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Clinical study (Prospective, Retrospective, Case Series)

Cryoablation as Second-line Therapy for Fibroadipose Vascular Anomaly

Kaufman, Clairea; Frodsham, Aaronb; Arnold, Ryanc

Author Information
Journal of Vascular Anomalies: March 2021 - Volume 2 - Issue 1 - p e008
doi: 10.1097/JOVA.0000000000000008
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Abstract

Introduction

Vascular malformations include a wide variety of disorders that involve the vascular and lymphatic systems. These congenital lesions are uncommon; venous malformations (VMs) have a reported incidence in the literature of 1–2 per 10,000.1 Fibroadipose vascular anomaly (FAVA) is a newly discovered distinct vascular anomaly first reported in the literature in 2014.2 FAVA are intramuscular lesions that replace the normal skeletal muscle with fibrofatty proliferation and phlebectasia. These lesions can closely resemble VMs to the untrained eye and were often previously misdiagnosed as such or as other anomalies such as cavernous hemangiomas.3 However, there are key imaging, clinical, and pathologic findings that help to differentiate FAVA from VM. Histologically, there is dense fibrofatty tissue surrounding the nerves, which also helps distinguish FAVA from intramuscular VM histologically. Clinically, these patients often present with symptoms of severe pain and contractures.2 On ultrasound FAVA appear echogenic and predominately solid due to the fatty component, whereas intramuscular VM characteristically have compressible vascular channels. On magnetic resonance imaging FAVA are heterogonous and moderately T2 hyperintense and demonstrate enhancement, and on T1 demonstrate characteristic hyperintense fat marbling throughout the lesion (Figures 1 and 2).4

Figure 1.
Figure 1.:
Imaging of patient number 3. A, Preprocedure T1-weighted postcontrast MRI shows diffuse enhancement of the lesion in the right vastus medialis with associated phlebectasia B, Preprocedure T2 fat saturated image demonstrates hyperintensity of the lesion. C, Preprocedure T1-weighted MRI demonstrates characteristic fat marbling within the focal lesion (arrow) with adjacent phlebectasia. D, Ultrasound of the lesion in the vastus medialis, showing characteristic findings of solid tissue with increased echogenicity and surrounding phlebectasia. E, CT-guided cryoablation showing 5 probes within the lesion with subsequent iceball formation. F, Postprocedure MRI T1-weighted postcontrast MRI performed 3 mo after cryoablation demonstrates no residual enhancement of the lesion with posttreatment changes. CT indicates computer tomography; MRI, magnetic resonance imaging.
Figure 2.
Figure 2.:
Ten-year old boy with symptomatic left proximal thigh FAVA. A, T1 axial image demonstrating fat marbling in the left adductor (arrow). B, Coronal T1 postcontrast scan demonstrating enhancement of the FAVA in the proximal left thigh. FAVA indicates fibroadipose vascular anomaly.

More traditional therapies include sclerotherapy or surgical resection; both have limitations and risks to the patient. Sclerotherapy, often used to successfully treat VMs, only treats the phlebectasia component of the FAVA, not addressing the dominant soft-tissue fibrofatty component. Surgical resection of vascular anomalies can be complicated by bleeding, muscle weakness/nerve damage, and recurrence.5,6

There is a significant lack of data and evidence to support specific treatments for FAVA. Cryoablation has recently emerged as a means of treating both VMs and FAVA.4,6–9 Cryoablation works by causing cell death of the ablated tissue. Rapid freezing and thawing lead to interstitial ice crystals and hyperosmolarity, thereby causing cell dehydration and damage to the cell membrane and organelles, leading to cellular death.10–12 Cryoablation treats not only the phlebectasia but also the soft tissue and fibrofatty infiltration, which proves an effective treatment for FAVA.4,8 The purpose of our study was to examine the outcomes of our FAVA patients with failed prior interventions who underwent cryoablation as second-line treatment.

