ࡱ>  Fbjbj-- 4HOO!pppppD,=!tl n n n n n n ,"c% ]p Ypp YYYppl Yl YYV@4 0 ?خ X  !0=!T &Y &4 Yp4 $ Y=! & 6:    10-9-08 Prostate Disease and Pathology Prostate Anatomy Location posterior to pubic symphysis, anterior to rectum, inferior to bladder Ducts urethra & ejaculatory ducts run through it Function adds secretions to ejaculate, not essential for survival Innervation from sacral roots, attach posterolaterally Lobes prostate has 5 lobes, but only 2 important: Transitional Zone where benign prostatic hyperplasia (BPH) arises usually Peripheral Zone where prostate cancer arises usually, easiest to find on DRE Prostate DRE DRE digital rectal can feel lateral lobe of prostate on left, look for: Contour smooth prostate (like thumb mus.), probably enlarge, no nodules/induration, Size should be walnut size, but can reach plum/peach/orange BPH usually detected as nodules in the transitional zone Prostate Cancer usually detected as growth of the peripheral zone Normal Prostate Histology Glands normally have large, undulating architecture, made up of basal cells and secretory cells Secretory cells columnar epithelium forming monolayer Basal cells layer deep to secretory cells, loss of these Dx of prostate cancer Stroma substance of prostate, surrounds glands, made up of fibroblasts and SM cells Cytokeratin Stain will stain basal cells ( loss of them = cancer Prostate Growth Androgens required for prostate growth, usually enters prostate in form of testosterone Source LH hypothalamus ( ACTH & LH pituitary ( testosterone (testes, adrenals) Testes stimulated by LH from pituitary, 95% testosterone Adrenal Glands  stimuated by ACTH from pituitary, 5% adrenal androgens Testosterone  free testosterone enters, converted to dihydrotestosterone DHT via 5-reductase DHT  after converted, binds to cytoplasmic androgen receptor proteins, forms complex DHT-AR complex translocates to nucleus of prostate cells, binds to response elements Response elements bind complex, activate promoter regions of target genes ( transcription BPH Transitional Zone enlarges, impinges on urethra causing slowed urination; can image with US Prevalence 10-25% US men require Tx for BPH, frequency increases w/ aging Symptoms often non-specific; obstructive voiding (slow, hesitancy, nocturia) urgency; HTN QUIZ: Prostate size has no correlation with symptom severity Urinalysis microhematuria (BPH cells), creatinine high, prostate-specific-antigen (PSA) high Other BPH Presentations acute urinary retentention, hematuria: Acute urinary retention inability to urinate; less common but obviously more severe Hematuria if not cancer, then next-most-likely cause of hematuria can be BPH BPH Progression & Sequelae Bladder wall hypertrophy decreased urine output ( higher bladder volume ( hypertrophy Reduced function - bladder dilation decompensates the bladder Ureter & renal pelvis dilation (hydronephrosis) from urine backing up from bladder Early renal dysfunction cant concentrate urine as well Late renal dysfunction azotemia, renal insufficiency Hydronephrosis very dilated ureter & renal pelvis, often visualized w/ contrast dye Bladder stones from urinary stasis of increased urine volume in bladder BPH Assessment International Prostate Symptom Index (IPSS) chart scoring severity of symptoms Flow Rate time a urination, measure urine dynamics (20-25 cc/sec is normal) BPH Treatment -Blockade  prevent constriction of urethra, includes non-selective & selective: Non-selective  doxazosin, terazosin ( will also reduce BP, cause dizziness, etc. Selective  tamsulosin (flomax) ( acts specifically on prostate, fewer SEs 5-Reductase Inhibitor (finasteride, dutastaride)  prevent DHT formation, less BPH stimulus Stenting  urethral stent