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Thursday, October 11, 2018

Carotid Artery Stent Placement and Carotid Endarterectomy: A challenge for Urgent Treatment after Stroke-Early and 12-month outcomes in a Comprehensive Stroke Center 


Summary


The manuscript presents the results comparing the safety, efficacy and outcomes (short term and 12 month) of patients that presented to a single major stroke center with TIA or Stroke and underwent revascularization within 7 days either with carotid artery stenting (CAS) or carotid endarterectomy (CEA).

Patients were evaluated in the acute phase by a neurologist (not involved in the study) that presented the option of CAS or CEA to the patient or family member after the diagnostic work up had identified the extracranial ICA as the source of the stroke. Revascularization criteria included a carotid lesion on the relevant side with >70% stenosis or unstable plaque with 50-69% stenosis. 110 patients were included, 62 underwent CAS and 48 CEA.

Clinical outcomes evaluated included: type of event, stroke severity, disability (evaluated at 6 time points), periprocedural and postprocedural complications. Outcome measures evaluated new onset of stroke or vascular death, neurologic worsening, brain or systemic hemorrhagic complications, functional outcome, lesion restenosis, cardiac events, cognitive symptoms, and nerve lesions.

The authors found that CAS patients had more instances of CAD and intracranial stenosis, higher ESR, had a higher number of major stroke and were treated later when compared to the CEA group.

Incidences of all complications were similar between both groups. The severity of the event showed significant treatment effect that was related to the lower severity in CEA patients. Functional improvement, survival, stroke and vascular death at 12 months were all similar between both groups.

The need for early revascularization has been documented by the decreased risk of stroke or death (6% in treated patients vs. 18.8% in non-treated patients). The authors highlight that the patients included here are representative of the population that is being evaluated in emergency departments (high proportion of stroke vs TIA). The authors point out that even though stroke severity was higher at admission and at 1 month in the CAS group, functional changes were similar to CEA patients. While the 12 month survival was similar, worse outcomes were observed in the CAS group, which could be the result of confounding factors and not the CAS procedure.

The study has some limitations: small sample size, retrospective nature and the lack of standardization of the CEA procedure. In addition, newer techniques such as Transcarotid artery revascularization with flow reversal, might influence the safety of CAS particularly in patients with plaque in the aorta and aortic arch.

The authors mention that confounding factors might have been minimized since the patients were all evaluated at a single stroke center with experienced surgeons and interventionalists.

The authors conclude that CAS proved to be equivalent to CEA in the early revascularization of patients with TIA or acute ischemic stroke (including severe stroke).



Figure- NIHSS scores across time in both CEA and CAS patients. Significant treatment effect was driven by the lower severity in CEA patients. Both groups showed improvement over time.

Commentary


This retrospective study makes a compelling argument that CAS should be considered at least equivalent to CEA in the early revascularization of patients that have suffered a TIA or stroke. While historically CEA has been considered superior, newer techniques and more technical experience have made CAS safer and more effective than the results of previous studies. This study included patients with more severe stroke (when compared to prior published studies), and found that CAS and CEA had similar survival, functional outcome, secondary stroke prevention and complication results, despite the CAS group presenting with higher severity scores and more comorbidities. This study evaluated a consecutive group of patients that closely resemble patients that present at stroke centers, and found that in the hands of experienced surgeons and IRs, the complication rates and clinical outcomes are similar. Modern techniques and more extensive experience might prove to make CAS equivalent in this patient population, and further studies are needed to validate the promising results presented in this manuscript.

Click here for abstract

Rocco A, Sallustio F, Toschi N, Rizzato B, Legramante J, Ippoliti A, Marchetti AA, Pampana E, Gandini R, Diomedi M. Carotid Artery Stent Placement and Carotid Endarterectomy: A Challenge for Urgent Treatment after Stroke-Early and 12-Month Outcomes in a Comprehensive Stroke Center. J Vasc Interv Radiol. 2018 Sep;29(9):1254-1261.e2. doi: 10.1016/j.jvir.2018.03.025. Epub 2018 Jun 21. PubMed PMID: 29935838.

