Lucas-Cava Vanesa, Sánchez-Margallo Francisco Miguel, Moreno-Lobato Beatriz, Dávila-Gómez Luis, Lima-Rodríguez Juan Rafael, García-Martínez Virginio, López-Sánchez Carmen, Sun Fei
Endoluminal Therapy and Diagnosis Unit, Jesús Usón Minimally Invasive Surgery Centre, Cáceres, Spain.
Scientific Director, Jesús Usón Minimally Invasive Surgery Centre, Cáceres, Spain.
Transl Androl Urol. 2022 Dec;11(12):1655-1666. doi: 10.21037/tau-22-423.
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.
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 PAO-group, 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.
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 4.87 ng/mL, P=0.002), whereas DHT was lower but no significant (112.52 138.35 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.
PAO induces hemorrhagic ischemia predominantly resulting in necrosis rather than apoptosis with prostate shrinkage. CPSE is a potential biomarker to assess the response to PAO in the canine prostate.
前列腺动脉栓塞术（PAE）是治疗男性有症状良性前列腺增生（BPH）的一种替代疗法。在犬前列腺模型中已开发出一种对传统PAE的技术改良，即使用奥尼克斯进行前列腺动脉闭塞（PAO），其治疗效果是前列腺缩小。然而，其潜在机制尚未完全阐明。本研究旨在评估PAO对犬前列腺治疗作用的生物学机制。
10只成年雄性比格犬（5.0±0.82岁）接受了用奥尼克斯-18进行的PAO（n = 7），并以前列腺动脉血管造影作为对照（n = 3）。在随访的不同时间点（基线、1周、2周、1个月、3个月和6个月）采集血样，以测量血清犬前列腺特异性酯酶（CPSE）。还进行了MRI检查，以记录随访不同时间点干预前后的前列腺体积（PV）。PAO组在2周时摘取2个前列腺，其余8个在6个月时摘取，通过ELISA法测定前列腺内睾酮和双氢睾酮（DHT），通过TUNEL法检测凋亡，并进行组织病理学研究。
与基线数据相比，PAO后2周开始至6个月，平均血清CPSE浓度随PV显著下降。此外，CPSE与PV之间存在中度但显著的相关性（r = 0.655，P = 0.000）。关于前列腺内雄激素，PAO后睾酮显著高于对照组（19.70±4.87 ng/mL，P = 0.002），而DHT较低但无显著性差异（112.5±138.35 pg/mL，P = 0.144）。组织学研究显示，PAO在2周时导致整个前列腺严重出血性坏死并伴有炎性细胞浸润，6个月时则出现弥漫性间质纤维化，腺上皮萎缩和前列腺内腔形成。所有标本均检测到凋亡，PAO组在2周时（7.35%）和6个月时（4.38%）的凋亡指数高于对照组（2.64%），但组间无统计学显著差异。
PAO诱导出血性缺血，主要导致坏死而非凋亡，同时伴有前列腺缩小。CPSE是评估犬前列腺对PAO反应的潜在生物标志物。
