1.

Teori Pembentukan Prostate

i. Teori dihidrotestosteron
Dihidrotestoteron atau DHT adalah metabolit androgen yang sgt penting
pada pertumbuhan sel-sel kelenjar prostate. Enzim 5-reduktase dengan
bantuan koenzim NADPH menukar testoteron kepada DHT.DHT yg
terbentuk berikatan dengan reseptor androgen membentuk kompleks
DHT-RA pada sel dan selanjutnya mensintesis protein growth factor yang
menstimulasi pertumbuhan sel prostate.

ii. Ketidakseimbangan antara estrogen-testosteron

Pada usia yg semakin tua,kadar testosterone menurun,sedangkan kadar
estrogen meningkat.Estrogen berperan dalam terjadinya proliferasi sel-sel
kelenjar prostate dgn cara meningkatkan sensitifitas sel-sel prostate
terhadap rangsangan hormone androgen . Ini menurunkan kadar
apoptosis yg menyebabkan ketidakseimbangan antara proses
pertumbuhan dan kematian sel.

iii. Interaksi stroma-epitel

Diferensiasi dan pertumbuhan sel epitel prostate secara tidak langsung
dikontrol oleh sel-sel stroma melalui mediator. Setelah mendapatkan
stimulasi dr DHT dan estradiol , sel-sel stroma mensintesis suatu growth
factor yg mempengaruhi sel-sel epitel secara parakrin. Stimulasi ini
menyebabkan terjadinya proliferasi sel-sel epitel maupun sel stroma.

iv. Berkurangnya kadar apoptosis

Apoptosis pada sel prostat adalah mekanisme fisiologik untuk
mempertahnkan homeostasis kelenjar prostat. Pada jaringan normal ,
terdapat keseimbangan antara laju proliferasi sel dgn kematian
sel.Berkurangnya jumlah sel-sel prostat yg mengalami apoptosis
menyebabkan jumlah sel-sel prostat secara keseluruhannya meningkat .
Diduga hormon androgen berperan dalam menghambat proses kematian
sel. Estrogen diduga mampu memperpanjang usia sel-sel prostate.

v. Teori sel stem

Untuk mengganti sel-sel yang telah mengalami apoptosis , selalu dibentuk
sel-sel baru. Sel stem mempunyai kemampuan berproliferasi sangat
ekstensif. Sel ini sangat bergantung pada hormone androgen .
 2. Lower urinary tract symptoms (LUTS)

Hiperplasia prostate

Penyempitan lumen uretra prostatika

Tekanan intravesikal tinggi

Buli-buli harus berkontraksi dgn lebih kuat untuk melawan tekanan tinggi
Terjadinya perubahan anatomi buli-buli

Timbulnya gejala yang disebut lower urinary tract symptoms(LUTS)

Obstuksi Iritasi
Hesitansi -frekuensi
Pancaran miksi lemah -nokturi
Intermitensi -urgensi
Miksi tidak puas -disuri
Menetes setelah miksi

3. Prostate Specific Antigen (PSA)

Prostate-specific antigen (PSA) is a protein produced by normal prostate

cells. This enzyme participates in the dissolution of the seminal fluid coagulum
and plays an important role in fertility. The highest amounts of PSA are found in
the seminal fluid; some PSA escapes the prostate and can be found in the
serum. This serum component has been used to track the response to therapy in
men with prostate cancer.

PSA evaluation was never intended to serve as a diagnostic test for

prostate cancer but is useful in helping to identify men in whom a prostate biopsy
would be appropriate. The PSA level tends to rise in men with benign prostatic
hyperplasia (BPH) and is a good marker for prostate volume. PSA levels are
usually elevated in men with acute bacterial prostatitis. The most valuable
measurement of PSA is its change over time rather than the actual serum level.
No identifiable PSA level guarantees normalcy; in addition, no specific level
indicates that a biopsy should be performed. Instead, PSA velocity or doubling
time has been shown to be a more accurate and reliable predictor for
recommending a prostate biopsy and treating patients with this disease.
 It is produced by the cells of the prostate gland and mammary gland. Low
concentrations of PSA have been identified in urethral glands, endometrium,
normal breast tissue, breast milk, salivary gland tissue, and in the urine of males
and females. PSA also is found in the serum of women with breast, lung, or
uterine cancer and in some patients with renal cancer. Normal for men to have
low level of PSA.It is recommended that early screening for men over 50 years
and men at high risk. PSA increased in Carcinoma prostate , DRE , Infection and
catheter insertion .Normal value = 4.Borderline = 4 10 .
PSAD is defined as the total serum PSA divided by prostate volume, as
determined by transrectal ultrasound measurement. Theoretically, PSAD could
help distinguish between prostate cancer and BPH in men whose PSA levels are
4-10 ng/mL..
PSA density = PSA level / prostate volume.
Indication for biopsy,
Nodule
PSA level > 10
PSAd > 0.15

PSA-V is used to monitor the change in PSA over time using longitudinal
measurements. Greater changes in PSA-V were detected in men with cancer
compared to those without cancer 5 years before the diagnosis was made.
Additional studies have shown that this difference can be detected up to 9 years
before prostate cancer diagnosis.

