Ablation of hepatocellular carcinoma

Radiofrequency ablation (RFA) has gained a wide acceptance as a first-line therapeutic option for small hepatocellular carcinoma (HCC). For very early-stage HCC, despite a higher rate of local tumour progression, RFA is considered as a viable alternative to surgical resection owing to its comparable long-term survival, reduced morbidity, and greater preservation of hepatic parenchyma. For HCCs larger than 2 cm, RFA can contribute to near-curative therapy when combined with chemoembolization. RFA can be used as part of a multimodal treatment strategy for more advanced or recurrent cases, and could be a useful bridging therapy for patients who are waiting for liver transplantation. However, the use of RFA is still limited in treating large tumours and some tumours in high-risk locations. To overcome its current limitations, other ablation techniques are being developed and it is important to validate the role of other techniques for enhancing performance of ablation therapy for HCC.     

Radiofrequency ablation of hepatocellular carcinoma: pros and cons

Among locoregional treatments for hepatocellular carcinoma (HCC), radiofrequency ablation (RFA) has been accepted as the most popular alternative to curative transplantation or resection, and it shows an excellent local tumor control rate and acceptable morbidity. The benefits of RFA have been universally validated by the practice guidelines of international societies of hepatology. The main advantages of RFA include 1) it is minimally invasive with acceptable morbidity, 2) it enables excellent local tumor control, 3) it has promising long-term survival, and 4) it is a multimodal approach. Based on these pros, RFA will play an important role in managing the patient with early HCC (smaller than 3 cm with fewer than four tumors). The main limitations of current RFA technology in hepatic ablation include 1) limitation of ablation volume, 2) technically infeasible in some tumors due to conspicuity and dangerous location, and 3) the heat-sink effect. Many technical approaches have been introduced to overcome those limitations, including a novel guiding modality, use of artificial fluid or air, and combined treatment strategies. RFA will continue to play a role as a representative ablative modality in the management of HCC, even in the era of targeted agents.     

Prospective double-blinded randomized controlled trial of Microwave versus RadioFrequency Ablation for hepatocellular carcinoma (McRFA trial)

BackgroundMicrowave (MWA) and radiofrequency ablation are the commonly used local ablation for hepatocellular carcinoma (HCC). Studies comparing both techniques are scarce. The aim of this study was to compare the efficacy of MWA versus RFA as a treatment for HCC.MethodsPatients with HCC who were suitable for local ablation were randomized into MWA or RFA. All patients were followed up regularly with contrast-enhanced computed tomography (CT) performed at 1, 3, 6 and 12 months after ablation. Both patients and the radiologists who interpreted the post-procedure CT scans were blinded to the treatment allocation. Treatment-related morbidity, overall and disease-free survivals were analyzed.ResultsA total of 93 patients were recruited. Among them, 47 and 46 patients were randomized to MWA and RFA respectively. Patients in two groups were comparable in baseline demographics and tumor characteristics. With a median follow-up of around 30 months, there were no significant difference in the treatment-related morbidity, overall and disease-free survivals. MWA had a significantly shorter overall ablation time when compared with RFA (12 min vs 24 min, p < 0.001).ConclusionsMWA is no different to RFA with respect to completeness of ablation and survivals. It is, however, as safe and effective as RFA in treating small HCC.     

Is percutaneous ethanol injection therapy still effective for hepatocellular carcinoma in the era of radiofrequency ablation?

Percutaneous ethanol injection (PEI) therapy has been replaced by more-effective thermal ablation techniques that have lower local recurrence rates. However, PEI therapy remains useful in certain settings. Since PEI can be performed in any portion of the liver, PEI therapy can be valuable when tumors are located in close proximity to intestinal loops or other positions that are risky for thermal local ablative techniques. PEI therapy is also valuable in other situations where radiofrequency ablation (RFA) is difficult, including technically difficult masses that are not detected with ultrasound (US), are located in the hepatic dome, in the subcapsular area, and exophytically, or are surrounded by large vessels. PEI therapy contributes to combination therapy with transcatheter arterial chemoembolization or RFA in advanced-stage hepatocellular carcinoma (HCC), and also to the treatment of large HCC or extrahepatic metastasis from HCC. These roles of PEI therapy should be stressed for the treatment of HCCs in appropriate clinical situations. This comprehensive review of articles related to PEI therapy illustrates the recent role and indications of this therapy, which is currently valuable for HCC in the era of RFA.     

