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Treatment of hepatocellular carcinoma adjacent to large blood vessels using 1.5T MRI-guided percutaneous radiofrequency ablation combined with iodine-125 radioactive seed implantation
European Journal of Radiology 81 (2012) 3079–3083
Contents lists available at SciVerse ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Treatment of hepatocellular carcinoma adjacent to large blood vessels using 1.5T MRI-guided percutaneous radiofrequency ablation combined with iodine-125 radioactive seed implantation Zheng-Yu Lin ∗ , Jin Chen 1 , Xiu-Fen Deng 1 The Department of Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, China
a r t i c l e
i n f o
Article history: Received 9 March 2012 Received in revised form 5 May 2012 Accepted 7 May 2012 Keywords: Magnetic resonance imaging Hepatocellular carcinoma Brachytherapy Radiofrequency ablation Blood vessel
a b s t r a c t Objective: The objective is to study the technology associated with and feasibility of the treatment of hepatocellular carcinoma (HCC) adjacent to large blood vessels using 1.5T MRI-guided radiofrequency ablation combined with iodine-125 (I-125) radioactive seed implantation. Methods: Sixteen patients with a total of 24 HCC lesions (average maximum diameter: 2.35 ± 1.03 cm) were pathologically confirmed by biopsy or clinically diagnosed received 1.5T MRI-guided percutaneous radiofrequency ablation (RFA) treatment. Each patient had one lesion adjacent to large blood vessels (≥3 mm); after the ablation, I-125 radioactive seeds were implanted in the portions of the lesions that were adjacent to the blood vessels. Results: All the ablations and I-125 radioactive seed implantations were successful; a total of 118 seeds were implanted. The ablated lesions exhibited hypointense signals on the T2WI sequence with a thin rim of hyperintense signals; they also exhibited significant hyperintense signals on the T1WI sequence with clear boundaries. The average follow-up period was 11.1 ± 6.2 months. There were 23 complete responses and one partial response in the 24 lesions. The alpha-fetoprotein (AFP) levels of the patients significantly decreased. Conclusion: The 1.5T MRI-guided RFA combined with I-125 radioactive seed implantation for the treatment of HCC adjacent to large blood vessels is an effective technology. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction In recent practice, radiofrequency ablation (RFA) has been used extensively to treat unresectable hepatocellular carcinoma (HCC) and has yielded good efficacy [1–3]. During RFA treatment of tumors adjacent to large blood vessels, the heat that is generated close to blood vessels can be lost, which leads to residual lesions or recurrence; this is called the heat sink effect [4–6]. Brachytherapy is the implantation of radioactive seeds into tumors to impart high-dose irradiation to the lesions and is a precise means of radiotherapy that has been extensively used for treating prostate cancer [7]. It was recently reported that the
Abbreviations: MRI, magnetic resonance imaging; TR, repetition time; TE, echo time; FA, flip angle; SL/GAP, slice thickness/gap; HCC, hepatocellular carcinoma; RFA, radio-frequency ablation; fs FRFSE, fat-suppressed fast-recovery fast spin echo; FSPGR, fast spoiled gradient recalled; 3D Dyn T1WI, three-dimensional dynamic T1 weighted imaging; I-125, iodine 125; AFP, alpha-fetoprotein. ∗ Corresponding author. Tel.: +86 59187982312; fax: +86 59187983309. E-mail addresses: [email protected] (Z.-Y. Lin), [email protected] (J. Chen), [email protected] (X.-F. Deng). 1 Tel.: +86 59187982312. 0720-048X/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejrad.2012.05.007
treatment of malignant hepatic tumors using brachytherapy yielded good efficacy [8,9]. Previous studies have shown that a combination treatment of thermotherapy and radiotherapy had a synergistic effect on the treatment of malignant tumors, and the efficacy of the dual treatment was better than radiotherapy or thermotherapy alone [10,11]. MRI does not use ionizing radiation but has high tissue resolution, has high imaging capability at any dimension, and is sensitive to temperature changes; this makes MRI an ideal imaging guiding device [12,13]. This prospective study evaluated the efficacy of 1.5T MRI-guided percutaneous radiofrequency ablation combined with I-125 radioactive seed implantation for treating HCC adjacent to large blood vessels (≥3 mm).
2. Materials and methods 2.1. Patients This study was approved by the Fujian Medical University ethics committee for research involving human subjects. Written informed consents were obtained from all patients.
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The MRI-guided RFA was performed on 24 lesions from 16 HCC patients (10 males and 6 females between 44 and 83 years of age with an average age of 53.7 ± 9.3 years) from June 2009 to April 2011. Each patient had one lesion (16 total lesions) adjacent to large blood vessels (≥3 mm); after RFA, I-125 radioactive seeds were implanted into those lesions, guided by MRI. Lesions in the patients were pathologically confirmed by biopsy (n = 7) or clinically diagnosed (n = 9) before operation. The clinical diagnosis of HCC was made based on the guideline proposed by the Ministry of Health of the People’s Republic of China [14]. According to these criteria, a patient is considered positive for HCC if the patient has the risk factors (cirrhosis and HBV infection and/or hepatitis C virus infection) and one of the following: the diameter of hepatic lesion ≥ 2 cm and a positive finding with at least one of the two typical imaging studies (dynamic contrast enhanced MRI and spiral CT); the diameter of hepatic lesion is 1–2 cm, the positive findings with CT & MRI and lasting a month of a serum alphafetoprotein (AFP) level ≥ 400 ng/ml or 2 months of a serum AFP level ≥ 200 ng/ml. A positive finding for typical HCC with dynamic CT or MRI is indicative of arterial enhancement, followed by venous washout in the delay/portal venous phase. The patients included in this study either were not suitable for surgery (i.e., due to the presence of multiple liver tumors, poor liver function, or the presence of a clinical condition that was not suitable for partial liver resection) or refused surgery and had at least one lesion adjacent to blood vessels larger than 3 mm. Four patients had received a partial hepatectomy only, 4 patients had received the transarterial embolization only, 3 patients had received partial hepatectomy and transarterial embolization, but above 11 patients still had residual lesions or recurrence; and 5 patients did not receive any other treatments before the operation. The coagulation test, routine blood tests, liver function, and AFP levels were examined before the operation. Before the operation and postoperative follow-up, plain MRI and dynamic enhancement scanning was performed on the liver using the 3.0T Magnetom Verio MRI (Siemens, Erlangen, Germany). The measurement of the locations and sizes of the lesions and the sizes of adjacent blood vessels were performed by two physicians with more than 10 combined years of MRI diagnosis experience.
