and active (Silber 1998; Meyerson et al. 2002; Tron et al. 2002; Dauerman et al. 2007). Passive closure devices assist or enhance manual compression and do not provide immediate (<5 min) hemostasis (Dauerman et al. 2007). Examples of passive closure devices (devices enhancing manual compression) include patches, wire‐stimulated track thrombosis, and pneumatic pressure devices (Nader et al. 2002; Applegate et al. 2007; Dauerman et al. 2007; Doyle et al. 2007; Jensen et al. 2008). Over the last decade, active closure devices have been used more commonly as compared to passive closure devices (Dauerman et al. 2007). Active closure devices include collagen‐based devices that may or may not have an anchor or suture included, suture alone devices, and staple/clip devices (Dauerman et al. 2007). Further development of active closure devices is being pursued, and it remains to be seen if these devices gain universal acceptance among those performing arteriotomy for IR procedures.
Vascular Occlusion Agents and Devices
To perform vascular occlusion via IO methods, a thorough understanding of the occlusive agents is mandatory. Two broad categories, based on the positioning of the agents in the vessels exist: those delivered into the vessel and carried passively to a target vessel (particles and liquids) and those that are positioned at the site where occlusion is needed (coils and balloons) (Kunstlinger et al. 1981; Ginat et al. 2009; Loffroy et al. 2009). The agent chosen depends on the goal of the procedure, and multiple agents may be indicated and used in the same patient.
Particles
Collagen sponges, conventional polyvinyl alcohol (PVA), and microspheres are the most commonly used particles (Loffroy et al. 2009). Collagen sponge particles are used for temporary occlusion (Abada and Golzarian 2007). Most studies suggest that recanalization occurs within 14 days (Abada and Golzarian 2007; Loffroy et al. 2009); however, one study found that 78% of cases were recanalized at 3 days (Louail et al. 2006). These sponges likely perform occlusion through physical effects and by enhancing thrombus formation (Abada and Golzarian 2007; Loffroy et al. 2009).
Conventional or nonspherical PVA particles are available in multiple sizes. These particles cause mechanical occlusion, and the subsequent blood stasis results in biological occlusion (Loffroy et al. 2009). Nonspherical PVA particles have an irregular shape and may aggregate, resulting in a more proximal occlusion; for instance, a third‐order vessel branch may be occluded when a fourth‐order branch occlusion is desired (Siskin et al. 2000; Loffroy et al. 2009). Nonspherical PVA particles are considered permanent vascular occlusion agents (Siskin et al. 2000; Patel and Soulen 2006); however, some reports have described recanalization of vessels that have been occluded with these particles (Siskin et al. 2000; Loffroy et al. 2009).
The majority of microspheres that are commercially available are made of trisacryl gelatin, PVA, or sodium acrylate/vinyl alcohol copolymer (Patel and Soulen 2006; Loffroy et al. 2009). Microspheres are available in 100–300 μm, 300–500 μm, 500–700 μm, 700–900 μm, and 900–1200 μm (Laurent 2007). Microspheres have several advantages over nonspherical PVA particles. Microspheres can be calibrated (developed with a predetermined size) and tend to reduce blood flow more quickly and reliably than nonspherical PVA (Laurent 2007; Loffroy et al. 2009). Nonspherical PVA particles can have variable behavior after discharge from a catheter, making the placement of these particles less predictable than microspheres (Laurent 2007). Another advantage of microspheres as compared to nonspherical PVA is that they do not result in catheter blockage as they do not aggregate prematurely (Loffroy et al. 2009).
Improvements in microsphere technology have allowed for even more sophisticated IO techniques. Microspheres with drug‐eluting capabilities are available and allow for delivery of high‐dose chemotherapy directly to a tumor, with minimal systemic effects (Liapi et al. 2007; Martin et al. 2009). Some of the drugs that have been incorporated into microspheres include doxorubicin, oxaliplatin, and irinotecan (Liapi et al. 2007; Kettenbach et al. 2008; Martin et al. 2009).
