Abstract
Objective: This study aimed to compare the effects of ultrasound and CT-guided radiofrequency ablation (RFA) on liver function, serum antagonist-II (PIVKA-II), alpha-fetoprotein (AFP) levels, and disease recurrence in patients with primary hepatocellular carcinoma (PHC). Methods: Ninety-eight patients with PHC were enrolled and treated with RFA. They were grouped as the ultrasound-guided group (n=51) and the CT-guided group (n=47) according to the specific guidance methods. The clinical efficacy, recurrence and survival after treatment, as well as the changes of liver function, serum PIVKA-II and AFP levels before and after treatment were compared between the two groups. Results: The total effective rate of the CT-guided group (87.23%) was significantly higher than that of the ultrasound-guided group (62.75%) (P < 0.05). Total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were reduced in both groups after treatment (P < 0.05) and were lower in the CT-guided group than in the ultrasound-guided group (P < 0.05). Albumin (ALB) levels were elevated in both groups after treatment (P < 0.05) and were higher in the CT-guided group than in the ultrasound-guided group (P < 0.05). PIVKA-II and AFP levels decreased in both groups after treatment (P < 0.05) and were significantly lower in the CT-guided group than in the ultrasound-guided group (P < 0.05). The 2-year and 3-year recurrence rates in the CT-guided group were 4.26% and 8.51%, respectively, significantly lower than 17.65% and 27.45% in the ultrasound-guided group (P < 0.05), and the 2-year and 3-year survival rates in the CT-guided group were 89.36% and 72.34%, respectively, significantly higher than 72.55% and 50.98% in the ultrasound-guided group (P < 0.05). Conclusion: Compared with ultrasound guidance, CT-guided RFA can more effectively improve liver function, reduce serum IVKA-II and AFP levels, reduce recurrence rate, and improve survival time in the treatment of PHC.
Keywords: Ultrasound-guided, CT-guided, radiofrequency ablation, liver function, PIVKA-II, methemoglobin, recurrence
Introduction
Primary hepatocellular carcinoma (PHC) is caused by the carcinogenesis of stem cells or intrahepatic bile duct cells and has a high morbidity and mortality, with the clinical manifestations of weakness, abdominal distension, ascites, and pain in the liver area. PHC has an insidious process, characterized by high malignancy and rapid progression. Most patients are already at a locally advanced stage when diagnosed, missing the best treatment window. Studies have shown that the occurrence of PHC is related to contaminated drinking water, viral hepatitis, genetics, tobacco, alcohol consumption, etc., and the mortality of PHC in China accounts for about 1/2 of the global cases, which seriously threatens the lives of patients [1,2].
There are different treatment options for different stages of PHC, including surgical resection, radiotherapy, chemotherapy, hepatic artery chemoembolization, and radiofrequency ablation (RFA). Liver metastasis and liver transplantation are the preferred options for the clinical treatment of PHC. However, since the early symptoms of PHC are subtle, early tumors may show multicentric, disseminated, metastatic characteristics and are accompanied by cirrhosis as well as inadequate liver function, making surgery more difficult. A study has shown that the success rate of radical resection in patients with PHC is only about 30% [3]. In contrast, only 20% to 30% of patients with PHC are suitable for surgery depending on the tumor location, size, and number, while 30% to 70% of patients experience recurrence after surgery [4,5]. Hepatic artery chemoembolization is commonly used clinically to treat patients with PHC who cannot undergo surgical resection. However, studies have shown that the tumor blood supply arteries in patients with PHC are very complex, and although hepatic artery chemoembolization shows efficacy in the short term, the long-term outcomes and prognosis are poor because hepatic artery chemoembolization cannot completely block the tumor blood supply, and patients with larger tumors are prone to recurrence after treatment [6,7].
