BPH

BENIGN PROSTATE HYPERTROPHY

embryology

·         From the primitive urethra, a series of solid epithelial buds develop and become canalised in a matter of weeks.

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

·         Skene’s tubules, which open on either side of the female urethra, are the homologue of the prostate.

surgical anatomy

·         Peripheral zone (PZ) - lies posteriorly (most carcinomas arise)

·         Central zone (CZ) - lies posterior to the urethral lumen and above the ejaculatory ducts as they pass through the prostate; the two zones like an egg in an eggcup.

·         Periurethral transitional zone (TZ) -  most BPH arises.

·         The distal striated urethral sphincter muscle is found at the junction of the prostate and the membranous urethra; it is horseshoe shaped with the bulk lying anteriorly and is quite distinct from the muscle of the pelvic floor.

·         The glands of the PZ lined by columnar epithelium

·         The glands of the CZ and TZ are shorter and unbranched.

·         All these ducts, the common ejaculatory ducts and the prostatic utricle open into the prostatic urethra.

·         BPH starts in the TZ → compresses the outer PZ of the prostate → 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 endopelvic fascia.

·         Between the anatomical capsule and the prostatic sheath lies the abundant prostatic venous plexus.

·         The prostatic sheath is contiguous with the fascia of Denonvilliers(separates 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

Blood supply Arterial supply - the inferior vesical artery (a branch of the IIA), a branch entering the prostate on each side at its lateral extremity. Venous - dorsal vein of the penis → prostatic plexus → drains into the IIV on each side. Some of the venous drainage passes to the plexus of veins lying in front of the vertebral bodies and within the neural canal. (*) *        valveless and constitute the valveless vertebral veins of Batson. *        This communication may explain the readiness with which carcinoma of the prostate spreads to the pelvic bones and vertebrae.

 
                                              

PHYSIOLOGY

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

·         The growth of the prostate is governed by many local and systemic hormones

·         The main hormone acting on the prostate is testosterone ←  Leydig cells of the testes under the control of LH ← anterior pituitary under the control of hypothalamic LHRH – 90%

·         Other androgens are secreted by the adrenal cortex, but their effects are minimal in the normal male (5-10%)

·         LHRH has a short half-life and is released in a pulsatile manner.

·         This pulsatile release is important, as receptors for LHRH will become desensitised if permanently occupied.

·         The administration of LHRH analogues in a continuous, non-pulsatile manner → receptor desensitisation and forms the basis for androgen deprivation therapy in prostate cancer.

·         Testosterone is converted to 1,5- dihydrotestosterone (DHT) by the enzyme 5α-reductase, which is found in high concentration in the prostate and the perigenital skin (type II).

·         ↑ levels of serum oestrogens → ↓ hypothalamus → ↓ LHRH (and hence LH) → ↓serum testosterone levels.

·         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 alpha and beta.

·         These undoubtedly play a part in normal and abnormal prostatic growth, but as yet their functions are unclear (Summary box 73.1).

Elaboration and secretion of prostate-specific antigen and acid phosphatases

·         PSA is a glycoprotein that is a serine protease → to facilitate liquefaction of semen, but it is a marker for prostatic disease.

·         There is no real normal upper limit.

·         The levels ↑ with age, with prostate cancer and with BPH.

·         Men aged 50–69 years → 3–4 ng/ml →  discussion about prostate biopsy.

·         Metastatic prostate cancer → >30 ng/ml and falls to low levels after successful androgen ablation.

·         Locally confined prostate cancer -  <10–15 ng/ms.

·         Although PSA is a reliable marker for the progression of advanced disease, it is neither specific nor sensitive in the differential diagnosis of early Ca and BPH with PSA in the range of 3–15 ng ml–1.

·         In general, one would advise men aged 50–69 years to undergo prostate biopsy if the PSA was more than ~ 3 ng ml–1. The threshold would be lower in younger men with a strong family history.

Causes of elevated Serum PSA

·         BPH

·         Ca Prostate

·         Acute Retention

·         Urinary catheterization

·         DRE

·         Prostitis

BENIGN PROSTATIC HYPERPLASIA

Aetiology of benign prostatic hyperplasia

Hormones

·         Serum testosterone levels ↓ with advancing age; however, levels of oestrogenic steroids are not ↓ equally.