to expand Laser vaporization, Bladder neck incision, Microwave thermotherapy  minimally invasive Trans-urethral resection of prostate surgically invasive, 70% effective Open Prostatectomy remove entire prostate, 80% effective BPH Pathology Proliferation nodular proliferation usually confined to transition zone Overgrowth stroma & epithelium both have potential to be hyperplastic; BPH often combines both Stromal nodules overgrowth of stroma; looks very solid Adenosis overgrowth of glands; many more papilla & infolding Differentiation cells still well-differentiated, has benign appearance Trans-urethral Resection of Prostate (TURP) chips can be analyzed pathologically after surgery Prostate Cancer Prevalence 30% of malignancies in men, 20% lifetime chance of developing, but treatable; (Lung ca. highest death rate) Risk Factors include age, race (African Americans), family Hx Staging T1 (non-palpable), T2 (palpable, elevated PSA), T3 (outside prostate), T4 (mass spread) Metastasis can metastasize to lymph nodes, spine/skeleton, lung, bladder anywhere really Symptoms most often asymptomatic, but can range up to very severe; will see: Urinary obstruction symptoms hematuria, bone pain/pelvic pain, BPH-mimicking Systemic anorexia/cachexia, uremia Peripheral Zone where bulk of prostate cancers occur, although some in transitional zone Prostate Cancer Dx Serum PSA shows elevated PSA at early stages, correlation does exist for PSA & tumor size; PSA also increases w/ age DRE also good diagnostic tool, can have prostate cancer without elevated PSA Biopsy guided by ultrasound through rectum, obtain tissue diagnosis Bone Scan indicated for staging when PSA > 10 b/c skeletal metastases are common MRI best test to find bony metastases Prostate Cancer Tx Radical Prostatectomy remove prostate completely, SEs include impotence, incontinence Radiation Therapy external beam or brachytherapy (radioactive seed implant), SEs same plus bowel symptoms Palliative induce androgen deprivation ( apoptosis of androgen-sensitive cells, but not cure Bilateral orchioectomy (remove testes) or pharm. Side effects decreased libido, hot flashes, breast enlargement/tenderness Screening controversial, due to lack of benefit evidence; give DRE & PSA for over 50 & at-risk Prostate Carcinoma Pathology Architectural Changes include changes in glandular structure and perineural invasion: Small gland infiltration very small round glands appearing between undulating benign glands Perineural invasion glands wrap around nerves of prostate, but infrequent Cell Changes include basal cell loss, nuclear changes, secretions, cytoplasmic amphophilia: Basal cell loss the hallmark of prostate cancer Nuclear enlargement enlarged nuclei with prominent nucleoli Cytoplasmic secretions see mucin and crystalloids in cancer cells ( very granular Prostate Cancer Grading Gleasons Score based on the architecture, score based on 1o + 2o patterning (or double 1o if only one) Pattern 1 very well differentiated, good prognosis but see in transition zone (rare) Pattern 2 well differentiated, glands round & regular see in transition zone (rare) Pattern 3 is most common pattern seen, infiltrative growth between benign glands, no fusion Pattern 4 small glands invading become fused, has a sieve-like growth pattern Pattern 5 a solid sheet of tumor cells, glandular architecture lost; sieve-like growth, necrosis Prognosis grading by Gleasons score has strong correlation with prognosis; 4/5 highly predictive of progression and metastasis Bins 2-6 is well diff; 7 is moderate; 8-10 poor Prostate Cancer Prostatectomy Evaluation Tumor size/margins smaller & within prostate is better Tumor stage how far tumor has spread: T2 confined to