RFA is a thermal coagulation therapy, which kills tumorigenic cells through thermal effects, and it is a minimally invasive technique that is inexpensive, safe and reliable, reproducible, and less invasive, providing radical treatment for PHC patients who are intolerant of surgical treatment [8]. RFA is an important method for the treatment of mid- to advanced-stage PHC, and its effectiveness for early PHC is comparable to that of surgery [9]. RFA can not only kill tumor cells, but also inhibit tumor angiogenesis, so as to improve the anti-tumor immunity of patients, and reduce the damage to the liver, which has become the key option of minimally invasive treatment for PHC [10,11]. Initially, RFA was mainly guided by ultrasound, and CT guidance was gradually adopted with more and more extensive application of RFA. It has been pointed out that CT guidance can compensate some of the shortcomings of ultrasound guidance and is more advantageous in some aspects [12]. However, it has also been shown that CT guidance cannot adjust the position of puncture needle in real time, and CT-guided RFA procedures have a longer treatment time, which leads to many problems [13]. Serum abnormal prothrombin (PIVKA-II) is synthesized by the liver, and alpha-fetoprotein (AFP) is secreted in large amounts when hepatocytes are not differentiated. Therefore, PIVKA-II and AFP levels will change during the treatment of PHC patients. In this study, the effects of ultrasound guided and CT-guided RFA were compared in PHC. The liver function, serum antagonist-II (PIVKA-II), alpha-fetoprotein (AFP) levels and recurrence of patients were also analyzed, providing an auxiliary reference for the clinical treatment of PHC.
Materials and methods
General data
Ninety-eight patients with PHC admitted to our hospital were included, and they were divided into the ultrasound-guided group (n=51) and the CT-guided group (n=47) according to the specific guidance methods. Inclusion criteria: (1) PHC diagnosed by imaging and pathology; (2) tumor diameter < 6 cm; (3) expected survival time > 6 months. Exclusion criteria: (1) those with cancerous thrombosis of the inferior vena cava, hepatic vein or portal vein; (2) those with abnormalities of the hematological system and immune system; (3) those with cancerous lesions caused by drugs, alcohol, autoimmune issues, etc.; (4) those with contraindications to radiofrequency ablation; (5) those with coagulation dysfunction; (6) those with distant lymph node metastases and extrahepatic metastases; and (7) those who withdrew from the study midway. This study was approved by the Ethics Committee of The First People’s Hospital of Fuyang Hangzhou. The research subjects and their families were informed and signed a fully-informed consent form.
Methods
All patients underwent preoperative systemic evaluation of liver and kidney function, routine blood work, blood biochemistry, and electrocardiogram, and hepatic magnetic resonance imaging (MRI) or contrast-enhanced CT scan using a GY-8100 radiofrequency ablation therapy instrument (Shanghai Hanfei Medical Equipment Co., Ltd.). (1) The CT-guided group received CT-guided RFA. The size, location, and number of tumors were determined by CT scan. Based on the surface markers, the location of the puncture point and the path of the needle into the tumor were planned. The guide needle was first used for rough positioning, followed by performing puncture. CT scans were repeated to adjust the angle and depth of the needle, so that the needle could accurately advance into the tumor. The power was adjusted 60-200 W, and the ablation time was 6-12 min/time. After the tumor was completely ablated, the puncture needle was withdrawn and the path is closed. (2) In the ultrasound-guided group, ultrasound was used to determine the size, location, and number of the tumors, and the RF needle was inserted into the tumor under the guidance of ultrasound with a power adjustment range of 60-200 W. The ablation time was 6-12 min/time, and after the tumor was completely ablated, the puncture needle was withdrawn and the needle path was closed. The effect of ablation was reviewed using enhanced MRI or CT after one month.
Outcome measurements
(1) Clinical efficacy was assessed according to the World Health Organization criteria related to solid tumors. Patients whose tumors completely disappeared for 1 month were considered to have complete remission (CR); patients whose tumors shrank by more than 50% but still had tumors were considered to have partial remission (PR); patients whose tumors shrank by less than 50% or increased by less than 25% were stable disease (SD); Patients with tumor enlargement of 25% and above were classified as progressive disease (PD). (2) Five mL of fasting venous blood was drawn from patients in the early morning before and 1 month after treatment, centrifuged at 3000 rpm for 10 min using a centrifuge. The supernatant was taken for measurement. An AU5800 automatic biochemical analyzer (Beckman Coulter, USA) was used to detect liver function indicators, including total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin (ALB) levels. ELISA kit (Shanghai Enzyme-Linked Biotechnology Co., Ltd) was used to detect PIVKA-II levels; UniCel DxI800 electrochemiluminescence immunoassay Analyzer (Beckman Coulter, USA) was used to detect AFP level. (3) Patients were followed up for 3 years and recurrence as well as survival was recorded.
