Safety and Efficacy of Peripheral Embolization with EASYX Liquid Embolic Agent: A Multicenter Prospective Study

Clinical question
Is EASYX, a new non-adhesive precipitating liquid embolic agent based on a polyvinyl alcohol ether polymer labeled with iodine molecules, safe and effective for peripheral embolization.

Take away point
EASYX is a novel copolymer liquid embolic agent that is safe and effective for peripheral embolization. The absence of tantalum allowed reduced CT artifacts on imaging follow-up, which was especially useful in patients with type II endoleaks.

Reference
Sapoval M., Vidal V., Dean C., Del Giudice C., Tradi F., Chevallier O., Charles-Nelson A., Pellerin O., Loffroy. Safety and Efficacy of Peripheral Embolization with EASYX Liquid Embolic Agent: A Multicenter Prospective Study. J Vasc Interv Radiol. 2021 Aug; 32 (8): 1136-1143

Click here for abstract

Study design
Prospective, observational analysis of embolization using EASYX on a range of indications including varicoceles, type II endoleaks, portal vein embolization before hepatectomy (PVE), acute arterial hemorrhage, and angiomyolipomas (AML).

Funding Source
The study was funded by a grant from Antia Therapeutics and Qmedics. The study was sponsored by Assistance Publique-Hôpitaux de Paris.

Setting
Academic setting. AP-HP - Hopital Europeen Georges-Pompidou Paris, France, Paris, Ile-de-France, France

Figure

Figure. Cone-beam computed tomography of the gonadal vein after previous coil embolization and re-embolization with EASYX. The gonadal vein was 100% occluded and because EASYX contains no tantalum, no beam artifacts were seen, comparing favorably to the artifact around the metallic coils that had been previously implanted.

Summary

EASYX liquid embolic is a new liquid embolic rendered radiopaque by iodine bound to the polymer backbone, thus minimizing beam-hardening artifacts on follow-up imaging associated with liquid embolics containing micronized tantalum as the radiopaque agent. Research of EASYX in a porcine model reported effective embolization without safety/technical issues; however, studies using humans have not been reported. The authors performed a multicenter, prospective, open label phase 2 study at 3 centers in France to assess the safety and efficacy of EASYX use in humans with a range of indications. A total of 8 interventional radiologists used the device for the study purpose, and embolization was performed according to the SIR guidelines for percutaneous transcatheter embolization for each indication. Statistical analysis used quantitative variables expressed as mean ± SD and range, and qualitative variables expressed as raw numbers (n) and proportion and percentages (%). Also, mean of variables before and after the procedure were compared using the paired Mann-Whitney U test.

The efficacy primary endpoint was the percentage of clinical success depending on the indication: target vessel occlusion (arterial hemorrhage), stability or reduction of the aneurysm maximal diameters on CT at 6 months compared to baseline (type II endoleak), growth of future liver remnant by >15% on presurgical CT compared with baseline (portal vein embolization), absence of reflux on ultrasound Doppler at 1 month (varicocele embolization), and >10% reduction of at least 1 diameter on MR or CT at 3 months compared with baseline (angiomyolipoma).

The primary safety endpoint was the expected and unexpected per-procedure serious adverse events related to the EASYX as adjudicated by an independent Critical Events Committee. A total of 3 major device related complications occurred in 2 patients:

• Non-target embolization in a patient with acute hemorrhage related to pseudoaneurysm in which distal coil protection was contraindicated due to a history of Ehlers-Danlos syndrome. 
• Non-target embolization and acute kidney failure in a patient referred for AML embolization which led to complete occlusion of the renal artery.

As for secondary endpoints, 6 patients died before the last study visit (6 months), all deaths adjudicated as the normal evolution of the index illness. The mean pain score was 0.5 ± 1.41 (range, 0–4) for type II endoleaks, 1.6 ± 2.59 (range, 0–8) for active bleeding, and 5.03 ± 2.11 (range, 2–8) for varicocele, assessed using a 0 to 10 visual analog scale in patients under local anesthesia. The satisfaction of the interventional radiologists was >90% for EASYX ease of use, ease of injection, cohesivity, and overall angiographic results.

There was reported operator dissatisfaction with fluoroscopic visibility compared to other ethylene vinyl alcohol-based agents; however, there was significantly less streak artifact on subsequent CT scans. Also, a higher rate of varicocele recurrence was reported, although no associated inflammatory responses were reported, as compared to sclerosants and coils. Overall, the above results demonstrate high user satisfaction and relatively low complications.

Commentary

The authors of this study describe EASYX as both safe and effective for embolization in human subjects for a variety of indications via positive primary and secondary endpoints. The heterogeneous nature of the procedures included introduces bias. Additional limitations include the small number of patients in some indications and short-term follow-up. However, the study provides support for a phase two study as EASYX was generally safe with few complications, easy to use, and effective for its indications. Future direct comparison of EASYX to standard embolics is necessary to establish its clinical value. Additionally, longer term follow-up and larger sample size in future studies will be needed.

