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125 Cards in this Set
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posterior urethral valves
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Pathology: increased bladder pressure, development of the urinary system under pressure – blows up the bladder, increase size of muscle in bladder, dilate ureters, eventually dilate kidneys
-most common cause in lower UTO in male children -appears in childhood (case was 5yo) -only the partial valves are seen clinically because the complete valve obstruction is deadly -1:5000-800 (the anterior valve is 1:40 000) -no obvious genetics -type I(most common, flap like a parasail) -type III (septum like a diaphragm fold with central hole) -type II (increased folds from the veru back to bladder neck) (type II is not actually a clinical problem) |
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what are the changes of a urinary system development "under pressure"?
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Partial obstruction results in development of the urinary system in utero under pressure:
Urinary dilation Bladder hypertrophy Vesicoureteral reflux Hydronephrosis Renal dysplasia |
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pathology on the kidney due to urinary system development "under pressure"?
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alteration in growth regulation
production of interstitial fibrosis alteration in developmental regulation of the renin-angiotensin system |
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changes in the bladder due to posterior UValve
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bladder becomes stiff and noncompliant (Marked increase in growth and connective tissue deposition)
Alteration in the local renin-angiotensin system |
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changes in the lungs due to PUV?
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the amniotic fluid is usually breathed - but here we have oligohydramnios -so if there's no volume to breathe, you end up with poorely developed lungs:
Impaired growth and maturation Mechanical or humoral mechanism? |
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what will reduce the pressure? ? PUV
alterations done to get rid of some of the pressure w/ PUV protective: "pop-off" mechanisms |
Calyceal rupture: kidney is ruptured and the urine goes into the retro-peritonum (don't really need the kidneys when in utero)
Bladder rupture Bladder diverticulum Severe unilateral reflux -VURD syndrome |
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most common presentation of PUV is prenatal - what is it?
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In utero hydronephrosis
Bilateral hydronephrosis (bladder as culprit?) Dilated bladder “key hole” sign oligohydramnios |
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presentation of PUV after birth
right after birth: at childhood: |
Varies dependent on renal damage and degree of oligohydramnios
Birth (severe degree): Septic shock Pulmonary failure Renal failure to Asymptomatic childhood presentation: UTI (especially boys) Incontinence Eneuresis Renal failure |
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pre-natal management of PUV
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Rarely is intervention suggested
Exception: severe oligohydramnios we also check if there still is some bladder function: urinary electrolytes (fetal bladder tap) High Na High Cl High B2-microglobulin These would say that salvage is worth it; fetal intervention: -prior to 22-24wks: vesicoamniotic shunt - suprapubic tube |
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management of PUV at birth
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Resuscitation
Antibiotics Placement of foley or feeding tube Await negative urine culture Nadir creatinine |
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management of PUV if there is no oligohydramnios and no indication for fetal surgery:
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If nl amniotic fluid levels, things don’t look too bad, allow complete gestation, monitor
At time of birth: 1) Could be lung impairment- might need to be resuscitated 2) Antibiotics: If under pressure and infected = disaster, so prophylax 3) Foley or other tube in bladder to vent pressure, allow system to drain Can temporarily fix with a catheter Make sure neg urine cultures – if at birth, urine will be unaffected; that would be acquired later 4)Await negative urine culture 5)Nadir creatinine: mom’s creatinine, so around 1; favorable if it trends down (baby’s don’t have much muscle to make a lot of creatinine); bad if trends up later: we go after it! 1) Transurethral valve ablation (TUR valves) Incise valve to damage leaflet Entire valve not removed Vesicostomy if small urethra (preterm child) Controversy if poor renal function is present: If very small, not feasible to take a telescope into their urethra b) May just leave catheter temporarily c)Decompress system using supravesicle – hole through abd wall into bladder d)Can also connect ureter, or put a tube in from the kidney want to bypass obstruction to vent system in a small/unstable child e)Do not cut valve then do diversion - Dry stricture No good data that one is better than the other No controversy in relatively healthy child: Endoscope valve ablation Follow nadir creatinine |
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TUR in older children??
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always Primary transurethral valve ablation
Watch for post obstructive diuresis in severe obstruction: If kidney has been pumping against a high pressure load, when you relieve that obstruction, may go into overdrive- pump out a lot of fluid = post obstructive diuresis If older child and thirst mechanism is intact, will manage themselves- will drink, keep appropriately hydrated If dependent on someone to give them liquid, have to be careful to keep up |
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what are other clinical problems we see with children with PUV?
