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CONTENTS

Page

Benign Prostatic Hyperplasia (BPH) ........................................................... 4

Classification of the Prostate ...................................................................... 4

Incidence ...................................................................................................... 6

Etiology .......................................................................................................... 7

Endocrinology & Pathogenesis .................................................................. 8

I. Androgen Factor ................................................................................... 9

The 5-alpha-dihydrotestosterone hypothesis .................................... 9

II. Factor Related to Ageing ..................................................................... 10

1. Oestrogen-Testosteron Imbalance ................................................. 10

2. Stem Cell Theory ................................................................................ 11

3. Reduced Cell Death Theory ............................................................ 12

4. Stromal-Epithelial Interaction Theory .............................................. 13

Pathology ...................................................................................................... 14

Pathogenesis ................................................................................................ 16

Diagnostic Tests ............................................................................................ 18

I. Mandatory tests ....................................................................................... 19

a. History or Symptoms ............................................................................ 19

Medical Complication of BPH ............................................................... 21

Quantification of Symptoms .................................................................. 23

Impact BPH on Daily Life ......................................................................... 25

b.Physical Examination ........................................................................... 26

Sign .......................................................................................................... 26

Digital Rectal Examination .................................................................. 27

c. Urinalysis and Renal Functions Assessment ...................................... 29

II. Recommended tests ............................................................................... 29

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Uroflowmetry ............................................................................................. 29

Residual Urine ........................................................................................... 30

III. Optional tests ........................................................................................... 32

Serum Prostatic Specific Antigen ......................................................... 32

Ultrasonography Examination (USG) ................................................... 33

Imaging of the upper urinary tract ...................................................... 34

Endoscopy of lower urinary tract ......................................................... 35

CT Sacanning & magnetic Resonance Imaging (MRI) .................... 35

Treatment ...................................................................................................... 36

I. Conservative Therapy .............................................................................. 36

a. Watchful Waiting ................................................................................. 36

b. Medical Treatment ............................................................................. 37

1. Endocrine Therapy .......................................................................... 38

a. 5 Alpha Reductase Inhibitor (5R) Therapy ............................ 38

b. Anti Androgen = Androgen Deprivation Therapy ................. 39

c. LHRH Analogue / LHRH Agonist ................................................. 39

d. Aromatase Inhibition and Anti Oestrogens ............................ 40

2. Alpha Adrenergic Antagonist Therapy ........................................ 41

Alpha Blocker (-Blocker) ................................................................ 42

Classification of the alpha blocker in the treatment of BPH ..... 43

3. Phytotherapy ..................................................................................... 45

Phytotherapy component .............................................................. 46

Active Ingredient .............................................................................. 47

Working Mechanism ......................................................................... 48

4. Combination Therapy ...................................................................... 49

II. Conventional Surgical Therapy .............................................................. 51

Indications ................................................................................................ 51

1. Open Prostatectomy ....................................................................... 52

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a. Supra Pubic Transvesical Prostatectomy .................................. 53

b. Supra Pubic-Retro Pubic Prostatectomy .................................. 55

c. Perineal Prostatectomy .............................................................. 60

2. Endoscopic Prostatectomy ............................................................ 62

a. Trans Urethral Resection of the prostate (TURP) = Trans

Urethral Prostatectomy ............................................................. 62

b. Trans Urethral Incision of the Prostate (TUIP) ......................... 65

III. Interventional Treatment = Minimal Invasive ...................................... 66

1. Ballon Dilatation ....................................................................... 66

2. Intra Prostatic Stent ................................................................. 68

3. Cryo Therapy ............................................................................ 71

a. Trans Urethral ...................................................................... 71

b. Transperineal ...................................................................... 72

4. Hyperthermia = Thermotherapy ............................................ 73

a. Microwave Thermo Therapy ........................................... 73

b. Laser .................................................................................... 75

c. Radiofrequency Energy ................................................... 77

d. High-Intensity Focused Ultrasound Therapy (HIFU) ...... 78

e. Vaporation of the prostate ............................................. 79

Catheterization ............................................................................................ 80

Prognosis ........................................................................................................ 81

References .................................................................................................... 82

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BENIGN PROSTATIC HYPERPLASIA (BPH)

BPH is the non cancerous growth of nodule in the region of the

prostate gland surrounding the urethra

Prostate gland is accessory male sex gland surrounds the prostatic

urethra and lies between the bladder outlet and the external sphincter

Prostate gland consist of three main types of tissues:

Epithelial element (20-30%) : 1.) Epithelial tissue, consisting of

prostatic acini glandular organ

Stromal element (70-80%): a fibromuscular tissue, consist of :

2.) Smooth muscle tissue (20-40%)

3.) Connective tissue (60-80%)

Its weight about 20 gr and length 2,5 cm

CLASSIFICATION OF THE PROSTATE (LOWSLEY)

Consists of :

1. The anterior lobe, lies in front of the urethra

2. The median lobe, project upwards beneath surround the two

lateral lobes which project into the urethra

3. The right lateral lobe

4. The left lateral lobe

5. The posterior lobe, lies behind the lateral lobes and distal to the

median lobe

The anterior lobe is dominated fibromuscular tissue

Prostatic adenoma (BPH) develops from periurethral gland of the site

of median and / or lateral lobes

The posterior lobe is prone to cancerous degeneration

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Fig.1. Anatomy of the prostate gland (Adapted from Lowsley, 1930) (Ref.

Scott p.26

ZONAL ANATOMY OF THE PROSTATE

Mc Neal (1968) has popularized the concept of zonal anatomy of the

prostate : (Fig.2)

1. Peripheral zones (PZ : 70% of the volume)

2. Central zone (CZ: 25%)

3. Transition zone (TZ : 5%)

The concept of zonal anatomy is more important in differentially

afflicted with neoplastic processes : (Mc Neal et al,1988)

1. 60-70% of ca. P originated in the peripheral zone

2. 10-20%in the transition zone

3. 5-10% in the central zone

4. BPH uniformly originates in transition zone

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Fig.2. Zonal anatomy of the prostate gland (Mc.Neal. A : Schematic lateral

view of the prostate. B : Cut section of the same, C : transverse View

of area show in B (Ref.Tanagho 15th Ed. p.400)

INCIDENCE

BPH is the most common benign tumor in men

Its incidence is age-related

BPH is ageing male disease

Life expectancy increase BPH increase

50% of all elderly men, at age approximately 75 years have complain of

decrease in the force and caliber of the urinary stream and 20-50% of

them undergo surgery

BPH in autopsy studies found : (Berry et al, 1984)

20% in men aged 41-50 years

To 50% in men aged 51-60 years

To over 90% in men older than 80 years

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Approximately 50% of men under the age of 60 who undergo surgery for

BPH may have heritable form of the disease. This form is most likely an

autosomal dominant trait

First degree male relative of such patients carry an increased relative risk

of approximately 4-fold (Sonda et al, 1994)

Incidence of BPH is lower in black males than white males but in Orleans,

USA, higher incidence in blacks than whites

The prevalence of BPH seems considerably lower in far Eastern country,

especially in Japan and China than in the West

South-East Asian migrating to the USA acquire a higher rate of BPH than

their counterparts remaining in South-East Asia

BPH is higher in man who consume milk than vegetable

ETIOLOGY

Unknown exactly

It seems to multi factorial and endocrine controlled

Each element of the prostate glands either alone or in combination can

give rise to hyperplastic noduls

Laboratory and clinical studies have identified two factors necessary for

the development of BPH :

1. Androgen factor : The presence of 5-alpha-dihydrotestosteron

(DHT)

2. Factor related to ageing

Other proposed risk factors for development of BPH :

1. Western diet

2. Industrialized environment

3. Hypertension

4. Diabetes mellitus

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ENDOCRINOLOGY & PATHOGENESIS

The prostate in man requires the presence of adequate levels of

circulating testosteron in order to develop and grow (Fig.3)

The decopeptide Luteinizing Hormone Releasing Hormone (LHRH) in

released from Hypothalamus

LHRH stimulates the pituitary to secrete Luteinizing Hormone (LH)

LH then in turn acts directly on the Leydig cells within the testis stimulating

them to secrete 90-95% of testosteron. The remaining 5-10% of daily

testosteron production is either directly by the adrenal gland or

peripheral metabolism

Adrenal gland required stimulating ACTH from pituitary to produce

adrenal-androgen

Fig.3. Control of androgen production and utilization. (ACTH,

adrenocorticotrophic hormone; LH, luteinizing hormone; LHRH,

luteinizing hormone releasing hormone) (Ref. Kirby p.15)

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TESTOSTERON

(in the Cytoplasma)

5 - Reductase

(in nucleus membrane)

Androgen

Receptor

+ Cell

Replication

Growth Factor

(In the Cytoplasma) mRNA

DHT

(in the nucleus)

+

I. ANDROGEN FACTOR :

THE 5-ALPHA-DIHYDROTESTOSTERONE HYPOTHESIS (Fig.4 & 5)

In the blood stream 98% of circulating testosterone is bound to human

serum albumin and Sex Hormone Binding Globulin (SHBG)

The remaining 2% as a free testosteron (T).