2.2. Equipment RFA and seed implantation was guided by 1.5T MRI (Signa Infinity TwinSpeed with Excite, GE, USA). The Torso body coil was used; there were two rectangular square holes in the coil to facilitate interventional operation. The scanning sequences and parameters were the following: (1) Fat-suppressed fast-recovery fast spin echo (fs FRFSE) T2WI: TR 6000.0 ms, TE 87.0 ms, FA 90◦ , SL 5.0 mm, and GAP 1.0 mm; (2) T1 fast spoiled gradient recalled (T1FSPGR): TR 165.0 ms, TE 2.2 ms, FA 25◦ , SL 5.0 mm, and GAP 1.0 mm; and (3) three-dimensional dynamic T1 weighted imaging (3D Dyn T1WI): TR 4.8 ms, TE 1.1 ms, FA 45◦ , and SL 3.0 mm. The fs FRFSE T2WI sequence used respiratory gating-controlled scanning, and the other sequences used breath-holding scanning. The RITA RF generator was from RITA Medical Systems (Model 1500X, Mountain View, CA). The 1.5T MRI-compatible multipolar radio frequency electrode (StarBurst MRI, 10/15 cm) had a 14gauge (14 G) rigid trocar that contained 9 expandable hooks with a diameter of 5 cm, and a 25-foot MRI extension cable. The 1.5T MRIcompatible monopolar RF electrode (17 G, UniBlate, 15/25 cm) had an ablation range of 1–3 cm; MRI-compatible needles (14 G/18 G, 10/15 cm, Daum, Germany) were also used. The I-125 seeds (diameter: 0.8 mm, length: 4.5 mm; Syncor, China) were enclosed in a 0.05-mm-thick titanium alloy. The activity of the I-125 seeds used for implantation was 0.8 millicuries (mCi)
per seed, and the half-life was 59.7 days. The mean energy of each seed was 27.4–35.5 keV, with a tissue penetration of 17 mm. A turnable implanting gun (Hokai China) was used. 2.3. Procedure 2.3.1. Preoperative preparation During the 2 weeks before the operation, plain MRI and enhancement scanning were performed to examine the location, size, and number of lesions (Figs. 1 and 2). Before the operation, I-125 seeds were loaded into the implanting gun and sterilized by autoclaving. The patients fasted on the day of the operation and were intramuscularly injected with 50 mg of bucinnazine. Blood pressure, heart rate, and respiration were monitored and maintained within the normal ranges. The RF generator was placed outside the scanning room and was connected by an extension cable. 2.3.2. Operation procedure The fs FRFSE T2WI plain scanning was first performed using vitamin E pills that were attached to the body surface as markers. A 3D Dyn T1WI sequence was then performed to determine the appropriate puncture routes; the puncture routes were to be as short as possible and to avoid important structures. Routine disinfection and draping were performed before the injection of 5 mL of 1% lidocaine for local anesthesia. After being guided by the MRI, the electrode gradually reached the edge of the tumor. During the puncturing, scanning was performed several times to ensure that the electrode was facing the right direction; the scanning directions were along oblique coronal, oblique sagittal, or oblique axial planes and were parallel to the RF probe. The inner thin electrodes were pushed inside the lesion, and the scanning was performed again to confirm the satisfactory distribution of electrodes (Fig. 3). The scanning bed was retreated to the original location, the wires of the RF needle and the skin electrode were connected to the extension cable, the power was set at 150 W, and the target temperature was set at 105 ◦ C. According to the different ablation ranges, electrodes were gradually expanded, and the appropriate ablation schedule and time were selected (2–5 cm/5–15 min). Using a monopolar needle for the ablation, a 14 G MRI-compatible puncture needle first reached the edge of lesion under MRI guidance; after removing the stylet, an RF electrode was inserted, the power was set at 30 W, the target temperature was maintained at 103 ◦ C. Based on the different ablation ranges, the length of the ablation tip and the appropriate ablation schedule and time (1–3 cm/1.5–15 min) were selected. After finishing the ablation, the power for the RF generator was turned off, and the wires were removed. Routine plain MRI scanning was performed to assess the effects and complications of the treatment. The tumor lesions that were completely covered by the ablation lesions were considered completely ablated; the tumor lesions that were not covered by the ablation lesions suggested the presence of residual lesions. Generally, the ranges of the ablated lesions were 0.5–1.0 cm beyond the edges of the tumor lesions, except for the portions of the lesions that were adjacent to the blood vessels. The signals of the non-necrotic residual tumor tissues were the same as those before ablation. If there were residual lesions, the ablation was supplemented; if the ablation was complete, the ablation was performed on the electrode route, and the electrodes were withdrawn. The 18 G MRI-compatible puncture needle was placed into the portions of the lesions that were adjacent to the blood vessels along the direction of blood vessels, and one I-125 seed was implanted every 0.8 cm, the distance between seed and vessel was less than 5 mm (Fig. 4). After the operation, the liver was routinely scanned to check for complications, such as bleeding and pneumothorax.
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Figs. 1–8. Female, 44 years of age, HCC. The lesion was located at S7 with a diameter of 3.2 cm and was adjacent to a branch of the right hepatic vein. During the operation and before ablation, the horizontal axis of the fs FRFSE T2WI (Figs. 1 and 2) revealed a long T2 HCC lesion adjacent to a branch of the right hepatic vein (white arrow) at S7, the RF needle and expanded electrodes exhibited hypointensity by 3D Dyn T1WI (Fig. 3), and the trocar and electrodes were clearly distinguished from the lesion. The ablated lesion exhibited hyperintense signals by T1 FSPGR (Fig. 4). The MRI-compatible puncture needle had an exaggerated artifact with hypointensity, and the metal seeds also had low signals (white arrow). Six months after the operation, follow-up MRI revealed the following: by TSE T2WI (Fig. 5), the ablated lesion exhibited hypointensity, and there was slight hyperintensity surrounding the rim; by TI fl2d (Fig. 6), the ablated lesion had hyperintense signals, and the seeds had spotty hypointense signals; and the ablated lesion did not show significant enhancement in the arterial phase (Fig. 7) or the portal phase (Fig. 8) by T1 vibe after enhancement.
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Table 1 Statistics for size of lesions and adjacent blood vessels.
Table 2 Comparison of the AFP value of pre- and post-ablation.
Analyzed data
Size (cm)
Time
Maximum diameter of the 24 lesions Maximum diameter of the 16 lesions that were adjacent to large blood vessels Diameter of the blood vessels that were adjacent to the lesions
2.35 ± 1.03 (0.8–4.5) 2.08 ± 0.94 (0.8–4.5)
Pre-ablation At the end of the follow-up P value*
0.43 ± 0.15 (0.3–1.0)
AFP values (ng/ml) 110.66 ± 129.53 (7–375) 24.48 ± 30.90 (6–90) 0.019
Note. Data are the mean ± standard deviation. Numbers in parentheses are ranges. * P value was calculated by using the independent samples t-test.
