Complete List of Terms and Definitions for Prostate Cancer
|What is Bicalutamide?||*Androgen receptor blocker|
|LHRH Agonists: Side Effects||
Bone Loss (Osteoporosis)
|Medical Adrenalectomy||Ketoconazole 400 mg po q8h|
|Describe the urothelium||A multi-layered transitional epithelium impermeable to fluids and solutes that is continuous with the ureters above and prostatic urethra below. It lines the urinary tract.|
|prostate cancer signs and sx||
lower extremity edema,
constipation/ bowel obstruction
|Antiandrogen Side Effects||
Impotence / Decreased libido
|What can alkaline phosphatase indicate if elevated in prostatic cancer?||Bone involvement|
|What are other possible biomarkers that can be used to detect prostate cancer besides PSA? (4)||
2. IV bisphosphonate
3. +/- calcitonin
|Antiandrogens: Hormone withdrawal||Mutations in the androgen receptor have been demonstrated allowing anti-androgens to become agonists and activate androgen receptors. Pt’s responses to withdrawal manifest as significant PSA reductions and improved clinical symptoms.|
|in this case you would attempt a posterior sagital anal repair. An intra-abdominal repair would be difficult this far deep into the pelvis and so the first attempt would be from the perineum. The patient may ultimately need a urinary diversion but this can be attempted first.|
|What causes high PSA that is NOT cancer? (false positives) (4)||
|Antiandrogens: Treatment of choice||
• Combination of anti-androgen and LHRH agonist
• Efficacy over 80-90 %, most relapse within 2 years
• Prolonged survival seen with initial combination therapy
• Mean Survival 35.6 months with combination vs. 28.3 months with LHRH agonist alone
|Do any anti-depressants or antipsychotics influence bladder function? If so, how?||Some anti-depressants such as amitriptyline antagonise muscarinic receptors in addition to their blockade of neuronal uptake of amines (which is the basis of their antidepressant activity). Thus, when elderly patients take these antidepressants they may develop urinary retention due to the unwanted anticholinergic activity. Similarly, chlorpromazine, which is a dopamine receptor antagonist and is used as a major tranquilliser, has anticholinergic activity. When these psychoactive drugs are given to patients, there is a small risk of urinary retention.|
|Is PSA more accurate at detecting early disease or at evaluating response to therapy?||Response to therapy|
|Screening for prostate||
normal risk- yearly at 50
high risk- yearly at 45
2. digital rectal
3. transrectal ultrasonagraphy
|What is Lupron?||*Leuprolide - it is a GnRH agonist, but given in a constant fashion will cause suppression of GnRH secretion and decrease testosterone levels.|
|Describe the pelvic parasympathetic nerves innervating the lower urinary tract||Pelvic parasympathetic nerves - These originate in 2nd to 4th sacral segments and projects to the pelvic plexus where the cholinergic postganglionic fibres provide efferent innervation to the detrusor muscle.|
|Describe the nervous transmission of the sensation of bladder fullness||Sensation of bladder fullness originates from the trigone and is mediated by sympathetic fibres to the thoraco-lumbar spinal cord and up to the pons and cerebral cortex.|
|Is Gleason Score a good predictor of outcome from prostate cancer? Can it be used to help decide on treatment?||Yes and Yes|
60-90 mg IV over 2-24 hr x 1 dose
AE: bone, joint, muscle pain,
fever, flu sx,
osteonecrosis of the jaw,
|Embryologically, from where does the testis arise? How does it know to be a testis and not an ovary?||The testis arises from the undifferentiated gonad on the medical surface of the embryonic mesonephros, with differentiation into a testis determined by the testis determining factor gene (tdf) on the Y chromosome.|
|Describe venous drainage of the prostate?||The prostate receives venous drainage from the dorsal vein of the penis. This drains into a rich plexus of veins around the plexus called Santorini's plexus. This drains into internal iliac veins but there is communication with the prevertebral plexus which may explain the predilection for prostate cancer to spread to bones.|
|What gleason score is more treatable and which tends to be more advanced?||Treatable 6-7, Aggressive = 8-10|
|What is the natural history of adenocarcinoma of the prostate? (4 possible fates)||
1. Tumour remains microscopic (latent)
2. Tumore remains confined to prostate gland (localized)
3. Local spread of prostate cancer via blood, lymphatics and nerves, mainly to seminal vesicles and base of bladder
4. Lymphatic spread + Hematogenous spread primarily to bone
|What are treatment options for localized prostate cancer? (5)||
1. Active surveillance
2. Radical prostatectomy (open, laproscopic, robotic) - most common treatment in young, healthy patients. Most definitive treatment with acceptable side effects.
