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 NADH menukar testoteron kepada DHT.DHT yg
terbentuk berikatan dengan reseptor androgen membentuk kompleks
DHT-!A pada sel dan selanjutnya mensintesis protein gro"th #a$tor yang
menstimulasi pertumbuhan sel prostate.
ii. %etidakseimbangan antara estrogen-testosteron
ada usia yg semakin tua&kadar testosterone menurun&sedangkan kadar
estrogen meningkat.Estrogen berperan dalam terjadinya proli#erasi sel-sel
kelenjar prostate dgn $ara meningkatkan sensiti#itas sel-sel prostate
terhadap rangsangan hormone androgen . 'ni menurunkan kadar
apoptosis yg menyebabkan ketidakseimbangan antara proses
pertumbuhan dan kematian sel.
iii. 'nteraksi stroma-epitel
Di#erensiasi dan pertumbuhan sel epitel prostate se$ara tidak langsung
dikontrol oleh sel-sel stroma melalui mediator. (etelah mendapatkan
stimulasi dr DHT dan estradiol & sel-sel stroma mensintesis suatu gro"th
#a$tor yg mempengaruhi sel-sel epitel se$ara parakrin. (timulasi ini
menyebabkan terjadinya proli#erasi sel-sel epitel maupun sel stroma.
i). *erkurangnya kadar apoptosis
Apoptosis pada sel prostat adalah mekanisme #isiologik untuk
mempertahnkan homeostasis kelenjar prostat. ada jaringan normal &
terdapat keseimbangan antara laju proli#erasi sel dgn kematian
sel.*erkurangnya jumlah sel-sel prostat yg mengalami apoptosis
menyebabkan jumlah sel-sel prostat se$ara keseluruhannya meningkat .
Diduga hormon androgen berperan dalam menghambat proses kematian
sel. Estrogen diduga mampu memperpanjang usia sel-sel prostate.
). Teori sel stem
+ntuk mengganti sel-sel yang telah mengalami apoptosis & selalu dibentuk
sel-sel baru. (el stem mempunyai kemampuan berproli#erasi sangat
ekstensi#. (el ini sangat bergantung pada hormone androgen .
2. Lower urinary tract symptoms (LUTS)
Hiperplasia prostate
enyempitan lumen uretra prostatika
Tekanan intra)esikal tinggi
*uli-buli harus berkontraksi dgn lebih kuat untuk mela"an tekanan tinggi
Terjadinya perubahan anatomi buli-buli
Timbulnya gejala yang disebut lower urinary tract symptoms(LUTS)
,bstuksi 'ritasi
Hesitansi -#rekuensi
an$aran miksi lemah -nokturi
'ntermitensi -urgensi
-iksi tidak puas -disuri
-enetes setelah miksi
3. Prostate Specific Antigen (PSA)
rostate-spe$i#i$ antigen .(A/ is a protein produ$ed by normal prostate
$ells. This enzyme parti$ipates in the dissolution o# the seminal #luid $oagulum
and plays an important role in #ertility. The highest amounts o# (A are #ound in
the seminal #luid0 some (A es$apes the prostate and $an be #ound in the
serum. This serum $omponent has been used to tra$k the response to therapy in
men "ith prostate $an$er.
(A e)aluation "as ne)er intended to ser)e as a diagnosti$ test #or
prostate $an$er but is use#ul in helping to identi#y men in "hom a prostate biopsy
"ould be appropriate. The (A le)el tends to rise in men "ith benign prostati$
hyperplasia .*H/ and is a good marker #or prostate )olume. (A le)els are
usually ele)ated in men "ith a$ute ba$terial prostatitis. The most )aluable
measurement o# (A is its $hange o)er time rather than the a$tual serum le)el.
No identi#iable (A le)el guarantees normal$y0 in addition& no spe$i#i$ le)el
indi$ates that a biopsy should be per#ormed. 'nstead& (A )elo$ity or doubling
time has been sho"n to be a more a$$urate and reliable predi$tor #or
re$ommending a prostate biopsy and treating patients "ith this disease.
