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Introduction: Radiofrequency ablation (RFA) is a widely accepted, minimally invasive treatment modality for patients with hepatocellular carcinoma (HCC). Accurate prognosis prediction is important to identify patients at high risk for cancer progression/recurrence after RFA. Recently, state-of-the-art transformer models showing improved performance over existing deep learning-based models have been developed in several fields. This study was aimed at developing and validating a transformer model to predict the overall survival in HCC patients with treated by RFA., Methods: We enrolled a total of 1778 treatment-naïve HCC patients treated by RFA as the first-line treatment. We developed a transformer-based machine learning model to predict the overall survival in the HCC patients treated by RFA and compared its predictive performance with that of a deep learning-based model. Model performance was evaluated by determining the Harrel's c-index and validated externally by the split-sample method., Results: The Harrel's c-index of the transformer-based model was 0.69, indicating its better discrimination performance than that of the deep learning model (Harrel's c-index, 0.60) in the external validation cohort. The transformer model showed a high discriminative ability for stratifying the external validation cohort into two or three different risk groups (p < 0.001 for both risk groupings). The model also enabled output of a personalized cumulative recurrence prediction curve for each patient., Conclusions: We developed a novel transformer model for personalized prediction of the overall survival in HCC patients after RFA treatment. The current model may offer a personalized survival prediction schema for patients with HCC undergoing RFA treatment., (© 2023. The Author(s).)

Objective: We reviewed nationwide follow-up data to determine outcomes of different treatments for early-stage hepatocellular carcinoma (HCC) in elderly patients., Summary Background Data: Outcomes of early-stage HCC treatments in elderly patients have not been prospectively compared., Methods: We included 6490 HCC patients, aged ≥75 years at treatment, who underwent curative hepatic resection (HR, n = 2020), radiofrequency ablation (RFA, n = 1888), microwave ablation (MWA, n = 193), or transcatheter arterial chemoembolization (TACE, n = 2389), and compared their characteristics and survival. We used matching propensity score analysis (PSA) between the HR and RFA subgroups with tumors ≤3 cm to overcome baseline bias., Results: The HR group had significantly longer recurrence-free survival (RFS) than the RFA, MWA, and TACE groups [RFA vs HR-hazard ratio: 1.22, 95% confidence interval (CI): 1.09-1.37, P < 0.001; MWA vs HR-hazard ratio: 1.51, 95% CI: 1.22-1.88, P < 0.001; TACE vs HR-hazard ratio: 2.70, 95% CI: 2.44-2.99, P < 0.001). HR and RFA patients had significantly longer overall survival (OS) than the TACE group (RFA vs HR-hazard ratio: 1.01, 95% CI: 0.87-1.17, P = 0.919, TACE vs HR-hazard ratio: 2.11, 95% CI: 1.86-2.40, P < 0.001). PSA successfully matched HR and RFA patients from with primary HCC tumors ≤3.0 cm and similar liver function and tumor characteristics; and showed significantly longer RFS (hazard ratio: 1.64, 95% CI: 1.29-2.10, P < 0.001) and OS (hazard ratio: 1.57, 95% CI: 1.12-2.20, P = 0.009) for HR than for RFA (including subgroup analyses). In Cox proportional hazard analysis, HR offered better prognosis than RFA., Conclusions: HR decreases recurrence risk and improves OS in patients aged ≥75 years with primary HCC tumors ≤3.0 cm.

Background and Aim: Because of the rarity of invasive treatment for hepatocellular carcinoma (HCC) in patients on hemodialysis (HD) for end-stage renal disease (ESRD), the risks associated with radiofrequency ablation (RFA) in such patients remain uncertain. We used a nationwide database to investigate in-hospital mortality and hemorrhagic complications following RFA in patients on HD for ESRD., Methods: Using the Japanese Diagnosis Procedure Combination database, we enrolled patients on HD for ESRD who underwent RFA for HCC. For each patient, we randomly selected up to four non-dialyzed patients using a matched-pair sampling method based on patient age, sex, treatment hospital, and treatment year. In-hospital mortality and hemorrhagic complications were compared between dialyzed and non-dialyzed patients following RFA., Results: We compared matched-pair samples of 437 dialyzed and 1345 non-dialyzed patients. In patients on HD for ESRD, mortality was significantly lower in those aged ≤70 years than in older patients (P = 0.02). In-hospital mortality was significantly higher in dialyzed ESRD patients than in non-dialyzed patients (1.1% vs 0.15%, respectively; odds ratio = 7.77, P < 0.001). Hemorrhagic complications differed significantly between dialyzed ESRD patients and non-dialyzed patients (3.4% vs 0.87%, respectively; odds ratio = 4.75, P < 0.001)., Conclusions: In-hospital mortality following RFA was higher in dialyzed ESRD patients than in non-dialyzed patients. The indications for RFA in dialysis-dependent patients should be considered carefully. Patient age may be a useful indicator when considering RFA for HCC in patients on HD for ESRD., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Vascular invasion in patients with hepatocellular carcinoma (HCC) is representative of advanced disease with an extremely poor prognosis. The detailed course of its development has not been fully elucidated., Methods: We enrolled 1057 consecutive patients with HCC who had been treated with curative intent by radiofrequency ablation (RFA) as an initial therapy from 1999 to 2008 at our department. We analyzed the incidence rate of and predictive factors for vascular invasion. The survival rate after detection of vascular invasion was also analyzed., Results: During a mean follow-up period of 4.5 years, 6075 nodules including primary and recurrent lesions were treated by RFA. Vascular invasion was observed in 97 patients. The rate of vascular invasion associated with site of original RFA procedure was 0.66% on a nodule basis. The incidence rates of vascular invasion on a patient basis at 1, 3, and 5 years were 1.1%, 5.9%, and 10.4%, respectively. Univariate analysis revealed that tumor size, tumor number, alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein were significant risk predictors of vascular invasion. In multivariate analysis, DCP was the most significant predictor for vascular invasion (compared with a DCP of ≤100 mAu/mL, the hazard ratio was 1.95 when DCP was 101-200 mAu/mL and 3.22 when DCP was >200 mAu/mL). The median survival time after development of vascular invasion was only 6 months., Conclusion: Vascular invasion occurs during the clinical course of patients initially treated with curative intent. High-risk patients may be identified using tumor markers.

