Prostatic artery occlusion: initial findings on pathophysiological response in a canine prostate model

Abstract

Background: Prostatic artery embolization (PAE) is an alternative treatment for symptomatic benign prostatic hyperplasia (BPH) in men. A technical modification of conventional PAE has been developed in a canine prostate model consisting of prostatic artery occlusion (PAO) using Onyx ® whose therapeutic effect is prostate shrinkage. However, the underlying mechanisms are not well clarified. The purpose was to evaluate the biological mechanisms responsible for therapeutic effects of PAO in the canine prostate.Methods: Ten adult male beagles (5.0±0.82 years) underwent PAO with Onyx-18 (n=7) and prostatic artery angiography as control (n=3). Blood samples were taken at different time points of follow-up (baseline, 1 week, 2 weeks, 1 month, 3 months and 6 months) to measure the serum canine prostate specific esterase (CPSE). MRI examinations were also performed to document the prostate volume (PV) before and after interventions at different time points of follow-up. Prostates were harvested at 2 weeks (n=2) in the PAOgroup, and the remaining ones (n=8) at 6 months for the determinations of intraprostatic testosterone and dihydrotestosterone (DHT) by ELISA, apoptosis by TUNEL assay and histopathological study. Results:The mean serum CPSE concentration started to decrease significantly from 2 weeks to 6 months after PAO along with PV compared with baseline data. In addition, a moderate but significant correlation was observed between CPSE and PV (r=0.655, P=0.000). Regarding intraprostatic androgens, testosterone was significantly higher after PAO than control (19.70 vs. 4.87 ng/mL, P=0.002), whereas DHT was lower but no significant (112.52 vs. 138.35 pg/mL, P=0.144). In histological study, PAO induced a severe hemorrhagic necrosis in the whole prostates along with inflammatory cell infiltration at early 2 weeks, and then diffuse interstitial fibrosis with atrophy of the glandular epithelium and intraprostatic cavity formation at 6 months.Apoptosis was detected in all specimens with higher apoptotic index after PAO at 2 weeks (7.35%) and at 6 months (4.38%) compared with control (2.64%), without statistically significant difference between groups.

Prostatic artery occlusion: a new strategy to improve clinical outcomes of prostatic artery embolization?

“…To study this point, other teams have assessed embolization with another liquid agent, N-Butyl Cyanoacrylate Glue, and showed the same clinical efficacy as with microparticles, with no more complications and shorter duration of embolizations, therefore less X-rays exposition (12). However, Lucas-Cava et al showed on angiographic controls at 6 months that, despite an initial complete occlusion by the liquid agent, either the prostatic arteries had repermeabilized or the prostate had recruited other arteries, highlighting the limits of this new technique (8). In addition, studies on repeated embolizations of prostatic arteries showed much lower efficacy, suggesting another unresolved mechanism at stake in the treatment of prostates possibly resistant to ischemia (10,11).…”

“…Lucas-Cava et al studied the effects of PAE on a canine model (8). They described a new technique of embolization with a complete occlusion of the prostatic arteries by a liquid agent, ethylene-vinyl alcohol copolymer or Onyx ® , an agent originally used for the embolization of vascular malformations (9).…”

“…Finally, by completely occluding the prostatic arteries, Lucas-Cava et al hoped to limit the inflow of testosterone into the prostatic bloodstream and thus have an additional anti-hormonal effect (8). The authors studied the effects of embolization on the blood concentration of canine testosterone and dihydrotestosterone.…”