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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 18  |  Issue : 2  |  Page : 183-188

Short-term outcomes of surgical resection and radiofrequency in treatment of hepatocellular carcinoma


1 Lecturer of Hepatogastroenterology and Infectious Disease, Al Zahraa University Hospital, Al-Azhar University, Egypt
2 Lecturer of General Surgery, Al Zahraa University Hospital, Al-Azhar University, Egypt

Date of Submission29-Jan-2020
Date of Decision13-Apr-2020
Date of Acceptance14-May-2020
Date of Web Publication24-Jul-2020

Correspondence Address:
MD Alshimaa M.M Eid
Lecturer of Hepatogastroenterology and Infectious Disease, Al Zahraa University Hospital, Al-Azhar University, Building No. 7084, Second floor, Street 9, Al-Mokattam, Cairo 11571
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_13_20

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  Abstract 


Backgroundand aim To evaluate surgical liver resection in comparison with radiofrequency in the treatment of early hepatocellular carcinoma (HCC) regarding intraoperative blood loss and transfusion, time of respectability, time of operation, ICU stay, hospital stay, postoperative morbidity, mortality, and overall survival.
Introduction Surgical resection and radiofrequency ablation (RFA) in the treatment of HCC are different modalities for the treatment of HCC.
Patients and methods This is a prospective study that included 60 patients with HCC randomized into hepatic resection and RFA groups at Al-Zahraa University Hospital from 2016 to 2019. Demographic and biochemical characteristics, intraoperative data, postsurgical complications, and overall survival rate were compared between groups.
Results Surgical resection group had longer operative time, resection time, blood loss and blood transfusion, hospital stay, and ICU stay than RFA group. Postoperative hemorrhage, bile leak, and chest infection were markedly decreased in RFA group than surgical resection group. Wound infection and ascites are similar in the two patient groups. Regarding the median follow-up during the 3 years, there were no significant differences between the treatment groups in 1- and 3-year overall survival.
Conclusion Surgical resection is considered the primary solution if the patient’s liver function and general conditions are good enough to undergo surgical intervention. RFA is considered superior to hepatic resection in the treatment of HCC in terms of operation duration and other complications like hemorrhage and bile leak. RFA revealed similar overall survival to surgical resection. RFA is accessible and a promising liver resection method with very good results.

Keywords: hepatocellular carcinoma, radiofrequency, surgical resection


How to cite this article:
Eid AM, Youssef HA. Short-term outcomes of surgical resection and radiofrequency in treatment of hepatocellular carcinoma. Al-Azhar Assiut Med J 2020;18:183-8

How to cite this URL:
Eid AM, Youssef HA. Short-term outcomes of surgical resection and radiofrequency in treatment of hepatocellular carcinoma. Al-Azhar Assiut Med J [serial online] 2020 [cited 2020 Oct 25];18:183-8. Available from: http://www.azmj.eg.net/text.asp?2020/18/2/183/290598




  Introduction Top


Primary liver cancer has been considered as the fifth most common tumor and as one of the most malignant tumors of humankind, and its incidence rate has increased in recent years [1]. Hepatocellular carcinoma (HCC) is considered the most common type of primary liver tumor, followed by intrahepatic cholangiocarcinoma. They represent more than 95% of primary liver tumors. HCC is one of the most important leading causes of cancer-related deaths throughout the world and has an incidence of more than 850 000 new cases every year internationally [2].

Liver cirrhosis affects largely the incidence of HCC, and ∼90% of patients with HCC have either chronic infections of hepatitis B or C virus, which are considered the basal diseases of cirrhosis [3].

Liver surgical resection is still the treatment of choice for HCC in patients with compensated liver cirrhosis, yet it is associated with high morbidity and mortality. Recently, the outcome of liver resection has been improved by proper patient selection, preoperative assessment, new surgical techniques with more attention paid to bloodless transection, and the use of intraoperative ultrasonography [4].

Parenchymatous liver transection is a basic phase of liver surgical intervention. Several instruments have been described for safe and good transection of the hepatic parenchyma, but the ideal procedure has not yet been identified [5].

The initial prototype technique of liver resection is clamp crush or finger fracture which is associated with high incidence of intraoperative bleeding during parenchymal transection and is the most common barrier to surgical success. Multiple local ablative treatments have been developed to treat HCC, and these include transarterial chemoembolization, percutaneous ethanol injection, and radiofrequency ablation (RFA) [6].

