Local recurrence of hepatocellular carcinoma after radiofrequency ablation

A 51-year-old Chinese male with a 20-year history of hepatitis B was diagnosed with hepatocellular carcinoma in the right anterior portion of the liver, sized 3.5 cm × 3.2 cm, and was treated with radiofrequency ablation (RFA) on December 18, 2001. The patient did not receive antiviral therapy for hepatitis B virus after RFA. The treated lesion reduced gradually and reached its minimum size of 1.7 cm × 1.5 cm seven years later on November 18, 2008. However computed tomography findings revealed that a recurr...     

Surgical vs percutaneous radiofrequency ablation for hepatocellular carcinoma in dangerous locations

AIM:To compare the long-term outcome of percutaneous vs surgical radiofrequency ablation(RFA) for hepatocellular carcinoma(HCC) in dangerous locations.METHODS:One hundred and sixty-two patients with HCC in dangerous locations treated with percutaneous or surgical RFA were enrolled in this study.The patients were divided into percutaneous RFA group and surgical RFA group.After the patients were regularly followed up for a long time,their curative rate,hospital stay time,postoperative complications and 5-year...     

Management of recurrent hepatocellular carcinoma after liver transplant

Hepatocellular carcinoma(HCC) is the leading cause of deaths in patients with hepatitis B or C, and its incidence has increased considerably over the past decade and is still on the rise. Liver transplantation(LT) provides the best chance of cure for patients with HCC and liver cirrhosis. With the implementation of the MELD exception system for patients with HCC waitlisted for LT, the number of recipients of LT is increasing, so is the number of patients who have recurrence of HCC after LT. Treatments for intrahepatic recurrence after transplantation and after other kinds of surgery are more or less the same, but long-term cure of posttransplant recurrence is rarely seen as it is a "systemic" disease. Nonetheless, surgicalresection has been shown to be effective in prolonging patient survival despite the technical difficulty in resecting graft livers. Besides surgical resection, different kinds of treatment are also in use, including transarterial chemoembolization, radiofrequency ablation, highintensity focused ultrasound ablation, and stereotactic body radiation therapy. Targeted therapy and modulation of immunosuppressants are also adopted to treat the deadly disease.     

较大肝癌局部消融的关键问题

近年来,超声、CT、MRI 引导下射频消融（RFA）和微波消融（MCT）作为微创热消融技术迅速发展,已证实热消融治疗肝癌安全、廉价、有效,且极具前景。对于小肝癌（〈3 cm）的疗效确切[1],目前被临床列为一线治疗方法[2]。对大于3 cm 的肝癌进行消融,虽有较高的坏死率[3],但由于受消融热场区限制,存在完全灭活困难,局部复发率高的问题[4]。鉴于在临床实际工作中,小肝癌比例较少,而3 cm 以上较大肝癌最常见,因此提高较大肝癌局部消融的疗效成为改善肝癌患者预后的关键。如何能做到穿刺次数少,又完全灭活肿瘤、减少消融治疗后肝癌的局部复发已成为重要的研究热点。     

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.     

A meta-analysis of adjuvant therapy after potentially curative treatment for hepatocellular carcinoma

BACKGROUND:

The high recurrence rate of hepatocellular carcinoma (HCC) after potentially curative treatment determines the long-term prognosis.

OBJECTIVE:

To evaluate the efficacy and safety of adjuvant therapies in patients with HCC who have undergone hepatic resection, transplantation or locoregional ablation therapy.

METHODS:

Several databases were searched to identify randomized controlled trials (RCTs) fulfilling the predefined selection criteria. Meta-analyses were performed to estimate the effects of adjuvant therapies of any modality on recurrence-free survival (RFS) and overall survival (OS).

RESULTS:

Eight adjuvant modalities were identified from 27 eligible RCTs conducted predominantly in Asian populations comparing adjuvant with no adjuvant therapy. Adjuvant chemotherapy, internal radiation and heparanase inhibitor PI-88 therapy failed to improve RFS or OS, while interferon (IFN) therapy yielded significant survival results. The findings of adjuvant vitamin analogue therapy required further examination. Adjuvant adoptive immunotherapy conferred significant benefit for RFS but not for OS. Although cancer vaccine therapy and radioimmunotherapy may improve survival after radical surgery, the results were from single, small-scale trials. Severe side effects were observed in the studies of adjuvant chemotherapy and of IFN therapy.

CONCLUSIONS:

Adjuvant IFN therapy can improve both RFS and OS; however, the benefits of using this agent should be weighed against its side effects. Combination of systemic and transhepatic arterial chemotherapy is not recommended for HCC after potentially curative treatment. Other adjuvant therapies produce limited success for survival. Additional RCTs with proper design are required to establish the role of adjuvant therapies for HCC.     