Objective: The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. The aim of this study is to evaluate the efficacy of radiofrequency ablation (RFA) in elderly patients with HCC and to investigate cause-specific excess deaths associated with increasing number of elderly patients., Materials and Methods: We enrolled 1401 naive patients with HCC who were treated initially by RFA from 1999 to 2011. Patients below 75 years of age were categorized as 'younger' and those at least 75 as 'elderly'. Differences in the demographic and laboratory data of these patients were assessed, along with Kaplan-Meier analysis of survival using the log-rank test. In addition, we assessed the causes of death, defined as liver related and liver unrelated, by competing risk analysis and risk factors for respective causes of death by a proportional subdistribution model., Results: Overall, 353 patients were categorized as elderly. Elderly patients were more likely to be women, infected with hepatitis C virus, and score better in the Child-Pugh classification. The mortality at 5 years was lower in the elderly than in the younger patients (47.3 vs. 37.1%; P<0.001). Competing risk analysis showed a significant difference in liver-unrelated death (P<0.001) between the two groups, whereas there were no significant differences in liver-related death (P=0.64). By the proportional subdistribution model, age was a significant risk factor only for liver-unrelated death., Conclusion: RFA provided satisfactory 5-year survival rates in elderly patients with HCC. The elderly tended to die from liver-unrelated causes.

Background: In the treatment of hepatocellular carcinoma (HCC), hepatic resection has the advantage over radiofrequency ablation (RFA) in terms of systematic removal of a hepatic segment., Methods: We enrolled 303 consecutive patients of a single naïve HCC that had been treated by RFA at The University of Tokyo Hospital from 1999 to 2004. Recurrence was categorized as either intra- or extra-subsegmental as according to the Couinaud's segment of the original nodule. To assess the relationship between the subsegments of the original and recurrent nodules, we calculated the kappa coefficient. We assessed the risk factors for intra- and extra-subsegmental recurrence independently using univariate and multivariate Cox proportional hazard regression. We also assessed the impact of the mode of recurrence on the survival outcome., Results: During the follow-up period, 201 patients in our cohort showed tumor recurrence distributed in a total of 340 subsegments. Recurrence was categorized as exclusively intra-subsegmental, exclusively extra-subsegmental, and simultaneously intra- and extra-subsegmental in 40 (20%), 110 (55%), and 51 (25%) patients, respectively. The kappa coefficient was measured at 0.135 (95% CI, 0.079-0.190; P<0.001). Multivariate analysis revealed that of the tumor size, AFP value and platelet count were all risk factors for both intra- and extra-subsegmental recurrence. Of the patients in whom recurrent HCC was found to be exclusively intra-subsegmental, extra-subsegmental, and simultaneously intra- and extra-subsegmental, 37 (92.5%), 99 (90.8%) and 42 (82.3%), respectively, were treated using RFA. The survival outcomes after recurrence were similar between patients with an exclusively intra- or extra-subsegmental recurrence., Conclusions: The effectiveness of systematic subsegmentectomy may be limited in the patients with both HCC and chronic liver disease who frequently undergo multi-focal tumor recurrence.