RF is a safe and good maneuver for resection of hepatic carcinoma. This is owing to systemic and local immunomodulatory effect that includes stimulation of Kupffer cells and effector CD-8 cells, which participate in decreasing postoperative complications [1].

Most guidelines for treatment of HCC recommend surgical resection and RFA as the first and second line of treatment, respectively, in patient with good liver functions and single tumor or no more than three tumors each measure less than 3 cm. RFA is considered for early HCCs, as it is minimally invasive, successful, and can be repeated at different times [7].


  Aim of the study Top


The aim of this study was to evaluate surgical liver resection in comparison with radiofrequency in the treatment of early HCC regarding intraoperative blood loss and transfusion, time of respectability, time of operation, ICU stay, admission in hospital, postoperative mortality, morbidity, and overall survival rate.


  Patients and methods Top


A total of 60 patients were diagnosed with HCC and prepared for surgical resection or RFA starting from March 2016 to February 2019 at Al-Zahraa University Hospital. The study protocol was approved by Al-Azhar Faculty of Medicine Committee for Medical Research Ethics and an informed consent was taken from each participant.

Inclusion criteria were as follows: (a) early focal lesion less than 5 cm or three tumors, where each is 3 cm or smaller; (b) patients with Child–Pugh A; (c) patients with no extrahepatic metastasis; (d) patients fit for surgery and general anesthesia; (e) patients with no other body malignancies; and (f) patients with no tumor thrombus in inferior vena cava or main portal or hepatic veins. Exclusion criteria included the following: (a) focal lesion more than or equal to 5 cm or more than three tumors; (b) patients with Child–Pugh B and C; (c) multicentric lesion (more than three tumors); (d) patients with extrahepatic metastasis; (e) patients with contraindications for surgery and general anesthesia, for example, tuberculosis and renal failure; (f) patients with any other body malignancies; and (g) for RFA, (a) tumor location near hilar structure, (b) past treatment for HCC with TACE, (c) percutaneous ethanol injection or chemotherapy, and (d) evidence of vascular invasion into major portal or hepatic vein branches.

Diagnostic workup and investigations

Numerous instruments of liver resection, such as the CUSA (Cavitron Ultrasonic Surgical Aspirator), RF, Ligasure (Valley Lab, Tyco Healthcare, Boulder, Colorado, USA), Harmonic Scalpel (Ethicon Endo-Surgery, Cincinnati, Ohio, USA), Tissue Link (Salient Surgical Technologies, Portsmouth, New Hampshire, USA), water-jet dissection, microwave assisted resection, vascular staplers, and others have been introduced to facilitate safe and easy resection of liver parenchyma [1]. Diagnosis of HCC with assessment of respectability depends on the following: (a) history taking, including personal, present, and past; (b) laboratory investigations, such as alanine aminotransferase, aspartate aminotransferase, prothrombin time, and PC %, as well as viral markers hepatitis C virus, hepatitis B virus, and tumor marker [α-feto protein (AFP)]; (c) imaging techniques, such as chest radiograph, abdominal ultrasound, spiral triphasic computed tomography (CT) scan, MRI, and upper gastrointestinal endoscopy; (d) staging of cirrhosis by Child–Pugh classification; and (e) staging of HCC by Barcelona Clinic Liver Cancer (BCLC).

Staging

There are different staging systems for HCC using patient and tumor factors to best stratify by prognosis and guide treatment based upon stage.

BCLC staging system is largely used in clinical practice and considered by most clinicians to be the best staging system. It includes the patient’s functional status, Child–Turcotte–Pugh score, and tumor characteristics (number and size of nodules, vascular invasion), and it divides patients as very early (0), early (A), intermediate (B), advanced (C), or terminal (D). Although the BCLC system is utilized and cited in most international guidelines, it has a number of disadvantages, in particular as it confined to its applicability for patients who may be candidates for surgical techniques including resection. As a result, other staging systems are available that can be more valuable for guiding surgical techniques and can better inform patients and providers irrespective of prognosis. Among the most important criteria of any given staging system is the inclusion of tumor-related factors as well as liver function and patient’s performance status. These are important components when choosing the appropriate treatment, in particular for patients being candidate for surgical management, as the ability to afford surgery and achieve benefits in long-term outcomes is determined in great part by the baseline liver function and capacity of the liver to recover following a major hepatic resection (HR).

