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Liver Cancer: Increased Microwave Delivery to Ablation Zone with Cooled-Shaft Antenna—Experimental and Clinical Studies¹

¹ From the Departments of Hepatobiliary Surgery (M.K., M.D.L.), Medical Ultrasonics (M.D.L., X.Y.X., H.X.X., G.J.L., Z.F.X., Y.L.Z., J.Y.L.), and Anesthesia (L.Q.M.), the First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China. Received December 12, 2005; revision requested February 7, 2006; revision received April 10; accepted May 17; final version accepted July 12. Address correspondence to M.D.L. (e-mail: lumd{at}21cn.com).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 
Purpose: To prospectively investigate whether the ablation zone induced with microwaves could be increased by delivering greater energy with a cooled-shaft antenna.

Materials and Methods: All studies were animal care and ethics committee approved. Written informed consent was obtained from all patients. Microwave ablation was performed by using a cooled-shaft antenna in 48 ex vivo and 12 in vivo experiments with porcine livers. The coagulation diameters achieved in different microwave ablation parameter groups (60–90 W for 5–25 minutes) were compared. Ninety patients (78 men, 12 women; mean age, 53 years; age range, 20–82 years) with 133 0.8–8.0-cm (mean, 2.7 cm ± 1.5 [standard deviation]) primary or metastatic liver cancers were treated with the same microwave ablation technique. Complete ablation (CA) and local tumor progression (LTP) rates were determined. Generalized estimating equations were used to compare differences in tumor size, ablation zone diameter, and CA and LTP rates between different patient subgroups.

Results: In the ex vivo livers, in vivo livers, and liver cancers, one application of microwave energy with 80 W for 25 minutes produced mean coagulation diameters of 5.6 x 7.4 cm, 3.5 x 5.9 cm, and 3.6 x 5.0 cm, respectively. Skin burn was not observed. CA rates in small (3.0-cm), intermediate (3.1–5.0-cm), and large (5.1–8.0-cm) liver cancers were 94% (81 of 86), 91% (31 of 34), and 92% (12 of 13), respectively. During a mean follow-up period of 17.4 months, LTP occurred in seven (5%) treated cancers. There was a significant difference in LTP rate between the cirrhosis and no-cirrhosis groups (P = .03). Four patients had major complications.

Conclusion: Delivery of greater microwave energy with cooled-shaft antennas yielded large ablation zones in ex vivo and in vivo livers and in liver cancers. Effective local tumor control was achieved during one microwave ablation session.

© RSNA, 2007

	INTRODUCTION

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Microwave ablation is one of the common thermal ablation therapies for treatment of liver malignancies (1–3). Microwaves are transmitted by a microwave generator to a monopole antenna inserted into the liver tumor. Theoretically, greater energy delivery yields greater coagulation necrosis. However, the temperature of the antenna shaft increases rapidly with the elevation of applied energy, and this may result in severe skin burns and unbearable pain. Consequently, a single application of microwave energy is usually performed at low power outputs and in short ablation durations, which produce relatively small areas of coagulation necrosis and incomplete eradication of the tumor in one treatment session (4–6). The purpose of our study was to prospectively investigate whether the microwave ablation—induced ablation zone can be extended by delivering greater energy with a cooled-shaft antenna.

	MATERIALS AND METHODS

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Microwave Ablation Equipment
Three sequential studies were performed: ex vivo and in vivo porcine liver studies and a clinical study. A microwave delivery system (FORSEA; Qinghai Microwave Electronic Institute, Nanjing, China) was used in all three studies. This system consisted of an MTC-3 microwave generator (FORSEA) with a frequency of 2450 MHz, a power output of 10–150 W, a flexible low-loss cable, and a 14-gauge cooled-shaft antenna. The generator was equipped with two output sources, which allowed simultaneous application of microwave energy through two antennas. The cooled-shaft antenna, which consisted of a 10-cm-long cable connection portion, a 16.5-cm-long shaft coated with Teflon, and a 1.5-cm-long active tip coated with polytetrafluoroethylene, was used to deliver energy to the liver tissue (Fig 1). The antenna shaft contained two lumina that enabled the delivery of 4°C saline solution to the tip of the shaft and the return of the warmed solution to a 500-mL plastic bag outside the body. A steady-flow pump (BT01-100 LanGe-Pump; LanGe Steady Flow Pump, Baoding, China) was used to push the chilled saline solution circulating within the lumina of the antenna shaft at 50–60 mL/min. The amount of circulating chilled solution could be adjusted to maintain a mean shaft temperature of 10°C ± 2 (standard deviation).