Further advancements in microsphere production include the use of microspheres that can be detected on MRIs and CTs and microspheres that can be resorbed in a controlled manner (Laurent 2007). Being able to visualize the location of a microsphere with CT and MRI allows the clinician to determine the final location of the microspheres and the subsequent tumor response based on that location. Resorption of the microsphere may allow these particles to be used for temporary occlusion.
Liquids
Several liquid agents are available for use in vascular occlusion including biological glues (such as cyanoacrylate), sclerosing agents, and gelling solutions (Loffroy et al. 2009). Liquids are not commonly used in the vascular occlusion of tumors. Cyanoacrylate embolizes very quickly upon contact with blood and endothelium (Greenfield 1980; Loewe et al. 2002; Patel and Soulen 2006). In cases of hepatocellular carcinoma that have been deemed nonresectable, glue has been used as an embolic agent (Loewe et al. 2002; Rand et al. 2005). Additionally, humans with liver or biliary neoplasia are sometimes treated by glue embolization of a portal vein branch preoperatively; this induces hypertrophy of the remaining liver (Nagino et al. 1995; de Baere et al. 2010). This hypertrophy of normal tissue may prevent liver failure after resection of the primary tumor (Nagino et al. 1995; de Baere et al. 2010). Sclerosing agents such as ethanol are used for embolotherapy. These agents cause necrosis of the blood vessel wall, and the resulting protein denaturation that occurs results in thrombus formation. Disadvantages of ethanol usage are the associated toxicities such as skin lesions, peripheral nerve palsy, renal failure, thrombophlebitis, lack of radiopacity, and postoperative pain (Wojtowycz 1990b; Valji 2006; Loffroy et al. 2009). In humans, ethanol has been successfully used in several reports for the embolization of renal neoplasia (Wojtowycz 1990b; Munro et al. 2003; Schwartz et al. 2006; Maxwell et al. 2007; Ginat et al. 2009). Gelling solutions consist of a polymer in a solvent, and the commercially available form is PVA copolymer in dimethylsulfoxide (Loffroy et al. 2009). These solutions have been used for treating arteriovenous malformations and endoleaks (persistent aneurysmal sac perfusion after endovascular repair); however, further investigation is necessary to elucidate the role of these agents in the treatment of neoplastic disease (Ginat et al. 2009; Lv et al. 2009; Stiefel et al. 2009; Nevala et al. 2010).
Coils
Coils are the most commonly used mechanical embolization device. Most coils are constructed from stainless steel, platinum, or nitinol; threads are often attached to increase thrombogenic potential (Lustberg and Pollak 2006; Valji 2006; Ginat et al. 2009). Coils can be made in a variety of shapes and sizes and are often delivered from a 5 French angiography catheter or 3 French microcatheter (Wojtowycz 1990b; Lustberg and Pollak 2006). A coil should be properly sized to the vessel that is being embolized. A coil that is too large may not fully “coil” and as a result protrude into a feeding vessel (Wojtowycz 1990b). A coil that is too small can migrate distally or proximally, leading to embolization of the wrong vessel (Valji 2006). Coils are generally used in the embolization of nononcologic diseases such as arteriovenous fistulas and traumatic bleeds; however, reports of coils for the preoperative embolization or definitive treatment of renal, biliary, and hepatic neoplasia exist (Madoff et al. 2003; Munro et al. 2003; Schwartz et al. 2006; Maxwell et al. 2007). Indications for renal embolization may include preoperative infarction, treatment of metastatic renal neoplasia, nonresectable renal neoplasia, and patients who elect not to undergo radical excision (Munro et al. 2003; Schwartz et al. 2006; Maxwell et al. 2007).
Balloons
Balloons can be used for vascular occlusion in both a temporary (nondetachable) and a permanent (detachable) fashion. Temporary occlusion or partial occlusion with a nondetachable balloon may be beneficial when delivering particulate embolic agents (Greenfield et al. 1978). The balloon can be used to decrease the rate of blood flow to prevent unwanted occlusion at a distal site (Greenfield et al. 1978). The use of detachable balloons as a permanent vascular occlusion device has fallen out of favor, as newer permanent vascular occlusion agents have developed (Lustberg and Pollak 2006).
Stents
Vascular and nonvascular stents have revolutionized