The free testosteron enter to prostatic cells (cyto plasma) by simple

diffusion

DHT produced from testosteron (T) by the enzym 5-alpha-Reductase (5-

R) in nuclear membrane

The binding of DHT to androgen receptor (AR) produces a

conformational change in the chromatine which facilitates transcription

of specific sequences of DNA into messenger RNA (mRNA) producing

growth factors that stimulate prostate growth (cell replication)

5 ALPHA-DIHYDROTESTOSTERON (5 - DHT)

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Fig. 4. Testosterone is converted in to DHT by a nicothinamide adenosine dinucleotide

phosphate (NADP) a dependent enzyme in the nuclear membrane and name 5 alpha reductase

BPH developes if : 1. Increased intraseluler DHT

2. Increased 5 reductase activity 3. Increased androgen receptor level

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Fig. 5. Development of BPH : The 5 DHT hypothesis (Ref. Kirby p.16)

II. FACTORS RELATED TO AGEING

1. OESTROGEN-TESTOSTERON IMBALANCE

In ageing male, there is decreased responsiveness of the testis to

bioactive LH, while plasma LH within normal limit

The consequence of this change is an age related decrease in free

testosteron

In ageing male, there is increased plasma level of oestrogen /

extradiol

Oestrogen in BPH :

Produced in man largely by aromatization of androgen

Induce stromal cell hyperplasia

Increase androgen receptor population in prostatic cell nuclei

Increased stromal cell longevity and inhibit the rate of prostate

death

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2. STEM CELL THEORY

Stem cell is a cell which have extensive proliferative potential to

maintain balanced cell numbers, in growth and death rates of the

organ, allowing a steady state to exist (Fig.6)

Stem cell produce amplifying cells and finally transit cell

Amplifying cell is a cell have limited proliferative potential

Transit cell is a cell have very limited proliferative potential and it is

determined by the level of androgen stimulation

Transit cell death it self, normally stimulates stem cell to produce new-

cells

Apoptosis occurred after androgen withdrawal. Epithelial cells are

more susceptible than stromal cells to the withdrawal of androgen

stimulus. Stem cells survive, however, that are capable of

regeneration if the androgen stimulus is restored

BPH is postulated to be the result of inappropriate activity of stem cell

with resultant overproduction of both stroma and epithelial cells

abnormal proliferation of stem cell

Fig.6. Stem cell theory for the development of BPH (Ref. Kirby p.22)

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3. REDUCED CELL DEATH THEORY

Barrack and Barry (1987) demonstrated rather elegantly that

oestrogen, when given in the presence of androgen, inhibit the rate

of cell death in the canine prostate (Fig.7)

This result clearly raise the possibility that BPH in man might not be due

to an increased in cell replication but rather be caused by a

decreased in cell death

Increasing oestrogen levels in later life may also play a role either by

inducing androgen receptors or decreasing the rate of either

epithelial or stromal cell death

Fig. 7. Reduced cell death resulting in BPH (Ref. Kirby p.22)

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4. STROMAL EPITHELIAL INTERACTION THEORY

This theory is based on significant of epithelial interaction the growth

and maintenance of the prostate gland

Reischeuer (1925) concluded that the initial lesion in BPH might be a

stromal node that would lead to a subsequent migration of epithelial

cells resulting in a new gland component (acinus)

Mc.Neal (1978) found that the initial (acinus) in BPH was not the

formation of stromal nodes but a glandular budding and branching,

mechanism which could create new alveoli on the pre prostatic

area.It suggest the occurrence of a potential embryonic

reawakening of the prostatic stroma during the adult phase as a

result of the similarities observed between epithelial budding and

glandular morphogenesis on the embryonal tissue. For that reason,

this theory is also called as embryonic reawakening theory

Cunha et al (1980) suggested that the potential presence of an

embryonal stroma induce on the epithelial prostatic cells of adult.

Stromal autocrine or paracrine growth factors may stimulate

epithelial reawakening, growth factors implicated, include,

epidermal growth factor (EGF) transforming growth factor beta (TGF-

), Fibroblast growth factor (FGF), etc

Other hypothesis (Lawson) is based on Basic Fibroblast growth factor

(b FGF). This factor is released by microinjury of distal prostatic duct

from voiding, ejaculation or infection and causes induction of

primitive mesenchym in the periurethral tissues BPH. The b FGF may

be released directly from epithelial cells with a resulting paracrine

action on adjacent stromal cells or released from injured stromal cell

with an autocrine effect on adjacent stromal cells. The 3rd alternative

is that b FGF released from the injured denuded basement

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membrane or extra cellular matrix by the action of the enzyme

heparitinase with stimulation of adjacent stromal cells.(Fig.8)

PATHOLOGY

The basic change of BPH is :

Epithelial hyperplasia of the prostatic gland

Muscle hypertrophy

Connective tissue hyperplasia

BPH be aims to appear from :

The 2nd to 3rd decades, microscopic pathological BPH

The end of the 4th decades, macroscopic pathological BPH

The 5th decade on there occurrence of clinical BPH

The hyperplasia originates in the transition zone and an adenoma is

formed, it compress the outer zone of the prostate, which forms a false

capsule as a called, surgical capsule

Fig. 8. Hypothesis for the role of growth factor in the genesis of

BPH. Paracrine and/or autocrine effects of growth factors may

play an important role in hyperplastic prostate growth. (Ref.

Herbert Lepor p.451)

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The gland may become extremely large if there much of the epithelial

but can remain quite small if the fibrous stroma chiefly affected

fibrotic prostate

Fibrous stroma hyperplasia of median lobe median bar

All lobes of the prostate may be affected and commonly may assume

any combination of these type : (Fig.9)

Isolated median lobe enlargement (30%)

Lateral lobes (Right & left) (15%) intrusion into the urethral

lumen they make a kissing lobes

Lateral and median lobes Trilobar (23%)

Posterior commissure (posterior vesical lip. or elevated bladder

neck) hyperplasia, sub cervical median lobe hyperplasia (15%)

Lateral and posterior commissure hyperplasia (17%)

Fig. 9. Commonly the hypertrophy may assume any combination of these

types (Ref. Scott p.221)

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PATHOGENESIS

The enlarged gland produces its harmful effect obstructing the

bladder neck and by upsetting the mechanisms which force open

and funnel the vesical orifice

I. Changes in the bladder

1. Early: As the degree of obstruction increase, the vesical detrussor

undergoes compensatory hypertrophy in order to overcome the

increasing urethral resistance. The muscle wall may become

more than 2 cm thick. This power of compensation varies :

One patient may have a few symptoms with a markedly

obstructive gland

Another may have great difficulty to void with a milder

obstruction

Thus, no relationship between the size of the gland and the

severity of symptoms.

As compensatory hypertrophy develops the following take place.(Fig.10)

a. Trabeculation of bladder wall intertwined muscle bundle lift up

the mucosa

b. Hypertrophy of the trigone and inter ureteric ridge

c. Cellules : The increasing intravesical pressure tends to push mucosa

between the superficial muscle bundles causing the formation of

small pockets or cellules

d. Diverticula: If cellules force their way entirely through the

musculature of the bladder wall, they become balloons or

diverticula in the perivesical fat. Diverticulum, sometimes grows to

large size and has no muscular wall. It can not emptying itself. The

urine, its contains, easily becomes infected.

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2. Late : If muscle of vesical compensation becomes exhausted,

when the muscle can no larger hypertrophy and

decompensation occurs resulting in the presence of residual

urine. Thereafter, infection may occurs, mucosa become

reddened and oedematous and may be stone formation.

If urine becomes infected, urine might be entered to ejaculatory

duct and then through vas deferens to epididymis and testicle

and at last epididymitis and orchitis occur.