3. Brachytherapy - good cure rate for early disease and has less side effects than external beam.
4. External Beam Irradiation - most effective treatment for locally advanced disease. High morbidity and proctatitis in 10-15 years so only use on older patients
5. Image Guided Minimally invasive - Cryosurgery: not very effective with similar morbidity. High intensity focused U/S: non-invasive and precise but data lacking
|Dx of hypercalcemia of malignancy||
1. low Cl-
2. corrected Ca
3. serum albumin
|What are the acute symptoms of radiation as primary treatment for prostate cancer?||Acute toxic effects of radiotherapy include urinary frequency, urgency, or dysuria reported by 11% to 18% of patients (without such problems at baseline) and rectal urgency, frequency, or pain in 13% to 15%. By 1 to 2 years after treatment, urinary symptoms typically subside, but1 in 10 men report rectal symptoms as becoming a persistently moderate or big problem.|
|What do the accessory sex glands excrete?||The bulbourethral glands secrete a mucous lubricant prior to ejaculation, while the other accessory glands, the seminal vesicles and the prostate, add secretions at ejaculation.|
|How are alpha1-adrenoceptors targeted pharmacologically to treat benign prostate hyperplasia?||The tone of the human prostate smooth muscle is maintained primarily by the action of noradrenaline (NA) released from adrenergic nerves. The release of NA from pre-synaptic nerve terminals binds to postjunctional alpha1-adrenoceptors. Thus, alpha1-adrenoceptor agonists block the function of NA thereby decreasing the tone of the prostate smooth muscle.|
|What is the mediastinum of the testis?||The mediastinum is the thickened posterior border of the white tunic (thick fibrous capsule that surrounds the testis). It houses the rete testis, (tubular network connecting the seminiferous tubules to the vasa efferentia), as well as the entry and exit of blood vessels and nerves|
|What is a good investigation to detect abnormalities in micturition?||Urodynamics. This involves measuring the intravesical pressure and abdominal pressure by small pressure transducers, which are placed in the bladder and the rectum. The bladder is then filled until capacity. After this the patient voids. Filling and voiding pressures are recorded on computer and analysed to assess function.|
|What can cause PSA to be elevated? (5)||Prostate cancer, BPH, prostatitis, ejaculation, instrumentation of the prostate gland|
|What is the tumour staging system for adenocarcinoma of the prostate?||
T1: Clinically inapparent
T2: Palpable or visible on imaging + confined to gland
T3:Extension beyond gland
T4: Invasion into other structures (bladder, rectum, pelvic wall)
N: Regional lymph node metastases
M: Distant metastases
|What are risk factors for prostate cancer? (3)||
Race (increased in African American, decreased in Asian)
Diet - high fat intake, low vit D, Vit. E etc.
|What comments does the SELECT trial have on the high dose vitamin E being associated with increased all cause mortality and cardiovascular events?||This study basically tries to debunk that. They weren't powered to study that and it wasn't there primary end point but the point they make is that we had thousands of these guys on high dose vitamin E for a long period of time and there wasn't an increased risk of cardiovascular event or mortality. They point that in many of the studies that the meta-analysis show that result in were in pateints with significant comorbidiites.|
|Where do extrinsic causes of upper urinary obstruction usually originate?||In the retroperitoneum or in the reproductive tract. Pregnancy may cause a functional obstruction due to the enlarging uterus but rarely requires treatment.|
|What causes of upper urinary tract obstruction should be considered in younger or more diseased patients?||In younger patients, renal calculi are the most common cause of obstruction. In patients with diabetes, analgesic nephropathy, or SLE a sloughed renal papilla should be considered, particularly in the presence of acute on chronic renal failure. In patients with gross haematuria blood clots may obstruct the urinary tract.|
|Describe the lumbar sympathetic nerves innervating the lower urinary tract||hese originate at T-10 to L-2 and fibres from the hypogastric plexus innervate the smooth muscle of the bladder base, bladder neck, and proximal urethra. They also modulate parasympathetic ganglionic transmission and has an inhibitory function during bladder filling.|
|What is the endocrine finction of the testis?||It involves the interstitial (or Leydig) cells, which have smooth endoplasmic reticulum for production of steroid hormones (androgens) and Sertoli cells, which secrete androgen binding protein to maintain high local levels of androgens. They also control spermatogenesis through secretion of inhibin which participates in a feedback loop with secretion of FSH by the pituitary|
|If a patient is to undergo radiation for primary treatment of their CaP, and they are high risk, is there a benefit to getting pelvic radiation to the lymph nodes?||The addition of radiation to the pelvis to treat pelvic lymph nodes has been evaluated in patients with high-risk cancers without a definitive survival benefit.|
|What is the effect of alpha agonists such as pseudoephedrine in bladder function?||
Because of the involvement of the sympathetic nervous system in bladder neck function, alpha-agonists can cause urinary retention, especially in older women.