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

Monday, October 8, 2018

First-in-Man Experience with a Novel Catheter-Based Renal Denervation System of Ultrasonic Ablation in Patients with Resistant Hypertension


Summary


Hypertension that is resistant to medical management (including at least three antihypertensive medications, including an anti-diuretic) is termed resistant hypertension. Sympathetic control of blood pressure is noted to have significant effect on blood pressure, and since the attempts of sympathectomy many decades ago, it has been posited that denervating this system may be an effective treatment for the severe hypertension these patients suffer with. There was considerable promise for percutaneous renal artery denervation with radiofrequency (RF) energy in initial non-US trials approximately 10 years ago, however the final US randomized trial failed to show benefit of the procedure compared to sham interventions (Simplicity HTN-3). Since that time, there has been a reappearance of efforts to evaluate renal nerve denervation (RDN) with new modalities.

The authors of manuscript describe their experience with RDN using use a 6-French TIVUS (Cardiosonic Ltd, Tel Aviv, Israel) catheter, which is an ultrasound-based catheter that can be placed in the renal artery without use of balloon occlusion. This first in man technique study is a prospective, multicenter, non-randomized, open-label clinical study consisting of three cohorts: Severe Resistant Hypertension (>160mmHg systolic in non-diabetic, >150mmHg in diabetic), Moderate Resistant Hypertension (>140mmHg systolic in non-diabetic, >130 in diabetic), and Failed RF Therapy (>150mmHg systolic in diabetic, >140mmHg in diabetic). Selection of patients was based on Office based blood pressures at 2 visits and 2-week home pressure monitoring, followed by 24-hour ambulatory blood pressure monitoring. If these were consistent with resistant hypertension, patients underwent screening renal angiography to ensure anatomical suitability, and then ultimately had RDN with either Unidirectional or Multidirectional catheters. Patients were followed for 6 months in clinic, which was the endpoint based on the commercial sponsor limitations. A total of 39 patients were enrolled, 20 of which had isolated systolic hypertension, and the remainder with combined systolic and diastolic hypertension. Two patients had prior RF denervation, now with recurrence of resistant hypertension. The authors found a mean reduction (-30mmHg systolic and -14mmHg diastolic) in blood pressure over the course of 6-month follow-up. The subsets of patients with the highest BP reduction included diabetics, those with combined systolic and diastolic hypertension and the patients who underwent multidirectional catheter denervation. There were no major adverse events and 6-month ultrasounds were normal in all patients.



Commentary


Options for patients with primary resistant hypertension are limited, and although prior denervation-based treatments were derailed by the anticipated 2009 Simplicity-HTN3 trial’s failure to show benefit, the resurgence of multi-modality denervation studies are promising. This study demonstrated significant improvement in cohorts of patients, which can help future studies in patient selection. The limitation of only 6 months of study related follow-up was discussed by the authors, which needs more prolonged follow-up to ensure durability of the results. Additionally, although treatment benefit was shown in patients with recurrent disease despite prior denervation may be considered a source of bias, the finding that they responded could be considered a potential benefit that should be explored. Lack of this being a randomized, blinded study blinded is a limitation however this study alludes to safety and efficacy of this reiteration of RDN, providing a positive outlook for future trial development.

Click here for abstract

Chernin G, Szwarcfiter I, Scheinert D, Blessing E, Diehm N, Dens J, Walton A, Verheye S, Shetty S, Jonas M. First-in-Man Experience with a Novel Catheter-Based Renal Denervation System of Ultrasonic Ablation in Patients with Resistant Hypertension. J Vasc Interv Radiol 2018; 29:1158-1166.

