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Thursday, August 16, 2018

Fluorescence Imaging of MMP-2 Activity as a Biomarker of Vascular Remodeling in HD Access


Summary


In a recent article in press, researchers from the Penn Image-Guided Intervention Laboratory at the University of Pennsylvania have presented their findings exploring the capability of near-infrared fluorescence (NIRF) imaging for the detection of matrix metalloproteinase 2 (MMP-2) activity as a biomarker of vascular remodeling (VR) in AVFs in vivo. The manuscript reports that 10 AVFs were created in 10 Wistar rats with sham procedures in the contralateral groins. 4 weeks post creation, a fistulogram was performed in a subset of animals from the left common carotid to confirm stenosis. A MMP-2-activated NIRF probe was given and NIRF imaging performed in vivo and ex vivo on both AVF and sham-treated vessels to measure radiant efficiency (RE) of MMP-2-activated NIRF signal over background. Histologic analysis was also done to assess degree of VR by intimal thickening. When compared with sham-treated vessels, AVFs had a significantly higher percentage of RE over background. There was a significant correlation between MMP-2 activity as measured by relative increase in RE for AVFs and thickness of MMP-2 stained neointima. The authors conclude that NIRF imaging can detect MMP activity in remodeled AVFs compared with sham treatment and MMP-2 may be used as a biomarker of vascular remodeling underlying stenosis.




Figure. Ex vivo near-infrared imaging of MMP-2 activation. (a) Representative near-infrared fluorescence and photographic images of MMPSense activity in explanted fistulae and sham-treated vessels. (b) Bar graph illustrating a higher percent increase in radiant efficiency over background for patent AVFs compared with sham-treated vessels after intravenous injection of MMPSense 750. (c) Bar graph illustrating the higher percentage increase in radiant efficiency over background for AVFs compared with sham-treated vessels after intra-arterial injection of MMPSense 750. (d) Bar graph illustrating the significantly higher percentage increase in radiant efficiency over background for AVFs compared with sham-treated vessels after intra-arterial or intravenous injection of MMPSense 750 (**P = .0078). (e) Bar graph illustrating the fold increase in radiant efficiency over sham-treated vessels for rats injected with MMPSense 750 through intravenous or intra-arterial routes. (f) Bar graph illustrating the significantly higher percent increase in radiant efficiency over background for AVFs after intravenous compared with intra-arterial injection of MMPSense 750 (**P = .00357).


Commentary


Treatment of patients with dysfunctional AVFs and AVGs can be challenging. Primary patency is <70% at one-year and patients return frequently with new stenotic lesions. While AVFs and AVGs have been studied extensively, our ability to accurately predict in which patients a stenosis will occur, why they occur, and how best to prevent/treat them is far less than optimal. Previous research has evaluated the morphologic characteristics of lesions within the AV access circuit and we know in what regions lesions are most likely to occur. While useful, this does not allow us to anticipate a dysfunctional AVF/AVG and prevent the need for endovascular treatment. There are several limitations in the provided manuscript including using animals without CKD, lack of pre-AVF NIRF imaging, and using a single time point for evaluation. However, the study is noteworthy as it advances our understanding of the pathophysiology of dysfunctional AV access and identifies a number of factors that can influence cellular proliferation in neointimal hyperplasia. Identifying access circuits that may be at increased risk of developing access site dynsfunction will be impactful on this patient population.

Click here for abstract

Nadolski GJ, Hunt SJ, Weber CN, et al. Near-infrared fluorescence imaging of matrix metalloproteinase 2 activity as a biomarker of vascular remodeling in hemodialysis access. Article in press. DOI: https://doi.org/10.1016/j.jvir.2018.04.032

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

Monday, August 13, 2018

Use of the Gore Tigris Vascular Stent in Advanced Femoropopliteal Peripheral Arterial Disease