Method of surgical resection

Tumor resection was carried out under general anesthesia by modified right subcostal incision with extension to left was made. Some cases were modified with upper midline removing xiphoid process. Abdominal ultrasound was done to confirm tumor site and size in all patients. Major liver mobilization was prevented, and only the side to be resected was mobilized in most cases. After the tumor was localized, the resection line was marked on the liver surface, 1 cm far from the edge of the tumor using an argon diathermy. Major hepatectomy was done as resection of at least three Couinaud’s segments, and minor hepatectomy as resection of fewer than three segments.

Method of radiofrequency ablation

RFA was done using the StarBurst RFA system (Angiodynamics, Model 70 and Model 90 Starburst XL needles, RITA Medical System, Mountain View, CA, USA). The electrode was successful in eliciting complete tumor necrosis, with ablation of a margin of normal tissue of 1 cm. The technique was done percutaneously by an experienced interventional radiologist using local anesthesia with intravenous sedation. Patients were sent to ICU department. Spiral contrast-enhanced CT was done 4 weeks after the intervention.

Follow-up

Early postoperative complications included time of the procedure, hemorrhage, and need for transfusion of packed red blood cells or other blood elements. Liver biochemistry and coagulation profile were repeated on days 1, 3, and 7 after the procedure. Treatment-related complications, including severe complications (Clavien–Dindo grade III or above), operative mortality, and hospital admission time were recorded prospectively in both groups. Operative mortality was defined as death after surgical intervention within the same hospital stay. Spiral CT is done after 1 week and after 1 month of the procedure. No complimentary treatment is used after the procedure. Regarding short-term outcomes, all patients came and were revised regularly at the outpatient clinic. Complete blood count, liver function tests, coagulation profile, serum AFP level, and spiral CT were repeated every 3 months in the first year and then every 6 months afterward. Recurrences were defined as local or distant at the end of 1 and 3 years.

Statistical analysis

Data were statistically analyzed using statistical package for social science (SPSS Inc., Chicago, Illinois, USA) software program, version 10.0.7. Mean±SD was used. c2 test was done for qualitative variable analysis. P value less than 0.05 was considered to be statistically significant.


  Results Top


Demographic and biochemical characteristics

Among the 60 patients, 30 patients (group A) underwent liver resections, performed using CUSA, which was the most available technique, and the other 30 patients (group B) underwent tumor ablation using the percutaneous RFA. Demographic and biochemical data of each group are tabulated and compared ([Table 1]). Regarding the age and sex distribution between both groups, group A included 24 (80%) males and six (20%) females, with a mean age of 56.1±6.1 years, whereas group B included 22 (73.3%) males and eight (26.6%) females, with a mean age of 52.14±6.8 years. There was no significant statistical difference.
Table 1 Demographic and biochemical comparison between the two groups of the study

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Perioperative conditions in both groups

Compared with the HR group, the RFA group had a shorter technique duration and less operative blood loss ([Table 2]). This was mainly because a less invasive technique (percutaneous) was used in most patients in the RFA group. The RFA group had significantly lower incidence of postoperative hemorrhage, bile leak, and chest infection than those in the HR group, whereas other complications are almost the same in both groups ([Table 3]).
Table 2 Intraoperative data

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Table 3 Postoperative complications

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Short-term outcomes

The mean follow-up time for the HR group was 32.33 months (range, 6–72 months), during which recurrence occurred in 15 (50%) cases. Local recurrence occurred in two (6.6%) cases, whereas intrahepatic recurrence occurred in 14 (46.6%) cases. Within these 14 cases of intrahepatic recurrence, pulmonary metastasis occurred in six cases and bone metastasis in one. The mean follow-up time for the HR group was 30.33 months (range, 6–71 months), during which recurrence occurred in 18 (60%) cases. Local recurrence occurred in nine (30%) cases, whereas intrahepatic recurrence occurred in nine (30%) cases ([Table 4]).
Table 4 Recurrence of hepatocellular carcinoma after hepatic resection and radiofrequency ablation

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Follow-up

Liver enzymes showed marked improvement after treatment. Alanine aminotransferase became near normal in both groups, with a mean value of 56.4±4.35 in liver resection group and 58.2±4.3 in RFA group, which showed no significant difference between both groups. Moreover, aspartate aminotransferase in both groups was near normal, with mean of 45.9±5.6 in liver resection group and 51.3±3.5 in RFA group, which showed no significant difference (P>0.05). AFP showed marked improvement in both groups after treatment with mean value of 58±17.3 in liver resection group and 63.5±16.3 in RFA group, which showed no significant difference between both groups. Median ICU and hospital admission was significantly shorter in the RFA group ([Table 5] and [Table 6]).
Table 5 Laboratory follow-up

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Table 6 ICU and hospital stay

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  Discussion Top


This study has revealed that RFA is superior to HR for treatment of early-stage HCC, in terms of operative blood loss, postoperative hemorrhage, bile leak, chest infection, ICU, and hospital stay.

