Week 4 Lectures Flashcards
What is the most common cause of PSA elevation?
BPH
Of all nodules felt on digital rectal exam, what percentage are cancer?
25%
Why would you do a Trans Rectal Ultrasound (TRUS)?
Only to help guide a prostate biopsy (or to help estimate size of prostate
When do you order a prostate biopsy?
BEST indication is a PSA velocity rising at 0.75/year or more
What are two characteristics of prostate cancer?
Multifocal and heterogenous (heterogeneity is unusual to this degree in a primary tumor–more common in metastasis)
What does prostate cancer’s heterogeneity and multifocal nature mean for treatment plans?
These two factors mean you can’t target a single area in prostate cancer for treatment–thus there is no focal treatment for prostate cancer
What is the most powerful prognostic tool for prostate cancer
Gleason score
What is the gleason score
Two numbers: A + B
A = most common cell type seen on slide
B = second most common
Add the two numbers together to get the Score
Score 1-6 = low risk (active surveillance)
Score 7 = intermediate risk
Score 8 and above = high risk
Score 7 and above requires treatment
60-70% of diagnosed prostate cancer is low risk
What does “high risk” prostate cancer mean?
Gleason score of 8 or above; higher risk of treatment failure, higher chance of metastasis, more aggressive
What areas of the prostate are of most concern for cancer (location)?
apex and base of prostate because these areas are close to the bladder and the urinary systems
What is the stage of the most common prostate cancers detected in men?
T1c (tumor found only on biopsy)
What are the treatment outcomes for localized prostate cancer? Metastatic?
Localized: treat to cure
Metastatic: non curable (fatal)
Why would you do surgery through perineum for prostate cancer?
Not done anymore except maybe for obese patients because less fat on the perineum so easier to reach
What is the most common radiation therapy for prostate cancer?
Brachytherapy
What radiation therapy would you use for more aggressive prostate cancers (gleason 8-9)? What about localized cancers?
Aggressive: External beam therapy (because dont want to miss any of the cancer)
Localized: Brachytherapy
What is active surveillance in prostate cancer treatment?
Periodic PSA, periodic rectal exams, periodic biopsies (to make sure there is no progression of the cancer) – 20-25% will progress
When would you use chemotherapy in prostate cancer?
only for patients with metastatic disease who have been treated with hormone therapy already but continue to have progressing diease
What chemo drug is used most often in prostate cancer?
Docetaxel
What drug is used before chemo in metastatic prostate cancer?
Abiraterone–a SIP 17 inhibitor
(used in castration resistant prostate cancer with metastasis before chemo)
–may also use Enzaltemide (androgen receptor antagonist)
What is the treatment for localized prostate cancer?
Surgery or radiation
What is the treatment for advanced prostate cancer?
Hormone therapy (and eventually chemo if unresponsive or continues progressing)
Most likely cause of painless hematuria
Neoplasm
Most likely cause of hematuria + renal colic
stones
Most likely cause of chills, fever, sepsis
infection
Most likely cause of increase urinary frequency, nocturia, reduced flow, anuria
BPH, neurogenic bladder, urethral strictures
Causes of urinary tract obstruction
Stones
BPH
Tumors (TCC, Bladder, Prostate, lymphadenopathy, pelvic neoplasms)
Congenital (UPJ, UVJ, post. urethral valves, ureterocele)
Inflammatory (RPF, abscess, urethral stricture)
Pregnancy–gravid uterus may compress ureter
Why use a radiograph KUB in UTO?
