Technique of radiofrequency ablation of hepatocellular carcinoma and method of efficacy evaluation

Technique and efficacy evaluation method of radiofrequency ablation for hepatocellular carcinoma (published in Chinese Journal of Hepatobiliary Surgery)
 
Wang Yuehua, Liu Jiafeng, Li Fei, Li Ang, Liu Qiang, Liu Dongbin, Liu Donggang Wang Yuehua, Department of General Surgery, Xuanwu Hospital, Capital Medical University
Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
 
Abstract
OBJECTIVE: To summarize the clinical experience of radiofrequency ablation (RFA) for hepatocellular carcinoma and to discuss the methods to evaluate the efficacy of RFA. METHODS: Forty-nine patients with hepatocellular carcinoma were treated with a uniform protocol of RFA, including 43 males and 6 females; ages ranged from 39 to 72 years, with an average of (56.4±9.3) years. The tumor diameter was 1.5-10 cm, among which 16 cases were ≤3 cm, 15 cases were 3.1-5 cm, and 18 cases were >5 cm. According to the liver function Child-pugh classification, 41 cases were grade A and 8 cases were grade B. The pathological diagnosis was hepatocellular carcinoma in 44 cases and bile duct cell hepatocellular carcinoma in 5 cases. The RITA radiofrequency ablation tumor treatment system (RF-1500) was used to perform RFA, and CT and TACE were routinely performed 3-4 weeks after RFA to evaluate the effect of RFA and consolidate the efficacy of hepatocellular carcinoma. RESULTS: All cases recovered well after RFA, and the overall 1-, 2-, and 3-year survival rates were 77.5%, 56.5%, and 44.0%. The conversion rate of those with positive AFP (≥25 μg/L) was 62.9% (22/35) 3 to 4 weeks after RFA for hepatocellular carcinoma. The improved RFA approach for hepatocellular carcinoma allowed for more complete ablation of tumors less than 5 cm in diameter, with 1-, 2-, and 3-year survival rates of 100%, 79.6%, and 61.9% for those ≤5 cm. The recent efficacy of liver cancer ablation was classified into three levels, and the 2-year survival rates were 85.7%, 60.0%, and 24.3% for those who obtained radical ablation (19 cases), subradical ablation (9 cases), and palliative ablation (21 cases) after RFA, respectively. Conclusion.
RFA of hepatocellular carcinoma is equivalent to functional resection of the tumor, and the three-level classification of recent efficacy of hepatocellular carcinoma ablation can evaluate the effect of RFA more objectively to guide the selection of adjuvant therapy.
Keywords: cancer, hepatocellular; radiofrequency ablation (RFA); survival rate; treatment effect
This work was supported by the National Natural Science Foundation of China (Grant No. 30772122). (See information on the attached page)
    [He was born in 1965, is a male, born in Luannan County, Hebei, China. Tel: 13301371938,
010-83198732, E-mail: [email protected]
Techniques of radiofrequency ablation for unresectable
primary liver cancer and outcome evaluation
WANG Yuehua, LIU
Department of general surgery, Xuanwu Hospital, Capital
Medical University, Beijing 100053, China.
E-mail: [email protected]
Abstract
Objective: To summarize the experience in treatment of unresectable primary
To summarize the experience in treatment of unresectable primary liver cancer (PLC) with
Methods: Over a 3-year period, 49 consecutive patients with solitary or
Over a 3-year period, 49 consecutive patients with solitary or multinodular PLC (Child-Pugh class A or B) underwent RFA.
The Histopathologic types were of hepatocellular carcinoma in 43 cases, and of cholangio-carcinoma in 6.
RFA was performed by a RITA expandable electrodes
device (RF-1500) followed by
Local efficacy was evaluated with computed tomography (CT) performed at an average of 4 weeks
There were no severe complications after RFA for all the patients.
The total 1, 2 and 3-year survival
The total 1-, 2- and 3-year survival rates were 77.5%, 56.5% and 44.0% respectively.
Tumors no more than 5cm in
Tumors no more than 5cm in diameter could be ablated inside out.
1, 2 and 3-year survival rates were 100%, 79.6%, 61.9%
The treatment response of RFA were assessed as curative
ablation (complete
tumor ablation with 0.5 – 1cm ablative
margin) in 19 cases, sub-curative ablation (complete tumor ablation with less
than 0.5cm
ablative margin) in 9 cases, non-curative (non-complete) ablation in 21 cases. The 2-year
survival rate was 85.7%, 60.0% and 24.3% respectively,
The 2-year survival rate was 85.7%, 60.0% and 24.3%, respectively, in patients with different types of response. Conclusion: RFA has similar
The classification method for the evaluation of RFA displays the results in 3 cases.