Therapeutic response assessment of RFA for HCC:Contrast-enhanced US,CT and MRI

Radiofrequency ablation(RFA)is commonly applied for the treatment of hepatocellular carcinoma(HCC)because of the facile procedure,and the safety and effectiveness for the treatment of this type of tumor.On the other hand,it is believed that HCC cells should spread predominantly through the blood flow of the portal vein,which could lead to the formation of intrahepatic micrometastases.Therefore,monitoring tumor response after the treatment is quite important and accurate assessment of treatment response is critical to obtain the most favorable outcome after the RFA.Indeed,several reports suggested that even small HCCs of≤3 cm in diameter might carry intrahepatic micrometastases and/or microvascular invasion.From this point of view,for preventing local recurrences,RFA should be performed ablating a main tumor as well as its surrounding non-tumorous liver tissue where micrometastases and microvascular invasion might exist.Recent advancement of imaging modalities such as contrast-enhanced ultrasonic,computed tomography,and magnetic resonance imaging are playing an important role on assessing the therapeutic effects of RFA.The local recurrence rate tends to be low in HCC patients who were proven to have adequate ablation margin after RFA;namely,not only disappearance of vascular enhancement of main tumor,but also an adequate ablation margin.Therefore,contrast enhancement gives important findings for the diagnosis of recurrent HCCs on each imaging.However,hyperemia of non-tumorous liver surrounding the ablated lesion,which could be attributed to an inflammation after RFA,may well obscure the findings of local recurrence of HCCs after RFA.Therefore,we need to carefully address to these imaging findings given the fact that diagnostic difficulties of local recurrence of HCC.Here,we give an overview of the current status of the imaging assessment of HCC response to RFA.     

Radiofrequency ablation of liver tumors: Actual limitations and potential solutions in the future

Over the past decade,radiofrequency ablation(RFA) has evolved into an important therapeutical tool for the treatment of non resectable primary and secondary liver tumors.The clinical benefit of RFA is represented in several clinical studies.They underline the safety and feasibility of this new and modern concept in treating liver tumors.RFA has proven its clinical impact not only in hepatocellular carcinoma(HCC) but also in metastatic disease such as colorectal cancer(CRC).Due to the increasing number of HCC and CRC,RFA might play an even more important role in the future.Therefore,the refinement of RFA technology is as important as the evaluation of data of prospective randomized trials that will help define guidelines for good clinical practice in RFA application in the future.The combination of hepatic resection and RFA extends the feasibility of open surgical procedures in patients with extensive tumors.Adverse effects of RFA such as biliary tract damage,liver failure and local recurrence remain an important task today but overall the long term results of RFA application in treating liver tumors are promising.Incomplete ablation of liver tumors due to insufficient technology of ablation needles,tissue cooling by the neighbouring blood vessels,large tumor masses and ablation of tumors in close vicinity to heat sensitive organs remain difficult tasks for RFA.Future solutions to overcome these limitations of RFA will include refinement of ultrasonographic guidance(accuracy of probe placement),improvements in needle technology(e.g.needles preventing charring)and intraductal cooling techniques.     

