Systematic Review of the Safety and Efficacy of Irreversible Electroporation

Summary

This article serves as a comprehensive review of the clinical application of irreversible electroporation (IRE) in the use of ablation of solid tumors of the liver, pancreas, kidney, and lung. A relatively novel treatment, the premise of IRE is its ability to induce cell death through non-thermal electrical disruption of the cell membrane while preserving the extracellular matrix. The putative advantage of this therapy is its ability to allow for ablations close to vital structures such as the biliary and portal venous systems without causing them damage. The authors consolidated all in-human published reports of the use of IRE in solid tumors, resulting, after exclusion, in 16 studies made up of 221 patients and 325 treated tumors. The vast majority of these treatments were those in the liver (n = 129) and pancreas (n = 69). There were a total of 43 (22%) likely IRE-related complications, of which 28 (64%) were mild/moderate complications (Grade I/II). It should be noted that of the 129 liver IRE procedures, only 6 reported damage to a portal triad structure. Due to the strong electric pulses used in IRE, the authors also reported cardiac arrhythmia rates and uncontrolled muscle contractions, finding an incidence of 4% and 0%, respectively. More benign atrial arrhythmias were observed when using a synchronized machine, and muscle paralytic was routinely administered. Efficacy data was most robust in the hepatic ablations, with a total of 106 patients and 185 tumors treated (median size 1-3 cm). Primary efficacy was reported as 67-100% over follow-up periods ranging from 3-18 months. The authors conclude that the available level of evidence for IRE is low, although it appears safe and relatively effective on smaller lesions.



Table 3. Efficacy of Hepatic IRE demonstrates overall primary efficacy ranging from 67-100% across a number of primary and metastatic liver lesions.

Commentary

This paper reviews a relatively new and unique technique to allow for a potentially curative therapy for patients who previously would not be offered such. This review is limited by the data which the reviewers had available to consolidate. The safety and efficacy profiles seem encouraging based on the available studies. However, there is a significant gap in the quality and quantity of the more traditional RF and microwave ablation data. The theory behind altered cell membrane permeability in the use of ablation has been well studied in the pre-clinical setting, and it does seem to have effectiveness in clinical practice. However, the complication rate is not trivial, and implementing IRE in practice requires careful planning from the operator to the anesthesia team. The fact that this therapy could become a primary curative treatment in some settings for central liver lesions as well as pancreatic lesions is encouraging. Future directions are promising with ten active studies investigating IRE.

Click here for abstract

Scheffer HJ, Nielsen K, de Jong, MC, et al. Irreversible Electroporation for Nonthermal Tumor Ablation in the Clinical Setting: A Systematic Review of Safety and Efficacy. J Vasc Interv Radiol. 2014; 25: 997-1011.

Post Author:
Daniel P. Sheeran, MD
Assistant Professor
Department of Radiology and Medical Imaging
Section of Vascular and Interventional Radiology
University of Virginia

Transabdominal Direct Sac Puncture Embolization of Type II Endoleaks after Endovascular Abdominal Aortic Aneurysm Repair

Summary

Researchers from the University of Toronto are reporting the experience with type II endoleak repair via a transabdominal direct sac puncture. This is a retrospective review of 30 patients. Inclusion criteria included the presence of safe, unobstructed access from the anterior abdominal wall to the perfused part of the sac, without needing to traverse organs or major intervening arterial structures. Patients without unobstructed access, and patients with isolated IMA endoleak without lumbar artery contribution, were excluded from the study. The authors used US-guidance to access the sac to avoid bowel and adjacent organs/vessels. An 18-gauge trocar needle was used with placement of a hemostatic valve at the hub following sac access. A 2.4 F microcatheter was then placed through the needle and used to select feeding vessels, if able. In treated patients, embolization materials included cyanoacrylate glue (45.5%), glue/coils (36.4%), and Onyx with or without glue/coils (18.1%). Technical success was defined as complete endoleak embolization on fluoro. The primary outcome was freedom from sac growth defined as ≤ 5% sac growth on CT or ≤ 5mm change in sac diameter on US. The team reported a technical success rate in 97% of patients with mean follow-up of 15.5 months. Freedom from sac growth was seen in 85.2% of patients. Complications were seen in only 3 of 33 procedures and included 1 nontarget embolization with transient neuropraxia and 2 self-limiting rectus sheath hematomas. The authors concluded that percutaneous transabdominal embolization is a safe and efficacious treatment for type II endoleak, with a short procedure time.