The classification method for the evaluation of RFA display the results in 3 grades, and it is useful for the selection of
The classification method for the evaluation of RFA display the results in 3 grades, and it is useful for the selection of adjuvant therapy.
Keywords: Carcinoma, hepatocellular; Radiofrequency
ablation; Survival rates; Treatment outcome
    Surgical resection was once the only promising means to cure hepatocellular carcinoma and has achieved good results [1, 2]. Radiofrequency ablation (RFA) for hepatocellular carcinoma has been widely recognized in the treatment of hepatocellular carcinoma since it was reported by Rossi [3] in 1995 [4, 5] and promoted in the treatment of small hepatocellular carcinoma, but the recurrence rate after RFA for larger hepatocellular carcinoma is high [6] and there are still more disagreements about RFA for large hepatocellular carcinoma. The authors et al. have carried out more than 200 cases of RFA for hepatocellular carcinoma since 2001, and designed and studied the application techniques and clinical efficacy evaluation methods of radiofrequency ablation for hepatocellular carcinoma since 2004, which are reported below.
Clinical data and methods
1.1 Patient data
Patients with hepatocellular carcinoma who were not suitable for or unwilling to undergo surgical resection were selected for this study and met the following conditions: tumor was confined to the liver, no extrahepatic metastases, maximum tumor diameter did not exceed 10 cm, no cancerous thrombus in the hepatic vein or portal vein trunk, and liver function Child-Pugh grade A or B. From April 2004 to March 2007, a total of 49 cases, including 43 males and 6 females, aged 39 to 72 years, with an average of 56.4±9.3 years, met the above conditions. The tumor diameter was 1.5-10 cm, including 16 cases of ≤3 cm, 15 cases of 3.1-5 cm, and 18 cases of >5 cm. There were 30 patients with single tumor and 19 patients with multiple tumors. According to the liver function Child-pugh classification, there were 41 cases of grade A or 8 cases of grade B. Eight of them had undergone RFA before RFA. Eight of them had undergone one to three times transcatheter hepatic artery chemoembolization (TACE) before RFA.
1.2 Methods of confirming the diagnosis
The clinical diagnosis was in accordance with the “Clinical Diagnostic Criteria for Primary Liver Cancer” revised by the Chinese Anti-Cancer Association in 2001 [7], in which 19 cases had an alpha-fetoprotein (AFP) ≥400 μg/L, 16 cases had 25-400 μg/L, and 14 cases had ≤25 μg/L. All cases were diagnosed by ultrasound, CT or MRI. There were 7 cases of percutaneous puncture biopsy, 42 cases of intraoperative puncture biopsy or excisional tissue biopsy, 44 cases of hepatocellular carcinoma and 5 cases of cholangiocellular hepatocellular carcinoma were diagnosed pathologically.
1.3 Radiofrequency ablation method
The RITA radiofrequency ablation tumor treatment system (RF-1500) of the United States was used, whose basic performance is that the maximum diameter of spherical ablation foci obtained by each needle ablation is 5 cm. The RF parameters were determined according to tumor size, lesion size and tumor location, including the selection of puncture points, RF range, number of times and duration of RF. For tumors less than 3 cm in diameter, single-stitch subablation was used, and for tumors between 3 cm and 5 cm, multiple superimposed methods were used. The basic scheme was to obtain a target ablation focus of 5 cm to 7 cm by ablation using a tumor ablation 3-layer 6-stitch needle deployment scheme (Figure 1). For tumors larger than 5 cm, the ablation method with more overlapping stitches was used. Eight cases of splenic artery ligation, four cases of cholecystectomy, and two cases of bile duct dissection to remove cancer emboli were performed simultaneously due to combined hypersplenism.
Figure 1 Tumor ablation 3-layer 6-stitch needle deployment scheme: the relationship between single-stitch ablation radius r, target ablation radius R, and distance X between single-stitch ablation center and tumor center is: r2 =R2/2+(R/21/2-
X)2, so that X = R/21/2-(r2-R2/2)1/2. To obtain a target ablation focus of 7 cm, X was 2.1 cm, with 4 stitches for mid-level ablation and one ablation for each of deep and superficial levels.