Summary


In a recent study from University of Siena, Italy, researchers published their experience on the new Tigris vascular stent (Gore) for complex femoropopliteal arterial disease. This is a self-expanding stent made of helically wound nitinol wire interconnected by an expanded poly- tetrafluorethylene (ePTFE) structure coated with bonded heparin. In this prospective study 31 patients with Rutherford stage 3 or greater and TASC type B or greater were included. The lesions were located in the common femoral, superficial femoral, popliteal arteries and a femoropopliteal bypass. There were 18 occlusions (58.1%) and 13 stenoses (41.9%). The mean diseased segment length was 15.5 ± 9.9 cm. Patients were treated with Tigris stent alone or in combination with the Viabahn stent (Gore). Technical success was 100% without complications. Primary patency rates at 6, 9, 12, and 15 months were, respectively, 100%, 90.5%, 88.9%, and 80%. Median postprocedural Rutherford stage was 1. Three occlusions occurred, leading to TLR of 9.7% and secondary patency of 100% at 15 months. Intrastent restenosis occurred in four cases (12.9%) without worsening symptoms. Lesion length was associated with re-occlusion (P < 0.003). No stent fractures were observed. The authors concluded that the Tigris stent alone or in combination with a Viabahn stent has an acceptable 12-month primary patency and low reintervention rate for femoropopliteal TASC B–D lesions.



Figure 3. An 83-year-old man with claudication (<100 mt) with TASC D popliteal (P1–P3) chronic occlusion. (a) Angiography demonstratcomplete occlusion of the P1–P3 segments, with hypertrophy of the geniculate vessel arising from the proximal edge of the occluded segment (asterisk). (b) Angiography performed with the knee (d) extended and (e) flexed demonstrate patency of the 5 _ 100 mm Tigris vascular stent. (c–f) 15-Month ultrasound follow-up. (c) Color Doppler examination confirms patency of the collateral geniculate vessel arising from the proximal edge of the stented segments (asterisk in a,c). (d–f) Color Doppler in-stent evaluation from proximal to distal demonstrates progressive increase of the peak systolic values until a ratio >2.0 is reached, indicating in-stent restenosis.

Commentary


Despite the fact that endovascular recanalization has become the first option in many cases of peripheral arterial disease, the femoropopliteal segment remains a challenging territory given its biomechanical properties. Therefore, technological advancements are welcome to help overcome the limitations of the current devices and improve clinical results. Over the years, new options have become available, including drug-eluting and interwoven stents. The Viabahn stent despite its great flexibility may lead to occlusion of collateral circulation, since it is a covered stent. The present study showed that this new Tigris stent (self-expanding non-covered) might be another valuable tool, especially for the distal SFA and popliteal artery, where accentuated “bending” forces are applied and many important collateral vessels are present.

Click here for abstract

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

Thursday, August 9, 2018

Radioembolization for Hepatocellular Carcinoma: A Nationwide 10-year experience 


Summary


This retrospective study evaluated the use and outcomes of Transarterial radioembolization (TARE) for HCC over the span of 10 years in the United States. The authors utilized the National Cancer Data base (NCDB) and identified patients between 2003-2012 with HCC that were treated with TARE. Patients that underwent resection or transplantation were removed; ultimately 1222 were included in this study. The authors evaluated demographics, insurance, socioeconomic status, tumor stage, tumor size, and hospital setting. Univariable and multivariable analyses were performed, and overall survival was estimated using log-rank test. The authors found that over the study period the number of HCC diagnoses and TARE treatments increased five times. Overall survival was 13.3 months, and did not change during the study period. Survival was not influenced by age or whether the procedure was done in an academic or community hospital, however female patients demonstrated improved survival, African American patients showed the lowest median survival, and patients with a higher socioeconomical and private insurance status trended towards improved survival. Survival was improved with tumors smaller than 5 cm, and decreased with increasing AJCC stage. Multivarite analyses showed that sex, tumor size, distance from hospital, insurance status and AJCC stage correlated with overall survival. In this cohort the median survival for patients with extrahepatic disease was 7.8 months, similar to the placebo group in the SHARP trial, therefore the authors suggest that the use of TARE in extrahepatic disease patients should be extensively discussed in a multidisciplinary manner before proceeding. Sex correlated with an improved prognosis however age was not a factor; therefore as long as elderly patients show a good functional status, outcomes will remain similar to their younger counter parts. After multivariate analyses African American patients showed a trend towards worse prognosis when compared to white patients. The authors found that this study is limited by the retrospective design, the use of the NCDB database, and the lack of cost analyses associated with TARE. Ultimately this study concluded that male sex, tumor size and extrahepatic HCC disease was associated with decreased overall survival after TARE treatment. However age alone, is not associated with a worse outcome.




