1 1 Urology in a Nutshell B. Mayer Grob, MD Division Of Urology VCU School of Medicine 2 Topics To Be Reviewed Prostatic disease – Cancer and BPH Other common GU malignancies – Bladder, kidney, testicular Urolithiasis Erectile dysfunction 3 Topics Not To Be Reviewed Incontinence Pediatric/congenital urologic conditions Prostatitis and other UTI’s Neurogenic bladder Infertility GU Trauma 4 Prostate Anatomy 5 Prostate Function Secretes certain proteins into ejaculate necessary for normal fertility, PSA, PAP, and PSP Highest conc of zinc of any human tissue, possible role as anti-infective Does not promote the normal flow of urine 6 Prostate Pathology Benign Prostatic Hyperplasia (BPH) Prostate cancer Prostatitis
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Urology in a Nutshell
B. Mayer Grob, MDDivision Of Urology VCU School of Medicine
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Topics To Be Reviewed
Prostatic disease– Cancer and BPH
Other common GU malignancies– Bladder, kidney, testicular
UrolithiasisErectile dysfunction
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Topics Not To Be Reviewed
IncontinencePediatric/congenital urologic conditionsProstatitis and other UTI’sNeurogenic bladderInfertilityGU Trauma
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Prostate Anatomy
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Prostate Function
Secretes certain proteins into ejaculate necessary for normal fertility, PSA, PAP, and PSPHighest conc of zinc of any human tissue, possible role as anti-infectiveDoes not promote the normal flow of urine
Prostate cancer– Obstructive symptoms are late – PSA usually higher– May co-exist with BPH
Urethral stricture disease– Hx of trauma, GC, or instrumentation– Main c/o is slow stream– Often younger
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Differential Diagnosis
Primary bladder neck dysfunction– No bulk obstruction– Often younger, type A personality– Bladder neck does not funnel on
urodynamicsNeurogenic– MS, DM, Parkinson's
Prostatitis– Usually associated with pain
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History
IPSSDuration of symptoms, acute vs. chronicBleeding, stones, recurrent UTI’s, renal insufficiencyHx of trauma or instrumentationFamily hxCo-morbidities
Surgical Treatments– TURP– TUIP– Photovaporization– Open prostatectomy
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BPHMedical Therapy
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BPHMedical Therapy
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19ALLHAT Group, JAMA, 283:1967, 2000
BPH – Medical Therapy
All alpha blockers have similar efficacyTamsulosin and alfuzosin have less orthostasisTamsulosin may have more retrograde ejaculationAlpha blockers should not be used to treat both BPH and hypertension as sole therapy
20PLESS Group, NEJM
BPH – Medical Therapy
5 alpha reductase inhibitors are indicated for men with LUTS and prostate enlargementPartially effective in relieving symptomsReduces the risk of urinary retention and BPH related surgeryReversible risk of decreased libido and ED
21MTOPS group, J Urol, 167: 1042, 2002
MTOPS Trial
Randomized men with LUTS to doxazosin alone, finasteride alone, combination therapy or observationCombination proved best in terms of reducing progression Only the arms with finasteridereduced risk of retention or BPH related surgery
22Gerber GS, et al, Urology, 2001
Saw Palmetto
Serenoa repens extract of dwarf palm treeProspective randomized trials are rareOne study did show a statistically significant difference in IPSS -4.4 vs. -2.2But no difference in flow rate, PSA, prostate size
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Minimally Invasive TherapyThermal-based Therapy
Microwave, radio frequency, high intensity ultrasound, hot water, interstitial laserHeating the prostate to > 45° C causes coagulation necrosisEffective in partially relieving symptomsProstatron®, Targis®, CoreThermTM, ThermatrixTM
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TARGIS®
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Surgical Therapies
TURPOpen prostatectomyPhotovaporization
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TURP
Gold standard for urinary retention and severe LUTSHospital stay and anesthesia requiredRisk of incontinence, bleeding, TUR syndrome, bladder neck contractureAlmost all have retrograde ejaculation
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Open Prostatectomy
For glands > 80 cc, avoids risk of TUR syndromeRequires an incision, longer hospital stay, greater risk of transfusionProbably more durable than TUR
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Photovaporization Of The Prostate
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Jemal et al, CA Cancer J Clin, 54: 8, 2004
Prostate Cancer
230,110 new cancers expected this year29,900 deaths
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Prostate CancerDiagnosis
PSADREDetection rates are highest with a combination of PSA and DRETransrectal Ultrasound (TRUS) used to systematically biopsy the prostate but not a screening tool by itselfWatch for new power Doppler with contrast
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Does Screening Reduce Prostate Ca Mortality?