Note. Data are the mean ± standard deviation. Numbers in parentheses are ranges.
2.4. Follow-up One month after the operation, 3.0T MRI and enhanced scanning were performed on the liver; after that, the patients were followedup every 2 months. The evaluation of the efficacy of treatment was performed using the WHO solid tumor evaluation criteria. 2.5. Statistical analysis Statistical analysis was performed using SPSS 12.0 software (SPSS, Chicago, IL). The comparison of AFP values before and after the ablation was performed using the independent samples t-test. A P value < 0.05 was considered significant. 3. Results 3.1. Preoperative conditions The size of lesions and the adjacent blood vessels were showed in Table 1. The AFP values of 7 patients were normal, and the AFP values of 9 patients increased. There were 6 lesions adjacent to 2 blood vessels and 1 lesion adjacent to 3 blood vessels; there were 3 lesions adjacent to both the hepatic vein and a branch of the portal vein. 3.2. Intraoperative condition 3.2.1. Treatment The multipolar electrode was used in 14 patients with a total of 22 lesions, while the monopolar electrode was used in 2 patients with a total of 2 lesions that were smaller than 1 cm. A total of 118 I125 seeds were implanted (a range of 3–16, with a median of 6 seeds per lesion). The ablation of the lesions and the seed implantation were both successfully completed; postoperative scanning showed that the disease lesions were completely covered by the ablation lesions. Five patients had significant pain during the operation; 3 patients had pain irradiating to the shoulder, but they all tolerated the operation. Postoperative scanning showed that 9 patients had a small amount of bleeding under the liver capsule; there were no significant complications (i.e., biliary fistula, diaphragmatic perforation, jaundice, or pneumothorax). One day after the operation, the patients exhibited different levels of transaminase elevation; after symptomatic treatment, the levels rapidly decreased within 3 days and returned to normal within 1–2 weeks. One patient had a fever after the operation with a body temperature of 38.5 ◦ C; 2 days after symptomatic treatment, the body temperature returned to normal. The average operation length was 103.5 ± 31.1 min (52–175 min, with a median time of 95 min). 3.2.2. Intraoperative MRI findings The presentation of the RF needle and the MRI-compatible puncture needle on all of the MRI sequences formed a stripe pattern with a low signal; after the thin electrodes expanded, it became an umbrella-shaped low signal. The signal of the metal seeds on the spin echo sequence was not clear, and the gradient echo sequence
formed a spotty pattern with a low signal (Fig. 4). Before the ablation, the disease lesions exhibited a hypointense signal on the T1WI sequence and a hyperintense signal on the T2W1 sequence. Ablated lesions exhibited hypointense signals on the T2WI sequence with a thin rim of high signals. Ablated lesions exhibited significantly hyperintense signals on the T1WI sequence, and the boundaries were clear. Compared to the hyperintensity of the surrounding ablated normal liver tissues, most of the tumor lesions had relatively lower signals with significant contrast after the ablation. Furthermore, the dynamic scanning during the 3 min–1 h after the ablation demonstrated that the signal intensity of the ablated lesions on T1WI increased over time. 3.3. Follow-up The average follow-up period was 11.1 ± 6.2 months (5–27 months). At the end of the follow-up period, all of the patients were still alive, and 3 patients received another RFA treatment to treat newly generated lesions. In the 24 lesions, there were 23 complete responses (95.8%) and 1 partial response (4.2%). There was only one recurrence from the original 24 ablated lesions. The front edge of that lesion was adjacent to the right branch of the portal vein, but there was no recurrence around the seed-implanted blood vessel; in contrast, the rear upper edge of the lesion that was not adjacent to the blood vessel had a nodular pattern with a long T1 and long T2 signal. The liver function indicators of the 16 patients after the operations were similar to those before the operations. Thirteen patients had normal AFP values, and 3 patients had elevated AFP values. The AFP value acquired at the end of follow-up was significantly lower than that before ablation (Table 2). The ablation lesions exhibited hyperintensity on the T1WI sequence and iso- or hypo-signal intensity on the T2WI sequence; there were circular hyperintensity signals around the rim (Figs. 5 and 6). After the enhancement, the ablated lesions were not significantly enhanced, the rims had circular-shape enhancement, and the rims of some ablated lesions had abnormal patchy-shaped perfusions (7/24) (Figs. 7 and 8). With time, the ablated lesions gradually diminished, and the abnormal perfusions disappeared. 4. Discussion MRI can reveal lesions that are difficult to see by CT and ultrasound and has unique advantages for the preoperative exploration and location of lesions [12,13]. Three lesions in this study could not be detected by CT and ultrasound, while they were clearly displayed by MRI. Using the guidance of CT and ultrasound, the lesions are usually covered by metal artifacts after the electrodes reach the target site and the hooks are expanded. The lesions exhibit hyperintensity on the FRFSE T2WI sequence, and the artifact of the MRI-compatible thin electrode metal is moderate, which allows the lesions to be better distinguished. Because of the flow void effect, the blood vessels can be clearly displayed without an injection of contrast agents, which is important for the precise implantation of seeds next to the blood vessels. The biggest advantage of MRI is the improved visualization of the ablated lesions. There were hyperintense signals on the T1WI sequence, hypointense signals on the
Z.-Y. Lin et al. / European Journal of Radiology 81 (2012) 3079–3083
T2WI sequence, and the edges of the lesions were clear, which is in significant contrast to the general long T1 and long T2 signal intensities generated by tumor tissues. The high-intensity T1 signal after the ablation may be associated with bleeding and protein coagulation, while the hypointense signal on T2 may be associated with dehydration after thermal damage of tissues [15,16]. Sironi et al. believed that MRI was an effective method for evaluating the efficacy of RFA [17]. This study showed that after the ablation of the tumor, the T1WI signals were still different from the signals generated from the surrounding ablated normal tissues; generally, the signals of the ablated tumor lesions were lower than the hyperintense signals of the surrounding ablated normal tissues, which may be associated with the high water content in tumor tissues. This signal feature is helpful for determining if the ablation range is adequate. Because of the heat sink effect, the tumors adjacent to large blood vessels are not easily ablated [4–6]. Lu et al. ablated 15 HCC lesions adjacent to large blood vessels (≥3 mm); liver transplantation was performed after an average of 7.5 months, and postoperative