Figure- Use of radioembolization in patients with HCC during the period 2003–2012.

Commentary


The findings of this study identify some prognostic factors that might influence the overall survival in HCC patients being treated with TARE. In the current environment where HCC can be treated with surgery, transplantation, catheter directed therapies (TAE, TACE, TARE), ablations, and systemic therapy, it is important to identify which patients will benefit the most from TARE therapy. The use of the NCDB database provides strength to this study since a large number of patients are included. Patients had various demographic characteristics, presented either to academic or community hospitals, possessed different types of insurance, belonged to different socioeconomic groups, and presented with different tumor sizes and tumor stages. Therefore this analysis evaluates many variables that are encountered in every day practice. The results in this study highlight that age of presentation is not as important as sex, AJCC stage, tumor size and insurance type. More studies are necessary to identify which HCC patients benefit the most from TARE treatment.

Click here for abstract

Tohme S, Bou Samra P, Kaltenmeier C, Chidi AP, Varley PR, Tsung A. Radioembolization for Hepatocellular Carcinoma: A Nationwide 10-Year Experience. J Vasc Interv Radiol. 2018; 29(7):912-919.

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

Monday, August 6, 2018

Biologic Drug Effect and Particulate Embolization of Drug-Eluting Stents versus Drug-Coated Balloons in Healthy Swine Femoropopliteal Arteries


Summary 


It has become clear that addition of antineoplastic drugs to intervention in peripheral vascular disease lesions has improved patency on all intervention platforms vs no drug. However, Drug coated Balloon (DCB) vs Drug eluting stent (DES) in femoro-popliteal artery remains an area of controversy with limited to non-existent robust direct head to head comparison studies.

Researchers recently published an animal study that contributes significant insight into this ongoing controversy. In their preclinical study in normal pig vessels they compared the biologic effects of POBA + DES vs DES + DCB vs DCB + BMS vs DCB alone in a direct head to head fashion. After 1 month, they measured local vessel histomorphometric parameters and objectively evaluated histologic changes in the downstream vessels for potential harmful effects of distal embolic paclitaxel. Angiographic diameter measurements were also performed.

The DES group demonstrated the best biological effect regardless of preceding POBA or DCB vs DCB + BMS or DCB alone. Of further significant note is that, downstream histological changes of damage from distal paclitaxel embolization were only seen in the limbs were a DCB had been utilized. No significant difference in luminal loss in all groups at 1 month.



Figure 1. Representative histologic images of the biologic responses to DCB + DES, PTA + DES, DCB + BMS, and DCB alone in swine iliofemoral arteries. Fibrin deposition in each treatment group is demonstrated in the middle panels, whereas depth of SMC loss is demonstrated with yellow arrows in the lower panels. Mild medial SMC loss with focal proteoglycan accumulation is observed in the DCB-alone group (a–c). Moderate medial SMC loss is observed in the DCB + BMS group, with minimal fibrin around stent struts (d–f). The greatest biologic drug effect is observed in the DCB + DES (g–i) and PTA + DES (j–l) groups in the form of extensive medial SMC loss and extensive fibrin around stent struts

Commentary


This animal study provides useful scientific concepts to assist in improving our understanding in addressing the current clinical conundrum of DCB vs stenting in lesions that otherwise have no mechanical issues causing flow limitations post intervention. The study findings suggest DES has superior biologic effects regardless of preceding PTA with POBA or DCB. Subgroup analysis of the study also suggests there is non-uniform biologic effects with DCB vs with DES.

We also learn from this study that DCBs appear to be the only ones associated with histologically significant downstream vessel damage/changes from paclitaxel distal embolization. Overall, the findings in principle appear to favor DES in terms of biological efficacy and potential histological side effects. It is also interesting to note in the same study that at 1 month there were no statistically significant differences in luminal change at angiography between all the groups studied. Although this is clearly a very short term follow up it raises the question about how significant these histological advantages may translate to meaningful clinical benefits or disadvantages in real world clinical patient scenarios.

With all these points in mind, the pragmatic appeal of treating a patient without having to leave a metal foreign body will require a lot more robust data and trials to move the dial in favor of DES in uncomplicated vascular lesions.

