Wednesday, April 18, 2018

From the SIR Residents and Fellows Section (SIRRFS)


Teaching Topic: Uterine Artery Embolization for Pedunculated Subserosal Leiomyomas: Evidence of Safety and Efficacy


Kim, YS, Han K, Kim M, Kim GM, Kwon JH, Lee J, Choi W, Won JY, Lee DY. Uterine Artery Embolization for Pedunculated Subserosal Leiomyomas: Evidence of Safety and Efficacy. 2018 Feb 22. doi: 10.1016/j.jvir.2017.11.022 [Epub ahead of print]

Click here for abstract

Uterine artery embolization (UAE), colloquially known as uterine fibroid embolization, has become a widely accepted and increasingly popular option for the treatment of symptomatic leiomyomas. Since its first report by Ravina et al. in 1995, the evidence supporting its safety and efficacy has become increasingly robust with large prospective, randomized controlled trials like the REST and EMMY trials. [1,2] Recently, emerging evidence is even broadening the conditions that UAE could be indicated for to include adenomyosis and premenstrual symptoms. [3] Despite these advances, the historical controversy surrounding UAE for pedunculated subserosal (PS) leiomyomas, particularly ones with narrow stalks, has persisted. Guidelines from the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) list PS leiomyomas with stalks that are less than 50% the diameter of the leiomyoma as a relative contraindication because of the risk of torsion and ischemic necrosis of the stalk and resulting separation of the leiomyoma from the uterus. These concerns largely stem from two early cases where necrotic PS leiomyomas detached and became a source of sepsis which required hysterectomy and bowel resection. [4] Because of this risk, PS leiomyomas were generally excluded from the major UAE trials, including the REST trial. However, the guidelines from the SIR Standards of Practice Committee explicitly refutes this contraindication citing four retrospective series of 12, 16, 18, and 29 patients who underwent successful UAE for PS leiomyomas. [5] In this study, Kim et al. present the largest and most comprehensive series to date of UAE for PS leiomyomas in 55 patients.

In this retrospective review, the authors present 55 patients with a total of 66 PS leiomyomas treated with UAE between 2007 and 2016. They further categorized leiomyomas with stalk diameters 25% or less of the diameter of the leiomyoma as high-risk (n=11) and leiomyomas with stalk diameters 50% or less of the diameter of the leiomyoma low-risk (n=55). Magnetic resonance imaging was performed 3 months after UAE to compare infarction rate and volume reduction between high-risk and low-risk groups and between PS leiomyomas and leiomyomas in other locations. The authors successfully embolized the uterine arteries bilaterally in 54/55 (98.2%) of patients. There was no significant difference in the mean volume of reduction in PS leiomyomas compared to non-PS leiomyomas (38.2% vs 38.4%, p=.953), though the mean infarction rate in PS leiomyomas was significantly lower than the rate in non-PS leiomyomas (86.0% vs 99.9%, p=.0025). All 66 stalks continued to enhance after UAE. Clinically, 53/55 patients reported symptomatic improvement. One of the patients who did not was the aforementioned technical failure due to non-embolized inferior mesenteric artery collaterals. It was not known what prevented symptomatic improvement in the other patient as volume reduction rates were in line with the other patients.
MR images before and after UAE for a high-risk PS leiomyoma showing complete infarction and remaining stalk enhancement. 


Clinical Pearls


What are the different locations of uterine leiomyomas?

Leiomyomas are typically classified by their location. Intramural leiomyomas, the most common type, occur in the muscular wall of the uterus. Subserosal leiomyomas are the rarest form and occur under the uterine serosa on the surface of the uterus. These can be pedunculated or sessile. They typically do not cause infertility. Submucosal leiomyomas occur under the endometrium and also may be pedunculated or sessile. Submucosal leiomyomas have the largest effect on fertility.

What imaging is required before a UAE?

MR imaging is generally performed before and after the procedure to evaluate leiomyoma amount, size, location, presence of adenomyosis and response to treatment. 3D reconstructed MRA imaging can be used for preprocedural planning and mapping of the uterine and ovarian artery and checking for variant anatomy. The authors of this study did not report if they used MRA preprocedurally and had one technical and clinical failure due to a collateral inferior mesenteric artery that was not embolized.

Questions to Consider


What are the potential complications and adverse events of UAE for PS leiomyomas?

In this study, the authors reported no major adverse events and 3 minor adverse events. Two of these consisted of the expulsion of submucosal leiomyomas. The third adverse event was a presentation to the emergency room 2 days after UAE for pelvic pain which resolved after 2 hours. Stalk necrosis causing separation and the subsequent infection is the primary fear with PS leiomyomas. This study compared stalk enhancement to adjacent myometrium and found no difference in enhancement in any of the 66 cases.

What is the evidence level of the SIR recommendation?

According to the 1998, United States Presentative Services Task Force (USPSTF) guidelines on levels of evidence, the recommendations by the SIR Standards of Practice Committee would be considered Level III evidence as it is expert opinion based on descriptive studies. This study adds 55 more patients to the previously documented 75 cases from the four case series. Level II evidence describes recommendations based from cohort, case-control, or non-randomized controlled trials. Recommendations require at least one randomized controlled to be considered Level I.