pathological examination confirmed that there were 8 recurrences or residual lesions. When they ablated 32 nonperivascular lesions, there were only 4 recurrent lesions [18]. Lu et al. performed an RFA study in the livers of 10 live pigs to evaluate the heat sink effect; this showed that there were viable perivascular tissues in 50% of the blood vessels between 3 and 5 mm (12/24), in 100% of the blood vessels larger than 5 mm (7/7), and in 11.7% of the blood vessels smaller than 3 mm (13/111). This confirmed the existence of the heat sink effect [4]. Therefore, in this study, the seeds were implanted next to the blood vessels with diameters larger than 3 mm. Interstitial implantation brachytherapy with I-125 seeds is usually used for treating prostate cancer, and it has a long irradiation time and few side effects; brachytherapy improves the survival rate [19]. Recently, brachytherapy has also been used for treating liver cancer, and it has a larger local irradiation dose and results in less damage to normal liver tissues [8,9]. In this study, I-125 seeds were implanted into lesions adjacent to large blood vessels after ablation; in the 24 lesions from 16 patients, only 1 lesion had a recurrence at a site away from blood vessels but not at the implanted site. The treatment efficacy was better than that of the method used by Rossi et al., who performed occlusion of the tumor blood supply before operation (11 of 62 lesions had a recurrence) [20]. A possible reason for this is that the irradiation has a stronger therapeutic effect on the thermal-damaged lesions due to the synergistic effect of radiotherapy and thermotherapy. Three lesions in this study were adjacent to both the portal and hepatic veins, which were not suitable for vascular occlusion technology. In this study, ablation was only performed in 24 lesions from 16 patients; the ablated lesions were smaller, with an average maximum diameter of 2.35 ± 1.03 cm (between 0.8 and 4.5 cm). The number of patients will be increased in future studies, and the lesions will be grouped based on lesion size to further investigate the treatment efficacy. The other limitation of this study was the use of MRI for follow-up studies, which lacks the pathological results as controls. Additionally, because the follow-up period is short, the recurrence rate can be easily underestimated, and the survival rate is not easily compared with other treatment methods. In summary, the treatment of HCC lesions adjacent to large blood vessels using 1.5T MRI-guided radiofrequency ablation combined with brachytherapy has the benefits of accurate positioning, and the clear display of blood vessels and ablation lesions. The
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synergistic effect of thermotherapy and radiotherapy has clinical importance in the prevention of residual lesions caused by the heat sink effect and the increase in ablation rates. Therefore, it is a safe and effective new technology. Acknowledgment This study was supported by the Fujian Provincial Medical Innovational Project (2009-CXB-20). References [1] Rossi S, Fornari F, Pathies C, Buscarini L. Thermal lesions induced by 480 kHz localized current field in guinea pig and pig liver. Tumori 1990;76:54–61. [2] McGahan JP, Browning PD, Brock JM, Tesluk H. Hepatic ablation using radiofrequency electrocautery. Investigative Radiology 1990;25:267–70. [3] Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Annals of Surgery 1999;230:1–8. [4] Lu DS, Raman SS, Vodopich DJ, Wang M, Sayre J, Lassman C. Effect of vessel size on creation of hepatic radiofrequency lesions in pigs: assessment of the “heat sink” effect. American Journal of Roentgenology 2002;178(January):47–51. [5] Lu DS, Limanond P, Raman SS, et al. Influence of large peri-tumoral vessel on outcome of radiofrequency ablation of liver tumors. Journal of Vascular and Interventional Radiology 2003;14:1267–74. [6] Patterson EJ, Scudamore CH, Owen DA, Nagy AG, Buczkowski AK. Radiofrequency ablation of porcine liver in vivo: effects of blood flow and treatment time on lesion size. Annals of Surgery 1998;227:559–65. [7] Hurwitz MD, Cormack R, Tempany CM, Kumar S, D’Amico AV. Threedimensional real-time magnetic resonance-guided interstitial prostate brachytherapy optimizes radiation dose distribution resulting in a favorable acute side effect profile in patients with clinically localized prostate cancer. Techniques in Urology 2000;6:89–94. [8] Dawson LA, Lawrence TS. The role of radiotherapy in the treatment of liver metastases. Cancer Journal 2004;10:139–44. [9] Nag S, DeHaan M, Scruggs G, Mayr N, Martin EW. Long-term follow-up of patients of intrahepatic malignancies treated with iodine-125 brachytherapy. International Journal of Radiation Oncology, Biology, Physics 2006;64:736–44. [10] Sakurai H, Hayakawa K, Mitsuhashi N, et al. Effect of hyperthermia combined with external radiation therapy in primary non-small cell lung cancer with direct bony invasion. International Journal of Hyperthermia 2002;18:472–83. [11] Maluta S, Dall’Oglio S, Romano M, et al. Conformal radiotherapy plus local hyperthermia in patients affected by locally advanced high risk prostate cancer: preliminary results of a prospective phase II study. International Journal of Hyperthermia 2007;23:451–6. [12] Khankan AA, Murakami T, Onishi H, et al. Hepatocellular carcinoma treated with radio frequency ablation: an early evaluation with magnetic resonance imaging. Journal of Magnetic Resonance Imaging 2008;27:546–51. [13] Kelekis AD, Terraz S, Roggan A, et al. Percutaneous treatment of liver tumors with an adapted probe for cooled-tip, impedance-controlled radio-frequency ablation under open-magnet MR guidance: initial results. European Radiology 2003;13:1100–5. [14] The diagnostic and therapeutic criteria of primary hepatic carcinoma. Beijing: Ministry of Health of the People’s Republic of China; 2011. Available http://www.moh.gov.cn/publicfiles/business/htmlfiles/mohyzs/s3586/ via 201110/53153.htm [accessed 14.10.11]. [15] Wlodarczyk W, Boroschewski R, Hentschel M, Wust P, Mönich G, Felix R. Three-dimensional monitoring of small temperature changes for therapeutic hyperthermia using MR. Journal of Magnetic Resonance Imaging 1998;8:165–74. [16] Limanond P, Zimmerman P, Raman SS, Kadell BM, Lu DS. Interpretation of CT and MRI after radiofrequency ablation of hepatic malignancies. American Journal of Roentgenology 2003;181:1635–40. [17] Sironi S, Livraghi T, Meloni F, De Cobelli F, Ferrero C, Del Maschio A. Small hepatocellular carcinoma treated with percutaneous RF ablation: MR imaging follow-up. American Journal of Roentgenology 1999;173:1225–9. [18] Lu DS, Yu NC, Raman SS, et al. Radiofrequency ablation of hepatocellular carcinoma: treatment success as defined by histologic examination of the explanted liver. Radiology 2005 Mar;234:954–60. [19] Van Gellekom MP, Moerland MA, Battermann JJ, Lagendijk JJ. MRI-guided prostate brachytherapy with single needle method – a planning study. Radiotherapy and Oncology 2004;71:327–32. [20] Rossi S, Garbagnati F, Lencioni R, et al. Percutaneous radio-frequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply. Radiology 2000;217:119–26.