Pseudoephedrine, a weak alpha-agonist, has some activity on the bladder neck causing increased sphincter tone.
|How does testosterone increase risk of developing prostate cancer?||Testosterone is converted to DHT by 5 alpha reductase. DHT also produced directly by prostate stromal cells. DHT acts on prostatic epithelial cells to promote cell growth and survival.|
|What are the 4 stages of local prostate tumor growth, which are localized vs advanced and what screening tests can detect each?||
T1 - Localized, PSA only
T2 - Localized, PSA and DRE
T3 - Locally advanced, PSA and DRE
T4 - Locally advanced, PSA and DRE
|If a patient is s/p RALP for prostate cancer, what is Dr. Pruthi's cut-off value for evidence of biochemical recurrence & referral for a patient for radiation?||
*0.4ng/dl. He states that there was research done here at UNC looking at the 0.2 levels and the 0.1 levels and there was a high percentage of those patients that returned back to undetectable levels and they weren't really real.
*0.4ng/dl is still early radiation, Dr. Pruthi was stating that they used to go to like 10 or 12 and still consider that early vs delayed radiation therapy for prostate cancer.
|What is a possible reason why vitamin E was not affective in preveinting prostate cancer in the SELECT trial?||
1.) Possible used to high of a dose, although the dose was chosen because the men in the ATBC study that had the highest reduction in prostate and lung cancer were those with the highest baseline vitamin E levels.
2.) Again these patients weren't smokers and some research has shwon that it is more protective in men that are smokers, and only a small subset of the SELECT trial were smokers.
|How do you add up Gleason patterns to give a final score?||Number of primary pattern + number of the next highest pattern present in the sample|
|Does the environment play a big role in BPH progression to prostate cancer?||Yes - when people move from country of low rates to country with high rights their risk increases alot|
|Antiandrogens: Drug Dosages||
Flutamide 250mg po tid
Biclutamide(Casodex)50mg po qd
Nilutamide 300mg po qd x1month then 150 mg po qd
CV events (MI)
Rapidly reduces circulating androgens to castrate levels < 50 ng/dL
|What is trade name for Flutamide?||*Eulexin|
|RF PROSTATE CANCER||
diet (high fat diet)
Adrenal Glands: 3% – 5%
|Which aspect of the adventitia is covered by peritoneum?||Posterior|
|What location in the prostate is cancer most likely to arise?||Posterior|
|severe hyper Ca>14||
2. IV bisphosphonate
4. +/- dialysis
|Chemotherapy in Prostate||
Mitoxantrone + Prednisone with decr. pain score but no impact on survival
Estramustine + Docetaxel
|How is picturition initiated?||
Afferent activity provides conscious awareness of bladder filling. When afferent activity to the pontine micturition centre reaches a threshold level (subject to suprapontine facilitation or inhibition) voiding is initiated.
The efferent activity is mediated via descending spinal pathways to the sacral spinal cord and the pelvic parasympathetic nerves. Acetylcholine is released by these nerve terminals which bind to muscarinic receptors on the detrusor muscle to cause a detrusor contraction. At the same time there is synchronous relaxation of the urethral sphincter mechanism again co- ordinated from the pontine micturition centre to allow unobstructed voiding until the bladder is empty.
|Corrected Ca equation||
= measured Ca+ 0.8 (4-serum alb)
>12 is abnormal and sx
|What is conformal radiation treatment for prostate cancer? What is intensity modulated radiation?||
Threedimensional conformal radiation uses images obtained from a computed tomographic scan to shape the radiation beams to the target tissue.