Fig 1
Ultrasound (a) with Doppler demonstrates an area of endoflow (arrow) in the posterior right of the aneurysm sac, which was (b) subsequently targeted, and a needle was advanced into it under ultrasound guidance, with the needle tip (arrow) positioned within the posterior aspect.



Fig 2
Fluoroscopic image demonstrates (a) a patent IMA (arrow), which was (b) subsequently coil embolized at sac origin to protect the IMA from nontarget embolization (arrow). In addition, a feeding right lumbar artery (arrowhead) and the aneurysm sac (asterisk) were embolized.

Commentary

This manuscript is noteworthy as it effectively shows that transabdominal direct sac puncture can be a safe and effective method for treatment of type II endoleaks. For anyone that is fortunate (or unfortunate) enough to treat type II endoleaks, they will understand well the challenge of treating endoleaks that lack a defined IMA source. Transarterial access into the culprit lumbar vessel(s) is always challenging and often impossible. Further, it is often difficult to prospectively identify patients that will be adequate candidates for a transarterial approach. The present study provides a convincing argument for incorporating transabdominal direct sac access into the treatment algorithm. This approach may not be suitable in all patients secondary to body habitus and need for continuous compression for bowel displacement at time of ultrasound-guided access. However, with a noteworthy 85% freedom from sac growth, it is worth considering in patients with a lumbar source of type II endoleak.

Click here for abstract

Zener R, Oreopoulos G, Beecroft R, Rajan DK, Jaskolka J, Tan KT. Transabdominal direct sac puncture embolization of type II endoleaks after endovascular abdominal aortic aneurysm repair. J Vasc Interv Radiol. 2018; 29: 1167-1173.

Post Author:
Luke R. Wilkins, MD
Assistant Professor
Department of Radiology and Medical Imaging
Section of Vascular and Interventional Radiology
University of Virginia
@LukeWilkins_UVA

Endovascular Removal of Fractured Inferior Vena Cava Filter Fragments: 5-Year Registry Data with Prospective Outcomes on Retained Fragments

Summary

This is a recent review of IVC filter fragment removal from Stanford University by Kuo and his collegues. The study included 82 patients as part of a prospective registry. The investigators reviewed outcomes of residual fragment removal after the main filter was removed. They included fragments that were intravascular per pre-procedure CT, procedural cone beam CT and/or intravascular US. 185 filter fragments were identified excluding the ones lodged in distal pulmonary artery. Eighty-seven of 185 fragments (47%) were deemed amenable to attempted removal: 65 IVC, 11 PA, 8 cardiac, 2 hepatic, and 1 aortic. Authors successfully removed 78 of 87 fragments (89.7%). There were 6 minor complications and 1 major complication (a cardiac tamponade that was successfully treated). Nineteen patients with retained cardiopulmonary fragments, 81% remained asymptomatic during long-term clinical follow-up of 845 days. Authors concluded that percutaneous removal of filter fragments had high technical success rate and low complication rate, except when fragments are intracardiac. Most residual fragments not amenable for retrieval remained asymptomatic and followed clinically.