Best to follow progress of known stone to see if it will pass
Why would you use IVP?
almost NEVER use if CT is available
Fairly good for stones, presence/absence of obstruction, congenital variants; less sensitive for RCC unless large
Advantages of Ultrasound
Risk free–no radiation or contrast
Disadvantages of US
ureter not seen unless dilated, therefore not good for ureteric stone or tumour; may see hydronephrosis but not the cause
Reasons to use US
Good for renal parenchyma (i.e masses, atrophy), renal stones, REALLY good for hydronephrosis
Can also look at bladder, prostate, assess post-void residual volue in bladder, all of which may be abnormal in BPH or other causes
What is CT-IVP used for
delayed images of the collecting system used to see EXCRETION
What is the cost of CT versus MRI
CT is less expensive than MRI (CT machine is expensive but the actual scan is not)
Radiation levels of CT
relatively high–be judicious in how many a patient gets
What is an advantage of CT over US
CT is good for comparing images which is harder for US because a lot of US depends on techniqe of the administrating clinician
Which imaging method is best for stones
CT-KUB is exquisite for stones–virtually all stones are radioopaque on CT, even uric acid stones, whereas they are luscent on plain films–“procedure of choice for renal calculi”
CT-KUB–>NOT for transitional cell carcinomas
What is a disadvantage to a CT-KUB
cant get any functional info about the kidney (+ radiation)
Why would you do a CT with contrast
Shows renal parenchymal enhancement–therefore can identify TUMORS, ABSCESSES, INFARCTS, some functional info
can add delayed views of collecting system at cost of more time and radiation
Disadvantages of CT with contrast
Stones may be obscured by contrast
Contrast can be nephrotoxic
Often higher dose of radiation than CT-KUB
What is direct pyelography
direct injection of contrast into collecting system (as opposed to IV)
Retrograde = via cystoscope into bladder, inject into ureters
Antegrade = via nephrostomy tract from back to kidney
Why would you do a direct pyelography imaging exam
Excellent depiction of calyces, renal pelvis, ureters
Retrograde can be therapeutic–remove stones, biopsy masses, place stents, evacuate bladder
When are urethrograms done?
Done done very often.
Retrograde urethrograms are done to assess urethral strictures, trauma (inject from meatus)
Voiding urethrograms done to assess for reflux, obstruction due to Posterior Urethral VAlves etc…
Are MRIs frequently done for urinary tract obstruction?
No
Advantages of MRI
No radiation (comparatively); gadolinium contrast is less nephrotoxic than iodinated contrast in CT; excellent anatomic depiction
What is a particular use for MRI in urinary tract obstruction diagnosis
in pregnancy if US not diagnostic can do MRI
Disadvantages of MRI
expensive, less readily available, rare toxicity of gadolinium especially in renal failure (nephrogenic systemic fibrosis)
What are nuclear medicine renograms used for?
to assess % function from each kidney
no nephrotoxicity
What guides choice on imaging modalities for urinary tract obstruction?
Hx, physical, lab results–what do you expect to find?
Which tests have:
- most radiation?
- least radiation?
- highest cost?
- lowest cost?
- most toxicity?
- highest accuracy?
- mid-accurate?
- least accurate?
- CT
- US, MRI
- Nuclear medicine, MRI
- CT-KUB, KUB plain film
- IVP, CT with contrast
- CT, MRI
- NM, CT-KUB, US, IVP
- KUB plain film
Which imaging tests are nearly always the initial tests in urinary tract obstruction
US and CT
Imaging test for hydronephrosis
US
Imaging test for stones
CT (i.e present with renal colic)
finds other cause in up to 1.3 of patients (i.e appendicitis)
First line test in children or pregnant women
US–if shows hydronephrosis, next line most likely voiding cystourethrogram
Imaging if suspect BPH
US
Causes of “surgical” renal failure
Bladder outlet obstruction (BPH, maybe tumor) Urethral stricture Neurogenic bladder SImgle kidney with hydronephrosis Bilateral ureteric obstruction
Best tests for painless hematuria
Cystoscopy = best test for bladder
Retrograde pyelogram for ureters (done together)
Painless hematuria likely a tumor
Most common congenital urinary tract obstruction
UPJ obstruction
If a patient presents with fever, chills and renal colic or chronic obstructive symptoms, what must be done?
URGENT evaluation–medical emergency.
