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Objectives: This study aimed to evaluate the incidence and clinical implications of bile duct changes following multibipolar radiofrequency ablation (mbpRFA) for hepatocellular carcinoma (HCC)., Materials and Methods: Radiological, clinical, and biological data from consecutive cirrhotic patients who underwent first-line mbpRFA between 2007 and 2014 for uninodular HCC ≤ 5 cm were retrospectively collected. Follow-up imaging was reviewed to identify bile duct changes and factors associated with biliary changes were assessed using multivariable analysis. Baseline and 6-month liver function tests were compared in patients with and without bile duct changes. Complications, cirrhosis decompensation, and survival rates were compared in both groups., Results: A total of 231 patients (mean age 68 years [39-85], 187 men) underwent 266 mbpRFA sessions for uninodular HCC (mean size 26 mm). Of these, 76 (33%) developed bile duct changes (upstream bile duct dilatations and/or bilomas) with a mean onset time of 3 months. Identified risk factors for these changes were the infiltrative aspect of the tumor (p = 0.035) and its location in segment VIII (p < 0.01). The average increase in bilirubin at 6 months was higher in the group with biliary changes (+2.9 vs. +0.4 µg/mL; p = 0.03). There were no significant differences in terms of complications, cirrhosis decompensation at 1 year (p = 0.95), local and distant tumor progression (p = 0.91 and 0.14 respectively), and overall survival (p = 0.4) between the two groups., Conclusion: Bile duct changes are common after mbpRFA for HCC, especially in tumors with an infiltrative aspect or those located in segment VIII. These changes do not appear to negatively impact the course of cirrhosis at 1 year or overall survival., Clinical Relevance Statement: Bile duct changes following mbpRFA for HCC are relatively common. Nevertheless, they do not raise clinical concerns in terms of complications, deterioration in liver function, or survival rates. Consequently, specific monitoring or interventions for these bile duct changes are not warranted., Key Points: • Bile duct changes are frequently observed after multibipolar radiofrequency ablation for hepatocellular carcinoma, occurring in 33% of cases in our study. • Patients with bile duct changes exhibited a higher increase in bilirubin levels at 6 months but no more cirrhosis decompensation or liver abscesses. • Biliary changes following multibipolar radiofrequency ablation for hepatocellular carcinoma are not alarming and do not necessitate any specific monitoring or intervention., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Introduction: We aim to assess the long-term outcomes of percutaneous multi-bipolar radiofrequency (mbpRFA) as the first treatment for hepatocellular carcinoma (HCC) in transplant-eligible cirrhotic patients, followed by salvage transplantation for intrahepatic distant tumour recurrence or liver failure., Materials and Methods: We included transplant-eligible patients with cirrhosis and a first diagnosis of HCC within Milan criteria treated by upfront mbp RFA. Transplantability was defined by age <70 years, social support, absence of significant comorbidities, no active alcohol use and no recent extrahepatic cancer. Baseline variables were correlated with outcomes using the Kaplan-Meier and Cox models., Results: Among 435 patients with HCC, 172 were considered as transplantable with HCCs >2 cm (53%), uninodular (87%) and AFP >100 ng/mL (13%). Median overall survival was 87 months, with 75% of patients alive at 3 years, 61% at 5 years and 43% at 10 years. Age (p = .003) and MELD>10 (p = .01) were associated with the risk of death. Recurrence occurred in 118 patients within Milan criteria in 81% of cases. Local recurrence was observed in 24.5% of cases at 10 years and distant recurrence rates were observed in 69% at 10 years. After local recurrence, 69% of patients were still alive at 10 years. At the first tumour recurrence, 75 patients (65%) were considered transplantable. Forty-one patients underwent transplantation, mainly for distant intrahepatic tumour recurrence. The overall 5-year survival post-transplantation was 72%, with a tumour recurrence of 2.4%., Conclusion: Upfront multi-bipolar RFA for a first diagnosis of early HCC on cirrhosis coupled with salvage liver transplantation had a favourable intention-to-treat long-term prognosis, allowing for spare grafts., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: HCC surveillance is challenged by the detection of hepatic focal lesions (HFLs) of other types. This study aimed to describe the incidence, characteristics, outcomes, and costs of non-HCC HFL detected during surveillance., Approach and Results: We retrospectively analyzed nonstandardized workup performed in French patients included in HCC surveillance programs recruited in 57 French tertiary centers (ANRS CirVir and CIRRAL cohorts, HCC 2000 trial). The overall cost of workup was evaluated, with an estimation of an average cost per patient for the entire population and per lesion detected. A total of 3295 patients were followed up for 59.8 months, 391 (11.9%) patients developed HCCs (5-year incidence: 12.1%), and 633 (19.2%) developed non-HCC HFLs (5-year incidence: 21.8%). Characterization of non-HCC HFL required a median additional of 0.7 exams per year. A total of 11.8% of non-HCC HFLs were not confirmed on recall procedures, and 19.6% of non-HCC HFLs remained undetermined. A definite diagnosis of benign liver lesions was made in 65.1%, and malignant tumors were diagnosed in 3.5%. The survival of patients with benign or undetermined non-HCC HFL was similar to that of patients who never developed any HFL (5-year survival 92% vs. 88%, p = 0.07). The average cost of the diagnostic workup was 1087€ for non-HCC HFL and €1572 for HCC., Conclusions: Non-HCC HFLs are frequently detected in patients with cirrhosis, and do not impact prognosis, but trigger substantial costs. This burden must be considered in cost-effectiveness analyses of future personalized surveillance strategies., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Aggressive intrasegmental recurrence (AIR) is a form of local recurrence associated with a dismal prognosis and defined by multiple nodules or by an infiltrative mass with a tumor thrombus, occurring in the treated segment, after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to identify radiological and/or histological characteristics of tumor biopsy predictive of AIR. We retrospectively analyzed patients treated by No-Touch multi-bipolar RFA (mbpRFA) for a first HCC with a systematic per-procedural tumor biopsy positive for diagnosis of HCC. The first recurrence was classified as non-aggressive local recurrence, AIR or intrahepatic distant recurrence. 212 patients were included (168 men; mean age 67.1 years; mean tumor size 28.6 mm, 181 cirrhosis). AIR occurred in 21/212 patients (10%) and was associated with a higher risk of death (57% in patients with AIR vs 30% without AIR, p = 0.0001). Non-smooth tumor margins, observed in 21% of the patients and macro-trabecular massive histological subtype, observed in 12% of the patients were independently related to a higher risk of AIR (HR: 3.7[1.57;9.06], p = 0.002 and HR:3.8[2.47;10], p = 0.005 respectively). Non smooth margins at imaging and macro-trabecular massive histological subtype are associated with AIR and could be considered as aggressive features useful to stratify therapeutic strategy., (© 2022. The Author(s).)