View larger version (13K): [in this window] [in a new window] [Download PPT slide]   Figure 1: Schematic diagram of cooled-shaft antenna. The 14-gauge cooled-shaft antenna consists of a 10-cm-long cable connection portion, a 16.5-cm-long shaft, and a 1.5-cm antenna. With use of a steady-flow pump, the 4°C saline solution circulates within the lumina of the antenna shaft so that the shaft maintains a mean temperature of 10°C ± 2 (standard deviation) during microwave ablation.

Ex Vivo Studies
Single-application microwave ablation was performed at room temperature (25°C) in 22 fresh porcine livers purchased from local markets.

Phase 1: comparing the coagulation achieved along the antenna track by using microwave ablation with noncooled- and cooled-shaft antennas.—A noncooled- or cooled-shaft antenna was inserted 6–9 cm into the liver tissue. Three antennas were inserted into one liver, and two livers were used in each ablation parameter group (n = 12). Twelve ablations each of 60 W for 5 minutes were performed. Immediately after each ablation procedure, the liver specimen was sectioned along the antenna track and the morphologic features of the track were compared. All procedures were performed by two authors (M.K., M.D.L.) who had 5 and 10 years of experience, respectively, with ablation procedures.

Phase 2: comparing the sizes of the coagulation zones induced by cooled-antenna microwave ablation at different energy levels.—Microwave ablation was performed by using a cooled-shaft antenna at 60, 70, 80, and 90 W for 5, 15, and 25 minutes. A total of 12 ablation parameter settings were tested in 18 livers. Each ablation parameter group was tested in triplicate, for a total of 36 experiments. After the ablation, the liver specimens were immediately sectioned along the longitudinal and transverse axes of each lesion. The visualized coagulated area was measured with calipers. The coagulation diameter along or perpendicular to the antenna track was measured in consensus between two observers (M.K., G.J.L.), and the size of the coagulation zone was described in terms of the short-axis times long-axis coagulation diameter. The coagulation diameters achieved in the different ablation parameter groups were compared.

In Vivo Studies
Three 42.0–48.0-kg Nanhai pigs were used to study the sizes of the coagulated areas produced with cooled-antenna microwave ablation in normal livers. Approval from the University Subcommittee on Animal Research Experiments was obtained before the initiation of these studies. General anesthesia was induced in the animals by means of intramuscular injection of ketamine hydrochloride (10–15 mg per kilogram of body weight) and maintained by means of intramuscular injection of pentobarbital sodium (3 g/100 mL, 0.25 mL/kg) and intravenous injection of diazepam (5–10 mg). Endotracheal intubation was performed. Cardiac and respiratory parameters were monitored throughout the procedures.

Laparotomy was performed, and the liver was exposed. With the use of 12-gauge guiding needles, cooled antennas were inserted approximately 7–9 cm into the liver parenchyma. Ultrasonographic (US) guidance helped us to avoid inserting the antennas into large intrahepatic vessels. Single applications of microwave energy were performed at 60 W for 5 minutes, at 70 W for 20 minutes, and at 80 W for 25 minutes. In addition, two parallel antennas spaced 2 cm apart were inserted into the liver and simultaneous microwave energy was delivered at 70 W for 20 minutes. Three experiments were performed for each parameter setting. Immediately after performing the ablations, we excised the livers for gross pathologic analysis and then sacrificed the animals by incising the inferior vena cava. The methods used to section the specimens and measure coagulation diameter were identical to those used in the ex vivo experiments. All ablation procedures were performed by two authors (M.K., X.Y.X.) with 4 and 8 years experience, respectively, with microwave ablation procedures.