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Renal failure / renal dysplasia:
-A result of chronic obstruction/pressure -Abnl drive on kidney – then fails to function appropriately Vesicoureteral reflux -May be secondary to obstruction -Wait 6-12m after valve ablation to see if it resolves -Initially, always think that reflux is secondary to the obstruction itself – wait for things to improve after obstruction has been cleared; manage while it is there – keep on abx or other things to reduce the problem Incontinence/enuresis -High volume dilute urine -Poor bladder compliance Alterations in kidney and bladder – can be long term problems 1) If bladder doesn’t store properly – frequency, urgency = Obstruct kidney – impair concentrating ability first thing 2)Becomes a double edged sword- making lots of urine, and can’t store it well – drive the problem to be more severe May have bed wetting a lot longer than other kids |
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causes of acute scrotum
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Testicular torsion (Fix immediately, but not most common cause)
Torsion of appendix testes Epididymal-orchitis Henoch-Schonlein Purpura Incarcerated hernia Scrotal wall process |
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types of testicular torsion
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Two types:
1) Extravaginal =Torsion of entire cord proximal to tunica vaginalis attachment; Almost exclusively in perinatal period, before anchored in testes; Salvage of torsed testes unlikely (b/c presentation is vague, babies cry but you don't suspect it till testes harden or other secondary signs - present late); Surgery to protect contralateral testes; Timing related to anesthetic risk; Asynchronous torsion has occurred; Can lose one then the other -- Sterility !! Hormonal insufficiency (as result of loss of both - rare); Remove necrotic/calcified testes Resportion of necrotic tests, inflammation can cause pain Less common than intravaginal torsion 2) Intravaginal: Perinatal and older Torsion distal to tunica vaginalis attachment - so it spins inside the tunica vaginalis; Bell-clapper or horizontal lie predisposes to torsion Age 8 – 30 y/o Older- rare, but does occur Younger- not uncommon |
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testicular torsion salvage rates
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0-6hr – 85-90%
6-12hr – 50% >24hr – 5% or less Intermittent torsion – very likely Never an absolute – not like a light switch; more like a dimmer – can impair venous drainage at first, then later with swelling and edema, gradually progressive process Can have longer term (>1d) that it never totally disrupted blood supply But if totally clamp it off- shorter duration folks who lose a testis |
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testicular torsion presentation
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Acute, severe pain
N/V Sympathetic response Tunica vaginalis is peritoneal – peritoneal irritation --> sympathetic response = N/V Physical exam: Erythema, edema, loss of cremasteric reflex, high riding testis Driven by inflammatory response Caveat: not all older children / adults have cremasteric reflex (lost) Absence does not mean torsion |
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testicular torsion management
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Manual reduction with narcotics
ONLY IF SURGERY NOT AVAILABLE “open the book” Both inward and outward rotation occurs Most of the time-> its internal rotation, so revolve external (70%). Pain will resolve. Prompt surgical exploration to confirm detorsion |
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if you don't think it's torsion, we do...
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USG- for "diagnosis" or r/o
Child’s age, operator, and machine dependent Definitive study prevents surgery Only obtain if you believe there is NOT torsion If you are convinced its torsion- just go fix it can also do Nuclear scan: Radioactive isotope concentrated in testes False negatives – increased erythema in the scrotal wall hides low flow testes Infants can be difficult Scrotum too small |
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Torsion of Appendix epididymis or testes
what are they? presentation? treatment? |
Embryologic remnants
Appendix testes – Mullerian sytem Appendix epididymis - mesonephros presentation: Slow gradual onset over days Less N/V Pain related to inflammation caused by necrotic structure "Not a lot of sx at time of torsion b/c not a lot of mass But after it becomes necrotic and dies – inflammation and swelling involved in resorption of it Relatively uncommon to have a large one and be fooled into thinking it’s torsion" Blue dot sign: Necrotic appendage seen through thin scrotal skin of the child Treatment: If dx certain, then treat with comfort care Anti-inflammatories Analgesics Scrotal support |
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Epididymal Orchitis
what is it? tx? |
Infection:
Infection that ascends to testes Swelling of testes Changes in type of infection with age: Children – UTI “Young man’s” – STD “Old guy’s” - UTI Treat with antibiotics For boys – evaluation for possible urinary anomaly A bad infection can result in loss of testis- compartment syndrome pearl: Less of an issue when someone is older – don’t really look for a valve or something else that would drive the infection Testes is a compartment – can lose the testes if lots of swelling in the scrotum b/c bound by tunica albugina (tough fascial sheeth) – can impair blood flow b/c presentation is that of acute scrotum, often want to document that wasn’t a torsion retrospectively Do some type of study to document that there’s blood flow, even if the story is classic; |
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Vesicoureteral Reflux
what is it? |
Flow of urine in a retrograde fashion from the bladder to the kidney with voiding
Related to “short” intra vesicle ureteral tunnel Ureter fails to collapse with voiding Flow of urine in a retrograde fashion from the bladder to the kidney with voiding |
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what's the problem with
Vesicoureteral Reflux |
Bacteria in bladder gain access to the upper urinary tract (kidney)
Cystitis becomes pyelonephritis Pyelonephritis results in scarring of kidney Scarring impairs renal function and predisposes to HTN |
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presentation
Vesicoureteral Reflux |
Prenatal hydronephrosis (swelling in utero)
Systemic illness -Pyelonephritis -Sepsis -Vomiting -Failure to thrive Sibling screening |
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causes of
Vesicoureteral Reflux |
Inherited
30% of siblings of index case (brother/ sister) 50% of children of index case (mom) |
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The nature of Infantile Reflux
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Prevalence inversely proportional to age
Children is more common than adults (because it resolves) Sex difference: When infection prompts w/u F>M When prenatal hydro prompts w/u M>F Neonates have higher grade reflux Reflux predisposes to pyelonephritis Resolution |
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why would the infantile reflux resolve?