Fig. 10. Changes the bladder developing from obstruction: a. normal

bladder and prostate, b. trabecula, cellules formation and

hypertrophy of the inter ureteric ridge. c. market trabeculetion and

diverticulum ( Ref. Tanagho 15th Ed. p.209)

II. Changes In The Upper Urinary Tract (Ureter and Kidney)

With secondary hypertrophy of the trigonal-ureteral complex, there is

increased downward traction on the intra mural ureteral segment,

a b

c

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thus increasing resistence to urine flow. This leads to progressive

proximal dilatation and is the common cause of hydrouretero

nephrosis

In the decompensated phase, significant residual urine leading to

chronic vesical distention may cause a vesico ureteral reflux which is

reflected in diminution in renal urinary secretion which is caused by

making largely hydrouretero nephrosis

If the vesico ureteral junction gives way, the infected urine may

ascend to the kidney, ureteristis and pyelonephritis develop

DIAGNOSTIC TESTS

Recommendation of the International Consensus Committee WHO

(1993) guidelines three classification of diagnostic tests and studies :

I. Mandatory tests : these should be performed on every patient

presenting to doctor with complaints of bladder outflow

obstruction :

a. History or symptoms and quantification of symptoms

b. Physical examination and digital rectal examination

(DRE)

c. Urinalysis and renal function assessment

II. Recommended tests of proven value in the evaluation of

most patients. Their use strongly encouraged during initial

evaluation :

a. Uroflowmetri

b. Residual urine

III. Optional tests of proven value in the evaluation of selected

patients only :

a. Pressure / flow studies

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b. Serum prostate specific antigen (PSA)

c. Transrectal ultrasound (TRUS)

d. Imaging of the upper urinary tract

e. Endoscopy of lower urinary tract

f. CT Scanning/ MRI

I. MANDATORY TESTS

a. HISTORY OR SYMPTOMS

Obtain an adequate history by enquiring about the urinary tract

especially the complaints of the patients why they present to their

doctors

All symptoms of BPH are known as a prostatismus but much bladder

neck obstruction or urethral obstruction can occur without BPH such

as urinary tract infection, bladder or urethral stone, neurogenic

bladder, urethral stricture, median bar or bladder neck contracture.

So, that term now about prostatismus is known as Lower Urinary Tract

Symptoms (LUTS)

CLINICAL FINDING

A. SYMPTOMS

The individual symptoms in a logical sequence of micturation

consist of :

1. Pre micturation symptoms

Frequency

Nocturia

Urgency and urge incontinence

Incontinence

2. Micturation symptoms

Hesitancy

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Intermittency

Straining to void

Dysuria

Reduction in the force and the caliber of stream

Terminal dribble

3. Post micturation symptoms

Feeling of incomplete emptying

Post micturation dribble

The symptoms of bladder outflow obstruction resulting from BPH have

been divided in two groups.

Obstructive or voiding symptoms :

1. Hesitancy

2. Straining to void

3. Weak stream (poor flow rate)

4. Terminal dribble/post micturation dribble

5. Prolonged micturation

6. Urinary retention

7. Incontinence

8. Incomplete emptying

9. Intermittent stream

Irritative or filling symptoms = storage symptoms

1. Frequency

2. Urgency of micturation

3. Urge incontinence

4. nocturia

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Obstructive component which produce obstructive symptoms can

be sub divided

a. Mechanical obstruction may result from intrusion into the

urethral lumen or bladder neck leading to a higher bladder

outlet resistance = BPO : Benign Prostate Obstruction

b. Dynamic obstruction may result from the contraction of the

smooth muscle compound of fibro muscular stroma caused by

stimulus of adrenergic nerve = BOO : Bladder Outlet

Obstruction

c. Decreased detrussor contractility produce reduction in the

force of urinary stream

Irritative voiding complaints of BPH may result from the secondary

response of the bladder to the increased outlet resistance.

Urodynamic evaluation in patients with BPH has demonstrated a loss

of compliance and unstable detrussor contractions during filling in up

to 70% patients. Muscle enlargement of the bladder with occurs and

this heightens the irritability of trigone the most sensitive part of the

bladder, which is located just inside the bladder neck

The presence of urinary tract infection or / and bladder stones may

result in progressive severity of symptoms of BPH

MEDICAL COMPLICATION OF BPH

1. Prolonged obstruction may bring further complication, such as

hydronephrosis with accompanying compromised renal function

2. Incomplete bladder emptying causes urinary stasis which predisposes

to infection and secondary inflammatory changes in the bladder and

urinary tract. Urinary stasis also predisposes to calculus formation

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3. Straining to void urine can congest superficial veins of prostatic

urethra and trigonum, leading to rupture and subsequent hematuria

4. Prolonged urinary retention may result in progressive renal failure and

azotemia

5. Infected urine that ascend to the ureter can be ureteritis and

pyelonephritis

6. Straining to void infected urine may press urine entered to ejaculatory

duct vas deferens epididymis and testis, resulting epididymitis

and orchitis

7. Acute urinary retention: A medical emergency that requires prompt

attention via the passage of a catheter into the bladder to drain off

urine. Less than 10% of patients will present initially with acute urinary

retention.

Bladder neck obstruction can occur in the absence of BPH which product

symptoms like a Prostatismus

1. Median bar = posterior vesical lip. Connective tissue stroma

hyperplasia of median lobe

2. Bladder neck contracture: occurrence hypertrophy of

connective tissue surround internal urethral orifice caused :

Congenital

Acquired infection cystitis

3. Chronic congestive prostatitis

This is a morbid condition in which there is distention of

the gland with a excessive amount of prostatic fluid

Etiology: Usually result from continued or repeated

unphysiological sexual practice. Sexual excitement

without ejaculation in the most common cause. This

occurs frequently in a married man who is accustomed

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to regular coitus, and whose wife becomes ill or

pregnant, also often occurs in a man whose wife dies or

who is away from home for several months. Sometimes it

is also found in unmarried men who do a lot of petting

but do not have coitus.

Therapy is prostate massage for 4-7 days

QUANTIFICATION OF SYMPTOMS

Symptoms should be quantified by using the International Prostate

Symptoms Score (I-PSS) and Quality of Life (QOL) assessment. This

scoring system was adopted from the American Urological

Association (AUA, 1991) (Fig.11)

This symptoms assessment in clinical studies, firstly was published by

Boyarsky et al in 1977, then followed by Madsen & Iversen (1983),

Fowler et al (1988) and Hald et al (1991 a group of Danish Urologists)

Division of urology, Department of Surgery, Faculty of Medicine of

University Indonesia, Jakarta has often used the Madsen & Iversen

system

Madsen & Iversen score :

Score consist of 9 symptoms. This score introduces the concept of

weighting symptoms. The scaling of each symptom is very variable:

frequency (0-3), nocturia (0-3), hesitancy (0 or 3), intermittency (0-3),

urgency (0-3), weak stream (0-4), feeling of incomplete emptying (0-

4), straining (0 or 2), incontinence (2)

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Fig. 11. International Prostate Symptom Score (I-PSS) consist 0f 7

symptoms/questions each symptom is scored as 0 5. Total score is 35 and divided in 3 categories 0 7: Mildly symptomatic, 8 19: Moderately, 20 35: Severely. In addition, a single question assesses the patients quality of Life (QOL) (Ref. Kirby p.28)

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IMPACT BPH ON DAILY LIFE

A Recent European study (1993) found that :

More than 50% of men with BPH are significantly restricted in an

aspect of daily life :

Limit fluid before travel and bedtime

Can not drive for two hours

Not enough sleep at night

Limit going to place without toilets

Limit playing outdoor sports

Limit going to cinema, theatre, church, etc

Despite like these, the study found that few of patients with BPH

consult their doctors with at least one of a number of restricted in their

participation of social life

Other reason, a small group of BPH patients, less than 10%, will present

to their doctor with acute urinary retention

Reasons why BPH patients do not present to their doctor :

Assumption that symptoms are part of ageing

Stigma associated with dribbling and urgency

Fear of surgery

Fear of diagnosis of ca.prostate

Reductance to submit to digital rectal examination

Symply do not want to bother the doctor

Many men regard the prostate as a genital, they may be

unwilling to admit any defect in its functioning

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b. Physical Examination

SIGNS

A physical examination, Digital Rectal Examination (DRE) and

focused neurologic examination are performed on all patients

Physical examination in BPH often provides less information than the

history

Physical examination should asses

General examination may reveal :

Loss of weight

Oedema

Pallor from anemi secondary to renal impainmant

Costo vetebral angle : pain or mass on palpable

Supra pubic area to rule out significant bladder tone and

mass of enlarged bladder

External genitalia to detect : Hernia, orchitis, epididimitis.

Anal and bulbo cavernous reflex plus brif assessment of

motor and sensory function in lower body. Include

external urethral spincther

A full examination of the respiratory and cardiovascular

system

Where the posibility of operation is raised the following investigation

are mandatory :

a. Electro cardiography to asses myocardial state

b. Chest X-Ray

c. Pulmonary function test

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DIGITAL RECTAL EXAMINATION (DRE)

Urinary bladder is emptied and bimanual DRE the 2nd finger of the

right hand in the rectum and left hand on supra pubis

The well lubricated finger should asses the prostate attention being

paid to :

Size and protrusion of the prostate gland into the rectal lumen

Consistency, like the tip of the nose or rubbery

Irregularities or hard nodules/induration (CaP)

Tenderness, smooth

Presence of fixation to the pelvic wall (CaP)

Symetry

Fibrotic prostate : small, hard DD : CaP

Degree of mobility of the rectal mucosa

Any rectal pathology

The median lobe is impalpable by DRE

BPH and CaP are two distinct disease, although they may be CaP

exist in the same patient

Patients should be reassured that if BPH is diagnosa, CaP is more likely

to be detected at an earlier stage

How to assess the length of protrusion of the prostate gland into the rectal

lumen

1

2

3

Make an imaginary line

from the left point of the

prostate and rectal wall

angle to right angle (1)

Make an imaginary line at

the top of protrusion of the

prostate to be parallel with

the first line (2)

Its range of two lines is the

length of protrusion (3)

Fig.12. The assessment of the length of the prostate protrusion in to the rectal lumen.