Background: Reported mortalities and morbidities of therapeutic procedures for liver tumors vary between studies, because of different designs and small sample sizes. We investigated the mortalities and complication rates for hepatectomy, radiofrequency ablation (RFA), and trans-catheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) in a large sample, using a nationwide Japanese database (the Diagnosis Procedure Combination database)., Methods: Data from the Diagnosis Procedure Combination database were analyzed for July 1 to December 31, 2007 and the same period in 2008. We identified 54,145 patients with HCC who underwent hepatectomy (n = 5,270), RFA (n = 11,688), or TAE (n = 37,187). In-hospital mortality and morbidity were analyzed for each procedure. The relationships between mortality and factors including patient characteristics and procedural backgrounds were assessed., Results: In-hospital mortalities associated with hepatectomy, RFA, and TAE were 2.6 % [95 % confidence interval (CI) 2.2-3.1], 0.3 % (0.2-0.4), and 1.0 % (0.9-1.1), and post-procedural complication rates were 14.5 % (13.5-15.5), 4.5 % (4.2-4.9), and 4.5 % (4.3-4.7), respectively. Increased mortality following hepatectomy was significantly associated with older age, extended lobectomy (vs. partial hepatectomy; odds ratio [OR] 3.80, p < 0.001), lower hospital volume (OR 2.74, p < 0.001), and renal comorbidity (OR 3.01, p = 0.02). Older age and cardiac comorbidity (OR 5.14, p = 0.001) were significantly associated with RFA-related mortality, and lower hospital volume was significantly associated with TAE-related mortality (OR 1.60, p < 0.001)., Conclusions: Mortalities and morbidities associated with therapeutic procedures for liver tumors were acceptably low in Japan, but were affected by patient and institutional characteristics.

Purpose: Recurrence of hepatocellular carcinoma (HCC) is very common even after curative resection or ablation. This retrospective study compared the radiologic features of recurrent HCC seen by computed tomography (CT) to evaluate our empirical protocol of CT surveillance using 4-month intervals., Materials and Methods: A total of 113 patients who were diagnosed with a first HCC recurrence after radiofrequency (RF) ablation between January 2005 and December 2006 were enrolled at a single center. Definite HCC was defined as hyperattenuation in the arterial phase with washout in the portal venous phase, and a diagnosis of naive and recurrent HCC was based on dynamic CT findings. Recurrent nodules were classified according to the enhancement patterns of previous CT images. The treatment modality for recurrent HCC and survival were evaluated., Results: One hundred seventy-seven nodules were diagnosed as recurrent HCC: 31 (17.5%) had already been diagnosed on previous CT images as typical HCC, 72 (40.6%) had arterial hypervascularity without washout in the portal venous phase, 21 (11.9%) showed portal venous phase washout without arterial hypervascularity, and no lesions were noted in the remaining 49 (27.7%). Tumor size at recurrence was smaller than 2 cm in diameter in 98 (86.7%) cases. One hundred four patients were treated for recurrent HCC with RF ablation. The 5-year survival rate after recurrence was 49.8%. There was no significant difference in survival among groups divided by the enhancement pattern on the previous CT examination., Conclusions: Dynamic CT in 4-month intervals is an acceptable recurrence-monitoring strategy because it detects most recurrent nodules at a stage at which RF ablation is still feasible., (Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.)

Objectives: Radiofrequency ablation (RFA) is widely performed for hepatocellular carcinoma (HCC). However, there has been no report on 10-year outcome of RFA. The objective of this study was to report a 10-year consecutive case series at a tertiary referral center., Methods: We performed 2,982 RFA treatments on 1,170 primary HCC patients and analyzed a collected database., Results: Final computed tomography images showed complete tumor ablation in 2,964 (99.4%) of 2,982 treatments performed for the 1,170 primary HCC patients. With a median follow-up of 38.2 months, 5- and 10-year survival rates were 60.2% (95% confidence interval (CI): 56.7-63.9%) and 27.3% (95% CI: 21.5-34.7%), respectively. Multivariate analysis demonstrated that age, antibody to hepatitis C virus (anti-HCV), Child-Pugh class, tumor size, tumor number, serum des-γ-carboxy-prothrombin (DCP) level, and serum lectin-reactive α-fetoprotein level (AFP-L3) were significantly related to survival. Five- and 10-year local tumor progression rates were both 3.2% (95% CI: 2.1-4.3%). Serum DCP level alone was significantly related to local tumor progression. Five- and 10-year distant recurrence rates were 74.8% (95% CI: 71.8-77.8%) and 80.8% (95% CI: 77.4-84.3%), respectively. Anti-HCV, Child-Pugh class, platelet count, tumor size, tumor number, serum AFP level, and serum DCP level were significantly related to distant recurrence. There were 67 complications (2.2%) and 1 death (0.03%)., Conclusions: RFA could be locally curative for HCC, resulting in survival for as long as 10 years, and was a safe procedure. RFA might be a first-line treatment for selected patients with early-stage HCC.

