Digestive Diseases
Dig Dis 2016;34:687-691 DOI: 10.1159/000448857
US-US Fusion Imaging in Radiofrequency Ablation for Liver Metastases
Yasunori Minami Tomohiro Minami Hirokazu Chishina Masashi Kono
Tadaaki Arizumi Masahiro Takita Norihisa Yada Satoru Hagiwara Hiroshi Ida Kazuomi Ueshima Naoshi Nishida Masatoshi Kudo
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
Key Words
Ablative margin . Liver metastasis . Radiofrequency ablation · US-US fusion imaging
Abstract
Objective: Radiofrequency ablation (RFA) induces gas bub- bles in ablation zones, and the ablative margin cannot be evaluated accurately on ultrasound (US) during and immedi- ately after RFA. This study assessed the usefulness of US-US fusion imaging to visualize the ablative margin of RFA for liv- er metastasis. Methods: RFA guided by US-US fusion imag- ing was performed on 12 targeted tumors in 10 patients. Sec- ondary hepatic malignancies included patients with colorec- tal cancer (n = 4), breast cancer (n = 2), lung cancer (n = 1), gastrointestinal stromal tumor (n = 1), pancreatic neuroen- docrine tumor (n = 1), and adrenocortical carcinoma (n = 1). The maximal diameter of the tumors ranged from 0.8 to 4.0 cm (mean ± SD 1.6 ± 0.9 cm). Results: The mean number of electrode insertions was 1.6 per session (range 1-3). Techni- cally, effective ablation was achieved in a single session in all patients, and safety ablative margins were confirmed on con- trast-enhanced CT for early assessment of tumor response. There were no serious adverse events or procedure-related complications. During the follow-up period (median 220 days, range 31-417 days), none of the patients showed local tumor progression. Conclusion: US-US fusion imaging could
show the tumor images before ablation and the ablative area on US in real time. The image overlay of US-US fusion imag- ing made it possible to evaluate the ablative margin three dimensionally according to the US probe action. Therefore, US-US fusion imaging can contribute to RFA therapy with a safety margin, that is, the so-called precise RFA.
@ 2016 S. Karger AG, Basel
Introduction
Liver metastasis is one of the critical factors that deter- mines the prognosis of patients with advanced stage can- cer. Although surgery can be a therapeutic choice for cure in patients with liver metastases, difficulties of surgical re- section may be related to the size, site, and number of tu- mors, vascular and extrahepatic involvement, as well as poor liver function. There is a need for an effective and less invasive technique for the treatment of unresectable he- patic malignancies. Recently, several local ablative tech- niques have been reported to be effective in patients con- sidered for liver-directed therapies. In particular, radio- frequency ablation (RFA) [1-4] has resulted in a higher rate of complete necrosis of metastatic lesions in the liver [5-8]. The advantages of minimal invasiveness and good survival with RFA have had a positive impact on the clin- ical management of patients with liver metastasis [9, 10].
KARGER
For technical success of the RFA procedure, the tumor and a safety margin must be included in the ablation zone [11]. The local recurrence rate differs markedly depend- ing on whether or not a 5 mm ablative margin is secured to eradicate potential microscopic invasion [12, 13]. However, ultrasound (US) is often restricted by the for- mation of gas bubbles that cause strong acoustic scatter- ing within the ablated area; the targeted region can be obscured by an irregular hyperechoic zone, so the safety margin cannot be evaluated accurately on US during and immediately after RFA [14]. Failure to establish a suffi- cient ablative safety margin is an independently signifi- cant risk factor for local tumor progression on multivari- ate analysis [15]. Local tumor progression after RFA is frequently encountered in patients with liver metastasis.
Recent advancements in technology permit two-di- mensional (2D) multiplanar reconstruction images of CT or MRI to display in the same plane as US images in real time. It was reported that fusion imaging-guided RFA was useful in the treatment of hepatic malignancies that were inconspicuous on B-mode US [16-21]. Moreover, the application of fusion imaging allows display of the tu- mor before and during/after ablation on the same US im- ages side by side, and the imaging overlays can show the tumor image before ablation within an ablated hyper- echoic zone in real time. Therefore, the image overlay of US-US fusion imaging can visualize the ablative margin three dimensionally according to the US probe action. The purpose of this study was to assess the usefulness of US-US fusion imaging in RFA for liver metastasis.
Materials and Methods
Patient Selection and Eligibility
Approval for this retrospective study was obtained from the lo- cal ethical review board. Written informed consent to perform RFA was obtained from all patients before treatment.