Statistical methods
All data were processed by SPSS 22.0. Count data were expressed as [n (%)] and examined by χ2 test. Measurement data were expressed as (x̅ ± s) analyzed with independent samples t-test for comparison between groups and paired t-test for comparison within the same group. Survival curves were analyzed using Kaplan-Meier analysis. Figure illustrations were created by GraphPad Prism 8. Statistically significant differences were indicated with P < 0.05.
Results
Baseline data
The ultrasound-guided group had 41 males and 10 females, aged 34 to 72 years, with a mean age of (51.69±7.26) years. The CT-guided group had 34 males and 13 females, aged 35 to 69 years, with a mean age (50.96±7.45) years. The baseline data showed no significant difference between the two groups (P > 0.05) (Table 1).
Table 1.
Comparison of baseline data for both groups [n (%)]
| Group | Number of cases | Age | Gender | Tumor Diameter | Number of tumors | Liver Function Child-Pugh Classification | ||||
|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|
||||||||
| Male | Female | Single | Multiple | Grade A | Grade B | Grade C | ||||
| CT-guided group | 47 | 50.96±7.45 | 34 (72.34) | 13 (27.66) | 4.12±0.67 | 32 (68.09) | 15 (31.91) | 28 (59.57) | 16 (34.04) | 3 (6.38) |
| Ultrasound-guided group | 51 | 51.69±7.26 | 41 (80.39) | 10 (19.61) | 4.11±0.71 | 33 (64.71) | 18 (35.29) | 32 (62.75) | 15 (29.41) | 4 (7.84) |
| t | 0.385 | 0.883 | 0.072 | 0.125 | 0.068 | |||||
| P | 0.701 | 0.347 | 0.943 | 0.724 | 0.794 | |||||
Clinical efficacy
After treatment, the CT-guided group had 29 cases (61.70%) of CR, 12 cases (25.53%) of PR, 5 cases (10.64%) of SD, and 1 case (2.13%) of PD, with a total effective rate of 87.23%; while the ultrasound-guided group had 18 cases (35.29%) of CR, 14 cases (27.45%) of PR, 13 cases (25.49%) of SD, and 6 cases (11.76%) of PD, with a total effective rate of 62.75%. After treatment, the clinical efficacy in the CT-guided group was better than that in the ultrasound-guided group (Z=3.306, P < 0.05), and the total effective rate of treatment in the CT-guided group was significantly higher than that in the ultrasound-guided group (P < 0.05) (Table 2).
Table 2.
Comparison of clinical outcomes after treatment between the two groups [n (%)]
| Group | Number of cases | CR | PR | SD | PD | Total effective |
|---|---|---|---|---|---|---|
| CT-guided group | 47 | 29 (61.7) | 12 (25.53) | 5 (10.64) | 1 (2.13) | 41 (87.23) |
| Ultrasound-guided group | 51 | 18 (35.29) | 14 (27.45) | 13 (25.49) | 6 (11.76) | 32 (62.75) |
| Z/χ2 | 3.036 | 7.719 | ||||
| P | 0.002 | 0.005 |
Liver function indicators
There was no significant difference in TBIL, DBIL, AST, ALT, ALB levels between the two groups before treatment (P > 0.05). After treatment, TBIL, DBIL, AST and ALT levels were decreased in both groups (P < 0.05) and were significantly lower in the CT-guided group [(30.24±5.38) μmol/L, (11.24±3.57) μmol/L, (31.67±9.67) U/L, (26.46±6.64) U/L] than in the ultrasound-guided group [(37.27±5.75) μmol/L, (18.96±5.26) μmol/L, (42.58±10.24) U/L, (36.92±7.96) U/L] (P < 0.05), while ALB levels were increased in both groups (P < 0.05) and were significantly higher in the CT-guided group [(40.48±4.71) g/L] than in the ultrasound-guided group [(35.58±4.94) g/L] (P < 0.05) (Table 3).