Temperature measurements were performed in all of the in vivo experiments. Three 20-gauge thermistor probes (response time < 1 second, accuracy 1.0°C) were placed 1, 2, and 3 cm from the antenna during single-application microwave ablation. To investigate the temperature change in the tissue surrounding two antennas during simultaneous microwave application, thermistor probes were placed 0, 2, and 3 cm from the parallel central line between the two antennas. Temperatures were recorded at 1-minute intervals for the 60-W ablation group and at 3-minute intervals for the other ablation groups.

Clinical Study
Patients.—The study was approved by our hospital ethics committee, and written informed consent was obtained from each patient. Between August 2003 and December 2004, 90 patients (78 men, 12 women; mean age, 53 years; age range, 20–82 years) with liver cancer underwent US-guided percutaneous microwave ablation with cooled-shaft antennas at our hospital. No patients were considered to be surgical candidates because they had bilobal tumors (n = 22), had previously undergone hepatectomy or transcatheter arterial embolization (n = 20), had insufficient liver reserve (n = 4), were advanced in age and had chronic heart or renal disease (n = 10), or had refused to undergo surgery (n = 34). Eligibility criteria included no evidence of extrahepatic metastases, no tumoral invasion of adjacent organs, five or fewer tumor nodules, and no severe coagulopathy (eg, platelet count < 50 x 10⁹/L or prolonged prothrombin time > 7 seconds).

Before treatment, pathologic proof of liver cancer was obtained in each patient by using US-guided fine-needle biopsy. Of the 90 patients, 74 had hepatocellular carcinoma (HCC); two, cholangiocarcinoma; and 14, hepatic metastases of colorectal (n = 11), gallbladder (n = 1), pancreatic (n = 1), or gastric (n = 1) origin. The numbers of patients with one, two, three, four, and five nodules were 62, 20, three, three, and two, respectively. A total of 133 tumors 0.8–8.0 cm in diameter were treated: 86 (64.7%) were small (3.0 cm); 34 (25.6%), intermediate in size (3.1–5.0 cm); and 13 (9.8%), large (>5.0 cm). The mean maximum diameters of the small, intermediate, and large tumors were 1.9 cm ± 0.5 (standard deviation), 3.6 cm ± 0.5, and 6.2 cm ± 1.0, respectively. Liver function status was classified as Child-Pugh class A in 84 (93%) patients and class B in six (7%). Sixty-eight (76%) patients had liver cirrhosis.

Imaging equipment.—A US scanner (Acuson Sequoia 512; Siemens, Berlin, Germany) with a 2–5-MHz vector transducer and a puncture guide device was used to estimate the maximum dimensions of the tumors and monitor the microwave ablation procedures and follow-up examinations. Tumor dimensions were estimated by one of four authors (X.Y.X., H.X.X., Z.F.X., or G.J.L.) with 13, 11, 6, and 5 years experience, respectively, with US. A spiral computed tomographic (CT) scanner (Xpress/SX; Toshiba, Tokyo, Japan), 1.5 mL/kg of iopromide (Ultravist 300; Schering, Berling, Germany) power injected at 3 mL/sec, and the following parameters were used to acquire contrast material–enhanced images: 10-mm-thick sections, 10-mm collimation, 1-second scan acquisition, pitch of 1:1, 120 kV, and 250 mA. In addition, a 1.5-T superconducting magnetic resonance (MR) system (Magnetom Vision or Magnetom Symphony; Siemens) with 25 mT/m maximum gradient capability and a phased-array body coil were used to obtain all of the MR images (8-mm-thick sections, 2-mm intersection gap). Dynamic gadolinium-enhanced MR images were obtained in the hepatic arterial, portal venous, and equilibrium phases after intravenous administration of 19 mL of gadopentetate dimeglumine (Magnevist; Berlex Laboratories, Wayne, NJ) at 2 mL/sec.