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CLASSIFICATION OF THE PROSTATE GRADING

1. Rectal grading : Based on the length of protrusion of enlargement

prostate gland into the rectal lumen. (Fig. 12)

Grade 1 : 1 2 cm : Prostate superior margin easy to reach

Grade 2 : 2 3 cm : Prostate superior margin can be reached

Grade 3 : 3 4 cm : Prostate superior margin can be reached which

bladder is pressed on supra pubic by left hand

Grade 4 : > 4 cm : Prostate superior margin can not be reached

despite it is maneuvered like third grade.

2. Clinical grading : based on residual urine which can be measured by

admitting catheter post voiding. Also can be measured by USG or IVU

post voiding

Grade 1 : residual urine approximately 50 cc

Grade 2 : residual urine approximately 100 cc

Grade 3 : residual urine approximately 150 cc

Grade 4 : residual urine approximately >1 50 cc or urinary retention

3. Radiological grading : based on Protrusion of enlargement prostate

gland into bladder cavity (caudal indentation) on IVU

Grade 1 : Protrusion below the half of range inter ureteric ridge and OUI

Grade 2 : Upper the half of range inter ureteric ridge and OUI

Grade 3 : Protrusion on inter ureteric ridge

Grade 4 : Protrusion upper the inter ureteric ridge

4. Endoscopic grading/intra urethral grading based on the length of kissing

lobes

Grade 1 : < 1 cm

Grade 2 : < 2 cm

Grade 3 : < 3 cm

Grade 4 : > 3 cm

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Grades Of

Sizes

Bergman, Turner Barnes, Hadley Turner, Belt

Weight Of Tissue Removed Weight Of Tissue Removed

1

2

3

4

About 20 gm

About 40 gm

About 70 gm

More than 120 gm

10 25 gm

26 50 gm

51 100 gm

More than 100 gm

Fig.13. Reported Grades Of Sizes On Dre And Their Corresponding Weights

Of Removed Prostatic Tissues (Ref. Tan p71)

c. URINALYSIS AND RENAL FUNCTION ASSESSMENT

Urinalysis to exclude infection or hematuria. If bacteriuria or leucocyt

sediment should be assessed urine culture and sensitivity test. May be

possible to give the antibiotic pre operative

Renal function assessment are required. Renal insufficiency may be

observed in 10% of patient with prostatism. Patients with renal

insufficiency are at an increased risk of developing post operative

complication following surgical intervention for BPH

II. RECOMMENDED TESTS

UROFLOWMETRY

Urine flow studies are the simplest of the range of urodynamic tests

which can be used to investigate patients with lower urinary tract

symptoms

Maximal urinary flow rate (Q max) is the best single measure, but a

low Q max does not distinguish between obstruction and decreased

bladder contractility

30

Because of great individual variability of flow rate and the volume of

dependency of the peak urinary flow rate, at least two uroflow

measurement should be obtained, with a resulting volume ideally

more than 150 ml

Urine flow decreases in the overall population with age. A normal

man of 60 years of age will not have the same flow as a normal man

of 20

In children under 10 the Q max should reach a minimum 10 ml/sec

and by 15 years a minimum of 15 ml/sec

In women the Q max before the menopause are generally in exess of

18 ml/sec and after the menopause in exsess of 15 ml/sec

In men before the age of 45 Q max are usually in excess if 18 ml/s, up

to the age of 55, 15 ml/sec and over 65, 13 ml/sec

Assessement an average volume of Q max :

> 15 ml/sec non obstruction

10 15 ml/sec border line

< 10 ml/sec obstructive

RESIDUAL URINE

In general, the quantity of residual urine is an indication of the severity

of the obstruction

But the presence of residual urine does not confirm the diagnosis of

prostatic hypertrophy for it is also associated with other condition,

however does aid in making a diagnosis and also helps guide the

clinician in this choice of treatment

The amount of residual urine is estimated :

31

The patient voids all he can, then a small catheter is gently

passed and the urine found to have been retained in the

bladder is meassured

In an excreatory urogram, take a post voiding film at the end of

the series of exposure, after the patients voids all he can and X-

ray at the bladder is taken immediately. Retained urine is

shown by the opaque fluid remaining in the bladder. The

opacity is approximately 1 cm, an average diameter for every

15 ml

The determination of residual urine can also be performed by non

invasive trans abdominal ultra sonography. This will simultaneously

provide information about bladder wall change, bladder stones,

diverticula and median lobe. An ultra sound estimate of residual urine

is perform after each void. Patients lying supine the bladder is

scanned in the transverse and coronal plans. The bladder diameter

Anterior-Posterior (D1), Cranial-Caudal (D2) and Lateral-lateral (D3)

are measured Post Voiding Residual urine is D1 x D2 x D3 x 0,7 (index

value)

The cystogram is a value in making diagnosis. When urinary

obstruction has persisted over a period of several months, the shape

of the bladder becomes pyramidal and its cystographic outline

irregular due to trabeculation and multiple cellules. This appearance

is called a christmas tree

32

III. OPTIONAL TESTS

SERUM PROSTATIC SPECIFIC ANTIGEN (PSA)

The clinical distinction between BPH and CaP can not be

accomplished with certainly by DRE and physical examination

PSA determination and DRE in combination provide the best means

to determine the pre treatment probability for CaP and

consequently, the need for TRUS and a prostate biopsy

PSA is not specific for CaP but specific for organ (prostate gland).

Other factors such as BPH, urethral instrumentation, infection, biopsy,

DRE can cause elevation of serum PSA

Normal values PSA depend on age of the patients. Age adjusted

reference ranges for PSA :

40 49 years of age : PSA 0 2,5 ng/ml

50 59 PSA 0 3,5 ng/ml

60 69 PSA 0 4,5 ng/ml

70 79 PSA 0 6,5 ng/ml

Normal value PSA average < 4 ng/ml

Free PSA: 10-40% of total PSA

Patients with PSA 4 10 ng/ml who may need a repeat biopsy

Free / Total PSA ratio: < 15% suggestive of cancer

> 25% suggestive of BPH

15 25% unknown

PSA level are elevated approximately 0,12 ng/ml per gram of BPH

tissue (other literature : 0,33 ng/ml). Thus, patients with enlarged

glands due to BPH may have elevated PSA levels more than 10

ng/ml. The ratio of PSA to gland volume is term the PSA density. Some

investigators advocated prostate biopsy if the PSA density exceeds

0,1 or 0,15

33

Patients whose serum PSA increase by 0,75 ng/ml/year, appear to be

at an increased risk of harboring cancer. Increasing PSA level/year is

term the PSA velocity

PSA level-adjusted reference ranges for elevated volume of prostate

gland

Level PSA :

0,2 1,3 ng/ml : volume of prostate gland 0,7 ml/y

1,4 3,2 ng/ml : volume of prostate gland 2,1 ml/y

3,3 9,9 ng/ml : volume of prostate gland 3,3 ml/y

In one study, the sensitivity and specificity of PSA velocity were 72%

and 90% respectively

ULTRASONOGRAPHY EXAMINATION (USG)

USG can be made by Trans abdominal ultrasonography, trans

urethral ultrasonography and transrectal ultra sonography

Trans abdominal USG of the bladder also provides relevant in

formation about bladder wall thickness, the presence of diverticula or

calculi and the post void residual urine (PVR). May also be visualized

the bladder tumor. Prostatic volume can be roughly estimated but

TRUS is more accurate for this, median lobe enlargement visualized.

More over renal USG can also be performed at the some sitting to

identify secondary upper tract dilatation or coincidented renal

pathology

Trans urethral ultrasonography approach during cystoscopy has been

recommended for tumor detection and staging

Trans rectal ultrasonography (TRUS) provides more accurate local

staging then does DRE. The sonographic feature homogenously. CaP

34

tends to appear as a hypoechoic lesion in peripheral zone. Biopsies

are usually obtained under TRUS guidence

TRUS also enable measurement of the prostate volume which is

needed in the calculation of PSA density. Typically a prolate ellipsoid

formula is used : (/6)x(anterior posterior diameter=D1)x(transverse

diameter=D2)x(sagittal diameter=D3) or : 0,52 x D1 x D2 x D3, TRUS is

also used the performance of cryosurgery and brachytherapy

IMAGING OF THE UPPER URINARY TRACT

Upper urinary tract imaging (intravenous pyelography) is

recomended only in the presence of concomitant urinary tract

disease or complication from BPH, hematuria, urinary tract infection,

pyelocaliectasis appearance on renal ultra sonography and history

of stone disease.