prostate T3a reaches outside of prostate T3b reaches out to seminal vesicle T4 invasion of adjacent organs Prostatitis Prostatitis enlarged prostate due to inflammation, includes non-bacterial/bacterial, acute/chronic Non-bacterial acute prostatitis common in younger men (usually STD chlamydia) Bacterial more progressive, occurs after age 30 Timeframe acute or chroniC   " < A p    d k " 3 C h w x  , ·ЬؠДІzh4Kh)Q5CJaJhh)Q56CJaJhE2h)Q5CJaJhvXh)Q5CJaJh ,h)QCJaJh)Q56CJaJhE2h)Q56CJaJh)QCJaJh)Q5CJaJh CJaJh 5CJaJjh65CJUaJ0); < p  d 4 x - ~  + " & Fgd)Q & Fgd)Qgd)Q & Fgd)Q & Fgd)Q, - 8 Z i j n } ~     4 D S  ">Duihfeh)Q5CJaJhsbh)Q5CJaJh+2h)QCJaJ jh+2h)QCJaJh5h)Q5CJaJh"h)Q5CJaJ jh"h)QCJaJh6ph)Q5CJaJh)Q56CJaJh)Q5CJH*aJh)QCJaJh)Q5CJaJhh)Q5CJaJ)"pe$p jPlWhx.Lgd)Q & Fgd)Q & Fgd)QDFLVnpvSdev$.HI]opx  Eej OP1V jh@zh)QCJaJhN0h)QCJaJh4dFh)QCJaJh)Q56CJaJh)QCJH*aJ jhNYh)QCJaJhfeh)QCJaJhfeh)Q5CJaJh)Q5CJaJh)QCJaJ8VWn,hwx.`:<*V*,78Jrs,-<MSUefqhrh)Q5CJaJh ,h)Q5CJaJh*h)Q5CJaJ jh*h)QCJaJh*h)QCJaJh6h)Q5CJaJh~Dh)QCJaJh)QCJaJh)Q5CJaJh@zh)QCJaJ8*,8s-fQb}(w  & Fgd)Qgd)Q & Fgd)Q & Fgd)Qq!PQl"|}(Dw̾vh4dFh)QCJaJh-mh)Q56CJaJh3 h)Q5CJaJh3 h)Q56CJaJh)QCJH*aJhh)Q5CJaJh ,h)Q56CJaJh ,h)QCJaJh,h)Q5CJaJhOch)Q5CJaJh)Q5CJaJh)QCJaJ.   *;FVfh j m !j!t!~!!!!!!"F"O"""#5#{####&$5$<$W$X$k$$̵̪̜̑h,h)QCJaJh ,h)QCJaJ jh0]h)QCJaJh(.h)QCJaJhh)Q5CJaJh)Q56CJaJh)QCJaJh ,h)Q5CJaJh3 h)Q5CJaJh)Q5CJaJh)Q5CJH*aJ4 j j!!!F"""#{##&$X$$$%m%%&z&&-' & Fgd)Q & Fgd)Q & Fgd)Qgd)Q & Fgd)Q$$$$$$$$$$$%"%.%@%A%E%F%^%_%`%l%y%%%%%&&&(&+&>&p&y&&&&&&&&&','6''''(E(Q(m(o((((((((( )`)h Bh)QCJaJh h)Q5CJaJh)QCJH*aJh)QCJH*aJh,h)QCJaJh,h)Q5CJaJ jh,h)QCJaJh)QCJaJh)Q5CJaJ?-''' (E(m((((((a)))D>DoDDDElEE+F;FFF & Fgd)Q & Fgd)Q & Fgd)Qgd)Q & Fgd)Q`)a)n))))))))*DDD=D>DTDnDwDDDDDDDDDDD E6EkElEqErE{EEEEEEEE*F+F8F9F@FyFFFFFFFFhtch)Q5CJaJh)QCJH*aJh)Q5CJH*aJhqzh)QCJaJUh)Q56CJaJh)QCJaJh)Q5CJaJhqzh)Q5CJaJ7c: Acute Prostatitis often has fever, boggy prostate on DRE Chronic Prostatitis no fever, unremarkable DRE Symptoms often asymptomatic, or dysuria, high freq., pelvic/perineal pain, pain w/ ejaculate Prostatitis Dx Urinalysis will show pyuria, can identify infectious organism Post-void residual urine make sure that patient can adequate evacuate urine Trans-rectal US (TRUS) used to exclude Dx of prostatic abscess if not responsive to antibiotics Urinary cytology/Biopsy exclude Dx of prostate/bladder cancer, dont use in acute (sepsis) Prostatitis Tx Acute admit patient, get blood & urine cultures, treat with broad-spectrum IV antibiotics Chronic give long course of oral fluoroquinolone, symptom relief (NSAIDs, warm soak) 21h:p)Q/ =!"#$% RZDd2%KKv  C RA:08Disclaimer-No_Citation_KeyRYҪG)dYDF\YҪG)JFIFHHICC_PROFILEappl mntrRGB XYZ  acspAPPLappl-appl rXYZ gXYZ4bXYZHwtpt\chadp,rTRCgTRCbTRCdesc@ocprt8vcgt0ndin8dscmLXYZ tK>XYZ Zs&XYZ (W3XYZ Rsf32 B&lcurvvcgtRRRndin8HW K'P T9textCopyright 2007 Apple Inc., all rights reserved.mluc enUS&~esES&daDK.deDE,fiFI(frFU(*itIT(VnlNL(nbNO&ptBR&svSE&jaJPRkoKR@zhTWlzhCNruRU"plPL,Yleinen RGB-profiiliGenerisk RGB-profilProfil Gnrique RVBN, RGB 000000u( RGB r_icϏPerfil RGB GenricoAllgemeines RGB-Profilfn RGB cϏeNGenerel RGB-beskrivelseAlgemeen RGB-profiel| RGB \ |Profilo RGB GenericoGeneric RGB Profile1I89 ?@>D8;L RGBUniwersalny profil RGBdescGeneric RGB ProfileGeneric RGB ProfiletExifMM*>F(iNHHC     C  " }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?~EO&2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QF2~EOh(?QEe6(QOȣi"e6(QOȣi"e6(QOȣi"e6( _#d~U{ggE/Q?*NE+Wiᰳ RUqSNVE/Q?*w E⾿8u&it ^eoaH 2I5W׾h ~$u{ֺق|5Ш˗_3d~TYv}-VT]Eqa- jfh8Fe8몺tK="[ 2)k}PkZNȌv'B.ҕ'}|z. ?>+h-l>*Xxxh >خ[>_z~)@NK$#%aE!UGaJn/ >_#7j_ hrxݼq\^i|NYIw7e J!x:O`խ2Bpq54R,%I)M;T]-ʏ/WrW~5kX -d@$w'99S֟x@k]w-n!מjqI a7? 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