Radiofrequency ablation compared to resection in early‐stage hepatocellular carcinoma

ObjectivesThis study aimed to compare survival outcomes after hepatic resection (HR) and radiofrequency ablation (RFA) in early‐stage hepatocellular carcinoma (HCC) at a Western hepatobiliary centre.MethodsDemographic details, clinicopathologic tumour characteristics and survival outcomes were compared among non‐transplant candidate patients undergoing HR (n= 50) and RFA (n= 60) for early‐stage HCC during 2001–2011.ResultsPatients who underwent HR had larger tumours, a longer length of stay and a higher rate of postoperative complications. After a median follow‐up of 29 months, there were no significant differences between the treatment groups in 1‐, 3‐ and 5‐year overall survival (OS) [RFA group: 86%, 50%, 35%, respectively; HR group: 88%, 68%, 47%, respectively (P= 0.222)] or disease‐free survival (DFS) [RFA group: 68%, 42%, 28%, respectively; HR group: 66%, 42%, 34%, respectively (P= 0.823)]. The 58 patients who underwent RFA demonstrated ablation success on follow‐up computed tomography at 3 months. Of these, 96.5% of patients showed sustained ablation success over the entire follow‐up period. In a subgroup analysis of patients with tumours measuring 2–5 cm, no differences in OS or DFS emerged between the HR and RFA groups. Similarly, no significant differences in outcomes in patients with Child–Pugh class A cirrhosis were seen between the RFA and HR groups.conclusionsRadiofrequency ablation is comparable with HR in terms of OS and DFS. It is a reasonable alternative as a first‐line treatment for HCC in well‐selected patients who are not candidates for transplant.     

Rapid progression of hepatocellular carcinoma after Radiofrequency Ablation

AIM:To report the results of radiofrequency ablation (RFA)of hepatocellular carcinoma (HCC) in cirrhotic patients andto describe the treatment related complications (mainly therapid intrahepatic neoplastic progression).METHODS:Eighty-seven consecutive cirrhotic patients with104 HCC (mean diameter 3.9 cm,1.3 SD) were submittedto RFA between January 1998 and June 2003.In all casesRFA was performed with percutaneous approach underultrasound guidance using expandable electrode needles.Treatment efficacy (necrosis and recurrence) was estimatedwith dual phase computed tomography (CT) and alpha-fetoprotein (AFP)level.RESULTS:Complete necrosis rate after single or multipletreatment was 100%,87.7% and 57.1% in HCC smallerthan 3 cm,between 3 and 5 cm and larger than 5 cmrespectively (P=0.02).Seventeen lesions of 88(19.3%)developed local recurrence after complete necrosis during amean follow up of 19.2 mo.There were no treatment-relateddeaths in 130 procedures and major complications occurredin 8 patients (6.1%).In 4 patients,although complete localnecrosis was achieved,we observed rapid intrahepaticneoplastic progression after treatment.Risk factors for rapidneoplastic progression were high preoperative AFP valuesand location of the tumor near segmental portal branches.CONCLUSION:RFA is an effective treatment for hepatocellularcarcinoma smaller than 5 cm with complete necrosis in morethan 80% of lesions.Patients with elevated AFP levels andtumors located near the main portal branch are at risk forrapid neoplastic progression after RFA.Further studies arenecessary to evaluate the incidence and pathogenesis ofthis underestimated complication.     

Heparanase and hepatocellular carcinoma: Promoter or inhibitor?

Heparan sulphate proteoglycans (HSPGs) consist of a core protein and several heparan sulphate (HS) side chains covalently linked. HS also binds a great deal of growth factors, chemokines, cytokines and enzymes to the extracellular matrix and cell surface. Heparanase can specially cleave HS side chains from HSPGs. There are a lot of conflicting reports about the role of heparanase in hepatocellular carcinoma (HCC). Heparanase is involved in hepatitis B virus infection and hepatitis C virus infection, the act...     

Radiofrequency ablation of hepatocellular carcinoma sized > 3 and ≤ 5 cm: Is ablative margin of more than 1 cm justified?