Post Author:
Kumar Madassery, MD
Assistant Professor, Vascular & Interventional Radiology
Director, Advanced Vascular & Interventional Radiology Fellowship
Rush University Medical Center, Chicago IL
Rush Oak Park Hospital, Oak Park IL
Twitter: @kmadass, @vir_rush

Thursday, October 4, 2018

Comparison of Stable and Unstable Ethiodized Oil Emulsions for Transarterial Chemoembolization of Hepatocellular Carcinoma: Results of a Single-Center Double-Blind Prospective Randomized Controlled Trial


Summary


This is a prospective single-center double-blind randomized control trial evaluating the safety and efficacy of two embolic mixtures for conventional TACE, one with a stable water-in-oil mixture, and one with an unstable mixture. The study authors enrolled 812 patients over a 5-year period and were blinded to the type of chemoembolic administered in the setting of locoregional therapy for patients with hepatocellular carcinoma.

The embolic technique and type was the premise of this study. Thus, it should be noted that the stable water-in-oil mixture was 50 mg epirubicin / 50 mg lobapatin / 6 mg mitomycin C mixed with 4 mL of solvent (5:1 Iopamidol 300 contrast : Distilled water) and 12 mL ethiodized oil; the unstable water-in-oil mixture was identical except for having 4 mL of distilled water as the solvent (no contrast dilution). This mixture was emulsified for 10 minutes on a test-tube shaker at 1,000 rpm prior to administration.

Once enrolled, patients stayed within that treatment arm but were allowed to undergo additional treatments to include if needed repeat chemoembolization (type not specified by the authors). The study follow-up ended 12-months after enrollment of the last patient. The primary endpoint was overall survival, and the authors saw no significant difference between treatment arms. In addition no difference was observed in tumor response, time to progression, or adverse events. They did note a significant increase in myelosuppression in those patients who received the unstable water-in-oil chemoembolic.

The authors also evaluated the peripheral plasma concentration of epirubicin following TACE in a small subset of patients, finding the peak concentration to be higher in the unstable mixture but with a similar AUC. They also conducted in vitro analyses of solution stability for both epirubicin with solvent (5:1 contrast:water felt most stable and matched specific gravity of ethiodized oil) and epirubicin solution with ethiodized oil (1:3 most stable and uniform).



Commentary


This study is useful given its prospective nature and large size in comparing different techniques for use in conventional TACE. The authors found no significant difference in treatment effects between the two arms. However, they did note differences in myelosuppression and peak epirubicin plasma concentrations with the unstable solvent, suggesting that a more stable chemoembolization solution may help with keeping the drug local in the liver. The in vitro analyses they performed also suggest similar results. Limitations with this study are that it may be hard to duplicate the administered embolic in clinical practice given available medications and contrast agents at one’s institution. Also, the practicality of using a test-tube shaker to achieve a uniform solution may be difficult depending on the clinical scenario. At the very least, this study serves as a baseline for the putative ideal conventional TACE chemoembolic solution, with regard to stability and uniformity of embolics.

Click here for abstract

He, M., Zou, R., Wei, W., et al. Comparison of Stable and Unstable Ethiodized Oil Emulsions for Transarterial Chemoembolization of Hepatocellular Carcinoma: Results of a Single-Center Double-Blind Prospective Randomized Controlled Trial. J Vasc Interv Radiol. 2018; 29(8): 1068-1077.

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

Monday, October 1, 2018

Percutaneous Cryoablation of Solitary, Sporadic Renal Cell Carcinoma: Outcome Analysis Based on Clear-Cell versus Papillary Subtypes


Summary


With the increasing drive towards individualized cancer care it has become imperative that we understand variation in treatment response patterns to loco-regional therapies, based on the different tumor biology and subtypes.

Percutaneous renal ablation has proven to be a robust locoregional therapy for management of T1a renal tumors however very little is known about variation in oncologic response/benefits based on tumor subtypes. Researchers from Mayo clinic Rochester, Minnesota recently published a retrospective review/analysis of their outcomes of percutaneous renal cryoablation of T1a tumors based on clear cell vs papillary subtypes.