PSA-V is calculated using the following equation:

i/2 ([PSA2 - PSA1 / time 1 in years] + [PSA3 - PSA2 / time 2 in years])

PSA1 = First PSA measurement
PSA2 = Second PSA measurement
PSA3 = Third PSA measurement

At least 3 PSA measurements are needed during a 2-year period or at least 12-
18 months apart to obtain maximal benefit from the results.

A PSA-V of 0.75 ng/mL or greater per year was suggestive of cancer (72%
sensitivity, 95% specificity). A PSA-V of 0.75 ng/mL or greater correlated with the
diagnosis of cancer in 72% of the patients, and only 5% had no cancer. The
limitations of PSA-V testing include that it is difficult to calculate, that PSA is not
cancer specific, and that PSA varies significantly with time and with different
assays. Nevertheless, a PSA-V greater than 0.75 ng/mL per year is useful in
some situations in helping to decide the need for initial or repeat biopsy.
4 . Transrectal Ultrasonography (TRUS)

Local anesthesia and the procedure

Most TRUS procedures and biopsies are performed without any surface
anesthetics; however, Xylocaine jelly or periprostatic block may be used. They
reinjected 2.5 mL of lidocaine on each side at the prostate base at the junction of
the prostate and the seminal vesicle (using a 5-in 22-gauge spinal needle
through the ultrasound probe).

Currently, the most widely used probe is a 7-MHz transducer within an

endorectal probe, which can produce images in both the sagittal and axial
planes. Scanning begins in the axial plane, and the base of the prostate and
seminal vesicles are imaged first. A small amount of urine in the bladder
facilitates the examination. Seminal vesicles are identified bilaterally, with the
ampullae of the vas on either side of the midline. The seminal vesicles are
convoluted cystic structures and are darkly anechoic. Dilated seminal vesicles
are seen in men who have abstained from ejaculation for a long period.

Next, the base of the prostate is imaged. The central zone comprises the
posterior part of the gland and often is hyperechoic. The mid gland is the widest
portion of the gland. The peripheral zone forms most of the gland volume.
Echoes are described as isoechoic and closely packed. The transition zone is the
central part of the gland and is hypoechoic. The junction of the peripheral zone
and the transition zone is distinct posteriorly and is characterized by a
hyperechoic region, which results from prostatic calculi or corpora amylacea. The
transition zone is often filled with cystic spaces in patients with BPH.

Scanning at the level of the verumontanum and observing the Eiffel tower
sign (anterior shadowing) help identify the urethra and the verumontanum. The
prostate distal to the verumontanum is mainly composed of the peripheral zone.
The capsule is a hyperechoic structure that can be identified all around the
prostate gland. Several hypoechoic rounded structures can be identified around
the prostate gland. These are the prostatic venous plexi. The position of the
neurovascular bundles can often be identified by the vascular structures. Imaging
in the sagittal plane allows visualization of the urethra. The median lobes of the
prostate are often visualized.

Volume measurement

Volume assessment of the prostate is an important and integral part of this

procedure. Several formulas have been used, but the most common one is the
ellipsoid formula, which requires measurement of 3 prostate dimensions.
Dimensions are first determined in the axial plane by measuring the transverse
and anteroposterior dimension at the estimated point of widest transverse
dimension. The longitudinal dimension is measured in the sagittal plane just off
the midline because the bladder neck often obscures the cephalad extent of the
gland. The ellipsoid volume formula is then applied, as follows:

Volume = height X width X length X 0.52

5 . Voiding Cystourethrogram

Vesicoureteral reflux

With normal urination, the bladder contracts and urine leaves the body
through the urethra. With vesicoureteral reflux, some urine goes back up into the
ureters and possibly up to the kidneys. Reflux exposes the kidneys to infection.
In children, particularly those in the first 6 years of life, urinary infection can
cause kidney damage. The injury to the kidney may result in renal scarring and
loss of future growth potential or widespread scarring and atrophy. Even a small
area of scarring in one kidney may be a cause of high blood pressure later in life.
Untreated reflux on both sides can, in the most severe instances, result in kidney
failure requiring dialysis or kidney transplantation.

