as it increases in size it compresses the outer PZ of the prostate which becomes the false capsule. There is also the outer true fibrous anatomical capsule; and external to this lie condensations of endopelvic fascia known as the periprostatic sheath of endo pelvic fascia. Between the anatomical capsule and the prostatic sheath lies the abundant prostatic venous plexus. The prostatic sheath is contiguous with the strong fascia of Denonvillier that separate the prostate and its coverings from the rectum. The neurovascular bundles supplying autonomic innervation to the corpora of the penis are in very close relationship to the posterolateral aspect of the prostatic capsule and are at risk of damage during radical cystoprostatectomy or radical prostatectomy; inadvertent diathermy in the region of these nerves may be the cause of erectile impotence after transurethral prostatectomy.

Physiology

The prostate has a sexual function, but it is a little unclear how important its secretions are to human fertility. That the normal adult prostate undergoes atrophy after castration was known to John Hunter.

Systemic hormonal influences (endocrine) and local growth factors (paracrine and autocrine)

The growth of the prostate is governed by many local and systemic hormones whose exact functions are not yet known. The main hormone acting on the prostate is testosterone which is secreted by the Leydig cells of the testes under the control of luteinizing hormone (LH), which is secreted from the anterior pituitary under the control of hypothalamic luteinizing hormone-releasing hormone (LHRH). Testosterone is converted to 5-di-hydrotestosterone (DHT) by the enzyme 5a-reductase, which is found in high concentration in the prostate and the perigenital skin. Other androgens are secreted by the adrenal cortex, but their effects are minimal. Oestrogenic steroids are also secreted by the adrenal cortex and in the ageing male may play a part in disrupting the delicate balance between DHT and local peptide growth factors, and hence increase the risk of BPH. Increased levels of serum oestrogens, by acting on the hypothalamus, decrease the secretion of LHRH (and hence LH) and thereby decrease serum testosterone levels. Therefore, pharma­cological levels of oestrogens cause atrophy of the testes and prostate by means of reductions in testosterone.

Other locally acting peptides are secreted by the prostatic epithelium and mesenchymal stromal cells in response to steroid hormones. These include epidermal growth factor, insulin-like growth factors, basic fibroblast growth factor and transforming growth factors a and 3. These undoubtedly play a part in normal and abnormal prostatic growth, but as yet their functions are unclear.

Elaboration and secretion of prostate-specific antigen (PSA) and acid phosphatase

PSA is a glycoprotein which is a serine protease. Its function may be to facilitate liquefaction of semen, but it is a marker for prostatic disease. It is measured by an immunoassay and the normal range can differ a little from laboratory to laboratory. The normal upper limit is about 4 nmollml. Its level in men with metastatic prostate cancer is usually increased to >30 nmol/ml and falls to low levels after successful andro­gen ablation. Men with locally confined prostate cancer usually have serum PSA levels <—15 nmol/ml. Although PSA is a reliable marker for the progress of advanced disease it is neither specific nor sensitive in the differential diagnosis of early prostate cancer and BPH, as both diseases are compatible with PSA in the range of 4—12 nmol/ml. PSA measurement has superseded measurement of serum acid phosphatase.

Benign prostatic hyperplasia

BPH occurs in men over 50 years of age; by the age of 60 years 50 per cent of men have histological evidence of BPH and 15 per cent have significant lower urinary tract symptoms

Aetiology of benign prostatic hyperplasia

Hormones

Serum testosterone levels slowly but significantly decrease with advancing age; however, levels of oestrogenic steroids are not decreased equally. According to this theory the prostate enlarges because of increased oestrogenic effects. It is likely that the secretion of intermediate peptide growth factors plays a part in the development of BPH.

Pathology

BPH affects both glandular epithelium and connective tissue stromal to variable degrees. These changes are similar to those occurring in breast dysplasia (see Chapter 45), where adenosis, epitheliosis and stromal proliferation are seen in differing proportions. BPH typically affects the submucous group of glands in the transitional zone, forming a nodular enlargement. Eventually, this overgrowth compresses the PZ glands into a false capsule and causes the appearance of the typical ‘lateral’ lobes.

When BPH affects the sub cervical central zone glands, a‘middle’ lobe develops which projects up into the bladder within the internal sphincter (Fig. 66.3). Sometimes both lateral lobes also project into the bladder, so that when viewed from within, the sides and back of the internal urinary meatus are surrounded by an intravesical prostatic collar.

Effects of benign prostatic hyperplasia

It is important to realise that the relationship between anatomical prostatic enlargement (BPH), symptoms of prostatism and urodynamic evidence of bladder outflow obstruc­tion (BOO) is complex (Fig. 66.4). Pathophysiologically, bladder outflow obstruction may be caused in part by increased smooth muscle tone which is under the control of alpha-adrenergic agonists. Consequences of BPH

  No symptoms, no bladder outflow obstruction (BOO)

No symptoms, but urodynamic evidence of BOO

Symptoms of prostatism, no evidence of BOO

Symptoms of prostatism and BO

Others (acute/chronic retention, haematuria, urinary infection and stone formation)

Anatomically, the effects are as follows.

Urethra

The prostatic urethra is lengthened, sometimes to twice its normal length, but it is not narrowed anatomically. The normal posterior curve may be so exaggerated that it requires a curved catheter to negotiate it. When only one lateral lobe is enlarged, distortion of the prostatic urethra occurs.

  Bladder

  If BPH causes bladder outflow obstruction, the musculature of the bladder hypertrophies to overcome the obstruction and appears trabeculated (Fig. 66.5). Significant BPH is associated with increased blood flow and the resultant veins at the base of the bladder are apt to cause haematuria.