't is produ$ed by the $ells o# the prostate gland and mammary gland. 1o"
$on$entrations o# (A ha)e been identi#ied in urethral glands& endometrium&
normal breast tissue& breast milk& sali)ary gland tissue& and in the urine o# males
and #emales. (A also is #ound in the serum o# "omen "ith breast& lung& or
uterine $an$er and in some patients "ith renal $an$er. Normal #or men to ha)e
lo" le)el o# (A.'t is re$ommended that early s$reening #or men o)er 52 years
and men at high risk. (A in$reased in 3ar$inoma prostate & D!E & 'n#e$tion and
$atheter insertion .Normal )alue 4 5.*orderline 4 5 6 72 .
(AD is de#ined as the total serum (A di)ided by prostate )olume& as
determined by transre$tal ultrasound measurement. Theoreti$ally& (AD $ould
help distinguish bet"een prostate $an$er and *H in men "hose (A le)els are
5-72 ng8m1..
(A density 4 (A le)el 8 prostate )olume.
'ndi$ation #or biopsy&
Nodule
(A le)el 9 72
(Ad 9 2.75
(A-: is used to monitor the $hange in (A o)er time using longitudinal
measurements. ;reater $hanges in (A-: "ere dete$ted in men "ith $an$er
$ompared to those "ithout $an$er 5 years be#ore the diagnosis "as made.
Additional studies ha)e sho"n that this di##eren$e $an be dete$ted up to < years
be#ore prostate $an$er diagnosis.
(A-: is $al$ulated using the #ollo"ing e=uation>
i8? .@(A? - (A7 8 time 7 in yearsA B @(AC - (A? 8 time ? in yearsA/
(A7 4 Dirst (A measurement
(A? 4 (e$ond (A measurement
(AC 4 Third (A measurement
At least C (A measurements are needed during a ?-year period or at least 7?-
7E months apart to obtain maFimal bene#it #rom the results.
A (A-: o# 2.G5 ng8m1 or greater per year "as suggesti)e o# $an$er .G?H
sensiti)ity& <5H spe$i#i$ity/. A (A-: o# 2.G5 ng8m1 or greater $orrelated "ith the
diagnosis o# $an$er in G?H o# the patients& and only 5H had no $an$er. The
limitations o# (A-: testing in$lude that it is di##i$ult to $al$ulate& that (A is not
$an$er spe$i#i$& and that (A )aries signi#i$antly "ith time and "ith di##erent
assays. Ne)ertheless& a (A-: greater than 2.G5 ng8m1 per year is use#ul in
some situations in helping to de$ide the need #or initial or repeat biopsy.
. Transrecta! U!trasonograp"y (T#US)
1o$al anesthesia and the pro$edure
-ost T!+( pro$edures and biopsies are per#ormed "ithout any sur#a$e
anestheti$s0 ho"e)er& Iylo$aine jelly or periprostati$ blo$k may be used. They
reinje$ted ?.5 m1 o# lido$aine on ea$h side at the prostate base at the jun$tion o#
the prostate and the seminal )esi$le .using a 5-in ??-gauge spinal needle
through the ultrasound probe/.
3urrently& the most "idely used probe is a G--Hz transdu$er "ithin an
endore$tal probe& "hi$h $an produ$e images in both the sagittal and aFial
planes. ($anning begins in the aFial plane& and the base o# the prostate and
seminal )esi$les are imaged #irst. A small amount o# urine in the bladder
#a$ilitates the eFamination. (eminal )esi$les are identi#ied bilaterally& "ith the
ampullae o# the )as on either side o# the midline. The seminal )esi$les are
$on)oluted $ysti$ stru$tures and are darkly ane$hoi$. Dilated seminal )esi$les
are seen in men "ho ha)e abstained #rom eja$ulation #or a long period.
NeFt& the base o# the prostate is imaged. The $entral zone $omprises the
posterior part o# the gland and o#ten is hypere$hoi$. The mid gland is the "idest
portion o# the gland. The peripheral zone #orms most o# the gland )olume.