Contents lists available at SciVerse ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Treatment of hepatocellular carcinoma adjacent to large blood vessels using 1.5T MRI-guided percutaneous radiofrequency ablation combined with iodine-125 radioactive seed implantation Zheng-Yu Lin ∗ , Jin Chen 1 , Xiu-Fen Deng 1 The Department of Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, China
a r t i c l e
i n f o
Article history: Received 9 March 2012 Received in revised form 5 May 2012 Accepted 7 May 2012 Keywords: Magnetic resonance imaging Hepatocellular carcinoma Brachytherapy Radiofrequency ablation Blood vessel
a b s t r a c t Objective: The objective is to study the technology associated with and feasibility of the treatment of hepatocellular carcinoma (HCC) adjacent to large blood vessels using 1.5T MRI-guided radiofrequency ablation combined with iodine-125 (I-125) radioactive seed implantation. Methods: Sixteen patients with a total of 24 HCC lesions (average maximum diameter: 2.35 ± 1.03 cm) were pathologically confirmed by biopsy or clinically diagnosed received 1.5T MRI-guided percutaneous radiofrequency ablation (RFA) treatment. Each patient had one lesion adjacent to large blood vessels (≥3 mm); after the ablation, I-125 radioactive seeds were implanted in the portions of the lesions that were adjacent to the blood vessels. Results: All the ablations and I-125 radioactive seed implantations were successful; a total of 118 seeds were implanted. The ablated lesions exhibited hypointense signals on the T2WI sequence with a thin rim of hyperintense signals; they also exhibited significant hyperintense signals on the T1WI sequence with clear boundaries. The average follow-up period was 11.1 ± 6.2 months. There were 23 complete responses and one partial response in the 24 lesions. The alpha-fetoprotein (AFP) levels of the patients significantly decreased. Conclusion: The 1.5T MRI-guided RFA combined with I-125 radioactive seed implantation for the treatment of HCC adjacent to large blood vessels is an effective technology. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction In recent practice, radiofrequency ablation (RFA) has been used extensively to treat unresectable hepatocellular carcinoma (HCC) and has yielded good efficacy [1–3]. During RFA treatment of tumors adjacent to large blood vessels, the heat that is generated close to blood vessels can be lost, which leads to residual lesions or recurrence; this is called the heat sink effect [4–6]. Brachytherapy is the implantation of radioactive seeds into tumors to impart high-dose irradiation to the lesions and is a precise means of radiotherapy that has been extensively used for treating prostate cancer [7]. It was recently reported that the
Abbreviations: MRI, magnetic resonance imaging; TR, repetition time; TE, echo time; FA, flip angle; SL/GAP, slice thickness/gap; HCC, hepatocellular carcinoma; RFA, radio-frequency ablation; fs FRFSE, fat-suppressed fast-recovery fast spin echo; FSPGR, fast spoiled gradient recalled; 3D Dyn T1WI, three-dimensional dynamic T1 weighted imaging; I-125, iodine 125; AFP, alpha-fetoprotein. ∗ Corresponding author. Tel.: +86 59187982312; fax: +86 59187983309. E-mail addresses: [email protected] (Z.-Y. Lin), [email protected] (J. Chen), [email protected] (X.-F. Deng). 1 Tel.: +86 59187982312. 0720-048X/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejrad.2012.05.007
treatment of malignant hepatic tumors using brachytherapy yielded good efficacy [8,9]. Previous studies have shown that a combination treatment of thermotherapy and radiotherapy had a synergistic effect on the treatment of malignant tumors, and the efficacy of the dual treatment was better than radiotherapy or thermotherapy alone [10,11]. MRI does not use ionizing radiation but has high tissue resolution, has high imaging capability at any dimension, and is sensitive to temperature changes; this makes MRI an ideal imaging guiding device [12,13]. This prospective study evaluated the efficacy of 1.5T MRI-guided percutaneous radiofrequency ablation combined with I-125 radioactive seed implantation for treating HCC adjacent to large blood vessels (≥3 mm).
2. Materials and methods 2.1. Patients This study was approved by the Fujian Medical University ethics committee for research involving human subjects. Written informed consents were obtained from all patients.
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The MRI-guided RFA was performed on 24 lesions from 16 HCC patients (10 males and 6 females between 44 and 83 years of age with an average age of 53.7 ± 9.3 years) from June 2009 to April 2011. Each patient had one lesion (16 total lesions) adjacent to large blood vessels (≥3 mm); after RFA, I-125 radioactive seeds were implanted into those lesions, guided by MRI. Lesions in the patients were pathologically confirmed by biopsy (n = 7) or clinically diagnosed (n = 9) before operation. The clinical diagnosis of HCC was made based on the guideline proposed by the Ministry of Health of the People’s Republic of China [14]. According to these criteria, a patient is considered positive for HCC if the patient has the risk factors (cirrhosis and HBV infection and/or hepatitis C virus infection) and one of the following: the diameter of hepatic lesion ≥ 2 cm and a positive finding with at least one of the two typical imaging studies (dynamic contrast enhanced MRI and spiral CT); the diameter of hepatic lesion is 1–2 cm, the positive findings with CT & MRI and lasting a month of a serum alphafetoprotein (AFP) level ≥ 400 ng/ml or 2 months of a serum AFP level ≥ 200 ng/ml. A positive finding for typical HCC with dynamic CT or MRI is indicative of arterial enhancement, followed by venous washout in the delay/portal venous phase. The patients included in this study either were not suitable for surgery (i.e., due to the presence of multiple liver tumors, poor liver function, or the presence of a clinical condition that was not suitable for partial liver resection) or refused surgery and had at least one lesion adjacent to blood vessels larger than 3 mm. Four patients had received a partial hepatectomy only, 4 patients had received the transarterial embolization only, 3 patients had received partial hepatectomy and transarterial embolization, but above 11 patients still had residual lesions or recurrence; and 5 patients did not receive any other treatments before the operation. The coagulation test, routine blood tests, liver function, and AFP levels were examined before the operation. Before the operation and postoperative follow-up, plain MRI and dynamic enhancement scanning was performed on the liver using the 3.0T Magnetom Verio MRI (Siemens, Erlangen, Germany). The measurement of the locations and sizes of the lesions and the sizes of adjacent blood vessels were performed by two physicians with more than 10 combined years of MRI diagnosis experience.
