|Year : 2022 | Volume
| Issue : 2 | Page : 329-335
Comparison of percutaneous microwave ablation with radiofrequency ablation for hepatocellular carcinoma adjacent to major vessels: A retrospective study
Qiang Shen1, Neng Wang1, Pan-pan Wu1, Bi-bo Tan2, Guo-jun Qian1
1 Department of Ultrasonic Intervention, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Changhai Rd, Shanghai, China
2 Department of Ultrasonography, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Changhai Rd, Shanghai, China
|Date of Submission||26-Aug-2021|
|Date of Acceptance||06-Jan-2022|
|Date of Web Publication||20-May-2022|
Department of Ultrasonic Intervention, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Changhai Rd 225, Shanghai
Source of Support: None, Conflict of Interest: None
Purpose: To compare the therapeutic efficacy and safety of percutaneous microwave ablation (MWA) with those of percutaneous radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC) adjacent to major vessels.
Methods: From January 2010 to April 2011, 78 patients with a single nodule, no >5 cm, adjacent to major vessels were enrolled in this study. Forty-four patients (forty-one men, three women; age range, 33–72 years) treated by MWA were compared with thirty-four patients (thirty-one men, three women; age range, 33–75 years) treated by RFA. Local tumor progression rate, overall survival rate, and disease-free survival rate were calculated using the Kaplan–Meier method, and differences between groups were estimated by log-rank test.
Results: No death related to treatment occurred in the two groups. The 1-, 2-, and 3-year local tumor progression rates were 6.8%, 11.4%, and 15.9%, respectively, in the microwave group versus 17.6%, 20.6%, and 20.6%, respectively in the radiofrequency group (P = 0.544). The rates of major complications associated with microwave and RFA were 2.3% (1/44) versus 0% (0/34; P = 0.376). The microwave group's 1-, 2-, and 3-year disease-free survival rates were 72.7%, 65.9%, and 51.8%, respectively, and those in the radiofrequency were 58.8%, 52.9%, and 47.1%, respectively (P = 0.471). The microwave group's 1-, 2-, and 3-year overall survival rates were 93.2%, 90.9%, and 83.6%, respectively, and those in the radiofrequency group were 91.2%, 88.2%, and 82.4%, respectively (P = 0.808) There was no significant difference in local tumor progression, complications related to treatment, and long-term results between the two modalities. The incidence of peritumoral structure damage on image scan was significantly higher in the microwave group than in the RFA group (P = 0.025).
Conclusions: Both RFA and MWA are safe and effective techniques for HCC adjacent to major vessels and have the same clinical value.
Keywords: Complication, heat-sink, hepatocellular carcinoma, microwave ablation, radiofrequency ablation
|How to cite this article:|
Shen Q, Wang N, Wu Pp, Tan Bb, Qian Gj. Comparison of percutaneous microwave ablation with radiofrequency ablation for hepatocellular carcinoma adjacent to major vessels: A retrospective study. J Can Res Ther 2022;18:329-35
|How to cite this URL:|
Shen Q, Wang N, Wu Pp, Tan Bb, Qian Gj. Comparison of percutaneous microwave ablation with radiofrequency ablation for hepatocellular carcinoma adjacent to major vessels: A retrospective study. J Can Res Ther [serial online] 2022 [cited 2022 Jun 25];18:329-35. Available from: https://www.cancerjournal.net/text.asp?2022/18/2/329/345526
| > Introduction|| |
Hepatocellular carcinoma (HCC) occurs at a high rate in China due to chronic hepatitis B virus infection. Liver transplantation, hepatic resection, local thermal ablation are three curative therapies for HCC (s). In theory, liver transplantation can simultaneously cure the tumor and cirrhosis and is regarded as the most effective for these patients, mainly corresponding to Milano criteria (solitary tumor ≤5 cm, or up to three nodules ≤3 cm)., However, the scarcity of appropriate donors is a major limitation. Until now, surgical resection is still the first-choice treatment for liver malignancies since it can obtain a relatively long-term survival rate. Unfortunately, hepatectomy may not be the first resort for every patient with HCC, as some patients are unwilling to undergo surgical therapy. In addition some situations are excluded, such as anatomical complications, multinodularity, and poor liver reserve., Various local ablation techniques such as radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation, and cryoablation have been developed demonstrating safety, effectiveness, low cost and minimal invasiveness.