Methods

A retrospective review was performed at the adult tertiary-care academic center and associated children’s hospital of all patients from October 2014 to October 2020 undergoing percutaneous image-guided cryoablation of lesions with preprocedure imaging or biopsy consistent with FAVA. This study was approved by the institutional board review at both institutions and carried out in compliance with the Health Information Portability and Accountability Act. Preprocedure, intraprocedural, and, when available, follow-up imaging was reviewed. Electronic medical record (EMR) review was performed to determine demographics, indication, prior treatments both interventional and surgical, symptoms, clinical response after the procedure, as well as any complications.

The lesions were diagnosed using clinical examination, and imaging such as ultrasound, magnetic resonance imaging, and computer tomography (CT). Biopsy results were reviewed if available. All patients were evaluated in interventional radiology clinic or the multidisciplinary vascular anomalies clinic prior to the procedure. Cryoablation was offered to patients if the interventionalist felt it was indicated and that the lesion was amenable to ablation. Extensive, diffuse cases of FAVA, and those patients with significant preexisting contractures were typically not treated with cryoablation.

Cryoablation technique

All procedures were performed after obtaining written informed consent from the patient or in the case of minors the patient’s parents. The ablation procedures were performed under sedation and, most commonly, general anesthesia; however, 1 adult patient’s ablation was performed under moderate sedation. All imaging was reviewed prior to the ablation. CT with or without adjunctive ultrasound was used for procedural guidance. The procedures were performed by 1 of 2 adult interventional radiologists or 1 pediatric interventional radiologist. An argon-gas–based cryoablation system (Boston Scientific, Marlborough, Massachusetts) was used for all procedures. The number and size of the probes, and the number of ablation sites were at the discretion of the performing interventionalist. This decision was dependent on the planned ablation zone using the available cryoablation needle isotherm data from the manufacturer. Ablation zones were planned to include the entire lesion; however, unlike cryoablation of malignant lesions, a 0.5–1 cm ablation kill zone margin was not required. The lesion was measured using real-time ultrasound or CT if needed prior to the ablation. The cryoablation probes were placed under either continuous ultrasound guidance or intermittent CT depending on the location of the lesion and operator preference. The probes were placed along the long axis of the lesion. In lesions where 2 ablation sites were planned, elongated lesions, the distal portion of the lesion was targeted first. After placement, the depth from the probe to the overlying skin was measured on ultrasound to make sure there was at least 5–10 mm from the predicted ablation zone to the skin. If the predicted ablation zone was less than this, the cryoablation needle was readjusted. After confirmation of appropriate positioning, 2 cycles of freezing/passive thaw were performed. A sterile glove filled with warm saline was placed on the overlying skin while freezing. Intermittent ultrasound was used to monitor the distance from the iceball to the skin. If the iceball approached 5 mm of the skin, the freeze was stopped. Due to shadowing on ultrasound from the ice, intermittent CT was often performed to evaluate the deep extent of the iceball. In patients with 2 sites planed, after ablation of the first site, the probes were retracted under ultrasound guidance and the procedure repeated as above.

The procedures were done either as an outpatient procedure or with overnight admit for pain control. Patients were discharged home after recovery with compression and pain medications, including a nonsteroidal antiinflammatory. A Medrol dose pack was sometimes given if there was concern for swelling. If needed, physical therapy was prescribed as an outpatient.

Follow-up

All patients were seen for follow-up in interventional radiology clinic, or if distance precluded physical clinic visit, a phone call or virtual visit follow-up was performed. Clinical responses were documented in the EMR. This was retrospectively categorized as complete resolution of pain, marked improvement (defined as the patient now able to perform activities previously limited by pain or no longer requiring pain medication), minimal improvement (defined as improved pain but still activity/mobility limitations or pain medication requirements), no improvement, or worsening of symptoms.

Results

There were 9 patients who underwent a total of 11 ablation procedures on 10 lesions. There were 6 females and 3 males with ages ranging from 9–53 years old. Five of the patients were under the age of 18 at the time of ablation. All procedures were technically successful. One lesion underwent a planned staged ablation procedure due to the location on the plantar surface of the foot.

Eight patients had a focal FAVA lesion (Table 1). One patient had a diffuse lesion involving the stump of a prior below knee amputation. Although we typically do not offer cryoablation for diffuse FAVA after a multidisciplinary discussion, the decision was made to attempt ablation in this patient to try to avoid above knee amputation and increased morbidity. This patient had worsening pain after ablation and was subsequently treated using Sirolimus.

