Pathology: urinary system
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What anatomical structures does the prostate gland lie next to?
- urinary bladder
- seminal vesicles
- vas deferens (ampulla)
- autonomic nerves (alpha-adrenergic)
- (pelvic lymph nodes)
In which zone does prostate cancer usually develop?
- peripheral zone
- (area adjacent to rectal wall)
In which zone does BPH develop?
Does family history correlate with increased risk for prostate cancer?
- FHx of prostate cancer: >2x increased risk
- no specific genes identified yet
Is there a minimal serum PSA value below which cancer is not found?
- (~ 7% of men with prostate cancer in this study has a serum PSA < 0.5 ng/ml)
There is NO threshold ABOVE which there is always cancer or BELOW which there is never cancer
How specific is an “abnormal” digital rectal exam (DRE) for cancer of the prostate?
- not very
- BPH: can have firm nodules but non-malignant
- Prostate cancer: malignant but does not normally form firm nodules
What are the 3 main risk factors for developing benign prostatic hyperplasia?
- 1. Age
- 2. Intact Androgen pathway
- (no BPH if prepubertal orchiectomy)
- 3. Family History of BPH
What (specific) complications might occur if BPH is not treated?
- Acute urinary retention
- Chronic obstruction:
- Bacterial cystitis & pyelonephritis
- Bladder stones
- Hydronephrosis & chronic renal failure
What (general) complications might occur if BPH is not treated?
- dilated renal collecting system (hydronephrosis, pyelonephritis)
- dilated ureters (hydroureter)
- dilated, trabeculated bladder
- chronic bladder obstruction (cystitis, ball-valve effect)
What are the 2 main components of "lower urinary tract syndrome"?
- 1. mechanical obstruction
- 2. neurogenic
What are the options for treating BPH?
- Removal of prostate tissue: TURP (transurethral resection of prostate), Suprapubic prostatectomy Androgen blockade
- Inhibition of alpha-adrenergic enervation
What are some side effects of trans-urethral resection of the prostate (TURP)?
- Side effects:
- 15 % develop symptoms requiring another TURP within 10 years
What are some risk factors for prostate cancer?
- Older age
- Intact hypothalamic-pituitary-testis axis
- African-Americans have prostate cancer at a younger age and higher rate than whites.
- Incidence increases 5-fold in Japanese who emigrate to the USA
- family history of prostate, breast or brain cancer.
A set of prostate biopsies showed prostate adenocarcinoma. What additional information provided in the biopsy is useful for deciding how to manage this patient’s cancer?
- The grade of the cancer: Grading is based on how well-formed the glands are (the Gleason system).
- Using the Partin tables, the grade, serum PSA and the clinical stage the probability of the cancer being confined to the prostate can be determined.
What is a "grade" of cancer?
- Grade = How well differentiated a tumor is
- How closely tumor histologically resembles non-tumor, normal cells of that organ:
- Low-grade = Close resemblance
- High- grade = Little resemblance
What is meant by a "stage" of cancer?
- Stage = Where the tumor is at time of diagnosis
- Localized = Tumor is confined to the organ of origin
- Regional spread = Tumor has invaded adjacent organs
- Metastatic = Discontinuous spread of tumor to other tissues
What is the lowest score on the Gleason cancer grading system? highest score?
- lowest score: 2 (1 + 1)
- highest score: 10 (5 + 5)
What are the advantages and limitations of different options for treating a primary prostate cancer?
- Choices of therapy:
- Radical prostatectomy
- Radiation therapy (Implantation of radioactive seeds (brachytherapy))
- External beam
- Hormonal blockade
- Watchful waiting/active surveillance
- Side effects:
- Loss of libido
What are the eligibility requirements for having an "active surveillance" approach to prostate cancer treatement? What is "active surveillance"?
- clinical stage T1
- PSA level ≤ 20 ng/mL
- Gleason score < 7
- PSA measured and a DRE conducted at 3-6 month intervals.
- Decision between continued monitoring or definitive therapy is informed by rate of rise of PSA and patient - clinician decision
- 80% of patients still on active surveillance at 10 yrs.
Which organ does metastatic prostate cancer preferentially affect?
- Prostate cancer has high proclivity for bone; these metastases are usually osteoblastic and the source of marked pain.
- The majority of patients who die of prostate cancer have widespread bone metastases
- 100% of bone metastases invasion in the right iliac decreasing slightly throughout the spine and the thoracic cage to 64% in the left humerus.
Some men whose cancers have been retarded by androgen deprivation therapy present later with metastatic cancer. What is the mechanism for prostate cancer progression in these cases?
- Presumably, the selection for prostate cancer cells that don’t depend on androgen receptor activation for proliferation.
- There is evidence that prostate cancer cells can produce sufficient androgen to activate androgen-dependent pathways
True/False: The majority of patients with prostate cancer die from the disease.
- Only a minority of patients develop progressive tumor
- Only a minority of these patients die of prostate cancer
- The majority die of cardiovascular disease
How will you screen a patient for prostate carcinoma and what is the effectiveness of these screening method(s)?
- Screening techniques:
- Digital rectal exam (DRE)
- Serum PSA
- DRE is insensitive and relatively nonspecific
- Specificity and sensitivity of serum PSA for detecting prostate cancer is low
- Diet5 alpha reductase blockade, i.e. finasteride
Is serum PSA a good screening assay for detecting primary prostate cancer?
- Serum PSA “measures” the size of the prostate regardless of whether there is cancer (either low- or high-grade)
True/False: Routine PSA exams are recommended for people over the age of 75.
- P.S.A. screening is currently not advised for those 75 and older.
What are the 4 basic medications that affect the androgen pathway and are used to prevent/treat prostate cancer? What are the common side effects of these drugs?
- 1. estrogens (prevent LHRH release from hypothalamus)
- 2. LHRH analogues (prevent pituitary stimulation)
- 3. finasteride; a.k.a. propecia (5-alpha-reductase inhibitor)
- 4. AR antagonists (prevent AR stimulation)
- side effects:
- hot flashes
- decreased libido
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