2.2. Equipment RFA and seed implantation was guided by 1.5T MRI (Signa Infinity TwinSpeed with Excite, GE, USA). The Torso body coil was used; there were two rectangular square holes in the coil to facilitate interventional operation. The scanning sequences and parameters were the following: (1) Fat-suppressed fast-recovery fast spin echo (fs FRFSE) T2WI: TR 6000.0 ms, TE 87.0 ms, FA 90◦ , SL 5.0 mm, and GAP 1.0 mm; (2) T1 fast spoiled gradient recalled (T1FSPGR): TR 165.0 ms, TE 2.2 ms, FA 25◦ , SL 5.0 mm, and GAP 1.0 mm; and (3) three-dimensional dynamic T1 weighted imaging (3D Dyn T1WI): TR 4.8 ms, TE 1.1 ms, FA 45◦ , and SL 3.0 mm. The fs FRFSE T2WI sequence used respiratory gating-controlled scanning, and the other sequences used breath-holding scanning. The RITA RF generator was from RITA Medical Systems (Model 1500X, Mountain View, CA). The 1.5T MRI-compatible multipolar radio frequency electrode (StarBurst MRI, 10/15 cm) had a 14gauge (14 G) rigid trocar that contained 9 expandable hooks with a diameter of 5 cm, and a 25-foot MRI extension cable. The 1.5T MRIcompatible monopolar RF electrode (17 G, UniBlate, 15/25 cm) had an ablation range of 1–3 cm; MRI-compatible needles (14 G/18 G, 10/15 cm, Daum, Germany) were also used. The I-125 seeds (diameter: 0.8 mm, length: 4.5 mm; Syncor, China) were enclosed in a 0.05-mm-thick titanium alloy. The activity of the I-125 seeds used for implantation was 0.8 millicuries (mCi)
per seed, and the half-life was 59.7 days. The mean energy of each seed was 27.4–35.5 keV, with a tissue penetration of 17 mm. A turnable implanting gun (Hokai China) was used. 2.3. Procedure 2.3.1. Preoperative preparation During the 2 weeks before the operation, plain MRI and enhancement scanning were performed to examine the location, size, and number of lesions (Figs. 1 and 2). Before the operation, I-125 seeds were loaded into the implanting gun and sterilized by autoclaving. The patients fasted on the day of the operation and were intramuscularly injected with 50 mg of bucinnazine. Blood pressure, heart rate, and respiration were monitored and maintained within the normal ranges. The RF generator was placed outside the scanning room and was connected by an extension cable. 2.3.2. Operation procedure The fs FRFSE T2WI plain scanning was first performed using vitamin E pills that were attached to the body surface as markers. A 3D Dyn T1WI sequence was then performed to determine the appropriate puncture routes; the puncture routes were to be as short as possible and to avoid important structures. Routine disinfection and draping were performed before the injection of 5 mL of 1% lidocaine for local anesthesia. After being guided by the MRI, the electrode gradually reached the edge of the tumor. During the puncturing, scanning was performed several times to ensure that the electrode was facing the right direction; the scanning directions were along oblique coronal, oblique sagittal, or oblique axial planes and were parallel to the RF probe. The inner thin electrodes were pushed inside the lesion, and the scanning was performed again to confirm the satisfactory distribution of electrodes (Fig. 3). The scanning bed was retreated to the original location, the wires of the RF needle and the skin electrode were connected to the extension cable, the power was set at 150 W, and the target temperature was set at 105 ◦ C. According to the different ablation ranges, electrodes were gradually expanded, and the appropriate ablation schedule and time were selected (2–5 cm/5–15 min). Using a monopolar needle for the ablation, a 14 G MRI-compatible puncture needle first reached the edge of lesion under MRI guidance; after removing the stylet, an RF electrode was inserted, the power was set at 30 W, the target temperature was maintained at 103 ◦ C. Based on the different ablation ranges, the length of the ablation tip and the appropriate ablation schedule and time (1–3 cm/1.5–15 min) were selected. After finishing the ablation, the power for the RF generator was turned off, and the wires were removed. Routine plain MRI scanning was performed to assess the effects and complications of the treatment. The tumor lesions that were completely covered by the ablation lesions were considered completely ablated; the tumor lesions that were not covered by the ablation lesions suggested the presence of residual lesions. Generally, the ranges of the ablated lesions were 0.5–1.0 cm beyond the edges of the tumor lesions, except for the portions of the lesions that were adjacent to the blood vessels. The signals of the non-necrotic residual tumor tissues were the same as those before ablation. If there were residual lesions, the ablation was supplemented; if the ablation was complete, the ablation was performed on the electrode route, and the electrodes were withdrawn. The 18 G MRI-compatible puncture needle was placed into the portions of the lesions that were adjacent to the blood vessels along the direction of blood vessels, and one I-125 seed was implanted every 0.8 cm, the distance between seed and vessel was less than 5 mm (Fig. 4). After the operation, the liver was routinely scanned to check for complications, such as bleeding and pneumothorax.
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Figs. 1–8. Female, 44 years of age, HCC. The lesion was located at S7 with a diameter of 3.2 cm and was adjacent to a branch of the right hepatic vein. During the operation and before ablation, the horizontal axis of the fs FRFSE T2WI (Figs. 1 and 2) revealed a long T2 HCC lesion adjacent to a branch of the right hepatic vein (white arrow) at S7, the RF needle and expanded electrodes exhibited hypointensity by 3D Dyn T1WI (Fig. 3), and the trocar and electrodes were clearly distinguished from the lesion. The ablated lesion exhibited hyperintense signals by T1 FSPGR (Fig. 4). The MRI-compatible puncture needle had an exaggerated artifact with hypointensity, and the metal seeds also had low signals (white arrow). Six months after the operation, follow-up MRI revealed the following: by TSE T2WI (Fig. 5), the ablated lesion exhibited hypointensity, and there was slight hyperintensity surrounding the rim; by TI fl2d (Fig. 6), the ablated lesion had hyperintense signals, and the seeds had spotty hypointense signals; and the ablated lesion did not show significant enhancement in the arterial phase (Fig. 7) or the portal phase (Fig. 8) by T1 vibe after enhancement.
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Table 1 Statistics for size of lesions and adjacent blood vessels.
Table 2 Comparison of the AFP value of pre- and post-ablation.
Analyzed data
Size (cm)
Time
Maximum diameter of the 24 lesions Maximum diameter of the 16 lesions that were adjacent to large blood vessels Diameter of the blood vessels that were adjacent to the lesions
2.35 ± 1.03 (0.8–4.5) 2.08 ± 0.94 (0.8–4.5)
Pre-ablation At the end of the follow-up P value*
0.43 ± 0.15 (0.3–1.0)
AFP values (ng/ml) 110.66 ± 129.53 (7–375) 24.48 ± 30.90 (6–90) 0.019
Note. Data are the mean ± standard deviation. Numbers in parentheses are ranges. * P value was calculated by using the independent samples t-test.
