Prostatic artery occlusion versus prostatic artery embolisation for the management of benign prostatic hyperplasia: early results in a canine model.

OBJECTIVE: To compare the technical efficacy and safety between prostatic artery occlusion (PAO) with ethylene vinyl alcohol copolymer (EVOH) and prostatic artery embolizsation (PAE) with microspheres in a canine model. METHODS: 17 adult male beagles underwent PAO (n = 7) with Onyx-18 or PAE (n = 10) with microspheres (300-500 µm). To evaluate the primary outcomes (technical efficacy and safety), MRI evaluations were performed immediately before and 1 week, 2 weeks, and 1 month after procedures to document prostate volume (PV); and all dogs were inspected for procedure-related complications during 1 month follow-up. The secondary outcomes included the prostate ischaemia size detected by MRI and recanalisation of prostatic artery by follow-up angiography. Differences between groups were statistically analysed. RESULTS: Both procedures were bilaterally successful in all animals. Compared with PAE, the mean fluoroscopy time (23.80 vs 36.24 min, p = 0.014) and radiation dose (68.19 vs 125.26 mGy, p = 0.003) were significantly less in PAO procedure. The mean percentage of PV change significantly decreased in both groups at 2 weeks (30.71% vs 37.89%) and 1 month (56.41% %vs 55.56%) after PAO and PAE respectively), without significant differences between groups at either time point. No major complications were observed except one animal after PAO with transient haematuria and acute urinary retention. The mean prostate ischaemia induced by PAO was significant greater compared with PAE at 1 week (43.44% vs 18.91%, p=0.001). PAO with EVOH is technically feasible and with comparable efficacy and safety with PAE. There are possible benefits to PAO over PAE. ADVANCES IN KNOWLEDGE: A new technical modification of the PAE consisting of the use of liquid embolic agent to occlude the prostatic artery trunk and its branches has been developed in pre-clinical study, showing to be an effective and safe procedure which can induce a significant prostate shrinkage for the management of symptomatic benign prostatic hyperplasia in patients. In addition, the findings have showed a similar therapeutic effect comparable with the conventional PAE using microspheres.

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

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 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. 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. Conclusions: 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.

Prostatic artery embolization: magnetic resonance image (MRI) findings in the early detection of prostate infarction in a canine spontaneous benign prostatic hyperplasia model.

BACKGROUND: The purpose was to assess the association between prostate infarction and prostate volume (PV) reduction after prostatic artery embolization (PAE) and define the best time point in detection of prostate infarction. METHODS: Ten male beagles (3.5-6.4 years) with spontaneous benign prostatic hyperplasia (BPH) underwent PAE. Magnetic resonance image (MRI) was conducted immediately before and 1 week, 2 weeks and 1 month after PAE to document prostate infarcts and measure PV. The sum of infarct areas (SUMIA) was measured and calculated using OsiriX software. Spearman's rank correlation was used to estimate the relationship of PV reduction rate with infarction percentage and SUMIA reduction. RESULTS: In comparison with baseline data, significant PV reduction (P<0.001) occurred at 2 weeks and continued to decrease substantially (P=0.004) from 2 weeks to 1 month after PAE. In the same fashion, significant decrease in both SUMIA and infarction percentage was observed from 1 to 2 weeks (P=0.002), and subsequently to 1 month (P=0.039 and P=0.016, respectively). Spearman's rank correlation test demonstrated infarction percentage at 1 week had a stronger correlation (r=0.880, P=0.001) with PV reduction rate at 1 month than infarction percentage at 2 weeks (r=0.733, P=0.016). PV reduction rate had a significant correlation with decrease in SUMIA (r=0.854, P=0.002) at 1 month after PAE. CONCLUSIONS: One week after PAE is an ideal time point to evaluate prostate infarction. Prostate infarction percentage at 1 week is a good predictor for prostate shrinkage at 1 month after PAE.