The straight X-ray may reveal the presence of urinary tract calculi or

soft tissue shadows such as an enlarged kidney or bladder

Attention should be paid to the skeleton for the presence of possible

osteoblastic metastasis from prostatic neoplasma

IVU is carried out and the feature which can be seen in the presence

of obstructive prostatic disease, include :

a. Complete suppression of renal function, usually bilateral

b. Hydronephrosis and hydroureter

c. Fish hooking of the lower ends of the ureters caused by

lateral lobe enlargement

d. Trabeculation of the bladder

e. Bladder diverticular formation

f. Filling defect in the bladder, usually basal, caused by the

enlarging prostate (caudal indentation) of the contrast

35

g. Residual contrast left in the bladder after micturation. The

experience eyes can usually estimate how much residual urine

is left

h. The voiding X-ray may reveal the presence of vesico ureteralis

reflux in the decompensated phase of detrussor muscle

i. The cystogram of the BPH which chronic urinary obstruction

the shape of the bladder becames pyramidal and outline

irregular due to trabeculation and multiple cellules. This

appearance it is called a Christmas tree bladder

ENDOSCOPY OF LOWER URINARY TRACT

It is not recommended except in indication :

Hematuria : to detect cause of hematuri such as bladder tumor

or stones

BPH is small on DRE while the symptoms are severity. There are

discrepancies between BPH measure and the symptoms

Urethro cystoscopy to see directly situation of the urethra, zise of

lumen, kissing lobes of BPH, contracture bladder neck, trabeculation

& cellular and diverticula

Before doing uretrocystoscopy may measure PVR

Endoscopy may also assist in choosing the surgical approach in

patients : TURP, TUIP or open prostatectomy

CT-SCANNING & MAGNETIC RESONANCE IMAGING (MRI)

For prostate disease. CT is used for detection of lymphadenopathy

and to evaluate prostatic abscess

In imaging the prostate gland, MRI stirred much interest because

multiplanar imaging and very good tissue contrast allow an excellent

36

display of anatomy and intra prostatic pathology. MRI is used in the

evaluation of congenital anomalies and in the staging of prostate

carcinoma

CT scanning and MRI is not recommended for BPH only

TREATMENT

After patients have been evaluated, they should be informed of the

various therapeutic options for BPH. It is important, therefore, when

considering treatment options, that the patient be actively involved

in the choice of therapy; this shared decision-making allows patients

to evaluate the benefits and risks of the various therapeutic options

for themselves

Three main options are currently available for the management of

BPH :

I. Conservative therapy

a. Watchful waiting

b. Medical therapy

II. Conventional surgical therapy

III. Minimally invasive therapy

I. CONSERVATIVE THERAPY

Ad.1a. WATCHFUL WAITING

Although watchful waiting has no direct effect on BPH, it is still a

management option. Any patients, however, complaining of overt

symptoms of BPH must by definition have overcome any inhibition to

present and merits the consideration of active treatment. The

International Consensus Committee (ICC-WHO 1993) recommended

37

that patients should be informed of all treatment options before

watchful waiting is chosen and then reevaluated yearly to determine

whether a change to active therapy is needed.

The patients with mild symptoms (IPSS: 0-7)

Watchful waiting is not an option for patients with severe BPH or for

patients with acute retention of urine and/or bothersome symptoms

During in watchful waiting time, all patients will not be suggest to

consume all foods that can increase the symptoms of BPH such as

alcohol, coffee, congestant drugs, etc

Ad.1b. MEDICAL TREATMENT

The idea of pill for the prostate has long been an allowing one for

patient, although the concept has been viewed with skepticism by

surgical oriented urologist for many years

However, data are accumulating to suggest that a number of

pharmacological agent may have reasonable safety and efficacy in

the longer term treatment of obstructive BPH

The treatment of BPH is according to its etiology by giving medical

treatment which blockades pathogenesis and pathophysiology of

BPH to decrease the volume of the prostate gland and relaxes the

contracted smooth muscles of the bladder neck, prostate, prostates

capsule and prostatic urethra.

Medical treatment is only given to BPH which has no indication for

operation, patients awaiting or unwilling to undergo surgery and

patients in whom surgery is contra indication

38

Three main options are currently available for medical treatment of

BPH and combination therapy :

1. Endocrine therapy (Hormonal therapy)

2. Alpha adrenergic antagonist therapy

3. Phytotherapy

4. Combination therapy

Ad.1. ENDOCRINE THERAPY

A number of different hormonal preparations have been used to improve

the symptom of BPH. These include:

a. Five alpha reductase (5-R) inhibitors,

b. Anti androgen (androgen deprivation therapy)

c. Luteinizing hormone releasing hormone (LHRH) agonist

d. Aromatase inhibitors and anti oestrogen

Ad. a. 5 Alpha Reductase Inhibitor (5R) Therapy

According to 5-DHT hypothesis, BPH develop as result of the

binding of DHT which product from testosterone by the enzyme

5 Reductase

Finasteride is a 5 reductase inhibitor that blocks conversion of

testosterone to DHT. This drug affects the epithelial component

of the prostate; resulting in a reduction in the size of the gland

and improvement in symptoms.

Six month of therapy are required to see the maximum effect of

prostate size (20-30%) reduction and symptomatic

improvement

Dozes of Finasteride 5 mg once daily

39

A number of Finasteride in Indonesia are :Proscar, (MSD), Finpro

(Interbat), Finered (Sunti Seduri), Prosh (Dexa Medica),

Prostakom (Combiphar), etc

Ad. b. Anti Androgen = Androgen Deprivation Therapy

Two type of anti androgen

1. Steroidal with intrinsic hormonal activity:

Cyproterone acetat 50 mg daily

Bromocriptine 2,5 mg / daily

2. Non steroidal that bind directly onto androgen receptor, but with no

intrinsic hormonal actvity :

Flutamide 100 mg 3 times a day

Bicalutamide (Casodex) 150 & 50 mg daily

Anti androgen drugs resulting in a reduction in the size of the gland

23%-30% in 6 month

Side effect of this drugs : gynecomastia & nipple pain 54%,

gastrointestinal disorders (diarrhea) 49%, decrease of libido and

impotence, cardiac side effect, oedem and thromboemboli

This is not acceptable in the elective management of BPH

At this time, significant side effects still seem to be prohibitive for routine

clinical use

Ad. c. LHRH Analogue / LHRH agonist

LHRH analogue therapy like an orchidectomy is a medical androgen

ablation. They inhibit LH & FSH and decrease testosterone. The use of

LHRH analogue agonists has been well deplored in numerous studies in

the treatment of advance Ca.P

40

Naferelin inj. s.c. 0,4 mg for 6 month. Prostate size decrease average

25%. After cessation of treatment, the prostate regrewth to original size

by 6 month

Some patients which was given Buserelin, Produce the reduction

prostate volume + 29%

After discontinuation, regrewth of the prostate occurred which

amounted to 97% of the original volume after 24 weeks

The side effect: loss of libido, impotence. To prevent it regrewth again, all

patient should be given continuous treatment, as well as the side effect

of medical castration and they did not believe that this form of therapy

would likely be of significant use in the general population of men with

prostatism

Ad. d. Aromatase Inhibitor and Anti Oestrogens

Aromatase is an enzyme complex responsible for converting androgen

to oestrogen. Aromatase is widely distributed in the reproductive tissue

of both sexes. Androgen extra testicular oestrogen E1 and androgen

testicular oestrogen E2

Oestrogens have long been implicated in the pathogenesis of BPH. BPH

can be induced by the administration of oestradiol.

Aromatase inhibitor leads to a lowering of plasma E1 and E2 in intact

males

The best known and most widely used aromatase inhibitor are :

Aminoglutethimide

Ketoconazole

However, ketoconazole is much more widely used as an anti fungal

agent and Aminoglutethimide has been used as a treatment for Ca.P.

Some report said that araomatase was not an effective treatment for

41

BPH because of pituitary feedback mechanism of the lowering of

plasma E1 and E2

A more logical approach would be to block the effect of oestrogen at

target cell by means of anti oestrogen therapy (i.e. an oestrogen

receptor antagonist)

Tamoxifen, as an oestrogen receptor blocker, at a dose of 80 mg daily

for 4 weeks, demonstrated no useful effect

Ad. 2. Alpha Adrenergic Antagonist Therapy

Infravesical obstruction in men with symptomatic BPH is comprise of

static and dynamic components

The dynamic component of obstruction is determined primarily by the

tone of the prostate smooth muscle, bladder neck and prostatic

urethra, while static obstruction by the prostate gland

The development of histochemical methods of identification of

cholinergic and adrenergic nerve ending and receptors demonstrated

the presence of adrenergic receptors in the prostate smooth muscle

bladder neck and prostatic urethra

Most of the treatments for BPH are essentially designed to correct the

obstructive factors. Static factor of prostate gland by surgical treatment

(TUR-P) and various of hormonal manipulation

However, alpha blockers are active on dynamic aspect of obstruction

The prostate smooth muscle, bladder neck & urethra are innervated by

the sympathetic nervous system. This nerve release nor-adrenaline or nor

epinephrine from the nerve ending of the post gangliomic fibre. Nor-

epinephrine acts on the adrenergic receptor of the smooth muscle fibre.