Table 1. - Patient Demographics and Ablation
Patient Age Location Size of Lesion No. of Probes # of Ablation Sites Symptoms Prior Treatment Outcome Complications Follow-Up in Months Subsequent Therapy
1 31 R calf 2.9 × 1.7 × 1.9 cm 1 1 Pain Surgery Resolution of pain A—small hematoma and numbness resolved 6 None
Limited activity requiring assistance for ambulation
1 31 L ankle 4.3 × 2.8 × 9.0 cm 1 1 Pain Surgery Marked improvement in pain None 2.5 None
2 17 L foot 5.7 × 3.2 × 1.7 cm 2 1 Pain worse with activity Surgery Minimal improvement in pain A—Mild numbness, resolved N/A Subsequent Cryoablation
2 17 L foot 5.7 × 3.2 × 1.7 cm 1 3 Residual but improved pain Surgery, cryoablation of the same lesion Minimal improvement in pain A—Mild numbness, resolved 12 Nerve block × 1 4 mo later
3 18 R thigh 6.3 × 4.5 × 10.7 cm 5 1 Pain Sclerotherapy, arterial embolization × 2 Marked improvement in pain None 3 None
4 10 L thigh 3.6 × 2.1 × 4.3 cm 3 1 Pain Surgery × 2, sclerotherapy, EVLT Marked improvement in pain None 96 None
5 31 R thigh 2.6 × 1.5 × 0.8 cm 1 1 Pain Surgery Resolution of pain None 30 None
6 53 R thigh 5.5 × 1.7 × 11.2 cm 2 2 Pain Surgery Marked improvement in pain None 5 None
7 9 L calf 8.6 × 2.1 × 2.8 cm 3 1 Pain Surgery Marked improvement in pain None 30 None
8* 12 L below knee stump Unable to determine 3 1 Pain Surgery—below knee amputation Worsening of symptoms C—worsening pain requiring intervention 24 Sirolimus
9 15 R thigh 6.2 × 1.7 × 9.3 cm 3 2 Pain Sclerotherapy Resolution of pain None 4 None
EVLT, endovenous laser treatment.
*Diffuse fibroadipose vascular anomaly.

Seven out of 9 patients had prior surgical intervention with recurrent disease on imaging and symptoms (Table 1). Three patients had undergone prior sclerotherapy with persistent symptoms. One of these patients (patient 3) had also undergone 2 prior arterial embolizations due to misdiagnosis at an outside hospital. One of these procedures was complicated by full thickness skin necrosis requiring a skin graft. One patient (patient 4) had prior endovenous laser ablation in addition to 2 surgeries and sclerotherapy.

Three lesions ablated had complete resolution of pain. Five lesions treated resulted in marked improvement in pain. Only 1 patient had worsening pain, the patient with diffuse FAVA, as described above. One patient had minimal improvement in pain and subsequently underwent a nerve block 4 months after ablation, which added in pain reduction.

There were 4 complications, all of which were considered minor. One patient had a small self-resolving hematoma after the procedure and numbness, which went away without therapy. Two other patients experienced transient numbness, which resolved. One patient, the patient with diffuse FAVA, had worsening pain requiring further treatment with Sirolimus.

Two patients were done as an outpatient with discharge the same day after recovering from anesthesia and evaluation by the attending interventional radiologist. These patients were discharged with compression, and pain medication including nonsteroidal antiinflammatory and narcotic medications. The remaining patients were admitted for overnight observation with intravenous pain medication.

Follow-up was performed in interventional radiology clinic: in person, virtually, or via telephone. Follow-up ranged from 2.5–96 months (median = 9 mo, mean = 21.25 mo). Five patients had follow-up imaging performed.

Discussion

FAVA are intramuscular lesions that cause significant morbidity via pain and contractures. These lesions can be either focal or diffuse. This recently recognized anomaly has characteristic imaging and clinical findings; however, it is often mistaken for intramuscular VMs by those not familiar with the lesion. It is not infrequent that these are treated as such with embolization, sclerotherapy, or surgery. Sclerotherapy that is standard of care for VMs only treats the phlebectasia portion of the lesion and does not address the fibrofatty overgrowth and perineural fibrosis, which are prominent in this disease. Surgery can be curative but only if the entire lesion is resected. A recent publication of surgical management of FAVA found 40% to have symptomatic residual or recurrent disease requiring further intervention.5 We present our series of patients with FAVA who had undergone prior treatment and were subsequently treated with cryoablation.