Ablation technique.—Microwave ablation was performed with the patients in a state of local anesthesia that was induced with 1% lidocaine. Conscious analgesia-sedation was induced by intravenously administering 0.1 mg of tramadol (Grunenthal, Aachen, Germany), 2.5 mg of droperidol (Xu Dong Hai Pu Pharmaceutical, Shanghai, China), and 0.1 mg of fentanyl (Yi Chang Pharmaceutical, Hu Bei, China). Ablation procedures were performed by one of four authors (M.K., M.D.L., X.Y.X., or H.X.X.). With real-time US guidance, the antenna was percutaneously introduced through the guiding needle into the tumors, and the active tip was placed in the deepest part of the nodule. The antenna was placed with the intent to completely eradicate the tumor along with an ablative margin of 0.5–1.0 cm.

For small tumors, single-application microwave ablation with 80 W for 25 minutes through one antenna inserted at the center of the tumor was performed. An exception to this protocol was that for tumors smaller than 2 cm, 70 W of microwave energy was delivered for 20 minutes. For intermediate nodules, simultaneous applications of microwave energy—each of 70 W for 20 minutes—were delivered through two antennas inserted parallel at the largest tumor surface 2.0 cm apart. To treat large tumors, multiple overlapping ablations (as many as six)—each of 70 W for 20 minutes—were performed with three or four inserted antennas. In these cases, two parallel antennas spaced 2.0–2.5 cm apart were initially placed in the tumor 1.0–1.5 cm from the tumor margin, and microwave energy was simultaneously delivered. Afterward, the antennas were withdrawn about 2 cm and another round of simultaneous ablations were performed. Finally, additional one or two antenna insertions and ablations were used to eradicate the tumor zones that had not been treated. All ablations were completed during one treatment session. To prevent possible tumor seeding, the needle track was cauterized for 10 seconds when the antenna was withdrawn.

Effectiveness and follow-up.—The local effectiveness of the microwave ablation was assessed by comparing the baseline contrast-enhanced CT or MR images with those obtained 1 month after treatment. The images were compared in consensus by two authors (H.X.X., G.J.L.) with 10 and 5 years experience, respectively, in CT and MR imaging. The long- and short-axis cross-sectional diameters of the ablation zones, which usually corresponded to the macroscopic findings (7), were documented according to the image reports. Complete ablation (CA) was defined as uniform hypoattenuation (at CT) or hypointensity (at MR) without enhancement in the ablation zone; otherwise, the zone was documented as having incomplete ablation. Additional microwave ablation sessions and the same type of image assessment were performed for tumors with incomplete ablation. Tumors with CA were followed up, while those with incomplete ablation after three microwave ablation sessions were considered to be unsuccessfully treated and were excluded from the current study. Local tumor progression (LTP) was defined as regrowth of tumor inside or adjacent to the nodule that initially was completely ablated. Distant recurrence was defined as the presence of new intra- or extrahepatic tumors. Primary CA rate was defined as the percentage of tumors completely eradicated after the first microwave ablation session. Any ablation-related complication or side effect was documented. In all patients, follow-up with abdominal color Doppler US; serum tumor marker analyses such as -fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9 level examinations; and liver function tests were performed monthly for the first 6 months and every 3–6 months thereafter. In cases of suspicious US findings, fine-needle biopsy and either contrast-enhanced CT or contrast-enhanced MR imaging were performed.

Statistical Analyses
Continuous data were expressed as means ± standard deviations. In the ex vivo and in vivo studies, an independent Student t test was used to compare coagulation diameters between different groups. In the clinical study, generalized estimating equations were used to compare the differences in maximum tumor diameter, ablation zone diameter, and CA and LTP rates between the HCC and liver metastasis patient subgroups and between the cirrhosis and no-cirrhosis subgroups. The ² test or Fisher exact probability test was used to compare the differences in distant recurrence and complication rates between the patient subgroups. Two-tailed P < .05 was considered to indicate statistical significance. The Stata software package (version 8.0; Stata, College Station, Tex) was used to perform generalized estimating equation analysis. SPSS software (version 10.0; SPSS, Chicago, Ill) was used to perform the other statistical analyses.

	RESULTS

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Ex Vivo Study
Phase 1: comparing coagulation along the antenna track induced by microwave ablation with noncooled- and cooled-shaft antennas.—Thermal effects on the antenna track outside the coagulation zone were observed in the noncooled-shaft-antenna ablation group but not in the cooled-shaft-antenna ablation group (Fig 2).

