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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 7  |  Page : 148-152

Analysis of therapeutic effectiveness and prognostic factor on argon-helium cryoablation combined with transcatheter arterial chemoembolization for the treatment of advanced hepatocellular carcinoma


Department of Radiology, Panyu Central Hospital, Guangzhou, Guangdong, China

Date of Web Publication21-Feb-2017

Correspondence Address:
Yi Huang
No. 8, Fuyu Road East, Qiaonan Street, Panyu District, Guangzhou 511400, Guangdong
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.200605

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 > Abstract 

Objective: The objective of this study was to evaluate the effectiveness on argon-helium cryoablation combined with transcatheter arterial chemoembolization (TACE) in treating advanced hepatocellular carcinoma (HCC) and its influence factor.
Materials and Methods: This trial was approved by the Guangzhou Panyu Central Hospital Ethics Committee. This was a prospective, single-center study conducted in Guangzhou Panyu Central Hospital. After informed consent was obtained, the prospective randomized clinical data of 120 patients with advanced HCC were collected. Based on the therapeutic scheme, the patients were divided into control group (TACE + argon-helium cryoablation) and observed group (TACE group). All the patients were followed up for 60 months. The pre- and post-operative cancer situation, hepatic function situation, complete remission (CR) rate, total effective rate, and survival time were evaluated. The short-term and long-term effectiveness were compared between the two groups.
Results: Both the CR rate and total effective rate of the combination group were significantly higher than those of TACE group (P < 0.05). Liver function damage of the combination group was lower than those of TACE group. The survival rate of the combination group was significantly longer than that of TACE group P < 0.05). The Cox regression model revealed that ages, tumor diameter, tumor periportal location, and liver function (Child-Pugh) were significant variables influencing survival time P < 0.05).
Conclusion: For the treatment of advanced HCC, argon-helium cryoablation combined with TACE is obviously effective and safe. The ages, tumor diameter, tumor periportal location, and grade of liver function (Child-Pugh) have obvious impacted the treatment effectiveness.

Keywords: Advanced hepatic neoplasm, cryoablation, therapeutic effect, transcatheter arterial chemoembolization


How to cite this article:
Huang C, Zhuang W, Feng H, Guo H, Tang Y, Chen H, Huang Y. Analysis of therapeutic effectiveness and prognostic factor on argon-helium cryoablation combined with transcatheter arterial chemoembolization for the treatment of advanced hepatocellular carcinoma. J Can Res Ther 2016;12, Suppl S3:148-52

How to cite this URL:
Huang C, Zhuang W, Feng H, Guo H, Tang Y, Chen H, Huang Y. Analysis of therapeutic effectiveness and prognostic factor on argon-helium cryoablation combined with transcatheter arterial chemoembolization for the treatment of advanced hepatocellular carcinoma. J Can Res Ther [serial online] 2016 [cited 2021 Sep 21];12:148-52. Available from: https://www.cancerjournal.net/text.asp?2016/12/7/148/200605


 > Introduction Top


Hepatocellular carcinoma (HCC) is one of the highest mortalities and morbidities of malignant tumor in the world; its morbidity is a trend of increasing incidence at present. If the cancer was found, it was always advanced HCC in China. Then, surgical resection rate is low, and the recurrence rate is high. Transcatheter arterial chemoembolization (TACE) and nonvascular interventional treatment methods have their own advantages and limitations, and different integrated application methods are complementary. Argon-helium cryoablation therapy can make frozen area tumor cells to cause irreversible coagulation necrosis. It is a good curative effect method and has been widely used in clinic.

Therefore, between 2011 and 2016, our team makes an attempt at argon-helium cryoablation combined with TACE for the treatment of advanced HCC. We use the prospective clinical controlled study method, and we study in the form of groups to investigate the clinical value on argon-helium cryoablation combined with TACE in treating advanced HCC and its influence factor.


