Microwave Ablation of Symptomatic Hepatic Hemangiomas Lubner Meghan G, Ziemlewicz Timothy J, Cohn Alexandra R, Center Marci L, Wells Shane A, Brace Chris L, Hinshaw J Louis, Lee Fred T Jr.

•Hemangiomas are the most common benign hepatic neoplasm, incidence of 0.4 to 7.3 % in autopsy series. 1

•Composed of dilated, endothelial-lined vascular spaces that can progressively enlarge, likely due to vascular ectasia .2,3 • Indolent course that generally requires no specific treatment or imaging follow-up. •Large or enlarging hepatic hemangiomas symptomatic due to mass effect or capsular distention.4,5 •Risk of rupture exceedingly low; however tumor rupture associated with a high mortality rate.6-8 •Giant hepatic hemangiomas can result in consumptive coagulopathy, Kasabach-Merritt syndrome.9 •Surgical resection associated with up to 25% morbidity, long recovery period, missed time from work, rare perioperative deaths.10,11

•Minimally invasive strategies (transarterial embolization, radiation) reported with variable success, some morbidity.12-17 •Radiofrequency generally effective for hepatic hemangiomas less than 5 – 7.5 cm

-May require long ablation times (29.4- 126.5 min) -Can have incomplete tumor devascularization requiring repeat ablation18-24

•Microwave ablation with potential advantages in treatment of hemangiomas25-31

•Particularly effective for the treatment of tumors with high water content.32 •Hemangiomas composed primarily of vascular spaces; large amounts of intratumoral water •We hypothesized that microwave would be a highly effective percutaneous treatment modality for hepatic hemangiomas. •We report the results of percutaneous microwave ablation for the treatment of symptomatic hepatic hemangiomas in humans.

Introduction/Objectives Patient Population: •From December 2010 to July 2012, five patients with six hepatic hemangiomas were treated with image-guided percutaneous microwave (MW) ablation (Figures). •Patient symptoms: Abdominal, back, or shoulder pain, nausea, vomiting, abdominal fullness, weight loss and early satiety. •No asymptomatic patients in the cohort, no alternative explanation for symptoms. •Diagnosis of hemangioma made based on contrast enhanced CT and/or MRI • Retrospective review performed under a waiver of informed consent provided by the IRB at our institution

Microwave Ablation Technique: •Single session image-guided, percutaneous microwave ablation performed in all patients. •All procedures done under general anesthesia •17-gauge MW antennas (Certus 140 LK, Precision/PR, Neuwave Medical, Madison WI) placed using real time sonography (Logiq E9, GE Medical Systems, Waukesha, WI) from an intercostal or subcostal approach with CT confirmation as needed. •Microwave energy (65W – 140W) with a 2.4GHz generator and monitored using real-time sonography. •Biphasic contrast-enhanced CT of the liver (Lightspeed Ultra, GE Medical, Waukesha, WI) performed immediately following antenna removal • In two patients, hydrodissection with 5% dextrose in water (D5W, mean volume 650 mL) was performed prior to ablation.

Follow-up: •Patients followed for post-procedure complications and symptom relief •Because patients were referred for treatment of symptoms, referring physicians were advised to obtain imaging on an as-needed basis

Materials/Methods

• All patients were women. Mean patient age was 47.7 years (range, 39-57) (Table 1)

• Three patients had single hemangiomas (Figure 1) and two patients had multiple hemangiomas

• Pre-treatment mean diameter and volume of the hepatic hemangiomas were 7.31 cm (range, 3.4-12.2 cm) and 315.6 cm3 (range, 20.6-951 cm3) respectively (Table 1)

• Mean ablation time 11.7 minutes (range, 5.0 to 24.5 minutes) (Table 1)

• Two tumors purposefully undertreated (approximately 90% tumor ablation) due to the central location of the neoplasm (Figure 2)

• Minimal procedural blood loss, no immediate post-procedural complications (0 %), no delayed adverse events (0 %).