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Flap valve gets better – get longer tunnels as they grow
Drive urine through a long narrow tube, more pressure than older – as age, less likely to have problems Defect of flap valve mechanism Short sub-mucosal tunnel Tunnel gets longer as you grow Discoordinated voiding- contract urinary sphincter as bladder is contracting – increasing pressure, more likely to be reflux there: Immature voiding pattern: Infant males void at high pressure + DSD voiding pattern Prenatal VUR has a higher rate of resolution: Lots more growth, lots more maturation |
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Grades of Ureteral Reflux
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Graded in severity by how far and how dilated the system is
Grade 1- only into ureter, not into kidney pelvis Grade 2- still sharp calyces Grade 3- blunt calyces somewhat, dilated Grade 4- more blunting, more dilation, a little bit of tortuosity Grade 5- big dilation of ureter, tortuosity, effacement of calyces- blunt whole thing out, cauliflower |
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Renal Scar from Ureteral Reflux
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Important issue you’re looking at long term
Easiest way to look for scarring is DMSA scan – tracer binds to tubules; more tubule mass = bind tracer; lack of tubule mass = won’t bind tracer Divots in tracer signal = scarred tissue Important outcome: a) loss of function b) loss of perfusion of that part of the kidney --> HTN |
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Management of Ureteral Reflux
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Actively work to find reflux pts:
Boys with UTI – VCUG Girls with febrile UTI or recurrent UTI – VCUG Confirmed prenatal hydronephrosis - VCUG Aggressive management of pts with reflux Prophylaxis or surgery Periodic VCUG for medical management pts Antibiotic prophylaxis -Trimethoprim-sulfa or Nitrofurantin -Yearly radiographs -Damage from infection prevented Surgery (Reimplants) -Breakthrough infections Management with VCUG under consideration: a) Parents and kids don’t like VCUGs – lots of unhappiness, esp in little girls b) Not clear that risk for renal scarring is the same with lots of good abx that you can access quickly surgery: Success ~95% (incredible!) Something they’ve gotten very good at - Can fix it if it needs to be fixed- question if need to do that Really great success rates Very few complications Complications -2% obstruction -4.7% new VUR current view: -Most children have insignificant self-limiting reflux -Progression to reflux nephropathy is rare but occurs -Both dysplasia and reflux nephropathy occur -Pyelonephritis can induce scaring -It is unclear how to best prevent pyelonephritis and scaring -Voiding dysfunction is a player -Age is not a risk factor in scarring |
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prostate cancer risk factors
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Advanced Age
African American -More common and presents at later stage Family history- 2-3X greater risk -Men with Prostate Cancer -Women with Breast Cancer Obesity High Fat Intake -Mono-unsaturated fat (also increases kidney cancer risk) |
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prostate cancer screening?
rationale algorithm |
Rationale:
Prostate cancer usually asymptomatic Late stage symptoms - incurable Bone pain Difficulty voiding Hematuria Renal failure Algorithm: Annually starting age 50 -At least 10-yr life expectancy High risk starting age 45 -First degree relative -African American Highest risk starting age 40 -Multiple first degree relatives diagnosed early |
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how do we screen for prostate CA?
limitations? |
50% sensitivety of digital rectal exam
PSA: -Secreted “only” by the prostate -Serine protease -Lyses seminal coagulum -In serum PSA is free or bound to alpha 1-antichymotrypsin -BPH - Higher percent of free PSA 25% or above -Prostate cancer – Lower percent of free PSA 10% or lower Guidelines for PSA: Starting age 40 yo If PSA is: > 1.0 ng/ml – re-test at age 45 1 – 2.5 – re-test annually > 2.5 – prostate biopsy **there are many things that can raise PSA: digital rectal exam, age, any inflammatory process in the pelvis/prostatitis, prostate density, **PSA velocity - check changes in PSA over time; **supersensitive PSA - esp after surgery |
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12 core-biopsies and then we grade and stage - how?
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Gleason score:
1 = normal 5 = anaplastic CA majority + worst (2-10) low grade up to 6 intermediate 6-7 high-grade >7 TNM grading: TX Cannot be assessed TO No evidence of tumor T1 Clinically unapparent & not palpable (DRE) [most are under capsule] 1a <5% of tissue in resection of benign disease has Ca 1b >5% of tissue in resection of benign disease has Ca 1c Detected from elevated PSA alone, normal DRE & TRUS T2 Palpable by DRE or visible tumor by TRUS, confined to prostate (a-one side, b-both sides of prostate) T3a Extension through prostate capsule T3b Seminal vesicle involvement T4 Fixed or invades adjacent structures |
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Prostate Cancer Treatment Options-
1) Localized cancer 2) Locally Advanced |
1) for localized cancer: (<7 or so -surveilence, but >8 younger man, treat for sure)
Surveillance Radiotherapy -External beam -Interstitial – Brachytherapy (Radioactive implants) -Combined external and interstitial [bad: takes many sessions, urethral irritation, secondary malignancies in future - bladder, cystitis - bladder bleeding; takes a long time for PSA to go down - can't use for monitoring] Radical Prostatectomy (robot) -Retropubic (current w/ robot or open) -Perineal (historic) then the PSA goes to 0 very fast -cyrotherapy (good for older pt; used as salveage after failure of radiation) -HighFU - ultrasound high frequency 2) Combined Hormone and/or chemotherapy with definitive local therapy: -Radical prostatectomy -Radiation therapy [hormone refractive cancer comes sooner or later] RISK: cardiovascular complications with anti-testosterone |
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Prostate Cancer Metastases
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Pelvic lymph nodes
-Obturator -Hypogastric -External iliac (7 or above, PSA>10 must get LN dissection) Axial skeleton, ribs Liver or lung in late stages only |
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Historical Management of Advanced Prostate Cancer With Monotherapy
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Bilateral orchiectomy
Diethylstilbesterol (DES) LHRH agonists Combined androgen blockade with LHRH agonist and non-steroidal anti-androgen: Flutamide, Nilutamide, Bicalutamide (combined is falling out of favor bc cardiovascular risks) |
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Prostate Cancer Chemotherapy
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doesn't work well, so we only use for palleation
Mitoxantrone + Prednisone -FDA approved for palliation Strontium chloride 89 -Calcium analogue emitting beta irradiation -Symptomatic bone metastases Bisphosphonates -Pyrophosphate analogue naturally inhibit bone resorption -Symptomatic bone metastases |
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Bladder cancer
incidence F vs M? RISKS |
Male:female 3:1
Cigarette Smoking ~50% cases -50% cases men; 35% in women -Smokers of > 2 packs/day have ~ 7 times the risk of nonsmokers Occupational exposure ~20% cases Arylamines -Rubber Aluminum -Leather Dye -Printing industry Infection - Schistosoma hematobium |
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Bladder cancer timing?