RFA and MWA are two of the most commonly used modalities for the ablation of liver malignancies. There has been avoidance when ablating tumors near major vessels because the vascular structure and bile duct may be injured directly by the needle and indirectly by the heat in the ablation procedure., However, some studies demonstrated that local ablation is a safe and valid method, even for tumors adjacent to large vessels (diameter >3 mm)., A phenomenon referring to RFA, the so-called “heat-sink effect,” occurring when liver tumors near large blood vessels are incompletely ablated because of heat loss, has been described as an unfavorable factor. Relative to RFA, MWA shows many theoretical and practical advantages to overcome this limitation. However, there are few published clinic data regarding the comparison between the two methods for such located tumors. Hence, our study aimed to compare RFA with MWA for patients with such tumors under ultrasonography guidance.
| > Materials and Methods|| |
This was a retrospective comparative study. Approval was obtained by the Ethics committee of Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University. Written informed consent was obtained from all patients enrolled in this study. From January 2010 to April 2011, 1021 patients diagnosed with malignant liver tumors received percutaneous local thermal ablation therapy in our department. Seventy-eight cases with single nodular ≤5 cm in maximum diameter and adjacent to major vessels receiving first therapy of MWA or RFA were enrolled in the current study. There is no clear determination of the choice of two methods. After pretreatment examination, our multidisciplinary team, including hepatologists, interventional radiologists, and surgeons, discussed all cases to assess the clinical diagnosis and determine whether the lesion qualified for local ablation. RFA or MWA was selected without randomization, and all patients were allowed to choose the treatment.
When informed of the risk of needle tract seeding in the biopsy procedure and adequate evidence of diagnosis HCC, all patients refused biopsy. The HCCs were clinically diagnosed using criteria established by the American Association for the Study of Liver Diseases, as follows: mass of 1–2 cm with two typical imaging techniques (n = 29) or mass of >2 cm with one specific imaging technique (n = 49). All patients were asked to remain in hospital. Medical history was obtained, and a physical examination was conducted. Patients were then screened with blood tests (hemoglobin, white blood cell, platelet count, internationalized normalized ratio, prothrombin time, hepatitis virus marker, tumor makers, etc.), chest radiography, abdominal ultrasound (US), and abdominal computed tomography (CT) and (or) magnetic resonance imaging (MRI). Requirements for inclusion in the present study were as follows: (a) age from 18 to 75 years old; (b) new single nodular ≤5 cm (defined as initial lesion or recurrence after hepatectomy without previous treatment); (c) Child-Pugh class A or B, prothrombin activity >50%; and a platelet count of >50,000/mm3 (50 × 109/L); and (d) no vascular invasion, no portal vein and/or hepatic vein thrombosis, no lymph node spread and/or distant metastasis.
The diagnosis, tumor size, and exact location of lesions were evaluated by CT and/or MRI by two radiologists (B. H., who had 6-year experience in diagnosis, H. Y. C., who had 20-year experience in diagnosis). And then, it was reconfirmed with abdominal US. One day before treatment by one US physician (B. B. T., who had 6-year experience). Location adjacent to major vessels was defined as tumors <5 mm from a first or second branch of the portal vein, the base of hepatic veins, or the inferior vena cava.
M. W. device
A FORSEA™ MW delivery system (Qinghai Microwave Electronic Institute, Nanjing, China) was used in this study. The system is composed of a MTC-3 MW generator with a frequency of 2,450 MHz and power output of 0-100 W, a flexible low-loss coaxial cable, and a 14-gauge cooled shaft antenna. The antenna consists of one 18-cm-long shaft coated with Teflon to prevent tissue adhesion; a 3-cm-long exposed antenna at its terminus with a 1.5-cm-long active tip covered with polytetrafluoroethylene.
R. F. device
A Cool-tip™ RF ablation system (Valleylab, Boulder, CO, U. S. A.) was used in this study. The system is composed of an R. F. generator with a maximum power output of 200 W, a 17-gauge and 18-cm-long internally cooled needle electrode. Two different types of the electrode were used: 2-cm activate tip and 3 cm activate tip.
All ablation sessions were performed by an experienced interventional radiologist (G. J. Q.), who had 17 years of experience in percutaneous interventional therapy. For percutaneous ablation, patients' posture and optimal insertion site were determined according to the tumor localization detection under real-time US (SSI-5500, Kaili Technology Co., Ltd., Shenzhen, China), which was also used for the guidance and monitoring of ablation procedures. All patients were under local anesthetic with 1% lidocaine combined with intravenous 0.1 mg of Tramadol. The skin has incised a hole in 2 mm with a small lancet. The treatments aimed to eradicate the tumor with a safety margin of no <1 cm. A single electrode/antenna was used when the tumor was 2.5 cm or less in diameter;; for tumors larger than 2.5 cm, two electrodes/antennas were required. To ensure adequate necrotic area, an ablation proposal of multiple insertions was applied. Microwave energy was set at 100 W for 3–5 min for each application. RF ablation was used for 12 min. At the end of ablation, the puncture tract was coagulated to prevent bleeding.
