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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-testosteronPada 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 apoptosisApoptosis 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 measurementPSA2 = Second PSA measurementPSA3 = 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 measurementVolume 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 bladderGrade I Vesicoureteral Reflux:urine (shown in blue) refluxes part-way up the ureterGrade II Vesicoureteral Reflux:urine refluxes all the way up the 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 calycesGrade 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 TreatmentMedical 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 ManagementA 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).