Incidence of death from ca prostate is declining: 40,400 in ’95 to 30, 200 in ‘02Clinical and pathologic stage is also improvedRandomized trials in Europe and US pendingNo randomized trial for pap smears in cervical cancer
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Sensitivity Of PSA
Difficult to know with certaintyIncreasing sensitivity results in decreasing specificityIf 4.0 is cutoff, about 80% sensitive;20% of tumors have PSA 2.5-4
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AGE RANGE
ASIAN AFR-AMER CAUCASIAN
40-49 0-2.0 0-2.0 0-2.5
50-59 0-3.0 0-4.0 0-3.5
60-69 0-4.0 0-4.5 0-4.5
70-79 0-5.0 0-5.5 0-6.5
Age-specific PSARace Adjusted
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Free-to-total PSA
PSA Circulates in free and complexed formsCaP is associated with less freePSA in 4-10 range: %free < 10 increased yield to 56%, while %free >25, +bx rate = 8%Different assays may result in different levels
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PSA Velocity
Change in PSA over time.75ng/ml/yr associated with increased risk of caArchived samples, homogenous population, long-term f/uNot reproducible in short-term due to biologic and analytic variability
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Prostate Cancer Staging
Bone scans reserved for PSA >10, Gleason >7, local stage >T2MRI Spectroscopy may offer advantages with local staging over any previous techniques
695 men randomized to observation vs. radical prostatectomyAt 6.2 yrs f/u statistically significant difference in metastasis free survivalOverall survival not significant (yet)PIVOT results pending
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Radical Prostatectomy
3-4 hrs in OR3-4 days in hospital1-2 weeks with Foley cath3-4 weeks to full pre-surgical activity levelLaparoscopic robotic approach is growing
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Radical ProstatectomyComplications
Life threatening complications like PE 1%Operative mortality .3%Incontinence <10% to 30%Erectile dysfunction 35% to 70% after attempt at nerve-sparing
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Radiation Therapy
External beamBrachytherapyCombinationHormonal ablation as adjunct
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CryotherapyUsing transtrectal ultrasound, cryotherapy probes are advanced into the prostate through the perineum.A combination of freezing and thawing provides cell death through burstingBiochemical failure rates between 14 and 69%Precise role has not been determined
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Bladder CA
Fifth most common adult cancer57,400 new cases and 12,500 deaths in 2003Disease of industrializationCigarette use, industrial carcinogens and schistosomiasis account for 80% of cases
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Bladder CA:Molecular Factors
RAS, MYC, and EGFR overexpressionRB mutationsP53 mutation correlate with progression of disease
CystoscopyUpper Tract ImagingUrinary CytologyCT scan or MRI for Invasive Disease
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Bladder CA Treatment
TURBT –transurethral resection of bladder tumorIntravesicle chemo or immune therapy with BCGRadical cystectomy for invasive diseasePartial cystectomy for small volume invasive diseaseBladder preservation with chemo and XRT
Normal individual excrete 1-2 million RBC’s/24 hours97% of healthy patients <5RBC/hpf of spun sedimentWork-up for >5RBC on at least 2 u/a’sGross hematuria
Classic triad– Flank pain, palpable mass, and hematuria
Solid enhancing lesion on CT or MRIParaneoplastic syndromes
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Renal Cell CATreatment
Radical Nephrectomy, open or laparoscopicPartial NephrectomyCryoablationImmune therapy– IL-2, interferon
On the horizon– Cell cycle inhibitors, multi-kinase inhibitors
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Testis Cancer
About 7500 new cases and 300 deaths per yearMost common solid tumor of young men
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Testis CAPathophysiology
95% arise from germ cellsMost common is seminomaNon-seminomatous tumors– Embryonal– Teratoma– Choriocarcinoma– Yolk Sac
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Testis CARisk Factors
10% cases are in pts with hx of cryptorchidism15-20% of those are in the contralateral testicle
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Testis CADifferential Diagnosis
HydroceleSpermatoceleHerniaParatesticular tumor
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Testis CAHistory and Physical
Painless (usually) SwellingWeight loss or back pain may signal spreadHx of orchidopexySolid mass in testis on examAdenopathy
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Testis CADiagnostic Studies
+U/A may indicate epididymitisSerum markers– AFP– ßHCG– LDH
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Testis CADiagnostic Studies
Scrotal sonogram to confirm solid nature and evaluate other testisMetastatic w/u includes cxr and abd/pelvic CTTrans-scrotal biopsy contra-indicated