Role of microRNA-regulated cancer stem cells in recurrent hepatocellular carcinoma

Among the most common cancers, hepatocellular carcinoma (HCC) has a high rate of tumor recurrence, tumor dormancy, and drug resistance after initial successful chemotherapy or radiotherapy. A small subset of cancer cells, cancer stem cells (CSCs), exhibit stem cell characteristics and are present in various cancers, including HCC. The dysregulation of microRNAs (miRNAs) often accompanies the occurrence and development of HCC. miRNAs can influence tumorigenesis, progression, recurrence, and drug resistance by regulating CSCs properties, which supports their clinical utility in managing and treating HCC. This review summarizes the regulatory effects of miRNAs on CSCs in HCC with a special focus on their impact on HCC recurrence.     

Current status and prospect of treatments for recurrent hepatocellular carcinoma

Owing to its heterogeneous and highly aggressive nature, hepatocellular carcinoma (HCC) has a high recurrence rate, which is a non-negligible problem despite the increasing number of available treatment options. Recent clinical trials have attempted to reduce the recurrence and develop innovative treatment options for patients with recurrent HCC. In the event of liver remnant recurrence, the currently available treatment options include repeat hepatectomy, salvage liver transplantation, tumor ablation, transcatheter arterial chemoembolization, stereotactic body radiotherapy, systemic therapies, and combination therapy. In this review, we summarize the strategies to reduce the recurrence of high-risk tumors and aggressive therapies for recurrent HCC. Additionally, we discuss methods to prevent HCC recurrence and prognostic models constructed based on predictors of recurrence to develop an appropriate surveillance program.     

Therapeutic effectiveness of echo-guided percutaneous radiofrequency ablation therapy with a LeVeen needle electrode in hepatocellular carcinoma

AIM:To investigate the results of radiofrequencyablation(RFA)in obtaining the necrosis of hepatocellularcarcinoma(HCC)in cirrhotic patients and to assessthe results of RFA in relation to recurrence of HCC andsurvival of the treated patients.METHODS:Fifty-six consecutive cirrhotic patients with63 HCCs were treated with RFA between May 2000 andMay 2004.The diameter of the HCCs ranged from 1 cmto 5 cm(mean 2.8 cm).In all cases RFA was performedwith percutaneous approach under ultrasound guidanceusing expandable needle electrode(LeVeen needle).Treatment efficacy and recurrence were evaluated withdual-phase spiral computed tomography(CT).RESULTS:Complete necrosis after single or multipletreatment was achieved in 96.8%(61/63)tumors.We observed recurrence after complete necrosis in 23patients(41%)during a mean follow-up of 32.3 months.The recurrences were local in 2 patients(8.6%)and indifferent segments in 21(91.4%).Major complicationsoccurred in 3 patients(4%).During follow-up period,32(57.1%)patients died;15 due to progression of HCC,11 from liver failure,3 from esophageal varices bleedingand 3 from the causes not related to liver disease.CONCLUSION:RFA with LeVeen needle is an effectiveand safe treatment for HCC<5 cm in cirrhotic patients.It has yet to be established how far this treatmentinfluences the survival rate of patients.It becomesimportant to establish treatments to prevent recurrencesin different segments,such as interferon therapy.     

Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma

Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2–3 years. No adjuvant treatments to prevent such an occurrence have been developed so far. However, a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable. Moreover, several pre- and post-transplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up. When recurrence occurs, the outcomes are poor with a median survival of 12 mo according to most retrospective studies. The factor that most impacts survival after recurrence is timing (within 1–2 years from LT according to different authors). Several therapeutic options may be chosen in case of recurrence, according to timing and disease presentation. Surgical treatment seems to provide a survival benefit, especially in case of late recurrence, while the benefit of locoregional treatments has been suggested only in small retrospective studies. When systemic treatment is indicated, sorafenib has been proved safe and effective, while only few data are available for lenvatinib and regorafenib in second line. The use of immune checkpoint inhibitors is controversial in this setting, given the safety warnings for the risk of acute rejection.     

Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.     

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.     