They reviewed 173 treated patients from a single center renal cancer registry with T1a tumors over a 13-year period. Three quarters of the patients had clear RCC and the rest papillary RCC – biopsies were performed prior to or during the cryoablation.

Recurrence rate was higher with cRCC (4 %) vs pRCC (0 %). The 5 yr progression free survival was higher with pRCC (100 %) vs cRCC (88 %). Clear cell RCC had a higher bleeding complication rate (5.2%) vs (0)%. Although none of these findings had statistically significant p values, the trend from these data is interesting.



Commentary


The paper asks a very pertinent question about variation of renal tumor response to minimally invasive percutaneous cryoablation. This is important in the era of personalized cancer care. By better understanding the variations in tumor response outcomes for T1a renal tumor we could potentially move towards personalizing the post cryoablation surveillance /follow up protocol based on the tumor type. Although this is promising and exciting, there remains a paucity of studies to address this issue, therefore further robust Level 1 studies are required before we can carve out clear evidence driven guidelines for personalizing the post treatment surveillance/follow up imaging.

The paper reaffirms that biopsy is the lynch pin of this new paradigm, therefore it is imperative to perform a biopsy of the renal masses especially as multiple studies including this current study now show a relatively low complication rate for renal mass biopsy. Whether it should be performed before treatment to guide therapy or during the ablation remains controversial. The authors provide their opinion on this matter in the paper.

There are several weakness’ in the paper which are acknowledged by the authors. The main weakness to highlight is that although they were interesting trends suggested by the data, none of the measure variables reached statistical significance. This is likely due the study being inadequately powered to demonstrate the statistical significance. Further pooled data and larger studies are required to address this.

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

Friday, September 28, 2018

Stent Extension below the Common Femoral Vein in Extensive Chronic Iliofemoral Venous Obstructions


Summary


The percutaneous endovascular treatment of post thrombotic syndrome can be challenging due to the presence of fibrotic venous obstructive lesions below the inguinal ligament. Stent placement below this level is not widely supported due to the fear that a stent in this location may negatively impact patency due to fractures or external compression. However, if iliocaval stenting is performed alone, there is a considerable risk of in-stent thrombosis due to poor inflow.

The authors of this retrospective review looked at 14 symptomatic patients with ultrasound (US) or magnetic resonance (MR) documented postthrombotic venous changes extending peripheral to the common femoral vein (CFV) who underwent primary stent placement peripheral to the femoral confluence. The deep femoral vein (DFV) was the target vein in all patients studied. Venous Clinical Severity Score was obtained before intervention for 13 patients (mean score 8.9 ± 4.4; range, 3–20). Venous Clinical Severity Score decreased significantly in the 13 patients evaluated (from mean score 8.9 ± 4.4; range, 3–20 to mean score 6.4 ± 3.5; range, 1–12; P 1⁄4 .03). There was a mean decrease of 5.7 points in the Villalta scale in these 13 patients before and after intervention with a mean score of 11.7 ± 4.3 (range, 5–20) before intervention and 6.0 ± 3.6 (range, 0–13) after intervention (P 1⁄4 .003). Venous claudication symptoms were present in 12 patients (92%) and it subsided in 8 of the patients, for an incidence of 38% (P 1⁄4 .016). A combined primary patency, assisted primary patency, and secondary patency of 92% was demonstrated with a median follow-up of 481 days (range, 411–792 d). During the entire follow-up period, 1 patient (7%) experienced stent occlusion.