 > Materials and Methods Top


This trial was approved by the Guangzhou Panyu Central Hospital Ethics Committee. This was a prospective, single-center study conducted in Guangzhou Panyu Central Hospital. After informed consent was obtained, the prospective randomized clinical data of 120 patients with advanced HCC were collected.

Participants

Inclusion criteria: (1) All the clinical manifestations, medical imaging findings, and/or pathology diagnosis clear diagnosis of HCC.(2) All patients with liver function Child-Pugh Class for A or B and renal function is normal.

A total of 120 patients who met the standards were selected, who were randomly divided into two groups including the control group and treatment group. The control group had undergone TACE alone, and the treatment group had undergone argon-helium cryoablation combined with TACE. Adopting the randomized controlled clinical study methods, those patients were randomly divided into two groups. Two groups at least undergo TACE at first; then, the control group continued to undergo TACE per month if patients survival. The treatment group underwent argon-helium cryoablation combined with TACE per month if patients survival.

Procedure

Under the digital subtraction angiography (DSA), puncture of femoral artery was carried out using Seldinger puncture; selective artery angiography was performed to observe celiac artery, superior mesenteric, the phrenic artery, renal artery, adrenal, and lumbar artery angiography. Then, we made an angiography by inserting the super selective catheter within the tumor blood supply artery. Then, through the catheter, we injected platinum (25–50 mg) + adriamycin (10–40 mg) + iodine oil (10–20 ml). Postoperatively, we protected liver function, and then, the control group continued to undergo TACE per month if patients survived.

The treatment group: After the first TACE, when liver computed tomography (CT) or magnetic resonance imaging (MRI) scanning shows that the cancer is not satisfied with iodine oil deposit area, the patients will undergo argon-helium cryoablation. In patients with lateral prostration or prone position, or CT positioning, we make markers and choose different specifications of superconducting needles (single or several knife combination) according to the tumor size. During regular disinfection, 2% lidocaine anesthesia was given, and skin incision of 8 mm was done; according to the needle point, direction, and depth, under CT guidance, frozen needles are inserted quickly and accurately to liver tumor targets. The low-temperature operation system was started. Refrigeration and heating are the two cycles. Single frozen time is 10–15 min and the lowest temperature is up to − 140°C. Single heating time is 10 min and the temperature is 40°C. Single-pole or double-pole overlap was adopted; frozen with frozen more than outer tumor edge 1 cm is advisable. In ice hockey, to cover the entire tumor is preferred. Port site is pressed by a bandage. CT or MR-enhanced scan or DSA imaging examines the patients in 4–6 weeks after argon-helium knife cryotherapy; if they have no clear tumor, their survival is observed closely. If obvious tumor blood vessel is seen, the patient must come back every 4 weeks with conventional treatment one time with argon-helium knife cryotherapy.

Follow-up

Patients in every group were followed up with CT or MR-enhanced scan or DSA imaging after 1 month for 5 years. If the patients did not come back, we would ask them by telephone.

Definitions

First evaluation of two groups of patients includes gender, age, tumor diameter, the number of tumor, tumor site, alpha-fetoprotein (AFP) and grade of the child, and liver function; there was no difference in two groups, and they clarify its influence factor. After 1-month review, hepatic enhancement was observed through CT or MRI, and according to the WHO objective efficacy evaluation criteria,[1] to evaluate the recent efficacy of patients, they were divided into complete remission (CR), partial response, no change (stable disease), development (progressive disease). Finally, after curative effect evaluation, imaging review was carried out on the patient every 1 month. Moreover, patients followed up recurrent lesions until death or lesion progress. If patients with tumor recurrence, progression again, we give intervention minimally invasive treatment (60-month follow-up time with the median follow-up period of 36 months), and we record each patient's overall survival (from the study time to the time of death).

