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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 2  |  Issue : 2  |  Page : 90-94

The overall survival rate for patients with hepatocellular carcinoma who underwent hepatic resection or radiofrequency ablation procedure for curative intent


1 Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia
2 Liver Disease Research Center, King Saud University Medical City, Riyadh, Saudi Arabia
3 Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Department of Oncology, Mcgill University, Montreal, Canada

Date of Web Publication2-Apr-2019

Correspondence Address:
Mohammed A Jameel
Department of Surgery, College of Medicine, King Saud University, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JNSM.JNSM_49_18

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  Abstract 


Background: Hepatocellular carcinoma (HCC) is currently one of the leading causes of cancer-related deaths worldwide. According to the data obtained from the last Saudi Cancer Registry 2014, liver cancer represents 4.3% of all cancers diagnosed in Saudi Arabia. This study aimed to measure the overall outcome and “disease-free” survival rates of HCC patients who underwent either a liver resection or radiofrequency ablation (RFA) rehabilitation procedures in Riyadh, Saudi Arabia. Methods: A retrospective study was conducted in Riyadh, Saudi Arabia, examining 41 patients with HCC who underwent either liver resection or RFA with curative intent from 2011 to May 2016. The study took place in King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, and utilized prospectively collected data. Among the patients who were studied, 7 patients underwent surgical resection and 34 patients underwent RFA. Patients' characteristics, overall survival (OS), and recurrence-free survival were analyzed. Results: Out of the 34 participants who underwent RFA, 17 (50%) experienced recurrence compared to only 3 (42.9%) participants who underwent liver resection. Seven (20.6%) patients who underwent RFA died out of a total of 34. However, only one patient (14.3%) from a total of seven who underwent liver resection died. Conclusion: When comparing the two treatment modalities, it was deemed that there was no significant difference in both recurrence and the OS in both groups.

Keywords: Hepatic resection, hepatocellular carcinoma, radiofrequency ablation


How to cite this article:
Al-Raddadi AK, Jameel MA, Al-Zulfi AA, Al-Shammari WK, Hussein WS, Robles EA, Al-Saif F, Al-Alem F, Al-Sharabi A, Madkhali A, Hassanain M. The overall survival rate for patients with hepatocellular carcinoma who underwent hepatic resection or radiofrequency ablation procedure for curative intent. J Nat Sci Med 2019;2:90-4

How to cite this URL:
Al-Raddadi AK, Jameel MA, Al-Zulfi AA, Al-Shammari WK, Hussein WS, Robles EA, Al-Saif F, Al-Alem F, Al-Sharabi A, Madkhali A, Hassanain M. The overall survival rate for patients with hepatocellular carcinoma who underwent hepatic resection or radiofrequency ablation procedure for curative intent. J Nat Sci Med [serial online] 2019 [cited 2019 Jun 25];2:90-4. Available from: http://www.jnsmonline.org/text.asp?2019/2/2/90/250745




  Introduction Top


Hepatocellular carcinoma (HCC) is currently the fifth most prevalent form of cancer as well as the second leading cause of cancer-related deaths worldwide. Liver cancer represents 4.3% of all cancers diagnosed in Saudi Arabia according to the last Saudi Cancer Registry 2014.[1] In Saudi Arabia, HCC was found to be the fourth most common cancer in males, whereas in females, it was the eighth highest form of cancer.[1] The highest incidence of HCC was found in Al-Bahah, a city in the Southwest of the Kingdom of Saudi Arabia followed by Riyadh and Assir, higher in males than in females with a ratio of 2:1.[1] In Saudi Arabia, we are experiencing major obstacles in relation to the referral system of patients which subsequently affect the delivery of the most appropriate modality of treatment to the patients concerned.[2] Among the Gulf Cooperation Council States, Qatar reported the highest incidence of HCC, which was closely followed by Kuwait.[3]

Chronic liver infection (hepatitis C virus/hepatitis B virus [HCV/HBV]) was deemed to be the primary underlying cause of HCC worldwide.[4] However, in the USA, chronic alcoholism and chronic liver diseases were considered to be the most common causes of HCC.[5] In Saudi Arabia, hepatitis C is considered to be a major risk factor (affecting up to 74% of patients) in the development of HCC.[6] The second most common risk factor is hepatitis B, which has been reduced since the establishment of the hepatitis B vaccination program in Saudi Arabia that started in 1989.[7] Based on several studies, obesity was found to contribute extensively to fatty liver disease and it is increasing in prevalence, which in turn increases the risk of developing HCC.[2] However, viral hepatitis C and B patients with concomitant obesity and diabetes were found to have 100 times more risk of developing HCC than patients who had no previous history of either diabetes mellitus or obesity.[8]

