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ORIGINAL ARTICLE
Year : 2015  |  Volume : 28  |  Issue : 2  |  Page : 447-452

Study of the role of transcatheter arterial chemoembolization using iodized oil with and without gel foam for the management of hepatocellular carcinoma


1 Department of Tropical Medicine, Faculty of Medicine, Menoufia University, Shebeen El Kom, Egypt
2 Department of Radiology, Faculty of Medicine, Menoufia University, Shebeen El Kom, Egypt

Date of Submission11-May-2014
Date of Acceptance02-Jul-2015
Date of Web Publication31-Aug-2015

Correspondence Address:
Ayman Abd El-Halim Mohammed El-Gamal
Department of Tropical Medicine, Faculty of Medicine, Menoufia University, Shebeen El Kom
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.163900

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  Abstract 

Objective
The aim of this study was to determine the effectiveness and safety of transcatheter arterial chemoembolization (TACE) using iodized oil with and without gel foam for the management of hepatocellular carcinoma (HCC).
Background
HCC is one of the most common malignant diseases worldwide, with an increasing incidence in the industrialized countries. The extensive application of surveillance programs for the early detection of HCC in high-risk patients has increased the number of tumors detected at a subclinical stage as well as those that are responsive to effective treatments.
Patients and methods
This study was carried out on 40 patients with HCC; of these, 20 patients were treated with TACE by lipiodol and adriamycin, group I, and 20 patients were treated with TACE by lipiodol and adriamycin, followed by gel foam, group II.
Results
A unique criterion of this study is that all the entire study population of the cirrhotic groups had posthepatitic cirrhosis (hepatitis C virus). After TACE, there was a decrease in tumor size, safe in liver function, and a decrease in α-fetoprotein.
Conclusion
TACE was safe and effective in the treatment of HCC. We found a trend toward greater survival when gel foam was used as the embolic agent for TACE for HCC, although this was not significant compared with lipiodol.

Keywords: adriamycin, gel foam, hepatocellular carcinoma, lipiodol, transcatheter arterial chemoembolization


How to cite this article:
Sabry HS, El-Abd UL, El Deeb GS, El-Lehleh AM, Mohammed El-Gamal AA. Study of the role of transcatheter arterial chemoembolization using iodized oil with and without gel foam for the management of hepatocellular carcinoma . Menoufia Med J 2015;28:447-52

How to cite this URL:
Sabry HS, El-Abd UL, El Deeb GS, El-Lehleh AM, Mohammed El-Gamal AA. Study of the role of transcatheter arterial chemoembolization using iodized oil with and without gel foam for the management of hepatocellular carcinoma . Menoufia Med J [serial online] 2015 [cited 2020 Apr 4];28:447-52. Available from: http://www.mmj.eg.net/text.asp?2015/28/2/447/163900


  Introduction Top


Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide, with an increasing incidence in the industrialized countries [1] .

Nonetheless, orthotopic liver transplantation in patients with small HCCs is limited owing to the high rate of HCC progression and death because of liver disease while the patient's name is on the waiting list. This limitation even applies in countries with a large number of available organs [2] .

For small HCCs (<3 cm), the results of different options such as hepatic resection, percutaneous alcohol injection, and thermoablation seem to show a survival benefit. For large HCCs (>3 cm), transcatheter arterial chemoembolization (TACE) remains the sole approach to inhibit cancer growth in most patients and has been used extensively in the western world and Asia to treat unresectable HCCs [3] .

In 2000, the European Association for the Study of the Liver suggested that a study is needed to clarify whether differences in treatment schedules including new agent combinations or the selection of patients may result in a more therapeutic benefit for at least a subgroup of patients with HCC who are not surgical candidates [4] . The aim of this work was to study the effectiveness and safety of TACE using iodized oil with and without gel foam for the management of HCC.