Figure 3. Images from a 41-year-old patient who presented for complex retrieval of an indwelling Bard Recovery filter (2,505 d). (a,b) Axial and coronal CT images show multifocal filter penetration, with one component penetrating into the aorta (arrows) and fractured within the lumen. (c,d) Spot image of the filter and subsequent cavogram show the extracaval component (arrows). (e) Following main filter body removal, an aortogram also confirms fragment location within the aortic lumen (arrow). (f–h) Fluoroscopic images show successful percutaneous fragment removal via transfemoral arterial access.

Commentary

The paper represents outcomes of attempted and retained filter fragments at a high volume clinically oriented academic interventional radiology practice with a dedicated IVC filter clinic. Of note senior author Dr. Kuo has described first in man utilization of laser for IVC filter removal. IVC filter removal has become an increasing trend during the past 5-10 years fueled by associated law suits related to fracture and migration of filters and broken fragments. As many of us witness commonly, it is not uncommon for existing commercial filters to have broken fragments that migrate into different locations in venous system as well as to extra-venous locations. Unfortunately, there is very limited data on potential complications related to those fragments. This is the first article reviewing a large cohort of filter fragment retrieval. Authors demonstrated that most of intravascular components (confirmed by imaging) can be removed using various techniques at a highly specialized center, but at the same time there were no significant clinical negative outcomes among the filter fragments that were left behind.

After review of this manuscript and through personal experience I would recommend retrieval of intravascular fragments especially if they have the risk for eventual migration to the heart. Intracardiac fragments carry higher risk of complication during retrieval but they also pose higher risk of complications when left alone (cardiac tamponade, arrhythmias, etc). Again, when feasible with cardiac surgery support these fragments should be managed at experienced centers. Low risk fragments can be monitored with imaging and confirm stability. Thanks to the authors for providing guidance in this difficult topic.

Click here for abstract

Andrew J. Kesselman, MD, Nam Sao Hoang, BA, Alexander Y. Sheu, MD, and William T. Kuo, MD Endovascular Removal of Fractured Inferior Vena Cava Filter Fragments: 5-Year Registry Data with Prospective Outcomes on Retained Fragments J Vasc Interv Radiol. 2018 Jun;29(6):758-764. doi: 10.1016/j.jvir.2018.01.786. Epub 2018 Apr 26.

Post Author:
Bulent Arslan, MD, FSIR
Associate Professor and Associate Chair of Radiology
Division Director, Vascular and Interventional Radiology
Department of Radiology and Nuclear Medicine
Rush University Medical Center
Chicago, IL
@arslanmd

Quantification of combined effects of transarterial embolization and microwave ablation 

Summary

Combining percutaneous ablation and transarterial embolization for treatment of tumors, including hepatocellular carcinoma (HCC), has been of interest for some time. Although each are effective as monotherapy, improved oncologic outcomes can theoretically be achieved when combining the therapies, especially if the tumor is large or infiltrative. It stands to reason that if the cooling effect from hepatic arterial blood flow can be decreased by first performing an arterial embolization, then ablation efficacy can be improved.

Researchers from Mayo Clinic in Rochester and University of Wisconsin-Madison recently published their results quantifying the effect of embolization on microwave ablation (MW) in an in vivo porcine liver model. They studied the effects of combined MW ablation and embolization in 6 swine. Hepatic artery catheterization was performed in each animal and embolization of 2 of the 4 liver lobes was performed using 100-300 um trisacryl gelatin microspheres. MW ablations were then done in an open manner within each liver lobe immediately after embolization using a 2.45-GHz system and single 17- gauge antenna. They performed cone-beam CT at short intervals during ablation to evaluate gas formation. Diameter, length, area and circularity of ablation zones were measured on gross tissue sections and microscopic and histologic evaluation of both embolized and nonembolized tissue sections performed. They found that the embolization/MW ablation zones had a significantly greater area (mean ± standard deviation, 11.8 cm2 ± 2.5), length (4.8 cm ± 0.5), and diameter (3.1 cm ± 0.6) compared with MW ablation alone (7.1 cm2 ± 1.9, 3.7 cm ± 0.6, 2.4 cm ± 0.3, respectively). CT showed faster and greater gas formation around the antennae in the embolized lobes. Both groups showed a central charred zone and a peripheral zone of noncharred coagulated tissue. However, only the MW group showed a hemorrhagic zone beyond the noncharred coagulated zone. It was this noncharred zone that was responsible for the larger size of the ablation zone in the embolization/MW ablation group (1.3 cm ± 0.4 vs 0.8 cm ± 0.2).