Local therapeutic efficacy was evaluated by contrast-enhanced CT or MRI scan in all patients. Follow-up CT/MRI was performed within 48 h, one month after, and then every 2-3 months after ablation to confirm local or distant recurrence (DR). Technical success was defined as uniform hypo-attenuation without contrast enhancement in the ablated area on CT/MRI within 48 h. Local tumor progression (LTP) is defined as any lesion inside or adjacent to ablated zone. DR was defined as the new presence of intra-or extra-hepatic lesion that was not adjacent to the ablated tumor. Major complication was described as an event that leads to substantial morbidity and disability, increased the level of care, resulting in hospital admission, or substantially lengthened hospital stay.
The follow-up period was calculated starting from the beginning of thermal ablation for all patients. The last follow-up date considered was October 30, 2013. The study's endpoints were 3-year survival, disease-free survival, complications, technical success, local tumor progression, DR.
The statistics were performed by the SPSS version 17.0 (SPSS, Chicago, Illinois, U. S. A.). The Chi-square test and Fisher's exact test were used for qualitative variables. For continuous variables, Student's t-test was applied. Local tumor progression, overall survival rate, and disease-free survival rate were calculated using the Kaplan–Meier method, and differences between groups were estimated by log-rank test. The survival time was calculated from the initial ablation performed for the HCC Survival curve was counted by month. Risk factors of local tumor progression were investigated using the Chi-square test. A two-tailed P < 0.05 was considered to be statistically significant.
| > Results|| |
The clinic characteristics of the study patients are summarized in [Table 1]. There was no significant difference between the two groups in sex, age, tumor size, Alpha-fetoprotein level, hepatitis background, and Child-Pugh class, tumor location. The median follow-up period was 37.6 months (range, 4.6–44.3 months) for the MWA group and 37.7 months (range: 3.0–42.8 months) for the RFA group (P = 0.779).
In the MWA group, one insertion with a single antenna was performed in 15 patients. Two insertions with a single antenna were performed in 3 patients. Multiple insertions (2, 3, and 4, respectively) with two antennas were performed in 26 patients (23, 2, and 1, respectively). In the RFA group, one insertion with a single electrode was performed in 15 patients. Two insertions with a single electrode were performed in 5 patients. Multiple insertions (2, 3, and 4, respectively) with two electrodes were performed in 14 patients (11, 1, and 2, respectively).
Tumor progression and treatment
Technical success was achieved in all patients. The 1-, 2-, and 3-year local tumor progression rates were 6.8%, 11.4%, and 15.9% in the MWA group versus 17.6%, 20.6%, and 20.6% in the RFA group, without significant differences between the two groups [[Figure 1], P = 0.544], respectively. The median progression time was 12.6 months (2.2–27.7 months) in the MWA group versus 4.2 months (1.6–22.3 months) in the RFA group, without significant differences between the two groups (P = 0.225). The Chi-square test, demonstrated that tumor size was an independent risk factor for local tumor progression after thermal ablation, with large tumors of 3–5 cm associated with a higher local recurrence rate compared with small tumors of ≤3 cm (P = 0.007). The 1-, 2-, and 3-year DR rates were 18.2%, 22.7%, and 34.4% in the MWA group, and the rates were 17.6%, 26.5% and 32.4% in the RFA group, respectively. There were no significant differences between the MWA and RFA groups regarding DR either (P = 0.907).
|Figure 1: Local tumor progression for percutaneous microwave ablation and radiofrequency ablation groups. P = 0.554 according to the long-rank test|
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In the follow-up time, 20 patients in the MWA group and 16 in the RFA group had developed tumor recurrence.
In the MWA group, both LTP. and DR were observed in 2 patients. They were treated with a second percutaneous MWA. In addition, LTPs were observed in 5 patients. Four were treated with a second percutaneous MWA, and one was treated with radiotherapy. DRs were observed in 13 patients. Ten were treated with 1-3 sessions (s) of MWA, two were treated with 2-3 sessions of TACE.