Commentary


Postthrombotic syndrome is a debilitating disease process which in many cases does not respond well to conservative therapies. Open and hybrid surgical options have modest patency rates and high morbidity. Percutaneous techniques carry considerably less morbidity but may ultimately fail if there is fibrotic disease involving and peripheral to the CFV, a not uncommon scenario in these patients, and iliocaval stenting alone is performed. The data obtained from this study is important because it shows encouraging results for stent placement peripheral to the CFV. Furthermore, the results suggest that stent placement into the DFV can be a viable option if the FV has extensive chronic disease and the DFV is the dominant inflow vessel. Of course, more patients must be studied and randomized controlled trials performed, but the data presented here offers a promising percutaneous treatment algorithm for this difficult group of patients.

Click here for abstract

Van Vuuren T, Wittens C, de Graaf R. Stent Extension below the Common Femoral Vein in Extensive Chronic Iliofemoral Venous Obstructions. J Vasc Interv Radiol. 2018; 29: 1142-1147.

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

Monday, September 24, 2018

Iodine-125 Seed Strand Implantation in Combination with TACE for Treatment of HCC with Tumor Thrombus


Summary


A recent study from researchers in Shanghai, China published their findings on comparing Iodine-125 (I-125) seed strand implantation in conjunction with transarterial chemoembolization (TACE) versus TACE alone in treatment of patients with hepatocellular carcinoma (HCC) and tumor thrombus. This retrospective study included 76 patients (20 in the I-125 and TACE group, 56 in TACE alone group) with overall survival as the primary end-point. Inclusion criteria consisted of Childs-Pugh A and B patients with intrahepatic HCC single tumor > 5 cm or multiple tumors > 3 cm) with type II tumor thrombus (involvement of right or left portal vein but not main portal vein). TACE was performed with epirubicin and lipiodol. I-125 implantation was performed through a single, percutaneous portal venous access with deployment of the I-125 strand to span the portal vein tumor thrombus. The mean I-125 dose was 62.6 Gy. The authors demonstrated a longer overall survival in the I-125 seed strand implantation group (28.0 vs 8.7 months in a propensity score matched cohort, P = .001). Using modified Response Evaluation Criteria in Solid Tumors, intrahepatic disease control rate favored the combined therapy group (60% versus 28.6%, P = .012) while tumor thrombus disease control rate was significantly improved in the combination therapy group (90% vs 33.9%, p < .001). There were no serious adverse events. Of note, the combined therapy group also received more additional TACE treatments during the follow up period. The authors conclude that combined treatment of HCC with portal vein tumor thrombus with TACE and I-125 seed strand is safe and effective.



Figure 2. (a) The 125I seed strand prepared for implantation. (b) Portography of a 65-year-old man shows filling defects in the right portal vein (arrows). (c) The 125I seed strand is located at the target position (arrow) and delivered through the 5-F sheath. (d) The 5-F sheath is removed and the transhepatic puncture track is occluded with the use of 3 3 coils (arrow). (e) Hepatic angiography (arrows) is immediately performed after the 125I seed strand implantation.

Commentary


This paper evolves the limited prior research on usage of Iodine-125 seed implantation for treatment/control of tumoral thrombus in patients with HCC. The reported outcomes, specifically overall survival and disease control rates, are exciting and intriguing. Portal vein tumoral thrombus is an important diagnostic finding, limiting treatment options and purporting poor prognosis. Limitations of this study include the retrospective nature, small sample size (19 patients ultimately in the propensity-score matched analysis), homogeneous population (Chinese study, hepatitis B), and disparate number of future TACE procedures. Technical success rate and procedure duration may prove inhibiting in other patient populations. How this compares to other treatments directed at treating/controlling portal vein tumoral thrombus, such as radioembolization and SBRT, would be interesting for future research. Percutaneous implantation of I-125 seed strand could prove to be another weapon in our armamentarium against HCC. Ultimately, further research is required to determine if/where this falls in the treatment paradigm for HCC.

Zhang, ZH, Zhang W, Gu JY, et al. Treatment of Hepatocellular Carcinoma with Tumor Thrombus with the Use of Iodine-125 Seed Strand Implantation and Transarterial Chemoembolization: A Propensity-Score Analysis. J Vasc Interv Radiol. 2018; 29: 1085-1093.