Prostatic artery embolization with polyethylene glycol microspheres: evaluation in a canine spontaneous benign prostatic hyperplasia model.

BACKGROUND: Prostatic artery embolization (PAE) is a minimally invasive technique for the management of symptomatic benign prostatic hyperplasia (BPH) relieving the lower urinary tract symptoms in patients. Various embolic agents have been tested in animal models and subsequently used in human patients. The purpose of this study was to evaluate the technical feasibility, effectiveness, and safety of PAE with polyethylene glycol microspheres in a canine spontaneous BPH model. RESULTS: Five adult male Beagle dogs (4.78 ± 1.11 years) were diagnosed by tranrectal ultrasonography of spontaneous BPH (prostate volume > 18 ml) and underwent PAE with polyethylene glycol microspheres (400 ± 75 µm). PAE procedures were performed successfully in all dogs. After PAE, all dogs were inspected for potential procedure-related complications during 1 month of follow-up. No major complications were observed any animal. Follow-up angiography was performed in each animal at 1 month of follow-up. Recanalization was demonstrated in all the embolized prostatic arteries or main branches at the end of the study. Magnetic Resonance Imaging (MRI) evaluations were performed immediately before PAE as baseline data, and 1 week, 2 weeks and 1 month after PAE. MRI study showed that the prostate shrank substantially with ischemic necrosis in each dog. There was a significant reduction in the mean prostate volume at 2 weeks and 1 month compared with the baseline data, from 19.95 ± 1.89 mL to 13.14 ± 2.33 and 9.35 ± 2.69 mL (p < 0.001), respectively. Histopathological study was conducted after 1-month follow-up angiography and confirmed the therapeutic responses with diffuse glandular atrophy and interstitial fibrosis. CONCLUSIONS: The findings of the present study support that PAE with the use of polyethylene glycol microspheres is a safe and feasible procedure that may induce a significant shrinkage of prostate due to the local ischemia and secondary glandular atrophy. Early recanalization of target arteries remains to be further addressed in both laboratory investigation and clinical practice.

Parasympathetic Tone Activity Evaluation to Discriminate Ketorolac and Ketorolac/Tramadol Analgesia Level in Swine.

BACKGROUND: Evaluation of nociceptive-antinociceptive balance during general anesthesia is still challenging and routinely based on clinical criteria. Analgesic drug delivered may be optimized with parasympathetic tone activity (PTA) monitor. This study compares ketorolac and ketorolac/tramadol balance analgesia using a PTA monitor. METHODS: Pain intensity response was assessed using a 0-100 numerical state scale (PTA) after nociceptive stimuli in pigs under stable sevoflurane anesthesia. Bispectral index, heart rate, noninvasive blood pressure, and respiratory parameters were also measured. Animals were divided into 3 groups: without analgesia, ketorolac, and ketorolac/tramadol. Mean values or mean areas under the curve (AUC) in selected time periods were compared over time and between groups through a mixed-model repeated measures analysis of variance and nonparametric Kruskal-Wallis tests, followed by Bonferroni or Dunn's multiple comparisons. RESULTS: It was observed a significant decrease in the PTA AUC mean value after application of the stimulus in animals treated without analgesia and only with ketorolac. The PTA AUC mean value in the control group was significantly lower than the corresponding mean in ketorolac group. The ketorolac/tramadol group showed the highest PTA AUC mean values, significantly different from those obtained for the other 2 groups, with no significant differences detected over time. Bispectral index means showed no statistically significant differences either over time periods or between different treatment groups. Heart rate showed only a statistically significant increase in AUC mean between without analgesia and ketorolac/tramadol group, in the time period after the stimulus application. Noninvasive blood pressure means showed no statistically significant differences over time and between treatment groups. CONCLUSIONS: This study shows that a low dose combination of ketorolac and tramadol is sufficient to block the pain responses induced with a needle holder in pigs 20 minutes after its administration. The PTA monitor was able to clearly recognize the analgesic level between treatments and may be used to optimize analgesic drug delivered.