In the RFA group, both LTP and DR were observed in 2 patients. One was treated with a second percutaneous RFA, and one was treated with percutaneous MWA, with one also receiving radiotherapy because of bile duct tumor thrombus. LTPs were observed in 5 patients. Four were treated with a second percutaneous RFA, and one was treated with percutaneous MWA. DRs were observed in 9 patients. In addition, one was treated with a second percutaneous RFA, and four were treated with 1-2 sessions (s) of MWA. Four patients were treated with 2-3 sessions of TACE.
The major complication of persistent jaundice (n = 1) was observed in one of the 44 patients (1/44, 2.6%) in the MWA group, which required drainage and other medical therapy [Table 2]. There was no significant difference in major complications rate (Chi-square test, P = 0.376) between treatment groups. Pain was most common in all patients during the ablation procedure, however was relieved soon after the therapy. Six (13.6%, 6/44) patients in the MWA group and five (14.7%, 5/34) in the RFA group complained of right upper abdomen pain, requiring the administration of analgesics (P = 0.893). Fever (>38.5°C) was observed after treatment in four (9.1%, 4/44) patients in the MWA group and five (14.7%, 5/34) in the RFA group (P = 0.441). Vasovagal reflex was observed in four (9.1%, 4/44) patients in the MWA group and one (2.9%, 1/34) patient in the RFA group (P = 0.272). In the follow-up, the CT/MRI scan demonstrated asymptomatic bile duct dilation in seven patients in the MWA group versus two patients in the RFA group, and ischemic changes in seven patients in the MWA group versus one patient in the RFA group [Figure 2]. This study had no peritoneal hemorrhage, tumor seeding, bile leak, biloma, and other complications. No death related to treatment occurred in the two groups.
|Figure 2: (a) Computed tomography scan acquired during artery phase shows hypervascular lesion abutting the left portal branch. (b) It shows a washout in the venous phase. (c) Magnetic resonance scan acquired 9 months after microwave ablation shows complete local ablation and dilatation of left liver bile duct, without jaundice. (d) Magnetic resonance imaging scan obtained during the artery phase shows a hypervascular lesion abutting the right hepatic vein. (e) It shows a washout in the venous phase. (f) Magnetic resonance scan acquired 2 months after microwave ablation shows complete local ablation and ischemic change upstream of the ablation zone|
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The disease-free survival rates at 1, 2, and 3 years were 72.7%, 65.9%, and 51.8%, respectively. The disease-free survival rates at 1, 2, and 3 years were 58.8%, 52.9%, and 47.1%, respectively [[Figure 3], P = 0.471]. The 1-, 2-, and 3-year overall survival rates for patients who underwent MWA were 93.2%, 90.9%, and 83.6%, respectively. For patients who underwent RFA, the 1-, 2-, and 3-year overall survival rates were 91.2%, 88.2%, and 82.4%, respectively [[Figure 4], P = 0.808]. There was no significant difference in disease-free survival rate and overall survival rate between the two modalities.
|Figure 3: Disease-free survival rate for percutaneous microwave ablation and radiofrequency ablation groups. P = 0.471 according to the long-rank test|
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|Figure 4: Overall survival rate for percutaneous microwave ablation and radiofrequency ablation groups. P = 0.808 according to the long-rank test|
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Cause of death
In the MWA group, seven (7/44, 15.9%) patients died. The causes of death were tumor progression in six and liver function failure in one. In the RFA group, six (6/34, 17.6%) patients died, and the causes of death were tumor progression in four, liver function failure in one, and upper gastrointestinal tract bleeding in one.
| > Discussion|| |
Both RFA and MWA depend on thermal energy to induce tissue necrosis. RF energy primarily is based on the agitation of ions when the RF current propagates through the tissue. The tissue heating is dependent primarily on thermal conduction. When the conduction area is adjacent to major vessels, continuous blood flow may carry heat away, resulting in local residual tumors., Microwave energy, on the other hand, uses electromagnetic radiation. The heating of the tissue is by forcing the polarized water molecule to rapidly oscillate in the electromagnetic field. Thus, within the microwave field, a heat-sink will not occur. Beyond the microwave field active heating, similar to RFA, energy is delivered by thermal conduction so that major vessels will have a heat-sink effect.