Post Author:
David M Mauro, MD
Assistant Professor
Department of Radiology
Vascular and Interventional Radiology
University of North Carolina
@DavidMauroMD

Friday, September 21, 2018

Multicenter Phase II Clinical Trial of Sorafenib Combined with Transarterial Chemoembolization for Advanced Stage Hepatocellular Carcinomas (Barcelona Clinic Liver Cancer Stage C): STAB Study


Summary


A phase II non randomized open label multicenter study designed to evaluate the efficacy and safety of combining Sorafinib with conventional Trans arterial chemoembolization (TACE) in patients with Barcelona Clinic Liver Cancer Stage C hepatocellular cancer(HCC) is described in this paper. Primary end point was completion rate of the treatment protocol defined as 2 months of treatment with Sorafinib after TACE. Secondary end points of the study included objective response rate, disease control rate, overall survival, progression free survival and incidence of adverse effects. Sorafinib 400 mg daily was administered after 4 weeks of lobar/segmental/sub segmental conventional TACE with lipoidol combined with any of the following 5 drugs: epirubicin, doxorubicin, cisplatin, miraplatin, mitomycin C. Dose interruptions and reductions were allowed when drug toxicity developed. 32 patients were enrolled, 1 was excluded as tumor was cholangiohepatoma and not HCC. All 31 patients were followed for a year or until death. 28 (90.3%) patients completed the protocol, 1 refused treatment with Sorafinb, 2 dropped out due to intolerance/ drug toxicity. Median number of TACE were 2, Sorafinib interruptions was required in 77.4% and dose reduction in 67.7%. Complete, partial response, stable disease and progressive disease were noted in 9.7,67.7,12.9 and 9.7% respectively using the mRECIST criteria. Objective response rate was 77.4% and disease control rate was 90.3%. Median overall survival and progression free survival were 17.3 months and 5.4 months respectively. Tumor response rate by mRECIST (P=0.42) and serum AFP(P=0.01) were the only significant prognostic factors that affected survival in multivariate analysis. The most common grade 3 or 4 AEs were increased AST (54.8% 17/31), increased ALT (45.2%, 14/31), hypertension (22.6%, 7/31), thrombocytopenia(19.4%, 6/31), increased amylase (9.7%, 3/31), and hand-foot syndrome (9.7%; 3 of 31) during the entire period of combination therapy. 


Fig 1 Kaplan Meier curve showing overall survival of patients included in the study

Commentary

This was a much needed study evaluating combination therapy in advanced disease. While the primary end point was achieved in over 90%, the tolerability of Sorafinib after TACE was variable with only 9.7% of the patient sticking to the original dosage regime.

Subgroup analysis of the SHARP and Asia-Pacific trials showed a median overall survival of 5.6-9.7 months in advanced stage HCC with Sorafinib monotherapy. The present study demonstrates an overall survival of 17.3 months compared to these trials. However, it should be noted that SHARP and Asia-Pacific trials were much larger trials with a more advanced patient population and more advanced BCLC stage than the presented study. The authors attribute the improved survival to patient selection and exclusion of patients with first order portal vein thrombosis. Similar studies comparing overall survival for TACE plus Sorafinib versus TACE alone and Sofafinib alone have shown benefit of combination therapy (7-11 months vs 4.9-6.0 months vs 5.9 months). These findings are concordant to the results of this study and highlight the benefit of combination therapy in Child A population with BCLC C disease. 


Sato Y, Nishiofuku H, Yasumoto T, et al. Multicenter Phase II Clinical Trial of Sorafenib Combined with Transarterial Chemoembolization for Advanced Stage Hepatocellular Carcinomas (Barcelona Clinic Liver Cancer Stage C): STAB Study. J Vasc Interv Radiol 2018; 29:1061-7. 

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