Assessment of radiofrequency ablation margin by MRI-MRI image fusion in hepatocellular carcinoma

AIM:To investigate the feasibility and clinical value of magnetic resonance imaging(MRI)-MRI image fusion in assessing the ablative margin(AM) for hepatocellular carcinoma(HCC).METHODS:A newly developed ultrasound workstation for MRI-MRI image fusion was used to evaluate the AM of 62 tumors in 52 HCC patients after radiofrequency ablation(RFA).The lesions were divided into two groups:group A,in which the tumor was completely ablated and 5 mm AM was achieved(n = 32);and group B,in which the tumor was completely ablated but 5 mm AM was not achieved(n = 29).To detect local tumor progression(LTP),all patients were followed every two months by contrast-enhanced ultrasound,contrast-enhanced MRI or computed tomography(CT) in the first year after RFA.Then,the follow-up interval was prolonged to every three months after the first year.RESULTS:Of the 62 tumors,MRI-MRI image fusion was successful in 61(98.4%);the remaining case had significant deformation of the liver and massive ascites after RFA.The time required for creating image fusion and AM evaluation was 15.5 ± 5.5 min(range:8-22 min) and 9.6 ± 3.2 min(range:6-14 min),respectively.The follow-up period ranged from 1-23 mo(14.2 ± 5.4 mo).In group A,no LTP was detected in 32 lesions,whereas in group B,LTP was detected in 4 of 29 tumors,which occurred at 2,7,9,and 15 mo after RFA.The frequency of LTP in group B(13.8%;4/29) was significantly higher than that in group A(0/32,P = 0.046).All of the LTPs occurred in the area in which the 5 mm AM was not achieved.CONCLUSION:The MRI-MRI image fusion using an ultrasound workstation is feasible and useful for evaluating the AM after RFA for HCC.     

Current surgical treatment strategies for hepatocellular carcinoma in North America

Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease. Many patients do not initially manifest any symptoms of HCC and present late when cure with surgical resection or transplantation is no longer possible. For this reason, patients at high risk for developing HCC are subjected to frequent screening processes. The surgical management of HCC is complex and requires an inter-disciplinary approach. Hepatic resection is the treatment of choice for HCC in patients without cirrhosis and is indicated in some patients with early cirrhosis (Child-Pugh A). Liver transplantation has emerged in the past decade as the standard of care for patients with cirrhosis and HCC meeting Milan criteria and in select patients with HCC beyond Milan criteria. Loco-regional therapy with transarterial chemoembolization, transarterial embolization, radiofrequency ablation and other similar local treatments can be used as neo-adjuvant therapy to downstage HCC to within Milan criteria or as a bridge to transplantation in patients on transplant wait list.     

Scattered and rapid intrahepatic recurrences after radio frequency ablation for hepatocellular carcinoma

AIM: To evaluate a series of patients with hepatocellular carcinoma (HCC) treated with several different protocols and devices. METHODS: We treated 138 patients [chronic hepatitis/ liver cirrhosis (Child-Pugh A/B/C), 3/135 (107/25/3)] with two different devices and protocols: cool-tip needle [initial ablation at 60 W (standard method) (n = 37) or at 40 W (modified method) (n = 28)] or; ablation with a LeVeen needle using a standard single-step, full expansion (single-step) method (n = 39) or a multi-step, incremental expansion (multi-step) method. RESULTS: Eleven patients experienced rapid and scattered recurrences 1 to 7 mo after the ablation. Nine patients were treated by the cool-tip original protocol (60 W) (9/37 = 24%) and the other two by the LeVeen single-step method (2/39 = 5%). The location of the recurrence was surrounding and limited to the site of ablation segment in three cases, and spread over one lobule or both lobules in the other eight cases. There was no recurrence in the patients treated with the modified cool-tip modified method (40 W) or the LeVeen multi-step method. CONCLUSION: There is a risk of rapid and scattered recurrence after RFA, especially when the standard cool-tip procedure is used. Because such recurrence would worsen the prognosis, we recommend that modified protocols for the cool-tip and LeVeen needle methods should be used in clinical practice.     

Risk factors for the recurrence of hepatocellular carcinoma after radiofrequency ablation of hepatocellular carcinoma in patients with hepatitis C

AIM: To analyze the risk factors of hepatocellular carcinoma (HCC) recurrence after radiofrequency ablation (RFA) treatment with HCV-associated hepatitis. METHODS: Twenty-six patients with HCV-associated HCC who were followed-up for more than 12 mo were selected for this study. Risk factors for distant intrahepatic recurrences of HCC were evaluated for patients in whom complete coagulation was achieved without recurrence in the same subsegment as the primary nodule.Twelve clinical and tumoral factors were examined: Age, gender, nodule diameter, number of primary HCC nodule, Child-Pugh classification, serum platelet, serum albumin, serum AST, post RFA AST, serum ALT, post RFA ALT, post RFA treatment. RESULTS: Distant recurrences of HCC in remnant liver after RFA were observed in 14 cases and in the number of primary HCC nodules (P = 0.047), and the serum platelets (P = 0.030), the clear difference came out by the recurrence group and the non-recurrence group. The cumulative recurrence rates after 1 and 2 years were 30.8% and 86.8%, respectively for primary multinodular HCC, and 15.4% and 29.5% respectively, for primary uninodular HCC. In addition the 1-year recurrence rates for patients with serum albumin more than 3.4 g/dL and less than 3.4 g/dL were 23.1% for both, but the 2-years recurrence rates were 89.0% and 23.1%, respectively. The number of primary HCC nodules (relative risk, 6.970; P = 0.016) were found to be a statistically significant predictor for poor distant intrahepatic recurrence by univariate analysis. CONCLUSION: Patients who have multiple HCC nodules, low serum platelets and low serum albumin accompanied by HCV infection, should be carefully followed because of the high incidence of new HCC lesions in the remnant liver, even if coagulation RFA is complete.     