View larger version (75K): [in this window] [in a new window] [Download PPT slide]   Figure 2a: Ex vivo porcine liver in which one application of microwave energy at 60 W for 5 minutes was performed by using (a) normal (noncooled-shaft) and (b) cooled-shaft antennas. (a) Microwave energy applied through a noncooled-shaft antenna produced an elliptical coagulated area (arrows). The antenna track (arrowheads) is also coagulated. (b) Coagulated area (arrows) produced by microwave ablation with a cooled-shaft antenna is almost spherical. The antenna track (arrowheads) is not coagulated.

View larger version (92K): [in this window] [in a new window] [Download PPT slide]   Figure 2b: Ex vivo porcine liver in which one application of microwave energy at 60 W for 5 minutes was performed by using (a) normal (noncooled-shaft) and (b) cooled-shaft antennas. (a) Microwave energy applied through a noncooled-shaft antenna produced an elliptical coagulated area (arrows). The antenna track (arrowheads) is also coagulated. (b) Coagulated area (arrows) produced by microwave ablation with a cooled-shaft antenna is almost spherical. The antenna track (arrowheads) is not coagulated.

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 3a: Gross specimens of porcine liver tissue treated with cooled-shaft-antenna microwave ablation in vivo. (a) An elliptical coagulation zone of 3.5 x 5.7 cm (arrows) was produced with one application of 80 W for 25 minutes. The antenna track (arrowhead) is not coagulated. (b) Simultaneous application of 70 W for 20 minutes through two antennas yielded a 5.7 x 6.5-cm coagulation zone (arrows). The antenna tracks (arrowheads) are not coagulated.

View larger version (85K): [in this window] [in a new window] [Download PPT slide]   Figure 3b: Gross specimens of porcine liver tissue treated with cooled-shaft-antenna microwave ablation in vivo. (a) An elliptical coagulation zone of 3.5 x 5.7 cm (arrows) was produced with one application of 80 W for 25 minutes. The antenna track (arrowhead) is not coagulated. (b) Simultaneous application of 70 W for 20 minutes through two antennas yielded a 5.7 x 6.5-cm coagulation zone (arrows). The antenna tracks (arrowheads) are not coagulated.

View larger version (180K): [in this window] [in a new window] [Download PPT slide]   Figure 4a: Transverse contrast-enhanced T1-weighted MR images (fast low-angle shot sequence, 150/4.1 [repetition time msec/echo time msec], 80° flip angle, 224 x 256 matrix, 260–340-mm field of view) in a patient who underwent microwave ablation of HCC. (a) Hepatic arterial phase preablation image shows a 2.3 x 2.5-cm HCC (arrow). (b) Image obtained 1 month after a single ablation with 80 W for 25 minutes shows a 3.5 x 4.5-cm nonenhancing zone of hypointensity enveloping the tumor (arrow).

View larger version (171K): [in this window] [in a new window] [Download PPT slide]   Figure 4b: Transverse contrast-enhanced T1-weighted MR images (fast low-angle shot sequence, 150/4.1 [repetition time msec/echo time msec], 80° flip angle, 224 x 256 matrix, 260–340-mm field of view) in a patient who underwent microwave ablation of HCC. (a) Hepatic arterial phase preablation image shows a 2.3 x 2.5-cm HCC (arrow). (b) Image obtained 1 month after a single ablation with 80 W for 25 minutes shows a 3.5 x 4.5-cm nonenhancing zone of hypointensity enveloping the tumor (arrow).

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 5a: Transverse contrast-enhanced CT scans in a patient who underwent microwave ablation of metastatic liver cancer. (a) Preablation scan shows a 3.7 x 4.1-cm liver metastasis (arrows) of colon origin. (b) Scan obtained 1 month after ablation involving simultaneous energy application through two antennas shows a 5.0 x 6.0-cm hypoattenuating ablation zone (arrows).

