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Monday, August 10, 2020

Genicular Artery Embolization for the Treatment of Knee Pain Secondary to Osteoarthritis


Clinical question
Is hyperemic synovial tissue embolization for knee pain secondary to osteoarthritis a safe procedure? Does the embolization of at least 1 genicular artery provide symptom relief?

Take-away point
Yes, genicular artery embolization for moderate-to-severe pain secondary to osteoarthritis refractory to conservative therapy is safe and efficacious in this 20 patient pilot study.

Reference
Genicular Artery Embolization for the Treatment of Knee Pain Secondary to Osteoarthritis. Bagla, S, Piechowiak, R, Hartman, T, Orlando, J, Gaizo DD, Isaacson, A. Journal of Journal of Vascular and Interventional Radiology (JVIR), Volume 31, Issue 7, 1096-1102.

Click for abstract

Study design
Single arm, prospective, two-center study of 20 patients with radiographic evidence of knee OA and moderate-to-severe pain refractory to conservative therapy who underwent embolization of at least 1 genicular artery with a follow-up of 6 months.

Funding Source
No funding source was disclosed.

Setting
Academic hospitals. Vascular Institute of Virginia, Woodbridge, Virginia and University of North Carolina Hospital, Chapel Hill, North Carolina.





Figure 3 and 4. Superior medial genicular artery angiography showing hypervascular “blush” (black arrows, left) over the medial inferior aspect of the knee which was “pruned” after embolization (right). The parent superior medial genicular artery remained patent.

Summary


Conventional and conservative treatments for knee osteoarthritis (OA) in patients not yet appropriate for total knee arthroplasty (TKA) have potential complications and demonstrate inconsistent efficacy. Recent research has shown that OA is associated with chronic inflammation, which drives the releases cytokines such as vascular endothelial growth factor (VEGF) and the resultant osteophyte formation, cartilage breakdown, and progressive knee pain.

Genicular artery embolization (GAE) has been described as safe and effective in post-TKA hemarthrosis. Similar techniques were also reported for OA-related pain palliation, including one large study using rapidly absorbable embolic antibiotics mixture with 72 patients and 95 knees, a clinical follow up of 36 months, and 80% clinical success rate. Safety and clinical efficacy using permanent embolic agent in GAE for knee pain secondary to OA remain scarce in the literature.

The authors performed a single-arm, prospective, two-center study of 20 patients with osteoarthritic knee pain who underwent GAE. Inclusion criteria included age 40+, mild-to-moderate knee OA by radiograph, pain 5+/10, and failure of conservative treatments for 3+ months. Exclusion criteria included rheumatoid arthritis, renal insufficiency, irreversible coagulopathy, previous arthroplasty, joint infection, Kellgren–Lawrence grade 4 radiographic findings, or MRI incompatibility. All 20 patients underwent further MRI delineation of the affected knee. The WOMAC questionnaire and VAS were used for clinical assessment at 1, 3, and 6 months after GAE. Technical success defined as embolization of 1+ genicular artery. Clinical success defined as 20% change in VAS or 16% change in WOMAC at 6-month follow-up without increase in pain medication use of intra-articular injection.

Procedural pearls included 1) digital subtraction angiography (DSA) at the distal superficial femoral artery to identify the target genicular arteries in the region of the maximal pain; 2) identify a hypervascular “blush”; 3) embolization with (9 mL contrast and 6 mL particle mixture) using either 75- or 100 µm spherical particles (Embozene); 4) 0.2 mL aliquots embolization with intermittent DSA after each injection until hypervascular “blush” is no longer evident. Patients were discharged on the same day.

20 embolization procedures were performed with 2.5 genicular arteries embolized on average. At 6-month follow-up, significant mean decreases from 76 to 31 for VAS and 61 to 31 for WOMAC were observed. 65% of patients reported decrease in daily analgesic use. Adverse events included 65% reporting skin discoloration without ulcer which resolved by the 3-month follow-up (class A), 1 small access site hematoma (class A), and 10% reporting great toe plantar numbness which resolved within 2 weeks (class B; which prompted the change from 75- to 100- µm particles from the 10th patient on with no further neurologic events reported).

Commentary


The authors in this paper have demonstrated that GAE using permanent embolic particles for osteoarthritic knee pain refractory to conservative management, especially with 100-µm sized particles, is safe and effective. It is important to remain cautious as this study has a relatively short follow-up period of 6 months, relatively small patient sample size of 20, and a pilot single-armed prospective design. As the authors have described, a control arm, preferentially double-blinded, may be necessary to determine the therapeutic effect masked by the placebo effect. A larger sample size may enable detailed analysis beneficial for optimal patient selection. In addition, long term adverse outcomes, such as accelerated progression of OA or potential issues with eventual TKA, could not be assessed. Nonetheless, GAE is a promising minimally-invasive alternative method of pain palliation in patients with moderate-to-severe osteoarthritic knee pain. Future larger, long-term, and placebo-controlled clinical trial designed in a scientifically rigorous manner similar to this presented work, is needed for full evaluation.

Post Author
Ningcheng (Peter) Li, MD, MS
Integrated Interventional Radiology Resident, PGY-4
Department of Interventional Radiology
Oregon Health and Science University, Dotter Interventional Institute
@NingchengLi

Friday, August 7, 2020

Adverse Events Related to Partial Splenic Embolization for the Treatment of Hypersplenism: A Systematic Review


Clinical question
What is the adverse event profile of partial splenic embolization in patients with hypersplenism?

Take-away point
Despite high technical success rates, partial splenic embolization demonstrated a high risk of minor complications including postembolization syndrome as well as a lower risk of major complications including gastrointestinal bleeding, splenic abscess, peritonitis, pleural effusion, and mortality.