Objectives: Reported rates of major complications and mortality of radiofrequency ablation (RFA), microwave ablation (MWA) and percutaneous ethanol injection (PEI) for the treatment of liver tumours were substantially heterogeneous among studies. The aim was to analyse the mortality and major complication rates of percutaneous RFA, PEI and MWA., Methods: MEDLINE and EMBASE search from January 1982 to August 2010. Randomised clinical trials and observational studies, age >18, more than 50 patients for each technique analysed, studies reporting mortality and major complications were included. Random effects model was performed, with assessment for heterogeneity and publication bias., Results: Thirty-four studies including 9531, 1185, and 1442 patients for RFA, MWA, and PEI, respectively were included. For all ablative techniques pooled proportion mortality rate was 0.16% (95% confidence interval [CI], 0.10-0.24). Pooled mortality rate associated with RFA, PEI and MWA was 0.15% (0.08-0.23), 0.59% (0.14-1.3) and 0.23% (0.0-0.58) respectively. Pooled proportion of major complications was 3.29% (2.43-4.28). Major complication rates associated with RFA, MWA, and PEI was 4.1% (3.3-5.1), 4.6% (0.7-11.8) and 2.7% (0.28-7.4) respectively., Conclusions: Percutaneous RFA, PEI and MWA can be considered safe techniques for the treatment of liver tumours.

Background and Aims: Kupffer imaging in contrast-enhanced ultrasonography (CEUS) with Sonazoid, which lasts for 60 min or longer, may be useful in ultrasound-guided percutaneous tumor ablation. The utility of Sonazoid in radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) was investigated in this study., Methods: We analyzed a total of 716 HCC nodules that were detected on dynamic computed tomography in 316 patients. Detectability of these nodules was compared between CEUS and conventional ultrasonography. The effectiveness in the treatment was assessed by comparing the mean numbers of treatment sessions of RFA in patients treated with CEUS and that in historical controls matched for tumor and background conditions., Results: Detectability of tumor nodule was 83.5% in conventional ultrasonography and 93.2% in CEUS (P=0.04). Sixty-nine nodules in 52 patients were additionally detected with CEUS. The number of additionally detected tumor nodules was positively correlated with serum albumin level (P=0.016). The number of RFA sessions was 1.33±0.45 with CEUS as compared to 1.49±0.76 in the historical controls (P=0.0019)., Conclusions: CEUS with Sonazoid is useful for HCC detection in patients with a well-conserved liver function reservoir. The decrease in RFA session numbers indicated the utility of Sonazoid in RFA treatment of HCC., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Although radiofrequency ablation has been accepted as a safe and effective treatment for small hepatocellular carcinoma, there are few studies addressing periprocedural pain. Our study aims were to investigate periprocedural pain and evaluate its related factors. Ninety-nine patients diagnosed as having hepatocellular carcinoma and who underwent radiofrequency ablation were consecutively enrolled. The pain intensity, mental preparation status for radiofrequency ablation, and demographic and clinical characteristics were investigated. We used an 11-point numerical rating scale to assess for pain. Forty-three percent of subjects reported the intensity of periprocedural pain as more than a level of six (severe pain). The longer duration of ablation (r(s) = .29, p = .004), the number of ablations (r(s) = .27, p = .008), higher pain anxiety (r(s) = .42, p < .001), and difficulty sleeping on the previous day (r(s) = .24, p = .019) were factors related to experiencing more severe pain. The major related factors to severe periprocedural pain were the longer duration of ablation and the more anxiety about pain. Clinicians should offer better information to radiofrequency ablation patients regarding pain expectations and carefully consider periprocedural analgesia requirements.

Background: Percutaneous radiofrequency ablation (RFA) has been widely accepted as an alternative to surgery for small hepatocellular carcinoma (HCC). In RFA, a portion of liver tissue surrounding tumour is also ablated to achieve a safety margin. The intrahepatic bile duct may be injured and result in chronic bile duct dilatation upstream of the injured site. However, the impact of such an injury on the overall prognosis has been unclear., Methods: Patients who showed bile duct dilatation following RFA were identified by a retrospective review of imaging studies. Each dilatation was classified as mild (limited to one hepatic subsegment) or severe (affecting two or more subsegments). The relation between the incidence of intrahepatic bile duct dilatation and HCC recurrence or survival was analysed using proportional hazard models., Results: Among 589 consecutive HCC patients treated with RFA, 70 (11.9%) and 21 (3.6%) patients showed mild and severe bile duct dilatation respectively. Patients with severe dilatation, but not those with mild dilatation, had lower survival and higher HCC recurrence than patients without dilatation. Severe dilatation, but not mild dilatation, was significantly associated with death [hazard ratio (HR) 2.17, P=0.035] and recurrence (HR 2.89, P<0.001)., Conclusion: Whereas mild bile duct dilatation after RFA is clinically negligible, bile duct dilatation affecting two or more subsegments should be regarded as a complication that may affect the prognosis and should be observed carefully., (© 2010 John Wiley & Sons A/S.)