Background: The ABO blood group system may influence tumorigenesis, but its prognostic value in liver transplantation (LT) for hepatocellular carcinoma (HCC) has never been assessed., Methods: All consecutive patients who underwent LT for HCC between 2013 and 2017 at 9 centers were analyzed. Predictors of tumor recurrence were identified using multivariable analysis, while comparison between group A and non-A recipients was performed after propensity score matching., Results: Among 925 LT recipients, 406 were blood group A, 94 group B, 380 group O, and 45 group AB. On multivariable analysis, group A was associated with tumor recurrence (hazard ratio [HR] = 1.574 [95% confidence interval; 95% CI = 1.034-2.394] P = 0.034). After propensity score matching, 1- and 5-y recurrence rates were 7.4% and 20.1% in group A recipients versus 3.3% and 13.2% in non-A recipients (HR = 1.66 [95% CI = 1.12-2.45], P = 0.011). One and 5-y recurrence-free survivals were 85.2% and 66.8% in group A recipients versus 88.5% and 71.3% in non-A recipients (HR = 1.38 [95% CI = 1.01-1.90], P = 0.045). Among recipients within Milan criteria (n = 604), 1- and 5-y recurrence rates were 5.8% and 12.7% in group A recipients versus 3.1% and 12.2% in non-A recipients (HR = 1.197 [95% CI = 0.721-1.987], P = 0.485). Among recipients outside Milan criteria (n = 182), 1- and 5-y recurrence rates were 12.1% and 43.8% in group A recipients versus 3.9% and 15.6% in non-A recipients (HR = 3.175 [95% CI = 1.526-6.608], P = 0.002)., Conclusions: ABO blood system influences the oncological outcome of recipients undergoing LT for HCC. Its incorporation in the prognostication model of LT for HCC may allow improving the management of LT candidates., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The percutaneous ablation of subcapsular hepatocellular carcinoma (S-HCC) may involve a risk of complications such as hemorrhage and tumor seeding, mainly linked to the direct tumor puncture often inevitable with mono-applicator ablation devices. The purpose of this study was to assess the efficacy and safety of no-touch multi-bipolar radiofrequency ablation (NTMBP-RFA) for the treatment of S-HCC ≤ 5 cm not puncturable via the non-tumorous liver parenchyma., Materials and Methods: Between September 2007 and December 2014, 58 consecutive patients (median age: 63 years [46-86], nine females) with 59 S-HCC ≤ 5 cm (median diameter: 25 mm [10-50 mm]), not puncturable via the non-tumorous liver parenchyma, were treated with NTMBP-RFA. Response and follow-up were assessed by CT or MRI. Complications were graded using the Cardiovascular and Interventional Radiological Society of Europe classification. Overall local tumor progression (OLTP)-free survival was assessed using the Kaplan-Meier method. A Cox proportional model evaluated the factors associated with OLTP. Signs of peritoneal or parietal tumor seeding were noted during follow-up imaging studies., Results: A complete ablation was achieved in 57/58 patients (98.3%) after one (n = 51) or two (n = 6) procedures. Three patients (5.2%) experienced complications (sepsis, cirrhosis decompensation; CIRSE grade 2 or 3). After a median follow-up period of 30.5 months [1-97], no patients had tumor seeding. The 1, 2 and 3-year OLTP-free survival rates were 98%, 94% and 91%, respectively. No factors were associated with OLTP., Conclusion: NTMBP-RFA is a safe and effective treatment for S-HCC not puncturable via the non-tumorous liver parenchyma.

Aims: To evaluate the diagnostic performance of CT, MRI and CEUS alone and in combination, for the diagnosis of HCC between 10 and 30 mm, in a large population of cirrhotic patients., Patients and Methods: In a multicentre prospective trial, 442 patients have been enrolled. Within a month, CEUS, CT and MRI were performed for all patients. A composite algorithm was defined to obtain the more accurate gold standard., Results: A total of 544 nodules in 381 patients have been retained for the performance analysis. Eighty-two percent of the patients were male, mean age was 62 years. For the 10-20 mm nodules (n=342), the sensitivity (Se) and specificity (Sp) for the diagnosis of HCC were, respectively, 70.6% and 83.2% for MRI, 67.9% and 76.8% for CT and 39.6% and 92.9% for CEUS. For the 20-30 mm nodules (n=202), the Se and Sp were, respectively, 72.3% and 89.4% for MRI, 71.6% and 93.6% for CT and 52.9% and 91.5% for CEUS. THE BEST COMBINATION FOR THE 10-20 MM NODULES WAS MRI + CT (SE: 55.1%, SP: 100.0%).: After a first inconclusive technique, CEUS as second image technique allowed the highest specificity with only a slight drop of sensitivity for 10-20 mm nodules and the highest sensitivity and specificity for 20-30 mm nodules., Conclusion: This large multicentre study validates the EASL/AASLD recommendations in daily practice. Specificity using CT or MRI in 10-20 mm HCC was low, but we do not recommend combined imaging at first as sensitivity would be very low. The best sequential approach combined MRI and CEUS., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose To assess the safety and efficacy of irreversible electroporation (IRE) in the treatment of patients with inoperable hepatocellular carcinoma (HCC) who are ineligible for thermal ablative techniques. Materials and Methods This retrospective study was approved by an ethics review board, and the requirement to obtain informed written consent was waived. From March 2012 to June 2015, 58 patients (median age, 65.4 years; range 41.6-90 years) with cirrhosis received IRE for the treatment of 75 HCC tumors. The median tumor diameter was 24 mm (range, 6-90 mm). IRE was selected because of tumor location (48 patients) or the patient's poor general condition (10 patients). Treatment response was assessed with magnetic resonance (MR) imaging 1 month after treatment and every 3 months thereafter. Overall local tumor progression-free survival (PFS) per nodule (including initial treatment failures) was assessed by using the Kaplan-Meier method. The marginal Cox proportional hazards model was used to assess the factors associated with overall local tumor PFS. Complications were recorded and graded according to the Clavien-Dindo classification. Results Of 75 tumors, 58 (77.3%), 67 (89.3%), and 69 (92%) were completely ablated after one, two, and three IRE procedures, respectively. After a median follow-up of 9 months (range, 3 days to 31 months), the 6- and 12-month overall local tumor PFS rates for the 75 treated nodules were 87% (95% confidence interval [CI]: 77%, 93%) and 70% (95% CI: 56%, 81%), respectively. A preablative serum α-fetoprotein level higher than 200 ng/mL (hazard ratio: 9.94 [95% CI: 2.82, 35.06], P = .0004) was the only factor linked with overall local tumor PFS. Complications occurred in 11 of the 58 patients (19%) and were classified as grade I in three patients, grade II in five patients, grade IV in two patients, and grade V in one patient. The three (5.2%) complications classified as grade III or higher were liver failures occurring in patients with Child-Pugh class B disease; one led to death. Conclusion IRE offers safe, complete ablation of HCC tumors in patients with contraindications to other commonly used ablative techniques. © RSNA, 2017 Online supplemental material is available for this article.