The valve system at the ureterovesical (ureter-bladder) junction may be

abnormal:

In some children the tunnel of the lower ureter through the muscular wall
of the bladder may not be long enough. For these children, there is a good
chance that growth may provide the necessary difference to allow the
valve to work.
The ureter may enter into the bladder abnormally (usually too much to the
side), resulting in a short tunnel. This reflux is less likely to resolve with
growth.
 Based on these studies, reflux can be classified into five grades - grade 1 is the
least and grade 5 is the worst. Mild degrees of reflux have a good chance of resolving
spontaneously with age. Chances of resolution with high-grade reflux (grade 4-5, or
reflux related to an anatomic problem such as a long-standing obstruction) are much
lower.

Normal kidney, ureter, and Grade I Vesicoureteral Reflux: Grade II Vesicoureteral Reflux:
bladder urine (shown in blue) refluxes urine refluxes all the way up the
part-way up the ureter ureter

Grade III Vesicoureteral Reflux:
urine refluxes all the way up the
ureter with dilatation of the
ureter and calyces (part of the
kidney where urine collects)
Grade IV Vesicoureteral Reflux:
urine refluxes all the way up the
ureter with marked dilatation of
the ureter and calyces
Grade V Vesicoureteral Reflux:
massive reflux of urine up the
ureter with marked tortuosity and
dilatation of the ureter and
calyces
Diagnosis
The following procedures may be used to diagnose VUR:

Nuclear cystogram (RNC)

Flouroscopic voiding cytourerthrogram (VCUG)
Ultrasonic cystography
Abdominal ultrasound

VCUG is the method of choice for grading and initial workup, while RNC is
preferred for subsequent evaluations as there is less exposure to radiation. A
high index of suspicion should be attached to any case a where a child presents
with a urinary tract infection, and anatomical causes should be excluded. A
VCUG and abdominal ultrasound should be performed in these cases

A voiding cystourethrogram (VCUG), is a test used to visualize the urethra

and urinary bladder that takes place during micturition (voiding). The test consists
of catheterizing the patient and allowing radiopaque contrast (typically
cystografin) to drip into the bladder. Under fluoroscopy (real time x-rays) the
radiologist watches the contrast enter the bladder and looks at the anatomy of
the patient. If the contrast refluxes into the ureters and back into the kidneys, the
radiologist gives the degree of severity a score. The exam ends when the patient
voids on the table while the radiologist is watching under fluoroscopy. It is
important to watch the contrast during voiding, because this is when the bladder
has the most pressure, and it is most likely this is when reflux will occur.

Indications
Recurrent urinary tract infections
Anything suggesting urethral obstruction (e.g. bilateral hydronephrosis)

Contraindications
Untreated urinary tract infection

Treatment
Medical treatment is the preferred mode of management but surgical
interventions may be necessary. Medical management is recommended in
children with Grade I-III VUR as most cases will resolve spontaneously. A trial of
medical treatment is indicated in patients with Grade IV VUR especially in
younger patients or those with unilateral disease. Of the patients with Grade V
VUR only infants are trialled on a medical approach before surgery is indicated,
in older patients surgery is the only option.
Medical Treatment

Medical treatment entails low dose antibiotic prophylaxis until resolution of

VUR occurs. Antibiotics are administered nightly at half the normal therapeutic
dose. The specific antibiotics used differ with the age of the patient and include:
-Amoxicillin or ampicillin - infants younger then 6 weeks
-Trimethoprim-sulfamethoxazole (co-trimoxazole) - 6 weeks to 2 months

Urine cultures are performed 3 monthly to exclude breakthrough infection.

Annual radiological investigations are likewise indicated. Good perineal hygiene,
and timed and double voiding are also important aspects of medical treatment.
Bladder dysfunction is treated with the administration of anticholinergics.

Surgical Management

A surgical approach is necessary in cases where a breakthrough infection

results despite prophylaxis, or there is non-compliance with the prophylaxis.
Similarly if the VUR is severe (Grade IV & V), there are pyelonephritic changes or
congenital abnormalities. Other reasons necessitating surgical intervention are
failure of renal growth, formation of new scars, renal deterioration and VUR in
girls approaching puberty.

There are three types of surgical procedure available for the treatment of
VUR: endoscopic (STING procedure); laparoscopic; and open procedures
(Cohen procedure, Leadbetter-Politano procedure).