Radiofrequency ablation versus percutaneous microwave coagulation therapy for small hepatocellular carcinomas: a retrospective comparative study

BACKGROUND/AIMS: Although local ablation procedures are useful in eradication treatment for small hepatocellular carcinoma (HCC), there have only been a few clinical studies comparing the response to radiofrequency ablation (RFA) and percutaneous microwave coagulation therapy (PMCT). We evaluated the clinical effect and safety of these two procedures for the treatment of small HCCs measuring 2cm or less in diameter. METHODOLOGY: Twenty-four patients with HCC who were treated by RFA and were compared with 39 patients with HCC who underwent PMCT. These procedures were repeated until complete tumor necrosis was achieved. The therapeutic and adverse effects were retrospectively compared between the two procedures. RESULTS: (1) There were significantly fewer treatment sessions (P < 0.001) in the RFA group than the PMCT group, and the necrotic area was significantly larger (P < 0.001) in the former group. (2) The local recurrence rate was significantly lower (P = 0.012) after RFA than after PMCT, even though the ectopic recurrence rate showed no significant difference. 3) The cumulative survival rate was significantly higher (P = 0.028) in the RFA group. (4) The incidence of pain and fever after treatment was significantly higher after PMCT than after RFA. Bile duct injury and pleural effusion were also more frequent in the PMCT group. CONCLUSIONS: RFA is more useful than PMCT in the treatment of small HCCs because it is minimally invasive and achieves a low local recurrence rate, high survival rate, and extensive necrosis after only a few treatment sessions.     

Radiofrequency ablation versus surgical resection as primary treatment of hepatocellular carcinoma meeting the Milan criteria: a systematic review

Background and Aim: Surgery is the standard treatment option for hepatocellular carcinoma (HCC) meeting the Milan criteria, defined as single HCC ≤ 5 cm in maximum diameter or up to three nodules ≤ 3 cm. However, favorable survival outcomes have also been reported for these HCCs following radiofrequency ablation (RFA). Methods: We performed a systematic review to compare the results of hepatic resection and percutaneous RFA as a primary treatment option of HCC meeting the Milan criteria. Studies were identified by searching MEDLINE on PubMed, the Cochrane Library database and CANCERLIT using appropriate key words. Results: In all six identified observational studies, there were no statistically significant differences in overall survival rates between the two treatment modalities. The results of two randomized trials are controversial, while the power of these randomized trials is too limited to reach a reliable conclusion. In practice, the choice of treatment between surgery and RFA largely depends on the relationship between the local recurrence and perioperative mortality rates of HCC patients. Following RFA, local recurrence rates are low when a minimal safety margin ≥ 4–5 mm is achieved. A previous simulation study of overall survival for very early stage HCC, defined as an asymptomatic solitary small HCC ≤ 2 cm, showed that primary RFA with a 9% local recurrence rate is comparable to surgical resection with a 3% operative mortality rate. Conclusion: Acquisition of a sufficient safety margin seems to be a critical factor before recommending wider application of RFA as primary treatment for HCCs that meet the Milan criteria.     

Value of radiofrequency ablation in the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a malignant disease that substantially affects public health worldwide. It is especially prevalent in east Asia and sub-Saharan Africa, where the main etiology is the endemic status of chronic hepatitis B. Effective treatments with curative intent for early HCC include liver transplantation, liver resection (LR), and radiofrequency ablation (RFA). RFA has become the most widely used local thermal ablation method in recent years because of its technical ease, safety, satisfactory local tumor control, and minimally invasive nature. This technique has also emerged as an important treatment strategy for HCC in recent years. RFA, liver transplantation, and hepatectomy can be complementary to one another in the treatment of HCC, and the outcome benefits have been demonstrated by numerous clinical studies. As a pretransplantation bridge therapy, RFA extends the average waiting time without increasing the risk of dropout or death. In contrast to LR, RFA causes almost no intra-abdominal adhesion, thus producing favorable conditions for subsequent liver transplantation. Many studies have demonstrated mutual interactions between RFA and hepatectomy, effectively expanding the operative indications for patients with HCC and enhancing the efficacy of these approaches. However, treated tumor tissue remains within the body after RFA, and residual tumors or satellite nodules can limit the effectiveness of this treatment. Therefore, future research should focus on this issue.     

Evaluation of transcatheter arterial embolization prior to percutaneous tumor ablation in patients with hepatocellular carcinoma: a randomized controlled trial.

