Nononcologic Embolization.

The scope of conditions managed by embolization, which was initially used for the treatment of hemorrhage and vascular malformations, is constantly expanding. Apart from oncologic indications, embolization is used to treat a wide range of benign pathology, including uterine fibroids and benign prostatic hyperplasia. While various particulate embolic agents are successfully used for benign embolization, there is growing evidence that unique properties of these may result in different outcomes. This article reviews available evidence comparing various particles used for uterine fibroid embolization and prostate artery embolization. In addition, we provide an overview of periprocedural pharmacology and protocols facilitating same-day discharge for these interventions.

embolization, uterine, prostate, benign, interventional radiology, postembolization syndrome, complication Nononcologic (benign) embolization is performed for a wide variety of medical conditions, from treating symptomatic benign disorders to stopping traumatic and nontraumatic hemorrhage. The most common indications for benign embolization include embolization of uterine arteries (uterine fibroids, adenomyosis), prostate arteries (benign prostatic hyperplasia), geniculate arteries (osteoarthritis), bronchial arteries (hemoptysis), renal arteries (angiomyolipoma), and vascular anomalies in various locations. Embolization can be performed with multiple materials and devices, including metallic coils, particulate embolic materials, liquid embolics, and sclerosants. Each embolic agent has unique characteristics, with strengths and weaknesses that dictate the clinical scenarios for which it is best fitted. This article provides an overview of microparticle embolic agents currently utilized for nononcologic embolization, followed by an overview of periprocedural pharmacology for uterine fibroid embolization (UFE) and prostate artery embolization (PAE). We also provide a comparison of UFE and PAE outcomes with various embolic agents and describe same-day discharge protocols for these interventions. Embolic Types Microparticles Embolization with microparticles is performed under fluoroscopic guidance. Angiography allows visualization of the vasculature to be embolized and helps guide selection of the appropriate embolic agent and a compatible microcatheter, if indicated. Multiple particle agents are available, and each product varies in composition, size, shape, and physical properties. These characteristics dictate the occlusive capacity of particles within blood vessels. Composition, compressibility, and elastic recovery are factors that influence particle distribution, from uniform to heterogeneous, and proximal to distal lodgment. Aggregation and particle cluster formation also influence the degree of occlusion. Depending on the desired long-term outcome, nonbiodegradable or temporary (biodegradable) agents can be utilized. A summary of currently available microparticle embolic agents is present in Table 1 . Other agents available for interventional oncology therapies, such as chemoembolization and radioembolization, as well as neurointerventions, are outside the scope of this review. Table 1. Microparticle embolic agents currently available. | Product | Supplier | Sizes (µm) | |---|---|---| | Nonspherical/irregular PVA | || | Contour PVA embolization particles | Boston Scientific (Marlborough, MA) | 45–150, 150–250, 250–355, 355–500, 500–710, 710–1,000, 1,000–1,180 | | PVA foam embolization particles | Cook Medical (Bloomington, IN) | 90–180, 180–300, 300–500, 500–710, 710–1,000, 1,000–14,000 | | Bearing nsPVA embolization particles | Merit Medical Systems (South Jordan, UT) | 45–150, 150–250, 250–355, 355–500, 500–710, 710–1,000, 1,000–1,180 | | PVA hydrogel microspheres | || | Bead Block | Boston Scientific (Marlborough, MA) | 100–300, 300–500, 500–700, 700–900, 900–1,200 | | Trisacryl gelatin microspheres | || | Embosphere | Merit Medical Systems (South Jordan, UT) | 50–100, 40–120, 100–300, 300–500, 500–700, 700–900, 900–1,200 | | Hydrogel microspheres with Polyzene-F coating | || | Embozene | Varian Medical Systems (Palo Alto, CA) | 40, 75, 100, 250, 400, 500, 700, 900, 1100, 1,300 (in 2-mL syringes) | | Polyethylene glycol microspheres | || | HydroPearl | Terumo Medical Corp (Somerset, NJ) | 75 ± 30; 200 ± 75; 400 ± 75; 600 ± 75; 800 ± 75; 1,100 ± 75 | Abbreviation: PVA, polyvinyl alcohol. Conventional (Nonspherical or Irregular) Polyvinyl Alcohol Particles Conventional, nonspherical or irregular, polyvinyl alcohol (PVA) is a nonbiodegradable agent and was the first type of PVA embolic available on the market. This product consists of PVA flakes with different shapes and sizes. When conventional PVA is infused within a blood vessel, the particles clump together and attach to the vascular endothelium. PVA aggregates create a scaffold for platelets and the coagulation cascade. Occlusion is achieved by mechanical obstruction as well as an inflammatory, foreign body–like reaction, which results in vascular thrombosis. Although it was originally thought that embolization with conventional PVA particles was permanent, it has been shown