  Patients and methods Top


This study was carried out in the Tropical Medicine Department, Menoufia University Hospital and Liver Institute. The study focused on two patient groups: group I included 20 patients treated with TACE by lipiodol and adriamycin and group II included 20 patients treated with TACE lipiodol and adriamycin, followed by gel foam. After providing an informed consent, each patient underwent the following:

  1. Detailed assessment of history: The presence of predisposing factors such as liver cirrhosis and viral hepatitis and the presenting complaints of the patient, which may be vague such as dyspepsia, abdominal pain, abdominal discomfort, or loss of weight, and deterioration of the general condition, were assessed.
  2. Clinical assessment: General and local abdominal examinations were performed.
  3. Investigation: Complete blood picture, liver profile including serum bilirubin, transaminases (SGPT and SGOT), serum albumin, prothrombin time, α-fetoprotein (AFP), and kidney function tests were performed.
  4. Upper endoscopy and liver biopsy were performed [5] .
  5. Radiological studies: Chest radiography, abdominal ultrasonography (US), and Doppler study of the portal vein, abdominal triphasic spiral computed tomography (CT), bone scan, selective hepatic angiography, coeliac arteriography and superior mesenteric arteriography, and digital substraction angiography were performed in all the patients [6] .
  6. Treatment program: After proper assessment of the two groups, all patients underwent 1-3 sessions of TACE 1-2 months apart. They were evaluated after each session by CT after 2 weeks to determine the response to treatment. TACE was then repeated according to the response.
  7. Post-transcatheter arterial chemoembolization follow-up: All patients are seen at least once weekly during the first month and every 2 months for 6 months after the TACE procedure for pyrexia, emesis and abdominal pain, liver function tests, and AFP. Abdominal US and triphasic spiral CT were performed every 2 weeks in the first month, and then every 2 months for 6 months thereafter. All patients who were entered into the study were followed up and classified according to the response as follows: complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). This program of follow-up continued for 6 months after the TACE intervention to evaluate side effects, the response rate of tumor size, newly formed tumors, liver functions, AFP, and evaluation of the survival rate between the studied groups.



  Results Top


There was no significant difference between the two groups in age, sex, and child class (P > 0.05; [Figure 1]. The present study showed that there was a significant difference in clinical symptoms such as pain, vomiting, and fever in group II compared with group I and immediate post-treatment side effects 2 weeks after TACE (P < 0.05). The present study showed that there were nonsignificant changes in serum alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin, albumin, and prothrombin levels in group II compared with group I (P > 0.05; [Table 1] and [Figure 2] and [Figure 3]. There was a highly significant decrease in serum AFP levels 6 months after compared with before TACE (P < 0.001) in group I and group II. The present study showed that there was a significant decrease in serum AFP in group II compared with group I (P < 0.05; [Table 1] and [Figure 4]. In the present work, there was a highly significant decrease in tumor size 6 months after compared with before TACE in group I/group II (P < 0.001; [Table 2] and [Table 3] and [Figure 5]. In the present work, the rate of reduction of tumor size in group I by US use was 58.1 versus 63.2% in group II; the rate of reduction in group II was more than the rate of reduction in group I, but this was not significant (P > 0.05; [Table 4]. The present study found that the rate of reduction of tumor size in group I was 63.2 versus 72.7% in group II by CT; the reduction in tumor size in group II was more than the reduction in group I, but this was not significant (P > 0.05; [Table 4]. Twenty-four lesions were evaluated in 20 patients in group I. In group I, there was a CR in 11 (45.5%) lesions, a PR in nine (37.5%) lesions, and SD in four lesions. Twenty-three lesions were evaluated in 20 patients in group II. There was a CR in 13 (53%) lesions, a PR in seven (34%) lesions, and SD in three (13%) lesions, with no statistically significant difference between both groups (P > 0.05) [Table 5].
Figure 1: Child classifi cation in the group s tudied

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Figure 2: Comparison of changes in aspartate aminotransferase (AST) in groups I and II

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Figure 3: Comparison of changes in alanine transaminase (ALT) in groups I and II before and after transcatheter arterial chemoembolization (TACE).

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Figure 4: Comparison of changes in ¦Á-fetoprotein changes in the group studied

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Figure 5: Comparison changes using ultrasonography (US) in Tumor size before and after transcatheter arterial chemoembolization (TACE).

