Ten-year survival of hepatocellular carcinoma patients undergoing radiofrequency ablation as a first-line treatment

AIM: To investigate the long-term survival and prognostic factors in hepatocellular carcinoma(HCC) patients undergoing radiofrequency ablation(RFA) as a first-line treatment.METHODS: From 2000 to 2013, 316 consecutivepatients with 404 HCC(1.0-5.0 cm; mean: 3.2 ± 1.1 cm) underwent ultrasonography-guided percutaneous RFA as a first-line treatment. There were 250 males and 66 females with an average age of 60.1 ± 10.8 years(24-87 years). Patients were followed for 1 year to 10 years after RFA(234, 181, 136, and 71 for 3, 5, 7, and 10 years, respectively). Overall local response rates and long-term survival rates were assessed. Survival results were generated using Kaplan-Meier estimates, and multivariate analysis was performed using the Cox regression model. RESULTS: In total, 548 RFA sessions were performed and major complications occurred in 10 sessions(1.8%). Local tumor progression and/or new tumor development were observed in 43.3%(132/305) of the patients during the follow-up period. Overall 5-and 10-year survival rates were 49.7% and 28.4%, respectively. Based on multivariate analysis, three factors were identified as independent prognostic factors for overall survival: Child-Pugh classification(HR = 4.054, P 0.001), portal vein hypertension(HR = 2.743, P = 0.002), and tumor number(HR = 2.693, P = 0.003). The local progression-free 5- and 10-year survival rates were 42.7% and 19.5%. In addition to the Child-Pugh classification and the number of tumors, the number of RFA sessions(HR = 1.550, P = 0.002) was associated with local progression-free survival.CONCLUSION: RFA can achieve acceptable outcomes for HCC patients as a first-line treatment, especially for patients with Child-Pugh class A, patients with a single tumor and patients without portal vein hypertension.     

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.     

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.     

Preoperative Alpha-Fetoprotein Has No Prognostic Role in Small Hepatocellular Carcinoma in Non-Cirrhotic Patients After Surgical Resection

Background: Alpha-fetoprotein (AFP) has been widely used as a tumor marker in the treatment of hepatocellular carcinoma (HCC) in patients with cirrhosis. However, a large number of HCC patients are diagnosed without cirrhosis, and the prognostic capability of AFP was unclear in HCC patients without cirrhosis. Our purpose was to investigate the prognostic efficiency of AFP in patients with non-cirrhosis, single, and small HCC who were treated with surgical resection.Methods: Among the 111 374 liver cancer patients included in the Surveillance, Epidemiology, and End Results database, we selected 224 patients without cirrhosis with a single HCC ≤3 cm in diameter who were identified at diagnosis and treated with surgical resection. The AFP test results were recorded as AFP-positive and AFP-negative levels.Results: Kaplan–Meier method showed that there was no significant survival difference between the AFP-positive and AFP-negative groups (P = .566). The same results were found in the subgroups of patients with tumor size ≤2 cm and 2-3 cm (P = .710 and .687, respectively). Receiver operating characteristic (ROC) curve analysis showed that AFP had inadequate accuracy to discriminate survivors and deceased patients in subgroups of patients with tumor size ≤3 cm, 2-3 cm, or ≤2 cm (area under the ROC curve = 0.449, 0.458, 0.443; 95% confidence interval = 0.366-0.533, 0.346-0.571, 0.317-0.569, respectively).Conclusion: AFP levels have no predictive value in well-compensated non-cirrhosis patients with single, small HCC (≤3 cm) treated with surgical resection for curative intent.     