Background & Aims: The primary aim of this study was to compare the rate of global radiofrequency ablation (RFA) failure between monopolar RFA (MonoRFA) vs. no-touch multi-bipolar RFA (NTmbpRFA) for small hepatocellular carcinoma (HCC) ⩽5cm in cirrhotic patients., Methods: A total of 362 cirrhotic patients were included retrospectively across four French centres (181 per treatment group). Global RFA failure (primary RFA failure or local tumour progression) was analysed using the Kaplan-Meier method after coarsened exact matching. Cox regression models were used to identify factors associated with global RFA failure and overall survival (OS)., Results: Patients were well matched according to tumour size (⩽30/>30mm); tumour number (one/several); tumour location (subcapsular and near large vessel); serum AFP (<10; 10-100; >100ng/ml); Child-Pugh score (A/B) and platelet count (30mm and HCC near large vessel were independent factors associated with global RFA failure. Five-year OS was 37.2% following MonoRFA vs. 46.4% following NTmbpRFA p=0.378., Conclusions: This large multicentre case-matched study showed that NTmbpRFA provided better primary RFA success and sustained local tumour response without increasing severe complications rates, for HCC ⩽5cm., Lay Summary: Using no-touch multi-bipolar radiofrequency ablation for hepatocellular carcinoma ⩽5cm provide a better sustained local tumour control compared to monopolar radiofrequency ablation., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: The goal of this study was to retrospectively evaluate the results of imaging-guided percutaneous ablation in patients with controlled intrahepatic hepatocellular carcinoma (HCC) with limited extrahepatic disease., Materials and Methods: Eleven patients with limited extrahepatic disease and/or potential short-term clinical manifestations with controlled primary intrahepatic HCC were included into the study. There were nine men and two women, with a mean age of 67.4 years±10.2 (SD) (range: 54-85 years). All patients had extrahepatic disease treated by either radiofrequency ablation or electroporation. Extrahepatic disease consisted of lymph node metastases (5 patients), tumor seeding along a needle tract (3 patients), adrenal gland metastasis, bone metastasis and pulmonary metastasis (one patient each)., Results: Response to treatment was complete in 7/11 patients (64%). The mean survival time after treatment was 18.8±12.7 (SD) months (median, 16 months; range: 4-42 months). No severe complications associated with percutaneous treatment were observed., Conclusion: Our results suggest that imaging-guided percutaneous ablation techniques should be considered as a useful option for the treatment of extrahepatic disease in patients with HCC. Further studies are needed, however to fully determine the potential role of these techniques in this elective application., (Copyright © 2016 Editions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Purpose To assess the long-term outcome in 108 consecutive patients treated with no-touch multibipolar radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) that met the Milan criteria. Materials and Methods This retrospective study was approved by the ethical review board, and the need to obtain informed consent was waived. Between November 1, 2006, and December 31, 2011, 132 HCC tumors (diameter, 10-45 mm; 39 tumors ≥ 30 mm) in 108 consecutive patients (106 with cirrhosis) that met Milan criteria were treated with no-touch multibipolar RFA, which consisted of activating, in bipolar mode, three or four electrodes inserted just beyond the tumor margins. Follow-up was performed every 3 months for 2 years and every 6 months thereafter with computed tomographic or magnetic resonance imaging. Survival probabilities were computed by using the Kaplan-Meier method. Predictive factors of tumor progression and overall survival were assessed by using the Cox proportional hazard model. Results No technical failure occurred, and complete ablation was achieved for all the nodules. After a median of 40.5 months (range, 2-84 months) of follow-up, 3- and 5-year local and overall tumor progression-free survival were 96%, 94%, 52%, and 32%, respectively. Neither tumor diameter greater than 30 mm nor location abutting a large vessel were associated with local tumor progression. Tumor diameter greater than 30 mm was the only parameter predictive of overall tumor progression (P = .0036). Independent factors associated with shorter overall survival were Child-Pugh class B disease, age greater than 65 years, and platelet count of less than 150 g/L (P < .003). Three major complications occurred (2.7%): hemothorax in one patient and liver failure in two, with major portal-systemic shunts. One patient (0.9%) died, and one underwent transplantation. Conclusion No-touch multibipolar RFA for HCC tumors that meet Milan criteria provides a high local tumor progression-free survival rate. An ongoing randomized trial might help to clarify the role of this new approach for the treatment of early HCC. (©) RSNA, 2016 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 30, 2016.