Note. Data are the mean ± standard deviation. Numbers in parentheses are ranges.
2.4. Follow-up One month after the operation, 3.0T MRI and enhanced scanning were performed on the liver; after that, the patients were followedup every 2 months. The evaluation of the efficacy of treatment was performed using the WHO solid tumor evaluation criteria. 2.5. Statistical analysis Statistical analysis was performed using SPSS 12.0 software (SPSS, Chicago, IL). The comparison of AFP values before and after the ablation was performed using the independent samples t-test. A P value < 0.05 was considered significant. 3. Results 3.1. Preoperative conditions The size of lesions and the adjacent blood vessels were showed in Table 1. The AFP values of 7 patients were normal, and the AFP values of 9 patients increased. There were 6 lesions adjacent to 2 blood vessels and 1 lesion adjacent to 3 blood vessels; there were 3 lesions adjacent to both the hepatic vein and a branch of the portal vein. 3.2. Intraoperative condition 3.2.1. Treatment The multipolar electrode was used in 14 patients with a total of 22 lesions, while the monopolar electrode was used in 2 patients with a total of 2 lesions that were smaller than 1 cm. A total of 118 I125 seeds were implanted (a range of 3–16, with a median of 6 seeds per lesion). The ablation of the lesions and the seed implantation were both successfully completed; postoperative scanning showed that the disease lesions were completely covered by the ablation lesions. Five patients had significant pain during the operation; 3 patients had pain irradiating to the shoulder, but they all tolerated the operation. Postoperative scanning showed that 9 patients had a small amount of bleeding under the liver capsule; there were no significant complications (i.e., biliary fistula, diaphragmatic perforation, jaundice, or pneumothorax). One day after the operation, the patients exhibited different levels of transaminase elevation; after symptomatic treatment, the levels rapidly decreased within 3 days and returned to normal within 1–2 weeks. One patient had a fever after the operation with a body temperature of 38.5 ◦ C; 2 days after symptomatic treatment, the body temperature returned to normal. The average operation length was 103.5 ± 31.1 min (52–175 min, with a median time of 95 min). 3.2.2. Intraoperative MRI findings The presentation of the RF needle and the MRI-compatible puncture needle on all of the MRI sequences formed a stripe pattern with a low signal; after the thin electrodes expanded, it became an umbrella-shaped low signal. The signal of the metal seeds on the spin echo sequence was not clear, and the gradient echo sequence
formed a spotty pattern with a low signal (Fig. 4). Before the ablation, the disease lesions exhibited a hypointense signal on the T1WI sequence and a hyperintense signal on the T2W1 sequence. Ablated lesions exhibited hypointense signals on the T2WI sequence with a thin rim of high signals. Ablated lesions exhibited significantly hyperintense signals on the T1WI sequence, and the boundaries were clear. Compared to the hyperintensity of the surrounding ablated normal liver tissues, most of the tumor lesions had relatively lower signals with significant contrast after the ablation. Furthermore, the dynamic scanning during the 3 min–1 h after the ablation demonstrated that the signal intensity of the ablated lesions on T1WI increased over time. 3.3. Follow-up The average follow-up period was 11.1 ± 6.2 months (5–27 months). At the end of the follow-up period, all of the patients were still alive, and 3 patients received another RFA treatment to treat newly generated lesions. In the 24 lesions, there were 23 complete responses (95.8%) and 1 partial response (4.2%). There was only one recurrence from the original 24 ablated lesions. The front edge of that lesion was adjacent to the right branch of the portal vein, but there was no recurrence around the seed-implanted blood vessel; in contrast, the rear upper edge of the lesion that was not adjacent to the blood vessel had a nodular pattern with a long T1 and long T2 signal. The liver function indicators of the 16 patients after the operations were similar to those before the operations. Thirteen patients had normal AFP values, and 3 patients had elevated AFP values. The AFP value acquired at the end of follow-up was significantly lower than that before ablation (Table 2). The ablation lesions exhibited hyperintensity on the T1WI sequence and iso- or hypo-signal intensity on the T2WI sequence; there were circular hyperintensity signals around the rim (Figs. 5 and 6). After the enhancement, the ablated lesions were not significantly enhanced, the rims had circular-shape enhancement, and the rims of some ablated lesions had abnormal patchy-shaped perfusions (7/24) (Figs. 7 and 8). With time, the ablated lesions gradually diminished, and the abnormal perfusions disappeared. 4. Discussion MRI can reveal lesions that are difficult to see by CT and ultrasound and has unique advantages for the preoperative exploration and location of lesions [12,13]. Three lesions in this study could not be detected by CT and ultrasound, while they were clearly displayed by MRI. Using the guidance of CT and ultrasound, the lesions are usually covered by metal artifacts after the electrodes reach the target site and the hooks are expanded. The lesions exhibit hyperintensity on the FRFSE T2WI sequence, and the artifact of the MRI-compatible thin electrode metal is moderate, which allows the lesions to be better distinguished. Because of the flow void effect, the blood vessels can be clearly displayed without an injection of contrast agents, which is important for the precise implantation of seeds next to the blood vessels. The biggest advantage of MRI is the improved visualization of the ablated lesions. There were hyperintense signals on the T1WI sequence, hypointense signals on the
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T2WI sequence, and the edges of the lesions were clear, which is in significant contrast to the general long T1 and long T2 signal intensities generated by tumor tissues. The high-intensity T1 signal after the ablation may be associated with bleeding and protein coagulation, while the hypointense signal on T2 may be associated with dehydration after thermal damage of tissues [15,16]. Sironi et al. believed that MRI was an effective method for evaluating the efficacy of RFA [17]. This study showed that after the ablation of the tumor, the T1WI signals were still different from the signals generated from the surrounding ablated normal tissues; generally, the signals of the ablated tumor lesions were lower than the hyperintense signals of the surrounding ablated normal tissues, which may be associated with the high water content in tumor tissues. This signal feature is helpful for determining if the ablation range is adequate. Because of the heat sink effect, the tumors adjacent to large blood vessels are not easily ablated [4–6]. Lu et al. ablated 15 HCC lesions adjacent to large blood vessels (≥3 mm); liver transplantation was performed after an average of 7.5 months, and postoperative