View larger version (171K): [in this window] [in a new window] [Download PPT slide]   Figure 5b: Transverse contrast-enhanced CT scans in a patient who underwent microwave ablation of metastatic liver cancer. (a) Preablation scan shows a 3.7 x 4.1-cm liver metastasis (arrows) of colon origin. (b) Scan obtained 1 month after ablation involving simultaneous energy application through two antennas shows a 5.0 x 6.0-cm hypoattenuating ablation zone (arrows).

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 6a: Transverse contrast-enhanced CT scans in a patient who underwent microwave ablation of HCC. (a) Preablation scan shows a 4.3 x 5.1-cm tumor (arrows) in the left lobe. (b) Scan obtained 1 month after ablation involving three energy applications through three antennas shows a 5.7 x 6.8-cm coagulation zone (arrows).

View larger version (173K): [in this window] [in a new window] [Download PPT slide]   Figure 6b: Transverse contrast-enhanced CT scans in a patient who underwent microwave ablation of HCC. (a) Preablation scan shows a 4.3 x 5.1-cm tumor (arrows) in the left lobe. (b) Scan obtained 1 month after ablation involving three energy applications through three antennas shows a 5.7 x 6.8-cm coagulation zone (arrows).

The mean follow-up periods were 17.4 months ± 4.4 (range, 8–26 months) for all patients, 17.3 months ± 4.3 for the patients with HCC, and 17.9 months ± 5.2 for the patients with hepatic metastasis. Thirty-five (39%) patients were followed up for more than 18 months; 47 (52%), for 12–18 months; and eight (9%), for less than 12 months. LTP was observed in seven (5%) tumors 1.8, 2.7, 3.2, 7.0, 8.0, 11.1, and 16.0 months after the first microwave ablation session. Tumors with LTP were close to the gastrointestinal tract (n = 3), liver capsule (n = 2), and inferior vena cava (n = 2). LTP rates were 6% (five of 86), 6% (two of 34), and 0% for the small, intermediate, and large tumors, respectively. The difference in LTP rate was significant between the cirrhosis and no-cirrhosis groups (P = .03) but not between the HCC and metastasis groups (P = .19). Four tumors with LTP were completely destroyed after additional microwave (n = 2) or ethanol (n = 2) ablation, one was surgically resected, and the remaining two were not treated because multiple distant recurrences were found and the patient refused to undergo further treatments. New intra- or extrahepatic tumors were found in 35 (39%) patients 1.0–12.3 months (mean, 3.2 months ± 3.0) after the first microwave ablation session. There was a significant difference in distant recurrence rate between the patients with HCC (25 [34%] of 74) and those with metastasis (10 [71%] of 14) (P = .002).

Most patients reported having grade 1 intraprocedural pain (according to National Cancer Institute common toxicity criteria) in the upper part of the abdomen, which resolved immediately after the ablation procedure ended. Grade 1 postprocedural pain was reported by 63 (70%) patients and usually resolved with a nimesulide (0.1 g/d) regimen within 3–4 days after the ablation. Fifty-eight (64%) patients had a low-grade fever that lasted 12–72 hours after the treatment. No skin burns were observed. In the majority of patients, serum transaminase levels increased two to six times the baseline levels during the first 3–5 days after ablation. Asymptomatic pleural effusion, self-limiting intraperitoneal bleeding, blood thrombus in the portal vein, and transient gross hematuria were observed in seven patients but required no medical intervention. No tumor seeding was observed in any patients. Major complications occurred in four (4%) patients: symptomatic pleural effusion requiring drainage (n = 2), subcutaneous abscess requiring drainage (n = 1), and colon leakage requiring drainage and parenteral nutrition therapy (n = 1) (Table 4). All patients with major complications were cured within 3 months.

	DISCUSSION

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Thermally mediated tumor ablation techniques such as radiofrequency (RF) and microwave ablation have been widely used as minimally invasive strategies to treat small liver tumors (8–10). However, a key limitation of these methods has been the small extent of coagulation necrosis produced with a single application of energy. Thus, subsequent developments have been focused on achieving large-volume tissue necrosis (11).