Intensity-modulated radiation therapy is a form of conformal radiation in which the radiation energy of small areas in each beam is modulated, allowing
refined shaping of the radiation dose around the target structure.
|In which prostatic zone is tumour rarest?||The central zone|
|What are 3 strategies to reduce mortality from prostate cancer?||
|Prostate Cancer: Risk Factors||
1) African Americans
2) Age > 65 y/o
|How does Wallen follow his patients post-prostatectomy that have a PSA that is undetectable post-op?||Wallen follow-up post-prostatectomy for prostate cancer is a PSA every 3 months for a year, every 6 months for a year, and then every year for 3 years for a total of 5 years of follow-up. If there PSA remains undetectable then they are done.|
|How does urinary obstruction present?||Patients with total obstruction may present with acute renal failure and anuria. Partial obstruction may present with fluctuating urine output. Pain is usually present in acute obstruction but not always in chronic obstruction. Recurrent urinary infection may be a sign that urinary obstruction is present.|
|From which cell type in the prostate does adenocarcinoma arise?||Glandular epithelial cells|
|What are adverse effects associated with androgen deprivation therapy? (6)||
Loss of bone mineral density
|A patient has radiation therapy as primary therapy for their prostate cancer. After treatment they have a rising PSA, how long before they will have clinically detectable disease?||increasing PSA precedes clinically detectable recurrent disease by 3-5 years on average.|
|What are common causes of lower urinary tract obstruction in males?||Prostatic hypertrophy, and less commonly malignancy, are the most likely cause of urinary obstruction, with urethral strictures, malignant and benign lesions in the bladder and a neurogenic bladder also causing functional obstruction. Occasionally anticholinergics, alpha adrenergic agonists or antihistamines can cause bladder dysfunction and functional obstruction - more commonly in males.|
|What are the lobules of the testis?||Intercommunicating lobules are partly divided by septa. Each lobule contains one to four looped seminiferous tubules|
|What are the seminal vesicles?||Paired glands, which lie behind the prostate, and these join the vas deferens to form the ejaculatory ducts|
|What is the outcome of minimally invasive, locally advanced and metastatic disease?||
Minimally invasive - excellent
Locally advanced - fair to good
Metastatic Disease - poor
|What are indications for androgen deprivation therapy? (4)||
1. Metastatic prostate cancer
2. Lymph node metastasis
3. Adjuvant after radiation in intermediate-high risk patient
4. Rising PSA after definitive local therapy
|Risks for Tumor Flair||
Is tumor in spinal cord or close to blocking off kidney's with risk of blocking kidney's
NO then LHRH alone OK
|What are the Partin Tables and when were they constructed? What parameters do they asses?||
Partin tables were initially constructed in the 1990s and updated in 2001, assisting in the
preoperative prediction of final pathologic stage in men with clinically localized prostate cancer undergoing radical
These tables look at PSA, Gleason grade, and clinical stage.
|What is the fluid from seminal vesicles?||Secretions from the seminal vesicles are rich in fructose and form the bulk of the ejaculate volume. Their role is thought to be nourishment of the sperm but the exact function is unknown.|
|What are the two types of intramural causes of upper urinary tract obstruction?||Either functional (such as vesicoureteric reflux) or anatomic (such as pelviureteric junction obstruction, ureteric strictures or transitional cell carcinoma of the renal pelvis or ureter). Other causes are relatively less common.|
|What does Prostate Specific Antigen (PSA) do?||It causes liquefaction of the seminal coagulum, so the sperm can travel more freely in the vagina|
|What are the three layers of the bladder?||Urothelium, muscular layer (detrusor), adventital layer|
|What are the risk factors for adenocarcinoma of the prostate? (4)||
1. Age: >50
2. Ethnic group: Blacks>Whites>Asian for gross cancer but all equal for latent, microscopic cancer
3. Environmental/dietary incluences
4. Hormones (androgens)
|How do you prevent the development of prostate cancer? (4)||
Nutrition: low fat, high soy
Micronutrients: Vit. E, D, selenium
Hormones: 5 alpha reductase inhibitors
|What is prostate specific antigen, where does it come from and how is it regulated?||PSA is a glycoprotein produced by prostate epithelial cells that is responsible for liquefaction of seminal coagulum and is androgen regulated|
|Why had selenium possibly worked to prevent prostate cancer in some early preclinical studies but not shown to be benefit in the SELECT trial?||
1.) Possible Selenium Format - They used L-selenomethionine as opposed to high-selenium yeast this is different format, but did for good reasons. Hard to get standardized form of the high selenium yeast, the active ingredient in that compound was thought to be the selenomethionine, there is potential toxicity with long term use of high selenium yeast, and in vitro data show that selenomethionine is affective in suppressing malignant prostate cells.
