Percutaneous radiofrequency ablation therapy for hepatocellular carcinoma: a proposed new grading system for the ablative margin and prediction of local tumor progression and its validation

Background

In the present study we classified the radicality of percutaneous radiofrequency thermal ablation (RFA) therapy according to the extent of the ablated margin. We measured the local recurrence rate for each radicality grade to evaluate the significance of the grading system in assessing the therapeutic effectiveness of RFA and predicting local tumor progression.

Methods

This retrospective study involved 269 patients with solitary hypervascular hepatocellular carcinoma who had undergone RFA. The mean?±?SD observation period after RFA, number of treatment sessions, and tumor diameter were 25.7?±?19.9?months, 1.2?±?0.5, and 2.1?±?0.7?cm, respectively. Patients were evaluated using dynamic computed tomography. We classified the radicality of RFA treatment into four grades (R grades: A, B, C, and D) according to the extent of the ablated tumor margin, calculated the post-RFA cumulative local recurrence rate for each R grade, and analyzed the factors (patient characteristics, biochemical data, contiguous vessels, and tumor marker) contributing to local recurrence.

Results

The cumulative local recurrence rates at 3?years were 6.7, 17.6, 55.8, and 82.2% for Grades A, B, C, and D, respectively. Using univariate analysis, R grade, tumor size (>2?cm), and des-??-carboxy prothrombin (DCP) (>200?mAU/mL) were shown to be significant factors contributing to local recurrence. However, using multivariate analysis, only the R grade was found to be a significant independent factor.

Conclusions

The proposed R grading method is a valid and useful method for assessing treatment efficacy, and for predicting local tumor progression after RFA.     

Radiofrequency ablation of hepatocellular carcinoma: The feasibility of magnetic resonance imaging with gadolinium ethoxybenzyl diethylene triamine pentaacetic acid for evaluating the ablative margin

Aim: The aim of this study was to evaluate the feasibility of gadolinium ethoxybenzyl diethylene triamine pentaacetic acid (Gd‐EOB‐DTPA) in magnetic resonance imaging (MRI) to assess the ablative margin of radiofrequency (RF) ablation to hepatocellular carcinoma (HCC). Methods: RF ablation was performed in the livers of six pigs after the i.v. administration of Gd‐EOB‐DTPA 20 min before ablation. Three pigs were killed 2 h after administration (group A), and the other pigs were killed 7 days after ablation (group B). Thereafter, correlation between pathological findings and MRI was investigated. Moreover, the Gd concentrations were examined in ablated and non‐ablated regions. An initial clinical evaluation was conducted for 28 HCC nodules. Percutaneous RF ablation was performed 20 min after administration, and T₁‐weighted images were taken 2, 24 and 72 h post‐treatment. Results: On T₁‐weighted images of the porcine liver, the RF ablated lesions showed hyperintense regions with hypointense rims, which histopathologically corresponded to sinusoidal congestion. The Gd concentrations in ablated regions in group A were significantly higher than those in non‐ablated regions, while the concentrations in both regions in group B fell to nearly undetectable levels. In 27 of the 28 HCC nodules, the treated area consisted of a hypointense region, indicative of the tumor, and a surrounding hyperintense rim 2 h after ablation. Subsequently, a thin hypointense region was observed in the outermost layer 24 and 72 h after ablation. Conclusion: Administration of Gd‐EOB‐DTPA in conjunction with RF ablation of HCC may be feasible for the assessment of an accurate ablative margin.     

Radiofrequency ablation versus surgical resection for single nodule hepatocellular carcinoma: Long-term outcomes

Background. Radiofrequency ablation (RFA) has been increasingly utilized for treatment of hepatocellular carcinoma (HCC). Long-term results of RFA, especially in comparison to surgical resection, have not been well described.Methods. Eighty-seven patients with single nodule HCC underwent surgical resection (N=47) or RFA (N=40) during a 9-year period. RFA was performed for 36 unresectable disease and 4 surgical refusals. Each group was further divided based on tumor size for analysis; Group 1: resection, ≤5 cm (N=18), Group 2: RFA, ≤5 cm (N=26), Group 3: resection, >5 cm (N=29) and Group 4: RFA, >5 cm (N=14). Follow-up ranged from 2 to 72 months (median 16 months). Patients'' characteristics, local recurrences and overall and disease-free survivals were compared.Results. Patients who underwent RFA were older (69 versus 60, p=0.0006), had more advanced Child-Pugh class and TNM stage (p=0.0002 and p=0.016, respectively), and had smaller tumors (4.6 versus 7.4 cm, p=0.0032). Local recurrence rates were 2% for resection and 10% for RFA (p=0.12). These local and other recurrences were subsequently treated with multimodal therapies as indicated. The median overall and disease-free survivals were equivalent both between Groups 1 and 2 (49 versus 51 months, p=0.44, 36 versus 22 months, p=0.84), and Groups 3 and 4 (47 versus 463 months, p=0.94, 28 versus 20 months, p=0.67).Discussion. Although the groups were not truly comparable, this retrospective study suggests that RFA may offer similar long-term results to surgical resection for single nodule HCC when combined with multimodal treatments.     

