Prostatic disease Flashcards
Hormonal control of prostatic growth
Testosterone from adrenals
–> dihydrotestosterone (by 5a reductase)
DHT –> prostatic growth (hypertrophy and hyperplasia and secretions
Both testosterone and DHT can bind same androgen R but DHT is much more potent stimulator of R –> amplified response compared to testosterone alone
Different types of 5a reductase and locations
Type 1- in most tissues
Type 2 - predominantly in prostate and gonads.
Ejaculate fractions and prevalence of prostatic disease in entire male dogs/cats
3 in dogs
1 and 3 are from prostate.
3rd should be clear
Subclinical prostatic disease may be as prevalent as 76%
Very rare in cats
Pathogenesis of BPH
As entire males age their testosterone levels fall while oestrogen levels remain the same → altered ratio.
Prostate hyperplasia and hypertrophy occur in response to testosterone/DHT
Oestrogen increases the expression of androgen receptors in the prostate → amplifying growth signal.
→ ongoing growth can result in excretory duct obstructions and under influence of oestrogen cellular metaplasia → cystic hyperplasia
Can also develop parenchymal cysts which predispose to prostatitis
Tx options for BPH other than castration (5)
Finasteride - 5a reductase inhibitor → less DHT → less androgen stimulus for growth → atrophy
→ reduces size by 30% in 4 weeks.
Oasterone - synthetic testosterone, binds receptor with less activation and reduces conversion of testosterone to DHT.
Well tolerated - may change activity level.
Medroxyprogesterone - progestin → inhibits androgen activity by competitive binding to receptors
→ may increase risk of insulin resistance, iatrogenic Cushings symptoms.
GnRH analogues (deslorelin) - reduces LH release through negative feedback to pituitary.
→ reduces prostate size >50% by 4 weeks.
→ administered every 6-12 months as long acting treatment. Effects on fertility are reversible.
Tamoxifen - anti-oestrogen treatment
→ 30-50% reduction in prostate size
Serological marker for prostate
Canine Prostate specific arginine esterase - high serum levels correlate well with BPH on histo (97% sens, 92% spec).
Not useful for detection of prostatic cancer as also produced by other tissuues
ISCAID recommended ABx and Tx duration for bacterial prostatitis
ISCAID Duration Recommendations
- Previously 4-8 weeks recommended for acute disease. No studies to determine optimal duration. In humans use 3-6 weeks
Culture 2 weeks after discontinuation not recommended during therapy
→ Clinical signs, prostatic size and u/s appearance of architecture are better indicators of successful treatment
→ in most cases semen quality improves with treatment
ABx that can penetrate blood-prostate barrier:
In acute disease this is disrupted by inflammation but as infection resolves drug will need to have adequate penetration → lipid soluble, weakly alkaline, not protein bound.
USE SERUM BREAKPOINTS (not urine)
- TMS: retrospective study reported comparable efficacy to fluoroquinolones (low LoE) but lacks anaerobe coverage.
- Fluoroquinolones: ciprofloxacin has less reliable bioavailability in dogs and penetration may be inferior to veterinary licensed products which are preferred (Enro, Prado, Marbo)
- Macrolides (clinda): good penetration but ineffective for G- bact which are most commonly involved.
- Fosfomycin: may be beneficial in MDR infections
Avoid:
Penicillins, Cephalosporins, aminoglycosides and tetracyclines due to poor penetration
Chloramphenicol: prostatic fluid concentrations ~60% that of serum so may not be therapeutic levels
Castration
→ in acute disease give ABx a few weeks to work then use as adjunct treatment (early castration can result in scirrhous spermatic cords)
→ chemical castration (finasteride, oasterone etc) not as effective a preventative long term but may be used in short term prior to castration.
recommendations or options and their limitations for prostatic cultures
Ejaculate - 3rd fraction used as this is prostatic fluid and less likely contaminated by urine.
May have difficulty with collection in dogs with acute disease due to pain associated with ejaculation.
Prostatic wash - generally prostatic fluid is not sterile, and CFU counts can be high in normal dogs.
FNA cultures- may be more specific for prostatic infection than wash or ejaculate as unlikely to be contaminated by urinary bact.
→ low risk of seeding bacterial infection into abdomen
NB: AVJ 2022 82 cases of prostatitis or abscess:
→ urine and prostatic cultures were discordant in 50%
Brucella testing (RSAT sens 90%, spec 40-60%; PCR, culture) in breeding dogs in geographically relevant areas
Recommended medical Tx for prostatic carcinoma
Overall poor MST of weeks to months
Piroxicam - can reduce size. Nearly 90% of the tumours expressed cox-2 and 14 dogs
treated with piroxicam lived longer than 15 untreated dogs; 7 months versus less than 3 weeks.
Combination with cisplatin caused partial response in 70%
Piroxicam + mitoxantrone: 35% measurable
response rate. Most importantly, subjective improvement in clinical signs occurred in 75% of treated dogs.
VCO 2018 - multi institutional study of outcome in medically Tx prostatic carcinoma
→ longer survival in NSAID + chemo (106d) vs NSAID alone (51d)