Over the years, the local effectiveness of RF ablation has improved, mainly owing to the use of multiprobe (12), multitined (13,14), and bipolar arrays (15) and internally cooled RF electrodes (16,17). The use of internally cooled RF electrodes might reduce the impedance of energy delivery caused by tissue vaporization, charring, and cavitations and with a single energy application produce a coagulation zone with a short-axis diameter of 3.5–4.0 cm. Microwave ablation is theoretically more efficient than RF ablation because microwaves penetrate more deeply than do RF waves and the delivery of microwave energy depends less on tissue texture and impedance (18). However, the temperature of the antenna shaft can rise quickly with an increase in microwave delivery and result in severe skin burn (19). Consequently, the application of microwave energy is usually limited to 60 W for 5 minutes, which produces only 2.6 x 3.7 cm of in vivo coagulation necrosis and necessitates two treatment sessions for complete eradication of one small tumor (20).

Attempts to increase the induced coagulation by using hepatic flow occlusion have yielded ablation zone sizes of 3–5 cm, but the occlusion procedure used was relatively invasive (21). Another microwave system produced 4 cm of coagulation with a 150-W output in the liver, but a 6.8-mm-diameter applicator had to be placed at laparotomy (22). In our study, we used a technique for producing large microwave ablation zones with greater energy delivery by using a cooled-shaft antenna.

Our ex vivo experiments revealed that the extent of the coagulation zone increased substantially with the increase in microwave delivery. However, only the use of a cooled-shaft antenna enabled the percutaneous delivery of greater microwave energy to treat liver tumors. Our ex vivo results also showed that compared with 70- and 80-W ablations, 90-W microwave ablation increased the long-axis rather than short-axis diameter of the coagulated area. Given that increased short-axis coagulation diameter is more important for ablating a liver tumor with the intent to create a spherical coagulation zone and that high energy power that produces an 8-cm-long area of coagulation may induce unexpected thermal damage to adjacent structures, 90-W microwave ablation was not used in our in vivo porcine liver and human liver cancer studies.

Although the microwave ablation–induced coagulation in the in vivo tissue was much smaller than that in the ex vivo tissue, one application of microwave energy with 80 W for 25 minutes produced coagulation with a mean size of 3.5 x 5.9 cm in the normal in vivo liver, equivalent to the coagulation induced by RF ablation with a cluster of cooled electrodes (23). A tissue temperature higher than 70°C that lasted 13 minutes during the microwave ablation 2 cm from the antenna may help explain the formation of such a size of coagulation since the cytotoxic temperatures that induce tumor destruction have been demonstrated to be 50°–54°C for 4–6 minutes (24). This microwave ablation setting was consequently used to ablate small liver tumors.

The short-axis diameter of in vivo coagulation produced by one microwave ablation of 70 W for 20 minutes reached a mean of 3.3 cm, which was considered suitable for the eradication of tumors smaller than 2 cm in diameter. Our clinical results showed that the use of this microwave ablation technique induced an ablation zone of 3.3 x 4.7 cm and a CA rate of 94% in the treatment of small liver tumors, comparable to the results reported for RF ablation (4,25). An important finding was that such a result could be achieved with one application of microwave energy and shows that the clinical indication for single-application microwave ablation may likely be 3.0-cm liver cancers.

The simultaneous and multiple microwave applications in our study yielded 4.8–8.0-cm ablation zones and a CA rate of 92% in 47 intermediate and large liver cancers. Only one treatment session and two to four antenna insertions were required to completely eradicate these tumors, fewer than the number of sessions and insertions needed for previously reported microwave ablations (1,20,25). It seems reasonable to suggest that this technique, as well as RF ablation with internally cooled electrodes, has potential for the treatment of large liver tumors (26). The microwave ablation technique that we used had similar local effectiveness in treating HCC and metastatic nodules. This finding suggests that this technique would benefit patients with primary or metastatic liver tumors. Unlike in RF ablation reports, in this study cirrhosis had limited influence on the ablation zone size, possibly owing to the greater penetration of the microwaves in the tissue. However, larger patient populations, especially those with tumors larger than 3 cm, are required to further confirm these presumptions.