·         According to this theory, the prostate enlarges because of ↑ 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 stroma to variable degrees (= breast dysplasia  → adenosis, epitheliosis and stromal proliferation are seen in differing proportions)

·         BPH typically affects the submucous group of glands in the TZ → nodular enlargement → compresses the PZ glands into a false capsule → appearance of the typical ‘lateral’ lobes.

·         When BPH affects the subcervical CZ glands → ‘middle’ lobe develops that projects up into the bladder within the internal sphincter

·         Sometimes, both lateral lobes also project into the bladder → the sides and back of the internal urinary meatus are surrounded by an intravesical prostatic collar.

Effects of BPH

·         BPH + LUTS + BOO → complex

Anatomically, the effects are as follows:

·         Urethra. The prostatic urethra is lengthened (2 times to normal), 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 BOO, the musculature of the bladder hypertrophies to overcome the obstruction and appears trabeculated. Significant BPH is associated with ↑ blood flow, and the resultant veins at the base of the bladder are apt to cause haematuria.

Lower urinary tract symptoms (LUTS)

·         Urologists prefer the term LUTS and discourage the use of the descriptive term ‘prostatism’.

·         The following conditions can coexist with BOO (Differential Dx)

*        idiopathic detrusor overactivity

*        neuropathic bladder dysfunction as a result of diabetes, strokes, Alzheimer’s disease or Parkinson’s disease

*        degeneration of bladder smooth muscle → impaired voiding and detrusor instability

*        BOO due to BPH.

Lower urinary tract symptoms can be described as:

Ø  voiding

v  – hesitancy (worsened if the bladder is very full);

v  – poor flow (unimproved by straining);

v  – intermittent stream – stops and starts;

v  – dribbling (including after micturition);

v  – sensation of poor bladder emptying;

v  – episodes of near retention.

Ø  storage

v  – frequency;

v  – nocturia;

v  – urgency;

v  – urge incontinence;

v  – nocturnal incontinence (enuresis).

Bladder outflow obstruction

·         Urodynamic concept → low flow rates + high voiding pressures.

·         It can be diagnosed definitively only by pressure–flow studies.

·         This is because symptoms are relatively non-specific and can result from detrusor instability, neurological dysfunction and weak bladder contraction.

·         Nonetheless, flow rates provide a useful guide for everyday clinical management.

·         Urodynamically proven BOO may result from:

Ø  BPH;

Ø  bladder neck stenosis;

Ø  bladder neck hypertrophy;

Ø  prostate cancer;

Ø  urethral strictures;

Ø  functional obstruction due to neuropathic conditions.

The primary effects of BOO on the bladder are as follows:

·         Urinary flow rates ↓ (for a voided volume > 200 ml, a peak flow rate of > 15 ml s–1 is normal, one of 10–15 ml s–1 is equivocal and one < 10 ml s–1 is low.

·         Voiding pressures increase (pressures > 80 cmH2O are high, pressures between 60 and 80 cmH2O are equivocal and pressures < 60 cmH2O are normal).

The long-term effects of bladder outflow obstruction are as follows:

1.      The bladder may decompensate so that detrusor contraction becomes progressively less efficient and a residual urine develops.

2.      The bladder may become more irritable during filling with a ↓ in functional capacity partly caused by detrusor overactivity, which may also be caused by neurological dysfunction or ageing, or may be idiopathic.

Aside from symptoms, the complications of BOO are as follows:

1.      Acute retention of urine is sometimes the first symptom of BOO.

2.      Chronic retention. residual volume is >250 ml or so → the tension in the bladder wall ↑ owing to the combination of a large volume of residual urine and ↑ resting and filling bladder pressures (a condition known as high-pressure chronic retention).

Ø  The increased intramural tension → functional obstruction of the upper UT with the development of bilateral hydronephrosis → UUTI and renal impairment

Ø  May present with overflow incontinence, enuresis and renal insufficiency.

3.      Impaired bladder emptying. If the bladder decompensates → large volume of residual urine → urinary infection and calculi are prone to develop.