Hepatic resection (HR) and liver transplantation (LT) are the only available curative options for patients with HCC. In terms of noncurative options, various ablative therapies including radiofrequency ablation (RFA) are currently available.[9] OLT provides an optimal choice of the management for patients with small HCCs and liver cirrhosis. On the other hand, HR is considered the most suitable treatment modality for patients with no evidence of cirrhosis or with early signs of cirrhosis, in addition to the absence of signs of clinically relevant portal hypertension.[2] The reported 5-year survival rate after liver resection is 70%.[10] In nonresection candidates as well as patients with early cirrhosis and lesions below 3 cm, ablation therapy is considered to be the optimal option with insignificant survival difference from HR. The Barcelona Clinic Liver Cancer (BCLC) system indicates either early or Stage A HCC (meaning nodules ≤3 cm each and having a performance status = 0), increased portal pressure, and/or bilirubin, and in the presence of associated diseases, RFA is recommended.[11]

In RFA, heat induces cell damage after introducing a high-frequency electrical current into tumor tissue when using imaging guidance technology.[9] The reported 5-year survival rate is approximately 70% after local ablative procedures.[11] When treating Child–Pugh A cirrhotic patients with a solitary HCC <3 cm, RFA has been a comparable recurrence-free survival (RFS) to surgical resection.[12]

Before treatment planning, all patients should be evaluated for the presence of cirrhosis and have their liver function checked. The use of staging systems, especially those that combine disease stage with liver function such as the BCLC staging system, is very helpful when it comes to assigning appropriate therapy.[2] Patients are also checked for the signs of clinically relevant portal hypertension and the presence of varices, splenomegaly, a platelet count <100,000, or a hepatic vein pressure gradient >10 mmHg.[2] Lastly the management plan for all presented cases discussed in multidisciplinary tumor board meeting involving hepatology, hepatobiliary surgeons and interventional radiology to optimize the care. Only the cases deemed untranslatable where offered either surgery or RFA based on location, disease distribution within the liver and the liver function.

In this study, the aim is to measure the overall outcome and “disease-free” survival rates of HCC patients who underwent either a liver resection or RFA rehabilitation procedures in Riyadh, Saudi Arabia.


  Methods Top


This is a retrospective study aimed to examine all patients with HCC who underwent either a HR or RFA with curative intent from 2011 to 2016, at our institution, applying a retrospective analysis on prospectively collected data, which was stored in the liver disease research center database. Children, pregnant, and patients with HCC metastasis, died from other comorbidities, lost follow-up, and palliative patients were all excluded from the study.

Patient data were categorized into two groups which were described as follows: “Group 1,” for whom HR was performed and “Group 2,” for whom RFA was performed. Outcome measure was recorded as overall survival (OS) and RFS. The OS rate was calculated from the day of surgery or RFA to the day of death or the day of the last follow-up visit. RFS was calculated from the day of surgery or RFA to the first follow-up visit where evidence of recurrence emerged. In order to evaluate the prognosis and recurrence of HCC, follow-up data were collected at intervals of 1 month, 3 months, and 6 months. After this, data were collected on a yearly basis postsurgery and included the history, physical examination, laboratory results, and imaging data of the patients.

Patients' characteristics such as gender, age, the etiology of cirrhosis for each individual case, the Child–Pugh class, and the number and size of lesions were reviewed both groups. The study was approved by the institutional review board (IRB) in our hospital.

Statistical analysis

The data of the patients were analyzed with the statistical computer software JMP® version 11 developed by the JMP business unit of SAS Institute. Continuous variables were expressed in medians and interquartile range. Categorical variables were analyzed using the Chi-square test, while the Student's t-test was used for continuous variables. OS and recurrence survival analyses were performed using the Kaplan–Meier method. Comparisons between the different groups were made using the logrank test. P < 0.05 was considered statistically significant.


  Results Top


This study was conducted using 41 participants in total. Out of these, 21 participants (51.2%) were males and 20 (48.8%) were females. The ages of the participants ranged from 16 to 85 years with a median age of 71 years. In this study, 4 participants presented with no risk factor (9.8%), 10 participants had HBV (24.4%), 19 participants had HCV (46.3%), and 5 participants had nonalcoholic fatty liver disease (NAFLD) (12.2%). Moreover, one participant had a family history of HCC (2.4%) and two participants had more than one risk factor (4.9%). The median number of days to the last follow-up visit was 535 days. Eight participants died (19.5%), while 33 are still alive (80.5%).

Cross-sectional body imaging was used to characterize the liver lesions; 68.3% had a single lesion. The median size of the liver lesions was 2.24 cm (1.4–2.7). Thirty-four (82.9%) of participants underwent RFA, while 7 (17.1%) participants underwent resection.

Based on the Child–Pugh score, 30 participants were categorized as being “Child A” (73.2%), while 11 were categorized as being “Child B” (26.8%). On the other hand, the BCLC staging system had 25 (61.0%) participants in Stage 1 and 16 (39.0%) participants in Stage 2.