Among nine tumors that were not completely eradicated after the first microwave ablation session, four small tumors and one large tumor were located near the diaphragm or gastrointestinal tract and appeared relatively unclear at US; thus, it was difficult to accurately place the antenna. Given that the ablation zones induced in these nodules were not smaller than the ablation zones induced in the tumors with CA, it seems that tumor location rather than tumor size influenced treatment effectiveness. The other three intermediate tumors and one small tumor without CA were close to major veins where the heat-sink effect had an important role, and this may explain why significantly smaller ablation zones were produced in these nodules compared with the ablation zones created in the tumors with CA. The use of induced pleural effusion and contrast-enhanced US helped to eradicate the residual tumors during an additional microwave ablation session. These results demonstrate that with an extended ablation zone, tumor location may become more important than tumor size in limiting the clinical effectiveness of ablation therapies. Techniques, such as contrast-enhanced US, that can provide more accurate guidance than B-mode US may help to reduce this negative influence.

The total complication rate (12%) in our study remained in the range reported in other microwave ablation studies (10%–14%) (27,28), and no treatment-related deaths occurred. Therefore, we believe the described microwave ablation technique is effective for treating patients with focal liver malignancies. The 2% complication rate observed in the treatment of patients with one small tumor is comparable to the reported complication rate with RF ablation (29). However, an increased frequency of antenna insertions to treat multiple or large nodules resulted in significantly higher complication rates. The relatively larger size of the guiding needle required and the unexpected overablation that occurs owing to the delivery of large levels of microwave energy may lead to complication rates that are relatively higher than those associated with RF ablation. Further technical innovations to reduce the needle size or increase the ablation zone achieved with a single application of microwave energy may help to decrease the complication rate.

The types of complications that we encountered were similar to those described in RF ablation reports. Tumor seeding was not observed, although lowering the antenna shaft temperature could result in increased incidences of this complication. There may be two reasons that tumor seeding did not occur: First, the needle track was cauterized by using a "hot withdrawal" method after the ablation was completed. Second, the long duration of the thermal ablation with a low-bleeding outcome may reduce the frequency of tumor seeding because blood potentially carries malignant cells.

The follow-up period of less than 2 years for most patients and the relatively small number of large tumors were limitations in this study. However, the primary goal of this investigation was not to assess the ultimate effectiveness of the described microwave ablation technique but rather to assess the size of the induced coagulation and the extent of subsequent local tumor control. Additional studies with longer follow-up periods and more patients are necessary for further survival analyses.

In conclusion, microwave ablation with a cooled-shaft antenna not only decreased the risk of skin burn in ablation therapies but also enabled greater delivery of microwave energy to produce large-volume coagulation in ex vivo and in vivo porcine livers and in liver cancers in humans. This technique, by producing a larger ablation zone in one application of energy and reducing the number of treatment sessions required to treat larger tumors, may therefore improve the effectiveness of microwave ablation of focal liver cancers.

	ADVANCES IN KNOWLEDGE

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 

• Microwave ablation with a cooled-shaft antenna enabled delivery of greater energy without concern about skin burns.
  
• Focal liver cancers up to 3 cm in diameter were completely eradicated with a single application of microwave energy.
  

	ACKNOWLEDGMENTS

 
We thank Li Jian Liang, MD, Bao Gang Peng, MD, PhD, Dong Ming Li, MD, Shao Qiang Li, MD, and Jia Ming Lai, MD, for assistance in the clinical portion of this study; Zhu Wang, MD, and Ms Pei Huang for assistance with the laboratory tests; and Feng Chen, PhD, for help with the statistical analyses.

	FOOTNOTES

 

Abbreviations: CA = complete ablation • HCC = hepatocellular carcinoma • LTP = local tumor progression • RF = radiofrequency

Authors stated no financial relationship to disclose.

Author contributions: Guarantor of integrity of entire study, M.D.L.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, M.K., X.Y.X., H.X.X.; clinical studies, M.K., M.D.L., X.Y.X., H.X.X., L.Q.M., G.J.L., Z.F.X., Y.L.Z.; experimental studies, all authors; statistical analysis, M.K.; and manuscript editing, M.K., M.D.L.

	References

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 

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