that neoangiogenesis, thrombus resorption, and luminal recanalization may occur, leading to tissue reperfusion. Compared with PVA microspheres and other available spheres, conventional PVA is less costly. The nonuniform size of individual PVA particles is a potential risk factor for undesired embolization; if smaller particles than expected are dislodged to more distal vessels, they may result in nontarget tissue infarction, while larger particles than expected can lead to a more proximal embolization and potential recanalization. Operator experience and postembolization angiography to evaluate the degree of occlusion with additional PVA particle administration, if necessary, can potentially prevent these undesired outcomes. Spherical Polyvinyl Alcohol Particles Spherical PVA particles theoretically address some of the disadvantages of irregular PVA as they are more uniform in size and possess a more regular surface. Spherical PVA particles are also less prone to aggregation and induce a milder inflammatory response. The compressibility and delayed elastic recovery of spherical PVA particles may lead to more distal embolization. Trisacryl Gelatin Microspheres Trisacryl gelatin microspheres (TAGM) consist of a trisacryl polymers embedded with gelatin that are tightly calibrated. As nonbiodegradable and nondeformable agents, TAGM microspheres exert their embolic effect via mechanical obstruction. These microspheres are hydrophilic and therefore are not prone to aggregation, favoring a more predictable embolization compared with PVA microspheres. TAGM microspheres are associated with minimal inflammation and vessel recanalization. Other Microspheres Hydrogel microspheres with Polyzene-F coating (Embozene) are nonbiodegradable agents and have been associated with very mild inflammatory and recanalization rates. These are tightly calibrated and available in limited sizes. Similarly, polyethylene glycol microspheres (HydroPearl) are hydrophilic, nonbiodegradable agents very precisely calibrated and available in narrow size ranges to promote a predictable and targeted embolization. Gelfoam Gelfoam is a water-insoluble, biodegradable gelatin sponge utilized as a hemostatic agent. Gelfoam provides structural support for thrombus formation by trapping platelets, inducing the clotting cascade and a foreign body–like reaction. Its occlusive effects are temporary, with gradual dissolution and recanalization of the treated vasculature within weeks to months. Therefore, it is most utilized to stop hemorrhage or obstruct blood flow to a hypervascular tumor prior to surgical resection. Another advantage to Gelfoam is its low cost compared with other embolic agents. Gelfoam is available as sheets, pre-cut cubes, or powder. The powder form, in particular, has a high risk of distal embolization and is no longer widely utilized. Prior to embolization, the mixture, also known as Gelfoam slurry, is prepared by mixing small pieces of Gelfoam with saline and contrast agent using a three-way stopcock. Gelfoam can also be used in pledget or torpedo-like form. Uterine Fibroid Embolization Basic Concepts UFE is a uterus-sparing therapy for uterine fibroids with similar symptom control and quality-of-life (QoL) improvements compared with hysterectomy/myomectomy, with shorter hospital stays and lower major complication rates. 1 2 The most common adverse event following UFE is moderate to severe pain, which may be attributed to fibroid ischemia and global transient uterine ischemia. Postembolization syndrome manifests as fatigue, low-grade fever, nausea, abdominal pain, and cramping. Therefore, the primary aim of periprocedural medications is to reduce the symptomatic effects of tissue ischemia and inflammation. Other aims include the control of nausea and constipation. In addition to nonsteroidal anti-inflammatory drugs (NSAIDs) and narcotics, other strategies that have been studied to reduce UFE-associated pain are preembolization intravenous (IV) dexamethasone, superior hypogastric nerve block, and postembolization uterine artery lidocaine administration. Single-dose dexamethasone IV 1 hour prior to the intervention has shown to be effective in reducing inflammation and pain during the first 24 hours post-UFE. Hypogastric nerve block, a technique whose details are outside the scope of this article, is considered a safe strategy to control post-UFE symptoms that has shown to reduce post-UFE pain and narcotic use, particularly in short-term follow-up. 3 A randomized controlled trial has shown that the administration of 1% lidocaine (100 mg) directly in the uterine arteries after embolization improves post-UFE pain and narcotic use. 4 Comparison of Embolic Agents for UFE Conventional PVA versus Spherical PVA Although spherical PVA was thought to have theoretical advantages over conventional PVA, the literature suggests better outcomes with irregular, nonspherical PVA. An animal study by Pelage et al examining the effects of comparable sized particles reported higher vessel occlusion and uterine necrosis with conventional PVA particles compared with spherical PVA. 5 Both products had superior necrosis rates with smaller particles compared with larger particles. 