Lymphocyte-to-monocyte ratio predicts survival after radiofrequency ablation for colorectal liver metastases

AIM: To test the correlation between lymphocyte-tomonocyte ratio(LMR) and survival after radiofrequency ablation(RFA) for colorectal liver metastasis(CLMs). METHODS: From July 2003 to Feb 2012, 127 consecutive patients with 193 histologically-proven unresectable CLMs were treated with percutaneous RFA at the University of Foggia. All patients had undergone primary colorectal tumor resection before RFA and received systemic chemotherapy. LMR was calculated by dividing lymphocyte count by monocyte count assessed at baseline. Treatment-related toxicity was defined as any adverse events occurred within 4 wk after the procedure. Overall survival(OS) and time to recurrence(TTR) were estimated from the date of RFA by Kaplan-Meier with plots and median(95%CI). The inferential analysis for time to event data was conducted using the Cox univariate and multivariate regression model to estimate hazard ratios(HR) and 95%CI. Statistically significant variables from the univariate Cox analysis were considered for the multivariate models.RESULTS: Median age was 66 years(range 38-88) and patients were prevalently male(69.2%). Median LMR was 4.38%(0.79-88) whereas median number of nodules was 2(1-3) with a median maximum diameter of 27 mm(10-45). Median OS was 38 mo(34-53) and survival rate(SR) was 89.4%, 40.4% and 33.3% at 1, 4 and 5 years respectively in the whole cohort. Running log-rank test analysis found 3.96% as the most significant prognostic cut-off point for LMR and stratifying the study population by this LMR value median OS resulted 55 mo(37-69) in patients with LMR 3.96% and 34(26-39) mo in patients with LMR ≤ 3.96%(HR = 0.53, 0.34-0.85, P = 0.007). Nodule size and LMR were the only significant predictors for OS in multivariate analysis. Median TTR was 29 mo(22-35) with a recurrence-free survival(RFS) rate of 72.6%, 32.1% and 21.8% at 1, 4 and 5 years, respectively in the whole study group. Nodule size and LMR were confirmed as significant prognostic factors for TTR in multivariate Cox regression. TTR, when stratified by LMR, was 35 mo(28-57) in the group 3.96% and 25 mo(18-30) in the group ≤ 3.96%(P = 0.02).CONCLUSION: Our study provides support for the use of LMR as a novel predictor of outcome for CLM patients.     

经肝动脉化疗栓塞术治疗肝细胞癌合并门静脉癌栓的预后影响因素分析

目的评估肝细胞癌(HCC)合并门静脉癌栓患者经肝动脉化疗栓塞术(TACE)治疗后的效果及影响预后的因素。方法回顾性分析2006年1月-2010年12月第四军医大学西京医院收治的152例行TACE治疗的HCC合并门静脉癌栓患者的临床资料。观察TACE术后肝衰竭、上消化道大出血、栓塞后综合征等发生情况,分析生存期资料与影响预后的因素。Kaplan-Meier法计算累积生存率,采用Log-Rank法进行单因素分析,Cox比例风险模型进行多因素分析。结果患者中位生存时间为5.0(95%可信区间:4.4~5.6)个月,6、12、18个月的累积生存率分别为37%、18%和9%。单因素分析显示肿瘤大小、肿瘤类型、肝两叶累及、远处转移和Child-Pugh分级是HCC合并门静脉癌栓患者行TACE治疗预后的影响因素(χ2值分别为5.108、11.542、6.036、12.319、22.574,P值均0.05);多因素分析显示肿瘤大小、肿瘤类型、远处转移和Child-Pugh分级是影响患者预后的独立危险因素(Wald值分别为11.243、5.021、7.651、25.876,P值均0.05);而HCC合并门静脉癌栓患者发生肝衰竭的唯一影响因素是Child-Pugh分级(P=0.015)。结论在肝功能良好的HCC合并门静脉癌栓患者中,TACE是安全有效的。肿瘤大小、肿瘤类型、远处转移、Child-Pugh分级是影响患者生存的最主要因素,为临床医生选择合适的介入治疗患者提供了有力证据。     

Sustained viral response prolonged survival of patients with C-viral hepatocellular carcinoma.