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you have to treat it right away! you can't just wait and try around with biopsies as you can with
kidney or prostate |
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bladder cancer
presenting signs and symptoms |
Hematuria present in 85% of cases
-Gross hematuria, Usually Painless -Microhematuria Painful urination Urinary frequency Frequency, Urgency, Dysuria Vesical Irritability (Consider Carcinoma in Situ) Mild “Nuisance” symptoms may delay the diagnosis 10% Present with symptoms secondary to metastases |
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Bladder cancer staging
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Low-grade: superficial, less likely to invade or metastasize, frequently reappears after resection but amenable to therapy, low mortality
High-grade: propensity to invade and metastasize, high mortality when invasive, but good response to treatment if detected early |
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why bladder cancer is so expensive?
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frequency, urgent treatment and
propensity to RECURR |
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TNM staging of bladder CA
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urothelium covers all where the urine is - this is where all the CA arises from;
85-95% Transitional cell Ta = urothelium only T1 = past urothelium but not invasion of muscle layer T2 = invasion of muscle layer T3a = micro invasion of fat T3b = invasion of fat T4 = invasion outside bladder |
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Bladder cancer
types: |
Transitional Cell Carcinoma (TCC) - 90%
Squamous Cell Carcinoma (SCC) - 7% ( US:due to Chronic irritation in bladder due to stones or spinal cord injury pt with chronic catheters; Egypt: Schistosoma) Adenocarcioma - 2% Grading scheme 1 - well differentiated 2 - moderate differentiation 3 - poorly differentiated |
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Treatment of superficial Bladder Cancer
Ta, Tis, T1 |
Surveillance (not often)
Intravesical Therapy -Thiotepa -Mitomycin C -Doxorubicin -BCG (most common!!!) this is the TB vaccine |
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Bladder Cancer: Treatment of Superficial Intravesical Therapy- Indications
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Any grade 3
Any T1 Tis Multiple (>3 tumors) Recurrent 99% after resection |
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radical cystectomy
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Ta, Tis, T1?
T2-T4 N1-2 MO |
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bladder cancer mets
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lung, liver, bone
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chemo for bladder CA
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MVAC
Methotrexate Vinblastine Doxorubicine Cisplatin |
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Kidney cancer
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Renal parenchyma 85%
Renal pelvis 15% Transitional Cell Carcinoma (TCC) Male:female 2:1 No racial preference Acquired renal cystic disease of dialysis 40 times risk of general population |
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Kidney cancer
hereditary?? |
Vin Hippel-Lindau
Clear cell renal cell carcinoma Tuberous Sclerosis Clear cell renal cell carcinoma Hereditary papillary renal cell carcinoma Met proto-oncogene mutations 7q 31-34 Encodes hepatocyte growth factor |
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risk for kidney cancer
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Obesity
Hypertension Cigarette Smoking |
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presentation kidney cancer
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Hematuria – gross or microscopic
Flank pain Palpable abdominal mass Classic triad rarely observed together Paraneoplastic syndromes common “Internist tumor” 25 – 30% have metastases at diagnosis Median survival 12 – 18 months Solitary metastases 35% five year survival |
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testicular cancer
incidence/risks |
Most common neoplasm in young men
Bimodal age distribution Risk factors -Undescended testicle -Maternal estrogen exposure -Contralateral testis tumor -Whites 5-6x more common than Blacks -25% subfertile semen parameters [treatment for metastatic disease: Single Metastasis – resect (Synchronous vs. Metachronous) High Dose Bolus IL-2 Interferon Alone Nephrectomy + Interferon] |
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testicular cancer
pathology - cell origin? |
Adult
Germ cell tumors Seminoma Non-seminoma Embryonal Choriocarcinoma (hCG) Yolk Sac Tumor (AFP) Lymphoma Most common over age 50 Pediatric Germ cell tumors Interstitial tumors e.g. Leydig cell |
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Congenital anomalies of the kidney
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common because they involve interaction of stromal and epithelial cell types of different origins
No kidney: agenesis Small kidney: Hypoplasia -No scars and less lobules Out of place: Ectopic kidney Abnormal form: Horshoe kidney |
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Polycystic kidneys
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Cystic renal dysplasia
-Persistence of abnormal structures (cartilage mesenchyme, immature collecting ducts) Polycystic kidney: Autosomal dominant: Adult (huge cysts of different sizes) -High penetrance -Bilateral, large homogeneous cysts -PKD1 gene (85%): chromosome 16p13.3 -Policystin: cell-cell-matrix interactions -PDK2 (10%): 4q13-23 Policystin 2: membrane protein (CA-NA channel ?) -PDK3 -Liver cysts, berry aneurysms!!!! Autosomal Recessive: Infantile (very thin cysts) -Longitudinal parallel peripheral cysts -Hepatic fibrosis!!! Medullary cystic kidney -Cystic dilation of the collecting ducts Acquired (most common with ERSD) |
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Diseases of the vessels in the kidneys
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Benign nephrosclerosis:
-Sclerosis of renal arterioles and small arteries-focal ischemia Malignant hypertension (280/160) -Fibrinoid necrosis of arterioles with high plasma levels of renin Renal artery stenosis -Chronic Atherosclerosis Fibro muscular dysplasia (middle aged women) -Acute Thrombi |
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Urolithiasis
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Calcium oxalate/phosphate: 75%
Hypercalciuria and hypercalcemia Hyperuricosuria Hypocitraturia Magnesium amoniun phosphate (struvite): 15% [staghorn calculus] Uric acid: 6 % Hyperuricemia/ hyperuricosuria Cystine 1-2% |
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Renal cell Carcinoma
types |
Forms
Sporadic: tobacco, obesity, unopposed estrogen Von Hippel-Lindau Syndrome Hemangioblastoma of cerebellum and retina, renal cysts and renal cell carcinoma;( HIF-1 mutation in the vHL gene leads to ..) Types -Clear Cell Carcinoma 85% (Deletion or unbalanced translocation of chromosome 3 (VHL gene) or methylation VHL gene: elongin: suppressor gene) Chromophobe: 5% (looks bad but behaves well) Papillary: 10-15% (Sporadic Familiar chromosome 7, MET (hepatocyte growth factor)) MUST KNOW: 1) yellow, variegated tumor, with fibrosis, clear cell CA because the cells look empty 1b) round yellow, pushing borders (clear cell CA) 2) ugly nuclei (Chromophobe) 3) Oncocytoma: red, central scar 4) Sarcomatoid: spinde cells, very lethal 5) papillary TCC - from urothelium 6) Angiomyolipoma - from stroma (should NOT have the kidney removed; most with tuberous sclerosis; Tumor from the stroma = it’s composed of fat, vessels and muscle; Has a characteristic radiologic appearance, Very important b/c this person should NOT have they’re kidneys removed – they just need the tumor removed) 7) Leiomyosarcoma |
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Bladder
purpose of urothelium |
has to guarantee that urine stays inside bladder - so it seals!!
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congenital anomaly of bladder
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Two: Bifid ureters
Outflow problems -Ureteropelvic obstruction -Diverticula -Hydroureter -Megaloureter -Vesicoureteral reflux (female) Exstrophy |
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cystitis
types presentions/causes |
Acute:
Frequency, lower abdominal pain and dysuria E coli, Proteus, Klebsiella, Enterobacter Virus and radiation Chronic: Granulomatous: Fungi and schistosoma Interstitial: Persistent and painful Women Mast cells Malacoplakia Cystitis glandularis et cystica |
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TCC
bladder |
Papillary TCC
-Papilloma Grade 1,2,3 -Carcinoma in situ; cancer still where it should be; the cells are on the surface BUT they have already aquired the ability to invade unlike other carcinomas in situ -Invasive TCC |
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Bladder is unique with respect to histology bc ...
so when they say cancer has invaded the.... it doesn't mean it's left the bladder |
it's got fat in the muscle layer
if it's invaded the fat, it doesn't mean that it came outside the bladder |
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Prostate function
zones |
produce nursing fluid for sperm
also in charge of pumping prostatic urethra: here is still embryonic from the urogenital sinus zones (different diseases at different areas): transitional zone in the center central zone peripheral zone |
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Prostatic urethra, membranous urethra, prox urethra
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Prostatic urethra, membranous urethra, prox urethra
* formed from lower end of urogenital sinus * endoderm = transitional epith, str columnar epith * prostatic urethra have endoderm outgrowth into mesoderm = prostate gland * membranous urethra have endoderm outgrowth into mesodem = bulbourethral glands * prox part of penile urethra have endoderm outgrowth into mesoderm = Littre’s glands |
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Acute and Chronic prostatitis
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Acute P: painful, increases PSA;
Chronic: everyone has it eventually; age associated |
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BPH
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not in the transition zone
enlargement happens in the peripheral zone: right around urethra replaced by glandular tissue related to age difficulty urinating |
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prostate cancer
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starts with: high grade intraprostatic intraepithelial hyperplasia
basal cell layer disappears = hallmark -loss of glandular differentiation -- Gleason grade increases -capsule of the prostate is checked -check the seminal vesicles NEUROTROPIC cancer -loves to wrap around nerves -one of the best discriminators of prostate specific death |
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testis pathology
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Granulomatous Orchitis
Torsion Hydrocele Amyloidosis adenomatoid (!!Don’t want to take the testis out for an amyloidoma or an adenomatoid tumor) |
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Testicular tumors
types |
Germ cell tumors
-seminoma -yolk sac -teratoma -Embryonal carcinoma Sex cord-stromal tumors -Leydig cell tumor -Sertoli cell tumor -rare variants Mixed (most) Seminoma vs Non-Seminoma: based on historical treatment considerations (Back then we only had XRT for seminoma – nothing else); BUT Currently treatment for Non-seminoma is almost as good; BUT still good to know if it's germ cell or not: Germ cell tumors of the testes is a predictable disease!! It’s predictable – it’s moves along central lymph nodes!! unless it's choriocarcinoma!! Hodgkins also predictable like that (that's why we distinguish Hodgkin vs non-hodgkin) |
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stages of testicular tumors:
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so it's important that we stage them