E$hoes are des$ribed as isoe$hoi$ and $losely pa$ked. The transition zone is the
$entral part o# the gland and is hypoe$hoi$. The jun$tion o# the peripheral zone
and the transition zone is distin$t posteriorly and is $hara$terized by a
hypere$hoi$ region& "hi$h results #rom prostati$ $al$uli or $orpora amyla$ea. The
transition zone is o#ten #illed "ith $ysti$ spa$es in patients "ith *H.
($anning at the le)el o# the )erumontanum and obser)ing the Ei##el to"er
sign .anterior shado"ing/ help identi#y the urethra and the )erumontanum. The
prostate distal to the )erumontanum is mainly $omposed o# the peripheral zone.
The $apsule is a hypere$hoi$ stru$ture that $an be identi#ied all around the
prostate gland. (e)eral hypoe$hoi$ rounded stru$tures $an be identi#ied around
the prostate gland. These are the prostati$ )enous pleFi. The position o# the
neuro)as$ular bundles $an o#ten be identi#ied by the )as$ular stru$tures. 'maging
in the sagittal plane allo"s )isualization o# the urethra. The median lobes o# the
prostate are o#ten )isualized.
:olume measurement
:olume assessment o# the prostate is an important and integral part o# this
pro$edure. (e)eral #ormulas ha)e been used& but the most $ommon one is the
ellipsoid #ormula& "hi$h re=uires measurement o# C prostate dimensions.
Dimensions are #irst determined in the aFial plane by measuring the trans)erse
and anteroposterior dimension at the estimated point o# "idest trans)erse
dimension. The longitudinal dimension is measured in the sagittal plane just o##
the midline be$ause the bladder ne$k o#ten obs$ures the $ephalad eFtent o# the
gland. The ellipsoid )olume #ormula is then applied& as #ollo"s>
:olume 4 height I "idth I length I 2.5?
$ . %oi&ing 'ystouret"rogram
:esi$oureteral re#luF
Jith normal urination& the bladder $ontra$ts and urine lea)es the body
through the urethra. Jith )esi$oureteral re#luF& some urine goes ba$k up into the
ureters and possibly up to the kidneys. !e#luF eFposes the kidneys to in#e$tion.
'n $hildren& parti$ularly those in the #irst K years o# li#e& urinary in#e$tion $an
$ause kidney damage. The injury to the kidney may result in renal s$arring and
loss o# #uture gro"th potential or "idespread s$arring and atrophy. E)en a small
area o# s$arring in one kidney may be a $ause o# high blood pressure later in li#e.
+ntreated re#luF on both sides $an& in the most se)ere instan$es& result in kidney
#ailure re=uiring dialysis or kidney transplantation.
The )al)e system at the uretero)esi$al .ureter-bladder/ jun$tion may be
abnormal>
'n some $hildren the tunnel o# the lo"er ureter through the mus$ular "all
o# the bladder may not be long enough. Dor these $hildren& there is a good
$han$e that gro"th may pro)ide the ne$essary di##eren$e to allo" the
)al)e to "ork.
The ureter may enter into the bladder abnormally .usually too mu$h to the
side/& resulting in a short tunnel. This re#luF is less likely to resol)e "ith
gro"th.
*ased on these studies& re#luF $an be $lassi#ied into #i)e grades - grade 7
is the least and grade 5 is the "orst. -ild degrees o# re#luF ha)e a good $han$e
o# resol)ing spontaneously "ith age. 3han$es o# resolution "ith high-grade re#luF
.grade 5-5& or re#luF related to an anatomi$ problem su$h as a long-standing
obstru$tion/ are mu$h lo"er.