BACKGROUND: We conducted this retrospective study to evaluate the position of interferon therapy in the curative treatment of hepatitis C virus-associated hepatocellular carcinoma (HCC). METHODS: We compared overall and recurrence-free survival rates between 191 patients who received interferon therapy before HCC development (15 with sustained virologic response (SVR)), 53 who received interferon therapy after HCC ablation (17 with SVR), and 399 HCC patients with Child-Pugh class A liver function who did not receive interferon (controls). RESULTS: The overall survival rate in the controls was 82.4%, 53.2%, and 28.3% at 3, 6, and 9 years, respectively, whereas that in patients who developed HCC after achieving SVR was 93.3%, 93.3%, and 93.3%; those with HCC after non-SVR, 87.8%, 56.5%, and 35.8%; SVR after HCC, 100%, 87.5%, and 59.7%; and non-SVR after HCC, 94.3%, 70.9%, and 53.2%. Cox proportional hazard regression analysis revealed that the risk of death was significantly reduced in patients with HCC after SVR and those with SVR after HCC, with a risk ratio of 0.124 (95% confidence interval (95% CI): 0.017-0.890, P = 0.0378) and 0.388 (95% CI: 0.169-0.887, P = 0.0250), respectively, compared with the controls. Improved survival was attributable mainly to sustained liver function among patients with SVR, and recurrence-free survival did not differ significantly. CONCLUSION: Interferon therapies before and after HCC development were both significantly associated with prolonged survival when SVR was achieved.     

Survival comparison between surgical resection and percutaneous radiofrequency ablation for patients in Barcelona Clinic Liver Cancer early stage hepatocellular carcinoma

Aim

To compare the survival outcome between surgical resection (SR) and radiofrequency ablation (RFA) for Barcelona Clinic Liver Cancer (BCLC) early stage hepatocellular carcinoma (HCC).

Methods

The retrospective study enrolled eighty-two patients with newly diagnosed BCLC early HCC (single nodule, size ≦3 cm, and Child-Pugh class A) treated either surgically (n?=?46) or with RFA (n?=?36) from year 2004 to 2009. The patients’ survival outcomes were compared.

Results

There were no significant differences in overall survival (OS) rates between SR and RFA (p?=?0.204). The 3- and 5-year disease-free survival (DFS) rates were 65.8 % and 53.7 % respectively, in the SR group, which were significantly higher than those in the RFA group (34.8 % and 14.9 % respectively) (p?=?0.009 and p?=?0.001). In subgroup analysis, the DFS was similar between RFA and SR in patients with presentation of lower platelet count (≦100,000/mL) and smaller tumor size (tumor size ≦1 cm). Multivariate analysis showed SR as a procedure type was a significant predictive factor for DFS [HR?=?2.26 (CI 1.462–5.227), p?=?0.002].

Conclusion

SR yielded similar OS but better DFS when compared to RFA for patients with BCLC early HCC (single nodule, ≦3 cm and Child-Pugh class A). In subgroup patients with lower platelet count (≦100,000/mL) and smaller tumor size (tumor size ≦1 cm), DFS was similar between both treatments.     

Percutaneous radiofrequency ablation as first‐line treatment for small hepatocellular carcinoma: Results and prognostic factors on long‐term follow up

Background and Aims: We evaluated the prognosis and associated factors in patients with small hepatocellular carcinoma (HCC; up to 3 nodules, each up to 3cm in diameter) treated with percutaneous radiofrequency ablation (RFA) as first‐line treatment. Methods: Eighty‐eight consecutive patients who underwent percutaneous RFA as first‐line treatment were enrolled, among whom 70 who had hypervascular HCC nodules which were treated by a combination of transcatheter arterial chemoembolization and RFA. RFA was repeated until an ablative margin was obtained. Results: The rate of local tumor progression at 1 and 3 years was 4.8% and 4.8%, respectively. The rate of overall survival at 3 and 5 years was 83.0% and 70.0%, and the rate of disease‐free survival at 3 and 5 years was 34.0% and 24.0%, respectively. On multivariate analysis, age (< 70 years; hazard ratio [HR] = 2.341, 95% confidence interval [CI] = 1.101–4.977, P = 0.027) and indocyanine green retention rate at 15 min (< 15%; HR = 3.621, 95% CI = 1.086–12.079, P = 0.036) were statistically significant determinants of overall survival, while tumor number (solitary, HR = 2.465, 95% CI = 1.170–5.191, P = 0.018) was identified for disease‐free survival. Overall survival of patients with early recurrence after RFA was significantly worse than that of patients with late recurrence. Tumor size was the only independent risk factor of early recurrence after RFA of HCC (tumor size > 2 cm; risk ratio [RR] = 4.629, 95% CI = 1.241–17.241, P = 0.023). Conclusion: Percutaneous RFA under the protocol reported here has the potential to provide local tumor control for small HCC. In addition to host factors, time interval from RFA to recurrence was an important determinant of prognosis.     