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Table 1 Comparison of liver function tests and ¦Á-fetoprotein after 6 months of treatment between group I and group II

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Table 2 Comparison of ultrasonography measurement of tumor size before and 2 weeks, 2, 4, and 6 months after treatment in group I

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Table 3 Comparison of ultrasonography measurement of tumor size before and 2 weeks, 2, 4, and 6 months after treatment in group II

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Table 4 Comparison of percentage of reduction in tumor size before and 6 months after transcatheter arterial chemoembolization by ultrasonography and computed tomography measurement

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Table 5 Comparison of tumor size before and 6 months after transcatheter arterial chemoembolization by computed tomography scan in group II

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  Discussion Top


HCC remains one of the most common lethal malignancies in the world and the prognosis for patients with HCC is in general poor. Although surgery remains the only hope for cure, very few patients (10-15%) are candidates [7] .

Concerns about the benefits of TACE for patients with HCC have been supported by the poor outcomes of patients treated in prospective trials. However, a meta-analysis study reviewing 18 randomized trials found an overall survival benefit with TACE compared with symptomatic treatment [8] . The results of the meta-analysis were driven by a well-constructed trial that reported significantly improved survival with TACE versus no treatment [9] .

The current study aimed at comparing and evaluating the safety and outcome of TACE using lipiodol versus using lipiodol and gel foam. To achieve this aim, 40 patients with inoperable HCC were enrolled and divided into two groups: 20 patients underwent TACE using lipiodol and the other 20 patients underwent TACE using lipiodol and gel foam. The chemotherapeutic drug was the same in all patients (adriamycin).

In the present study, 28 patients were men and 12 were women; their age ranged from 40 to 70 years, mean 54.6 ± 7.8 years, and this is consistent with other studies. It was found that the incidence of HCC increases with age and is more common in men than in women [10] .

All patients participating in this study were hepatitis C virus (HCV)-antibody positive; none of them was found to be alcoholic or had an apparent other cause for HCC. In contrast to our study, it was found that infection with HBV is probably the most common underlying factor associated with HCC worldwide and seems to be most prevalent in high-incidence countries [11] . However, it was found that infection with HCV has been identified as a leading cause of HCC in many countries including the USA, in which a definite increase in the incidence of HCC has been reported recently, largely attributable to the increasing incidence of hepatitis C infection [12] . Our results could be attributed to an increasing incidence of HCV infection in Egypt [13] .

The postembolization syndrome (fever, vomiting, and/or right hypochondrial pain) was found in 40% of patients in group I and in 65% of patients in group II (P < 0.001) following chemoembolization for 3-5 days. However, no major life-threatening treatment-related complications were encountered in any of the patients. Our results are in agreement with those of Miyoshi et al. [14] who found that the complication rates of chemoembolization vary considerably and that the chemoembolization morbidity rate is usually high, ranging from 20 to 55%, but most complications are generally well treated with conservative management.

In terms of liver function tests, there was an initial worsening in both groups 2 weeks after treatment as there was a significant increase in ALT and AST in both groups and a significant increase in bilirubin only in group II. No significant change was observed in albumin and prothrombin concentrations. TACE may cause liver function to decrease temporarily because noncancerous liver parenchyma is also damaged. However, there was a gradual improvement in liver functions during further follow-up. In fact, statistically significantly higher values of some parameters were observed after 6 months of TACE, namely, ALT (P < 0.001) and AST (P < 0.05) in group I and ALT (P < 0.001), AST (P < 0.05), and bilirubin (P < 0.01) in group II.

Many authors have reported results that are in agreement with the current results, where they found that the adverse effects are transient and liver function returned to its initial status or to normal within 2-3 weeks [15],[16] .

Other studies have reported irreversible deterioration in liver function or even acute liver failure in patients who have undergone TACE, especially if a severe impairment in functional reserve (Child-Pugh advanced class B or C) existed before treatment [17],[18] .

In the current study, serum baseline AFP levels ranged between 52 and 10 000 ng/ml, mean 2747.5 ± 4671.9 ng/ml in group I and 2347.1 ± 4300 ng/ml in group II. Our results are in agreement with another study, which found that the development of HCC is usually accompanied by a steady increase in serum AFP levels [19] .