Figure. Gross pathologic specimens demonstrate increased size of the embolization/MW ablation zone (a) compared with MW ablation only (b). The increased size of the ablation zone was predominantly the result of a wider peripheral noncharred coagulative zone (asterisks). The charred central portion (triangles) was not significantly different between the groups (P 1⁄4 .2611).

Commentary

While other studies have shown the clinical benefits of combining transarterial embolization with ablation, the effects have not been well quantified. This study is a step towards gaining an understanding of how combining these therapies influences the ablation zone-embolizing first can be theorized to promote coagulation in tissue that otherwise may not be affected due to persistent arterial flow-and hopefully, ultimately, allowing one to predict the enhanced ablation zone when this technique is utilized. Of course, more studies are necessary to determine whether combination therapy has the same effect on the ablation zone in tumoral, cirrhotic livers and also whether chemoembolization makes a difference.

Click here for abstract

Knavel EM, Green CM, Gendron-Fitzpatrick A, Brace CL, Laeseke PF. Combination Therapies: Quantifying the Effects of Transarterial Embolization on Microwave Ablation Zones. Journal of vascular and interventional radiology : JVIR. 2018;29:1050-1056.

Post Author
Zagum Bhatti, MD
Assistant Professor
Department of Radiology, Interventional Radiology Division
University of Texas Health Science Center at Houston, Houston, TX
@UTHouston_IR
@ZagumBhatti

JVIR EDITORS’ RESEARCH HIGHLIGHTS

Randomized Controlled Trial Comparing Radiologic Pigtail-Retained Gastrostomy and Radiologic Mushroom-Retained Gastrostomy” Kichang Han et al. Volume 28, Issue 12 (December 2017)

• Prospective randomized controlled trial compared 14-F pigtail-retained gastrostomy (PG; 50 patients) and 20-F mushroom-retained gastrostomy (MG; 49 patients) (level of evidence 1b).
• Technical success rate was 100% for both groups.
• Minor complication rate was higher in the PG group (34%) than in the MG group (12.2%; P = .016) owing to higher rates of tube occlusion (16% vs 0%) or dislodgment (4% vs 0%) and peristomal leakage (6% vs 2%).
• Major complication rate was 2% in the PG group and 0% in the MG group (P > .05).

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A Comparison of Concomitant Tributary Laser Ablation and Foam Sclerotherapy in Patients Undergoing Truncal Endovenous Laser Ablation for Lower Lime Varicose Veins 

Summary

A prospective non randomized controlled study comparing the efficacy and safety of simultaneous tributary vein ablation with either Foam Sclerotherapy (FS) or Endovenous Laser ablation(EVLA) while performing EVLA of the greater saphenous vein was conducted. 418 patients were enrolled (CEAP score between 2 and 6), 163 underwent tributary vein EVLA at 8 Watts while 255 underwent FS with 3% Polidoconol using the Tessari technique. Outcomes were measured at 3 days, 4 weeks and 6 months using the Aberdeen Varicose Vein Questionnaire(AVVQ), EuroQol Group 5(EQ-5D) and Numerical rating scale for pain. At 4 weeks and 6 months respectively, the EVLA group exhibited poorer QoL than the FS group (P<0.001 for AVVQ ;P<0.01 for EQ-5D) and (P<0.5 for AVVQ; P<0.05 for EQ-5D). At 6 months the FS group had lower (4.9%) visible varicosities than the EVLA group (21.6%). FS group reported significantly higher post procedural pain only at 4 weeks (P<0.001. Persistent ecchymosis, pigmentation and local induration were significantly higher in the FS group at both 4 weeks and 6 months (9.3%vs 6.2%). The authors concluded that concomitant tributary ablation with FS during truncal laser ablation of the GSV is more efficacious and improves Qol compared to EVLA.