I: Confined to testis II: Retroperitoneal nodes below diaphragm III- Mets beyond Germ cell tumors of the testes is a predictable disease!! It’s predictable – it’s moves along central lymph nodes!! unless it's choriocarcinoma!! Hodgkins also predictable like that (that's why we distinguish Hodgkin vs non-hodgkin) |
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treatment based on stages of testicular cancer
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Stage I:
a) High Risk: orchiectomy + lymphadenectomy or chemo b) Low Risk: orchiectomy + watchful waiting if patient is compliant Stage II and above get full treatment |
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Germ cell tumor: markers only
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Seminoma: LDH and variants, PLAP
Embryonal carcinoma: various Yolk sac tumors: AFP Choriocarcinomas: hCG Teratoma |
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Germ cell tumor
histology of types |
Seminoma:
-Homogeneous population of cells with large nucleoli and lymphocytes, bland -Anaplastic (ugly) -Spermatocytic (older men, diff dx lymphoma) Does not arise from ITGCN Embryonal carcinoma -CARCINOMA: bad nuclei Yolk sac tumors: AFP -Delicate lacy architecture with blandish nuclei -Infantile and adult. Infantile does not arise from ITGCN Choriocarcinoma HCG -Resembles placenta -Vascular invasion (loves blood vessels because placenta loves blood vessels - important to know if there is a chorioCA component because it's more likely to invade to liver lung brain due to this vascular love) Teratoma -Mature (Better prognosis but not responsive to TX) Immature |
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Penile intra-epithelial neoplasia
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-Low grade PeIN 33 yrs
-High grade PeIN 3-7 yrs later -Bowen disease vs. erythoplasia of Queyrat (in situ lesions of penis) -Bowenoid Paulosis -Subtypes NOS Warty Basaloid |
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Causes of penile cancers
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Major causes:
-unCircumcision -HPV -Tobacco -BXO -PUVA Minor causes -Hailey-Hailey -Lichen planus -Burns -Asbestos -Sinus tracts -Hypospadia -Mineral oil injection -Sexual activity -Zoon’s plasmacellular balanitis Not associated: Herpes virus, Epstein Barr virus, Syphilis |
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Circumcision and HPV
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Circumcision also has a protective effect against HPV infection, urinary tract infections and HIV.
The foreskin provides a permissive microenvironment for infectious organisms and for the progression of HPV lesions. Penile cancers do occur in circumcised males |
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what are obstructive voiding symptoms?
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impaired flow
hesitancy incomplete emptying intermittency straining to void urinary retention / overflow |
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what are Irritative voiding symptoms?
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dysuria
urgency frequency nocturia urge incontinence overtime, pt with outlet obstruction gets an overactive bladder causing these sx |
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Ddx of obstructive voiding sx, and especially irritative voiding sx?
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BPH: Benign prostatic hypertrophy
DM: Diabetes mellitus BOO: bladder outlet obst NGB:Neurogenic bladder CIS: Carcinoma insitu OAB: Overactive bladder urethral stricture UTI prostate cancer medication side effects critical Primary Care role |
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medical treatment of BPH
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alpha-adrenergic blocking agents:
selective, long-acting (alpha 1 selective, relax the smooth muscles – vs the alpha 2(yohimbine)) terazosin (Hytrin) doxazosin (Cardura) tamsulosin (Flomax) - alpha1a specific alfuzosin (Uroxatrol) SE: Alpha blockers: orthostasis, dizziness, fall risk in elderly, cardiovascular effects, ejac. dysfn 5-alpha reductase inhibitors (prevent testosterone conversion to DHT) finasteride (Proscar) (type 2 inhib. only) dutasteride (Avodart) (type 1 and 2 inhib.) These drugs cause a decrease of PSA by 50% SE: ED, loss of libido, ejac. dysfn, gynecomastia; PSA reduction by 50%! |
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surgeries for BPH
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Minimally invasive procedures:
microwave, thermotherapy radio frequency ablation (TUNA, etc.) stent Surgery TURP; Open prostatectomy (gland size) |
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indications for surgery of BPH
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Indications for surgical therapy:
Failure to respond to med./min. invasive therapy Complications of BPH - monitoring/recognition! -Hematuria -Bladder stones -Recurrent infection -Lower tract anatomic deterioration -Recurrent retention; large residual? -Upper tract anatomic deterioration, renal insufficiency |
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Types of incontinence
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1) Stress incontinence (meds)
bladder neck hypermobility (common in post-partum) intrinsic sphincteric deficiency neurogenic dysfunction 2) Urge incontinence (surgery) unstable bladder, detrusor instability detrusor hyperreflexia (can be simple overactive bladder) 3) Overflow incontinence -underactive or atonic detrusor -outlet obstruction (male- prostatic disease, urethral stricture; female- prolapse, post-surgical) |
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Changes of age which predispose to incontinence
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>60
reduction in functional bladder capacity(bladder gets smaller in age) increased frequency of uninhibited contractions Women: decrease in functional urethral length reduction in urethral closure pressure Men: prostatic hyperplasia, neoplasia |
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why do urodynamic testing?