2.) Could have been chance finding in the previous NPC study because was small sample size and there was multiple testing done on that group
3.) The NPC trial was done in men deficient in selenium and the SELECT trial patients had normal baseline selenium.
|What are the complications of PLND?||*For men with RRP the risk of lymphocele is there and subsequent nerve compression and symptoms from the lymphocele. For robotic prostatectomy since you are intraperitoneal the risk of lymphocele is almost zero, but not zero and Wallen states that you can sometimes get them anyway.|
|Were patients in the SELECT trial required to have annual PSA & DRE examinations?||No, no standardized across all study centers as this was a multi-instiution study, as there wasn't strong evidence at the time that this study was began for this practice patients were screened based on the practice pattern of the institution that they were at.|
|What is the pontine micturition centre and what does it do?||The pontine micturition centre in the rostral pons is responsible for co- ordinated micturition with detrusor contraction and synchronous relaxation of the sphincter. This may be facilitated or inhibited by cortical centres.|
|Which has greater influence on bladder function- sympathetic or parasympathetic?||The influence of the sympathic nervous system on bladder function is less than that of the cholinergic neural control.|
|What happens to blood flow during erection?||In erection, there is increased blood flow into relaxed arteries and into large vascular sinuses in the spongy and cavernous bodies. Venous return is limited by compression of these dilated vessels against the thick connective tissue surrounding the cavernous bodies.|
|What is cryptorchidism and what are the potential health problems associated with it?||Failure to descend into the scrotum after early childhood leads to increase risk of testicular carcinoma, requiring surgery to ensure descent and avoid sterility.|
|Describe the muscular layer of the bladder||This has no specific orientation but in the area between the ureteric orifices and the bladder outlet (the trigone) there is an additional superficial layer of smooth muscle derived from the ureters. This is thought to have a role in preventing vesico-ureteric reflux (i.e. urine up the ureters) with bladder filling and detrusor contraction and may also aid in opening the bladder neck during voiding.|
|Why did the SELECT trial happen at all?||Essentially there were a few trials before it namely the Nutritional Prevention of Cancer (NPC) trial and the Alpha Tocopherol, Beta Carotene Cancer Prevention study (ATBC) that showed prostate cancer risks were reduced by 63% for selenized yeast and 32% for a-tocopherol. There was also a large scale randomized controlled trial that showed that a combination of selenium, vitamin E, and beta carotene reduced overall cancer mortality. This was all epidemiological and preclinical data and therefore the SELECT trial.|
|How many men needed to be screened to prevent one death from CaP in the european trilal? How does that compare with other things such as fecal occult blood tests or mammograms?||
Notably, 1410 men
needed to be screened to prevent 1 prostate cancer death;
however, the number of screenings to prevent 1 cancer
death was similar to the numbers reported in studies of
mammographic screening for breast cancer and fecal
occult blood testing for colorectal cancer.
|What is the "stage" in reference to prostate cancer?||It refers to the extent ( spread) of the tumor. TNM staging system is used|
|How are cancers of the prostate graded?||
Grade with most cancers is based on tumor cell appearance on history, with prostate cancer however the most useful grading system looks at glandular architecture. (Gleason grading). The architectural pattern, on low power magnification, is graded between 1 and 5.
Grade the largest area, then the next largest area and add them to obtain the Gleeson grade.