In terms of the etiology of liver disease, there was a significant difference (P = 0.043) when comparing the differences between the two treatment groups. Out of 34 patients who underwent RFA, 10 had HBV, while no patients had HBV and underwent HR. Out of 34 patients who underwent RFA, 14 had HCV, while 5 out of the 7 who underwent HR had HCV. Out of the 34 patients who underwent RFA, 5 had NAFLD while no patients had NAFLD and underwent HR. Out of the 34 patients who underwent RFA, 4 had no risk factors whereas no patients with no risk factors underwent HR. Out of the 34 patients who underwent RFA, no patients had a family history of HCC although 1 patient who had a family history of HCC underwent HR. Out of the 34 patients who underwent RFA, 1 patient had more than one risk factor. However, 1 patient presented with more than one risk factor also underwent HR.

Twenty (48.8%) patients had recurrence, 17 (41.5%) of these patients experienced intra-hepatic, compared to 3 patients (7.3%) who suffered extra-hepatic recurrence. The Median recurrence survival was 750 days (414 to 1553) with 500, 1000, and 1,500-day survival rates of 66%, 40%, and 32%, retrospectively, as shown in [Figure 1].
Figure 1: The recurrence survival

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The Median overall survival was 1,934 days (1.934 to 1,962 days) as shown in [Figure 2]. The median disease-free survival was 443 days.
Figure 2: The overall survival

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Comparisons between the patients who underwent these treatment modalities are outlined and compared in [Table 1]. Out of the 34 participants underwent RFA, 17 participants (50%) experienced recurrence compared to the 3 participants (42.9%) who underwent HR with no significant difference between two groups. Seven (20.6%) patients who underwent RFA died out of the original cohort of 34. Only one (14.3%) patient from a total of seven who underwent HR died however. Therefore, there is no significant difference in terms of outcome.
Table 1: The baseline characteristics of 41 patients

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When comparing the recurrence of lesion sites between the two treatment groups, a significant difference was observed (where P < 0.05). Moreover, 16 out of 17 patients who underwent RFA suffered a recurrence in intrahepatic lesions, while in the HR group, only 1 out of 7 suffered recurrence of intrahepatic lesions.


  Discussion Top


Hepatobiliary surgery has progressed rapidly in recent years along with the use of advanced procedures in treating HCC. Such procedures include the use of RFA, which accompanied by various improvements in the multidisciplinary approach to treat patients with HCC that led to a significant decrease in the mortality rate of such patients.[13] RFA is effective in the treatment of small HCC tumors (<3 cm; very early-stage disease, and early-stage disease using the BCLC system). However, the superiority of ablation over surgical resection for patients with small HCC tumors remains controversial.[14]

In this study, when comparisons were made between the patients who underwent these two different treatment modalities, it was found that there was no significant difference in both recurrence survival and OS in both groups. In fact, previous meta-analysis studies have compared the efficacy of RFA versus HR in the treatment of small HCCs, and certain conclusions were drawn; as a result, Cucchetti et al. conducted a meta-analysis of the data of 388 cirrhotic patients which suggested that there was no difference between HR and RFA procedures apart from the efficacy of the resection itself. It also pointed out that the ablation procedure was dependent on other factors such as tumor number, tumor size, and the degree of liver dysfunction sustained by the patient.[15] In contrast to this; however, Qi et al. conducted a meta-analysis of three randomized controlled trials of patients, which met the Milan criteria. He subsequently reported that HR might improve the OS and RFS in small HCC patients, whereas the risk of complications and hospitalization of the patient (postsurgery) may increase.[16] In addition to these findings, Xu et al. conducted a meta-analysis of 31 studies using a total of 16,103 patients. Accordingly, he reported that the OS rate and the disease-free survival rate in the HR group were significantly higher than those in the RFA group for HCCs ≤3 cm, whereas there were no significant differences between the two groups for HCCs ≤2 cm. The main reason for this finding was thought to be insufficient ablation of the primary tumor, the heat sink effect, and the limitations of imaging modalities which could lead to a higher local recurrence rate.[17]

Our study showed that the recurrence sites were significantly different between the two treatment groups (P = 0.034). Intrahepatic recurrence was found in 16 out of 17 of patients who experienced recurrences in RFA group compared to 1 out of 3 patients who experienced recurrence in HR group. A further study conducted by Ng et al. of 209 patients received RFA; among them, 117 patients (56%) had unresectable HCC, whereas 92 patients (44%) underwent RFA as the primary treatment option and reported that intrahepatic recurrence of lesion occurred in 136 patients (70.8%), while 20 patients (10.4%) developed extrahepatic metastases.[18]

In our region, no previous studies have been conducted to compare ablative therapies with surgical resection for the treatment of small HCCs. Accordingly, the Saudi Arabian guidelines pertaining to the treatment of HCC were based on international data due to a lack of national studies regarding HCC. Our study might, therefore, help other researchers to establish guidelines based on our population. As this paper is a retrospective study, it suffers all the limitations that apply to this type of study, including missing data and the problems associated with selection bias.