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you want to find out if it's their detrusor dysfunction or their bladder outlet obstruction before you do procedures...
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management of urinary incontinence:
first: Identify and correct transient factors |
delerium
infection atrophic vaginitis drug side effect (any drugs with anti-cholinergic SE - parkinsons, antihistamines...) impaired mobility fecal impaction all Common issues in geriatric patient |
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medical therapy for overactive bladder
side effects: contraindication |
detrusor is cholinergic
bladder outlet is adrenergic Anticholinergic agents (relaxing detrusor): -oxybutinin chloride (Ditropan) -propantheline bromide (Pro-Banthine) -tolterodine tartrate (Detrol) -trospium chloride (Sanctura) -long-acting versions; increased selectivity; pharmacologic properties; growing list of options Tricyclic agents: -imipramine hydrochloride (Tofranil) Alpha-adrenergic agonists: (Sudafed) side effects: side effects of anticholinergic therapy: -blurred vision -dry mouth -constipation -cardiac effects -mental status changes contraindications (narrow angle glaucoma) |
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what are the nerves controlling the
bladder detrusor vs bladder outlet? cholinergic/adrenergic...? |
detrusor is cholinergic
bladder outlet is adrenergic so, for incontinence we use: anti-cholinergics and adrenergic agonists |
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contraindication to anti-cholinergic therapy
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narrow angle glaucoma
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treatment for stress incontinence
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surgical usually:
-bladder neck suspension -fascial sling -artificial urinary sphincter -urethral bulking agents (collagen, Durasphere) |
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treatment for urge incontinence
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augmentation cystoplasty
neuroelectrical stimulator systems |
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treatment for overflow incontinence
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correct obstruction
if it's a detrusor dyfunction, sometimes we have to start: self - intermittent catheterization in order to preserve the upper urinary tract |
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UTI
2 types |
1) uncomplicated: no anatomic problems and not immuno-compromised host
2) complicated: opposite; often need urology |
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urogenital infections
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Urinary tract infection
uncomplicated, complicated Sexually transmitted diseases Genital infection balanitis, balanoposthitis, urethritis, epididymitis, orchitis, prostatitis, pyelonephrits, abscess Acute, chronic, bacterial, atypical |
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Urogenital infections: when do we have to worry?
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Simple recurring
-(changing organisms) vs. relapsing (same organism); -search for underlying anatomic or functional predisposing factor [higher yield with relapsing] |
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Antibiotic therapy:
UTI |
Antibiotic therapy:
uncomplicated: -short course therapy; commonly used agents -drug resistance; when to culture complicated: -correction of underlying factors (examples) -longer course therapy |
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prevalence of ED
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40% at 40
70% at 70 vascular, neurogenic, endocrine, psychogenic |
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treatment of ED
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behavioral interventions, sex therapy
oral agents: know mechanism, characteristics (PDE-5 inhib.: inhibit the destruction of cGMP --> vascular dilation continues) -Sildenafil, Vardenafil – short action, Cialis – long) -nitrate contraindication (combination would cause severe hypotension) -alpha-blocker concomitant use recs (4-hr min).(combination would cause severe hypotension) -common side effects (headache, dyspepsia, flushing, blue vision) VED (vacular erection device) Intraurethral alprostadil (MUSE) Intracavernosal injection therapy Surgical implants |
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ED is early warning sign of what dangerous disease?
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artherosclerotic disease -
check their lipids, make sure they don't get a heart condition |
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stone diseases
types Clinical presentation management |
Chemical forms:
-CaOx, CaPhos (opaque; hypercalcuria, hypocitraturia, can't be dissolved) -Uric acid (lucent; gout; dissolution therapy - CaCitrate / alkaline agents) -Struvite (triple phosphate; infection, urease-producing org.) -Cystine (genetic) Underlying disease processes Clinical presentation: can be acute or indolent; Acute presentation usually means OBSTRUCTION Clinical evaluation: history, physical exam., laboratory imaging (noncontrast CT, U/S) metabolic, crystallographic Management: Emergency management issues: establish strategy, plan: trial of passage?, pain control hydration, monitoring acute infection with obstruction is a surgical emergency; drainage critical; treat stone later! Elective management options: ESWL:shock wave – ultrasound Ureteroscopy, laser lithotripsy Percutaneous lithotripsy Metabolic evaluation, follow-up |
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genital emergencies
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Trauma
Priapism Acute infectious states Testicular torsion Genital gangrene |
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Priapism risks:
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Priapism – risk:
sickle cell disease, pt on psychophamacologic, increased blood viscosity |
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causes of infertility
male/female/both |
20% both
30% male 50% female |
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why do you have to ask about childhood diseases that can affect the testes?
