From the SIR Residents and Fellows Section (SIRRFS)

Teaching Topic: Outcomes of Ultrasound–Guided Thrombin Injection of Nongroin Arterial Pseudoaneurysms

Valesano JC, Schmitz JJ, Kurup AN, Schmit GD, Moynagh MR, Atwell TD, Lewis BD, Lee RA, Callstrom MR. J Vasc Interv Radiol. 2017 Jun 1. pii: S1051-0443(17)30477-3. doi: 10.1016/j.jvir.2017.05.003. [Epub ahead of print]

Link to Abstract

Arterial pseudoaneurysms are among of the most frequently encountered complications of interventional vascular procedures. Pseudoaneurysms are contained pulsatile hematomas that arise from arterial puncture sites that fail to fully seal. Historically, pseudoaneurysms required surgical vessel closure, though now ultrasound-guided thrombin injection has now become the mainstay first-line treatment. The safety and efficacy of ultrasound-guided thrombin injection for femoral pseudoaneurysms has been well established in large trials and systematic reviews. [1] However, despite the increasing popularity of upper extremity endovascular access, reports of non-groin pseudoaneurysms treatment are limited.

In this study, Valesano et al. at the Mayo Clinic retrospectively review 39 cases of thrombin injection treatment for non-groin pseudoaneurysms. Of these 29 were in the upper extremity and 20 of those were of the brachial artery. Thirty-six were iatrogenic of nature and 22 of those were from arterial access. They report a 100% success rate in achieving zero Doppler flow immediately after thrombin injection and an 84.8% success rate in sustained thrombosis at 1-3 days after treatment

Clinical Pearls

Though there are many techniques, what are the general steps in ultrasound guided thrombin injection?

The authors describe their technique as follows:

1. Obtain baseline arterial duplex US imaging and Dopper waveforms of both the pseudoaneurysms and the origin artery proximal and distal to the site.

2. Evaluate pulses with ultrasound or palpation. Additionally, assess the relevant baseline sensorimotor function.

3. Using sterile technique and 1% lidocaine for anesthesia, advance a 20-25 gauge needle under ultrasound visualization until the tip of the needle is in the pseudoaneurysm sac.

4. Incrementally inject small aliquots of about 100 IU of 1000 IU/1 mL recombinant topical thrombin (The Medicines Company, Parsippany, New Jersey).

5. With intermittent Doppler imaging, monitor the pseudoaneurysm during injection until complete elimination of Doppler signal.

6. Reassess proximal and distal artery with US, pulses, and sensorimotor symptoms.

7. Follow-up imaging with duplex and Doppler US is recommended one day after the procedure.

What are the characteristics of pseudoaneurysms at higher risk of treatment failure?

It is difficult to draw conclusions from the small number of treatment failures from this series, however it appeared that the neck size was more predictive than the total size. The average size of pseudoaneurysms that remained successfully thrombosed at follow up were larger at 2.3cm +/- 1.6, while the average size for treatment failures were 2.0cm +/- 0.7. The neck diameter for treatment failures averaged 2.6 mm +/- 0.5 and 2.1 mm +/- 0.8 for treatment successes. Because of the small sample size, these results trended towards, but did not show statistical significance. Of the treatment failures, three were successfully treated with one retreatment, and the other two were successfully treated after two retreatments.

Questions to Consider

Though the authors reported no complications, what are the potential complications of this procedure?

In the small previous reports, there have been two incidents of brachial artery thrombosis. In 2014, Garvin et al reported 14 cases of treatment with thrombin in the upper extremities. [2] In one of these cases, brachial artery thrombosis was identified by decreased Doppler amplitude distal to the pseudoaneurysm fifteen minutes after treatment. Emergent surgical revascularization was performed. Kang et al reported 5 upper extremity treatments in 2000. [3] In one case, the neck of the pseudoaneurysm persisted after initial thrombin injection, and after a small amount was injected into the residual neck, the patient began to experience symptoms of hand ischemia. Pulses returned and symptoms resided in less than ten minutes after treatment with 5000 IU of heparin.

What special considerations should be taken in patients on anticoagulation therapy?