Table 3.
Comparison of liver function indices before and after treatment (x̅ ± s)
| Group | Time point | TBIL (μmol/L) | DBIL (μmol/L) | AST (U/L) | ALT (U/L) | ALB (g/L) |
|---|---|---|---|---|---|---|
| CT-guided group (n=47) | Before treatment | 45.29±8.24 | 35.24±6.19 | 74.07±15.84 | 65.27±13.66 | 30.64±6.62 |
| After treatment | 30.24±5.38 | 11.24±3.57 | 31.67±9.67 | 26.46±6.64 | 40.48±4.71 | |
| ta | 10.485 | 23.026 | 15.663 | 17.518 | 8.303 | |
| Pa | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | |
| Ultrasound-guided group (n=51) | Before treatment | 44.68±8.57 | 35.72±6.45 | 76.06±15.64 | 64.94±13.81 | 30.68±6.16 |
| After treatment | 37.27±5.75 | 18.96±5.26 | 42.58±10.24 | 36.92±7.96 | 35.58±4.94 | |
| ta | 5.128 | 14.381 | 12.79 | 12.554 | 4.432 | |
| Pa | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | |
| Tb | 0.359 | 0.375 | 0.625 | 0.119 | 0.031 | |
| Pb | 0.721 | 0.708 | 0.533 | 0.906 | 0.975 | |
| tc | 6.235 | 8.429 | 5.411 | 7.031 | 5.016 | |
| Pc | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | |
Note: ta, Pa indicate within-group comparisons, tb, Pb indicate pre-treatment comparisons, and tc, Pc indicate post-treatment comparisons.
Serum PIVKA-II, AFP levels
The pre-treatment PIVKA-II and AFP levels in the CT-guided group were (1562.49±129.19) mAU/mL and (132.56±17.29) ng/mL, respectively, which were not significantly different from (1535.72±126.37) mAU/mL and (136.05±15.65) ng/mL in the ultrasound-guided group (P > 0.05). After treatment, both groups exhibited decreased PIVKA-II and AFP levels (P < 0.05). PIVKA-II and AFP levels were (567.33±59.89) mAU/mL and (86.88±10.31) ng/mL in the CT-guided group, respectively, significantly lower than (788.95±85.23) mAU/mL and (102.56±11.23) ng/mL in the ultrasound-guided group (P < 0.05) (Table 4; Figure 1).
Table 4.
Comparison of PIVKA-II, AFP levels before and after treatment (x̅ ± s)
| Group | Number of cases | PIVKA-II (mAU/mL) | t | P | AFP (ng/mL) | t | P | ||
|---|---|---|---|---|---|---|---|---|---|
|
|
|
||||||||
| Before treatment | After treatment | Before treatment | After treatment | ||||||
| CT-guided group | 47 | 1562.49±129.19 | 567.33±59.89 | 47.912 | < 0.001 | 132.56±17.29 | 86.88±10.31 | 15.557 | < 0.001 |
| Ultrasound-guided group | 51 | 1535.72±126.37 | 788.95±85.23 | 34.988 | < 0.001 | 136.05±15.65 | 102.56±11.23 | 12.416 | < 0.001 |
| t | 1.037 | 14.776 | 1.049 | 7.181 | |||||
| P | 0.303 | < 0.001 | 0.297 | < 0.001 | |||||
Figure 1.
Comparison of PIVKA-II and AFP levels before and after treatment between the two groups. There was no significant difference in PIVKA-II and AFP levels between the two groups before treatment (P > 0.05). After treatment, PIVKA-II and AFP levels were reduced in both groups, and the levels in the CT-guided group were lower than those in the ultrasound-guided group (P < 0.05).