The adrenergic receptors are divided into two groups :

42

Alpha receptor and beta receptor

Stimulation of the alpha receptor produces contraction of the

bladder neck and prostate muscle and beta receptors produces

relaxation

There are two groups of alpha receptors

1. The -1 receptors are only present on the target cell and mediate

effect exerted on it

2. The -2 receptors are mainly present on the post-gangliomic nerve

terminals and locally control the uptake of excess norepinephrine

The bladder neck and prostate principally contain -receptor, while the

detrussor contain muscarinic receptor and adrenergic receptors and

-adrenergic receptors are present in only small amount

ALPHA BLOCKER (-BLOCKER)

At present at least six different types of alpha adrenergic receptor have

been identified and classified into two main groups : -1 receptors and

-2 receptors

Consequently, certain drugs are almost exclusively -1 antagonist, -2

antagonist and mixed antagonist

Alpha adrenergic receptor of the bladder neck, urethra and prostate

are essentially -1 receptor an alpha-1 blocking effect have therefore

been more frequently proposed in the treatment of BPH

Many of the -blockers were initially prescribed for their hypotensive

action which could constitute an adverse effect in the context of BPH

So, therefore indication and contra indication to -blocker treatment in

BPH

43

INDICATION TO -BLOCKERS TREATMENT

1. Symptomatic relief of BPH in patient without an absolute indication for

surgery

2. Patients in whom surgery is contraindicated

3. Patients unwilling to undergo surgery

4. Patients awaiting surgery

5. Prophylaxis of acute retention in patients undergoing intercurrent surgery

CONTRA INDICATION TO -BLOCKERS TREATMENT

a. Absolute Contra Indication

1. Renal failure secondary to obstructive BPH

2. Gross bladder over distension due to obstructive BPH

3. Postural hypotension

4. Repeated acute retention due to BPH

5. Repeated UTIs associated with BPH

b. Relative contra indication

1. Recent cerebrovascular disease

2. Strong positive history of syncope

3. Bladder stones associated with BPH

4. Gross hematuria

CLASSIFICATION OF THE ALPHA BLOCKER IN THE TREATMENT OF BPH

There are three sub groups of -blockers

a. Non selective -blockers (mixed -1 and -2 blocker):

Phenoxibenzamine

Pentolamin

Nicergoline

Thymoxamine

44

b. Short acting selective - blockers:

Prazosine

Alfuzosine

Indoramine

c. Long acting selective -1 blockers:

Terazosine

Doxazosine

Tamsulosine

Phenoxibenzamin is non selective -blocker is presently approved in

the USA for the treatment of pheochromocytoma. The dose may be

titrated up to 40 mg 3 times a day. In BPH phenoxibenzamin at a dose

0f 10 ml twice a day. Incidence and severity adverse reaction are

tiredness, dizziness, impaired ejaculation, nasal stuffiness, difficultly

with visual accommodation and sometimes gastric carcinoma after

prolonged high dose treatment. Because of this possibility its use is no

longer recommended

Prazosin for the treatment of BPH at a dose of 2 mg twice a day, the

peak urinary flow rate improved 59%. This drugs was initially introduce

as an anti hypertensive agent. Prazosin has been shown to inhibit

noradrenalin induced contraction of strips of both prostatic

adenoma and capsule in vitro experiment. The action of prazosin in

BPH demonstrated a significant improvement in symptom, a

significant increase of both the mean and maximum flow rate and

significant reduction in the post micturition residual volume

A variety of -adreno receptor blockers with distinct properties have

been develop as a possible treatment of BPH, the one most used is a

selective long acting -1 blockers group :

Terazosin (Abbot : Hytrin ) : 1 mg. 2 mg. 5 mg)

45

Doxazosin (Pfizer : Cardura ) : 1 mg 2 mg

Tamsulosin (Yamanouchi : Harnal ) : 0,2 mg

Terazosin and doxazosin has given dose titration : 1 mg. 2 mg. 5 mg.

20 mg and 1 mg. 2 mg. 4 mg. 8 mg. 12 mg. once daily

Side effect of Terazosin is tiredness , headache, palpitation, nasal

congestion, chest pain, nausea, dyspneu and decrease of libido

Side effect of doxazosin is : dizziness, fatigue, and headache

Doxazosin can be given the BPH patients whose in hypertensive or

unhypertensive condition

The most recommended is tamsulosin which is an -1A blockers, has

around a 30 fold selectivity, as compared with other -1 blockers to

smooth muscle of the prostate, its capsule and urethra. There are

negligible effects on the muscle of the blood vessels. The reasonable

efficacy and very low incidence of cardio vascular side effects,

makes tamsulosin when given once daily in a dosage of 0,2 mg or 0,4

mg without titration procedure as other -1 blockers.

Ad.3. PHYTOTHERAPY

The use of plants or plant extract for the treatment of symptoms

associated with BPH has been done since ancient times. It was

written on Egyptian Papyrus in the 15th century B.C.

It is also widely used in the Western hemisphere especially in Europe

In Germany and Austria, phytotherapy is the first line of drugs

treatment for LUTS caused by BPH, from mild to moderate symptoms

and represent more than 90% of all drugs used in treating BPH

In Italy 49% drugs used in treating BPH are plant extract where else

5-R inhibitor and 1-blockers are only used 5% each

46

Also, in Indonesia especially the use of Serenoa repens, pumpkin

seeds and those used in traditional mixtures

Compared with other medicamentous therapy, several researches

obtained result which displayed resemblance to Finasteride but for

more less efficacious compare with 1-blockers (Alfusozin or

Tamsulozin)

The working mechanism and active ingredients of phytoterapeutic

agents have not been identified and conformed because there is a

lot of controversy among researches depending on their experience

and clinical trial

PHYTOTHERAPY COMPONENT

This component can be divided into 4 groups :

Phytoterapeutic agents

Cholesterol lowering agent phytosterol with active

component, sitosterol and beta sitosterol

Amino acid complexes

Organ extract

These 4 groups overlap one another, so they are considered as one

group: Phytotherapeutic agents

Among the many plants commonly use, which extract is taken from :

the leaves, flower, fruit, seeds, bark, branch, root or the whole plant

as phytoterapy are :

Pygeum Africanum (African plum tree)

Populus Tremula (Aspen)

Serenoa Repens (Dwarf palm tree)

Echinacea Purpurea (Purple Cone Flower)

Cucurbita Pepo (Pumpkin Seeds)

47

Secale Cereola (Rye Pollen)

Hypoxis Rooperi (South Africans Star Grass)

Urtica Dioica (Stinging Nettle)

Aletrius Farinosa (Unicorn Root)

Sabal Cerula (Sago Palm)

For Example, the part of the plant extracted:

Taken from:

Root : Hypoxis Rooperi and Echinacea Purpurea

Fruit : Serenoa Repens

Bark : Pygeum Africanum

Seeds : Cucurbita Pepo

Leaves : Trembling Poplar

Flower/Pollen: Extract Protaflor

ACTIVE INGREDIENT

Plant extracts are a combination of several chemical components

There are water soluble and fat soluble

The active ingredients in lipids are composed of 85% - 95% fatty acid

and sterol

The fatty acid :

Free Fatty Acids (FFAs)

Fatty Acid ethyl-Esthers (FAEs)

Fatty alcohol

Phytosterol

Triterpenes

The sterol fraction :

Beta-sitosterol

48

Stigmasterol

Cycloartenol

Lupeol

Lupenone

Methyl-cycloartenol

Further studies of these extracts, its known that the ingredients that

inhibit 5-reductase are :

Lauric acid

Linoleic acid

Linolenic acid

WORKING MECHANISM

The actual working mechanism of the active ingredients is still not

clear, but a few hypotheses have been brought forth:

1. Anti inflammatory effects through interference with

prostaglandin metabolism

2. Alteration of cholesterol metabolism

3. Inhibiting prostate growth

4. Anti androgenic effect

5. Anti oestrogenic effect

6. Action within the liver reducing the production of Sex hormone

binding globulin (SHBG)

7. Inhibiting the production of Growth Hormones (bFGF & EGF)

8. Reducing smooth muscle tone around bladder neck, prostate,

prostate capsule and urethra prostatica

9. Inhibiting 5-reductase

10. Cytotoxic effect towards hyperplastic cells

11. Inhibiting the growth of prostate cancer cells

49

SEVERAL TYPE OF MEDICINAL PHYTOTHERAPY

Permixon (fruit serenoa repens), 320 mg / day for 1 month

Curbicin (cucurbita pepo & sabal serulata), 80 mg in dose 3x2 tab /

day for 3 month

IDS 89 (strogen) (serenoa repens), 3x2 caps (160 mg) / day for 12

week

Tadenan (Pygeum Africanum) with doses 2x1 capsule (50 mg) which

prevent contractil disfunction bladder neck given for 2 month

showed improved urinating symptom

Other researches that compared serenoa repens with finasteride and

1-blocker showed that finasteride was almost as effective as

serenoa repens (permixon 2 x 160 mg) but less effective than 1-

blocker (Alfusozin 3x2,5 mg)

SEVERAL DRUGS CIRCULATING IN INDONESIA

1. Lanaprost (Landson) Serenoa Repens extract 1-2 tab. (80-160 mg) /

day

2. Prostakur (Medikon) serenoa repens extract 2x1 caps. (160 mg)

3. Tadenan (Fourniers) Pygeum Africanum 2x1 caps. (50 mg)

4. Soprost (Soho) combination of Serenoa repens 80 mg with Cucurbita

pepo 80 mg + Zinc picalinate 15 mg / capsule. Dosage is 1-2 cap/day.