Radiofrequency ablation of hepatocellular carcinoma in difficult locations:Strategies and long-term outcomes

AIM:To investigate the treatment strategies and longterm outcomes of radiofrequency ablation(RFA) of hepatocellular carcinoma(HCC) in difficult locations and to compare the results with non-difficult HCC.METHODS:From 2004 to 2012,a total of 470 HCC patients underwent ultrasound-guided percutaneous RFA.Among these HCC patients,382 with tumors located ≤ 5 mm from a major vessel/bile duct(n = 87),from peripheral important structures(n = 232) or from the liver capsule(n = 63) were regarded as difficult cases.There were 331 male patients and 51 female patients,with an average age of 55.3 ± 10.1 years old.A total of 235 and 147 patients had ChildPugh class A and class B liver function,respectively.The average tumor size was 3.4 ± 1.2 cm.Individual treatment strategies were developed to treat these difficult cases.During the same period,88 HCC patients with tumors that were not in difficult locations served as the control group.In the control group,74 patients were male,and 14 patients were female,with an average age of 57.4 ± 11.8 years old.Of these,62 patients and 26 patients had Child-Pugh class A and class B liver function,respectively.Regular follow-up after RFA was performed to assess treatment efficacy.Survival results were generated from Kaplan-Meier estimates,and multivariate analysis was performed using the Cox regression model.RESULTS:Early tumor necrosis rate in the difficult group was similar to that in the control group(97.6% vs 94.3%,P = 0.080).The complication rate in the difficult group was significantly higher than that in thecontrol group(4.9% vs 0.8%,P = 0.041).The followup period ranged from 6 to 116 mo,with an average of 28 ± 22.4 mo.Local progression rate in the difficult group was significantly higher than that in the control group(12.7% vs 7.1%,P = 0.046).However,the 1-,3-,5-,and 7-year overall survival rates in the difficult group were not significantly different from those in the control group(84.3%,54.4%,41.2%,and 29.9% vs 92.5%,60.3%,43.2%,and 32.8%,respectively,P = 0.371).Additionally,a multivariate analysis revealed that tumor location was not a significant risk factor for survival.CONCLUSION:There was no significant difference in long-term overall survival between the two groups even though the local progression rate was higher in the difficult group.     

原发性肝癌的射频消融治疗

原发性肝癌在我国是死亡率居第二位的恶性肿瘤,其治疗主要是以外科切除为主的多学科综合治疗模式.上世纪90年代兴起的射频消融(radiofrequency ablation,RFA)近年来发展迅速,在肝癌综合治疗体系中发挥着重要作用,已在肝癌的临床治疗中得到广泛应用.RFA治疗肝癌的原理是通过射频产生热能,使局部达到高温而杀死肿瘤细胞.相对于其他局部消融治疗方法,RFA在消融范围、消融形态、调控方式、电极针种类以及安全性方面仍然有着无可比拟的技术优势[1],是临床应用最广的局部消融技术.     

Radiofrequency ablation as a salvage procedure for ruptured hepatocellular carcinoma

Spontaneous rupture of hepatocellular carcinoma is a distinct presentation causing acute abdomen. Different treatment approaches have been advocated including emergency hepatectomy, initial hemostasis by hepatic artery ligation or transarterial embolization and second-stage hepatectomy. Unrecognized ruptured hepatocellular carcinoma during laparotomy is often encountered in countries where the incidence of hepatocellular carcinoma is low. Radiofrequency ablation is a new localized thermal ablative technique for the treatment of unresectable hepatic tumors including hepatocellular carcinoma. We report a case where radiofrequency ablation was used as a salvage procedure for ruptured hepatocellular carcinoma during emergency laparotomy.     

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.     