Obesity did not diminish the efficacy of percutaneous ablation for hepatocellular carcinoma.

Background: Overweight and hepatic steatosis can increase the risk of hepatocarcinogenesis. In addition, overweight may affect the treatment efficacy of ultrasound‐guided percutaneous ablation. We evaluated the impact of overweight on the safety and efficacy of percutaneous ablation to hepatocellular carcinoma (HCC). Methods: We enrolled 743 patients with naïve HCC who were treated by percutaneous ablation including ethanol injection, microwave coagulation, and radiofrequency ablation (RFA) between 1995 and 2003. Patients were divided into two groups by body mass index (BMI): 219 overweight patients with BMI>25 kg/m² and 524 control patients with BMI≤25 kg/m². The effects of BMI on complications of percutaneous ablation, HCC recurrence, and overall survival were analyzed, together with others including tumor and liver function‐related factors. Results: The overweight group required a significantly larger number of sessions by RFA (P=0.01). Major complications were identified in 8.7% in the overweight group and 7.6% in the control group (P=0.94). There was no significant difference in cumulative recurrence rate and local tumor‐progression rate between the two groups (P=0.63 and 0.44). Cumulative survival rates at 1, 3, and 5 years were 95.4%, 75.7%, and 57.8%, respectively, in the overweight group and 94.1%, 78.0%, and 58.8% in the control group (P=0.99). Conclusions: The results indicated that overweight did not increase complications nor affect HCC recurrence and overall survival. However, the number of sessions of RFA was significantly greater in overweight patients, suggesting that overweight was associated with minor technical difficulties.     

Radiofrequency ablation for single hepatocellular carcinoma 3 cm or less as first-line treatment

AIM:To evaluate long-term outcomes of radiofrequency(RF) ablation as first-line therapy for single hepatocellular carcinoma(HCC) ≤ 3 cm and to determine survival and prognostic factors.METHODS:We included all 184 patients who underwent RF ablation as a first-line treatment for single HCC ≤ 3 cm between April 2005 and December 2013.According to the criteria of Livraghi,the 184 patients were divided into two groups:those suitable for surgical resection(84 cases) and those unsuitable for surgical resection(100 cases).The primary endpoints were the overall survival(OS) rate and safety;the secondary endpoints were primary technique effectiveness and recurrence rate.RESULTS:There were 19(10.3%) cases of ablation related minor complications.The complete tumor ablation rate after one RF session was 97.8%(180/184).The rate of local tumor progression,extrahepatic metastases and intrahepatic distant recurrence were 4.9%(9/184),9.8%(18/184) and 37.5%(69/184),respectively.In the 184 patients,the 1-,3-,and 5-year OS rates were 99.5%,81.0%,and 62.5%,respectively.The 1-,3-,and 5-year OS rates were 100%,86.9%,and 71.4%,respectively,in those suitable for surgical resection and 99.0%,76.0%,and 55.0%,respectively,in those unsuitable for surgical resection(P = 0.021).On univariate and multivariate analyses,poorer OS was associated with Child-Pugh B class and portal hypertension(P 0.05).CONCLUSION:RF ablation is a safe and effective treatment for single HCC ≤ 3 cm.The OS rate of patients suitable for surgical resection was similar to those reported in surgical series.     