Successful pseudoaneurysm treatment with thrombin in the setting of concurrent anticoagulation therapy has been well documented for femoral pseudoaneurysms in patients on heparin, warfarin, clopidogrel, and aspirin. [4] While the authors of this study did not report the anticoagulation status of the treated patients, in the previously mentioned study of 14 cases, 9 patients were on anticoagulants for atrial fibrillation. The efficacy in anticoagulated patients compared to ultrasound-guided compression remains one of the leading justifications for thrombin therapy.

Additional Sources

1. Tisi PV, Callam MJ. Treatment for femoral pseudoaneurysms. Cochrane Database Syst Rev. 2013 Nov 29;(11):CD004981. doi: 10.1002/14651858.CD004981.pub4. Review. PMID: 24293322.

2. Garvin RP, Ryer EJ, Yoon HR, Kendrick JB, Neidrick TJ, Elmore JR, Franklin DP. Ultrasound-guided percutaneous thrombin injection of iatrogenic upper extremity pseudoaneurysms. J Vasc Surg. 2014 Jun;59(6):1664-9. doi: 10.1016/j.jvs.2014.01.009. Epub 2014 Feb 20. PMID: 24560862.

3. Kang SS, Labropoulos N, Mansour MA, Michelini M, Filliung D, Baubly MP, Baker WH. Expanded indications for ultrasound-guided thrombin injection of pseudoaneurysms. J Vasc Surg. 2000 Feb;31(2):289-98. PMID: 10664498.

4. Krueger K, Zaehringer M, Strohe D, Stuetzer H, Boecker J, Lackner K. Postcatheterization pseudoaneurysm: results of US-guided percutaneous thrombin injection in 240 patients. Radiology. 2005 Sep;236(3):1104-10. Epub 2005 Jul 29. PubMed PMID: 16055694.

Post Author
Charles Hyman, MS4
Warren Alpert Medical School of Brown University

Midterm Clinical Outcomes and MR Imaging Changes after Transcatheter Arterial Embolization as a Treatment for Mild to Moderate Radiographic Knee Osteoarthritis Resistant to Conservative Treatment

Summary

Osteoarthritis (OA) is a common and debilitating condition that leads to decreased functional status and quality of life in the affected population. Low grade inflammation with associated angiogenesis is now recognized as part of the etiopathophysiology of OA symptoms. Okuno et al. present a prospective, single-center observational study on outcomes following transcatheter arterial embolization for mild-to-moderate knee osteoarthritis. 95 knees in 72 patients with symptoms resistant to conservative therapy, of median duration 30 months, were included. All patients with osteonecrosis, local infection, malignancy, rheumatoid arthritis, and previous knee surgery were excluded. The embolization procedures were performed using antegrade femoral artery access, with a 3-French catheter to select the popliteal artery. Additional selective arteriography was performed with a 1.7-French catheter if needed. Abnormal vessels were identified from a mean of 3.2 arteries per knee. Embolization was performed with imipenem and cilastatin sodium in the majority of patients and 75 um Embozene in the minority of patients with hypersensitivity to the antibiotics. Embolization endpoint was suppression or reduction of filling of the abnormal popliteal vasculature and reduction in local tenderness by palpation. The authors state that patients described pain, itching, or heat sensation at the site of symptoms when the culprit vessel was embolized. All cases were technically successful. The most common adverse events were puncture site bleeding in 12 patients and transient cutaneous color changes in 4/7 patients treated with Embozene, with no major adverse events. At all follow-up time points, there were significant reductions in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores compared to baseline (mean 12.1 at baseline versus 6.2, 4.4, 3.7, 3.0, and 2.6 at 1, 4, 6, 12, and 24 months, respectively; all P< .001). There was no difference in clinical outcomes between embolization with imipenem and cilastatin sodium and Embozene. Magnetic resonance imaging follow-up in 35 knees of 29 patients at 2 years showed decrease in synovitis, with no osteonecrosis or other evidence of aggressive progression in degenerative OA changes.



Figure. Angiographic findings before and after transcatheter arterial microembolization in a 69-year-old patient treated with imipenem and cilastatin. (a) Selective arteriography from the descending genicular artery before embolization showing abnormal neovessels (arrow) adjacent to the medial condyle (MC). (LC ¼ lateral condyle.) (b) Post-embolization arteriography demonstrating elimination of hypervascularity.