4.      Haematuria. This may be a complication of BPH. Other - causes must be excluded

5.      Other than pain from retention, pain is not a symptom of BOO, if present → exclude acute retention, urinary infection, stones, Ca Prostate and bladder.

ASSESSMENT OF THE PATIENT WITH LUTS

History

Ø  Symptom score sheets such as the International Prostate Symptom Score (IPSS)

Ø  In addition to the IPSS, a frequency–volume diary completed by the patient before attending the clinic is invaluable in revealing fluid intake habits, diurnal variation in outputs and low-volume, frequent voiding.

Ø  Ask for LUTS symptoms

EXIMINATION

Abdominal

Ø  In patients with chronic retention → a distended bladder, Ballotable Kidney will be found

Ø   General physical examination → signs of chronic renal impairment with anaemia and dehydration.

Ø  The external urinary meatus → to exclude stenosis, and the epididymides are palpated for signs of inflammation.

Rectal examination

Ø  BPH → the posterior surface is smooth, convex and typically elastic, may be firm in consistency. The rectal mucosa can be move over the prostate. Residual urine may be felt as a fluctuating swelling above the prostate → if there is a considerable amount of residual urine present, it pushes the prostate downwards, making it appear larger than it is.

The nervous system

Ø  to eliminate a neurological lesion. DM, tabes dorsalis, disseminated sclerosis, cervical spondylosis, Parkinson’s disease and other neurological states

Ø  If these are suspected →  pressure–flow urodynamic study should be carried out to diagnose BOO.

Ø  Examination of perianal sensation and anal tone is useful in detection of an S2 to S4 cauda equina lesion.

INVESTIGATIONS

Essential investigations

v  Urine analysis by dipstick for blood, glucose and protein (Urine RE)

v  Urine culture for infection

v  Serum creatinine

v  Urinary flow rate and residual volume measurement

Additional investigations

v  PSA if indicated

v  Pressure–flow studies

Serum PSA

v  Informed about the test → the risks of the prostate biopsy, the risks of the detection of a cancer and positive aspects of the early discovery of a small prostate cancer → measurement of serum PSA

v  Men in whom a diagnosis of early prostate cancer might influence treatment option (such as those under 70 years or those with a positive family history who might be offered radical treatment) should be offered a PSA measurement.

v  If this is in excess of 2.5–4 nmol/L→ TURS + multiple transrectal biopsies (10 biopsies) should be considered.

v  If rectal examination is quite normal with no suspicion of cancer →  then there is little point in the routine measurement of PSA in men with uncomplicated BOO.

Flow rate measurement

·         2 or 3 voids should be recorded - the voided volume should be in > of 150–200 ml.

·         A typical history and a flow rate < 10 ml/s (for a voided volume of >200 ml) → recommend treatment.

·         Usually, a flow rate measurement + US measurement of post-void residual urine.

·         The machine must be accurately calibrated. The patient must void volumes in excess of 150 ml, and two or three recordings are needed to obtain a representative measurement.

Pressure–flow urodynamic studies

They should be performed on the following patients:

1.      men with suspected neuropathy (Parkinson’s disease, dementia, longstanding diabetes, previous strokes, multiple sclerosis);

2.      men with a dominant history of irritative symptoms and men with lifelong urgency and frequency;

3.      men with a doubtful history and those with flow rates in the near normal range (~ or > 15 ml s–1);

4.      men with invalid flow rate measurements (because of low voided volumes).

IMAGING

Upper tract imaging

·         Most urologists no longer carry out imaging of the upper tract in men with straightforward symptoms.

·         Obviously, if infection or haematuria is present, then the upper tract should be imaged by means of intravenous urogram or ultrasound scan.

Cystourethroscopy

·         should always be done immediately prior to prostatectomy → to exclude a urethral stricture, a bladder carcinoma and the occasional non-opaque vesical calculus.

·         The decision of whether to perform prostatectomy must be made before cystoscopy.

·         This should be based on the patient’s symptoms, signs and investigations.

·         Direct inspection of the prostate is a poor indicator of BOO and the need for surgery.

Transrectal ultrasound scanning

·         There is no need to carry this out routinely.