Laparoscopic radiofrequency ablation of unresectable hepatocellular carcinoma: long-term follow-up

Background. Hepatocellular carcinoma (HCC) has seen a dramatic rise in the USA over the last 30 years. Unresectable disease is present in 80–90% of patients, for which radiofrequency ablation (RFA) is an option. The aim of this study is to report the long-term survival after laparoscopic RFA. Methods. This is a prospective analysis of 104 patients who underwent 122 ablations for unresectable HCC from April 1997 to December 2006 at a tertiary care center. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan–Meier curves, excluding 11 patients who subsequently underwent liver transplantation. Patients were analyzed using Child-Pugh classification, Barcelona Clinic Liver Cancer (BCLC) staging and various clinical parameters. Results. Median (range) data: age 63 years (41–81), lesion size 3.5 cm (1–10), number of lesions 1 (1–5), AFP 26.5 ng/ml (3.7–43588.5) and time from diagnosis to RFA 2 months (mos) (1–42). The median Kaplan–Meier survival for all patients was 26 mos (OS) while DFS was 14 mos. Univariate analysis demonstrated improved OS for the absence vs. presence of ascites (31 vs. 15 mos, p=0.003), Bilirubin <2 mg/dl vs. ≥2 mg/dl (27 vs. 19 mos, p=0.01), AFP <400 vs. ≥400 (29 vs. 13 mos, p<0.0001) and Child-Pugh Grade (A = 28, B = 15, C = 5 mos, p=0.01). Significant factors for improved DFS: absence vs. presence of ascites (16 vs. 5 mos, p=0.02), Bilirubin <2 vs. ≥2 (14 vs. 5 mos, p=0.0278), AFP <400 vs. ≥400 (15 vs. 4 mos, p=0.0025), Child-Pugh Grade (A = 16, B = 10, C = 3 mos, p=0.03). Patient age, largest tumor size, number of lesions, INR and albumin did not reach clinical significance. Three and five-year actual survival rates are 21% and 8.3%, respectively. Conclusions. Our study suggests that RFA may have a positive impact on survival for unresectable HCC. It also determines which patients fare best after RFA, by determining predictive factors that improve their survival.     

Meta-analysis of radiofrequency ablation in combination with transarterial chemoembolization for hepatocellular carcinoma

AIM: To compare radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA monotherapy in hepatocellular carcinoma (HCC). METHODS: We searched PubMed, Medline, Embase and Chinese databases (CBMdisc and Wanfang data) for randomized controlled trails comparing RFA plus TACE and RFA alone for treatment of HCC from January 2000 to December 2012. The overall survival rate, re-currence-free survival rate, tumor progression rate, and safety were analyzed and compared. The analysis was conducted on dichotomous outcomes and the standard meta-analytical techniques were used. Pooled odds ratios (ORs) with 95%CIs were calculated using either the fixed-effects or random-effects model. For each meta-analysis, the χ2 and I2 tests were first calculated to assess the heterogeneity of the included trials. For P<0.05 and I 2>50%, the assumption of homogeneity was deemed invalid, and the random-effects model wasused; otherwise, data were assessed using the fixed-effects model. All statistical analysis was conducted us-ing Review manager (version 4.2.2.) from the Cochrane collaboration. RESULTS: Eight randomized controlled trials were identified as eligible for inclusion in this analysis and included 598 patients with 306 treated with RFA plus TACE and 292 with RFA alone. Our data analysis indicated that RFA plus TACE was associated a sig-nificantly higher overall survival rate (OR 1-year=2.96, 95%CI: 1.84-7.74, P<0.001; OR 2-year=3.72, 95%CI: 1.24-11.16, P=0.02; OR 3-year=2.65, 95%CI: 1.81-3.86, P<0.001) and recurrence-free survival rate (OR 3-year=3.00, 95%CI: 1.75-5.13, P<0.001; OR 5-year=2.26, 95%CI: 1.43-3.57, P=0.0004) vs that of RFA alone. The tumor progression rate in patients treated with RFA alone was higher than that of RFA plus TACE (OR=0.60, 95%CI: 0.42-0.88, P=0.008) and there was no significant difference on major complications between two different kinds of treatment (OR=1.20, 95%CI: 0.31-4.62, P=0.79). Additionally, the meta-analysis data of subgroups revealed that the     