This cohort study was conducted as a retrospective analysis in a single institution. This study included patients with liver metas- tasis who underwent RFA and who had undergone dynamic CT 1 month previously. Between October 2014 and March 2016, 10 patients (5 men, 5 women; age range 41-89; mean age ± SD 60.9 ± 12.2 years) with 12 liver metastases were analyzed. Secondary he- patic malignancies included patients with colorectal cancer (n = 4), breast cancer (n = 2), lung cancer (n = 1), gastrointestinal stromal tumor of the stomach (n = 1), pancreatic neuroendocrine tumor (n = 1), and adrenocortical carcinoma (n = 1). Before RFA, all pa- tients with liver metastasis had undergone systemic chemotherapy after surgical resection of the primary tumor. Nine patients had not been treated previously for these hepatic lesions. One patient with a metastasis had shown local tumor progression after RFA. The maximal diameter of the tumors ranged from 0.5 to 4.0 cm
(mean ± SD 1.6 ± 0.9 cm) on dynamic CT. The distance from the skin to the deepest edge of the tumor on sonography ranged from 1 to 9 cm (mean ± SD 4.1 ± 2.7 cm).
Patients were considered eligible for RFA if the diagnosis of liver metastasis was confirmed by typical radiologic findings. Ad- ditional eligibility criteria included less than 3 nodules ≤3 cm each; good liver function (Child-Pugh class A or B); absent or trace as- cites; albumin level of more than 2.0 g/dl; alanine aminotransferase and aspartate aminotransferase levels of less than 5 times the upper normal limit; total serum bilirubin level of less than 3.0 mg/dl; pro- thrombin time-international normalized ratio less than 1.5; serum creatinine level of less than 2.0 mg/dl; and platelet count of at least 30,000/mm3. The exclusion criteria were as follows: poor patient cooperation; patients with target lesions that could be confidently localized on contrast-enhanced US (CEUS); and a target lesion lo- cated in a sonographically blind area (e.g., anterior subphrenic area of the right liver). All patient characteristic data at baseline were collected and reviewed before RFA.
Equipment
A US machine (LOGIQ E9, GE Healthcare, Chalfont St. Giles, UK) coupled with a low magnetic field generator was used. Two electromagnetic position sensors connected with a position-sens- ing unit were attached on the probe (4.0 MHz curvilinear C1-6, GE) through a bracket. Both the transmitter and the sensors were connected to a position-sensing unit embedded in the US ma- chine.
Patients were treated using the RFA (VIVA RF ablation system; STARMed Co., Goyang, Gyeonggi, South Korea). Twenty-centi- meter-long, 17-gauge, monopolar internally cooled electrodes (VIVA RF electrode; STARMed) were used to deliver radiofre- quency energy, and the active metallic tip could be adjusted in 5 mm intervals up to 3 cm long. A 200-W, 480-kHz monopolar radiofrequency generator regulated by impedance (VIVA RF gen- erator, STARMed) and having 3 styles of power distribution (Gen- eral, Auto, Continuance modes) was used as the energy source.
A multidetector CT (LightSpeed VCT, GE Healthcare, Chal- font St. Giles, UK) was used for diagnosis. Triple-phase contrast- enhanced CT scans were performed with a 5.0-mm slice thickness at 30, 60, and 180 s after initiating the injection of contrast medium to obtain hepatic arterial, portal venous and equilibrium phase im- ages, respectively. A total of 100 ml of nonionic contrast material containing 300 mg of iodine/ml (Iomeprol, Eisai Co., Tokyo, Japan) was injected intravenously at a rate of 3 ml/s using an auto- matic power injector.
US-US Fusion Imaging and RFA Procedure
Before inserting the radiofrequency needle, the three-dimen- sional (3D) US volume was obtained by scanning the liver in a manual sweeping manner with the patient in a breath-holding state. The scanning area had to include not only the tumor but also intrahepatic vessels around the tumor. This 3D volume data con- tained the spatial information in the generated magnetic field. A cross-section of the 3D US volume was selected based on the larg- est diameter dimension of the tumor, and 2 green squares on the screen were arranged to fix a perpendicular line through the center of the tumor image. Then, 6 rotated sections passing through the tumor center were automatically displayed. Thereafter, the region of interest was manually drawn along the tumor border in each rotated sections, with the result that the tumor border could be
a
b
c
traced three dimensionally. The interior was colorized, and 3D-US volume data were stored within the US machine.
Immediately after ablation, the clinical role of US is markedly limited because of the initial hyperechoic ablated zone, the so- called echogenic cloud, and the resultant acoustic shadowing. This echogenic cloud persists for a period ranging from 15 min to 6 h after RFA [22]. As the acoustic shadowing gradually disappeared, the 3D-US volume data was fused with the real-time 2D US image. These 2 images were displayed simultaneously on a split-screen display, and then this fusion imaging allowed comparison of the tumor images before ablation and the ablative area on US in real time. Moreover, the 2 images could be overlaid, and the image overlay allowed easy visualization of the ablative margin on US.