Purpose: To compare histopathologically the completeness of radiofrequency (RF) ablation to treat hepatocellular carcinoma (HCC) with monopolar or multipolar technique., Materials and Methods: Thirty-five consecutive patients (mean age, 59 y) with cirrhosis and HCC (n = 59) within Milan criteria received RF ablation and subsequently underwent liver transplantation (LT) for tumor progression or liver failure. Data were extracted retrospectively from a prospective database. Thirty nodules were treated with a monopolar device with internally cooled (n = 17) or perfused (n = 13) electrodes, and 29 were treated with a multipolar technique with internally cooled electrodes based on the "no-touch" concept. This consisted of inserting two or three straight electrodes around the nodule to avoid intratumor puncture to the greatest extent possible. Effectiveness of the three devices was compared by histopathologic examination of explants. Fisher exact and χ(2) tests and multivariate logistic regression analysis were performed., Results: Mean sizes of nodules ablated (25, 22, and 21.6 mm) and median times from ablation to LT (11, 7.5, and 8.4 months) for patients treated with the monopolar internally cooled electrode device (MoICD), monopolar perfused electrode device (MoPED), and multipolar internally cooled electrode device (MuICD), respectively, were similar (P = .8 and P = .9, respectively). Pathologic examination showed complete necrosis for eight of 17 and six of 13 nodules treated with the MoICD and MoPED, respectively, versus 26 of 29 treated with the MuICD (P = .0019). In multivariate analysis, RF technique remained the predictive factor for complete necrosis (P = .005)., Conclusions: Ablation of small HCCs with multipolar RF ablation based on the no-touch concept improves the rate of complete necrosis during pathologic examination compared with monopolar techniques., (Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The prognosis of hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA) is mainly linked to tumor recurrence. So far, no tissue biomarker of recurrence has been validated in biopsy samples. We aimed at investigating the prognostic value of tissue biomarkers in HCC biopsy samples of patients treated with RFA., Methods: All consecutive naive patients from 3 university hospitals, with compensated cirrhosis, early-stage (BCLC 0/A) uninodular HCC treated with RFA, and available tumor biopsy, were included. Edmondson's grade, and the expression of cytokeratin 19, glutamine synthase, beta-catenin, epithelial cell adhesion molecule (EpCAM), and endothelial cell-specific molecule 1 (ESM-1) were assessed. Main clinical end points were overall and early recurrence. Statistical analyses were performed using Kaplan Meier, Log-rank test, and Cox models., Results: 150 patients were included. Recurrence, death or liver transplantation occurred in 85, 51, and 12 patients, respectively. Median follow-up was 27months. ESM-1 expression by HCC stromal endothelial cells was observed in 58 patients (40%) and was associated with higher serum AFP levels, larger tumor, and more frequent expression of EpCAM and surrogate markers of activation of the Wnt-ß-catenin pathway. The 2 independent predictive factors of overall recurrence were serum AFP (HR 1.11 [1.002; 1.22], p=0.045) and ESM-1 expression (HR 1.56 [1.004; 2.43], p=0.048). ESM-1 expression was also an independent predictive factor of early recurrence (HR 1.81 [1.02; 3.21], p=0.042)., Conclusions: ESM-1 expression by stromal endothelial cells, in tumor biopsy samples, has an independent predictive value of early recurrence after RFA., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Proteoglycans are involved in neoangiogenesis and transduction of oncogenic signals, two hallmarks of carcinogenesis., Methods: This study sought to assess the prognostic value of serum levels of three proteoglycans (endocan, syndecan-1, and glypican-3) and VEGF in 295 patients with alcoholic cirrhosis: 170 without hepatocellular carcinoma, 58 with early hepatocellular carcinoma, and 67 with advanced hepatocellular carcinoma at inclusion. We analyzed the association between proteoglycan levels and prognosis using Kaplan-Meier and Cox methods., Results: Serum levels of the three proteoglycans and VEGF were increased in patients with advanced hepatocellular carcinoma compared with those without hepatocellular carcinoma or with early hepatocellular carcinoma. In multivariate analysis, high levels of serum endocan (>5 ng/mL) were independently associated with death [HR, 2.84; 95% confidence interval (CI,) 1.18-6.84; P = 0.02], but not with hepatocellular carcinoma occurrence, in patients without hepatocellular carcinoma at baseline. High serum endocan (>5 ng/mL) and syndecan-1 (>50 ng/mL) levels were significantly associated with greater risk of tumor recurrence (P = 0.025) in patients with early hepatocellular carcinoma treated by radiofrequency ablation. In patients with advanced hepatocellular carcinoma, high serum levels of endocan (P = 0.004) and syndecan-1 (P = 0.006) were significantly associated with less favorable overall survival. However, only a high level of serum syndecan-1 (>50 ng/mL) was independently associated with greater risk of death (HR, 6.21 95% CI, 1.90-20.30; P = 0.0025)., Conclusion: Serum endocan and syndecan-1 are easily assessable prognostic serum biomarkers of overall survival in alcoholic cirrhosis with and without hepatocellular carcinoma., Impact: These new biomarkers will be useful to manage patients with hepatocellular carcinoma developed on alcoholic cirrhosis., (©2013 AACR)