Statistical analysis

Data were analyzed using SPSS 20.0 statistical software (IBM SPSS China, Shang hai, China) for statistical analysis; two sample was compared with normal distribution and homogeneity of variance. If it was normal distribution, t-test is adopted, otherwise the nonparametric test. The comparison of rates was carried out by Chi-square test. Single factor analysis model uses Kaplan–Meier model; multifactor analysis uses Cox Proportional hazards model. P < 0.05 was considered statistically significant.


 > Results Top


Eligible patients were not lost to follow-up; all patients in every group were followed up CT or MR-enhanced scan or DSA imaging after 1 month for 5 years. If the patients did not come back, we would ask them by telephone.

For the control group and treatment group of patients with baseline data comparison, we found that two groups of patients with preoperative in age, sex, tumor site, tumor diameter and grade of the Child-Pugh, AFP levels, leukocyte, liver function were not statistically significant in baseline level (P > 0.05) [Table 1].
Table 1: The analysis of ages, sex tumor site, tumor diameter, the Child-Pugh, alpha-fetoprotein levels, blood routine, liver function

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Short-term effect

The aspect of transaminase, total bilirubin, and albumin was statistically difference (P < 0.05) between two groups after 1 month. Child-Pugh grading also was statistically difference (u = 2.60, P = 2.60); Argon-helium cryoablation combined with TACE not only showed no increase in liver damage but also can improve liver function [Table 2].
Table 2: The analysis of ages, sex tumor site, tumor diameter, the Child-Pugh, alpha-fetoprotein levels, blood routine, liver function after 1 month

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Long-term effect

All patients were followed up for 60 months. Seventeen follow-up lost cases were supposed to be death. The treatment group is statistically significant (P < 0.05) than the control group after 1, 3, and 5 years [Table 3],[Table 4],[Table 5].
Table 3: The analysis of long-term effect after 1 year

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Table 4: The analysis of long-term effect after three year

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Table 5: The analysis of long-term effect after five year

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Survival curve and survival rate

Survival analysis showed that the survival rate of the treatment group is 73.5%, 54.3%, 22.6%, and 6.5% in 6 months and 1, 3, and 5 years, respectively [Figure 1].
Figure 1: Survival rate of two groups shows statistical significance (P < 0.05). 0: The control group, 1: The treatment group

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Multi-factor analysis

Cox proportional hazards model shows that tumor diameter, tumor periportal location, Child-Pugh, age factors had significant relationships with survival rate. The occurrence of them had adverse effects on overall survival rate [Table 6].
Table 6: Multi-factor analysis use COX Proportional hazards mode

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 > Discussion Top


HCC is one of the most common malignant tumors in the world. TACE is the most important and preferred primary treatment to patients who missing surgery condition;[2] however, in recent years, the study found that the single TACE of liver cancer with complete necrosis rate is low, long-term efficacy is limited, and repeatedly with conventional treatment can increase liver dysfunction, and it restricts conventional application in liver cancer. The Food and Drug Administration approves cryoablation for clinical application in 1999. The main mechanism is the combination of ultra-low temperature and heating technology, rapid freeze the cancer to ice hockey, intracellular matters became crystal formation, and ice crystals of mechanical damage break the cell membrane. Hence, it made cells dehydration, shrivel, physical, and chemical properties. Protein and pH change, the blood silt up and microthrombosis, etc. These will eventually destroy the tumor.[3] After the 91th annual meeting of the North American radiation Radiological Society of North America which held in Chicago, the United States, argon-helium cryoablation was accepted in liver cancer, lung cancer, prostate cancer, renal tumor such as extensive recognition.[4],[5],[6],[7] Fengtao et al.[8] reported 388 cases of liver cancer patients with cryoablation and TACE analysis showed that the total in 1, 2, 3, and 5 years survival rate was 70.4%, 52.3%, 23.5%, and 70.4%, respectively. Moreover, 80% of the patients can get out of bed on the same day. The treatment is little injury, so patients recover quickly, patients can tolerate.