Background: Although radiofrequency ablation (RFA) is widely accepted as a percutaneous treatment for liver tumors; serious complications may occur resulting in 0.1% to 0.5% mortality. This study analyzed the risk factors and management of hemorrhagic complications, such as hemoperitoneum, hemothorax, and hemobilia., Methods: We performed 4133 RFA treatments in 2154 patients with primary and metastatic liver tumors from February 1999 to December 2007. Of these, we enrolled patients with hemorrhagic complications and reviewed their medical records thoroughly. The risk factors for each hemorrhagic complication were analyzed using unconditional logistic regression., Results: Hemorrhagic complications occurred in 63 out of 4133 treatments (1.5%), including hemoperitoneum in 29 (0.7%), hemothorax in 14 (0.3%), and hemobilia in 20 (0.5%). Eleven, 8, and 4 of these patients, respectively, were categorized as major complications requiring blood transfusion or drainage. Two patients died after hemoperitoneum. Logistic regression analysis revealed large tumor size [odds ratio (OR) 1.06 per 1 mm increase in diameter] and low platelet count (OR 0.88 per 10,000/microL increase) were significant risk factors for hemoperitoneum. The location of tumor nodules was a significant risk factor for hemothorax (segment 7, OR 2.31) and hemobilia (segment 1, OR 3.30). Other factors, including the number of needle insertions or the duration of ablation, were not significant., Conclusions: Although hemorrhagic complications were relatively rare with percutaneous RFA, specific treatments, such as blood transfusion and drainage, were required in some cases. Care must be taken, especially in high-risk patients.

Our patient was a 70-year-old man with hepatocellular carcinoma (HCC) and liver cirrhosis (Child-Pugh B). He had a history of distal gastrectomy with Billroth II reconstruction for duodenal ulcer and hepatectomy for HCC. One month after percutaneous radiofrequency ablation (RFA) for recurrent HCC, biliocutaneous fistula was observed. The cholangiogram demonstrated leakage of contrast material from an intrahepatic duct into the fistula, and a nasobiliary catheter was placed. Subsequently, the discharge of bile steadily decreased and stopped. Follow-up cholangiogram revealed no evidence of bile leakage. Biliocutaneous fistula is an extremely rare complication after percutaneous RFA, and the present case report suggests that endoscopic drainage is the first-line therapy for bile leaks after RFA.

Objective: Management of hepatocellular carcinoma is a major problem in the care of patients undergoing regular hemodialysis treatments, mainly because of a high prevalence of hepatitis C virus infection. The purpose of this study was retrospective assessment of the safety and efficacy of percutaneous radiofrequency ablation of hepatocellular carcinoma in the care of patients with end-stage renal disease undergoing regular hemodialysis treatments., Materials and Methods: Between October 2004 and June 2008, 14 carefully selected hemodialysis patients with hepatocellular carcinoma (five naïve, nine recurrent) underwent a total of 19 radiofrequency ablation treatments. An internally cooled or expandable electrode was used. After tumor ablation, the insertion site at the liver surface was subjected to additional ablation to reduce the bleeding risk., Results: The Child-Pugh score was 6 or better in all patients but one. The number of tumors was one or two, and the tumor diameter was 35 mm or less in all treatments. No complication such as intraperitoneal hemorrhage was found in any treatment. Local tumor progression was found after one treatment and was successfully managed with subsequent radiofrequency ablation. During the mean observation period of 343 days, there was only one death, of heart failure, among the five patients with naïve tumors., Conclusion: The safety and effectiveness of radiofrequency ablation were not compromised in this series of selected patients with hepatocellular carcinoma who were undergoing hemodialysis. Radiofrequency ablation is a promising option for small hepatocellular carcinomas in patients undergoing regular hemodialysis treatments.

Background and Aims: Visceral fat accumulation reportedly increases the risk of hepatocellular carcinoma (HCC) development in patients with chronic liver disease. However, it has not been fully elucidated whether visceral fat accumulation increases the risk of HCC recurrence after curative treatment in patients with suspected non-alcoholic steatohepatitis (NASH). Therefore this was investigated in the current study., Methods: 62 patients with naive HCC with suspected NASH were enrolled. All were curatively treated with percutaneous radiofrequency ablation between 1999 and 2006. The visceral fat area (VFA) was determined in each patient from CT images, taken at the time of HCC diagnosis. Patients were divided into two groups based on VFA: the high VFA group (>130 cm(2) in males, >90 cm(2) in females, n = 27) and the others (n = 35). The effects of VFA on HCC recurrence were analysed together with other factors including patients' background, tumour-related factors and liver function-related factors., Results: The cumulative recurrence rates differed significantly between the two groups; 15.9, 56.5 and 75.1% at 1, 2 and 3 years, respectively, in the high VFA group, and 9.7, 31.1 and 43.1%, respectively, in the controls (p = 0.018). Multivariate analysis indicated visceral fat accumulation (risk ratio 1.08, per 10 cm(2), p = 0.046) and older age (risk ratio 1.06 per 1 year, p = 0.04) as independent risk factors of HCC recurrence., Conclusions: Visceral fat accumulation is an independent risk factor of HCC recurrence after curative treatment in patients with suspected NASH.