射频消融对比手术切除治疗小肝癌的Meta分析

目的:比较射频消融术与外科手术切除在治疗小肝癌中的疗效.方法:计算机检索1991-2011年发表的有关采用射频消融术(radiofrequency ablation,RFA)与外科手术肝切除(surgical hepatic resection,HR)治疗小肝癌的对照试验,按照Cochrane系统评价员手册4.2.2版所推荐的质量评价标准来筛选试验,评价纳入研究的方法学质量,用RevMan5.0.25版软件对研究进行系统评价及Meta分析.结果:共纳入2个随机对照试验,9个非随机对照试验,其中英文9篇,中文1篇,韩文1篇.所纳入的研究共包括2965例患者:其中射频消融组患者1459例、外科手术切除组患者1506例.Meta分析表明:外科手术组在3年、5年生存率及1、3、5年无瘤生存率上明显高于射频消融组,差异均有统计学意义(P<0.05),两者1年生存率相比无显著差异(P>0.05);术后严重并发症射频消融组明显低于外科手术组(P<0.05).结论:现有的证据表明,对于小肝癌,射频消融术后严重并发症明显少于外科手术切除,但是外科手术切除治疗小肝癌总体疗效仍明显优于射频消融治疗.     

Radiofrequency ablation vs. surgery for perivascular hepatocellular carcinoma: Propensity score analyses of long-term outcomes

1. Download high-res image (104KB)
2. Download full-size image

     

射频消融在肝细胞癌治疗中的研究进展

近年来,肝细胞癌(HCC)发病率居高不下,而射频消融(RFA)自临床开展以来对HCC的治疗取得了令人瞩目的成绩。此文就RFA治疗HCC的进展作一综述。     

Radiofrequency ablation for hepatocellular carcinoma in so-called high-risk locations

We evaluated the efficacy and safety of radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) in presumably high-risk locations. Between February 1999 and December 2001, we performed RF ablation on 1419 nodules in 636 consecutive HCC patients, of which 231 nodules in 207 patients were in high-risk locations, defined as less than 5 mm from a large vessel or an extrahepatic organ. Eighty-one patients had a nodule adjacent to a large vessel, 145 patients had a nodule adjacent to an extrahepatic organ, of whom 19 also had one adjacent to a large vessel. Early complications and local tumor progression were analyzed with regard to the location of each nodule. The mean nodule diameter and average number per patient were 27 mm and 2.3, respectively. Early complications, within 30 days after ablation, occurred in 12 of 207 patients (5.8%) with a nodule in a high-risk location and in 15 of 429 patients (3.5%) without (P = .1776). There was no significant difference in local tumor progression rate between nodules in high-risk locations (1 year: 2.1%, 2 years: 3.1%, 3 years: 3.1%) and those elsewhere (1 year: 0.6%, 2 years: 1.7%, 3 years: 2.5%) (P = .2745). In conclusion, HCC nodules adjacent to a large vessel or extrahepatic organ were treated with RF ablation without compromising the efficacy of the procedure. However, even though without significant difference, some complications occurred at risky locations and need to be carefully considered.     

Radiofrequency ablation,PEIT, and TACE for hepatocellular carcinoma

At detection or over time, hepatocellular carcinoma (HCC) is multicentric in origin, against a background of chronic hepatic disease at different stages. Orthotopic liver transplantation (OLT) is the only therapy able to definitely cure both diseases. When OLT is not feasible, all other options can be only palliative. Owing to the multicentricity, surgical resection may be one possible option at the initial detection in selected patients, whereas percutaneous interventional techniques (percutaneous ethanol injection [PEI], radiofrequency ablation [RFA], selected transcatheter arterial chemoembolization [TACE]) are the options more often used. The range of their indications is becoming wider. Although it is understood that partial resection assures the greatest local control, the survival rates after surgery are roughly comparable with those obtained with PEI. The explanation for this result reflects a balance among the advantages and disadvantages of the two therapies. PEI survival curves are better than curves of resected patients who present with adverse prognostic factors, and this means that a better selection of the patients for surgery is needed. An open question remains the choice among percutaneous techniques. In our department we currently use RFA in most patients but consider PEI and selected TACE complementary, and use them according to the features of the disease and the response.     

