Gisèle N’Kontchou

Survival after radiofrequency ablation and salvage transplantation in patients with hepatocellular carcinoma and Child-Pugh A cirrhosis

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 studys 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.

A variant in myeloperoxidase promoter hastens the emergence of hepatocellular carcinoma in patients with HCV-related cirrhosis

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.

Comparison of no-touch multi-bipolar vs. monopolar radiofrequency ablation for small HCC

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 (</⩾100G/L), p=1 for all. One case of perioperative mortality was observed in the NTmbpRFA group and the rate of major complications was 7.2% in both groups (p=1). The cumulative rates of global RFA failure at 1, 3 and 5years were respectively 13.3%, 31% and 36.7% for MonoRFA vs. 0.02%, 7.9% and 9.2% for NTmbpRFA, p<0.001. Monopolar RFA, tumour size >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.

Ethanol versus radiofrequency ablation for the treatment of small hepatocellular carcinoma in patients with cirrhosis: A retrospective study of efficacy and cost

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.

ESM-1 expression in stromal cells is predictive of recurrence after radiofrequency ablation in early hepatocellular carcinoma

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. Edmondsons 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.

Influence de la proximité des gros vaisseaux sur les résultats du traitement des carcinomes hépato-cellulaires par radiofréquence : une étude contrôlée

Resume Objectif Evaluer les risques d’echec du traitement par radiofrequence des carcinomes hepato-cellulaires (CHC) lies au contact des gros vaisseaux. Materiel et methodes De mai 2000 a octobre 2002, parmi 83 patients traites par radiofrequence pour CHC dans un meme centre, 13 patients qui avaient une tumeur ≤ 3,5 cm situee au contact d’un vaisseau ≥ 3 mm (groupe A) ont ete apparies a 13 malades presentant des tumeurs de meme taille mais situees a distance des vaisseaux (groupe B). La reponse immediate et l’incidence des recidives locales ont ete evaluees par tomodensitometrie. Resultats Apres un delai de surveillance moyen de 39 ± 16,5 mois dans le groupe A et de 39 ± 14 mois dans le groupe B, une recidive locale a ete identifiee respectivement dans 7/12 versus 1/12 tumeurs (P = 0,03). Dans le groupe A, 6/7 recidives locales etaient clairement au contact d’un vaisseau. Conclusion L’effet refroidissant des flux sanguins accroit largement le risque de controle local incomplet des petits CHC peri vasculaires traites par radiofrequence.

Multibipolar Radiofrequency Ablation for the Treatment of Mass-Forming and Infiltrative Hepatocellular Carcinomas > 5 cm: Long-Term Results

Aims and Background: Only few patients with cirrhosis and hepatocellular carcinoma (HCC) larger than 5 cm are amenable to resection or straight liver transplantation, and in such circumstances, multibipolar radiofrequency ablation (mbp-RFA) could be a reliable alternative. This study was aimed to assess the long-term outcome in patients treated with mbp-RFA for unresectable HCC > 5 cm. Methods: Eighty-three consecutive patients with cirrhosis (median age 70 years [37–93 years], 67 males, BCLC A/B/C: 54/21/8, 74 naive) with up to three HCCs, the largest > 5 cm in diameter (median: 6.2 cm, 5.1–9 cm, 22 infiltrative forms, 12 with segmental portal invasion of which 10 were infiltrative forms) were treated with mbp-RFA. Overall (OS) and recurrence-free (RFS) survival and their associated predictive factors were assessed. Results: Complete ablation was observed in 78/83 (94%) patients. Thirty-one side effects occurred, including 6 (7%) severe complications. After a median follow-up of 26.1 months (1–112 months), in naive patients the 3- and 5-year OS was 51% (38–62) and 24% (13–36), 63 and 30% for mass-forming and 25 and 6% for infiltrative form, respectively. Infiltrative form (HR: 2.5 [1.33–4.69], p = 0.004) was the only independent OS predictor. In naive patients with mass-forming and infiltrative form, the 3- and 5-year RFS were 47 and 17 and 18 and 18%, respectively. Alpha-fetoprotein (HR: 2.86 [1.32–6.21], p = 0.008), multinodular form (HR: 2.74 [1.4–5.38], p = 0.003) and infiltrative form (HR: 3.43 [1.67–7.01], p = 0.0007) were independent RFS predictors. Conclusions: mbp-RFA offers good OS in inoperable patients with cirrhosis and large HCC, with acceptable safety profile. For infiltrative forms, although mbp-RFA leads to complete responses in more than 80% cases, few only remain tumor progression-free in long-term.

Radiofrequence des carcinomes hepatocellulaires : evaluation de l’effet des flux sanguins

Objectifs Evaluer le risque d’echec du traitement par radiofrequence des carcinomes hepatocellulaires (CHC) situes au contact des vaisseaux. Materiels et methodes Dans un meme centre, de mai 2000 a octobre 2002, parmi 83 patients traites par radiofrequence pour CHC, 13 patients avaient une tumeur ≤ 3,5 cm situee en contact d’un vaisseau ≥ 3 mm (groupe A). Dans ce groupe la reponse immediate et la recidive locale ont ete evaluees par tomodensitometrie puis compares aux resultats obtenus chez 13 patients presentant des tumeurs de meme taille non perivasculaire (groupe B). Resultats Dans chaque groupe un patient presentait un reliquat tumoral, sur l’examen tomodensitometrique de controle realise un mois apres le traitement. Apres un delai de surveillance moyen de 39±16,5 mois dans le groupe A et de 39±14 mois dans le groupe B, une recidive locale a ete identifie respectivement dans 7/12 versus 1/ 12 tumeurs ( P = 0,03). Dans le groupe A, 6/7 recidives locales etaient clairement au contact d’un vaisseau. Conclusion L’effet refroidissant des flux sanguins multiplie par 4 le risque de controle local incomplet des petits CHC perivasculaires traites par radiofrequence. Des modifications techniques et technologiques sont requises pour ameliorer les capacites de destruction de la radiofrequence en presence de flux.