Commentary

This paper evaluates the utility of concomitant treatment of tributary veins using 2 different techniques. Advantage of simultaneously treating tributary varicosities include lesser cost and reduced need for a second procedure. Simultaneous treatment is associate with longer procedure time and post-procedure discomfort. Supported by recent randomized studies favoring simultaneous treatment, the National Institute for Health and Care Excellence has set simultaneous tributary vein treatment as the standard of care. Phlebectomy is more invasive than EVLA and FS. Based on the paper, the treatment of choice for tributary veins appears to be FS.

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Wang JC, Li Y, Li GY, et al. A Comparison of Concomitant Tributary Laser Ablation and Foam Sclerotherapy in Patients Undergoing Truncal Endovenous Laser Ablation for Lower Limb Varicose Veins. J Vasc Interv Radiol 2018; 29:781-9.

Post Author:
Anil K Pillai, MD
Associate Professor and Section Chief,
University of Texas Health Science Center, Houston, TX 77030
Anil Pillai@AnkupiMD

Vaccum-Assisted Thrombectomy in AVF and AVG

Summary

This prospective study included 35 patients with acutely thrombosed AVF and AVG that underwent Thrombectomy using the Indigo device. The study sought out to evaluate if the Indigo system would be safe, effective, decrease procedure time and complications. No patient was excluded during the study period. The authors used systemic heparin (no TPA), obtained antegrade and retrograde access to treat the thrombus, with adjunctive use of angioplasty and or stents for stenosis, occlusion balloon for thrombus in the arterial anastomosis and Trerotola device for adherent thrombus in an aneurysmal segment. The authors evaluated technical and clinical success, primary patency, primary assisted patency, and secondary patency, procedure time, blood loss and complications. Technical success was 34 out of 35 patients, with clinical success in 32 out of 35 patients. Three complications were not attributed to the device. As expected 93% of patients required angioplasty, 2 patients stent grafts, 1 patient required Trerotola device and 2 patients occlusion balloon. Average procedure time was 38 minutes, average blood loss was 122 mL, 6 month primary patency, primary assisted patency and secondary patency was 71%, 80% and 88.5%. The results of this study demonstrate high technical and clinical success, comparable or better to other studies published. Average procedure time (38 minutes) was also improved when compared to Angiojet (78 minutes), mechanical thrombolysis (126 minutes). Similarly patency rates compare favorably compared to other systems such as Angiojet, Trerotola, etc. Changes in hemoglobin were not seen in 17 patients that had hemoglobin levels checked after the procedure. The biggest limitation is the small number of patients, lack of cost analysis and lack of control group for comparison. The authors conclude that the indigo system is safe and effective with promising patency rates and procedural times when compared to other systems or techniques.

Figure- Representative fistulogram demonstrates the initial injection with thrombus in the graft (A), fistulagram after antegrade thrombectomy but before angioplasty of the stenotic lesion (B), fistulagram after thrombectomy and angioplasty of the lesion (C), fistulagram from the brachial artery showing thrombus in the arterial end (D), and final fistulagram after retrograde thrombectomy.

Commentary

This study provides promising data regarding the use of the Indigo system for the treatment of thrombosed dialysis access. With low procedural times, high patency rates at 6 months and low complications rates, this system has the potential to replace other systems. The authors required the use of adjunctive systems in 3 separate cases, and as expected angioplasty was required in the majority of the cases to threat the underlying lesions. The biggest limitation in this study was the lack of cost analysis and lack of control group. Future studies that compare the indigo system against other systems (mechanical thrombectomy, Angiojet, Trerotola, etc) and provides a cost analysis will elucidate if the Indigo system can become a first line system in the treatment of thrombosed dialysis access.