Reference

Talwar A, Gabr A, Riaz A, et al. Adverse Events Related to Partial Splenic Embolization for the Treatment of Hypersplenism: A Systematic Review. J Vasc Interv Radiol. 2020;31(7):1118-1131.e6.

Click here for abstract

Study design
Systematic Review

Funding source
Self-funded or unfunded

Setting
Multiple studies






Summary


Partial splenic embolization (PSE) is a non-surgical alternative to splenectomy in the treatment of hypersplenism. While proven to be an effective alternative with advantages of decreased procedure time, early ambulation, and preservation of spleen function, PSE is not without its risks. Presently, there is limited pooled data on the specific complications associated with this procedure in patients with hypersplenism.

This systematic review analyzed 30 original studies reporting complications of PSE for the treatment of hypersplenism. Outomes included specific adverse events during or after the procedure and technical success rate. Complication rates were calculated only for patients with successful embolization. Complications were classified as either major or minor, with major complications being defined as those requiring surgical intervention, resulting in a hospital stay >30 days post-procedure, or associated with splenic abscess, refractory ascites, massive pleural effusion causing shortness of breath, post-procedure gastrointestinal bleeding, paralytic ileus, vasospasm, pseudoaneurysm, peritonitis, pancreatitis, or sepsis. Results were stratified by both extent of splenic embolization and Child-Pugh class.

Of the 976 PSEs analyzed, 963 procedures were technically successful (99%). Of the remaining 13 procedures, 9 failures were attributed to failure to catheterize the splenic artery, 2 were attributed to splenic artery dissection, 2 were not specified, and 1 was attributed to inadvertent total splenic embolization.

Of the 963 technically-successful procedures, 73.4% experienced postembolization syndrome, 9.4% had pleural effusion, 8.1% had ascites, 2.4% had thrombosis, 1.3% had bacterial peritonitis, 1.3% had splenic abscesses, 0.6% had gastrointestinal bleeding, and 1.0% experienced PSE-related deaths. Causes of death included liver failure, variceal bleeding, sepsis, hepatic encephalopathy, pneumonia, pleural effusion, and myocardial infarction. There were 98 major (10%) and 913 minor (95%) complications. The relative risk of developing a major complication was 10.39 (4.70–22.97, p<.0001) for patients with >70% embolization versus those with ≤70% embolization and 11.63 (3.56–38.01, p<.0001) for Child-Pugh class C patients versus class A or B patients.

Commentary


Most patients undergoing PSE experienced at least minor complications. Major complications, while rare, carried the possibility of death and occurred significantly more often in patients with advanced Child-Pugh class and with greater extent of embolization. This systematic review was limited by the overall quality of the studies included. Additionally, the cited studies had limited post-procedural length of stay data. While PSE is an effective minimally-invasive solution to hypersplenism despite its risks, newer alternatives such as radiofrequency/microwave ablation, radioembolization, and high-intensity focused ultrasound (HIFU) therapy show promise of similar benefit with lower complication rates. Increased outcomes data with their use will confirm their value in reducing procedural risk compared to PSE.


Post Author
Jared Edwards, MD
General Surgery Intern (PGY-1)
Department of General Surgery
Naval Medical Center San Diego, San Diego, CA

@JaredRayEdwards

Monday, August 3, 2020

Yttrium-90 Radioembolization in Intrahepatic Cholangiocarcinoma: A Multicenter Retrospective Analysis


Clinical question
What are the outcomes of treating unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization?

Take-away point
Y90 radioembolization is a safe treatment option for intrahepatic cholangiocarcinoma, however its role in treatment is unclear

Reference
Stefan Buettner et al. Yttrium-90 Radioembolization in Intrahepatic Cholangiocarcinoma: A Multicenter Retrospective Analysis. Journal of Vascular and Interventional Radiology. 2020: 31; 1035-1043.


Study design
Retrospective Review

Funding source
Self-funded or unfunded

Setting
Multi-Center





Summary

Despite being the second most common primary liver malignancy, intrahepatic cholangiocarcinoma (ICC) is unresectable in the vast majority of patients. Median survival is 3-8 months, and is improved to 11.7 months with gemcitabine and cisplatin. Smaller studies have demonstrated a survival benefit of radioembolization in ICC. This study provides a retrospective review of patients with ICC after radioembolization. Data from 6 centers over a 10 year 8 month period was reviewed. Both glass and resin microspheres treatments were included. 114 patients were included, 92 treated with resin and 22 treated with glass microspheres.

25% of patients had partial presence by RECIST criteria following glass microsphere treatment compared to 3% after resin microspheres. 62% of patients had disease progression following glass microsphere treatment compared to 76% after resin microspheres. Laboratory toxicity was seen in 45% of the glass microsphere cohort compared to 42% of the microsphere cohort. However, less than 10% had significant toxicity. Median overall survival after diagnosis was 22 months in the glass microsphere group and 30 months for the resin group. Median overall survival after treatment was 9 months for the glass microsphere group and 11 months for the resin group.


Commentary

RECIST response rate favored glass microspheres, however survival outcomes did not differ. A small percent, 4%, were able to be downstaged to resection. As with many interventional oncology studies, the heterogeneity of the patient population, notably prior and subsequent treatment, clouds evaluation of survival data. While radioembolization is clearly safe, its benefit compared to standard chemotherapy is unclear with post treatment survival being inferior to previously published data of survival after chemotherapy. RECIST data favored glass microsphere treatment over resin, this did not bare out on survival data.

Ongoing and future studies comparing yttrium-90 to comparative first line treatment will help elucidate the role of radioembolization in the treatment of ICC.

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

@DavidMauroMD