Process and principle are different between cryoablation and interventional embolization treatment. (1) Cryoablation is performed with the ultra-low temperature(− 140°C) which leads to the formation of a cell inside and outside the ice crystals cell; then, toxicity of dehydration and electrolyte concentration lead to capillary rupture and hypoxia combined to kill the cells.[4] Interventional embolization destroys cancer cells by chemotherapy drugs and blocking tumor blood supply artery.[9] Frozen ice crystals in the cell are physical injury, and it results in irreversible necrosis of tumor cells. In addition, cryotherapy can also treat cancer with the positive immune regulating effect.[10] Cryoablation destroys major treatment zone cells, which do not depend on the degree of tumor cells of oxygenation and cell proliferation; moreover, interventional embolization damage cell with rich blood supply and good oxygenation is greater.[11]

This study combined cryoablation and TACE to improve the effect of the liver cancer treatment, improve the patient's survival, and reduce liver function damage. Hence, cryoablation and TACE have a complement effect. It provides a new treatment for advanced HCC.

Therefore, the treatment combined cryoablation and TACE is ideal choice. Because the effect is good, the treatment reduces liver damage, prolongs survival rate, and improves the quality of life. Argon-helium cryoablation combined with TACE has significant meaning to advanced HCC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Yan S, Zhichang Z. Clinical Oncology Manual. Beijing: People's Medical Publishing Company; 2003. p. 97-113.  Back to cited text no. 1
    
2.
Mengchao W, Han C, Feng S. Minimally invasive surgical therapy of liver cancer in the position. Chin J Minim Invasive Surg 2002;2:69-70.  Back to cited text no. 2
    
3.
Feng D, Shouzhou F, Bing W. Argon-helium knife cryoablation combined hepatic artery embolism chemotherapy of 17 cases of primary liver cancer. Med J Commun 2013;27:402-3.  Back to cited text no. 3
    
4.
Hinshaw JL, Lee FT Jr. Cryoablation for liver cancer. Tech Vasc Interv Radiol 2007;10:47-57.  Back to cited text no. 4
    
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Pusceddu C, Sotgia B, Fele RM, Melis L. CT-guided thin needles percutaneous cryoablation (PCA) in patients with primary and secondary lung tumors: A preliminary experience. Eur J Radiol 2013;82:e246-53.  Back to cited text no. 5
    
6.
Gangi A, Tsoumakidou G, Abdelli O, Buy X, de Mathelin M, Jacqmin D, et al. Percutaneous MR-guided cryoablation of prostate cancer: Initial experience. Eur Radiol 2012;22:1829-35.  Back to cited text no. 6
    
7.
Castro A Jr., Jenkins LC, Salas N, Lorber G, Leveillee RJ. Ablative therapies for small renal tumours. Nat Rev Urol 2013;10:284-91.  Back to cited text no. 7
    
8.
Fengtao Y, Qiping L, Jianshan S. Efficacy of cryoablation combined with transarterial chemoembolization for unresectable liver cancer and prognostic factors. Fu Bu Wai Ke 2013;26:313-6.  Back to cited text no. 8
    
9.
Wang Y, Shen Y. Unresectable hepatocellular carcinoma treated with transarterial chemoembolization: Clinical data from a single teaching hospital. Int J Clin Exp Med 2013;6:367-71.  Back to cited text no. 9
    
10.
Ravindranath MH, Wood TF, Soh D, Gonzales A, Muthugounder S, Perez C, et al. Cryosurgical ablation of liver tumors in colon cancer patients increases the serum total ganglioside level and then selectively augments antiganglioside IgM. Cryobiology 2002;45:10-21.  Back to cited text no. 10
    
11.
Murata S, Mine T, Ueda T, Nakazawa K, Onozawa S, Yasui D, et al. Transcatheter arterial chemoembolization based on hepatic hemodynamics for hepatocellular carcinoma. ScientificWorldJournal 2013;2013:479805.  Back to cited text no. 11
    


    Figures

  [Table 1], [Figure 1]
 
 
    Tables

  [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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