Blood, urine cultures; electrolytes
Catheterize (Foley) if think lower tract obstruction
CT or US to see if stone/mass/hydro
Urgent drainage by percutaneous nephrostomy, or less often by cystoscopy and retrograde stent insertion
Reasons to do a percutaneous nephrostomy
for drainage of obstructed kidney
What condition is associated with rising creatinine, Hx of frequency, nocturia, weak stream?
BPH–>Ultrasound
Source of sympathetic nerves
T1-L2
Source of parasympathetic nerves
S2, 3, 4 and cranial nerves
How do the afferent nerves of the ANS reach their cell bodies in the posterior root ganglion?
Via the white ramus communicans
Source of
- greater splanchnic
- lesser splanchnic
- least splanchnic
- T5-T9
- T10-T11
- T12
What nerves are responsible for the sympathetic innervation of the urinary system?
Splanchnic nerves (T5-T12)
White ramus communicans
carry myelinated axons of preganglionic fibers from the spinal nerve to the paravertebral ganglia of the sympathetic trunk
Gray ramus communicans
Carry postganglionic nonmyelinated axons to the spinal nerves from sympathetic trunk
Why are the sphlanchnic nerves unusual?
They pass through the sympathetic trunk without synapsing–leave myelinated and pass the diaphragm to take part in formation of the abdominal autonomic plexi
Name the cranial nerves that form part of the efferent parasympathetic nervous system
III, VII, IX, X
oculomotor, facial, glossopharyngeal, vagus
Name the sacral nerves that are involved in the parasympathetic systm
S2, 3, 4–the pelvic splanchnic nerves
What stimulates the afferent neurons of the ANS?
Stretch and lack of O2 (i.e ischemia)–NOT heat or touch
Where are the parasympathetic ganglia located?
Close to or within the walls of the organs
What plexus gives rise to the renal, testicular/ovarian, and ureteric plexi?
intermesenteric plexus (part of aortic plexus of nerves between superior and inferior mesenteric arteries)
How do the postganglionic nerves travel to the organs? (or preganglionic in the case of parasympathetic)
with the blood vessels
Kidney innervation
- Sympathetic
- Parasympathetic
- T10-L1–vasoconstrict renal arteries within kidney
2. vagus–vasodilate renal arteries
Ureter innervation
- Sympathetic
- Parasympathetic
- T11-L2–convey pain sensation, i.e resulting from obstruction and consequent distention
- S2, 3, 4
What is the only organ that receives preganglionic nerve fibers from the SNS
medulla of the adrenal cortex–because itself acts as a ganglion
Urethra innervation
- Sympathetic
- Parasympathetic
- L1, L2–tightens internal urethral sphincter (alpha 1)
2. S2, 3, 4–releases internal urethral sphincter
Urinary bladder innervation
- sympathetic
- parasympathetic
- T11/L2–in males, strong action of the internal urethra sphincter around the neck (Beta 2)
- S 2, 3, 4–contracts bladder (muscarinic)–also in charge of sensing STRETCH receptors and PAIN within the bladder
What is the dermatome that would be involved if bladder stretched too much (site of referred pain)?
external genitalia (because S 2, 3, 4)
What is the function of the SNS in the pelvis
- contraction of internal urethral sphincter in men; internal anal sphincter in both sexes
- smooth muscle contraction in association with reproductive tract with accessory glands of the reproductive system
- moving secretions from epididymis and associated glands to the urethra to form semen
What is the function of the parasympathetic system in the pelvis
- vasodilation (kidneys)
- bladder contraction
- stimulates erection
Describe the physiology of normal filling of the bladder
- bladder stretches (elastic properties)–>leads to SYMPATHETIC reflex–>ALPHA adrenergic receptors at bladder neck activated and increase resistance at bladder neck (“tightens it”)
- Beta 3 receptors are also activated in the detrusor, inhibiting contraction
- Direct inhibition of the detrusor muscle motor neurons in the sacral spinal cord
- as urethral pressure increases due to filling, the pudendal nerve (S234) fires which activates the external sphincter (tightens it) forming a seal
Describe the physiology of normal bladder emptying
- increased bladder stretching/filling produces more pressure causing sensation of distention
- the PMC coordinates: the firing of the PNS pathway (contraction of the detrusor and relaxation of the urethral smooth muscle); inhibition of the sympathetic pathways (smooth sphincter relaxation); inhibition of the pudendal nerve firing (external sphincter relaxes)
bladder emptying
What does PMC stand for
pontine micturition center
From where does the PMC receive input?