Some experiment models and clinical dates have demonstrated that the efficacy of RFA is reduced when the tumor abuts major vascular structures due to the so-called heat sink effect.,,, It is also a significant factor associated with LTR after RFA However, MWA offers many substantial advantages of RFA while possibly overcoming the limitation of the heat sink effect. MWA can achieve a larger ablated zone than RFA,, but a larger ablation zone may not always provide optimum results. There were few clinical reports concerning ablation of perivascular tumor by microwave and no clinical studies of comparison the two techniques for HCC adjacent to major vessels. In the present study, patients with HCC adjacent to major vessels were selected as the basis of the study. There was no significant difference in local tumor progression between the two groups within follow-up periods. Of all the variables, tumor size was a significant risk factor of local tumor progression. That was in line with Hori's report.
Concerning complications, in the current study, there was no significant difference between patients who complained of pain in the MWA groups and RFA groups, during the ablation procedure or post-ablation. MWA may increase the risk of damage to the peritumoral structures due to its larger ablated zone compared to RFA. This may explain why vasovagal reflex was greater in the patients who underwent MWA than those who underwent RFA. Moreover, on the CT/MRI scan in the follow-up time, asymptomatic bile duct dilation and ischemic changes in the MW group were more frequent than those in the RF group, but no one needed further medical therapy.
Persistent jaundice as only one major complication related to treatment was observed in the MWA group, but no one (0%) in the RFA group. There was no significant difference in major complications rate (P = 0.376) between the two treatment groups. Marchal et al. found biliary stenosis and dilation, even complete interruption of the bile duct on pig models when ablating hepatic parenchyma near the bile duct. Teratani et al. reported 6 (7.6%) of 79 nodules near a sizeable portal vein in the incidence of bile ducts injury. Some experiments showed cooling bile ducts could reduce the incidence of bile duct injury., According to Liang's experience, using thermocouples to monitor temperature near the liver's hilum could prevent bile duct injury. According to the results of some experiments,,, ablation of tumors adjacent to major vessels is safe in normal perfusion. Meanwhile, blood flow in the portal vein could cool the bile duct when in normal perfusion.
The literature reported vascular complications of RFA and MWA included intravascular thrombosis and hepatic infarction., Thus, damage to peritumoral vessels may result in endothelial necrosis and thrombosis. That might explain the mechanism of ischemic change upstream of the ablation zone on the image scan.
As for survival rates, there was also no significant difference between MWA and RFA groups. Similar results of comparison between the two methods had been shown in other studies., Conversely, different conclusions were drawn from a study by Ohmoto et al., that RFA gains a higher survival rate than MWA The poorer prognosis of the patients who underwent MWA was attributed to a higher rate of incomplete ablation. However, they performed MWA with lower output power in a shorter time so that they could not achieve adequate safety margins resulting in a residual tumor. Achieving complete necrosis might be a beneficial influence on survival.
The low rate of complication and good survival results in such high-risk locations can be attributed to: (a) all ablation sessions were performed by experienced radiologists; (b) all patients had a single nodule (≤5 cm); most patients had the liver function of Child-Pugh class A. These attributes allow patients to well-tolerate the treatments; and (c) two cooled-shaft types of equipment were applied for ablation. These may be attributed to reducing the rate of complications compared with other types.,
There were several limitations in this study. Firstly, the main impediment to the current study was a single-institution retrospective study involving a relatively small population. Therefore, further prospective randomized control studies in more patients are required. Secondly, all the procedures were performed under US guidance. Finally, when the blood vessels block the puncture pathway, piercing into vessels directly should be avoided, which results in insertion angle deviation. Therefore, optimal punctures angles can be impacted.
In conclusion, this present study revealed that both RFA and MWA are safe and effective methods for the treatment of HCC (≤5 cm) adjacent to major vessels (≤3 mm). RFA demonstrates the same local tumor progression rate, disease-free survival rate, overall survival rate, and complications rate as MWA Meanwhile, MWA may be more likely to cause vascular structure and bile duct damage.
Advances in knowledge
Both radiofrequency and microwave ablation are safe and effective methods for treating hepatocellular carcinoma (≤5 cm), adjacent to significant vessels. Radiofrequency ablation demonstrates similar local tumor progression rate, disease-free survival rate, overall survival rate, and complications rate compared to microwave ablation when the tumors are located in the proximity of major vessels. However, microwave ablation may be more likely to cause vascular structure and bile duct damage.
Implication for patient care
If hepatectomy cannot be performed for patients with HCC (≤5 cm) adjacent to major vessels, either MWA or RFA may be a better choice because of its safety and efficacy.
The authors thank Jian-feng Yao, MD, for statistical analysis and graphics preparation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]