·         Accurate estimation of prostatic size is also possible by transabdominal USG.

MANAGEMENT OF MEN WITH BPH OR BOO

Options for treatment of LUTS secondary to BPH

·         Conservative measures include watchful waiting in conjunction with fluid restriction and reduction in caffeine intake

·         Drug therapy is with α-blockers or, in men with a large prostate, a 5α-reductase inhibitor, or both

·         Interventional measures include TURP (gold standard) , open prostatectomy for large glands

Strong indications for treatment (usually prostatectomy) include:

1.      Acute retention in fit men with no other cause for retention

2.      Chronic retention and renal impairment: a residual urine of 200 ml or more, a raised blood urea, hydroureter or hydronephrosis demonstrated on urography and uraemic manifestations

3.      Complications of BOO: stone, infection and diverticulum formation.

4.      Haemorrhage: venous bleeding from a ruptured vein overlying the prostate

5.      Severe symptoms:

v  ↑ difficulty in micturition, with considerable frequency day and night, delay in starting and a poor stream.

v  Severe symptoms, a low maximum flow rate (< 10 ml s–1) and an increased residual volume of urine (100–250 ml) are relatively strong indications

v  The exact cut-off for operative or non-operative treatment will depend on careful discussion between the patient and the urologist

6.   Failed a preliminary trial of medical therapy

Treatment

Men with symptoms attending for elective treatment (excluding acute and chronic retention)

Conservative treatment

v  men with relatively mild symptoms, reasonable flow rates (> 10 ml–1) and good bladder emptying (residual urine < 100 ml)

v  Waiting for a period of 6 months after careful discussion → repeat assessment of symptoms, flow rates and ultrasound → stable symptoms → No Treatment.

v  Advice over limiting fluid intake in the evening and careful use of propantheline to help with irritative symptoms is also useful.

Drugs

v  In men who are very concerned about the development of sexual dysfunction after transurethral resection of the prostate (TURP), the use of drugs may be helpful.

v  α-Adrenergic blocking agents inhibit the contraction of smooth muscle that is found in the prostate → work more quickly → side-effect (+)

v  5α-reductase inhibitors → inhibit the conversion of testosterone to DHT, the most active form of androgen → result in a 25% shrinkage of the prostate gland in a year ( take times, fewer side-effect).

v  Drug therapy results in improvements in maximum flow rates by about 2 ml s–1 → mild (20%) improvement in symptom scores.

v  TURP →  maximum flow rates from 9 to 18 ml s–1 and a 75% improvement in symptom scores.

v  These drugs are expensive

v  They may be best targeted at men who have failed an initial trial of watchful waiting and who wish to avoid surgery for a period.

Operative treatment

v  Apart from the strong indications for operative treatment mentioned above, the most common reason for TURP is a combination of severe symptoms and a low flow rate < 12 ml s–1.

v  The key is to assess symptoms carefully and to counsel men about sideeffects and likely outcome before advising operative treatment.

Operative Management of BPH

Counselling men undergoing prostatectomy (Complications)

1.      Retrograde ejaculation. occurs in about 65% of men after prostatectomy.

2.      Erectile impotence. 5% usually those whose potency is waning.

3.      The success rate.

·         90% who was operated for severe symptoms and UD proven BOO → symptoms ↓ and flow rates ↑.

·         65% of those with mild symptoms or those with weak bladder contraction as the cause of their symptoms do well.

·         Men with unobstructed detrusor instability do not respond well to TURP.

4.      The risk of reoperation. After TURP, this is about 15% after 8–10 years.

5.      The morbidity rate.

·         Death -                 < 0.5%

·         severe sepsis -            6%

·         Severe haematuria (requiring transfusion of > 2 units of blood) - about 3%.

·         After DC, about 15–20% of men subsequently require antibiotic treatment for symptoms of urinary infection.

·         Risk factors for complications include admission with retention, prostate cancer, renal impairment and advanced age.

Methods of performing prostatectomy

(1)   transurethrally (TURP),

(2)   retropubically (RPP),

(3)   through the bladder (transvesical; TVP) or

(4)   from the perineum

Transurethral resection of the prostate

·         TURP has largely replaced other methods

·         Men with indwelling catheters, recent UTI, chronic retention or prosthetic material or heart valves → broadspectrum prophylactic Ab with IV amoxicillin + cefuroxime or gentamicin at induction of anaesthesia.