Purpose: The objective of this study was to assess the results and tolerance of radiofrequency ablation in patients with cirrhosis and hepatocellular carcinoma (HCC) older than 75 years., Patients and Methods: Over a period of 9 years from January 2001, 235 patients with cirrhosis and 3 or less HCC≤5 cm of diameter were treated by radiofrequency ablation. Among them, 52 patients older than 75 years were selected for this study., Results: The mean age was 79.4±3. 5 years. There were 36 males, cirrhosis was classified Child-Pugh class A (n=52) related to alcohol (n=13), HCV infection (n=33), or other causes (n=6). The mean tumour diameter was 32.5±10.6 mm, and 14 patients had a multifocal HCC. A complete ablation was obtained in 50/52 patients (96%). No severe complication occurred. The estimated overall survival rates were 62%, 52% and 36% at 3 years, 4 years and 5 years, respectively; it was similar to those observed in patients younger than 75 years., Conclusion: In patients with cirrhosis older than 75 years, radiofrequency ablation of 3 or less HCC≤5cm is well tolerated and survivals rates are similar to those of younger patients., (Copyright © 2011 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Background & Aims: Genetic dimorphisms modulate the activities of several pro- or antioxidant enzymes, including myeloperoxidase (MPO), catalase (CAT), manganese superoxide dismutase (SOD2), and glutathione peroxidase 1 (GPx1). We assessed the role of the G(-463)A-MPO, T(-262)C-CAT, Ala16Val-SOD2, and Pro198Leu-GPx1 variants in modulating HCC development in patients with HCV-induced cirrhosis., Methods: Two hundred and five patients with HCV-induced, biopsy-proven cirrhosis but without detectable HCC at inclusion were prospectively followed-up for HCC development. The influence of various genotypes on HCC occurrence was assessed with the Kaplan-Meier method., Results: During follow-up (103.2±3.4 months), 84 patients (41%) developed HCC, and 66 died. Whereas the Ala16Val-SOD2 or Pro198Leu-GPx1 dimorphisms did not modulate the risk, HCC occurrence was increased in patients with either the homozygous GG-MPO genotype (HR=2.8 [1.7-4.4]; first quartile time to HCC occurrence: 45 vs. 96 months; LogRank <0.0001) or the homozygous CC-CAT genotype (HR=1.74 [1.06-2.82]; first quartile time to HCC occurrence: 55 vs. 96 months; LogRank=0.02). Compared to patients with neither of these two at risk factors, patients with only the CC-CAT genotype had a HR of 2.05 [0.9-4.6] (p=0.08) and patients with only the GG-MPO genotype had a HR of 3.8 [1.5-9.1] (p=0.002), while patients with both risk factors had an HR of 4.8 [2.2-10.4] (p<0.0001). However, only the GG-MPO genotype was independently associated with the HCC risk in multivariate Cox analysis., Conclusions: The high activity-associated GG-MPO genotype increases the rate of HCC occurrence in patients with HCV-induced cirrhosis., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma is responsible for around 6 000 deaths each year in France. About 90% of patients have underlying liver cirrhosis. The annual incidence rate in such patients is estimated at between 2% and 4%, but it is largely dependent on the cause and severity of the underlying liver disease, as well as on epidemiological factors such as age, sex, and the body mass index. Multiple genetic polymorphisms are also involved. Screening for hepatocellular carcinoma is indicated for patients with cirrhosis, based on ultrasonographic examination every six months. It allows early diagnosis and curative treatment in most cases but is still under-used.

Background & Aims: In patients with hepatocellular carcinoma (HCC) within the Milan criteria, liver transplantation (LT) may be the best therapeutic option. However, the shortage of grafts, leads to attempt liver resection (LR) or radiofrequency ablation (RFA) as a first-line treatment for patients with Child-Pugh A cirrhosis., Methods: We report results, obtained between 2000 and 2007 from a single center, involving 67 patients (mean age: 57 years) eligible for LT, who were treated with RFA, followed by LT if there was recurrence or liver failure., Results: Eighty three tumors were treated (mean size: 29±9 mm; 16 binodular forms). RFA achieved complete ablation in 96% of nodules. No mortality occurred. During a post-RFA median follow-up of 48 months, 38 patients experienced recurrence, corresponding to a 5-year recurrence rate of 58%. Of these, 14 patients did not receive a transplant because they fell outside the Milan criteria, 21 were transplanted, and 3 were treated by RFA after refusing LT. Binodularity (95% CI HR=2, 1.0-4.0; p=0.049) was the unique risk factor for recurrence. By the study's end-point, 24 patients had undergone LT (21 for HCC recurrence and three for liver failure). No HCC recurrence occurred after LT. Among the 43 non-transplant patients, 12 died due to HCC progression, and 27 were alive without detectable viable tumor. The probability rates for 5-year overall and tumor-free survival were 74% and 69%, respectively., Conclusions: First line RFA followed by salvage LT allows survival figures that are at least as good as a first-line LT, while limiting the number of grafts., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Unlabelled: Detection of small hepatocellular carcinoma (HCC) eligible for curative treatment is increased by surveillance, but its optimal periodicity is still debated. Thus, this randomized trial compared two ultrasonographic (US) periodicities: 3 months versus 6 months. A multicenter randomized trial was conducted in France and Belgium (43 sites). Patients with histologically proven compensated cirrhosis were randomized into two groups: US every 6 months (Gr6M) or 3 months (Gr3M). For each focal lesion detected, diagnostic procedures were performed according to European Association for the Study of the Liver guidelines. Cumulative incidence of events was estimated, then compared using Gray's test. The prevalence of HCC ≤30 mm in diameter was the main endpoint. A sample size of 1,200 patients was required. A total of 1,278 patients were randomized (Gr3M, n = 640; Gr6M, n = 638; alcohol 39.2%, hepatitis C virus 44.1%, hepatitis B virus 12.5%). At least one focal lesion was detected in 358 patients (28%) but HCC was confirmed in only 123 (9.6%) (uninodular 58.5%, ≤30 mm in diameter 74%). Focal-lesion incidence was not different between Gr3M and Gr6M groups (2-year estimates, 20.4% versus 13.2%, P = 0.067) but incidence of lesions ≤10 mm was increased (41% in Gr3M versus 28% in Gr6M, P = 0.002). No difference in either HCC incidence (P = 0.13) or in prevalence of tumors ≤30 mm in diameter (79% versus 70%, P = 0.30) was observed between the randomized groups., Conclusion: US surveillance, performed every 3 months, detects more small focal lesions than US every 6 months, but does not improve detection of small HCC, probably because of limitations in recall procedures., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Background & Aims: The expression of biliary lineage markers such as cytokeratin (K) 7 by hepatocytes is thought to reflect an altered regeneration pathway recruiting a stem cell compartment, more prone to carcinogenesis. We aimed to investigate the presence of these so-called intermediate hepatobiliary cells (IHC) in liver biopsies of patients with hepatitis C-related cirrhosis and their potential influence on the subsequent occurrence of hepatocellular carcinoma (HCC)., Methods: From a cohort of patients with hepatitis C-related cirrhosis, prospectively screened for HCC, we retrospectively selected those with a liver biopsy performed for the initial diagnosis of cirrhosis. Presence of IHC was recorded when foci of K7-positive, intermediate-sized hepatocytes were detected., Results: A total of 150 patients were included (87 men; mean age, 57 y; range, 19-84 y; body mass index, 25 kg/m(2)). After a median follow-up period of 4.85 years, HCC was diagnosed in 36 patients (24%). Baseline liver biopsy showed intermediate hepatobiliary cell foci in 61 patients (41%). Intermediate cells co-expressed both hepatocytes markers and the progenitor cell markers Ep-CAM and K19. The presence of intermediate hepatobiliary cells was associated independently with HCC occurrence (Fine and Gray model; hazard ratio, 2.48; 95% confidence interval, 1.24-4.96; P = .01). Other predictors of HCC were diabetes and low platelet count. The HCC annual incidence rate was significantly higher in patients with IHC compared with patients without (8.14% vs 3.12%, Gray's test, P = .003)., Conclusions: The aberrant expression of biliary K by hepatocytes in patients with hepatitis C virus-related cirrhosis is related independently to HCC occurrence., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001) vaccination in patients with advanced HCC., Methods: 40 patients with advanced HCC were treated with 300 mg/m2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses., Results: None of the patients had a complete or partial response to treatment, 17 patients (45.9%) demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4+CD25+Foxp3+ regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination., Conclusions: Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC., Trial Registration: NCT00444782.