• All patients were hospitalized overnight for observation (mean length of hospital stay=1 day)

• Mean patient follow-up 8.7 months (range, 0.5 to 19 months) • Immediate post-ablation mean diameter and volume of treated

hemangiomas 5.5 cm (range, 3.02 to 7.89 cm) and 111.5cm3 (range, 14.1 to 268.0 cm3); immediate 21 % decrease in tumor diameter and 48 % decrease in volume

• Two patients have undergone delayed imaging follow-up (mean 7.5 months, range 3 to 12 months). That demonstrated a continued decrease in mean ablated tumor diameter (9.75 cm to 6.4 cm) and volume (581.5 mL to 152 mL); a 35 % decrease in tumor diameter and 74 % decrease in tumor volume (Figures 3, 4).

• All patients had complete relief or substantial improvement of pain following the procedure

• Two patients developed recurrence of pain, described as different in quality and character more consistent with biliary colic

• Resolution of nausea and intermittent vomiting in the 3 patients who endorsed these symptoms pre-procedure.

• Persistent early satiety in one patient.

Results Table 1: Patient Characteristics and Radiologic Outcome

Patient Gender Age Follow up (mo)

Ablation time (min)

Mean Power (W)

Pre-ablation Diameter

(cm)

Post-Ablation Diameter

(cm)

Percent Diameter Change

Pre-Ablation Volume

(cc)

Post-Ablation Volume

(cc)

Percent Volume Change

1 F 39 19 15 88 8.9 5.4 -39 382 82 -79

2 F 57 11 8 65 7.3 6.1 -16 212 120 -43

3 F 42 11 24.5 65 12.2 7.9 -35 951 268 -72

4 F 40 2 9 65 8.1 6.5 -20 289 151 -48

5a 5b

F 57 0.5 5 65 4.1 4.0 -2 39 34 -13

8.5 70.3 3.4 3.0 -12 21 14 -33

Mean 47 8.7 11.7 66.1 7.3 5.5 -21 316 112 -48

Discussion

• A small number of patients with large hemangiomas present with pain due to capsular stretching or impingement on adjacent structures.4, 5

• No definitive test to determine whether a particular hemangioma is responsible for symptoms or is an incidental co-existent condition.

• With the uncertainties of treating individual patients in mind, the ideal treatment modality would be minimally invasive, safe with very low morbidity, highly effective in reducing symptoms, and allow a rapid return to normal function.

• Open surgical resection of hemangiomas is a definitive treatment method, but is associated with substantial morbidity, rare mortality, and a prolonged recovery period.10, 11

• Less invasive surgical techniques such as laparoscopic or robotic liver resections are becoming more common and hold promise to reduce morbidity and speed recovery in selected patients.33, 34

• Various percutaneous treatment methods have been proposed for hepatic hemangiomas, and the largest experience to date is with RF ablation.

• While the results of small case series have been excellent, particularly for smaller hemangiomas18,19,22,23, RF is limited by smaller ablation zones and long ablation times. For example, in one study of RF for hemangiomas, the mean treatment time was 39 minutes for tumors that ranged between 2.5-9.5 cm in diameter (no mean size was reported). The 9.5 cm tumor in that study required seven separate RF electrode insertions and 125 minutes of RF ablation.18 At our institution a 7.5 cm hemangioma treated by RF required 40 minutes of ablation with three electrodes.22

• MW devices create larger ablation zones in shorter times when compared to RF.36,37

• The mean treatment time in the current MW study was 11.7 minutes with fewer punctures with small gauge needles (17g)

• This more rapid treatment time and decreased number of punctures has the potential to decrease anesthesia and bleeding complications.

• The inherently high water content of hepatic hemangiomas appears to be a near ideal substrate for heating by microwaves, and the very slow circulation time in the tumor may limit vascular mediated cooling--a common reason for failure with all heat-based ablation methods, but less prominent for MW.