Comparison of recurrence rate
The 1-year recurrence and survival rates in the CT-guided group were 4.26% and 93.62%, respectively, which had no significant difference from 5.88% and 90.20% in the ultrasound-guided group (P > 0.05). The 2-year and 3-year recurrence rates were 4.26% and 8.51%, respectively, in the CT-guided group, significantly lower than 17.65% and 27.45% in the ultrasound-guided group (P < 0.05). The 2- and 3-year survival rates were 89.36% and 72.34%, respectively, in the CT-guided group, significantly higher than 72.55% and 50.98% in the ultrasound-guided group (P < 0.05) (Table 5; Figure 2).
Table 5.
Comparison of recurrence rates as well as survival rates [n (%)]
| Group | Number of cases | Recurrence rate | Survival rate | ||||
|---|---|---|---|---|---|---|---|
|
|
|
||||||
| 1 year | 2 years | 3 years | 1 years | 2 years | 3 years | ||
| CT-guided group | 47 | 2 (4.26) | 2 (4.26) | 4 (8.51) | 44 (93.62) | 42 (89.36) | 34 (72.34) |
| Ultrasound-guided group | 51 | 3 (5.88) | 9 (17.65) | 14 (27.45) | 46 (90.20) | 37 (72.55) | 26 (50.98) |
| χ2 | 0.134 | 4.402 | 5.852 | 0.382 | 4.424 | 4.701 | |
| P | 0.715 | 0.036 | 0.016 | 0.537 | 0.035 | 0.030 | |
Figure 2.
Comparison of 3-year survival curves between the two groups during the follow-up. The survival of the CT-guided group was superior to that of the ultrasound-guided group (P < 0.05).
Discussion
CT guidance and ultrasound guidance are the most common guidance methods for RFA in clinical practice. Ultrasound guidance is flexible and relatively easy to operate, and can determine the puncture route by real-time multidimensional scans. Therefore, the puncture needle technique can advance into the tumor avoiding ligamentous structures, bile ducts, and large vessels with high safety [14,15]. CT-guided images are clearer and can ensure the best optimal position of the puncture needle into the lesion with more accurate localization [16]. Meanwhile, CT guidance can combine with liver-enhanced MRI at special sites, such as lesions at the paramedian duct, the top of the diaphragm, and even lesions that cannot be clearly shown under ultrasound guidance; thus showing the location of the tumor more precisely, and the echogenic changes during RFA treatment do not affect the judgment resulting from CT guidance [17]. In RFA, the results regarding the effects of ultrasound guidance and CT guidance are different. This study compared the effects of the two guidance methods.
Evidence has shown that the occurrence and the development of PHC are related to the dysregulation of immune function [18]. Patients with PHC have impaired immune function and thus relatively low immune function, and liver function indicators can reflect the degree of liver function injury in PHC patients [19]. Bilirubin includes TBIL and DBIL, whose levels are increased when hepatocytes are damaged [20,21]. ALT is involved in the metabolism of proteins, and its levels will rise in the blood during liver inflammation [22]. AST is abundant in the heart muscle, followed by the liver, and serum AST concentrations increase in the presence of hepatocyte necrosis [23]. As the source of nutrition, ALB is a protein maintaining osmotic pressure of the body, which is mainly synthesized by the liver, and the decrease of its level can reflect the impairment of liver function [24]. TBIL, DBIL, AST, and ALT levels were decreased in both groups after treatment, and they were lower in the CT-guided group than in the ultrasound-guided group. ALB levels were increased in both groups and were higher in the CT-guided group than in the ultrasound-guided group. The results of the study showed that both modalities could improve liver function injury, but CT-guided RFA was more effective.
PIVKA-II is synthesized by the liver, and acts as an autologous growth factor during the growth of liver tumors. Serum PIVKA-II is highly expressed in PHC patients, and PIVKA-II can better reflect early liver tumors and hepatocellular carcinoma nodules [25]. AFP is a tumor marker and is sourced from embryonic hepatocytes, and fetuses secrete large amounts of AFP because their hepatocytes are not fully differentiated. Hepatocytes of PHC patients are undifferentiated and therefore their AFP levels are also highly expressed [26]. In this study, PIVKA-II and AFP levels were decreased in both groups after treatment, and were lower in the CT-guided group than in the ultrasound-guided group. The results of the study showed CT-guided RFA was more effective in improving serum PIVKA-II, AFP levels.