Seven of the 9 patients had undergone prior attempted surgical resection with recurrence of pain. Of these patients, all had improvement in pain after cryoablation except for the 1 patient with diffuse FAVA. These findings support the other studies showing a high recurrence rate of FAVA after surgical resection.5

Several small studies have showed safety and clinical success of cryoablation for focal FAVA lesions.7–9 The first-published report of cryoablation used to treat FAVA proved it is safe and effective therapy. Of the 26 lesions treated in their study, 27% had prior surgery and 35% had prior sclerotherapy.4 Ramaswamy et al.6 presented a series of 11 patients with vascular anomalies who underwent successful cryoablation. Five of these patients had FAVA, 1 of which was treated previously with sclerotherapy. The results of these studies are in support to our finding that cryoablation can be used to successfully treat FAVA, which have failed prior therapy.

Patients with FAVA often present to tertiary-care facilities after failing prior therapy. This may be due to the novelty of the lesion and unfamiliarity of the lesion with some providers. If it is not correctly identified, the lesion may be treated as other vascular anomalies, with poor response rates. FAVA can be very difficult to treat. Cryoablation is becoming increasingly recognized as a good potential option for FAVA.4,6 Our experience supports that not only should cryoablation be considered as the first-line treatment for focal FAVA lesions but can be considered safe and effective as a second-line therapy for those patients who have failed prior treatment.

Our 1 major complication, increased pain after ablation requiring further intervention, occurred in a patient with diffuse FAVA of the left calf. This is not surprising as it was not possible to perform cryoablation of the entire lesion. This patient was subsequently treated with Sirolimus with improvement in symptoms. Sirolimus, otherwise known as rapamycin, is an United States Food and Drug Administration-approved mTor inhibitor, which has been shown to be safe and effective in treating complex vascular malformations.13 A recent case series reported 2 cases of diffuse FAVA treated with Sirolimus resulting in marked improvement in pain and quality of life.14 Although this was only 1 patient, this raises the question that cryoablation may not be as effective in diffuse FAVA and other treatments should be considered.

There are several limitations to our study. Our sample size was small due to the infrequent nature of these lesions even at a tertiary-care center. This was a retrospective review and therefore unable to quantify pain using a quantitative scale instead was determined based on follow-up records in the EMR. The lesions were heterogeneous in size and location.

FAVA lesions are rare often-misdiagnosed vascular anomalies that can be difficult to treat. Cryoablation has been previously been shown to be safe and effective treatment for FAVA. Our findings suggest that cryoablation is safe and effective therapy not only as a primary treatment but also as second-line therapy in patients with failed prior interventions.

References

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2. Alomari AI, Spencer SA, Arnold RW, et al. Fibro-adipose vascular anomaly: clinical-radiologic-pathologic features of a newly delineated disorder of the extremity J Pediatr Orthop. 2014; 34:109–117
3. Fernandez-Pineda I, Marcilla D, Downey-Carmona FJ, et al. Lower extremity fibro-adipose vascular anomaly (FAVA): a new case of a newly delineated disorder Ann Vasc Dis. 2014; 7:316–319
4. Shaikh R, Alomari AI, Kerr CL, et al. Cryoablation in fibro-adipose vascular anomaly (FAVA): a minimally invasive treatment option Pediatr Radiol. 2016; 46:1179–1186
5. Wang KK, Glenn RL, Adams DM, et al. Surgical management of fibroadipose vascular anomaly of the lower extremities J Pediatr Orthop. 2020; 40:e227–e236
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13. Adams DM, Trenor CC III, Hammill AM, et al. Efficacy and safety of sirolimus in the treatment of complicated vascular anomalies Pediatrics. 2016; 137:e20153257
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Keywords:

Fibroadipose vascular anomaly; Vascular malformation; Cryoablation

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Society for the Study of Vascular Anomalies.