Radiofrequency ablation for treatment of hepatocellular carcinoma with cirrhosis

BACKGROUND/AIMS: The majority of hepatocellular carcinoma patients with cirrhosis are not candidates for surgical resection, and local thermal therapy producing destruction of cancer cells was one of the ideal options for treatment. Heat from radiofrequency ablation is generated through agitation caused by an alternating electrical current. The heat of radiofrequency energy results in local cell coagulation and causes cellular ablation necrosis of tumor tissue. METHODOLOGY: Eighteen cases of hepatocellular carcinoma were treated with radiofrequency ablation in our institute. We used a RFA 2000 generator (Boston Scientific Co, USA) with LeVeen needle with the maximum diameter of 3.5 cm when the array electrodes were fanned out. The indications for this method included; i) normal prothrombin profile, ii) no ascites, iii) tumor can be detected and approached by ultrasound, iv) tumor cannot be resected or patient is not willing to take the operation. RESULTS: No specific complication was noted during or after the procedure. Only two cases needed more analgesics after the procedure. One case was found with burning of the stomach serosa proved by laparoscopic examination, in which radiofrequency ablation was performed to the tumor located in the left lobe of the segment 3. Impedance could not raise up completely in two cases with larger size tumor more than 5 cm. The decreased levels of alpha-fetoprotein were significant (P = 0.005) after radiofrequency ablation treatment. Residual tumor was found in four cases (20%) in the follow-up abdominal computed tomography scan. CONCLUSIONS: Radiofrequency ablation resulted in a higher rate of complete necrosis of tumor tissue and the complication rate was low as well. Therefore, we believed that radiofrequency ablation is an ideal treatment modality for most liver tumors, which cannot tolerate the conventional surgical procedures.     

Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients

Background and Aim: With the aging of society, the number of elderly patients with hepatocellular carcinoma (HCC) has been increasing in Japan. The Government of Japan defines elderly as being over 65 and has divided the elderly into two stages: the first elderly stage (< 75 years old) and the second elderly stage (≥ 75). We investigated the efficacy and safety of radiofrequency ablation therapy (RFA) in patients in the second elderly stage in comparison with other HCC patients, retrospectively. Methods: Two hundred six patients with HCC, who were within the Milan criteria, with low‐grade performance status (0 or 1) and a Child‐Pugh classification of A or B were enrolled. All were treated with RFA from January 2000 to December 2008 as an initial therapy and were divided into elderly HCC group (e‐HCC group; ≥ 75, n = 63) and non e‐HCC group (< 75, n = 143), and their clinical data and survival rates were compared. Results: Age and the level of protein induced by vitamin K absence or antagonist (PIVKA‐II) were higher in the e‐HCC group as compared with the non e‐HCC group (78.3 ± 3.2 vs 64.2 ± 7.5 years, 676.3 ± 2643.7 vs 142.4 ± 442.2 mAU/mL: P < 0.01, respectively). There were no significant differences for Child‐Pugh class, tumor node metastasis stage, and Japan Integrated Stage score and in survival rates after 3, and 5 years between the groups (e‐HCC group: 82.5% and 49.7%, respectively; non e‐HCC group: 78.3% and 57.5%, respectively). There were no severe complications in the e‐HCC group. Conclusions: Elderly HCC patients, who have good performance status, should be treated in the same manner and with the same strategy as young HCC patients.     

A measure to assess the ablative margin using 3D-CT image fusion after radiofrequency ablation of hepatocellular carcinoma

ObjectivesTo examine the feasibility of three-dimensional computed tomography (3D-CT) image fusion in facilitating assessment of the ablative margin (AM) after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC).MethodsThis study involved 75 patients with solitary HCC who underwent RFA. The AM was evaluated using 3D-CT image fusion. All cases were categorized into two groups based on the extent of the AM: in Group A, sufficient AM was obtained, which was greater than or equal to 5 mm; in Group B, the lesion was also ablated successfully, but a 5 mm AM was not obtained.Results3D-CT Image Fusion was performed on 36 and 39 patients in Group A and Group B, respectively. The 1, 3, 5 year RFS was 87.6%, 63.2%, 50.6% for Group A, and 77.2%, 51.5%, 35.6% for Group B, respectively (P = 0.042); the corresponding OS was 94.3%, 73.8%, 64.6%, and 86.2%, 60.5%, 47.6%, respectively (P = 0.046). Multivariate analysis showed that the AM (P = 0.048, HR = 2.15, 95% CI 1.01–4.60) and Pre-NLR were independent prognostic factors for PFS.Conclusions3D-CT image fusion is a feasible and useful method to evaluate the AM after RFA of HCC.