Management of sub-centimeter recurrent hepatocellular carcinoma after curative treatment: Current status and future

Hepatocellular carcinomas (HCCs) frequently recur despite initial successful surgical resection or local ablation therapy. Diagnostic methods for small HCCs have improved with the introduction of gadoxetic acid-enhanced liver magnetic resonance imaging and diffusion-weighted imaging (DWI). Currently, sub-centimeter recurrent nodules showing typical hallmark imaging findings of HCC are frequently detected in patients with a treatment history for HCC. With five typical magnetic resonance findings, including arterial enhancement, washout on portal or transitional phase, high signal intensity on both T2-weighted image and DWI, and low signal intensity on hepatobiliary phase, sub-centimeter recurrent HCC can be diagnosed with high accuracy. Although more information is needed to determine the treatment of choice, local ablation therapy under fusion imaging and/or contrast-enhanced ultrasound guidance or cone-beam computed tomography-guided chemoembolization seem to be promising as they are effective and safe for the management of sub-centimeter recurrent HCCs.     

Hyperglycemia is a significant prognostic factor of hepatocellular carcinoma after curative therapy

AIM:To evaluate whether metabolic factors are related to distant recurrence of hepatocellular carcinoma(HCC) and survival after curative treatment.METHODS:This retrospective study included 344 patients whose HCC was treated curatively by radiofrequency ablation(RFA) therapy.The mean age was 67.6 years and the mean observation period was 4.04 years.The etiological background of liver disease was hepatitis B virus infection in 30,hepatitis C virus infection in 278,excessive alcohol drinking in 9,and other in 27 patients.The Child-Pugh classification grade was A(n = 307) or B(n = 37).The number of HCC nodules was one in 260,two in 61,and three in 23 patients.For surveillance of HCC recurrence after curative therapy with RFA,patients were radiologically evaluated every 3 mo.Factors associated with distant recurrence of HCC or survival were studied.RESULTS:Inadequate maintenance of blood glucose in diabetic patients was associated with higher incidence of distant recurrence.The 1-,2-,and 3-year recurrence rates were significantly higher in diabetic patients with inadequate maintenance of blood glucose compared with the others:50.6% vs 26.8%,83.5% vs 54.4%,and 93.8% vs 73.0%,respectively(P = 0.0001).Inadequate maintenance of blood glucose was an independent predictor of distant recurrence [adjusted relative risk 1.97(95%CI,1.33-2.91),(P = 0.0007)] after adjustment for other risk factors,such as number of HCC nodules [2.03(95%CI,1.51-2.73),P < 0.0001] and initial level of serum alpha fetoprotein(AFP) [1.43(95%CI,1.04-1.97),P = 0.028].Obesity was not an independent predictor of recurrence.The incidence of distant recurrence did not differ between diabetic patients with adequate maintenance of blood glucose and non-diabetic patients.Among 232 patients who had HCC recurrence,138 had a second recurrence.The 1-,2-,and 3-year rates of second recurrence were significantly higher in diabetic patients with inadequate maintenance of blood glucose than in the others:9.0% vs 5.9%,53.1% vs 24.3%,and 69.6% vs 42.3%,respectively(P     

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.     

肝癌根治术后肝内复发合并肝外转移积极手术治疗10例

目的:探讨对严格选择的肝癌根治术后肝内复发并肝外转移患者采取积极外科治疗策略的临床价值.方法:回顾性分析10例肝癌根治术后肝内复发伴肝外孤立转移灶病例的外科治疗情况.并与行保守治疗的肝癌根治术后肝内复发伴肝外转移的48例患者的生存情况进行比较.结果:Kaplan-Meier生存分析显示积极外科治疗组复发后中位生存时间为45.0mo±5.1mo,保守治疗组复发后中位生存时间仅为12.0mo±2.1mo.Log-rank检验对两组生存时间比较,发现积极手术治疗组生存时间显著长于保守治疗组(P<0.01)结论:对于严格选择的病例采取肝外孤立转移灶切除联合肝内复发灶切除或局部治疗的积极外科治疗策略能够显著提高患者生存时间.