Similar to Curbicin but without Zinc and dosage of 3x2 tablets a day.

Ad.4.COMBINATION THERAPY

BPH can be treated with 1-adrenergic blockers drugs that relax

prostatic smooth muscle, bladder neck and prostatic urethra or with

drugs that inhibit 5-reductase and therefore reduce tissue androgen

50

concentration / prostate gland. However, the effects of the two types

of drugs have not been compared.

As compared 1-adrenergic blockers drugs with 5 reductase

inhibitor, finasteride, the onset of action of the 1-adrenergic blockers

is more rapid, they have no effect on serum concentration of PSA

and they can improve hypertension at the same time

As compared 5-reductase inhibitor, finasteride, with 1-blockers,

finasteride has minimal side effect, does not required titration at the

first of therapy and decrease prostatic size

Since this the different mechanism which these two type of

medications act, the next principal advance may come from using

them in combination

Lepor et.al. (1996). Compared the safety and efficacy of placebo

terazosin (10 mg daily), finasteride (5 mg daily) and combination of

both drugs in 1229 men with BPH. AUA symptom score and peak

urinary flow rates were determined at base line and periodically for

one year

This result from the base line in the symptoms score in the placebo,

finasteride, terazosin and combination therapy groups were

decrease of 2,6 , 3,2 , 6,1 , and 6,2 points, respectively (p < 0,001) for

the comparisons of both terazosin and combination therapy with

finasteride and with placebo.

In the peak urinary flow rate were increase of 1,4 , 1,6 , 2,7, 3,2 per

second, respectively (p < 0,001) for the comparisons of both terazosin

and combination therapy with finasteride and with placebo.

51

Conclusion :

In men with BPH terasozin was effective therapy whereas finasteride

was not, and the combination of terazosin and finasteride was no

more effective than terasozin alone

II. CONVENTIONAL SURGICAL THERAPY

The indication for prostatectomy may be divided into: Absolute and

Relative indication

Absolute indications :

1. Chronic obstruction and azotemia

2. Chronic obstruction and bladder neck stone

3. Recurrent retention of urine

4. Chronic obstruction with upper tract dilatations bladder

trabeculation and diverticulation

5. Recurrent urinary tract infection

6. Recurrent hemorrhage from prostatic vessel

7. IPSS severity

8. Urine flow: maximum flow rate of urine (Q-max): < 10 ml /sec.

Relative indications :

1. Total acute urinary retention for the first times

2. Chronic obstruction with mild changes of the upper urinary

tract

3. Recurrent prostatitis

4. Bladder stone

5. Clinical grading III (residual urine > 100 ml)

6. BPH associated with :

Asthmatic patient

Cardio-vascular disease

52

Diabetes mellitus

Hernia

7. IPSS moderately

8. Urine flow : Maximum flow rate of urine (Q-max) : 1015 ml/sec

Although most patients will now be considered able to tolerate the

regional/spinal or general anasthesia necessary for prostatic surgery

there are still some important contraindications :

1. Severe anesthetic risk due to pulmonary or cardiac disease

2. Anti coagulation or bleeding disorders

3. Neurological disease such as Alzheimers, Parkinsons, cerebral

hemorrhage

4. Striated spinchter weakness

There are two procedures of the conventional surgery therapy :

1. Open prostatectomy, consist of :

a. Supra pubic transvesical prostatectomy

b. Supra pubic retro pubic prostatectomy

c. Perineal prostatectomy

2. Endoscopy prostatectomy :

a. Trans urethral resection of the prostate (TUR-P)

b. Trans urethral incision of the prostate (TUI-P)

Method procedure of surgery depending upon the size of gland as

assessed by digital rectal examination and trans rectal ultra

sonography (TRUS)

A report focuses on a pilot study now underway dividing men with

significant signs and symptoms of BPH into three classes :

Class I : BPH is 20-50 grams in size : Randomization will be TURP,

balloon dilatation, medical therapy or watchful waiting

53

Class II : BPH is 51-80 gram in size : randomization is between TURP

and open prostatectomy

Class III : BPH is greater than 81 gram in size all patients undergo

open prostatectomy

In the Wahidin Sudirohusodo general hospital Makassar TURP for the

gland which less than 50 gram in size. While, BPH which more than 50

gram reserve to open prostatectomy for the trainee / resident of

Department of Surgery of Medical Faculty, Hasanuddin University

The choice of operation procedure is a personal matter the surgeon /

urologist and the patient what it is preferred

Ad. 1a. SUPRA PUBIC TRANSVESICAL PROSTATECTOMY

This approach to the removal of the very large prostate gland or

patients where there is co.existing bladder pathology e.q. large-stone

or diverticulum

TECHNIQUE:

This technique was popularized by Peter Freyer (1902)

1. The patient is positioned supine and in the little Trendelenburg

position

2. The supra pubic mid line incision or a transverse Phannenstiel incision

which is more preferred

Fig.14. This position to allow the intestine to fall away from the area of the

bladder (Ref. Scott p.235)

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3. After the abdominal wall is opened, urinary bladder is filled water or

saline about 150-200 cc, to identify the bladder with aspiration the

water

4. A longitudinal incision in the bladder

5. After the bladder is opened, it is inspected for coexisting pathology,

prostate gland & internal urethral orifice and ureteric orifices

6. Circular incision is made in the bladder mucosa a round the bladder

neck/internal urethral meatus, with careful avoidance of injury to the

ureteric orifice and avulsion of the bladder mucosa, when the

adenoma is enucleated

7. The internal meatus is identified and the index finger passed into this

meatus to stretch it. This maneuver should break the anterior

commisura and allow separation of the lobes of the prostate (Fig.15a)

8. The plane between the false capsule and the prostatic adenoma is

found and the lateral lobes are enucleated. The enucleation usually

breaks the urethra at the apex of the prostate. This may be assisted

by the presence of the gloved index finger in the rectum. The apical

enucleation and breaks, the urethra should be done sharply to avoid

injury to the external urethral sphincter. (Fig.15 b)

9. A self retaining catheter-three ways 24 F is inserted to urethra

10. Under direct vision any obvious bleeding points in the prostatic-bed

are diathermied

11. Hemostatic suture are inserted through the junction of the prostatic

fossa and the bladder neck (Hryntschaks suture) (Fig.15c)

12. The bladder and wound are closed and a tube drain is left on the

retro pubic space (Fig.15d)

13. Catheter was put in traction and fixation at the medial part of the

right patella

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14. The bladder is irrigated to wash out any blood clot

Fig. 15. Supra pubic transvesical prostatectomy technique. (Ref.Scott p.235-

236)

Ad. 1b. SUPRA PUBICRETRO PUBIC PROSTATECTOMY

Retro pubic prostatectomy (RPP) was developed and popularized by

Terrence Millin and is preferred by most urologists

It give a more direct approach to the prostate by virtue of the fact

that the bladder is not opened

Sometimes a preliminary cystoscopy is performed and the bladder is

inspected to eliminate any coincidental pathology

a b

c d

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TECHNIQUE

1. The patients is positioned with head down to allow the intestine to fall

away from the area of the bladder and to open up the retro pubic

space (Fig.16a)

2. A transverse Phannenstiel incision is preferred

3. The bladder which should be empty is identified and retracted

posteriorly. This further open up the retro pubic space (Fig.16b)

4. Prostatic capsule is identified and a transverse incision in the anterior

prostatic capsule after ligation of the overlying venous plexus

(Fig.16c)

Fig.16 a,b,c. Supra pubic retropubic prostatectomy technique. (Ref.Scott

p.232)

5. The plane between the prostatic adenoma and the false capsule

and adenoma is enucleated with the index finger and using scissors

the urethra is divided proximal the external urethral sphincter with

care being taken to avoid injury to the sphincter (Fig.16 d,e,f)

a b c

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6. Control hemorrhage with a swab is placed in the prostatic cavity and

any obvious bleeding points are diathermied (Fig.16 g)

7. Any small tags tissue are excised and a wedge of tissue is removed

from the posterior bladder neck

Fig. 16 d,e, f, g. Supra pubic retropubic prostatectomy technique. (Ref.Scott

p.233)