  Conclusion Top


Ultimately, there was no significant difference in the recurrence survival and the OS rates among the HR patients and the RFA patients. Importantly, there was no conclusive study has yet been conducted in Saudi Arabia which addresses the proper management of HCC. Hence, in view of the findings of this study, we recommend that a multicentric sampling of HCC-affected patients takes place to produce a better representation of the studied parameters.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
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2.
Abdo AA, Hassanain M, AlJumah A, Al Olayan A, Sanai FM, Alsuhaibani HA, et al. Saudi guidelines for the diagnosis and management of hepatocellular carcinoma: Technical review and practice guidelines. Ann Saudi Med 2012;32:174-99.  Back to cited text no. 2
    
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Rasul KI, Al-Azawi SH, Chandra P, Abou-Alfa GK, Knuth A. Status of hepatocellular carcinoma in gulf region. Chin Clin Oncol 2013;2:42.  Back to cited text no. 3
    
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Ringelhan M, McKeating JA, Protzer U. Viral hepatitis and liver cancer. Philos Trans R Soc Lond B Biol Sci 2017;372. pii: 20160274.  Back to cited text no. 4
    
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El-Serag HB, Kanwal F. Epidemiology of hepatocellular carcinoma in the United States: Where are we? Where do we go? Hepatology 2014;60:1767-75.  Back to cited text no. 5
    
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Sanai FM, Sobki S, Bzeizi KI, Shaikh SA, Alswat K, Al-Hamoudi W, et al. Assessment of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma in middle eastern patients. Dig Dis Sci 2010;55:3568-75.  Back to cited text no. 6
    
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Al-Faleh FZ, Al-Jeffri M, Ramia S, Al-Rashed R, Arif M, Rezeig M, et al. Seroepidemiology of hepatitis B virus infection in Saudi children 8 years after a mass hepatitis B vaccination programme. J Infect 1999;38:167-70.  Back to cited text no. 7
    
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Wang CS, Yao WJ, Chang TT, Wang ST, Chou P. The impact of type 2 diabetes on the development of hepatocellular carcinoma in different viral hepatitis statuses. Cancer Epidemiol Biomarkers Prev 2009;18:2054-60.  Back to cited text no. 8
    
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Aragon RJ, Solomon NL. Techniques of hepatic resection. J Gastrointest Oncol 2012;3:28-40.  Back to cited text no. 9
    
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Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: Resection versus transplantation. Hepatology 1999;30:1434-40.  Back to cited text no. 10
    
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Saraswat VA, Pandey G, Shetty S. Treatment algorithms for managing hepatocellular carcinoma. J Clin Exp Hepatol 2014;4:S80-9.  Back to cited text no. 11
    
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Parisi A, Desiderio J, Trastulli S, Castellani E, Pasquale R, Cirocchi R, et al. Liver resection versus radiofrequency ablation in the treatment of cirrhotic patients with hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2013;12:270-7.  Back to cited text no. 12
    
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Petrou A, Neofytou K, Mihas C, Bagenal J, Kontos M, Griniatsos J, et al. Radiofrequency ablation-assisted liver resection: A step toward bloodless liver resection. Hepatobiliary Pancreat Dis Int 2015;14:69-74.  Back to cited text no. 13
    
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Goldberg SN, Ahmed M. Minimally invasive image-guided therapies for hepatocellular carcinoma. J Clin Gastroenterol 2002;35:S115-29.  Back to cited text no. 14
    
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Cucchetti A, Piscaglia F, Cescon M, Serra C, Colecchia A, Maroni L, et al. An explorative data-analysis to support the choice between hepatic resection and radiofrequency ablation in the treatment of hepatocellular carcinoma. Dig Liver Dis 2014;46:257-63.  Back to cited text no. 15
    
16.
Qi X, Tang Y, An D, Bai M, Shi X, Wang J, et al. Radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma: A meta-analysis of randomized controlled trials. J Clin Gastroenterol 2014;48:450-7.  Back to cited text no. 16
    
17.
Xu Q, Kobayashi S, Ye X, Meng X. Comparison of hepatic resection and radiofrequency ablation for small hepatocellular carcinoma: A meta-analysis of 16,103 patients. Sci Rep 2014;4:7252.  Back to cited text no. 17
    
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Ng KK, Poon RT, Lo CM, Yuen J, Tso WK, Fan ST, et al. Analysis of recurrence pattern and its influence on survival outcome after radiofrequency ablation of hepatocellular carcinoma. J Gastrointest Surg 2008;12:183-91.  Back to cited text no. 18
    


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