·         Strips of tissue are cut from the bladder neck down to the level of the verumontanum

·         Cutting is performed by a HF diathermy current,

·         Coagulation of bleeding points can be accurately achieved, and damage to the external sphincter is avoided provided one uses the verumontanum as a guide to the most distal point of the resection.

·         The ‘chips’ of prostate are then removed from the bladder using an Ellik evacuator.

·         The risks of hyponatraemia are reduced by using 1.5% isotonic glycine for irrigation,

·         At the end of the procedure, careful haemostasis is performed,

·         a three-way,self-retaining catheter irrigated with isotonic saline is introduced into the bladder to prevent any further bleeding from forming blood clots.

·         Irrigation is continued until the outflow is pale pink, and the catheter is usually removed on the second or third postoperative day.

·         In men with small prostates or bladder neck dyssynergia or stenosis, it is better to divide the bladder neck and prostatic urethra with a diathermy ‘bee-sting’ electrode.

Retropubic prostatectomy (Millin)

·         Low, curved transverse suprapubic Pfannenstiel incision → the rectus sheath, the recti are split in the midline and retracted to expose the bladder.

·         With the patient in the Trendelenburg position, the surgeon separates the bladder and the prostate from the posterior aspect of the pubis.

·         Anterior capsule is incised with diathermy below the bladder neck → complete control of bleeding from divided prostatic veins by suture ligation.

·         The prostatic adenoma is exposed and enucleated with a finger.

·         The exposure of the inside of the prostatic cavity → control of haemorrhage before closure of the capsule over a Foley catheter

Transvesical prostatectomy

·         The bladder is opened, and the prostate enucleated by putting a finger into the urethra, pushing forwards towards the pubes to separate the lateral lobes, and then working the finger between the adenoma and the false capsule.

·         In Freyer’s  → the bladder was left open widely and drained by a SP tube with a 16-mm lumen in order to allow free drainage of blood and urine.

·         Harris → control of the prostatic arteries by lateral stitches inserted with his boomerang needle, the bladder wall was closed and the wound drained.

Perineal prostatectomy (Young)

·         This has now been abandoned for the treatment of BPH.

·         After treatment Most urologists irrigate the bladder with sterile saline by means of a three-way Foley catheter for 24 hours or so.

Complications of prostatectomy

Early Complication

·         Primary Haemorrhage

·         Perforation of the bladder or the prostatic capsule

·         Extravasations

·         TUR Syndrome

·         Sepsis e.g. amoxicillin plus cefuroxime, or gentamicin.

·         Clot Retension

·         Epididmyo-orchitis

·         Incontinence

Intermediate Complication

·         Secondary Haemorrhage

·         Retrograde ejaculation

·         Erectile Failure

Late Complications

·         Bladder Neck Stenosis

·         Urethral stricture

·         Re-operation

TUR Syndromes

It is the clinical condition resulting from absorption of large amount irrigation fluid into the circulation.

Its commonly lead to

·         Water intoxication

·         Circulatory Overload

·         Dilutional Hyponatreamia

Characterized by

·         Mental confusion, ↓ conscious level, change in sensorium

·         Fits & convulsions

·         Visual disturbances

·         Nausea & Vomiting

·         Hypertension, CCF, Acute Pulmonary Edema

·         Haemolysis due to water-loaded RBC → ATN → ARF

Prevention of TUR Syndrome

·         Types of fluid – No water, Use 1.5% isotonic glycine

·         Height of Irrigating Fluid – Level of fluid should not higher than 60 cm

·         Operative time – should not exceed > 60 min

·         Prostate Size -  should not exceed 60 gm in weight

§  Weight of prostate = 0.7 x length (cm) x breadth (cm) x depth of prostate (cm)

  From : B&L 25th Edition

·         Operative time – should not exceed > 60 min

·         Prostate Size -  should not exceed 60 gm in weight

Weight of prostate = 0.7 x length (cm) x breadth (cm) x depth of prostate (cm)