GU afferents as well as areas in the brain (cerbellum, cerebrum, basal ganglia)
What does the PMC do?
coordinates micturition by turning off the sympathetic signals and turning on the parasympathetic signals
allows for contraction of detrusor and relaxation of bladder outlet + external urethral sphincter
Causes of transient urinary incontinence
DIAPERS
Delerium Infection Atrophic vaginitis/urethritis Pharmacologic Excess urine output Restricted mobility Stool impaction
List general classifications of urinary incontinence
Transient incontinence (DIAPERS) Overflow Incontinence Stress incontinence Total incontinence Urgency/Urge incontinence
What is overflow incontinence
uncontrollable leakage of small amounts of urine from a bladder that does not empty well
What is the mechanism behind the clinical pathology of urinary incontinence
retention of urine in a bladder that does not empty well causes an increase in pressure causing small amounts to dribble out
bladder becomes overfilled due to obstruction, weak bladder contraction or medications
What might be some obstructions associated with overflow incontinence
stones, urethral stricture, BPH, constipation
What might a cause other than obstruction be for overflow incontinence
- weak bladder contractions due to detrusor muscle hyporeflexia secondary to a lower motor neuron (sacral spinal cord damage or peripheral nerve damage i.e diabetes mellitus, surgery or radiation therapy)
- chronic dilation of the bladder
- anticholinergics (TCAs, SSRIs, antipsychotics), Opiods, and Beta blockers (Beta 3 receptors) can interfere with bladder contraction
- alpha 1 antagonists promote internal sphincter contraction (i.e cold/sinus meds)
Treatment for overflow incontinence
treat underlying problem
- BPH–alpha antagonists, 5 alpha reductase inhibitors, TURP
- urethral stricture–dilation with catheter, urethrotomy
- catheterization to drain bladder
What is stress incontinence
uncontrollable loss of small amounts of urine due to sudden increases in abdominal pressure caused by coughing, sneezing, laughing, lifting, during valsalva, or other changes in position
what population most experiences stress incontinence
young and middle aged women
what are some causes of stress incontinence
- weakness of urinary sphincter (from trauma, childbirth, pelvic surgery, or an abnormal position of the urethra or uterus in women)
- lack of estrogen (causes deterioration of the urethral mucosal lining, thereby reducing resistance)
- Obesity (extra weight places increased stress on the bladder)
- damage to upper part of urethra or bladder neck
What meds can exacerbate stress incontinence
ACE inhibitor due to coughing side effect
use of alpha 1 antagonists
treatment for stress incontinence
- kegel exercises + biofeedback to ID muscles that are being exercised
- pessaries
- alpha 1 agonists for internal sphincter contraction
- estrogen to increase mucosal lining, increasing resistance
- sling procedures–transvaginal tape procedure is most common
- injection of bulk forming agents such as collagen around urethra
- artificial urinary sphincter
what is total incontinence
complete inability to store or control urinary leakage, independent of activity
what is the most common cause of total incontinence
damage to nerves controlling bladder (i.e congenital, post surgical, childbirth, pelvic disease, radiation therapy)
What are other causes of total incontinence (other than nerve damage)
- fistulas between ureters or bladder with vagina or rectum
2. scarring of the urethra in women preventing sphincter constriction
treatment for total incontinence
treat underlying problem
surgically close fistula
artificial urinary sphincter if applicable
what is urgency/urge incontinence
involuntary loss of urine following a strong desire to void–bladder contractions overwhelm cerebral inhibitions
bladder muscles are usually over-reactive–contraction before bladder is full
increase in frequency of urination in day and night
possible causes of urgency/urge incontinence
- constipation
- diuretics
- detrusor hyper-reflexia secondary to upper motor neuron lesions (cerebral injury, basal ganglia disease like Parkinsons’s, suprasacral spinal cord damage)
- most common in elderly
treatment for urgency/urge incontinence
- fluid and dietary restriction–no caffeine, ETOH, acidic/spicy foods or fluids
- scheduled voiding
- treat constipation
- kegel exercises
- estrogen in females to increase urethral resistance
- anticholinergics to relax bladder
- improve home environment for continence–bedside urinal
When is a chronic urethral catheter used for incontinence?