This study also showed that the overall treatment efficiency in the CT-guided group (87.23% vs. 62.75%) was significantly higher than that in the ultrasound-guided group. The 2-year recurrence rate (4.26% vs. 17.65%) and 3-year recurrence rate (8.51% vs. 27.45%) in the CT-guided group were significantly lower than those in the ultrasound-guided group; and the 2-year survival rate (89.36% vs. 72.55%) and 3-year survival rate (72.34% vs. 50.98%) in the CT-guided group were significantly higher than those in the ultrasound-guided group. The results of the study showed that CT-guided RFA was more effective in reducing recurrence rates and improving survival time for the treatment of PHC. The underlying reasons may be that the resolution of ultrasound is poorer compared to CT, and during RFA, the vaporization effect of ultrasound guidance will interfere with visualization, which makes it more difficult for the operator to judge the ablation effect and perform multiple ablations. If the two tumors are located close to each other, the vaporization effect produced by the first ablation will obstruct the field of view of the later ablation, so the treatment effect and survival time under ultrasound guidance are worse and the recurrence rate is higher compared to CT guidance [27,28].
In conclusion, patients with PHC have liver function damage and high expression of serum IVKA-II and AFP levels. RFA can effectively improve the liver function damage and reduce serum IVKA-II and AFP levels of patients. Compared with ultrasound guidance, CT-guided RFA was more effectively in treating PHC. However, this study is a retrospective analysis, and the guidance mode of RFA treatment is chosen by the operator, which may cause bias in the selection. Both CT guidance and ultrasound guidance were operated by surgeons. They are not as professional as sonographers in terms of operation, which may have a certain impact on the curative effect, and the study sample is relatively small, and further larger sample size studies are needed.
Disclosure of conflict of interest
None.
References
- 1.Lei C, Ren D, Fu M, Sun C, Ren H, Pan Q, Li Y. Curative effect of endostar combined with oxaliplatin in the treatment of primary hepatic carcinoma and its influence on immune cells. Oncol Lett. 2019;17:3665–3670. doi: 10.3892/ol.2019.10022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Liang D, Yang B. Short-term efficacy of oral low-dose Tegafur chemotherapy after transarterial chemoembolization in primary hepatic carcinoma. J BUON. 2019;24:171–177. [PubMed] [Google Scholar]
- 3.Mao JX, Teng F, Yuan H, Liu C, Fu H, Sun KY, Ding GS, Guo WY. Primary hepatic squamous cell carcinoma with abdominal incision metastasis after hepatectomy. Hepatobiliary Pancreat Dis Int. 2019;18:194–198. doi: 10.1016/j.hbpd.2018.12.004. [DOI] [PubMed] [Google Scholar]
- 4.Koh YX, Tan HJ, Liew YX, Syn N, Teo JY, Lee SY, Goh BKP, Goh GBB, Chan CY. Liver resection for nonalcoholic fatty liver disease-associated hepatocellular carcinoma. J Am Coll Surg. 2019;229:467–478. e461. doi: 10.1016/j.jamcollsurg.2019.07.012. [DOI] [PubMed] [Google Scholar]
- 5.Di Sandro S, Centonze L, Pinotti E, Lauterio A, De Carlis R, Romano F, Gianotti L, De Carlis L. Surgical and oncological outcomes of hepatic resection for BCLC-B hepatocellular carcinoma: a retrospective multicenter analysis among 474 consecutive cases. Updates Surg. 2019;71:285–293. doi: 10.1007/s13304-019-00649-w. [DOI] [PubMed] [Google Scholar]