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Testis CATreatment
1st step is almost always radical orchiectomyOther treatment is stage and histology dependent and may involve abdominal irradiation, systemic chemotherapy or retroperitoneal node dissection
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Urolithiasis
Along with UTI’s and prostate disease, among the most common urologic complaintsMay be asymptomatic or present as life-threatening emergency
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Urolithiasis
Stone formation based on supersaturation– Urinary pH, ionic strength, solute
concentration, and complexationCrystal formation involves nucleation, growth and aggregation
Struvite-magnesium, ammonium and phosphate– Urea splitters: Proteus, Pseudomonas,
Providencia, Klebsiella, Staphylococci, and Mycoplasma
Uric acidCystine
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Renal Colic
Acute flank pain may radiate to the groin, waxes and wanes and very severeOften accompanied by nausea and vomitingFever implies some associated UTIUrinary frequency may imply a very distal stone
U/A and cultureRenal colic CTKUBSonogram in pregnancy
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Management
Treat associated infectionHydration and pain controlRetrograde stent or percutaneous nephrostomyExtracorporeal shockwave lithotripsy(ESWL)Ureteroscopy with laser lithotripsyPercutaneous nephrolithotomyOpen stone procedures
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Indications for Urgent Treatment
Solitary kidneyAcute renal insufficiencyUTI with feverPain or vomiting unresponsive to conservative management
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Erectile Dysfunction
Anatomy and PhysiologyDiagnosis and EvaluationTreatment
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Erectile Dysfunction
EndocrineVascular Nervous systemBrain– “The brain is the most important sexual
organ”• Freud
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Erectile Dysfunction
The persistent inability to achieve an erection that is satisfactory for sexual activity
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Erectile DysfunctionAnatomy
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Erectile DysfunctionEvaluation
History– Sexual– Medical
Physical examinationLaboratory testing
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Erectile DysfunctionSexual History
Loss of libidoPainful or bent erectionsMorning erectionsPremature ejaculationOnset and duration of difficulties with ED
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Erectile DysfunctionMedical History
Diabetes:27-59%Chronic renal failure:40%Hepatic failure:25-70%Multiple sclerosis:71%Depression: 90%Vascular disease is cause in 50%
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Erectile DysfunctionMedical History
Spinal cord injuryPelvic surgery and radiationMedications: beta-blockers, thiazides, ACE inhibitors, Calcium channel blockers, digoxin, hormonal therapiesSmoking magnifies effects of other risk factorsAlcohol abuse
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Erectile DysfunctionPhysical Exam
Focused examVascular system: pulsesNeuro examRectal exam if indicated
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Erectile DysfunctionLaboratory Evaluation
Morning testosteroneIf abnormal, proceed with LH, FSH, prolactinBasic chemistry, lipid panel, liver functionThyroid function if indicatedPSA if indicated
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Erectile DysfunctionTreatment
Treat specific cause when one is identified– Depression, hypogonadism, hypothyroid
Lifestyle changesIn no specific cause is found, provide patient with options to improve erectile fxn– Oral medications– Intraurethral and intracavernosal drugs– Vacuum device– Prosthesis
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Erectile DysfunctionPDE –5 Inhibitors
Sildenafil (Viagra®), Tadalafil (Cialis®), Vardenafil (Levitra®)Effects of Cialis® may last 24-36 hoursAll work by inhibiting breakdown of cGMPDo not cause erections without stimulationDo not improve libido directly
Any nitrate containing compound-NTG, Isosorbide, Amyl nitrate: absolute contraindicationShould not use Levitra® or Cialis®with alpha-blockers although Flomax® ok with Cialis®
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Erectile DysfunctionTreatment
Transurethral Alprostadil (MUSE®)Intracavernosal Injections Alprostadil (Caverject®, Edex®), papaverine, phentolamineRisk of priapism is increased over other treatments
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MUSE
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Erectile DysfunctionVacuum device
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Penile Prosthesis
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Penile Prosthesis
Malleable or inflatableHigh patient satisfaction rateLow morbidityIrreversibleMay have to be removed for infections or mechanical malfunction