only as a last resort
- use in patient with unresponsive incontinence with skin complications despite barrier creams and absorbent pads inside diapers
- change every 4-6 weeks
- increased risk of UTIs and therefore bladder and renal stones
What is the physiological basis for the voiding dysfunction seen in men with obstructive uropathy (BPH)
BPH causes urinary incontinence through a few different mechanisms leading to a common outcome
- enlargement of the prostate through the mechanism of BPH causes impingement of the prostatic portion of the urethra and the bladder uvula–>causes an obstruction to urine flow out of the bladder; this in turn (if present chronically) will lead to thickening of the bladder wall (normal response produced by the PMC)–>this means that there is a combo of both urge incontinence (an increased spasticity of the bladder) along with overflow incontinence (b/c of increased amounts of urine present in bladder)
- over time, the bladder wall may become fatigued and will be less able to propel urine out of the bladder while it is full (a form of overflow incontinence)
What situations complicate the voiding issues seen as a result of BPH
may be complicated by stasis or the urine in the bladder
stasis may lead to an increased chance of having urinary tract infections within the bladder and potentially up to the kidneys
this causes an increased sensitivity of the bladder, and leads to spasm of the bladder wall (again leading to urge incontinence)
Is BPH progressive?
yes–worsening of clinical parameters over time
List complications of BPH
- urinary retention–acute (AUR) or chronic
- renal failure–due to hydronephrosis–>pyelonephrosis–>pyelonephritis
- recurrent UTIs–due to urine stasis
- bladder stones
- need for surgery–for AUR or symptoms relief
alarm symptoms with BPH
hematuria
UTI
bladder stones
renal failure
How might prostate cancer present clinically
usually asymptomatic (most are detected with an abnormal PSA or abnormal DRE)
if locally extensive/large however, it can cause obstructive voiding symptoms because it compresses the urethra/bladder neck
if it has metastasized (commonly to axial skeleton) it can cause back pain
How might BPH present clinically?
can either cause obstructive or irritative symptoms
describe the obstructive symptom presentation of BPH
hesitancy decreased force and caliber of stream sensation of incomplete bladder emptying double voiding straining post void dribbling
due to prostatic enlargement, which causes obstruction of the urine outlet pathway
How can the obstructive symptoms of BPH be further subdivided?
into “mechanical” and “dynamic” obstruction
what is BPH “mechanical” obstruction?
intrusion of the tumor into the urethral lumen or bladder neck, causing higher bladder output resistance
what is BPH “dynamic” obstruction?
due to autonomic stimulation of the prostate, which causes elevated tone and therefore constriction
describe the irritative symptoms clinical presentation of BPH
due to secondary response of the bladder to the increased outlet resistance
bladder outler obstruction–>detrusor muscle hypertrophy and hyperplasia, collagen deposition–>decreased bladder compliance
what are the symptoms of prostatitis?
urinary: dysuria, frequency, urgency
constitutional: fever, chills, malaise, perineal/back/rectal pain
irritative symptoms are due to inflammatory processes occurring close to the bladder neck
In general, what conditions are associated with frequency?
either due to increased urinary output or decreased functional bladder capacity which may result from
a) bladder outlet obstruction (increased residual urine volume results in lower functional capacity)
b) neurogenic bladder disorders
c) extrinsic bladder compression
c) psychological factors
List a differential diagnosis for a prostatic nodule
prostate cancer (30%) BPH prostate calculus prostate infarct prostatitis (infection) prostate cyst TB prostatitis (chronic granulomas) previous TURP or biopsy
what is the most effective method for early detection of prostate cancer?
combined use of DRE and serum PSA testing
How useful is the DRE in screening for prostate cancer?
