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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

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Prostate Pathology

Benign Prostatic Hyperplasia (BPH)Prostate cancerProstatitis

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BPH

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Consequences of BPH

Lower Urinary Tract Symptoms (LUTS)BleedingUTI’sBladder stonesUrinary retentionObstructive uropathy

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Differential Diagnosis

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

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Focused neurologicalDRE

Physical Examination

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Work-up

Urinalysis– To r/o bladder cancer and UTI

PSA– In pts with > 10 yr life expectancy and the

presence of ca prostate would change their tx

Optional– Urine cytology, flow rate, post-void

residual, urodynamics, cystoscopy, prostate u/s

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Treatment Options

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Treatment Options

Watchful waiting (for mild symptoms)Medical Therapy– Alpha-adrenergic antagonists– 5 Alpha-reductase inhibitors

Phytotherapy– Saw Palmetto

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Treatment Options

Minimally Invasive Therapy– Microwave– TUNA– Urolume stent

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

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MRI Spectroscopy

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Prostate CA Treatment Options

Watchful waitingHormonal ablationExternal Beam RadiationBrachytherapyRadical ProstatectomyCryoablation

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Holmberg L et al, NEJM, 347:781, 2002

Watchful Waiting

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

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Histology

Transitional cell 90%Squamous cell 5%AdenocarcinomaSmall cell, Rhabdomyosarcoma

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Staging

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Clinical Features

Hematuria 80%Urgency and Irritative symptoms 20%

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Bladder CA Work-Up

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

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Urinary Diversion after Radical Cystectomy

Ileal conduitNeo-bladderContinent catheterizable pouch

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Renal Masses and CA

IncidentalHematuriaFlank Pain

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Hematuria

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

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History and Physical

PainFeverTraumaFamily HistoryOccupational Exposure

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History and Physical

Abdominal or Flank MassVaricoceleAdenopathy

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Diagnostic Studies

Upper Tract Imaging-IVP, sono or CTMRI with/without GadoCystoscopy to rule out bladder lesion

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Renal Cysts

Simple cystsIndeterminate cystsCystic neoplasm

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Benign Tumors

Oncocytoma-cannot be distinguished clinically from renal cellAngiomyolipoma (AML)– Hamartoma consisting of blood vessels,

smooth muscle and fat– Associated with tuberous sclerosis– Tend to bleed and require intervention

when >4cm60

Malignant Renal Tumors

Renal Cell CATransitional CellSarcomaWilmsLymphomaMetastatic tumor

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Renal Cell CAClinical Features

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

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Urolithiasis

Calcium stones– Absorptive, resorptive, renal leak– Hyperuricosuric, hyperoxaluric, hypocitrituric

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

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Differential Diagnosis

CholecystitisAppendicitisPIDDiverticulitisAAABowel obstructionMusculoskeletal sprains/spasmsZoster

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Diagnostic Evaluation

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

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Erectile DysfunctionPDE –5 Inhibitors:Contraindications

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