The study has several limitations, most of which are well acknowledged by the authors. I would add that the biological benefits of DES with regards to Smooth muscle Cell (SMC) loss may have been confounded and potentially overestimated by the natural SMC loss that occurs with stent centrifugal compression. Despite these limitations, the study moves the ball forward in helping our understanding of this controversial topic and perhaps sets up a good platform for robust true direct head to head clinical RCTs.

Click here for abstract

Torii S, Yahagi K, Mori H, et al. Biologic Drug Effect and Particulate Embolization of Drug-Eluting Stents versus Drug-Coated Balloons in Healthy Swine Femoropopliteal Arteries. J Vasc Interv Radiol. 2018; 29:1041-1049.

Post Author:
Rodrick C Zvavanjanja, MD, MSc, FRCR, DABR(VIR/DR)
Assistant Professor
Department of Diagnostic and Interventional Radiology
University of Texas at Houston McGovern Medical School
@RodZvavanjanja

Thursday, August 2, 2018

Long-Term Outcome of Portal Vein Stent Placement in Pediatric Liver Transplant Recipients: A Comparison with Balloon Angioplasty


Summary


Portal vein stenosis remains a significant cause of graft failure and postoperative morbidity in liver transplant recipients. In the case of pediatric liver transplants it is particularly important because these patients have much longer life expectancies and there are frequent size discrepancies between the donors and recipients. In this study the investigators retrospectively analyzed the cases of 50 patients with a median age of 14 months who underwent percutaneous transhepatic balloon angioplasty (n=12), transhepatic stent placement (n=18), or intraoperative transmesenteric (n=20) stent placement. For the evaluation of patency of angioplasty vs. stent placement, primary patency was defined as the lack of portal vein restenosis detected via ultrasound and/or CT. The authors also looked at procedural complications, functional stent stenosis, and stent fractures. Within these groups the 1-, 5-, and 10-year primary patency rates were 75% (angioplasty), 100% (transhepatic stent), and 85-90% (transmesenteric stent). Clinical success was seen in 8 out of 9 cases of angioplasty only, 16 out of 16 cases of transhepatic stent, and 20 out of 20 cases of transmesenteric stent placement. There were 3 recurrences seen with angioplasty only and with transmesenteric stent placement. There was only one major complication seen with transhepatic stent placement which was a portal vein tear during post-stent angioplasty. There were three major complications seen with transmesenteric stent placement which manifested as acute stent thrombosis. No major complications were seen with angioplasty only. The researchers ultimately concluded that there was no statistically significant difference between the three groups in terms of the long term primary patency rates and that angioplasty should be considered as the first line treatment for portal vein stenosis in pediatric liver transplant recipients.



Figure 4. An 11-month-old boy who underwent lateral-segment living donor liver transplantation and transmesenteric stent placement. (a) Venogram via the inferior mesenteric vein after end-to-end portal vein anastomosis shows near total occlusion of the main portal vein (arrow). (b) A self-expandable stent (8-mm diameter) was placed in the main portal vein, followed by balloon angioplasty (6-mm diameter). (c) Post-procedural fluoroscopy shows a remaining waist deformity (arrows) in the stent. (d) Coronal reconstructed computed tomography obtained 2 weeks after stent placement shows fully expanded stent with portal vein flow maintenance. (e) Doppler ultrasonography obtained 114 months after liver transplantation shows brisk portal vein flow.

Commentary


This paper emphasizes the importance of starting conservatively in treating portal vein stenosis following pediatric liver transplant. It also emphasizes the fact that regardless of method, these patients still require very close follow up and often require repeated angioplasty for re-stenosis early in life. While stenting in these patients is often inevitable, it does not come without risks and can even limit the ability to undergo future repeat liver transplant if needed. As with all things IR, every case poses unique challenges and there will likely be instances when using a stent as the first line treatment may be necessary. This article opens the door for future research, as there is currently no consensus on specific indications and timing of stent placement.

Click here for abstract

Shim D, Ko G, Sung K, Gwon D, Ko H. Long-Term Outcome of Portal Vein Stent Placement in Pediatric Liver Transplant Recipients: A Comparison with Balloon Angioplasty. J Vasc Interv Radiol. 2018; 29: 800-808.

Post Author:
Caleb L. Mills, MD PGY-4
Department of Radiology
Wake Forest Baptist Medical Center
@WakeForest_IR




Monday, July 30, 2018

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

Thursday, July 26, 2018

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