- palpable areas of induration, or asymmetric firmness of the gland, suggest the presence of prostate cancer, but these findings can also be caused by prostate inflammation (especially granulomatous prostatitis), by BPH, and by prostatic stones
- DRE hasonly fair reproducibility in the hands of experienced examiners
- DRE misses 23-45% of the cancers that are subsequently detected by prostate biopsies done for elevated serum PSA
- prostate cancers detected by DRE are at an advanced pathological stage (>T2) in more than 50% of men
How useful is PSA in screening for prostate cancer?
it is not recommended for screening unless there is a risk factor for prostate cancer or patient agrees to monitor PSA velocity starting from age 50
what does an abnormal PSA entail?
- absolute levels >4 (lower for asian males)
- > 10 is strong indication of CaP (between 4-10 is grey zone)
- if in the grey zone, look at free-PSA to PSA ratio (rations >25% are at significantly lower risk of CaP)
what are some risk factors that would push you towards testing PSA?
african american descent
family Hx of CaP
previous abnormal biopsy
What other conditions can cause an elevated PSA?
prostatitis BPH infarction instrumentation inflammation
(test has poor specificity)
Will CaP always present with high PSA?
no sometimes it can present with low PSA
therefore test has poor sensitivity as well
list drugs commonly used to treat problems with bladder function
alpha agonists
alpha antagonists
beta agonists
beta antagonists
mechanism of action of alpha agonists
used to facilitate storage by increasing outlet resistance via sphincter constriction
alpha agonists potential SEs
hypertension due to vasoconstriction
alpha antagonists mechanism of action
used to facilitate emptying of the bladder by decreasing outlet resistance via sphincter relaxation
alpha antagonists potential SEs
retrograde ejaculation
beta agonists mechanism of action
used to facilitate storage by decreasing bladder contractility (smooth muscle relaxation)
bind beta-3 receptors on bladder to promote relaxation
beta agonists potential SEs
increased HR and contractility
beta antagonists mechanism of action
will apparently cause urinary retention due to increase in sphincter resistance–probably due to presence of beta-3 Rc on sphincter–if blocked, no urination
Treatment options for prostate cancer: local disease
- radical prostatectomy –open retropubic; perineal–if retropubic approach is contraindicated (good for obese men); laparoscopic
- radiotherapy–brachytherapy (has to be low/intermediate stage); external beam (3D conformal, conventional, IMRT)
complications of radical prostatectomy
- intraoperative: bleeding, rectal injury, damage to obturator nerve, damage to ureters
- postoperative: incontinence (10% require 1 pad/day for stress incontinence at year 1), improves for up to 2-3 years; erectile dysfunction (2 nerves spared–50-60%; 1 nerve spared–20-30%)
complications for radiotherapy
- radiation exposure to bladder and rectum
- nerves may be damaged, cause ED
- urinary incontinence
treatment for locally advanced/metastatic prostate cancer
hormonal therapy
- LHRH analogue–causes initial hormone flare which can cause bad effects by sudden enlargement of prostate, so need to lair this with antiandrogen
- LHRH antagonist
- estrogen–not used much in canada because causes thromboembolic toxicity, CVS toxicity, prominent feminizaton
- steroidal antiandrogen, non steroidal antiandrogen–not used as monotherapy, used with GNRH analogue to prevent initial hormone flare
indications for hormone therapy
- neoadjuvantly–before radiation/prostatectomy (rarely used)
- primary therapy for advanced prostate cancer
- adjuvantly (during/after radical therapy)
- failures after radical therapy
treatment for castrate resistant prostate cancer
aka hormonal resistant prostate cancer
- docetaxel + prednisone is the only therapy shown to work–is the standard of care for HRPC with metastatic disease
- new agents in development: abriratone, ipilumimab, OGX-011, ZD4054