Most clinical cancers diagnosed have a Gleason score between 5 and 7
|How does Androgen Receptor gene determine genetic predisposition to developing prostate cancer?||Number of CAG repeats in AR gene is inversely correlated with risk of prostate cancer.|
|What type of trial was the SELECT trial?||This was a phase III trial, which means that there is preliminary data that this drug may reduce the risk of prostate cancer in phase I & II trials and that it can go ahead with phase II or larger trials. It was a randomized, placebo controlled trial. Patients got either selenium, vitamin E, selenium + vitamin E, or placebo with the primary end point of prevention of prostate cancer. The trial took place between 2001 & 2008.|
|What is Lupron? What are some typical side effects?||
Lupron is a medication that we use for advanced prostate cancer. It is an analog of LH-RH that causes the release of LH or it is an LH agonist. This causes initially an increase in testosterone produciton which then will shut off testosterone production because the body typically produces LH in pulses and when this is shut off and the body gets a constant amount of LH without pulsatile nature then it becomes an antagonist.
When looking at research trials with this agent there was a surge in testosterone for the first week that may be associated with increased symptoms such as bone pain, UTIs, urinary obstruction, etc if not combined with an adrogen receptor antagonist. Levels go back to baseline around the second week and the decrease after that.
Ginger's book states that typical side effects can include headaches, bloating, difficulty concentrating.
|What gene mutations may play a role in prostate cancer? (germline, somatic)||
Germline: BRCA2 - 20x increase in risk but is rare
Somatic: ETS-TMPRSS2 rearrangement, GSTP1 promoter (most common)
|What was the basic design of the SELECT trial?||
It was designed to be a 4 group trial with 5 prespecified comparisons. The groups were selenium vs placebo, vitamin E vs placebo, selenium + vitamin E vs placebo, selenium vs selenium + vitamine E, vitamin E vs selenium + vitamin E.
The really fascinating thing about this study is the assumptions that they had to make to determine how many patients would be needed for to power the study, these are listed in the study.
|Tumor Flare Blocked by:||Antiandrogens|
|LHRH Agonists: Dosage||
Leuprolide depot 7.5 mg/month
Leuprolide 4 month 30mg/16week
Leuprolide 3 month 22.5mg/12week
Leuprolide daily 1 mg SQ daily
Goserelin 3.6 mg q 28 days / 10.8 mg q 12 wks
|Has neo-adjuvant hormone therapy proven to show a survival benefit for men with prostate cancer before prostatectomy, low, intermediate, or high risk patients?||
therapy prior to prostatectomy showed reduction in pathological stage after androgen suppression but showed no benefit in cancer-free survival.
|Supportive care for hypercalcemia||
2.maintain phosphorous 2.5-3
3.normal saline hydration 200-500ml/hr
4. furosemide 20-40 mg IV q12 after rehydration
The most common adverse effect reported with LH-RH agonist therapy including a disease flare up during the first week of therapy
cause by initial induction of LH and FSH by the LH-RHY agonist and manifests clinically as either bone pain or increased urinary symptoms
|What percentage of prostate cancer is familial (genetically inherited)?||10%|
|Mild hyper Ca<12||
hydration IV or PO
PC-Spes (Canada / Mexico) Removed from market b/c FDA issues
DHEA (Testosterone Derivitave and dangerous)
Saw Palmetto (5-alpha reductase activity) for BPH no effect in prostate cancer
Lycopene (Prevention reported with high tomato intake)
|What is Casodex?||*Bicalutamide - an GnRH antagonist, people will give it with Lupron initially to block the potential testosterone surge.|
|How much has mortality due to prostate cancer been reduced in the past 10 years?||25%|
4-8 iu/kg sq im q12 hrs
ae: flushing, nausea, rare hypersensitivity rxn, tachyphylaxis
|What is vantus?||
Histrelin, which is a GnRH agonist (just like Lupron or Leuprolide). Used for treatment of advanced prostate cancer.
Inserted once very year subcutaneously.
|What is the precursor lesion of adenocarcinoma of the prostate called?||Prostatic Intraepithelial Neoplasia|
|What is the lifetime probably of getting prostate cancer?||1 in 6|
|Current Strategy for Hormonal Therapy:||
Orchiectomy and monitor PSA for dropping. Other tx if rising
LHRH+Antiandrogen FRONTLINE (efficacy 80-90% with relapse in 2 yrs)
|What is contained within the brachytherapy seeds?||
These sealed sources contain radioactive iodine 125, palladium
103, or cesium 131 and emit low-energy radiation with doses limited to within millimeters of the seeds; none of these isotopes has been shown to be superior.