BACKGROUND: Transcatheter arterial embolization (TAE) may reduce the risk of hepatocellular carcinoma (HCC) recurrence when performed before percutaneous tumor ablation (PTA), either percutaneous ethanol injection therapy (PEIT) or radiofrequency ablation (RFA). We conducted a randomized, controlled trial comparing the use of TAE combined with percutaneous ethanol injection therapy (TAE/PEIT) to the use of PEIT only to assess the effects on HCC recurrence and survival. We continued the study after the introduction of RFA and compared TAE combined with RFA (TAE/RFA) with RFA only. METHODS: Between March 1997 and April 2001, 42 HCC patients were enrolled who satisfied the following inclusion criteria: (1) uninodular HCC as determined by angiography under computed tomography, (2) arterial hypervascularity, and (3) no prior history of HCC treatment. Twenty-two patients were treated with TAE/PTA (PEIT, 12; RFA, 10) and 20 patients with PTA only (PEIT, 14; RFA, 6). RESULTS: There were four cases of local recurrence in the PTA-only group and none in the TAE/PTA group (P=0.043). The four patients with local recurrence were treated with PEIT. None of the patients treated with RFA showed local recurrence. The effect of TAE on overall recurrence was not significant (P=0.4179). In the multivariate analysis, prior TAE was not significant for survival (P=0.514). CONCLUSIONS: TAE has a limited use in suppressing local recurrence when performed before PEIT but not before RFA.     

Comparison of tissue pressure and ablation time between the LeVeen and cool-tip needle methods

Background  

Radio frequency ablation (RFA) has been accepted clinically as a useful local treatment for hepatocellular carcinoma (HCC). However, intrahepatic recurrence after RFA has been reported which might be attributable to increase in intra-tumor pressure during RFA. To reduce the pressure and ablation time, we developed a novel method of RFA, a multi-step method in which a LeVeen needle, an expansion-type electrode, is incrementally and stepwise expanded. We compared the maximal pressure during ablation and the total ablation time among the multi-step method, single-step method (a standard single-step full expansion with a LeVeen needle), and the method with a cool-tip electrode. Finally, we performed a preliminary comparison of the ablation times for these methods in HCC cases.     

Role of radiofrequency ablation in the treatment of small hepatocellular carcinoma

Radiofrequency ablation (RFA), one of the most advanced loco-regional ablative therapeutic methods, is widely utilized in the treatment of hepatocellular carcinoma (HCC). Because of its minimal invasiveness and high efficacy, RFA has been regarded as a curative therapy as alternative to surgical resection and liver transplantation. It brings new hope and a new treatment pattern for small HCC. In this article, we summarize the important role of RFA in the treatment of small HCC according to our clinical experience over six years. The prognosis of small HCC after RFA is comparable to that of surgical resection but with higher safety, less complications, wider applicability, and good long-term survival. RFA will play a more and more important role in the clinical treatment of small HCC.     

Radiofrequency ablation of liver tumors: experience with open and percutaneous approach.

BACKGROUND: Radiofrequency ablation (RFA), a thermal coagulation technique, has been used for ablation of primary and secondary liver tumors. METHODS: Over a 24-month period, 41 patients, including 20 with hepatocellular cancer (HCC), 14 with liver metastases from colorectal tumors and 7 with metastases from other tumors, underwent RFA in our institution. Ablation was done using intra-operative (n=27) or percutaneous ultrasonographic (n=14) guidance. A zone of ablation larger than the size of the lesion on CT scan indicated successful RFA. RESULTS: The mean size of lesions was 4.9 cm for HCC and 3.1 cm for metastases. Among 20 patients with HCC, 16 had complete tumor ablation and one had failure of localization. All patients with liver metastases had successful tumor ablation. There was no procedure-related death. Two patients had hemoperitoneum and one experienced skin burn. During a median follow up of 16 months, five patients with HCC and two with colorectal metastases died. One patient had tumor recurrence at the ablation site and two developed fresh solitary metastatic lesions; all three are disease-free after repeat ablation treatment. CONCLUSIONS: RFA is a safe and promising technique for the treatment of non-resectable HCC and liver metastases, in the short term.     