Additional Citations

1. The Rest investigators (2007) Uterine-artery embolization versus surgery for symptomatic uterine fibroids. N Engl J Med 356:360–370

2. Hehenkamp WJK, Volkers NA, Birnie E, Reekers JA, Ankum WM (2008) Symptomatic uterine fibroids: treatment with uterine artery embolization or hysterectomy. Results from the randomized clinical embolization versus hysterectomy (EMMY) trial. Radiology 246:823–832

3. Jang D, Kim MD, Lee SJ, Kim IJ, Park SI, Won JY, Lee DY. The effect of uterine artery embolization on premenstrual symptoms in patients with symptomatic fibroids or adenomyosis. J Vasc Interv Radiol. 2014 Jun;25(6):833-838.e1. doi:10.1016/j.jvir.2014.01.036. Epub 2014 Mar 20. PubMed PMID: 24657088.

4. Braude, P., Reidy, J., Nott, V., Taylor, A., and Forman, R. Embolization of uterine leiomyomata: current concepts in management. Hum Reprod Update. 2000; 6: 603–608

5. Dariushnia, S.R., Nikolic, B., Stokes, L.S., and Spies, J.B. Quality improvement guidelines for uterine artery embolization for symptomatic leiomyomata. J Vasc Interv Radiol. 2014; 25: 1737–1747

Post Author:
Charles Hyman, MS4
Chair, Communications Committee, SIRRFS
Warren Alpert Medical School of Brown University

Friday, April 13, 2018

Embolization for RCC: shift in treatment paradigm?


Summary


Researchers from Karolinska University Hospital in Stockholm have recently published their results of a prospective controlled trial on renal cell carcinoma (RCC) embolization. RCC is typically managed through nephron-sparing surgery, radical nephrectomy, ablation, or active surveillance. In this manuscript, the authors compared doxorubicin eluting embolic (DEE) to bland TAE. A total of 12 patients with average tumor size of 3.2 cm +/- 0.62 were randomized to receive DEE or TAE before a planned surgery. Size of embolic was determined on basis of degree of vascularity and ranged from 75-150 micron, 100-300 micron, and 300-500 micron. A CT was performed prior to surgical removal to assess treatment response. DEE transarterial chemoembolization (n = 6) resulted in a significantly (P = .018) higher degree of necrosis with an average of 88.3% compared with TAE (n = 5), which resulted in an average of 29.4%, as evaluated by CT. Histopathologic evaluation showed similar results (P = .016) with an average necrosis of 87.5% for DEE transarterial chemoembolization (n = 4) versus 26% for TAE (n = 5). Percentage of necrosis seen on microscopy correlated significantly (P = .0005) with radiologic findings, as 4 tumors in each arm were evaluated by both CT and microscopy. No major complications were observed in either group. The authors concluded that TACE is safe to be performed for localized RCC and has a significantly superior effect when compared with TAE.
Images of RCC treated by transarterial chemoembolization in patient 12. (a) Subtraction angiography image obtained after selective catheterization of the left renal artery showed contrast-filled intratumoral vessels (arrowhead) before transarterial chemoembolization. (b)Subtraction angiography image obtained during transarterial chemoembolization showed no contrast-filled vessels in the center of the tumor owing to ongoing embolization. The area adjacent to RCC (arrowhead) shares its blood supply with the tumor. (c) CT imageobtained before transarterial chemoembolization showed contrast enhancement in RCC (arrowhead). (d) CT image obtained 4 weeks after transarterial chemoembolization showed no contrast enhancement in RCC (arrowhead). Infarcted renal tissue (arrow) is adjacent to the treated tumor.

Commentary


This manuscript is noteworthy as it opens the avenue for more catheter-based research for RCC locoregional treatment. The authors were able to demonstrate a statistically significant increased response to doxorubicin DEB compared to bland embolic. While both embolics contained residual tumor on pathologic evaluation, DEB had significantly better tumor response. This is interesting as systemic doxorubicin is not known to have a significant impact on RCC. Further, many tumors can become resistant to the effects of doxorubicin when they are ischemic (as with embolization). Clearly, there is more happening at the tumor level than we currently understand. However, is this all a moot point given the current treatment paradigm in RCC? There is a relatively low likelihood that a patient would not be a candidate for partial nephrectomy or ablation and have a tumor undergoing rapid enough growth to require palliative treatment. As such, this manuscript may be more impactful in what it says about the local effects of embolization and image-guided drug delivery and is unlikely to change RCC treatment algorithms.

Click here for abstract

Karalli A, Ghaffarpour R, Axelsson R, Lundell L, Bozoki B, Brismar T, Gustafsson O. Transarterial Chemoembolization of Renal Cell Carcinoma: A Prospective Controlled Trial. J Vasc Interv Radiol. 2018; 12:1664-1672

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