Institutional review board approval was obtained for this study.
Patients, equipment and consent
Patients who were treated with bilateral PAE for symptomatic benign prostatic hyperplasia at a single institution during (approximately) a 1-year period, from October 2018 to November 2019, were retrospectively reviewed. Pre-procedural evaluation, inclusion and exclusion criteria were the same with previous work (Moschouris et al. 2019) and with other PAE studies (Pisco et al. 2016). To eliminate the effects of the learning curve, patients treated during the first 2 years of the local PAE practice (July 2016–September 2018) were excluded. Also excluded were cases of unilateral or failed PAE (n = 6 and n = 2, respectively) during the study period and procedures which were performed after November 2019, with newer equipment (Axiom Artis Zee, Siemens Healthineers, Erlangen, Germany, instead of Axiom Artis MP, Siemens, which was utilized for all the patients of this study).
Written informed consent was obtained from all patients prior to treatment.
Technique
Pre-procedural clinical and imaging evaluation was performed according to the institute’s standard protocol (Moschouris et al. 2019). Computed-Tomographic Angiography (CTA) was performed for treatment planning to all patients prior to PAE (Table 1 of supplementary material). The origin and course of the PAs was studied on axial CT slices and on Maximum Intensity Projections (MIPs) on coronal, sagittal and oblique sagittal planes. Anatomic landmarks that facilitated localization of the origin of PAs on anteroposterior MIP projections were noted, for subsequent correlation with anteroposterior pelvic digital subtraction angiography (DSA). For each pelvic side, the type of origin of PA was defined according to the classification system (Fig.1), proposed by de Assis et al. (2015). The diameter of the PA was measured at its origin. The tortuosity of the pelvic arteries was assessed and graded, using a practical categorization of a previous PAE study (Enderlein et al. 2020): Grade 1 (mild: kinking < 30 o in both pelvic sides), Grade 2 (moderate: maximum kinking 30 o- 60o in at least 1 pelvic side), and Grade 3 (severe: multiple kinking 30 o- 60 o in both sides and kinking of > 60o in at least 1 pelvic side). Angles were measured in coronal MIP images. Finally, in line with a previous report (Hacking et al. 2019), the diameter of the internal iliac arteries was visually assessed and atheromatous stenoses were classified as: Grade 0, 1, 2 and 3 (for no, mild, moderate and severe stenoses, respectively).
With the exception of patients with indwelling bladder catheter (IBC), PAE was performed without previous bladder catheterization. Vascular access was obtained via the right common femoral artery or left radial artery. The latter access (preceded by the Barbeau test and preferred when preprocedural CTA indicated severe tortuosity and/or significant stenoses of the external iliac and femoral arteries) entailed ultrasonographically guided cannulation of the radial artery 1–2 cm proximal to the radial styloid process and utilization of an appropriate introducer (Prelude radial sheath introducer, Merit Medical, South Jordan, UT, USA). The internal iliac arteries (IIAs) were catheterized with a 5 French (Fr.) angiographic catheter. In case of femoral access, 65–80 cm double angle or reverse curve catheters (Cobra1, Simmons 1, Contra 2 or Uterine Artery catheter, Merit Medical, or Boston Scientific, MA, USA,) were utilized for the ipsilateral IIA. If catheterization of the contralateral IIA could not be achieved with these catheters, they were exchanged for a hydrophilic one (Vertebral Glidecath, Terumo Corporation, Japan). In case of left radial access, an 125 cm Multipurpose or Vertebral catheter (Merit Medical) was utilized.
Anteroposterior DSA of the IIAs was performed with manual injection of 10-20 ml of contrast through the angiographic catheter. One or more of the following techniques were applied, in order to perform PAE with anteroposterior imaging only (AP-PAE): 1) Identification of the origin of PA on DSA and subsequent attempt for catheterization, usually with the aid of a roadmap. 2) Utilization of anatomic landmarks from the planning CTA, in order to approach the origin of the PA. 3) Distal advancement of the microcatheter/microguidewire or (preferably) advancement of the 5Fr. angiographic catheter over the hydrophilic guidewire in the anterior division of IIA, far from the origins of superior and inferior gluteals and closer to the expected PA origin. Anteroposterior angiograms performed from this distal position depicted the target vessels without superposition of the muscular (superior/inferior gluteal) branches and facilitated identification of the PA. 4) Gentle probing with microcatheter and microguidewire at the expected site of origin of the PA. A common combination was a microcatheter with angled tip (Direxion 2.4Fr, Bern shape, Boston Scientific) and a double-angled 0.016”microguidewire (Meister- Asahi Intecc co, Japan).