- 6.Xu X, Meng Q. Drug effect analysis of sorafenib combined with transcatheter arterial chemoembolization in the treatment of advanced hepatocellular carcinoma. Pak J Pharm Sci. 2018;31:1751–1755. [PubMed] [Google Scholar]
- 7.Lin EY, Lee RC, Guo WY, Wu FC, Gehrisch S, Kowarschik M. Three-dimensional quantitative color-coding analysis of hepatic arterial flow change during chemoembolization of hepatocellular carcinoma. J Vasc Interv Radiol. 2018;29:1362–1368. doi: 10.1016/j.jvir.2018.04.012. [DOI] [PubMed] [Google Scholar]
- 8.Kim HJ, Park BK, Chung IS. Comparison of general anesthesia and conscious sedation during computed tomography-guided radiofrequency ablation of T1a renal cell carcinoma. Can Assoc Radiol J. 2018;69:24–29. doi: 10.1016/j.carj.2017.07.003. [DOI] [PubMed] [Google Scholar]
- 9.Cesareo R, Naciu AM, Iozzino M, Pasqualini V, Simeoni C, Casini A, Campagna G, Manfrini S, Tabacco G, Palermo A. Nodule size as predictive factor of efficacy of radiofrequency ablation in treating autonomously functioning thyroid nodules. Int J Hyperthermia. 2018;34:617–623. doi: 10.1080/02656736.2018.1430868. [DOI] [PubMed] [Google Scholar]
- 10.Tsukamoto M, Yamashita YI, Imai K, Umezaki N, Yamao T, Kaida T, Mima K, Nakagawa S, Hashimoto D, Chikamoto A, Ishiko T, Baba H. Long-term favorable outcomes of radiofrequency ablation for hepatocellular carcinoma as an initial treatment: a single-center experience over a 10-year period. Anticancer Res. 2018;38:1047–1052. doi: 10.21873/anticanres.12321. [DOI] [PubMed] [Google Scholar]
- 11.Wang WD, Zhang LH, Ni JY, Jiang XY, Chen D, Chen YT, Sun HL, Luo JH, Xu LF. Radiofrequency ablation combined with transcatheter arterial chemoembolization therapy versus surgical resection for hepatocellular carcinoma within the milan criteria: a meta-analysis. Korean J Radiol. 2018;19:613–622. doi: 10.3348/kjr.2018.19.4.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Yuan H, Liu F, Li X, Guan Y, Wang M. Transcatheter arterial chemoembolization combined with simultaneous DynaCT-guided radiofrequency ablation in the treatment of solitary large hepatocellular carcinoma. Radiol Med. 2019;124:1–7. doi: 10.1007/s11547-018-0932-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Bartos A, Bartos D, Spârchez Z, Iancu I, Ciobanu L, Iancu C, Breazu C. Laparoscopic contrast-enhanced ultrasonography for real time monitoring of laparoscopic radiofrequency ablation for hepatocellular carcinoma: an observational pilot study. J Gastrointestin Liver Dis. 2019;28:457–462. doi: 10.15403/jgld-263. [DOI] [PubMed] [Google Scholar]
- 14.Zhang L, Li Q, Wang CY, Tsui PH. Ultrasound single-phase CBE imaging for monitoring radiofrequency ablation. Int J Hyperthermia. 2018;35:548–558. doi: 10.1080/02656736.2018.1512160. [DOI] [PubMed] [Google Scholar]
- 15.O’Neal D, Cohen T, Peterson C, Barr RG. Contrast-enhanced ultrasound-guided radiofrequency ablation of renal tumors. J Kidney Cancer VHL. 2018;5:7–14. doi: 10.15586/jkcvhl.2018.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Hsieh MF, Chen CB, Chen YL, Chou CT. Hemobilia after CT-guided radiofrequency ablation of liver tumors: frequency, risk factors, and clinical significance. Abdom Radiol (NY) 2019;44:337–345. doi: 10.1007/s00261-018-1693-y. [DOI] [PubMed] [Google Scholar]
- 17.Feigl GC, Mattersberger C, Rosmarin W, Likar R, Avila González C. Lumbar CT-guided radiofrequency ablation of the medial branch of the dorsal ramus of the spinal nerve: anatomic study and description of a new technique. Schmerz. 2018;32:99–104. doi: 10.1007/s00482-018-0283-9. [DOI] [PubMed] [Google Scholar]