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because unilateral problems can affect the other testis:
torsion, trauma, tumor, varicocele, cryptochidism |
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Have you had any serious medical illness or surgery → impaired ejaculation or testicular function?
like what? |
High fevers/debilitating illnesses
Retroperitoneal surgery (retrograde ejaculation? check the urine) Pelvic injury Y-V plasty; TURP(prostate) Herniorrhaphy (Mesh)[fibers causing scarring of the inguinal floor] - now we do this without mesh, but with robot |
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Have you been exposed to any chemicals, taken medication or used drugs that can affect sperm production?
like what? |
Tobacco
Chemotherapy Radiotherapy Alcohol Marijuana Recreational drugs Anabolic steroids Azulfidine Pesticides (DBCP) Workplace Chemicals e.g. solvents offer them to have their semen banked if they are going to get cancer |
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Physical exam
for male infertility |
check meatus
testis size: 4 cm x 2 cm = > 20 cc varicocele - common, found in 18%; graded, if it's only grade 1 - he has to bear down |
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diagnosing varicocele?
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Physical Examination:
Standing Position Valsalva Testicular Measurements Venography Doppler Stethoscope 99mTc - Pyrophosphate Testicular Scan High Resolution Ultrasonography Duplex Ultrasonography - greater than 3cmm + reversal of flow |
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Doppler criteria for varicocele?
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Duplex Ultrasonography
- greater than 3cmm + reversal of flow |
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what's the most important lab value in determining damage to the sperm producing part of testis?
want to know if the Leydig are working? want to know about the higher centers of control - what lab value? in obese pt you want |
FSH = sperm
LH + testosterone = leydig cells prolactin = higher lvls estrogen (estradiol) b/c their estrogen is being made into estradiol by the aromatase in their fat |
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Y chromosome deletions
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Incidence
0.7% oligospermia (< 5mil/cc) 10% severe oligospermia (< 1 mil/cc) 15% azoospermia Frequency of specific deletions (Yq11) AZFc deletion: most common, in 40% of pt we still find sperm AZFb/a deletion: no viable sperm |
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what's normal/average
vs what's adequate?? sperm number? |
Houston: mean sperm density:
80.7 mil/ml this does not mean, that if you have 50mil, that you'll be infertile; there are criteria, that determine the limit, below which, your chance of being infertile increases: The following limits of “adequacy” are usually used: On at least two occasions: Ejaculate volume 1.5 - 5.0 cc Sperm density > 20 million/cc Motility > 50% Forward Progression > 2 (1-4) Normal Morphology > 30% And: No significant sperm agglutination No significant pyospermia (white cells - on the lab slip:"round cells" does not mean it's WBC, it could be immature sperm! so you have to do monoclonal Ig test with CD45) No hyperviscosity |
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Leukocytes vs Germ cell? ?
what causes infertility here? |
when they're detected with monoconal antibodies, and have sx, then they have an infection;
total WBC count is clearly higher in the infertile men this can be due to: the WBC make ROS (reactive oxygen species/oxidants) Direct damage to sperm Lipid peroxidation via chain reaction Possible sperm DNA damage |
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what's always in the culture medium for artificial insemination?
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ANT-OXIDANTS (because the ROS from WBC can cause Direct damage to sperm
Lipid peroxidation via chain reaction Possible sperm DNA damage) so we add: Alpha-tocopherol (vitamin E) Ascorbic acid (vitamin C) NSAIDS to decrease WBCs |
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Tests of Sperm Function
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Computer assisted Analysis (CASA)
Hypo-osmotic swelling (HOS) Acrosomal staining (T-6) Hemizona assay (HZA) Sperm penetration assay (SPA) Strict morphology index (SM) DNA fragmentation assay determine of the fertilization takes place and the embryo grows Sperm morphology: "Patients with < 4% normal forms…had a fertilization rate of 7.6% of the oocytes (normal > 50%)" |
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Kruger morphology criteria
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Normal sperm:
Smooth, oval head Acrosome that is 40-70% of the head volume No abnormalities of the neck, midpiece, or tail No cytoplasmic droplets > half the head size |
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management of pt with strict morphology problem
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Varicocelectomy
Improves strict morphology Isolate® sperm wash Marked increase in Nl forms (9.0% → 21.5%) IVF v. ICSI 38.9% pregnancy/cycle with ICSI with total teratozoospermia (0% normal |
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sperm DNA tests
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Sperm of infertile men has increased level of DNA damage:
DNA damage is associated with impaired post fertilization embryo cleavage (so they fertilize, but embryo can' grow) Seen with unexplained infertility or repeated early miscarriage Sperm chromatin structure assay (SCSA) TUNEL assay Comet assay Limits of normal approximately the same for all three assays: DNA Fragmentation < 30% |
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how to improve sperm DNA?
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↓ Reactive-Oxygen Species
Abn SM + Elevated ROS → DNA damage Rx of ROS improves pregnancy and implantation Varicocelectomy Improves DFI: 27.7% → 24.6% (p<0.05) Testicular vs. ejaculated sperm TESE → improved implantation and pregnancy in patients with increased DFI (the testicular sperm has less fragmentation) |
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transrectal ultrasound for who?
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Perform TRUS:
-Azoospermia -Severe oligospermia -Asthenospermia with normal testes and FSH duct narrowing?? obstruction?? stones/cysts/stenosis |
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Seminal Vesicle Aspiration
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sperm in the seminal vesicle?? from reflux - shouldn't have any sperm, but if there is reflux it will;
Preparation similar to prostate biopsy Ejaculation in last 24 hours Positive test >3-5 sperm/hpf TUR-ED indicated |