Is radiofrequency ablation the treatment of choice for patients with small hepatocellular carcinoma?

Liver resection is widely considered the mainstay of curative therapy for small hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) was initially developed as a treatment for small HCC in patients with considerable cirrhosis and inadequate liver function reserve for liver resection. However, in some centers, RFA is now used for small HCC, as an alternative to liver resection or even as the preferred treatment. This Practice Point commentary discusses the findings and limitations of a retrospective cohort study by Livraghi et al. that analyzed the outcomes of a group of patients with small, single HCC who underwent treatment with RFA. The authors reported a low major complication rate and a local complete response rate similar to that after resection. This commentary highlights the issues to consider when interpreting and generalizing these results, in particular that these findings need to be interpreted in the light of studies that suggest a high rate of local recurrence and incomplete histopathological response after RFA of small HCC.     

Cost-effectiveness of radiofrequency ablation and surgical therapy for small hepatocellular carcinoma of 3cm or less in diameter.

BACKGROUND: Cost-effectiveness of radiofrequency ablation (RFA) was assessed in treatment of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: During 5 years, 153 patients with HCC of 3cm or less received RFA, and 60 underwent surgery. Judgment after RFA therapy was classified into three grades: residual tumor (grade 1), necrotic area with a less safety margin of 5mm (grade 2), and necrosis with a safety margin of 5mm in all directions (grade 3). RESULTS: Local recurrence rates after RFA and surgery were 7.9% and 0% at the third year. The rates in patients with grades 2 and 3 after RFA were 18.7% and 1.2% at the third year, respectively (P=0.0005). Among 91 patients with grades 1 and 2 necrosis after initial therapy, 52 received additional ablation. Although local recurrence rate was 24.9% in 39 patients without additional therapy, the rates after therapy repetition were 10.9% in 21 patients with eventual grade 2 necrosis, and 0% in 31 patients with grade 3 (P=0.038). Median costs of single RFA, repeated RFA, and surgery were yen849,900, yen1,086,000, and yen1,745,100, respectively. Additional ablation reduced local recurrence by 20.7% at the cost of yen236,100. CONCLUSION: Cost-effectiveness of RFA in the treatment of small HCC was superior to that of surgery.     

射频消融在肝癌多学科综合治疗中的应用

以射频消融（RFA）为代表的局部消融治疗已成为肝癌的重要治疗手段,在肝癌治疗中得到广泛的应用。其主要适应证为肿瘤单发、直径≤5 cm;或者肿瘤2～3个、最大直径≤3 cm。数个临床研究表明射频治疗小肝癌的效果与手术切除相当,国内外多个肝癌临床治疗指南已经将射频与手术切除一样,并列为小肝癌的根治性治疗方法。临床上RFA常常与手术切除、血管介入、瘤内无水酒精注射术、放射治疗、化疗、靶向药物治疗、免疫生物治疗等方法联合应用,在肝癌多学科综合治疗领域中起着越来越重要的作用。     

Percutaneous radiofrequency ablation with artificial ascites for hepatocellular carcinoma adjacent to the diaphragm

Surgical resection is the first-line curative treatment of hepatocellular carcinoma (HCC). However most patients are unable to undergo surgical resection because of advanced tumoral stage, severe liver dysfunction or poor clinical status. Therefore, image-guided tumor ablation techniques have been introduced for the treatment of unresectable HCC. Among them, radiofrequency ablation (RFA) has been demonstrated to be an effective alternative curative therapy. However, local ablative therapy for tumors located close to structures such as the diaphragm or gastrointestinal tract is technically challenging because of the risk of collateral thermal damage to nearby structures or incomplete treatment of the HCC resulting from poor visibility on sonography. The introduction of artificial ascites can separate adjacent organs from the tumor and improve the sonic window. The aim of this study was to evaluate the feasibility, safety and efficacy of RFA with artificial ascites for HCC adjacent to the diaphragm.     