Background: Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is ordinarily indicated for those with three or fewer nodules, none of which exceeds 3 cm in diameter. This study investigated whether an apparent threshold exists in the diameter and number of nodules in terms of the prognosis of patients with HCC., Methods: We enrolled 663 naïve patients with HCC who were treated with RFA at our hospital between 1999 and 2005. We analyzed the patients' prognosis using multivariate Cox proportional regression with the diameter and number of nodules as covariates and Child-Pugh class as a stratification factor. The diameter and number were categorized as 5 cm and 1, 2-3, 4-5, and >5, respectively., Results: The adjusted hazard ratio of patients whose largest nodule was 5 cm was 1, 1.51, 2.56, 2.25, and 2.71, respectively. The adjusted hazard ratio of patients with one, two or three, four or five, and more than five nodules was 1, 1.35, 1.70, and 2.12, respectively. Therefore, patients with three or fewer nodules, none of which exceeds 5 cm in diameter, have a 5-year survival of 40%., Conclusions: The prognosis of the patients worsened gradually as the diameter and number of nodules increased. No apparent threshold in the diameter or number of HCC nodules was detected. RFA can be applied beyond the conventional indications.

Background: Neoplastic seeding reportedly occurs in up to 12.5% of patients treated with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The aim of this study is to assess the incidence, risk factors, and prognosis of neoplastic seeding after RFA among a large number of patients with a long-term follow-up., Method: From February 1999 to December 2004, 1,031 patients underwent a total of 1,845 treatments with RFA for a total of 3,837 HCC nodules. The following variables were assessed to elucidate the risk factors of neoplastic seeding: age, sex, positivity for viral markers, tumor size, number of tumor nodules, number of RFA sessions, tumor location, percutaneous biopsy prior to RFA, alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP) and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) levels, and the degree of tumor differentiation., Results: Neoplastic seeding was detected in 33 patients (3.2% per patient) at intervals of 4.8-63.8 (median, 15.2) months after RFA. On multivariate logistic regression analysis, only the poor differentiation degree was associated with the risk of neoplastic seeding (P= 0.012). Of tumor factors, tumor size, and AFP, DCP, and AFP-L3 levels were significantly associated with the poor differentiation degree. The cumulative survival rates 1 and 2 yr after the detection of neoplastic seeding were 86% and 47%, respectively., Conclusion: Poor differentiation degree was the risk factor of neoplastic seeding after RFA for HCC. The surrogate markers for poor differentiation degree were larger tumor size and elevated tumor marker levels. Indication for RFA should be carefully considered for HCC patients under these conditions.

Background: Intrapleural fluid infusion improves ultrasonographic visualization of tumours in the hepatic dome. The aim of this study was to assess the safety and long-term efficacy of ultrasonographically guided percutaneous radiofrequency ablation for tumours in the hepatic dome with intrapleural infusion., Methods: Of 2575 patients with hepatocellular carcinoma or hepatic metastases treated with radiofrequency ablation, intrapleural fluid infusion was performed in 587 patients for tumours in the hepatic dome. After the tip of a 14-G metallic needle was positioned in the pleural cavity under ultrasonographic guidance, 500-1000 ml of 5 per cent glucose solution was infused in 5-15 min. Radiofrequency ablation was performed using an internally cooled electrode. Long-term results were evaluated in 347 patients with a single hepatocellular carcinoma who were naive to any treatment., Results: Intrapleural fluid infusion was successfully performed in all 587 patients. The major complication rate on a per tumour basis was similar for patients treated with and without intrapleural infusion (1.6 versus 1.6 per cent; P = 0.924). The overall and recurrence-free survival were both similar for naive patients with a single hepatocellular carcinoma treated with and without intrapleural infusion (P = 0.429 and P = 0.109 respectively). Intrapleural infusion was not associated with lower overall survival in multivariable analysis., Conclusion: With intrapleural fluid infusion, radiofrequency ablation for tumours in the hepatic dome was safe and effective, resulting in satisfactory overall and recurrence-free survival., (Copyright (c) 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background and Aim: Local ablation therapy has been shown to be effective for small hepatocellular carcinoma (HCC); however, HCC recurrence is very frequent even after apparently curative treatment. In particular, recurrent HCC may be more prone to subsequent recurrence, although quantitative data are lacking. The aim of this study was to evaluate the difference in the risk for subsequent recurrence, if any, between primary and recurrent cases., Methods: A retrospective analysis was conducted of 376 patients with HCC (uninodular and 100 ng/mL, treatment other than radiofrequency ablation, HCV antibody positivity, and tumor multinodularity also remained as significant predictors., Conclusion: Hepatocellular carcinoma at second or later recurrence is three times as prone to subsequent recurrence as is primary HCC, when compared with adjustment for other tumor and hepatic factors.