No more than 3–5 min of operation time and approximately 1 min of fluoroscopy per pelvic side were devoted to these attempts. If they proved fruitless, steep oblique DSAs were acquired (25-45o with additional caudal-cranial angulation 8-12o,taking into account the angle of oblique MIPs that optimized detection of PA origin), as per standard PAE technique (S-PAE).
Prostatic arteries were subsequently catheterized with the microcatheter and microguidewire; nitroglycerin (250 μg) was administered through the microcatheter for vasodilation and additional angiograms (only anteroposterior, in case of AP-PAE) were performed with manual injection of 2-4 ml of contrast through the microcatheter. Embolization was started at the (preferably distal) extraprostatic part of the PA, after advancement of the microcatheter beyond the potential origin of collateral branches to the bladder, rectum or penis. When complete flow stasis was observed, advancement of the microguidewire (followed by the microcatheter) into the intraprostatic branches was attempted (“PErFecTED” technique: “Proximal Embolization First, Then Embolize Distal”, Carnevale et al. 2014).PAE was performed with microspheres (Embozene- Boston Scientific, or Embosphere-Merit Medical) with diameters of 100–500 μm. Prerequisites for selection of smaller microspheres (Embozene 250, or Embosphere 100–300) were: i) Advancement of the microcatheter at the distal extraprostatic part of the PA, or into the prostate. ii) Absence of large intraprostatic anastomoses with penile or rectal branches. iii) Safe distance of the microcatheter tip from the origins of vesical, penile or rectal arteries. All other cases were treated with Embozene 400, or Embosphere 300–500 microspheres. Selection of the one manufacturer over the other depended on the material availability at the time of intervention.
For all PAE procedures the same angiographic protocol of the equipment (‘General DSA’) was selected. All DSA acquisitions were performed at 1frame/second (fr/s) and fluoroscopy at 7.5 fr/s. Additional exposure parameters are provided in Table 2 of supplementary material. A Cone-Beam Computed Tomography (CBCT) facility was not available during the study period. Intraprocedural contrast-enhanced ultrasonography (CEUS), with a second-generation echo enhancer (SonoVue, Bracco, Milan, Italy), with a portable unit (M8 Mindray, Nanshan, Shenzhen, China) was utilized to depict the area fed by the catheterized vessel and to evaluate the ischemic effect immediately post PAE (Moschouris et al. 2020). All procedures were performed by two interventional radiologists, each with 2 years of previous experience in PAE and more than 12 years in other pelvic embolization procedures. Postoperative care was similar to previous work (Moschouris et al. 2019). In case of transradial access, patients were discharged 5–6 h post PAE.
Evaluation of procedural parameters, efficacy and safety
After each PAE procedure, several parameters (fluoroscopy time, dose-area product-DAP, number of acquisitions with the respective C-arm projections, field size, irradiation parameters) were recorded by the angiographic unit and were extracted for analysis.
For the purposes of this study, a limited, short-term evaluation of imaging and clinical outcomes was performed. Transabdominal CEUS was performed in all patients 18–24 h post PAE to measure the extent of prostatic infarction. Transabdominal US was performed 3 months post PAE and changes (compared to baseline measurements) in prostate volume and post-void residual were recorded Further details on sonographic intra- and postprocedural monitoring of embolization are provided in Table 3 of supplementary material. The International Prostate Symptom Score (IPSS) was also calculated 3 months post PAE and compared with baseline. Clinical success was defined as an IPSS≤15 points with a decrease of at least 25% from the baseline and with no need for additional medical or surgical treatment post PAE. For patients with IBC, clinical success was defined as permanent catheter removal with spontaneous micturition and post void residual (PVR) < 100 ml. In these patients, trials of catheter removal were performed every week for the first month post PAE and every 2 weeks for the second month.
Comparisons and statistical analysis
Patients who underwent bilateral embolization, with AP-PAE of at least one pelvic side formed the AP-PAE group; patients who underwent bilateral embolization with standard technique (first with anteroposterior and then with oblique imaging of both pelvic sides) formed the S-PAE group. Descriptive statistics were calculated for quantitative and qualitative data for both groups. Differences in baseline characteristics, procedural, technical parameters and outcomes between the two groups were evaluated. Particularly for the S-PAE group, comparable anteroposterior and oblique angiographic runs (of the same anatomic area and with the same frame number and collimation) were identified and the respective DAPs were recorded. Several tests were used for comparisons, depending on the kind, sample size and distribution of each variable (t-test, Welch test, Mann-Whitney U test, Chi-Square test). Statistical significance was defined as a p value of < 0.05.