8. The bladder mucosa of the posterior lip of the bladder neck is then

suture down into the row cavity of the posterior urethra (Fig.16 h)

d e

f g

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9. A simplastic self retaining three ways catheter no 24 F is passed up

the urethra into the bladder and the prostatic capsule is closed

(Fig.16i)

10. The wound is closed after a tube drain is inserted into the retro pubic

space (Fig.16 i)

Fig.16 h, i. Supra pubic retropubic prostatectomy technique. (Ref.Scott

p.234)

POST OPERATIVE MANAGEMENT OF TRANSVESICAL AND RETRO PUBIC

PROSTATECTOMY

Care must be paid to the efficient drainage of the catheter, irrigation

should be discourage as it may be infection

Sedation and analgetic, beside antibiotic, should be aimed at keeping

feels pain, there is tendency for him to strain. This will cause pelvic an

engorgement and promote venous hemorrhage and clot formation

catheter will be obstructed

Intra venous fluids will be required for the first 24 hours after operation or

until the patients is able to drinks freely without gastrointestinal upset

h i

59

Early mobilization is to be encourage and the patient should sit out of

bed the day after the operation

When the urine is relatively free from blood the urethra catheter is

removed 4-5 day after operation, if the fluid at the drain tube from retro

pubic space has eliminated

The patients is warned that initial his urinary control may be poor but is

encourage to perform perineal exercises to regain control quickly

(Kegels exercises)

POST OPERATIVE COMPLICATION OF TRANSVESICAL AND RETRO PUBIC

OPERATION

1. Hemorrhage :

Varying hemorrhage during operation

Profuse from all surface of the prostatic cavity

Arterial hemorrhage

Secondary hemorrhage :

It commonly arise about the 6th 8th post operative day

and can be quite perfuse

Secondary hemorrhage is not uncommon if there is any

degree bladder infection

2. Incontinence may be caused by sphincter injury or long term

catheterization

3. Infection are common after prostatectomy and may present in different

sites : wound, bladder, urethra, kidney, epididimitis/orchitis

4. Urinary fistula are usually due to deficient closure of the bladder of

prostatic cavity

60

5. Bladder neck stenosis can occur as a result of healing where excessive

fibrous tissue is laid down or where excessive Hryntschaks suture. This

may be promoted be bladder infection

6. Urethral stricture can develop in the posterior urethra

7. Impotence and retro grade ejaculation. The impotence is most likely to

be permanent and does not to administration of androgens

Ad. 1C. PERINEAL PROSTATECTOMY

This method of prostatectomy is not employed in this country (Indonesia)

but is more commonly used in USA. (Formerly about 1950-1965 Indonesia

had a expert in this method: dr. Rudi E. Tan : First chief of Department of

Surgery, Medical Faculty, Hasanuddin University).

TECHNIQUE

1. The patient is placed in the exaggerated lithotomy position (Fig.17a)

2. The incision is made the anterior to the subcutaneous anal sphincter.

Care is taken to avoid damage to the anterior rectal wall (Fig.1b)

3. The perineal muscle are separated to expose the prostatic capsule

4. The capsule is opened and the plans of cleavage between the

adenoma and the false capsule identified (Fig.17c)

a b c

Fig.17 a,b,c. Perineal prostatectomy technique (Ref.Scott 240)

61

5. The prostatic urethra is identified under vision and divided at the apex of

the prostate (Fig.17d)

6. The hypertrophy portion of the gland is removed and the bladder neck is

sutured to the membranous urethra after is inserted a self retaining three

ways catheter 24 F (Fig.17e)

7. The prostatic capsule then sutured and the perineal wound is closed

with adequate drainage

Fig. 17 d,e, Perineal prostatectomy technique (ref. Scott p.241)

COMPLICATION:

1. Impotence. It is a most complication of this method. For this reason this

method is little employed to do it, and it seem the main contra

indication especially the slightly younger patient

2. Hemorrhage

3. Damage to the rectal wall

4. Urinary fistula

5. Infection

d e

62

2A. TRANS URETHRAL RESECTION OF THE PROSTATE (TURP) = TRANS URETHRAL

PROSTATECTOMY

TURP is the most widely accepted method of treating prostatic

urethral obstruction in patients with BPH and is considered the Gold

standard against which other treatment should be compared

PROCEDURE

1. The patient is anesthetized (usually spinal) and lithotomy position.

Preliminary cystoscopy is perform to identify the ureteral orifices, bladder

neck and Verumontanum (Fig.18a)

2. A well lubricated resectoscope is passed

3. The irrigating fluid is a glycin is preferred to prevent hemolysis should

some be absorbed into the prostatic plexus. For this reason is not be

suggested to use water, since is always occurred hemolysis and other

post TURP syndrom e.q. hypervolemic, hyponatremic state due to

absorption of the hypotonic irrigating solution, likely water

(aquabidestilata). Clinical manifestation of the post TURP syndrome

include: nausea, vomiting, confusion, hypertension, Bradycardia and

visual disturbances. The risk of TURP syndrome increase with resection

time over 60 minutes

4. Resection is begun by excising the tissue in the bladder neck. This is

usually from a median bar or a formal median lobe to above the

verumontanum. Resection should not be carried out below the

landmark (verumontanum) to prevent damage at the external urethral

sphincter. The posterior urethra were regarded as a time piece this part

of resection would be from 5 oclock to 7 oclock (fig.18b & c)

5. The lateral lobes are then excised at position 10 oclock and 2 oclock.

The lateral lobes will fall towards the mid line making resection easier. The

63

prostate is excised fully till the cris-cros fibers of the fats capsule are

seem. Any obvious bleeding points are controlled under vision by

diathermy

6. The anterior lobes and the apex of the gland near the verumontanum

and external urethral sphincter are the resected (Fig.18d)

7. The resected pieces of chippings of prostate are evacuated with Elics

evacuator

8. A self retaining three ways catheter is inserted and urine is drained

continuously. Catheter is tracted and fixation in the medial part of the

right knee

Fig. 18a, b. (ref. Kirby p.48)

Trans urethral resection of the

prostate (TURP) is accomplished

using the cutting loop of a

resectoscope

a

b

Enlargement of the right

and left lobes prostate

gland and verumontanum under cystoscopic viewed

64

Fig. 18.c,d . Ref. Kirby p.49

HAZARD OF TURP

1. Hemorrhage :

Primary hemorrhage hemorrhage during operation or after post

operatively

Secondary hemorrhage 7-12 days post operatively, can develop if

there is bladder infection

2. Damage the ureter during the resection

3. Perforation of the bladder especially at the posterior of the bladder neck

The prostate is removed piecemeal and

the chippings are evacuated from the

bladder. Careful haemostasis is then

achieved using diathermy coagulation

c

d

65

4. Damage to the external urethral sphincter : such damage can lead to

dribbling incontinence

5. Damage to the urethra at operation may lead to urethral stricture. This

can be at the external meatus or in the posterior urethra

6. Epididymitis. This can occur especially if the urine is infected pre

operatively

7. Impotence can occur after transurethral resection of the prostate.

8. Post TUR-P Syndrome

This syndrome resulting from a hypervolemic, hyponatriemic state due to

absorption of the hypotonic irrigating solution. Clinical manifestation of

the TUR-P syndrome includes nausea, vomiting, confusion, hypertension,

dyspneu due to lung oedem, bradycardia and visual disturbances. The

risk of TUR syndrome increase with resection time over 60-90 minute. In

severe cases, treatments include diuresis and hypertonic saline (Sol NaCl

3%) administration, but the patient sometimes died.

Advantages of TURP:

Avoidance of an abdominal wound

Blood loss tend to be less than for operation

Period of catheter drainage is slightly shorter

Stay in hospital is shorter

2b. TRANS URETHRAL INCISION OF THE PROSTATE (TUIP)

TUIP is made with the Collins knife between the trigonum and the

verumontanum at seven oclock position

Incision line runs from the ureteric orifice to the verumontanum. This

procedure is associated with less retrograde ejaculation and a lower

complication rate than the standard TURP (Fig.19a)

66

Once the incision has been made, usually be electro cautery the

bladder neck and prostatic urethra should spring open resulting in an

improved flow rate and more complete bladder emptying (Fig.19b)

Fig.19a,b. Incision from the ureteric orifice to the verumontanum (ref.

Kirby p.50)

III. INTERVENTIONAL TREATMENT = MINIMAL INVASIVE

= INVASSIVE NON OPERATIVE TREATMENT

All patients for minimally therapy must really be BPH for that reason. It is prior

biopsy to eliminate Ca.P.

1. BALLOON DILATATION

There are two types of prostatic balloon dilatation system :

a b

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a. A disposable endoscopic system allowing visualization to

ensure correct position of the balloon, so the distal sphincter

was not dilated (Fig.20)

b. Optilume prostatic balloon. This type used a l