Normal kidney& ureter& and
bladder
;rade ' :esi$oureteral !e#luF>
urine .sho"n in blue/ re#luFes
part-"ay up the ureter
;rade '' :esi$oureteral !e#luF>
urine re#luFes all the "ay up the
ureter
;rade ''' :esi$oureteral !e#luF>
urine re#luFes all the "ay up the
ureter "ith dilatation o# the
ureter and $aly$es .part o# the
kidney "here urine $olle$ts/
;rade ': :esi$oureteral !e#luF>
urine re#luFes all the "ay up the
ureter "ith marked dilatation o#
the ureter and $aly$es
;rade : :esi$oureteral !e#luF>
massi)e re#luF o# urine up the
ureter "ith marked tortuosity and
dilatation o# the ureter and
$aly$es
Diagnosis
The #ollo"ing pro$edures may be used to diagnose :+!>
Nu$lear $ystogram .!N3/
Dlouros$opi$ )oiding $ytourerthrogram .:3+;/
+ltrasoni$ $ystography
Abdominal ultrasound
:3+; is the method o# $hoi$e #or grading and initial "orkup& "hile !N3 is
pre#erred #or subse=uent e)aluations as there is less eFposure to radiation. A
high indeF o# suspi$ion should be atta$hed to any $ase a "here a $hild presents
"ith a urinary tra$t in#e$tion& and anatomi$al $auses should be eF$luded. A
:3+; and abdominal ultrasound should be per#ormed in these $ases
A )oiding $ystourethrogram .:3+;/& is a test used to )isualize the urethra
and urinary bladder that takes pla$e during mi$turition .)oiding/. The test $onsists
o# $atheterizing the patient and allo"ing radiopa=ue $ontrast .typi$ally
$ystogra#in/ to drip into the bladder. +nder #luoros$opy .real time F-rays/ the
radiologist "at$hes the $ontrast enter the bladder and looks at the anatomy o#
the patient. '# the $ontrast re#luFes into the ureters and ba$k into the kidneys& the
radiologist gi)es the degree o# se)erity a s$ore. The eFam ends "hen the patient
)oids on the table "hile the radiologist is "at$hing under #luoros$opy. 't is
important to "at$h the $ontrast during )oiding& be$ause this is "hen the bladder
has the most pressure& and it is most likely this is "hen re#luF "ill o$$ur.
'ndi$ations
!e$urrent urinary tra$t in#e$tions
Anything suggesting urethral obstru$tion .e.g. bilateral hydronephrosis/
3ontraindi$ations
+ntreated urinary tra$t in#e$tion
Treatment
-edi$al treatment is the pre#erred mode o# management but surgi$al
inter)entions may be ne$essary. -edi$al management is re$ommended in
$hildren "ith ;rade '-''' :+! as most $ases "ill resol)e spontaneously. A trial o#
medi$al treatment is indi$ated in patients "ith ;rade ': :+! espe$ially in
younger patients or those "ith unilateral disease. ,# the patients "ith ;rade :
:+! only in#ants are trialled on a medi$al approa$h be#ore surgery is indi$ated&
in older patients surgery is the only option.
-edi$al Treatment
-edi$al treatment entails lo" dose antibioti$ prophylaFis until resolution o#
:+! o$$urs. Antibioti$s are administered nightly at hal# the normal therapeuti$
dose. The spe$i#i$ antibioti$s used di##er "ith the age o# the patient and in$lude>
-AmoFi$illin or ampi$illin - in#ants younger then K "eeks
-Trimethoprim-sul#amethoFazole .$o-trimoFazole/ - K "eeks to ? months
+rine $ultures are per#ormed C monthly to eF$lude breakthrough in#e$tion.
Annual radiologi$al in)estigations are like"ise indi$ated. ;ood perineal hygiene&
and timed and double )oiding are also important aspe$ts o# medi$al treatment.
*ladder dys#un$tion is treated "ith the administration o# anti$holinergi$s.
(urgi$al -anagement
A surgi$al approa$h is ne$essary in $ases "here a breakthrough in#e$tion
results despite prophylaFis& or there is non-$omplian$e "ith the prophylaFis.
(imilarly i# the :+! is se)ere .;rade ': L :/& there are pyelonephriti$ $hanges or
$ongenital abnormalities. ,ther reasons ne$essitating surgi$al inter)ention are
#ailure o# renal gro"th& #ormation o# ne" s$ars& renal deterioration and :+! in
girls approa$hing puberty.
There are three types o# surgi$al pro$edure a)ailable #or the treatment o#
:+!> endos$opi$ .(T'N; pro$edure/0 laparos$opi$0 and open pro$edures
.3ohen pro$edure& 1eadbetter-olitano pro$edure/.