Resection or ablation versus transarterial therapy for Child-Pugh A patients with a single small hepatocellular carcinoma

Data from a direct comparison of the long-term survival outcomes of surgical resection (SR) or radiofrequency ablation (RFA) versus transarterial therapy in Child-Turcotte-Pugh (CTP)-class A patients with a single small T1/T2 stage hepatocellular carcinoma (HCC) (≤3 cm) are still lacking. This study retrospectively compared the therapeutic outcomes of these treatment types for CTP-A patients with a single small HCC.Using a nationwide Korean registry, we identified 2314 CTP-A patients with SR (n = 722), RFA (n = 731), or transarterial therapy (n = 861) for a single (≤3 cm) T1/T2 stage HCC from 2008 to 2014. The posttreatment overall survival (OS) of transarterial therapy with either SR or RFA were compared using the Inverse Probability of treatment Weighting (IPW). The median follow-up period was 50 months (range 1–107 months).After IPW, the cumulative OS rates after SR or RFA were significantly higher than those after transarterial therapy in all subjects (all P values < .05). The OS rates after SR or RFA were better than those after transarterial therapy in patients with the hepatitis B or C virus (all P values < .05), and in patients aged <65 years (all P values < .05). The cumulative OSs between RFA and transarterial therapy were statistically comparable in patients with a 2 to 3 cm HCC and aged ≥65 years, respectively. For all subjects, the weighted Cox proportional hazards model using IPW provided the adjusted hazard ratios (95% confidence interval) for the OS after SR versus transarterial therapy and after RFA versus transarterial therapy of 0.42 (0.30–0.60) (P < .001) and 0.78 (0.61–0.99) (P = .044), respectively.In CTP-A patients with a single (≤3 cm) T1/T2 HCC, SR or RFA provides a better OS than transarterial therapy, regardless of the HCC etiology (hepatitis B virus or hepatitis C virus), especially in patients with HCC of <2 cm and aged <65 years.     

Wait Time for Curative Intent Radio Frequency Ablation is Associated with Increased Mortality in Patients with Early Stage Hepatocellular Carcinoma

IntroductionRadiofrequency ablation (RFA) is a recommended curative intent treatment option for patients with early stage hepa-tocellular carcinoma (HCC). We investigated if wait times for RFA were associated with residual tumor, tumor recurrence, need for liver transplantation, or death.Material and methodsWe conducted a retrospective study of patients diagnosed with HCC between January 2010 and December 2013 presenting to University Health Network (UHN) in Toronto, Canada. All patients receiving curative intent RFA for HCC were included. Multivariable Cox regression was used to determine if wait times were associated with clinical outcomes.Results219 patients were included in the study. 72.6% were male and the median age was 62.7 years (IQR 55.6-71). Median tumor size at diagnosis was 21.5 mm (IQR 17-26); median MELD was 8.7 (IQR 7.2-11.4) and 57.1% were Barcelona stage 0. The cause of liver disease was viral hepatitis in 73.5% (Hepatitis B and C). The median time from HCC diagnosis to RFA treatment was 96 days (IQR 75-139). In multivariate analysis, wait time was not associated with requiring liver transplant or tumor recurrence, however, each incremental 30-day wait time was associated with an increased risk of residual tumor (HR = 1.09; 95% CI 1.01-1.19; p = 0.033) as well as death (HR = 1.23; 95% CI 1.11-1.36; p ≤ 0.001).ConclusionIncremental 30-day wait times are associated with a 9% increased risk of residual tumor and a 23% increased risk of death. We have identified system gaps where quality improvement measures can be implemented to reduce wait times and allocate resources for future RFA treatment, which may improve both quality and efficiency of HCC care.     

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).     