• The results of this study demonstrate that microwave ablation is a highly effective and safe treatment modality that rapidly devascularizes even very large hepatic hemangiomas.

• Secondary benefits of the treatment appear to be extensive tumor shrinkage (48% by volume in this series) and rapid resolution of abdominal pain, apparently related to capsular distention.

• The patients in our series recovered quickly post treatment and were able to rapidly resume the activities of daily living, including strenuous exercise .

• Although several patients did re-develop symptoms, this may not represent treatment failure, as it is possible the symptoms were not due to or were only partially due to the hemangioma.

• Limitations: Small number of patients and tumors, not a direct comparison with either surgery or other treatment modalities, and not every patient reported complete pain relief after treatment.

• In summary, microwave ablation of hepatic hemangiomas with a high-powered microwave device appears to be safe and effective in providing tumor devascularization, shrinkage, and pain relief.

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Figure 1: First symptomatic hemangioma treated in our practice. CT image (a) demonstrates a single lesion in the right hepatic lobe measuring 8.3 x 8.8 cm (arrow). Grayscale US re-demonstrates the lesion prior to (b) and during treatment (c). Initially, a single antenna was powered at 140 W for 5 minutes to treat tumor vascularity. Note the gas cloud nearly completely encompassing the tumor after an additional 10 minutes of ablation using three 17-g gas cooled MW antennas (Certus 140 LK, Neuwave Medical, Madison Wisconsin) powered at 65 W (arrows, c). CT image obtained after ablation demonstrates a 9.2 x 7.7 x 6.6 cm ablation zone nearly completely covering the hemangioma (arrows, d). D5W was used for hydrodissection to protect the body wall (*,d).

a b c d

Figure 1: Symptomatic hemangioma in a 39 yr old female with right sided abdominal pain

Figure 2: Hemangioma abutting the portal vein. Axial and coronal images demonstrate a large hemangioma (arrows, a, b) extending to abut the portal venous bifurcation (arrowhead,b). Post ablation coronal CT images demonstrate intentional sparing of the tumor at the level of the portal vein (arrows, c,d).

a b c d

Figure 2: Hemangioma abutting the portal venous bifurcation

a b c d e f g

Figure 3: Large hepatic hemangioma in a 42 yr old female with right upper quadrant pain

Figure 3: Large hemangioma at the right posterior hepatic dome seen on T1W post contrast axial (a) and T2W MRI (b) images (arrows). On the pre-ablation images, the hemangioma measures 12.2 cm in transverse and 13.1 cm in craniocaudal dimension. Grayscale US images obtained prior to and during ablation re-demonstrate the hyperechoic hemangioma (arrow, c) being partially encompassed by gas early in the ablation (arrow, d). Ablation was performed using 3 gas-cooled MW ablation antennas powered at 65 W. A total of 20 minutes of ablation were performed and the antennas were repositioned 4 times (5 min at each position). Immediate post procedure contrast enhanced CT (e) demonstrates near complete treatment of the lesion with gas tracking out to the periphery (arrow). Images obtained 12 months post (f, g) demonstrate marked decrease in size of the lesion, now measuring 6.1 cm in craniocaudal dimension.

Figure 4: Hemangioma in a 57 yr old female with nausea, vomiting and early satiety Figure 4: Large hemangioma (arrows) measuring 6.7 x 4.5 x 4.8 cm at the central hepatic dome abutting the IVC as seen on coronal SSFSE MR image (a) and CECT axial image (b). Immediate post ablation axial and coronal CT images demonstrate shrinkage of the tumor after treatment with 3 gas cooled antennas powered at 65 W for 8 minutes. Coronal SSFSE MR image obtained 3 months post procedure demonstrates marked decrease in size of the lesion, now 4.4 x 3.5 cm.

a b c d e

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Corresponding Author Meghan G. Lubner, M.D.

mlubner@uwhealth.org