HR is considered as the treatment of choice for early-stage HCC with good hepatic function. Anatomical HR with curative intent has the advantage of eradicating potential tumor cells through the portal venous branches [8].

RFA may have many advantages over HR. It carries low morbidity and mortality rates in comparison with HR. It also allows better preservation of hepatic function, as little nontumorous hepatic cells are destructed. Surgical stress and immune inhibition are less in RFA than in HR [2].

The present study compared intraoperative and postoperative data for resection versus RFA in patients with early-stage HCC. Studies have shown that RFA gives favorable operative results in terms of blood loss, postoperative recovery, hospital admission, postoperative morbidity, and mortality [9],[10]. This study investigated the oncological results following the use of CUSA or RFA for HR. Here, we compared both groups to decrease confounders such as serum albumin, serum bilirubin, and serum AFP. The analysis of instant results in our study revealed that the mean blood loss need for blood transfusion and requirement for vascular inflow control were significantly lower in the RFA group than the HR group. This might be illustrated by the fact that RFA utilizes radiofrequency energy to coagulate the blood vessels, whereas the ability of surgical resection has been restricted by the need of manual activation to coagulate the blood vessels [11],[12],[13]. In agreement with other study, we also found that surgeon’s experience in using surgical liver resection has an important effect on the surgical outcome [14].

The duration of hospital stay reached statistical significance between both the studied groups. However, one study showed no significant difference between both groups [2]. The current study did not report any deaths in either group, which can be related to the recent advances in the surgical techniques and better preoperative and postoperative care, making HR a reasonably good treatment modality.

Further data analysis of postoperative complications showed significant difference between both groups in terms of postoperative hemorrhage, bile leak, and wound infection. Studies showed that complications did not show any statistical difference in the studied groups [1],[2].

The favorable oncological results with RFA can be explained on the basis of systemic and local immunomodulatory response of radiofrequency. The necrotic tissues produced following RF-induced coagulative necrosis during HCC resection liberates tumor antigens and chemokines. These chemokines attract inflammatory cells, such as neutrophils, macrophages, NK cells, dendritic cells, as well as CD4+ and CD-8+ T lymphocytes. The cellular entry at the ablated resection margin leads to phagocytoses of these necrotic and tumor tissues. Tumor antigens also drain to nearby lymph nodes and stimulate immature dendritic cells and naive T-cells, thus provide systemic immunomodulation [15],[16],[17].The liver is the only organ that maintains delicate balance between not over-reacting to the antigens absorbed by the gut and eliciting accurate immune responses to eliminate the tumor antigen [16]. HCC is characterized by chronic inflammatory process and immune reduction. Immune suppression owing to inhibitory checkpoints is claimed to be an important cofactor for induction of immune suppression in this setting and subsequent development and progression of HCC. Tregs and myeloid-derived suppressor cells are considered to play an important role in preventing the tumor from being removed by activated cytotoxic CD-8+ T cells. High level of Tregs in tumor cells has been related to poor prognosis in HCC [18],[19],[20].


  Conclusion Top


RFA was better than HR for the treatment of HCC in terms of operative time, intraoperative hemorrhage, amount of blood transfusion, hospital admission time, and postoperative complications like hemorrhage and bile leak. RFA is accessible and an encouraging liver resection method, with very good results.

RFA is a safe and good option for treating early-stage HCC. However, considering the better survival rate after HR and its ability to prevent recurrence, HR has an undisputable role in the treatment of HCC, which makes it the first choice for this tumor.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Huang KW, Lee PH, Kusano T, Reccia I, Jayant K, Habib N. Impact of cavitron ultrasonic surgical aspirator (CUSA) and bipolar radiofrequency device (Habib-4X) based hepatectomy for hepatocellular carcinoma on tumour recurrence and disease-free survival. Oncotarget 2017; 8:93644.  Back to cited text no. 1
    
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Gameiro SR, Higgins JP, Dreher MR, Woods DL, Reddy G, Wood BJ et al. Combination therapy with local radiofrequency ablation and systemic vaccine enhances antitumor immunity and mediates local and distal tumor regression. PLoS ONE 2013; 8:e70417.  Back to cited text no. 15
    
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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