Commentary

Although joint replacement is an effective management of severe OA, conservative treatment is used for most patients with mild-to-moderate OA. Many of these patients struggle with symptom control and new therapies could have an impactful role in improving quality of life and functional mobility. The recognition that synovitis and associated neovascularity underlie OA symptoms has raised interest of transcatheter embolization for symptomatic OA. At this nascent stage in investigation of this therapy, this study from Okuno et al. provides an important groundwork by delineating the technical approach, confirming a favorable safety profile, and demonstrating promising midterm clinical and imaging follow-up results. No patients in this study had any ischemic complications, including osteonecrosis, and did not have significant progression of OA from the decreased pain and increased mobility and joint loading. The authors also used a small volume of embolic material to reduce the risk of embolization-associated inflammation which could theoretically contribute to short-term worsening of joint inflammation. This study was limited by the lack of a control group and blinding and additional studies are certainly needed to validate efficacy and safety. Nonetheless, this work provides a promising foundation for subsequent studies into transcatheter embolization as a novel treatment approach for symptomatic OA.

Click here for abstract

Okuno Y, Korchi AM, Shinjo T, Kato S, Kaneko T. Midterm Clinical Outcomes and MR Imaging Changes after Transcatheter Arterial Embolization as a Treatment for Mild to Moderate Radiographic Knee Osteoarthritis Resistant to Conservative Treatment. J Vasc Interv Radiol. 2017;28(7):995-1002.

Post Authors:
Jeffrey Forris Beecham Chick, MD, MPH, DABR
Assistant Professor of Vascular and Interventional Radiology
Vice Quality Assurance and Safety Officer
Venous Health Program Faculty
University of Michigan Health System
Michigan Medicine

James X. Chen, MD
Resident in Radiology
Hospital of the University of Pennsylvania

From the SIR Residents and Fellows Sections (SIRRFS)

Teaching Topic: Randomized Controlled Trial of Octyl Cyanoacrylate Skin Adhesive versus Subcuticular Suture for Skin Closure after Implantable Venous Port Placement

Martin JG, Hollenbeck ST, Janas G, Makar RA, Pabon-Ramos WM, Suhocki PV, Miller MJ, Sopko DR, Smith TP, Kim CY. J Vasc Interv Radiol. 2017 Jan;28(1):111-116.

Click here for abstract

Implanting central venous port catheters has become an everyday occurrence for most interventional radiologists. In 1992, interventional radiologists implanted slightly less than 13 thousand central venous port catheters per Medicare claims data. By 2011, this number had exploded to over 83 thousand. [1] Likewise, the proportion placed by radiologists compared to other specialists increased from 17% to 27% in the same period. While port placement has become an essential tool in every interventional radiologist’s armamentarium, it remains one of the few procedures that require large incisions and full thickness skin closure. Traditionally, skin closure is performed with a deep dermal suture layer and a superficial subcuticular suture layer. The use of tissue adhesives made from octyl cyanoacrylate, such as Sure+Close II (Chemence Medical) and Dermabond (Ethicon), have been studied extensively in other specialties’ literature as an alternative for subcuticular suture closure. In this study, Martin et al. at Duke University conducted a randomized controlled trial comparing tissue adhesives and subcuticular sutures in port placement.

The authors randomly assigned 109 subjects after initial port placement and deep dermal suture closure to either receive subcuticular suture closure or adhesive closure. Subjects were followed up for infection, dehiscence, and photographs were obtained at 3-months post-procedure. Photographs were then examined by a blinded plastic surgeon and rated for cosmetic appearance on a validated 10-point scale. Additionally, each closure was timed by handheld stopwatch. There was no significant difference between groups in infection and dehiscence rates or cosmetic scores. However, using tissue adhesive was much faster taking only 1.4 minutes compared to the 8.6 minutes suturing required

Clinical Pearls

What is the purpose of superficial skin closure?

It is important to keep in mind that the ideal superficial skin closure is intended to appose epidermal edges with a slight eversion to prevent unsightly scar depression. The deep dermal stitches are used to minimize dead-space and should bear the nearly all the tension required for closure. The superficial tissues lack the strength to hold the incision closed and tension on the superficial layer causes scar widening. This is a particularly important consideration in port placement since the bulk of the port increases the tension across the incision.

How do these results compare to the use of skin adhesives in other procedures?