- 18.Ma Q, Jiang L, Bonda S, Luo D, Zhang W. A rare case of hepatic sarcomatoid carcinoma: exceeding expectations in a stage IV primary hepatic sarcomatoid carcinoma patient. Int J Clin Exp Pathol. 2019;12:378–383. [PMC free article] [PubMed] [Google Scholar]
- 19.Zhang LX, Lv Y, Xu AM, Wang HZ. The prognostic significance of serum gamma-glutamyltransferase levels and AST/ALT in primary hepatic carcinoma. BMC Cancer. 2019;19:841. doi: 10.1186/s12885-019-6011-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Liu W, Liu Q, Wang W, Wang P, Chen J, Hong T, Zhang N, Li B, Qu Q, He X. Differential diagnostic roles of the serum CA19-9, total bilirubin (TBIL) and the ratio of CA19-9 to TBIL for benign and malignant. J Cancer. 2018;9:1804–1812. doi: 10.7150/jca.25093. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Xu C, Dong M, Deng Y, Zhang L, Deng F, Zhou J, Yuan Z. Relation of direct, indirect, and total bilirubin to adverse long-term outcomes among patients with acute coronary syndrome. Am J Cardiol. 2019;123:1244–1248. doi: 10.1016/j.amjcard.2019.01.019. [DOI] [PubMed] [Google Scholar]
- 22.Chen KW, Meng FC, Shih YL, Su FY, Lin YP, Lin F, Lin JW, Chang WK, Lee CJ, Li YH, Hsieh CB, Lin GM. Sex-specific association between metabolic abnormalities and elevated alanine aminotransferase levels in a military cohort: the CHIEF study. Int J Environ Res Public Health. 2018;15:545. doi: 10.3390/ijerph15030545. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Ha YS, Kim SW, Chun SY, Chung JW, Choi SH, Lee JN, Kim BS, Kim HT, Yoo ES, Kwon TG, Kim WT, Kim WJ, Kim TH. Association between De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) and oncological outcomes in bladder cancer patients after radical cystectomy. BMC Urol. 2019;19:10. doi: 10.1186/s12894-019-0439-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Wu B, Hu X, Jin H, Zhou L, Zhang D, Man Z, Wang Y, Yang S, Pang Q, Liu H, Cui P. Albumin-bilirubin and platelet-albumin-bilirubin grades for hepatitis B-associated hepatocellular carcinoma in Child-Pugh A patients treated with radical surgery: a retrospective observational study. Medicine (Baltimore) 2019;98:e17394. doi: 10.1097/MD.0000000000017394. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Payancé A, Dioguardi Burgio M, Peoc’h K, Achahboun M, Albuquerque M, Devictor J, Chor H, Manceau H, Soubrane O, Durand F, Castera L, Bouattour M, Paradis V. Biological response under treatment and prognostic value of protein induced by vitamin K absence or antagonist-II in a French cohort of patients with hepatocellular carcinoma. Eur J Gastroenterol Hepatol. 2020;32:1364–1372. doi: 10.1097/MEG.0000000000001652. [DOI] [PubMed] [Google Scholar]
- 26.Liang J, Wang J, Zhang L, Wang S, Yao C, Zhang Z. Conductometric immunoassay of alpha-fetoprotein in sera of liver cancer patients using bienzyme-functionalized nanometer-sized silica beads. Analyst. 2018;144:265–273. doi: 10.1039/c8an01791c. [DOI] [PubMed] [Google Scholar]
- 27.Ye L, Wen C, Liu H. Ultrasound-guided versus low dose computed tomography scanning guidance for lumbar facet joint injections: same accuracy and efficiency. BMC Anesthesiol. 2018;18:160. doi: 10.1186/s12871-018-0620-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Huo J, Aloia TA, Xu Y, Chung TH, Sheu T, Tina Shih YC. Comparative effectiveness of computed tomography-versus ultrasound-guided percutaneous radiofrequency ablation among medicare patients 65 years of age or older with hepatocellular carcinoma. Value Health. 2019;22:284–292. doi: 10.1016/j.jval.2018.10.004. [DOI] [PMC free article] [PubMed] [Google Scholar]