Successful initial ablation therapy contributes to survival in patients with hepatocellular carcinoma

AIMTo evaluate the outcome predictors of percutaneous ablation therapy in patients with unresectable hepatocellular carcinoma(HCC),especially to identify whether the initial treatment response contributes to the survival of the patients.METHODSThe study cohort included 153 patients with single(102)and two or three(51)HCC nodules 5 cm or less in maximum diameter.As an initial treatment,110 patients received radiofrequency ablation and 43 patients received percutaneous ethanol injection.RESULTSThe Kaplan-Meier estimates of overall 3-and 5-year survival rates were 75% and 59%,respectively.The log-rank test revealed statistically significant differences in the overall survivals according to ChildPugh class(P = 0.0275),tumor size(P = 0.0130),serum albumin level(P = 0.0060),serum protein induced by vitamin K absence or antagonist Ⅱ level(P = 0.0486),and initial treatment response(P = 0.0130).The independent predictors of survival were serum albumin level(risk ratio,3.216;95% CI,1.407-7.353;P = 0.0056)and initial treatment response(risk ratio,2.474;95% CI,1.076-5.692;P = 0.0330)based on the Cox proportional hazards regression models.The patients had a serum albumin level 3.5 g/dL and the 3-and 5-year survival rates of 86% and 82%.CONCLUSIONIn HCC patients treated with percutaneous ablation therapy,serum albumin level and initial treatment response are the independent outcome predictors.     

Comparison of percutaneous radiofrequency ablation and CyberKnife? for initial solitary hepatocellular carcinoma: A pilot study

AIM: To compare therapeutic outcomes and adverse events in initial solitary hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) and CyberKnife^®.METHODS: Seventy three consecutive patients with initial solitary HCC treated with RFA (38 patients; RFA group) and CyberKnife^® (35 patients; CK group) were enrolled in this study. Background factors were compared between the two groups. Local and intrahepatic distant recurrence control, and cumulative survival rates were compared between the two groups. These were determined using the Kaplan-Meier method, and the significance of differences was analyzed by log-rank test. The presence of more grade 3 on CTCAE ver. 4.0 early and late adverse events was investigated.RESULTS: In background factors, age was significantly higher (P = 0.005) and the tumor diameter was significantly larger (P = 0.001) in the CK group. The 1-year local recurrence control rates were 97.4% and 97.1% in the RFA and CK groups, respectively (P = 0.71); the 1-year intrahepatic distant recurrence control rates were 85.6% and 86.1%, respectively (P = 0.91); and the 1-year cumulative survival rates were 100% and 95.2%, respectively (P = 0.075), showing no significant difference in any rate between the two groups. There were no late adverse event in the RFA group, but 11.4% in the CK group had late adverse events. In the CK group, the Child-Pugh score at 12 mo after treatment was significantly higher than that in the RFA group (P = 0.003) and significantly higher than the score before treatment (P = 0.034).CONCLUSION: The occurrence of adverse events is a concern, but CyberKnife^® treatment is likely to become an important option for local treatment of early HCC.     

经肝动脉化疗栓塞术治疗伴门静脉癌栓肝细胞癌的效果及预后评价模型分析

目的探讨肝细胞癌(HCC)合并门静脉癌栓患者采用经肝动脉化疗栓塞术(TACE)治疗的效果,并评估现有肝癌预后评价模型的指导价值。方法筛选2010年1月—2016年5月在全国24家三级医院行TACE治疗的HCC患者,最终共纳入266例合并门静脉癌栓的HCC患者进行回顾性分析。采用Kaplan-Meier法绘制生存曲线,并采用log-rank法进行比较;采用Cox回归分析进行单因素和多因素分析,建立Cox回归模型;计算HAP评分、mHAP评分、mHAP2评分、mHAP3评分及6&12标准的受试者工作特征曲线下面积(AUC)和C指数,比较各种模型的预测性能。结果所纳入患者中位生存时间为9.867个月,根据Child-Pugh分级,Child-Pugh A级患者中位生存时间为10.067个月,明显长于Child-Pugh B级患者的5.967个月(χ2=5.181,P=0.023)。AFP≤800 ng/ml的患者中位生存时间13.10个月,而AFP>800/ml的患者中位生存时间8.13个月,差异有统计学意义(χ2=8.643,P=0.003)。单因素分析结果显示肿瘤数目、肿瘤直径、总胆红素、血清白蛋白、AST、ALT与患者的生存有关(P值均<0.05)。多因素分析结果显示肿瘤数目(HR=1.186,95%CI:1.058~1.329,P<0.05)、肿瘤直径(HR=1.047,95%CI:1.001~1.095,P<0.05)是影响患者生存的独立影响因素。6&12标准的1年、2年、3年AUC分别为0.651、0.655、0.641,高于其他模型,而6&12标准和新建模型的C指数分别为0.577和0.579,高于其他模型。结论在AFP水平较低、肝功能良好的HCC合并门静脉癌栓患者中,TACE是安全有效的。肿瘤直径和肿瘤数目为筛选合适的患者行TACE治疗提供了可靠依据。现有的原发性肝癌TACE治疗的预后评价模型中,6&12标准具有较好的预测能力。     