Analysis of AFP values before and after treatment in the groups studied showed that there was a highly significant reduction in its levels during the follow-up period, being maximal at the end of 6 months (P < 0.001), where in group I, its mean baseline level was 1510 ± 2434.8and 162.9 ± 155.9 ng/ml after 6 months. In group II, the mean baseline AFP level was 2347.1 ± 4300 ng/ml, whereas it was 129.7 ± 88.5 ng/ml after 6 months. The reduction of the AFP level is as result of tumor necrosis induced by treatment and thus, AFP level is a good tumor marker for monitoring the effect of treatment in patients with HCC. This result is consistent with another study that found that tumor resection or necrosis by TACE is always associated with a decrease in the serum AFP level, and can thus be considered an excellent indicator for follow-up of treatment modalities [20] .

In the current study, the mean US measurement of the longest diameter of the focal lesions was 5.25 ± 1.06 cm in group I and 5.40 ± 1.0 cm in group II (P > 0.05) before TACE treatment. Six months after treatment, there was a highly significant reduction in tumor size in both groups, where the mean longest diameter was 2.20 ± 1.16 cm in group I (%reduction = 58.1%) and 1.89 ± 0.93 cm in group II (%reduction = 65%) (P < 0.001), with no significant difference between group I and group II; this is in agreement with other results, which showed a significant reduction in tumor size after TACE [21] .

In terms of the CT scan, the mean baseline longest diameter of the focal lesion was 5.43 ± 1.06 cm in group I and 5.50 ± 0.85 cm in group II. Six months after treatment, there was a highly significant reduction in tumor size, where the mean longest diameter was 2.00 ± 1.20 cm in group I (%reduction = 63.2%) and 1.50 ± 0.85 cm in group II (%reduction = 72.7%) (P < 0.001). There was no significant difference between both groups. These results are in agreement with a study carried out by the Groupe d'Etude et de traitement du Carcinome Hepatocellulaire (1995), who compared a chemoembolization group and a conservative group. They found a significant reduction in tumor size in the chemoembolization group and an increase in more than half of the patients on conservative management. This finding is in agreement with another study that reported the same results [22] .

In the current study, 45.5% of lesions in group I showed a CR to treatment, 37.5% showed a PR, and 17% showed no change. In group II, 56.5% of lesions showed a CR, 30.5% showed a PR, and 13% showed no change, with no significant difference between the two groups studied. Our results are in agreement with other studies that reported the same results [23] .

In terms of overall survival, of the 40 patients studied, nine died during the 6-month course of follow-up, a survival rate of 77.5%. In group I, the 6-month survival rate was 75%, whereas in group II, it was 79%, with no significant difference between both the groups studied (P > 0.05).

These and several similar reports from the 1990s consistently show a two-fold or three-fold increase in median survival after chemoembolization compared with untreated control patients, with a high degree of statistical significance [24] .

Another study found no difference in survival between a group undergoing therapy with doxorubicin-based chemoembolization and another group treated by embolization alone. However, they did find significantly greater decreases in serum AFP levels of patients treated with doxorubicin, suggesting a greater antitumor effect when chemotherapy was added to the mixture [25] .

Another study ended their prospective trial when TACE showed a significant survival benefit versus symptomatic treatment alone. TACE was associated with a higher survival rate at the time the trial was terminated. However, embolization alone was far outpacing symptomatic treatment and it is intriguing to postulate whether this group would have gained significant survival benefit as well [26] .

There are several reasons why the selection of an appropriate embolic agent is important. Gel foam can recanalize as quickly as 2 weeks after administration. However, occlusion for a shorter period of time may be enough to achieve satisfactory ischemia to overcome cell pumps that normally expel the chemotherapeutic agents and result in levels that are high enough to lead to tumor necrosis. Gel foam sponge led to a six-fold increase in chemotherapeutic agent retention in tumors compared with the surrounding noncancerous liver at an average of 55 days after therapy (range 13-114 days) at evaluation of resected tumors [27] .


  Conclusion Top


We found a trend toward greater survival when gel foam was used as an embolic agent for TACE for HCC, although this did not reach significance compared with lipiodol alone.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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