In order to increase the efficacy of RFA for hepatocellular carcinoma, we took the following measures during open RFA: ① freeing the liver, paying attention to protecting the gallbladder (or removing the gallbladder), large intrahepatic vessels, gastrointestinal tract and diaphragm; ② ligation of hepatocellular carcinoma collateral circulation vessels from sources other than hilar vessels, such as adherent diaphragmatic vessels and gastric omentum; ③ transient blockage of hemihepatic blood flow during RFA, and transient blockage of whole liver blood flow for those in the middle lobe. ④ The first target is to puncture the RFA in the direction of the vessel entering the liver segment, and finally achieve ablation of the liver segment where the tumor is located or the joint liver segment, but more than 2 cm from the secondary branches of the hilar choroid; ⑤ For the tumor immediately adjacent to the hilar bold duct, a fine catheter is inserted into the common bile duct to instill low-temperature saline to cool it down and avoid bile duct burns; ⑥ Real-time ultrasound intraoperative monitoring is used to flexibly select the puncture point and the direction of needle entry.
1.4 Methods of efficacy evaluation
Judging the degree of local ablation by ultrasound or CT imaging, ① complete ablation: complete ablation of single small hepatocellular carcinoma (5cm), the ablation range reaches 0.5-1cm ablation margin as required by the principle of tumor eradication (1cm in general, 0.5cm near the large vessel side); ② basic complete ablation: single tumor or less than 3 lesions, maximum 5cm, all tumors are ablated but the ablation The range does not reach 0.5cm ablation margin; ③incomplete ablation: in the case of the above two types of lesions, most of the tumors obtain ablation, but there are clear residual tumor margins; or liver cancer with more than 3 lesions, no matter how to ablate; or any type of liver cancer has been accompanied by metastatic foci and cancer thrombi, no matter how to ablate.
The authors et al. combined the stage of hepatocellular carcinoma, the degree of local radiofrequency ablation and the treatment effect, and classified the recent efficacy after radiofrequency ablation of hepatocellular carcinoma into three levels of radical ablation, subradical ablation and palliative ablation to guide the efficacy evaluation, with the following criteria. (2) Sub-radical ablation: tumor markers decreased significantly and reached or nearly normal; CT, MRI or DSA images showed that the lesion was basically completely ablated, but the radical ablation margin was less than 0.5cm; there was no residual cancer and no daughter foci.
1.5 Follow-up review and treatment
After 4 weeks of RFA, liver function, blood routine, AFP, enhanced CT or enhanced MRI scans, and TACE were performed routinely to evaluate the effect of RFA and consolidate the therapeutic effect of hepatocellular carcinoma. The Seldinger method was used for hepatic arteriography and TACE. 5-15 ml of iodinated oil was used in each case, and chemotherapeutic agents were 5-fluorouracil 500 mg-1000 mg, mitomycin 16-20 mg, and adriamycin 40-60 mg. 30 mg of adriamycin was mixed with iodinated oil and emulsified thoroughly. For those with incomplete radiofrequency ablation or the presence of recurrence or metastasis, TACE was performed again once every 2-3 months. The correlation between the two groups of efficacy evaluation methods was analyzed by one-dimensional linear correlation, and the cumulative survival rate was calculated by the life table method at a follow-up of 6 months to 3 years.
Results
2.1 Overall efficacy
All cases showed mild impairment of liver function after RFA, but no jaundice occurred, and all recovered and were discharged without surgical death or serious complications. 6 cases who developed ascites for more than 1 week improved after liver preservation treatment. The overall 1-, 2-, and 3-year survival rates were 77.5%, 56.5%, and 44.0%, among which the 1-, 2-, and 3-year survival rates were 100%, 79.6%, and 61.9% for those with tumor diameter ≤5 cm.
2.2 Extent of local tumor RFA
  The improved RFA method for hepatocellular carcinoma can provide relatively complete ablation of tumors less than 5 cm in diameter, while for larger tumors, more overlapping stitches and longer RFA are required, with the longest RFA case taking up to 6 hours. Intraoperative ultrasound can observe ablation in three-dimensional space, determine the extent of RF ablation and estimate the degree of local ablation. According to the intraoperative evaluation, 21 cases were completely ablated, 10 cases were basically completely ablated, and 18 cases were incompletely ablated (Table 1).
Table 1 The extent of radiofrequency ablation of hepatocellular carcinoma and the recent efficacy

Degree of local ablation

Recent efficacy

Total

Radical ablation

Subradical ablation

Palliative ablation

Complete ablation

18

3

0

21

Basic complete ablation

1

6

3

10

Incomplete ablation

0

0

18

18

Total

19

9

21

49