Background: Percutaneous radiofrequency ablation (RFA) of liver tumours adjacent to the gastrointestinal tract is controversial. This study assessed the value of an intraperitoneal water infusion (artificial ascites) technique for percutaneous RFA of such tumours., Methods: Before ablation in 52 patients (55 treatments, 58 tumours), between 250 and 3000 (mean 681) ml 5 per cent glucose solution was infused into the abdominal cavity using a 14-G needle, with the aim of preventing thermal injury by separating the liver from the gastrointestinal tract., Results: There were no adverse events associated with the artificial ascites technique. In 43 (78 per cent) of the 55 treatments, the liver and gastrointestinal tract were separated successfully. In the other 12 treatments, in which the separation was not confirmed by real-time ultrasonography, there was one case of perforation of the ascending colon after RFA; adhesion of the liver and colon resulting from previous laparotomy may have been related to the injury., Conclusion: Production of artificial ascites can be undertaken safely, making RFA safe and effective for hepatic tumours adjacent to the gastrointestinal tract. In patients with possible postoperative adhesions, confirmation of separation of the liver from surrounding organs is mandatory to avoid thermal injury.

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.

Percutaneous radiofrequency (RF) ablation is feasible for the treatment of unresectable hepatocellular carcinoma, and experience at the authors' institution during 5 years indicates that percutaneous RF ablation can be performed safely in most cases. However, early or late complications related to mechanical or thermal damage may be observed at follow-up examination. Complications may be classified in three groups: vascular (eg, portal vein thrombosis, hepatic vein thrombosis with partial hepatic congestion, hepatic infarction, and subcapsular hematoma), biliary (eg, bile duct stenosis and biloma, abscess, and hemobilia), and extrahepatic (eg, injury to the gastrointestinal tract, injury to the gallbladder, pneumothorax and hemothorax, and tumor seeding). Most complications can be managed with conservative treatment, percutaneous or endoscopic drainage, or surgical repair. Because an early and accurate diagnosis is necessary for proper management, radiologists should be familiar with the imaging features of each type of complication., (Copyright RSNA, 2005.)

Background & Aims: Percutaneous radiofrequency ablation is a recently introduced treatment for hepatocellular carcinoma, whereas ethanol injection is now a standard therapy. We compared their long-term outcomes., Methods: Two hundred thirty-two patients with hepatocellular carcinoma who had 3 or fewer lesions, each 3 cm or less in diameter, and liver function of Child-Pugh class A or B were entered onto a randomized controlled trial. The primary end point was survival, and the secondary end points were overall recurrence and local tumor progression., Results: One hundred eighteen patients were assigned to radiofrequency ablation and 114 to ethanol injection. The number of treatment sessions was smaller (2.1 times vs 6.4 times, respectively, P < .0001) and the length of hospitalization was shorter (10.8 days vs 26.1 days, respectively, P < .0001) in radiofrequency ablation than in ethanol injection. Four-year survival rate was 74% (95% CI: 65%-84%) in radiofrequency ablation and 57% (95% CI: 45%-71%) in ethanol injection. Radiofrequency ablation had a 46% smaller risk of death (adjusted relative risk, 0.54 [95% CI: 0.33-0.89], P = .02), a 43% smaller risk of overall recurrence (adjusted relative risk 0.57 [95% CI: 0.41-0.80], P = .0009), and an 88% smaller risk of local tumor progression (relative risk, 0.12 [95% CI: 0.03-0.55], P = .006) than ethanol injection. The incidence of adverse events was not different between the 2 therapies., Conclusions: Judging from higher survival but similar adverse events, radiofrequency ablation is superior to ethanol injection for small hepatocellular carcinoma.

Background and Aims: Percutaneous tumour ablation (PTA), such as ethanol injection and radiofrequency ablation, is now recognised as a primary treatment for hepatocellular carcinoma (HCC). Although PTA is a relatively safe procedure, it can cause biliary obstruction as a rare complication. As patients with cirrhosis undergoing surgery or endoscopic retrograde cholangiopancreatography/sphincterotomy have a high mortality rate from bleeding, we adopted the use of endoscopic papillary balloon dilatation (EPBD) in these patients and now report the results. We retrospectively analysed the incidence of biliary obstruction after PTA and the efficacy of treatment with EPBD., Patients and Methods: A total of 1043 patients with HCC were treated by PTA, of whom 538 were treated with transarterial embolisation with up to eight years of follow up., Results: There were 17 (1.6%) cases of hilar obstruction due to tumour progression and 35 (3.4%) cases of extrahepatic obstruction. Apart from the expected causes of biliary obstruction (haemobilia n = 11, gallstones n = 11, and three miscellaneous causes), we found that 10 patients had obstruction due to biliary casts. This is the first description of biliary casts after percutaneous tumour ablation therapy. Extrahepatic biliary obstruction by procedure related haemobilia occurred within three days of PTA while other causes occurred between 0 and 17 (average 4.9) months. Biliary casts occurred more frequently after ethanol injection than after radiofrequency ablation. EPBD successfully dissipated biliary obstruction in 33 of 35 cases, while two died due to hepatic failure despite successful drainage., Conclusions: Extrahepatic biliary obstruction is an uncommon complication after PTA for HCC, and can be safely and effectively treated with EPBD, despite impaired liver function.