Post Author
Colin Marshall, D.O.
PGY-3 Diagnostic Radiology Residency
University Hospitals Cleveland Medical Center
@colinradsIR

Edited and formatted by @NingchengLi

Embolization versus Surgery for Stabilized Patients with Solid Organ Injury

Clinical question
Compare the in-hospital survival after embolization versus laparotomy in hemodynamically unstable patients who responded to resuscitation and initial CT identified isolated solid organ injury.

Take away point
No significant difference was seen between in-hospital survival in those receiving embolization versus laparotomy.

Reference
Embolization versus Surgery for Stabilized Patients with Solid Organ Injury. Aoki, M.. et al. Journal of Vascular and Interventional Radiology, Volume 32, 1150-1155.

Click here for abstract

Study design
Retrospective cohort study from the Japan Trauma Data Bank between 2004-2018.

Funding Source
No funding

Setting
Multi-center.

Figure

Summary

Hemorrhage in the setting of trauma is often successfully managed surgically or with embolization depending on the clinical scenario and resources available. Currently, embolization is recommended for hemodynamically stable patients with solid organ injury, while surgical management is recommended for patients with hemodynamic instability. Those who respond to initial resuscitation may be appropriate for embolization. This study compares in-hospital survival following embolization versus laparotomy in hemodynamically unstable patients with solid organ injury who respond to initial resuscitation.

This is a retrospective cohort study performed in Japan between 2004-2018 using the Japan Trauma Data Bank. Patient selection included: patients over the age of 15, completion of abdominal CT, liver and/or splenic injury, sBP <90mm Hg and received a blood transfusion within 24 hours. Patient exclusion included: severe abdominal injury (AIS >3), except for splenic or liver injuries, AIS of 6, dead on arrival, administration of CPR and aortic cross-clamping. Patients were then divided into groups based on having received laparotomy or embolization (see figure above). The primary outcome was in-hospital survival. Secondary outcomes included, complications, length of hospital stay, percentage of patients discharged to home, and rate of splenectomy. Notable analysis technique included propensity score matching analyses, comparing the following models: original cohort (PSM1), cohort minus the penetrating mechanism (PSM2), and cohort adjusted by the time to transfusion and to treatment (PSM3).

Of the baseline characteristics, there were significant differences in sex, sBP, GCS and ISS in PSM 1 and 2, and GCS in PSM3. There was no significant difference between laparotomy and embolization in the 3 propensity score matching models regarding in-hospital mortality, liver injury, splenic injury, time to treatment or analyzed complications. Notable limitations include lack of information on which organ was embolized, their definition of hemodynamic instability and possible confounders not included in their PSM analysis. In addition, the authors note a high degree of access to CT scanners and a short time to embolization. This may be due to CT scan and embolization availability in many of the OR suites in Japan included in this study.

Commentary

Regardless of OIS scores, this study demonstrates no significant difference in in-hospital mortality between laparotomy and embolization in stabilized patients who had received a CT scan. This data helps underscore the utility of endovascular techniques in trauma, particularly those that may be deemed hemodynamically unstable. The authors define instability as a sBP <90 mm Hg and having received a blood transfusion. The American College of Surgeons defines hemodynamic instability “as global or regional perfusion that is not adequate to support normal organ function”. They also note that relying on sBP is not sufficient, due to multiple compensatory mechanisms that exist to prevent hypotension. Overall, hemodynamic instability is often a gestalt, which is challenging to define by objective numbers. Additionally, although there is high availability of CT scans in Japan, the inclusion criteria of having received a CT scan often suggests some element of stability.

The greatest challenge is the applicability of these findings in healthcare settings where access to CT may be limited or prompt endovascular treatment may be logistically challenging. In this study, patients had timely access to both imaging and endovascular treatment. Time to treatment is immensely important in trauma patients, therefore care should not be delayed to pursue an endovascular option. If the patients by definition are hemodynamically unstable, the facility should have access to hybrid operating rooms or the ability to rapidly transfer to surgical management. In the US, the majority of hospitals are not level 1 trauma centers, and are often able to surgically manage patients more quickly. In the correct clinical and healthcare setting, these findings demonstrate endovascular treatments are an appropriate treatment option in the unstable trauma patient. Future research noting specific organ embolization and treatment techniques may help establish protocols and help guide clinical decision making.

Post Author
Marissa Stumbras, MD
Interventional Radiology Resident, PGY3
Oregon Health & Science University
@MarissaStumbras

Edited and formatted by @NingchengLi

Catheter-Directed Hemorrhoidal Dearterialization Technique for the Management of Hemorrhoids: A Meta-Analysis of the Clinical Evidence

Clinical question
Is catheter-directed hemorrhoidal dearterialization (CDHD) a safe and effective treatment strategy for the management of hemorrhoidal bleeding?