AIM:To investigate whether an ablative margin(AM)>1.0 cm might reduce chance of recurrence for patients with hepatocellular carcinoma(HCC)tumors 3.1to 5.0 cm in size,compared with an AM of 0.5-1.0 cm.METHODS:From October 2005 to December 2012,936 consecutive patients with HCC who received radiofrequency ablation were screened.Of these,281 patients,each with a single primary HCC tumor of 3.1 to5.0 cm in size on its greatest diameter,were included in the study.Based on the AM width,we categorized patients into the 0.5-1.0 cm group and the>1.0 cm group.Local tumor progression(LTP)-free survival,intrahepatic distant recurrence(IDR)-free survival and overall survival(OS)rates were obtained using the Kaplan-Meier method.RESULTS:The 1-,2-,3-,4-,and 5-year LTP-free survival rates and IDR-free survival rates were significantly higher in the>1.0 cm group compared with the 0.5-1.0cm group(97.5%,86.3%,73.6%,49.5%and 26.4%vs 91.3%,78.4%,49.5%,27.8%,and 12.8%;95.1%,90.3%,77.0%,61.0%and 48.3%vs 95.2%,85.9%,62.6%,47.2%and 28.5%;P<0.05).The 1-,2-,3-,4-,and 5-year OS rates were 98.6%,91.5%,69.2%,56.0%and 42.2%,respectively,in the 0.5-1.0 cm group and 100%,98.9%,90.1%,68.7%and 57.4%,respectively,in the>1.0 cm group(P=0.010).There were no significant differences in complication rates between the two groups.Both univariate and multivariate analyses identified AM as an independent prognostic factor linked to LTP,IDR,and OS.CONCLUSION:For HCC tumors>3.0 cm and≤5.0cm,AM>1.0 cm could reduce chances of recurrence compared with AM of 0.5-1.0 cm,emphasizing the need for a more defensive strategy using AMs>1.0 cm for ablating HCC tumors of 3.1 to 5.0 cm.     

Control of oxidative stress in hepatocellular carcinoma: Helpful or harmful?

Oxidative stress is becoming recognized as a key factor in the progression of chronic liver disease(CLD) and hepatocarcinogenesis. The metabolically important liver is a major reservoir of mitochondria that serve as sources of reactive oxygen species, which are apparently responsible for the initiation of necroinflammation. As a result, CLD could be a major inducer of oxidative stress. Chronic hepatitis C is a powerful generator of oxidative stress, causing a high rate of hepatocarcinogenesis among patients with cirrhosis. Non-alcoholic steatohepatitis is also associated with oxidative stress although its hepatocarcinogenic potential is lower than that of chronic hepatitis C. Analyses of serum markers and histological findings have shown that hepatocellular carcinoma correlates with oxidative stress and experimental data indicate that oxidative stress increases the likelihood of developing hepatocarcinogenesis. However, the results of antioxidant therapy have not been favorable. Physiological oxidative stress is a necessary biological response, and thus adequate control of oxidative stress and a balance between oxidative and anti-oxidative responses is important. Several agents including metformin and L-carnitine can reportedly control mechanistic oxidative stress. This study reviews the importance of oxidative stress in hepatocarcinogenesis and of control strategies for the optimal survival of patients with CLD and hepatocellular carcinoma.     

Characteristics of atypical large well-differentiated hepatocellular carcinoma: a specific subtype of hepatocellular carcinoma?

BackgroundHepatocellular carcinoma (HCC) de-differentiation is thought to correlate with size, therefore well-differentiated HCC ≥3 cm are considered rare and not fully understood.MethodsPatients who underwent hepatectomy for HCC between 1998–2016 were retrospectively analyzed. Patient's characteristics and recurrence-free (RFS) and overall (OS) survival were compared between those with atypical- (well-differentiated-HCC ≥3 cm) and typical-HCC (moderate-to-poorly-differentiated HCC ≥3 cm).ResultsOf 176 patients included in this study, 37 (21%) had atypical-HCC. Patients with atypical-HCC were less likely to be Asian ethnicity (3% vs. 17%, p = 0.062), have lower rate of viral infection (14% vs. 43%, p = 0.003), cirrhosis (8% vs. 27%, p = 0.015). The tumors were less likely to demonstrate vascular invasion (30% vs. 59%, p = 0.002), and were associated with a lower alpha-fetoprotein level (3.5 ng/ml vs. 33.2 ng/ml, p < 0.001). Patients with atypical-HCC had a longer RFS (5-y RFS: 58.3% vs. 35.7%, p = 0.016) and OS (5-y OS: 79.1% vs 53.3%, p = 0.029) as compared to those with typical-HCC following univariate analysis, however this did not appear following multivariate analysis.ConclusionPatients with atypical-HCC have different characteristic in terms of epidemiology, etiology, cirrhosis and vascular invasion as compared to typical-HCC. The etiology of atypical-HCC may be non-alcoholic fatty liver disease-related and/or malignant transformation of hepatocellular adenoma.     