The dropout from the waiting list for liver transplantation among patients with hepatocellular carcinoma (HCC) is reportedly as high as 12% to 40% per year, mostly due to tumor progression. Considering the scarcity of donor organs, it would be beneficial if we could retain them within the Milan criteria with a bridging therapy. We retrospectively analyzed the prognosis of 288 HCC patients with relatively preserved liver function we treated with ablation therapy between 1997 and 2001, concentrating on whether they subsequently remained in the criteria, and analyzed the risk factors of dropout with Cox proportional hazards model. During a median follow-up period of 39 months (range, 1-86 months), 33 (11%) died without tumor progression, while 85 (30%) dropped out due to tumor progression. The overall dropout rate was 9.0% and 32.8% at 1 and 3 years, respectively, and that due to tumor progression was 6.2% and 23.0%. Cox regression analysis indicated that a high serum level of alpha-fetoprotein or des-gamma-carboxy prothrombin, and a tumor size exceeding 3 cm in diameter affected the dropout due to tumor progression, while low albumin concentration was a risk factor of death independently of tumor progression. In conclusion, local ablation therapy for HCC was effective in containing the tumor progression within the Milan criteria in selected patients.

Background: Radiofrequency ablation (RFA) was introduced recently as a therapeutic modality for hepatocellular carcinoma (HCC), an alternative to percutaneous ethanol injection therapy (PEIT), which is coming into use worldwide. Previously reported treatment efficacy and complication rates have varied considerably., Methods: Between February 1999 and February 2003, the authors performed 1000 treatments of RFA to 2140 HCC nodules in 664 patients with a cooled-tip electrode at the University of Tokyo Hospital (Tokyo, Japan). Short-term and long-term complications were analyzed by treatment and session basis. Cumulative survival was also assessed in 319 patients who received RFA as primary treatment (naive patients) and 345 patients who received RFA for recurrent tumor after previous treatment including resection, PEIT, microwave coagulation therapy, and transarterial embolization (nonnaive patients)., Results: A total of 40 major complications (4.0% per treatment, 1.9% per session) and 17 minor complications (1.7% per treatment, 0.82% per session) were observed during the observation period until March 31, 2004. There were no treatment-related deaths. Surgical intervention was required in one case each of bile peritonitis and duodenal perforation. The cumulative survival rates at 1, 2, 3, 4, and 5 years were 94.7%, 86.1%, 77.7%, 67.4%, and 54.3% for naive patients, whereas the cumulative survival rates were 91.8%, 75.6%, 62.4%, 53.7%, and 38.2% for nonnaive patients, respectively., Conclusions: The authors confirmed the safety and efficacy of RFA for HCC in a large-scale series and long-term prognosis was satisfactory.

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.

In Japan, approximately 30,000 patients died of hepatocellular carcinoma (HCC) in 2003. Ten percent had hepatitis B virus infection and 80% had hepatitis C virus (HCV) infection, indicating that viral hepatitis accounted for >90% of cases of HCC. In comparison, only 3% (1.5%, hepatitis B virus; 1.5%, HCV) of the general population is infected with these viruses. We treated 1238 patients between 1992 and the end of 2003 by means of percutaneous tumor ablation (PTA): 524 patients, by percutaneous ethanol injection therapy (PEIT); 85 patients, by percutaneous microwave coagulation therapy; and 629 patients, by radiofrequency ablation (RFA). Three-, 5-, 7-, and 10-year survival rates of the 1238 patients were 69%, 50%, 34%, and 19%, respectively. When limited to tumors

We have performed percutaneous tumor ablation (PTA) including percutaneous ethanol injection therapy (PEIT) for 90% of the patients with hepatocellular carcinoma. Until December 1998, the 793 patients received PTA, 5 years survival rate reached 39.8%. Excluding the patients with Child C whose hepatic function were extremely low, 5 years survival rate reached to the level of 41.2%. Since 5 years survival rate in stage IV-A reached 24.4%, the patients of stage IV-A may be considered to have an indication for PTA. We have confirmed the effectiveness of the local treatment including radiotherapy for advanced hepatocellular carcinoma with portal vein invasion. We are attempting to perform PTA for the extra-hepatic lesions that had no indication of other treatment. However the indication of PTA is limited by the presence of diffuse nodules, exacerbation of the hepatic function, or tumor invasion to portal vein, bile duct, inferior vena cava.