Click here for abstract

Marcelin C, D'Souza S, Le Bras Y, Petitpierre F, Grenier N, van den Berg JC, Huasen B. Mechanical Thrombectomy in Acute Thrombosis of Dialysis Arteriovenous Fistulae and Grafts Using a Vacuum-Assisted Thrombectomy Catheter: A Multicenter Study. J Vasc Interv Radiol. 2018 Jul;29(7):993-997.

Post Author: 
Carlos J. Guevara, MD
Assistant Professor
Department of Radiology, Interventional Radiology Division
University of Texas Health Sciences, Houston
@UTHouston_IR

Contralateral DVT after Iliac Vein Stent Placement in May-Thurner Syndrome: location, location, location... 

Summary

Investigators from Inha University Hospital in the Republic of Korea published their analysis on the incidence and potential causes of contralateral deep vein thrombosis (DVT) after common iliac vein (CIV) stenting in patient with May-Thurner syndrome (MTS). Retrospective analysis included 111 patients (women: 73%). Median follow-up was 36 months. Stent location was determined by venogram and classified as extended to the inferior vena cava (IVC), covered the confluence, or confined to the iliac vein. The relationship between stent location and contralateral DVT was analyzed. Potential causes of contralateral DVT were presumed based on venographic findings. Ten patients exhibited contralateral DVT at a median timing of 40 months (9%). Potential causes were venous intimal hyperplasia (VIH) in the distal IVC (n=7), “jailing” of the contralateral CIV (n=2), and indeterminate (n 1⁄4 1). All patients with VIH had previous CIV stents overextended to the IVC. Overextension of CIV stent was associated with contralateral DVT (P < .001). The authors concluded that contralateral DVT after CIV stenting has a relatively high incidence, and overextension of the stent to the IVC wall is associated with contralateral DVT, having VIH as a potential cause.



Fig.1: Categorization of left iliac vein stent position on venogram: (a) extended to the IVC, (b) covered the confluence, and (c) confined to the ipsilateral iliac vein. Arrows indicate tips of stents. Asterisks indicate the confluence. (d) A diagram illustrating the 3 categories of iliac vein stent: 1) overextension, 2) complete confluence coverage, and 3) without confluence involvement.

Commentary

This study helps in understanding the incidence and potential associated factors for contralateral DVT after CIV stenting in patients with MTS. Endovascular stent insertion has been recognized as the treatment of choice for venous outflow obstruction given its safety and effectiveness. Appropriate stent placement is critical for satisfactory long term results, and this study suggests that overextension of the stent into IVC to ensure complete coverage of the lesion may not go unpunished. At the same time research provides plausible explanation for the increased incidence of contralateral DVT. First, persistent insult of the distal IVC wall by the stent struts, leading to VIH. Second, “jailing” of the contralateral CIV disrupting normal blood outflow. On the other hand, not extending the stent into the IVC may prevent complete coverage of the stenotic lesion, causing recurrent ipsilateral symptoms. It would be interesting to see a comparison of freedom from target lesion recanalization (FLR) between those 3 groups with different stent position. Nonetheless, the study highlights the importance of appropriate stent placement. Utilization of additional imaging guidance such as intravascular ultrasound should be common practice, and industry must continue to improve device design to ensure better biocompatibility and precise deployment.

Click here for abstract

Le TB, Lee TK, Park KM, Jeon YS, Hong KC, Cho SG. Contralateral Deep Vein Thrombosis after Iliac Vein Stent Placement in Patients with May-Thurner Syndrome. J Vasc Interv Radiol. 2018 Jun;29(6):774-780.

Post Author:
Ricardo Yamada, MD
Assistant Professor
Department of Radiology
Division of Vascular and Interventional Radiology
Medical University of South Carolina