Unlabelled: Alcohol increases reactive oxygen species (ROS) formation in hepatocyte mitochondria and by reduced nicotinamide adenine dinucleotide phosphate oxidases and myeloperoxidase (MPO) in Kupffer cells and liver-infiltrating neutrophils. Manganese superoxide dismutase (MnSOD) converts superoxide anion into hydrogen peroxide, which, unless detoxified by glutathione peroxidase or catalase (CAT), can form the hydroxyl radical with iron. Our aim was to determine whether Ala16Val-superoxide dismutase 2 (SOD2), G-463A-MPO, or T-262C-CAT dimorphisms modulate the risks of hepatocellular carcinoma (HCC) and death in alcoholic cirrhosis. Genotypes and the hepatic iron score were assessed in 190 prospectively followed patients with alcoholic cirrhosis. During follow-up (61.1 +/- 2.7 months), 51 patients developed HCC, and 71 died. The T-262C-CAT dimorphism did not modify hepatic iron, HCC, or death. The GG-MPO genotype did not modify iron but increased the risks of HCC and death. The hazard ratio (HR) was 4.7 (2.1-10.1) for HCC and 3.6 (1.9-6.7) for death. Carriage of one or two Ala-SOD2 allele(s) was associated with higher liver iron scores and higher risks of HCC and death. The 5-year incidence of HCC was 34.4% in patients with both the GG-MPO genotype and one or two Ala-SOD2 alleles, 5.1% in patients with only one of these two traits, and 0% in patients with none of these traits. Corresponding 5-year death rates were 37.6%, 11.6%, and 5%., Conclusion: The combination of the GG-MPO genotype (leading to high MPO expression) and at least one Ala-SOD2 allele (associated with high liver iron score) markedly increased the risks of HCC occurrence and death in patients with alcoholic cirrhosis.

Unlabelled: For the treatment of small hepatocellular carcinoma (HCC), radiofrequency ablation (RFA) is in some centers considered a first-line therapeutic option. However, such a strategy is still under debate with regard to tumor and patient characteristics. In this single-center study we assessed the 5-year survival and prognosis factors in 235 consecutive patients with cirrhosis (Child-Pugh A/B: 205/30) who received RFA as first-line treatment for up to three HCC

Purpose: To prospectively evaluate the safety and effectiveness of percutaneous multipolar radiofrequency (RF) ablation for the treatment of large (>or=5.0 cm in diameter) hepatocellular carcinomas (HCCs)., Materials and Methods: Twenty-six patients (four women, 22 men; median age, 72 years) with cirrhosis (Child-Pugh class A disease, 22 patients; Child-Pugh class B disease, four patients) and at least one 5.0-9.0-cm-diameter HCC without invasion of the portal trunk or main portal branches were treated with multipolar RF ablation performed by a single operator. The procedure was performed with three separate bipolar linear internally cooled electrodes with ultrasonographic guidance. Twenty-seven of the 33 tumors treated had a diameter of 5.0 cm or greater (median diameter, 5.7 cm; range, 5.0-8.5 cm); 12 of these 27 tumors were infiltrative, and four invaded segmental portal vein branches. Ten patients had a serum alpha-fetoprotein level higher than 400 microg/L. Results were assessed by using computed tomography. Primary effectiveness, complications, tumor progression, and survival rates were recorded. Probabilities of survival were calculated by using the Kaplan-Meier method., Results: One to two RF ablation procedures per patient (mean, 1.15 +/- 0.43 [standard deviation]) led to the complete ablation of 22 (81%) of the 27 tumors (18 tumors after one and four tumors after two procedures), including three tumors that showed segmental portal vein invasion. All patients experienced postablation syndrome, and one experienced subcapsular hematoma and a segmental liver infarct, but no major complication occurred. After a mean follow-up of 14 months (range, 3-34 months), local and distant tumor progression and actual survival rates were 14% (three of 22), 24% (five of 21), and 65% (17 of 26), respectively. The probabilities of 1- and 2-year survival, respectively, were 68% (95% confidence interval: 49%, 86%) and 56% (95% confidence interval: 51%, 81%)., Conclusion: HCCs larger than 5.0 cm (but smaller than 9.0 cm)--even those that are infiltrative and those that involve a segmental portal vein--can be completely and safely ablated with multipolar RF ablation., ((c) RSNA, 2008.)

Purpose: To compare the results of radiofrequency (RF) ablation with internally cooled electrodes (ICEs) versus perfused electrodes (PEs) in patients with cirrhosis with small (

Purpose: To evaluate the risk of radiofrequency ablation treatment failure for hepatocellular carcinomas (HCC) next to large vessels., Materials and Methods: Between May 2000 and October 2002, from a total of 83 patients treated by radiofrequency ablation for HCC in a single center, 13 patients with tumoror=3 mm in diameter (Group A) were matched with 13 patients with similar size tumors located away from large vessels (Group B). Immediate response and recurrence rate were evaluated on CT., Results: After mean follow-up interval of 39+/-16.5 months for Group A and 39+/-14 months for Group B, local recurrence rates were 7/12 versus 1/12 respectively (p=0.03). For Group A, 6/7 local recurrences clearly contacted a large vessel., Conclusion: The cooling effect from flowing blood in large vessels markedly increases the rate of local failure of radiofrequency ablation for small HCC located near large vessels.

Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) worldwide due to the high prevalence of HCV infection and the high rate of HCC occurrence in patients with HCV cirrhosis. A striking increase in HCC incidence has been observed during the past decades in most industrialized countries, partly related to the growing number of patients infected by HCV. HCC is currently the main cause of death in patients with HCV-related cirrhosis, a fact that justifies screening as far as curative treatments apply only in patients with small tumors. As a whole, treatment options are similar in patients with cirrhosis whatever the cause. Chemoprevention could be also helpful in the near future. It is strongly suggested that antiviral treatment of HCV infection could prevent HCC occurrence, even in cirrhotic patients, mainly when a sustained virological response is obtained.

SELDI-based proteomic profiling of body fluids is currently in widespread use for cancer biomarker discovery. We have successfully used this technology for the diagnosis of hepatocellular carcinoma (HCC) in hepatitis C patients and now report its application to serial serum samples from 37 hepatitis C patients before development of HCC, with HCC and following radiofrequency ablation of the tumour. As with alpha-fetoprotein, an accepted biomarker for HCC, we hypothesised that HCC-associated proteomic features would 'return to normal' following successful treatment and the primary aim of our study was to test this hypothesis. Several SELDI peaks that changed significantly during HCC development were detected but they did not reverse following treatment. These data may be interpreted to suggest that the characteristic SELDI profile is not linearly related to tumour burden but may result from the progression of underlying liver disease or from the emergence of precancerous lesions. beta2-Microglobulin, a protein previously reported to be markedly elevated in patients with HCV related HCC, was also the most significantly HCC associated proteomic feature (m/z 11720) in this study.

Objective: To compare cost effectiveness of radio-frequency (RF) ablation versus percutaneous ethanol (Pe) ablation for treatment of small hepatocellular carcinoma., Methods: 57 patients with 72 hepatocellular carcinomas (HCC) treated with ethanol ablation were retrospectively compared with 60 new patients who had 72 HCC treated with RF ablation. All patients had Child-Pugh A cirrhosis and HCC less than 3.5 cm in diameter. Therapeutic efficacy was evaluated with tri-phase spiral computed tomography. Cost of hospital stay, supplies and follow-up including complications were calculated. Survival was estimated by Kaplan-Meier method and prognostic value of treatment methods by Log Rank test and multivariate Cox proportional hazard model., Results: The two groups had similar baseline characteristics. The rate of severe complications associated with RF was 15% (9/60) vs 6,9% (9/60) with Pe (P=0,11) The two-year overall survival, disease free survival and local tumor free survival in the ethanol and radiofrequency groups were 70.8% vs. 91.2% (Odd Ratio=3.7, P=0.006), 48.6% vs. 71.1% (Odd Ratio=2.2, P=0.01), and 68.5% vs. 80.7%, (Odd Ratio=1.9; P=0.09), respectively. The treatment method was the sole significant factor related to overall and tumor free survival. Costs per patient of ethanol and radiofrequency treatments were 1534 euro and 1196 euro, respectively., Conclusion: This retrospective study suggests that RF is the most cost effective strategy, with higher 2-year disease free survival rate.

Background & Aims: Influence of being overweight and diabetes mellitus on the occurrence of hepatocellular carcinoma (HCC) in patients with cirrhosis has not been evaluated prospectively. The aim of this study was to show the predictive value of these factors in a cohort of 771 patients with well-compensated alcohol- or hepatitis C (HCV)-related cirrhosis who were screened prospectively for HCC., Methods: The predictive value for HCC occurrence was assessed by using the log-rank test and the Cox proportional hazards model. At enrollment, the mean age was 61.4 +/- 10 years and 431 patients were men. Cirrhosis was caused by alcohol (n = 478), HCV (n = 220), or the association of both factors (n = 73). The mean body mass index (BMI) was 25.4 kg/m(2) and 231 patients were diabetic., Results: During a mean follow-up period of 4.2 +/- 3 years, 220 patients developed HCC. In univariate analysis, a BMI of 25 kg/m(2) or more, diabetes, male sex, age older than 60 years, and HCV infection were risk factors for HCC. In multivariate analysis, predictive factors were a BMI between 25-30 kg/m(2) (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.4-2.7), BMI of 30 kg/m(2) or more (HR, 2.8; 95% CI, 2.0-4.0), diabetes (HR, 1.6; 95% CI, 1.2-2.1), age 60-70 years (HR, 2.4; 95% CI, 1.3-4.3), age older than 70 years (HR, 3.0; 95% CI, 1.7-5.5), male sex (HR, 2.0; 95% CI, 1.4-2.7), HCV (HR, 1.6; 95% CI, 1.1-2.2), and mixed (HR, 2.6; 95% CI, 1.7-4.0) etiology. We found a positive linear relationship between BMI level and HCC incidence during follow-up evaluation., Conclusions: Overweight and diabetes mellitus are associated with an increased risk of HCC occurrence in patients with HCV- or alcohol-related cirrhosis.

Early diagnosis of hepatocellular carcinoma (HCC) is the key to the delivery of effective therapies. The conventional serological diagnostic test, estimation of serum alpha-fetoprotein (AFP) lacks both sensitivity and specificity as a screening tool and improved tests are needed to complement ultrasound scanning, the major modality for surveillance of groups at high risk of HCC. We have analysed the serum proteome of 182 patients with hepatitis C-induced liver cirrhosis (77 with HCC) by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI). The patients were split into a training set (84 non-HCC, 60 HCC) and a 'blind' test set (21 non-HCC, 17 HCC). Neural networks developed on the training set were able to classify the blind test set with 94% sensitivity (95% CI 73-99%) and 86% specificity (95% CI 65-95%). Two of the SELDI peaks (23/23.5 kDa) were elevated by an average of 50% in the serum of HCC patients (P<0.001) and were identified as kappa and lambda immunoglobulin light chains. This approach may permit identification of several individual proteins, which, in combination, may offer a novel way to diagnose HCC.