Single hepatocellular carcinoma ranging from 3 to 5 cm: radiofrequency ablation or resection?

Background. The optimal therapy for hepatocellular carcinoma (HCC) is transplantation. For all those patients not eligible for transplantation (or on the waiting list) among the treatments of choice used more frequently in recent years are resection (RES) and radiofrequency ablation (RFA). RFA is less efficacious for HCC ranging over 3 cm. The aim of this study was to compare RFA to RES in a restricted cohort of patients with a single naive HCC ranging from 3 to 5 cm in size and without end-stage liver disease. Patients and methods. A total of 102 patients who had never been treated before were enrolled. Those patients whose HCC position would have required too much parenchymal loss at RES (central or close to main vascular structures) were treated with RFA (n=60), and the others underwent RES (n=42). The two groups were similar for HCC size and liver disease status. The outcome was considered in terms of overall survival (OS) and disease-free survival (DFS) calculated by the Kaplan–Meier method. Differences among groups were validated by log-rank test. Results. The RES group seemed to present a better long-term OS (91%, 57%, and 43% vs 96%, 53%, and 32% at 1, 3, and 5 years, respectively) and DFS (74%, 35%, and 14% vs 68%, 18%, and 0%, respectively) but there was no statistical significance. Age, gender, virus etiology, HCC size and α-fetoprotein levels did not correlate with survival. Patients with recurrence within the first 12 months after treatment showed a worse long-term survival (p=0.011). Patients in Child-Pugh class B had poor prognoses compared with those in class A (p=0.047). Conclusion. Even if RES seemed to promise better long-term results, in the medium term this difference had no statistical significance. Survival in this series was more closely related to the stage of the underlying liver disease than to treatment (RES/RFA).     

CD40 in hepatocellular carcinoma: relevant or not?

The expression of the CD40 receptor in different tumours suggests that it might be involved in tumour development and proliferation. In this article, we discuss recent findings on CD40 expression in hepatocellular carcinoma, its possible biological role for tumour development, and different experimental therapeutic strategies such as gene therapy and immunotherapy protocols.     

Single hepatocellular carcinoma ≤ 3 cm in left lateral segment: Liver resection or radiofrequency ablation?

AIM:To evaluate the long-term results of radiofrequency ablation(RFA)compared to left lateral sectionectomy(LLS)in patients with Child-Pugh class A disease for the treatment of single and small hepatocellular carcinoma(HCC)in the left lateral segments.METHODS:We retrospectively reviewed the data of133 patients with single HCC(≤3 cm)in their left lateral segments who underwent curative LLS(n=66)or RFA(n=67)between 2006 and 2010.RESULTS:The median follow-up period was 33.5mo in the LLS group and 29 mo in the RFA group(P=0.060).Most patients had hepatitis B virus-related HCC.The hospital stay was longer in the LLS group than in the RFA group(8 d vs 2 d,P<0.001).The 1-,2-,and 3-year disease-free survival and overall survival rates were 80.0%,68.2%,and 60.0%,and 95.4%,92.3%,and 92.3%,respectively,for the LLS group;and 80.8%,59.9%,and 39.6%,and 98.2%,92.0%,and 74.4%,respectively,for the RFA group.The disease-free survival curve and overall survival curve were higher in the LLS group than in the RFA group(P=0.012 and P=0.013,respectively).Increased PIVKA-Ⅱlevels and small tumor size were associated with HCC recurrence in multivariate analysis.CONCLUSION:Liver resection is suitable for single HCC≤3 cm in the left lateral segments.     

Helicobacter pylori and hepatocellular carcinoma: Correlated or uncorrelated?

Helicobacter pylori can be detected in liver tissue resected from patients with hepatocellular carcinoma. Conflicting reports regarding the relationship between H. pylori and hepatocellular carcinoma mean it is uncertain whether H. pylori acts as a troublemaker, co-risk factor or innocent bystander to the development of hepatocellular carcinoma. Clinical studies in patients without known causes of hepatocellular carcinoma are important to discover whether H. pylori is involved in the carcinogenesis of hepatocellular carcinoma. High quality prospective studies in patients with hepatocellular carcinoma, hepatitis C virus infection and no cirrhosis are needed to determine whether H. pylori is a co-risk factor for hepatocellular carcinoma.