Skin adhesives have not shown statistically significant differences in cosmetic outcome in traumatic wound and surgical incision closure in many different procedures on various body parts. Perhaps the most relevant of these studies comes from the Plastic Surgery literature, where Nahas et al. compared the two methods side to side in mammoplasty and along the same incision in abdominoplasty. They found no significant cosmetic difference in 3, 6, and 12 month follow up. [2] This study design helps control for patient factors by using side to side or same wound comparison. Abdominoplasty incisions are usually closed under large amounts of tension and usually require various tension reducing techniques like quilting sutures and patient positioning to reduce the risk of dehiscence. Mammoplasty closure bears some similarities to port placement closure in that they are both on the chest and over and implanted foreign bodies. However, port placement is unique in that the implant is very superficial and the patients are theoretically at higher risk for poor wound healing secondary to the diseases which the port is intended to be used to treat.

Questions to Consider

How does radiation therapy affect your decision for skin closure?

Radiation can cause skin atrophy, fibrosis, ulceration, and vessel rupture. In radiated skin, all phases of the wound healing process are disrupted to some degree. [3] Fibroblasts and keratinocytes have have reduced production of crucial growth factors as well as disorganized collagen production. This study excluded patients with prior radiation therapy to the chest or plans for radiation. There is no RCT specifically comparing the different superficial closure techniques in radiated skin, but the safe use of tissue glues has been described in breast reconstruction after radiation. [4] It is likely that radiation increases the complication risks in both tissue glue and subcuticular suture closure.

What is the role of antibiotics in port placement?

The authors of this study prophylactically administered intravenous antibiotics (cefazolin 1g or clindamycin 600 mg) and irrigated the port pocket with a saline solution containing cefazolin or clindamycin. The use of antibiotic prophylaxis in implanted central venous access ports is somewhat controversial. While many retrospective studies have found decreased infection rates, the most recent Cochrane systematic review found that prophylactic antibiotics did not reduce Gram positive infection rates in RCT’s of long-term central venous catheters in oncology patients. However, flushing and locking the catheter with a combined antibiotic and heparin solution reduced the risk of Gram positive catheter-related sepsis. [5] The 2011 Guidelines for the Prevention of Intravascular Catheter-related Infections from the CDC recommend against prophylactic antibiotics. [6]

Additional Sources

1. Duszak R Jr, Bilal N, Picus D, Hughes DR, Xu BJ. Central venous access: evolving roles of radiology and other specialties nationally over two decades. J Am Coll Radiol. 2013 Aug;10(8):603-12. doi: 10.1016/j.jacr.2013.02.002. Epub 2013 Jun 14. PMID: 23770064.

2. Nahas FX, Solia D, Ferreira LM, Novo NF. The use of tissue adhesive for skin closure in body contouring surgery. Aesthetic Plast Surg. 2004 May-Jun;28(3):165-9. Epub 2004 Jul 30. PMID: 15383885.

3. Haubner F, Ohmann E, Pohl F, Strutz J, Gassner HG. Wound healing after radiation therapy: review of the literature. Radiat Oncol. 2012 Sep 24;7:162. doi: 10.1186/1748-717X-7-162.

4. Colwell AS. Current strategies with 1-stage prosthetic breast reconstruction. Gland Surgery. 2015;4(2):111-115. doi:10.3978/j.issn.2227-684X.2015.02.05.

5. van de Wetering MD, van Woensel JB, Lawrie TA. Prophylactic antibiotics for preventing Gram positive infections associated with long-term central venous catheters in oncology patients. Cochrane Database Syst Rev. 2013 Nov 25;(11):CD003295. doi: 10.1002/14651858.CD003295.pub3. PubMed PMID:24277633.

6. O’Grady NP, Alexander M, Burns LA, et al. Guidelines for the Prevention of Intravascular Catheter-related Infections. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 2011;52(9):e162-e193. doi:10.1093/cid/cir257.