Purpose: To evaluate the effectiveness of radiofrequency (RF) ablation for liver tumors located in the caudate lobe., Materials and Methods: Ten patients (46-79 years of age; median, 70 y), eight with hepatocellular carcinoma (HCC) and cirrhosis and two with colorectal metastases in the caudate lobe, were treated with 5.8% NaCl tissue-perfused monopolar (n=7) or bipolar (n=3) RF ablation. The median tumor diameter was 41 mm (range, 25-70 mm). Procedures were performed under ultrasound and computed tomography (CT) guidance in eight and two patients, respectively. One month later, the treatment response was assessed by CT., Results: Transhepatic right intercostal and transomental anterior epigastric routes were used for tumor puncture in eight and two patients, respectively. The entire RF ablation treatment required one or two procedures (median, 1.5), including two to 15 electrode repositionings (median, 6). After RF ablation procedure, one patient experienced jaundice that resolved spontaneously. In one patient, CT follow-up showed asymptomatic segmental biliary duct dilations. Median total hospital stay was 3 days (range, 2-9 d). Complete ablation was achieved in nine of 10 tumors. In one patient, ethanol ablation was necessary to complete RF ablation treatment. After a median follow up of 9.5 months (range, 5-25 mo), three patients remained tumor-free and seven had tumor relapse: two local, four distant, and one mixed. Repeat RF ablation was successfully performed in four cases., Conclusion: RF ablation of liver tumors located in the caudate lobe is effective despite the deep location of tumors and the vicinity of major vessels.

Background and Aims: A genetic dimorphism encodes for either alanine (Ala) or valine (Val) in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD), and modulates its mitochondrial import. However, the role of this dimorphism in the susceptibility of alcoholic patients to develop cirrhosis is controversial, and its influence on the occurrence of hepatocellular carcinoma (HCC) and death in patients with alcoholic cirrhosis is unknown., Methods: We compared MnSOD genotypes in 94 control subjects and 264 patients with alcoholic cirrhosis. Patients were included at the time of the first liver biopsy examination showing cirrhosis, and were followed-up prospectively., Results: Alcohol consumption was similar, whatever the patients' genotype. At inclusion, the percentage of Val/Val homozygotes was lower in patients than in controls (16% vs. 31%), whereas the percentage of Ala/Ala homozygotes was higher in patients than in controls (30% vs. 21%) ( P = .008). During follow-up evaluation, only 9% of Val/Val patients developed HCC, vs. 30% and 29% of Ala/Val and Ala/Ala patients, respectively ( P = .02). Only 28% of Val/Val patients died or were transplanted, vs. 49% and 50% of Ala/Val and Ala/Ala patients, respectively ( P = .03). Because of the progressive decrease in surviving Ala patients, the genotypic distribution in patients surviving for 5 or 10 years no longer differed from the genotypic distribution in controls., Conclusions: The presence of at least 1 Ala MnSOD allele increases the risk for developing cirrhosis in French alcoholics, and increases the rates of HCC development and death in cirrhotic patients.

Screening programs for patients with cirrhosis are designed to detect hepatocellular carcinoma at an early stage when effective treatment is feasible and may provide long-term survival benefits. However, only a minority of these patients will be considered candidates for liver transplantation or surgical resection and hence, most cases will be evaluated for other medical options. While systemic therapy has never been shown to bear a relevant antitumoral activity with an impact on survival, there are several locoregional options that can achieve a high rate of objective responses (this includes complete necrosis or partial reduction in tumor burden). Percutaneous ablation by any of the available methods (ethanol injection, radiofrequency, microwave, acetic acid injection, laser) is extremely useful in patients with small solitary tumors. Results indicate that 90% of tumors < 2 cm will be completely ablated using the percutaneous approach. However, when tumor size exceeds 3 cm and/or the number of nodules is greater than 3, the rate of treatment success is significantly reduced. In patients with large/multifocal disease, the sole option that has been shown to provide treatment efficacy with moderate improvement in survival is chemoembolization. New therapeutic agents should target biological mechanisms in a tailored strategy, and the demonstration of beneficial results for patients should be obtained by large, randomized, controlled trials comparing active intervention versus no treatment.

Purpose: To retrospectively evaluate patients' tolerance and the effectiveness of percutaneous intraarterial ethanol injection (PIAEI), alone or combined with conventional percutaneous ethanol injection (PEI), for treatment of advanced hepatocellular carcinoma (HCC)., Materials and Methods: Neither institutional review board approval nor informed consent was required for this retrospective study; however, all patients had given their consent to be treated with PIAEI. Fourteen men and four women with cirrhosis and HCC who were ineligible for conventional curative treatment (largest tumor diameter, 35-90 mm; mean, 52 mm +/- 16 [standard deviation]) and whose supplying arteries were visible on computed tomographic (CT) and color Doppler ultrasonographic (US) images were treated with US-guided PIAEI-either alone or combined with PEI. Twelve patients had infiltrative tumors, and six had nodular tumors. Four patients had portal venous tumor involvement. Tumor necrosis and recurrence were evaluated with CT, and 1- and 2-year survival rates were evaluated with Kaplan-Meier analysis., Results: In four patients, the main tumor was treated with PIAEI only, and in 14 patients, the main tumor was treated with combined PIAEI and PEI. One patient died of myocardial infarction before CT evaluation. Tumor necrosis was complete in 15 (88%) and incomplete in two (12%) of 17 patients. Results of subsequent surgery performed in three patients confirmed the radiologic findings: complete tumor necrosis in two patients and incomplete necrosis in one patient. Two severe PIAEI-related complications occurred: liver abscess, which resolved, and fatal acute pancreatitis. During the follow-up period (mean, 15 months +/- 6.7), six patients died owing to recurrent HCC, and 10 patients were alive with no detectable tumor after a mean follow-up period of 18 months +/- 11. One- and 2-year survival rates were 76.6% and 44.5%, respectively., Conclusion: For patients with advanced HCC who are ineligible for other curative options, PIAEI could be an effective treatment, despite the associated risk of severe complications., ((c) RSNA, 2004.)