Predictors and clinical outcomes for spontaneous rupture of hepatocellular carcinoma

AIM:To determine the risk factors for hepatocellular carcinoma(HCC) rupture,and report the management and long-term survival results of patients with spontaneous rupture of HCC.METHODS:Among 4209 patients with HCC who were diagnosed at Eastern Hepatobiliary Surgery Hospital from April 2002 to November 2006,200(4.8%) patients with ruptured HCC(case group) were studied retrospectively in term of their clinical characteristics and prognostic factors.The one-stage therapeutic approach to manage ruptured HCC consisted of initial management by conservative treatment,transarterial embolization(TACE) or hepatic resection.Results of various treatments in the case group were evaluated and compared with the control group(202 patients) without ruptured HCC during the same study period.Continuous data were expressed as mean ± SD or me-dian(range) where appropriate and compared using the unpaired t test.Categorical variables were compared using the Chi-square test with Yates correction or the Fisher exact test where appropriate.The overall survival rate in each group was determined using the Kaplan-Meier method and a log-rank test.RESULTS:Compared with the control group,more patients in the case group had underlying diseases of hypertension(7.5% vs 3.0%,P =0.041) and liver cirrhosis(87.5% vs 56.4%,P 0.001),tumor size 5 cm(83.0% vs 57.4%,P 0.001),tumor protrusion from the liver surface(66.0% vs 44.6%,P 0.001),vascular thrombus(30.5% vs 8.9%,P 0.001) and extrahepatic invasion(36.5% vs 12.4%,P 0.001).On multivariate logistic regression analysis,underlying diseases of hypertension(P = 0.002) and liver cirrhosis(P 0.001),tumor size 5 cm(P 0.001),vascular thrombus(P = 0.002) and extrahepatic invasion(P 0.001) were predictive for spontaneous rupture of HCC.Among the 200 patients with spontaneous rupture of HCC,105 patients underwent hepatic resection,33 received TACE,and 62 were managed with conservative treatment.The median survival time(MST) of all patients with spontaneous rupture of HCC was 6 mo(range,1-72 mo),and the overall survival at 1,3 and 5 years were 32.5%,10% and 4%,respectively.The MST was 12 mo(range,1-72 mo) in the surgical group,4 mo(range,1-30 mo) in the TACE group and 1 mo(range,1-19 mo) in the conservative group.Ninety-eight patients in the control group underwent hepatic resection,and the MST and median diseasefree survival time were 46 mo(range,6-93 mo) and 23 mo(range,3-39 mo) respectively,which were much longer than that of patients with spontaneous rupture of HCC undergoing hepatic resection(P 0.001).The 1-,3-,and 5-year overall survival rates and the 1-,3-and 5-year disease-free survival rates in patients with ruptured HCC undergoing hepatectomy were 57.1%,19.0% and 7.6%,27.6%,14.3% and 3.8%,respectively,compared with those of 77.1%,59.8% and 41.2%,57.1%,40.6% and 32.9% in 98 patients with-CONCLUSION:Prolonged survival can be achieved in selected patients undergoing one-stage hepatectomy,although the survival results were inferior to those of the patients without ruptured HCC.