Post Author:
Charles Hyman, MS4
Warren Alpert Medical School of Brown University

Segmental Y90 vs Segmental TACE for Localized HCC

Summary

Embolotherapies play an important role in the management of hepatocellular carcinoma (HCC), but the optimal modality remains controversial. Transarterial chemoembolization (TACE) remains the most widely accepted option for HCC, but some studies have suggested that transarterial radioembolization (TARE) may have superior outcomes. Padia et al present a single center retrospective series comparing segmental TARE versus TACE for HCC. Due to inherent biases in the use of these modalities over time (i.e. preferential use of TACE to bridge for liver transplantation), there were baseline differences in the patient population including higher ECOG performance scores in the TACE group (p=0.003), larger tumor size in the TARE group (mean diameter 3.2 versus 2.6 cm, p<0.001), higher volume of tumor infiltration in the TARE group (23% versus 9%, p=0.01), and greater incidence vascular invasion in the TARE group (18% versus 1%, p<0.001). Recognizing the potential for bias from these baseline differences, the authors used a propensity score adjustment approach for the analyses. TARE was performed with glass microspheres (Therasphere) in all cases, with target doses of >200 Gy for ablative intent (median administered dose: 1.59 GBq). TACE was performed using drug eluting beads (100-300 um LC beads loaded with doxorubicin) or conventional ethiodized oil, doxorubicin emulsion following by 300-500 um microspheres. Tumor responses were assessed in the index lesion as well as whole liver per RECIST 1.1. TARE demonstrated significantly higher complete response rate, both by index lesion (TARE 92% versus TACE 74%, p=0.001) and overall liver (TARE 84% versus TACE 58%, p<0.001), with statistical significance in both unadjusted and propensity-score adjusted analyses. Survival analysis from the time of first embolotherapy demonstrated significantly longer median progression-free survival (PFS) in the TARE group (564 days) compared to TACE (271 days), p=0.02, with significance maintained on inverse probability of treatment weighting (IPTW) propensity score adjustment. Overall survival (OS) was; however, not significantly different between the two groups. At 1 year, the local tumor recurrent rate was significantly lower following TARE (8%) compared to TACE (30%). A significantly higher proportion of patients receiving TARE achieved optimal response after 1 treatment compared to TACE (93% versus 79%, p=0.012). Both modalities had low rates of clinical and biochemical toxicities (Common Terminology Criteria for Adverse Events grade 3 or higher), with no significant difference in the overall rate of complications, although there was a higher rate of pain in the TARE group (7.6% versus 1%), and higher rate of post-embolization syndrome in the TACE group (8.8% versus 2.3%).



Commentary

In HCC, extensive experience with TACE has cemented the modality as the mainstay choice for many providers and institutions, but there is a growing body of evidence supporting TARE. Comparisons between embolotherapy modalities are inherently challenging due to variations in patient selection and technical approach, particularly in retrospective studies, which contribute bias and limit generalizability of results. To circumvent some of these challenges, Padia et al focused on only cases of segmental TARE and TACE and applied propensity score adjustment to their outcomes analysis. The findings of improved index lesion and whole liver complete response rates and longer median PFS following segmental TARE using an “ablative” dose suggest that this approach may be superior to TACE. These results were echoed by findings of the PREMIERE trial (a prospectively randomized controlled trial comparing TARE [lobar and selective] with conventional TACE, Salem et al. Gastroenterology 2016) that also demonstrated significantly longer median time to progression in the TARE group, although no difference in imaging response rate was shown. In this study, additional benefits of TARE included lower 1-year local recurrence rates, which were similar to rates reported following thermal ablation or surgery, and ability to achieve optimal response after 1 treatment in a higher percentage of patients compared to TACE. There are several limitations to consider when evaluating these results, in addition to the inherent biases of retrospective approach. Although the authors used a sound statistical approach to reduce the impact of baseline differences in treatment populations, there may still be residual bias in the results. Furthermore, it is never stated whether the patients in the study were embolotherapy naïve, or the degree of treatment crossover that occurred following the first treatment, which could confound the survival analysis. Nonetheless, this study provides convincing support for the use of segmental TARE over TACE for HCC to achieve better local tumor control. Many institutions preferentially use TACE as a bridge to liver transplantation, and results like these suggest that TARE could potentially be the superior modality for reducing the rate of waitlist drop-out.

Click here for abstract

Padia SA, Johnson GE, Horton KJ, et al. Segmental Yttrium-90 Radioembolization versus Segmental Chemoembolization for Localized Hepatocellular Carcinoma: Results of a Single-Center, Retrospective, Propensity Score-Matched Study. J Vasc Interv Radiol 2017; 28:777-85 e1.

Post Authors:
Jeffrey Forris Beecham Chick, MD, MPH, DABR
Assistant Professor of Vascular and Interventional Radiology
Vice Quality Assurance and Safety Officer
University of Michigan Health Systems

James X. Chen, MD
Resident in Radiology
Hospital of the University of Pennsylvania