|What bladder pressures are generated during micturition? What urinary flow rate does this result in?||During micturition, the bladder generates a pressure not more than 40 cm water to produce a maximum urinary flow rate of about 20-25 mls/s.|
|What are prognostic factors for adenocarcinoma of the prostate? (4)||
Tumor grade (Gleason score), Pre-operative PSA
Surgical margin status
|What are the advantages and disadvantages of screening for prostate cancer?||
Advantages - mortality reduction, improved curability, simple/inexpensive, NNT comparable to breast
Disadvantages - Imperfect, risk of overdiagnosis/overtreatment
|What patients are bad candidates for brachytherapy?||
Brachytherapy is contraindicated in prostates larger than
60 mL in size due to anatomic constraints of the pubic arch
that preclude delivery of a sufficient distribution of seeds
for adequate radiation dose.56 In addition, men with significant
obstructive lower urinary tract symptoms prior to treatment
may require long-term catheterization and are not optimal
candidates for brachytherapy.
Also brachytherapy alone not good idea in men with intermediate risk prostate cancer....
What innervates the smooth muscle elements of the prostate?
What drugs take advantage of this?
|Alpha adrenergic nerves via the synthetic nervous system. Hence alpha adrenergic antagonists (e.g prazosin, terazosin or tamsulosin) can cause relaxation of prostatic smooth muscle and improve urinary flow rate. This is used clinically in patients with bladder outlet obstruction due to prostatic hypertrophy.|
|What happens in the epididymis?||The spermatozoa mature as they pass along the epididymis, becoming capable of progressive movement in the tail of the epididymis. This is also the main storage site for spermatozoa prior to ejaculation, with the distal parts of the duct system having thicker muscular walls for transport.|
What is the effect of anticholinergic drugs on the bladder?
In which clinical situations might it be relavent?
|The classic anticholinergic drug, atropine, decreases contractility of the detrusor muscle and increases tone in the sphincter. These effects may result in urinary retention. Atropine is given to patients as part of anaesthetic premedication for some cardiac arrhythmias which are due to excessive tone of the vagus nerve. Ipratropium bromide is an anticholinergic bronchodilator administered via the inhaled route. With large inhaled doses there may be sufficient systemic absorption to result in anticholinergic effects. Thus, elderly patients with a mild degree of bladder dysfunction may develop urinary retention. Tiotropium, which is an inhaled anticholinergic drug, used in the treatment of COPD, also has the potential to interfere with bladder function.|
|What are the Gleason Scoring patterns?||
1 - Well circumscribed, well differentiated (can't see on core biopsy because need whole gland)
2. Small glands, well differentiated (can't see on core biopsy because need whole gland)
3. small glands, diffusely infiltrative
4. Merged glands, diffusely infiltrative
5. No identifiable glandular differentiation
|What makes prostate cancer a suitable cancer for screening?||
1. Cause of substantial morbidity/mortality
2. High prevalence of pre-clinical state
3. Screening test with high sensitivity low cost and convenient (PSA+DRE+history)
4. Mortality reduction due to earlier detection (ie-improved treatment)
|Hypercalcemia of malignancy - signs and sx||
1. renal -polyuria, stones, failure
2. GI-NV, constip, anorexia, pain, dipsia
3. neuro-lethargy, confusn, somn, coma
4. misc- hypovolemia, arrythmias
5. low CL as Ca binds
|People have looked at choline PET/CT scanning to help determine if post curative treatment (radical prostatectomy or radiation therapy) PSA rises represent local recurrent disease or metastatic disease. Why is it not a recommended modality in looking at p||*This is because benign prostatic tissue as well as tumoural prostate tissue presents a physiological uptake of choline and therefore some believe that PET/CT is not suitable for detection of local recurrences after EBRT as the remaining viable benign prostate tissue after treatment will also light up.|
|The most substantial risk of mitoxantrone therapy is what?||*This is a chemotherapeutic that his used for hormone resistance prostate cancer. It has the risk of cardiotoxicity and patients who have symptoms at all should have a MUGA scan before initiation of therapy and be monitored closely during therapy.|
|Describe the bladder neck (internal sphincter) mechanism||This is an involuntary smooth muscle sphincter, which is rich in sympathetic innervation and remains closed during bladder filling to provide a continence mechanism. It is important in males in preventing retrograde ejaculation.|
|What evidence supports that High Grade Prostatic Intraepithelial Neoplasia is the precursor of Prostate cancer? (3)||