pathological examination confirmed that there were 8 recurrences or residual lesions. When they ablated 32 nonperivascular lesions, there were only 4 recurrent lesions [18]. Lu et al. performed an RFA study in the livers of 10 live pigs to evaluate the heat sink effect; this showed that there were viable perivascular tissues in 50% of the blood vessels between 3 and 5 mm (12/24), in 100% of the blood vessels larger than 5 mm (7/7), and in 11.7% of the blood vessels smaller than 3 mm (13/111). This confirmed the existence of the heat sink effect [4]. Therefore, in this study, the seeds were implanted next to the blood vessels with diameters larger than 3 mm. Interstitial implantation brachytherapy with I-125 seeds is usually used for treating prostate cancer, and it has a long irradiation time and few side effects; brachytherapy improves the survival rate [19]. Recently, brachytherapy has also been used for treating liver cancer, and it has a larger local irradiation dose and results in less damage to normal liver tissues [8,9]. In this study, I-125 seeds were implanted into lesions adjacent to large blood vessels after ablation; in the 24 lesions from 16 patients, only 1 lesion had a recurrence at a site away from blood vessels but not at the implanted site. The treatment efficacy was better than that of the method used by Rossi et al., who performed occlusion of the tumor blood supply before operation (11 of 62 lesions had a recurrence) [20]. A possible reason for this is that the irradiation has a stronger therapeutic effect on the thermal-damaged lesions due to the synergistic effect of radiotherapy and thermotherapy. Three lesions in this study were adjacent to both the portal and hepatic veins, which were not suitable for vascular occlusion technology. In this study, ablation was only performed in 24 lesions from 16 patients; the ablated lesions were smaller, with an average maximum diameter of 2.35 ± 1.03 cm (between 0.8 and 4.5 cm). The number of patients will be increased in future studies, and the lesions will be grouped based on lesion size to further investigate the treatment efficacy. The other limitation of this study was the use of MRI for follow-up studies, which lacks the pathological results as controls. Additionally, because the follow-up period is short, the recurrence rate can be easily underestimated, and the survival rate is not easily compared with other treatment methods. In summary, the treatment of HCC lesions adjacent to large blood vessels using 1.5T MRI-guided radiofrequency ablation combined with brachytherapy has the benefits of accurate positioning, and the clear display of blood vessels and ablation lesions. The
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synergistic effect of thermotherapy and radiotherapy has clinical importance in the prevention of residual lesions caused by the heat sink effect and the increase in ablation rates. Therefore, it is a safe and effective new technology. Acknowledgment This study was supported by the Fujian Provincial Medical Innovational Project (2009-CXB-20). References [1] Rossi S, Fornari F, Pathies C, Buscarini L. Thermal lesions induced by 480 kHz localized current field in guinea pig and pig liver. Tumori 1990;76:54–61. [2] McGahan JP, Browning PD, Brock JM, Tesluk H. Hepatic ablation using radiofrequency electrocautery. Investigative Radiology 1990;25:267–70. [3] Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Annals of Surgery 1999;230:1–8. [4] Lu DS, Raman SS, Vodopich DJ, Wang M, Sayre J, Lassman C. Effect of vessel size on creation of hepatic radiofrequency lesions in pigs: assessment of the “heat sink” effect. American Journal of Roentgenology 2002;178(January):47–51. [5] Lu DS, Limanond P, Raman SS, et al. Influence of large peri-tumoral vessel on outcome of radiofrequency ablation of liver tumors. Journal of Vascular and Interventional Radiology 2003;14:1267–74. [6] Patterson EJ, Scudamore CH, Owen DA, Nagy AG, Buczkowski AK. Radiofrequency ablation of porcine liver in vivo: effects of blood flow and treatment time on lesion size. Annals of Surgery 1998;227:559–65. [7] Hurwitz MD, Cormack R, Tempany CM, Kumar S, D’Amico AV. Threedimensional real-time magnetic resonance-guided interstitial prostate brachytherapy optimizes radiation dose distribution resulting in a favorable acute side effect profile in patients with clinically localized prostate cancer. Techniques in Urology 2000;6:89–94. [8] Dawson LA, Lawrence TS. The role of radiotherapy in the treatment of liver metastases. Cancer Journal 2004;10:139–44. [9] Nag S, DeHaan M, Scruggs G, Mayr N, Martin EW. Long-term follow-up of patients of intrahepatic malignancies treated with iodine-125 brachytherapy. International Journal of Radiation Oncology, Biology, Physics 2006;64:736–44. [10] Sakurai H, Hayakawa K, Mitsuhashi N, et al. Effect of hyperthermia combined with external radiation therapy in primary non-small cell lung cancer with direct bony invasion. International Journal of Hyperthermia 2002;18:472–83. [11] Maluta S, Dall’Oglio S, Romano M, et al. Conformal radiotherapy plus local hyperthermia in patients affected by locally advanced high risk prostate cancer: preliminary results of a prospective phase II study. International Journal of Hyperthermia 2007;23:451–6. [12] Khankan AA, Murakami T, Onishi H, et al. Hepatocellular carcinoma treated with radio frequency ablation: an early evaluation with magnetic resonance imaging. Journal of Magnetic Resonance Imaging 2008;27:546–51. [13] Kelekis AD, Terraz S, Roggan A, et al. Percutaneous treatment of liver tumors with an adapted probe for cooled-tip, impedance-controlled radio-frequency ablation under open-magnet MR guidance: initial results. European Radiology 2003;13:1100–5. [14] The diagnostic and therapeutic criteria of primary hepatic carcinoma. Beijing: Ministry of Health of the People’s Republic of China; 2011. Available http://www.moh.gov.cn/publicfiles/business/htmlfiles/mohyzs/s3586/ via 201110/53153.htm [accessed 14.10.11]. [15] Wlodarczyk W, Boroschewski R, Hentschel M, Wust P, Mönich G, Felix R. Three-dimensional monitoring of small temperature changes for therapeutic hyperthermia using MR. Journal of Magnetic Resonance Imaging 1998;8:165–74. [16] Limanond P, Zimmerman P, Raman SS, Kadell BM, Lu DS. Interpretation of CT and MRI after radiofrequency ablation of hepatic malignancies. American Journal of Roentgenology 2003;181:1635–40. [17] Sironi S, Livraghi T, Meloni F, De Cobelli F, Ferrero C, Del Maschio A. Small hepatocellular carcinoma treated with percutaneous RF ablation: MR imaging follow-up. American Journal of Roentgenology 1999;173:1225–9. [18] Lu DS, Yu NC, Raman SS, et al. Radiofrequency ablation of hepatocellular carcinoma: treatment success as defined by histologic examination of the explanted liver. Radiology 2005 Mar;234:954–60. [19] Van Gellekom MP, Moerland MA, Battermann JJ, Lagendijk JJ. MRI-guided prostate brachytherapy with single needle method – a planning study. Radiotherapy and Oncology 2004;71:327–32. [20] Rossi S, Garbagnati F, Lencioni R, et al. Percutaneous radio-frequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply. Radiology 2000;217:119–26.