Olivier Seror

Radiofrequency ablation of hepatocellular carcinoma: Long‐term results and prognostic factors in 235 Western patients with cirrhosis

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 ≤5 cm (307 tumors; mean diameter: 29 ± 10 mm; 53 multinodular forms). Among these patients, 67 satisfied the criteria for resection according to the Barcelona Clinic Liver Cancer. Complete ablation was obtained in 222 patients (94%). Overall, 337 RFA sessions were performed including iterative RFA for recurrence. Major complications occurred in three patients (0.9%), including one treatment‐related death. After 27 ± 20 months of mean follow‐up, local or distant, or both, tumor recurrence occurred in 16, 88, and 11 patients, respectively. Twenty‐nine patients underwent transplantation and were removed from the study at this point. Overall 5‐year, recurrence‐free, and tumor‐free (including results of iterative RFA) survival rates were, respectively, 40%, 17%, and 32%. The overall 5‐year survival rate was 76% for operable patients. Factors associated with overall survival were prothrombin activity (hazard ratio [HR] = 0.97, 0.96–0.98; P < 0.0001) and serum levels of α‐fetoprotein (AFP) (HR = 1.02, 1.02–1.02; P < 0.0001), and factors associated with tumor recurrence were multinodular forms (HR = 2.34; 1.52–3.6; P = 0.0001) and serum AFP levels (HR = 1.015, 1.014–1.016; P = 0.015). Tumor size was associated with local recurrence but not with overall and tumor‐free survival. Conclusion: RFA is a safe and effective first‐line treatment of HCC up to 5 cm in diameter, especially for patients with a single tumor, a low serum AFP level, and well‐preserved liver function. (HEPATOLOGY 2009.)

Large (≥5.0-cm) HCCs: Multipolar RF Ablation with Three Internally Cooled Bipolar Electrodes—Initial Experience in 26 Patients

PURPOSEnTo 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).nnnMATERIALS AND METHODSnTwenty-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.nnnRESULTSnOne 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%).nnnCONCLUSIONnHCCs 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.

Partial splenic embolization in patients with cirrhosis: efficacy, tolerance and long-term outcome in 32 patients.

Background Although partial splenic embolization (PSE) has been proposed in patients with cirrhosis in cases when thrombocytopenia or neutropenia may cause clinical manifestations or if there are contra-indications to other therapeutic procedures, there are limited data on long-term outcome. We provide a retrospective review of results and the tolerance of all PSE procedures in patients with cirrhosis in our department. Patients and methods Thirty-two consecutive patients with cirrhosis were included over a 6 year period. Indications for PSE were as follows: (1) severe cytopenia preventing necessary antiviral treatment (n=14), percutaneous destruction of hepatocellular carcinoma (n=8) or major surgery (n=3), severe purpura (n=3); (2) painful splenomegaly (n=4). After superselective catheterization, embolization was performed with up to 50% reduction of splenic blood flow. Results Thrombocyte and leucocyte counts increased markedly (185% and 51% at 1 month; 95% and 30% at 6 months). Thirty-one and 20 patients had platelet count >80u2009000/mm3 at months 1 and 6 vs only one before PSE. Overall, the aim of PSE was achieved in 27 patients (84%) (planned treatment: 20/25; disappearance of purpura and splenic pain: 7/7). Severe complications occurred in five patients (16%): transient ascites (n=2), splenic and/or portal vein thrombosis (n=2) that resolved after anticoagulation therapy, and splenic abscess (n=2) leading to death. These two patients had splenic necrosis >70%. Conclusion In patients with cirrhosis, PSE may resolve cytopenia and the clinical complications related to hypersplenism or splenomegaly. However, due to a high risk of severe complications, particularly splenic abscess, the indications of PSE should be very limited and the extent of necrosis should be strictly controlled during the PSE procedure.

Identification of Serum Proton NMR Metabolomic Fingerprints Associated with Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis

Purpose: Metabolomics depicts metabolic changes in biologic systems using a multiparametric analysis technique. This study assessed the metabolomic profiles of serum, obtained by proton nuclear magnetic resonance (NMR) spectroscopy, from cirrhotic patients with and without hepatocellular carcinoma (HCC). Experimental Design: The study included 154 consecutive patients with compensated biopsy-proven alcoholic cirrhosis. Among these, 93 had cirrhosis without HCC, 28 had biopsy-proven HCC within the Milan criteria and were eligible for curative treatment (small HCC), and 33 had HCC outside the Milan criteria (large HCC). Proton spectra were acquired at 500 MHz. An orthogonal partial latent structure [orthogonal projection to latent structure (OPLS)] analysis model was built to discriminate large HCC spectra from cirrhotic spectra. Small HCC spectra were secondarily projected using previously built OPLS discriminant components. Results: The OPLS model showed discrimination between cirrhotic and large HCC spectra. Metabolites that significantly increased with large HCC were glutamate, acetate, and N-acetyl glycoproteins, whereas metabolites that correlated with cirrhosis were lipids and glutamine. Projection of small HCC samples into the OPLS model showed a heterogeneous distribution between large HCC and cirrhotic samples. Small HCC patients with metabolomic profile similar to those of large HCC group had higher incidences of recurrence or death during follow-up. Conclusions: Serum NMR-based metabolomics identified metabolic fingerprints that could be specific to large HCC in cirrhotic livers. From a metabolomic standpoint, some patients with small HCC, who are eligible for curative treatments, seem to behave as patients with advanced cancerous disease. It would be useful to further prospectively investigate these patients to define a subgroup with a worse prognosis. Clin Cancer Res; 18(24); 6714–22. ©2012 AACR.

Low-grade steatosis and major changes in portal flow as new prognostic factors in steroid-treated alcoholic hepatitis.

The aim of this study was to assess the prevalence and prognostic value of major alterations of portal flow in patients with steroid‐treated alcoholic hepatitis. Fifty patients with severe, histologically proven alcoholic hepatitis were enrolled. Clinical data, liver test results, and hepatic Doppler ultrasound findings were collected at inclusion and at month 2. Patients were followed for 1 year or until death. Major changes in portal flow were defined as reversed or alternating flow in the portal trunk and/or in intrahepatic portal branches. Changes in portal flow were observed in 24 (48.0%) of 50 and 17 (39.5%) of 43 patients at inclusion and month 2, respectively. Univariate analysis showed that age older than 50 years, steatosis less than 20% on initial liver biopsy, presence of major changes in portal flow, Child‐Turcotte‐Pugh score higher than 12, factor V level higher than 45%, and hepatofugal splenic blood flow were associated with a lower 1‐year survival. Cox regression analysis showed that steatosis < 20% (relative hazard [RH] = 9.3, P = .0009) and major changes in portal flow (RH = 3.1, P = .04), were independently associated with poor survival. In conclusion, major changes in portal flow are frequent in patients with severe alcoholic hepatitis. Altered portal flow and steatosis < 20% are new prognostic factors in steroid‐treated alcoholic hepatitis and must be taken into account in patient management. (HEPATOLOGY 2004;40:1370‐1378).

L'imagerie de susceptibilité magnétique : théorie et applications

Resume L’imagerie de susceptibilite magnetique (ou SWI pour Susceptibility Weighted Imaging) est une nouvelle technique d’imagerie par resonance magnetique exploitant l’effet BOLD et les differences de susceptibilite magnetique entre tissus. Elle utilise une sequence 3D en echo de gradient caracterisee d’une part, par un temps d’echo long, choisi de facon a annuler de facon optimale le signal des veines et d’autre part un post-traitement specifique faisait intervenir les images de phase comme source de contraste supplementaire. Elle est particulierement utile pour la detection des veines normales ou pathologiques. Elle detecte les hemorragies, notamment celles de petite abondance mieux que les sequences en echo de gradient conventionnel. Son utilisation est encore limitee du fait d’un temps d’acquisition long et de la persistance d’artefacts.

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

BACKGROUND & AIMSnIn 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.nnnMETHODSnWe 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.nnnRESULTSnEighty 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.nnnCONCLUSIONSnFirst 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.

Radiofrequency Ablation for the Treatment of Liver Tumors in the Caudate Lobe

PURPOSEnTo evaluate the effectiveness of radiofrequency (RF) ablation for liver tumors located in the caudate lobe.nnnMATERIALS AND METHODSnTen 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.nnnRESULTSnTranshepatic 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.nnnCONCLUSIONnRF ablation of liver tumors located in the caudate lobe is effective despite the deep location of tumors and the vicinity of major vessels.

Hepatocellular Carcinoma within Milan Criteria: No-Touch Multibipolar Radiofrequency Ablation for Treatment—Long-term Results

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.

Serum proteoglycans as prognostic biomarkers of hepatocellular carcinoma in patients with alcoholic cirrhosis

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. Cancer Epidemiol Biomarkers Prev; 22(8); 1343–52. ©2013 AACR.