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/.