All RFA procedures were performed by 3 experienced hepa- tologists (M.T., Y.M., and H.I., with 5, 19 and 20 years of experi- ence, respectively). The tip length choice for the active RF elec- trode was 0.5-1.0 cm over the tumor size. Under auto mode, pow- er was usually begun at 40 W with a 2-cm exposed-tip RF electrode or at 50 W with a 3-cm exposed-RF tip. After a few times of power roll-off, the RFA procedure was terminated if the ablative hyper- echoic zone had expanded over the tumor with the safety margin.
Assessment of Technical Effectiveness and Follow-Up
A few days after treatment, the technical effectiveness of abla- tion was assessed based on contrast-enhanced CT scan findings. A tumor was considered to have been successfully ablated when there were no longer any enhanced regions within the entire tumor during the arterial phase and at least a 0.5 cm margin of appar- ently normal hepatic tissue surrounding the tumor during the por- tal phase. Part of the tumor was diagnosed as remaining viable when images of the ablated area showed nodular peripheral en- hancement [23, 24].
If 1-month follow-up CT images showed successful ablation and no new tumors, 3-phase contrast-enhanced CT scans were re- peated at 3-month intervals. All patients were followed for at least 1 month after RFA and underwent at least one follow-up CT ex- amination by 2 radiologists who had more than 20 years of experi- ence. Any complications were recorded.
Results
In the post-vascular phase, all of the 10 liver metastases (83%) were depicted as defects with a clear margin, and 2 nodules (17%) were depicted as defects with an unclear margin. The mean number of electrode insertions was 1.6 per session (median 1, range 1-3). The technical effec- tiveness of ablation was achieved in a single session in all patients, and safety ablative margins were confirmed on contrast-enhanced CT for early assessment of tumor re- sponse (fig. 1). There were no serious adverse events or procedure-related complications (e.g., hemorrhage, in- fection, hepatic failure or death). Grade 1 to 2 pain on the Common Toxicity Criteria of the National Cancer Insti- tute was the most common side effect, reported by 6 pa- tients.
Follow-up time ranged from 31 to 417 days (mean 206 days, median 220 days). During the follow-up period, none of the patients showed local tumor progression. However, a single patient demonstrated distant multiple metastases in the liver.
Discussion
The ablative margin of RFA cannot be fully evaluated on B-mode US and/or CEUS. However, this US-US fu- sion image overlay is a revolutionary technology, allow- ing us to visualize the ablative margin three dimension- ally. To the best of our knowledge, this is the first report to display the ablative margin of RFA on US. Our study showed that good local control was obtained by RFA
guided by US-US fusion imaging in patients with liver metastasis, although local tumor progression is often en- countered in such patients after RFA. Our results could confirm the sufficient ablative margin of RFA by design in patients with liver metastasis.
US-US fusion imaging has 3 clinical applications in RFA therapy. The first is the real-time monitoring of RFA lesion formation. Clinicians can employ B-mode US to observe the bubble-related hyperechoic region and preliminarily evaluate the ablation zones comparing the pre-ablation image of the tumor using US-US fusion im- aging. The second application is related to decision mak- ing about additional ablation. We could confirm any le- sion with a poor ablative margin during the session, and then extend the necrotic area by additional ablation. The third is visualization of the safety margin on US. Al- though the endpoint of conventional RFA cannot be based on objective evidence with US, US-US fusion im- aging offers an evidence-based quality improvement in RFA therapy.
Many have reported that the local recurrence rate in- creased with larger size of tumor in RFA [25-28]. A larg- er tumor requires multiple ablations to prevent recur- rence, and it is often difficult to obtain a sufficient ablative margin over the whole nodule with larger hepatic malig- nancies. However, US-US fusion imaging enables ob- taining a safety margin even for larger tumors because it allows 3D visualization of the ablative margin. However,
this US-US fusion imaging system still has room for improvement. The setup process of US-US fusion imag- ing requires multiple steps and it is complicated. Espe- cially, it is complicated to trace the border of the tumor for colorization of the tumor on 6 rotated images. We strongly anticipate the resolution of these disadvantages by simplifying the setup process of US-US fusion imag- ing.
The principal limitation of this study was its retrospec- tive design. The second was that this study could suffer from selection bias because the patients were enrolled ac- cording to the tumor size and/or number for RFA indica- tion.
Another limitation is the preliminary nature of this study with a relatively small number of patients and a short follow-up time. Further prospective studies of this technique with larger number of patients are warranted.
In conclusion, US-US fusion imaging could show tu- mor images before ablation and the ablative area on US in real time. The image overlay of US-US fusion could visualize the ablative margin of RFA on US. Therefore, US-US fusion imaging can contribute to RFA therapy with a safety margin, that is, the so-called precise RFA.
Disclosure Statement
The authors declare that no conflict of interest exists.
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