1. Both predominate the peripheral zone
2. HGPIN ofen seen in proximity to cancer
3. HGPIN and cancer share many genetic alterations
|What are 3 methods to achieve androgen deprivation?||
1. Surgical castration
2. LHRH analogues (mainstay): injections, reversible but can have "flare". Act by negative feedback.
3. Anti-androgens: less effective, oral, can cause gynecomastia when used alone
|A 55 year old man undergoes a difficult radical perineal prostatectomy that lasts six hours. Postop he has weakness of the left foot with inability to dorsiflex. The nerve most lkely injured is the what?||*Peroneal nerve. It leaves the popliteal fossa and crosses to the anterior part of the leg laterally around the bony prominence of the knee and can be exposed to compression and stretch injury in prolonged lithotomy cases. It supplies the tibialis anterior and patients can't dorsifelx.|
|Describe the somatic motor innervation of the lower urinary tract||This originates in S-2 to S-3 and travels to the external urethral sphincter via the pudendal and pelvic nerves.|
|What is the exocrine function of the testis?||It involves production of spermatozoa in seminiferous tubules (spermatogenesis). Spermatogonia divide and differentiate into spermatocytes (becoming haploid in meiosis), then transform into smaller spermatids which undergo cytological changes without further cell division (spermiogenesis) to form much smaller spermatozoa.|
|What is the D'Amico criteria for high risk prostate cancer?||
*this is based on the convential pre-op information that we have for patients w/ prostate cancer such as PSA, grade, biopsy results, & clinical T stage.
*Criteria state that men w/ PSA >20ng/dl, gleason grade 8-10, and or clinical stage greter than or equal to stage T2c, based on 92 system for TNM staging where this is bilateral palpable disease.
|What is the result of the cholinergic parasympathetic innervation of the bladder wall?||auses contraction (via activation of M 3 muscarinic receptors) of the detrusor muscle and the innervation of the bladder neck causes relaxation (which may be due to the release of relaxant neuropeptides from the ganglia or from the parasympathetic nerve fibres) of the trigone and external sphincter|
|How do prostate tumours keep growing when androgen supply has been blocked?||Mutations cause AR to be activated by other ligands or allows bypass of AR for gene prostate cell survival|
|What is the TNM staging for prostate cancer?||
pT0 - no tumor identified
pT1a - tumor found in <5% of TURP specimen & grade <7
pT1b - tumor found in >5% of TURP specimen &/or grade >7
pT1c - tumor identified based on screening PSA & then prostate biopsy.
pT2 disease in general is organ confined disease
pT2a- disease in less than one half of one lobe
pT2b - tumor involves more than one lobe
pT3 - palpable tumor beyond prostate
pT3a - unilateral extracapsular extension
pT3b - bilateral extracapsular extension
pT3c - tumor invades seminal vesicles
pT4 - tumor is fixed or invades adjacent organs
pT4a - tumor invades bladder neck, rectum, or external sphincter
pT4b - Tumor invades levator muscle and/or fixed to pelvic wall
|When is bone spread seen? How is this seen on imaging and why?||
Blood spread can be relatively early, and has a predeliction for bone, especially to the axial skeleton.
It usually produces new bone formation (dense on x-ray) and appears as a hot spot on a bone scan
|You have a patient that has a history of prostate cancer s/p XRT for treatment with now recalcitrant hemorrhagic cystitis. You have decided to start him on po Amicar. What is the dosage for Amicar? What is the generic name and how does it work?||
*Amicar is also known as Epsilon - Aminocaproic acid. It can be given either po/iv or intravesical as a solution.
*Amicar works by inhibiting the activity of urokinase, which breaks plasminogen down into plasmin. Plasmin is a protein that works to break down fibrin clots.
The po and IV doses are the same with the maximum dosage of 30 grams a day.
Oral - give 5 grams during first hour, following by 1-1.25 grams/hour for approximately 8 hours or until bleeding stops.
IV - Give 4-5 grams in 250ml of diluent during first hour followed by continuous infusion at the rate of 1-1.25gram/hour in 50ml of diluent, continue for 8 hours or until bleeding stops.
|How do you screen for prostate cancer using PSA?||
Baseline PSA at age 40
q 5 years from 40 to 50
q 1-2 years from 50 to 70