Microwave ablation of hepatocellular carcinoma

Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma (HCC) in patients with well compensated cirrhosis, thermal ablation techniques provide a valid non-surgical treatment alternative, thanks to their minimal invasiveness, excellent tolerability and safety profile, proven efficacy in local disease control, virtually unlimited repeatability and cost-effectiveness. Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules. Among them, radiofrequency (RF) currents are the most used, while microwave ablations (MWA) are becoming increasingly popular. Starting from the 90s’, RF ablation (RFA) rapidly became the standard of care in ablation, especially in the treatment of small HCC nodules; however, RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks. MWA, first introduced in the Far Eastern clinical practice in the 80s’, showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors, resulting in a poor coagulative performance and a relatively high complication rate, nowadays shows better results both in terms of treatment controllability and of overall coagulative performance, thanks to the improvement of technology. In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems, and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications, both in absolute terms and in comparison with RFA.     

Transarterial chemoembolization in hepatocellular carcinoma treatment: Barcelona clinic liver cancer staging system

Hepatocellular carcinoma(HCC),the fifth most common cancer that predominantly occurs in liver cirrhosis patients,requires staging systems to design treatments. The barcelona clinic liver cancer staging system(BCLC) is the most commonly used HCC management guideline. For BCLC stage B(intermediate HCC),transarterial chemoembolization(TACE) is the standard treatment. Many studies support the use of TACE in early and advanced HCC patients. For BCLC stage 0(very early HCC),TACE could be an alternative for patients unsuitable for radiofrequency ablation(RFA) or hepatic resection. In patients with BCLC stage A,TACE plus RFA provides better local tumor control than RFA alone. TACE can serve as bridge therapy for patients awaiting liver transplantation. For patients with BCLC B,TACE provides survival benefits compared with supportive care options. However,because of the substantial heterogeneity in the patient population with this stage,a better patient stratification system is needed to select the best candidates for TACE. Sorafenib represents the first line treatment in patients with BCLC C stage HCC. Sorafenib plus TACE has shown a demonstrable effect in delaying tumor progression. Additionally,TACE plus radiotherapy has yielded better survival in patients with HCC and portal venous thrombosis. Considering these observations together,TACE clearly has a critical role in the treatment of HCC as a stand-alone or combination therapy in each stage of HCC. Diverse treatment modalities should be used for patients with HCC and a better patient stratification system should be developed to select the best candidates for TACE.     

A multi-step, incremental expansion method for radio frequency ablation: optimization of the procedure to prevent increases in intra-tumor pressure and to reduce the ablation time.

BACKGROUND/AIMS: Radio frequency ablation (RFA) has been accepted clinically as a useful local treatment for hepatocellular carcinoma (HCC). However, intra-hepatic recurrence after RFA has been reported. We initially hypothesized that recurrence was attributable to increases in intra-tumor pressure during RFA, and we subsequently measured the pressure and optimized the procedure. METHODS: A block of pig liver sealed in a rigid plastic case was used as a model of an HCC tumor with a capsule. We compared the pressure between a single-step full expansion of the needle (single-step method) and incremental, stepwise expansion (multi-step method), and evaluated the effect of varying the electrical power. Finally, we performed a preliminary comparison of the ablation times for these methods in HCC cases. RESULTS: The multi-step method resulted in a significantly lower pressure and shorter total ablation time than the single-step method. Furthermore, incremental expansion in 10 steps resulted in a lower pressure and shorter ablation time than four steps. Seventy W-ablation resulted in a lower pressure and shorter time than 30- or 50 W-ablation. In HCC cases, the multiple-step method had a significantly shorter ablation time than the single-step method. CONCLUSION: The multi-step method can be recommended to reduce the ablation time, and suppress the increase in pressure.