This case series proof of concept study demonstrated that the use of PHIL as an embolization agent using the balloon occlusion microcatheter pressure cooker technique via the Scepter XC was technically feasible and was safe and efficacious in the treatment of the canine HAVMs.
In humans, liquid embolic agents are the preferred treatment for brain AVMs, with N-butyl cyanoacrylate and Onyx being used most frequently. (Vollherbst et al., 2017; Leyon et al., 2017) Onyx has also been successfully used for the treatment of peripheral and hepatic AVMs in dogs, highlighting that liquid embolic agents that are successful in human brain AVMs have similar benefits and outcomes in canine species. (Chanoit et al., 2007; Vollherbst et al., 2017; Culp et al., 2014)
New embolic agents have been investigated to improve the efficacy of AVM obliteration, intraprocedural handling and fluoroscopic visibility. An ideal embolic agent should provide permanent embolization and low chance of recanalization. The precipitation time of the embolic agent should be short and should have no toxigenic effects on the tissues. (Vollherbst et al., 2017) PHIL is a relatively new liquid embolic agent consisting of a non-adhesive copolymer (polylactide- co-glycolide and polyhydroxyethylmethacrylate) which is dissolved in dimethyl sulfoxide (DMSO), with triiodophenol as the iodine component. (Vollherbst et al., 2017) Studies where PHIL has been used in the treatment of brain AVMs in humans have shown promising results, with PHIL offering numerous advantages compared to other embolic agents. PHIL’s relative ease of use is highlighted by faster plug formation, good forward flow and less CT and MRI artefacts during follow up imaging compared to tantalum-containing materials such as Onyx. (Kocer et al., 2016). PHIL also takes up iodinated contrast to provide radio-opacity, leading to an increased capacity for target embolization. PHIL therefore overcomes the limitations of other liquid embolic materials, where there are more imaging artefacts and forward flow is difficult. (Leyon et al., 2017) PHIL is available in ready to use syringes and has a precipitation time of approximately 3 min, compared to Onyx which requires up to 20 min of preparation time and has a precipitation time of 5 min. Furthermore, PHIL is available in three concentrations: PHIL 25, 30 and 35, each increasing in viscosity and concentration, with the least viscous formulation being used for deeper penetration and more effective filling of the AVM nidus. (Vollherbst et al., 2017) The use of PHIL as an embolic agent has been shown to require less product to achieve the same occlusive effect as other embolic agents. (Vollherbst et al., 2017) Both PHIL and Onyx exhibit dose-related angiotoxic effects, however angionecrosis was shown to be absent in PHIL-filled vessels during the treatment of human brain AVMs, thus making it a potentially safer agent for a paediatric population. However, it has been shown that waiting times between injections had a considerable effect on the degree of embolization using PHIL, which may increase the likelihood of technical errors such as subtotal filling of the AVM due to premature embolization of the proximal AVM or distal off-target embolization during the procedure. (Vollherbst et al., 2017) As PHIL shows promise as a safe and effective embolic agent, further trials may be necessary to establish its use in the treatment of HAVMs in dogs and humans.
Although HAVMs in dogs and humans differ in terms of relative prevalence and the vessels involved, the overarching similarities in the vascular malformation allows translational experience for imaging and treatment modalities between the two species. HAVMs in humans and dogs are angiographically similar, with a network of arteries connecting to veins via a central nidus, suggesting that embolization techniques are likely to have similar results in both species. In dogs, the communication is between the hepatic artery and portal vein, whereas in humans, communication is typically between the hepatic artery and hepatic vein. (Raj, 2015) As PHIL has been successfully used in the treatment of cerebral and spinal arteriovenous fistulas in humans, its use may be extended to treating hepatic AVMs in the paediatric population. There are a lack of trials exploring the use of PHIL in the human paediatric population, with patients treated with PHIL for cerebral AVMs having a mean age of 58. (Leyon et al., 2017) However, given the dogs in this study are young and of small size, PHIL may potentially be a safe and effective agent for the endovascular embolization of HAVMs in the paediatric population, although the long-term outcomes of treatment with PHIL are yet to be explored.
The use of the Scepter XC DMSO-compatible dual lumen compliant balloon catheter in the peripheral circulation for the treatment of HAVMs is a novel application as it has previously only been described for use intracranial and cervical AVMs in humans. (Jagadeesan et al., 2013) Whilst other single-lumen balloon catheters require a balloon specific 0.010″ guide wire, the Scepter XC balloon catheter is compatible with a 0.014″ guide wire, which allows for easier navigation through tortuous arteries with a greater degree of steerability and trackability, allowing for better repositioning of the balloon catheter. The Scepter XC balloon catheter also has a soft distal tip that allows for steam shaping, allowing tortuous arteries to be tracked with greater precision whilst inhibiting blood reflux back into the balloon. (Rho et al., 2013) Because reflux of the embolic agent is avoided with the use of Scepter XC, the embolization of the AVM is improved and complications such as proximal branch occlusion or entrapment of the catheter is avoided. (Kin & Kong, 2017) Additionally, the use of Scepter XC does not show problems associated with the repeated inflation and deflation of the balloon. (Rho et al., 2013) Although a proximal Onyx plug is essential for many AVM embolizations, it is not required when the Scepter XC balloon is used which increases the efficacy of AVM occlusion allowing for high-pressure embolic injection in the “pressure cooker” technique. (Chapot et al., 2014) The principle of the pressure cooker technique is to create a plug to avoid backflow reflux and enable a more comprehensive, forceful and continuous injection of embolic agent through the AVM nidus vessels. Fluoroscopy and procedural times have also reported to be lower for embolization procedures using Scepter XC compared to conventional balloon catheters. (Jagadeesan et al., 2013)