Take away point
Preliminary evidence supports CDHD as an effective, safe treatment for grade I-III hemorrhoids and suggests embolization with a combination of coils and particles decreases rebleeding rates compared to coils alone.

Reference
Makris G,Thulasidasan N, Malietzis G, Kontovounisios C, Saibudeen A, Uberoi R, Diamantopoulos A, Sapoval M, Vidal V. Catheter-Directed Hemorrhoidal Dearterialization Technique for the Management of Hemorrhoids: A Meta-Analysis of the Clinical Evidence. J Vasc Interv Radiol. 2021;32(8):1119-1127. doi:10.1016/j.jvir.2020.03.548

Click here for abstract

Study design
Systematic review and meta-analysis.

Funding Source
No reported funding.

Setting
Studies selected from PubMed, Cochrane, and Scopus databases.

Figure

French bleeding score before and after rectal artery embolization.

Summary

Catheter-directed hemorrhoidal dearterialization (CDHD) for the treatment of hemorrhoidal bleeding is an emerging technique described in small studies and case reports as a minimally invasive alternative to surgical management. In an effort to evaluate the current evidence regarding the efficacy and safety of CDHD for rectal bleeding, the authors performed a systematic review and meta-analysis of 14 studies assessing CDHD.

Keyword searches via PubMed, Cochrane, and Scopus were performed to include clinical studies that evaluated patients with confirmed rectal bleeding secondary to hemorrhoids, treated patients with CDHD and reported clinical outcomes, and recruited five or more patients. Animal studies and case reports were excluded.

Data were extracted regarding study design, patient characteristics, disease burden, technique details, clinical follow up (including complications and symptom recurrence), and technical and clinical success rates. Statistical analyses were performed, primarily calculating and comparing means (range; standard deviation) via t tests.

A total of 14 studies met criteria (8 prospective, 6 retrospective) with a total of 362 patients. In all studies, the superior rectal artery (SRA) was embolized, most commonly using a combination of coils and other embolics (including particles, spheres, polyvinyl alcohol, gelatin sponge, and/or ethanol) versus coils alone.

There was no statistical difference among technical success rates, with an average of 97.8% (90-100%; 3.5%). Mean clinical success was 78.9% (66-96.9%; 10.6%). Four studies (n=98) reported bleeding score with a mean pre-embolization score of 6.78 (5.5-7.6; 0.90) and post-embolization score of 3.95 (2.8-5.0; 0.90) (p=.004). Average bleeding recurrence over the mean maximum follow-up of 12.1 months (1-28; 7.3), was 22.5% (5.4-44%). Of these, five studies (n=111) used coils alone for primarily grade II hemorrhoids with a mean rebleeding rate of 21.5% (0-44%; 18.2), one study used particles alone for primarily grade III hemorrhoids with a mean rebleeding rate of 29%, and four studies (n=108) used a combination of coils and particles for primarily grade III hemorrhoids with a mean rebleeding rate of 10.1% (5-15.7%; 4.8). Rebleed rates were statistically lower in the coils plus particles group compared to the coils alone group (p<.0001).

Reported major complications included one instance of IMA dissection that did not result in bowel ischemia, and one instance of puncture site arterial thrombosis and patient death.

Commentary

The authors perform a systematic review of 14 studies describing CDHD for the treatment of hemorrhoidal bleeding in a total of 362 patients. The aggregation of data in this meta-analysis offers more robust results compared to individual smaller studies, which more confidently supports the conclusion that CDHD is safe and effective in treating hemorrhoidal bleeding.

The authors discuss that there is a significant lack of comparative data between CDHD and surgery. Only one nonrandomized, non-blinded study attempted to directly compare stapled hemorrhoidectomy with coil and particle SRA embolization and reported significantly better pain and bleeding scores in the CDHD group (which included older patients with more comorbidities). They also discuss the lack of standardized technique, although highlight the statistically lower rebleed rates in studies that used a combination of coils and particles.

The mean follow-up period of 12.1 months likely underestimates the true complication and rebleeding rates. Additionally, publication bias against inconclusive or negative results and the absence of randomized, controlled trials introduce substantial confounds that may be amplified in subgroup analyses. Nonetheless, this meta-analysis is a valuable summarization of the existing primary data suggesting CDHD as a safe and effective treatment strategy for hemorrhoidal bleeding. Future studies should focus on direct comparison with surgical treatment to more confidently inform clinical decision-making.

Post Author
Catherine (Rin) Panick, MD
Resident Physician, Integrated Interventional Radiology
Dotter Interventional Institute
Oregon Health & Science University
@MdPanick

Edited and formatted by @NingchengLi