5 A prospective trial by Rasuli et al reported superior fibroid shrinkage and symptomatic improvement (menorrhagia, pressure sensation, and urinary frequency) in patients treated with conventional PVA. 6 Conventional PVA versus TAGM Studies have shown similar clinical outcomes in patients treated with conventional PVA versus TAGM. In a clinical trial from early 2000 by Spies et al, the treatment groups achieved similar fibroid necrosis rates, symptom severity scores, and QoL scores. 7 The authors also reported a significantly higher volume of embolic administration for complete occlusion in the TAGM cohort, while the PVA cohort had higher rates of microcatheter occlusion. 7 More recently, Han et al reported similar fibroid necrosis rates and symptom control between treatments, yet higher inflammatory responses, transient global uterine ischemia, and requirement for rescue analgesia in the conventional PVA group compared with TAGM. 8 Conventional PVA versus Hydrogel Microspheres The Particles Used in Uterine fibRoid Embolisation (PURE) study, a recent randomized controlled trial on conventional PVA versus hydrogel microspheres, reported a significantly higher rate of fibroid infarction on MRI at 6 months in the conventional PVA cohort (92.7 vs. 61.8%) yet similar symptom and QoL scores between treatment cohorts. 9 Spherical PVA versus TAGM An animal study by Laurent et al observed different patterns of deposition between spherical PVA and TAGM; spherical PVA had a greater deformation as well as more distal and heterogeneous distribution than TAGM. 10 Human studies evaluating the performance of spherical PVA for UFE have shown inferior results compared with TAGM. An initial trial by Spies et al evaluating the efficacy of spherical PVA and TAGM in 36 patients resulted in significantly inferior fibroid infarction and improvement in QoL scores in patients treated with spherical PVA. 11 In line with these findings, Siskin et al and Yu et al demonstrated higher degrees of fibroid infarction with TAGM versus spherical PVA. 12 13 In summary, spherical PVA is considered obsolete in UFE by most. Experienced operators now opt for conventional PVA or various non-PVA microspheres. Same-Day Discharge Protocol UFE has been historically performed as an inpatient procedure to manage postprocedural discomfort. However, many have found that patients may be eligible for a same-day discharge protocol without compromising pain management. In preparation for UFE, symptom control may be achieved with Tylenol 1 g IV, Decadron 10 mg IV, oral (PO) Flexeril 10 mg, and placement of a Scopolamine patch. Once the patient is in the interventional suite, antibiotics, Zofran 8 mg, and Benadryl 50 mg are administered IV. Following administration of moderate sedation, transfemoral or transradial access is gained. Embolization of the perifibroid plexus is generally achieved with particles ranging from 500 to 700 μm, avoiding smaller agents to prevent endometrial/myometrial infarction or inadvertent treatment of ovarian artery anastomoses. Toradol 30 mg IV is provided at the time of embolization to get ahead of the inflammation that will occur with embolization. After embolization, preservative-free 1% intra-arterial lidocaine is slowly infused within each uterine artery. 4 Patients are discharged home with scheduled Ibuprofen 600 mg PO three times per day for 4 days, scheduled Tylenol 650 mg PO three times per day for 4 days, Oxycodone 5 mg 1 to 2 tabs PO every 4 hours as needed, Zofran as needed, and Colace while a narcotic is being taken. Investigators are reviewing similar versions of this same-day discharge protocol for publication in the literature. As of yet it has shown an anecdotal ability for UFE experts to convert to same-day discharge. Prostate Artery Embolization Basic Concepts PAE has emerged as a safe and effective alternative treatment to gold-standard transurethral resection of the prostate (TURP) for patients with benign prostatic hyperplasia. Compared with TURP, PAE achieves similar improvements in symptom scores up to 24 months posttreatment, with shorter hospitalization stays and fewer adverse events. 14 Although PAE is frequently performed through femoral access, radial access is also common. Special medications used for the radial artery approach are outside the scope of this article. PAE pharmacology aims to prevent infection and potential periprocedural side effects related to inflammation and post-PAE syndrome (i.e., rectalgia, dysuria, constipation, fever). Antibiotic prophylaxis with an agent of choice based on local common organisms is recommended even in the absence of a history of urinary tract infections or positive cultures. Patients with increased risk of infection include those with advanced age, diabetes, previous urethral instrumentation, bacteriuria, renal stones, and chronic renal failure. To decrease the risk of anticipated symptoms, NSAIDs or antiemetics may be administered, and stool softeners prescribed short-term following the procedure. Worsening of previous urinary symptoms or post-PAE syndrome, characterized by urinary frequency, incomplete voiding, and dysuria, is a transient adverse side effect related to prostatic inflammation that may be managed with analgesics and NSAIDs. 15 These medications are also useful to minimize perineal, suprapubic, rectal, and testicular/scrotal pain. Comparison of Embolic Agents Conventional PVA versus Spherical PVA PVA microspheres have shown to result in similar or slightly improved results compared with irregular PVA. A large, single-center study by Bilhim et al reported no differences in clinical outcomes between treatment cohorts, even though the spherical PVA cohort had a significantly greater decrease in prostate volume, post-void residual, PSA level, and International Index of Erectile Function score. 16 Later, a small clinical study by Hwang et al demonstrated significantly higher reductions in total prostate and transition zone volumes in patients treated with spherical PVA. In addition, the spherical PVA cohort exhibited greater, although not statistically significant, improvements in International Prostate Symptom Score (IPSS), QoL scores, and peak urinary flow. 17 Conventional PVA Size Studies have aimed to define if particle size is associated with PAE outcomes. As smaller particles are theoretically capable of occluding more distal vessels, Wang et al aimed to evaluate if combining 50 µm + 100 µm PVA particles would lead to greater prostatic volume reduction and clinical improvement than 100 µm PVA particles alone. 18 The results of this randomized study showed similar rates of adverse events between groups, with significantly better improvements at 24 months in IPSS, QoL scores, peak urinary flow, post-void residual, and prostatic volume reduction, in the patients treated with 50 µm + 100 µm PVA particles. 18 In a prospective study, Bilhim et al compared the outcomes of patients treated with 100 versus 200 µm PVA particles, reporting a tendency for improved clinical outcomes in the 200µm PVA particle cohort. 19 TAGM Size Similarly, the use of small- and medium-sized microspheres has been studied to determine if a specific particle size is associated with better outcomes. A prospective study by Gonçalves et al compared patients treated with 100 to 300 µm TAGM versus 300 to 500 µm TAGM, finding similar clinical and imaging outcomes between groups, with a higher, yet not statistically significant, incidence of adverse events in the 100 to 300 µm cohort. In summary, there are mixed results and practices with regard to particle size for PAE. The tendency of experienced operators, per conversations with the authors of this article, is to utilize moderate-sized particles (e.g., 300–500 μm) to achieve solid clinical outcomes while avoiding adverse events that may be related to smaller particle size. Same-Day Discharge Protocol Prior to PAE, antibiotic prophylaxis is recommended as per institutional practice. Urinary catheterization may be performed to facilitate localization of the prostate and to avoid contrast buildup in the bladder, which may cause artifact and increased radiation dose during the procedure. Following administration of moderate sedation, transfemoral or transradial access is gained. Once the prostate arteries have been catheterized, nitroglycerin can be infused intra-arterially to prevent vasospasm of these small vessels prior to embolization. Preembolization angiography may reveal significant intraprostatic anastomoses with flow diversion to extraprostatic arteries. These anastomoses increase the risk of ischemic complications in surrounding anatomic structures such as the bladder, penis, and rectum. To avoid nontarget tissue embolization, flow can be redirected to the prostatic branches via occlusion of nontarget vessels using Gelfoam pledgets or microcoils. 20 21 22 Temporary redirection of blood flow can be achieved via pressure-enabled delivery devices or antireflux catheters. Intra-arterial verapamil (3–5 mg verapamil HCL, 0.5 mg/mL in normal saline) has also been shown to temporarily redirect blood flow in intraprostatic anastomoses and prevent ischemic complications. 23 Embolization of the prostatic arteries is performed with either small or medium particles, with literature suggesting 300 to 500 µm particles have equivalent results with decreased adverse events compared with 100 to 300 µm particles as discussed earlier. 24 Particle infusion is done slowly to avoid reflux and nontarget embolization. To control lower urinary tract symptoms and prevent procedure-related side effects, patients are discharged home with oral NSAIDs, analgesics, antibiotics, and stool softeners. An example of this regimen is ibuprofen for 5 days, phenazopyridine for 3 days, ciprofloxacin for 7 days, and docusate sodium for 5 days.

Endovascular therapy for benign medical conditions, including UFE and PAE, is gaining traction due to outcomes comparable to surgical procedures with favorable side-effect profiles. Understanding of characteristics and current evidence behind use of various embolic agents facilitates optimization of outcomes and improves confidence of choice. Same-day discharge protocols allow for improved patient satisfaction with reduced financial burden on health systems. Footnotes Conflict of Interest None declared.

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