Hepatocellular carcinoma--what's new?

The increasing incidence of hepatocellular carcinoma (HCC) has led several countries to standardize and update its management. This review aims at summarizing these evolutions through six questions focusing on diagnosis and treatment. The radiological diagnosis of this tumor has been refined. Besides being hypervascular at the arterial phase, the "washout" in particular at the late phase of injection has become a prominent feature. Although routine ultrasound remains the corner stone of screening, contrast ultrasound has become a very reliable characterization tool as it allows continuous monitoring of the vascular kinetics. Biopsy of the tumor allows identification of conventional or molecular prognosis features, some of which could be used in current practice. The metabolic syndrome is an increasing etiology of HCC and carcinogenesis in this context may not always require the development of formal underlying cirrhosis. Associated (in particular cardiovascular) conditions account for an increased morbidity-mortality following surgery. Liver transplantation is the most effective treatment of early-stage tumors. The limited availability of grafts has led some countries including France to implement new allocation rules that are still evaluated and might need to be refined. Sorafenib is the first medical treatment shown to be effective in the treatment of HCC. This efficacy is however still limited and its indication is therefore restricted to Child-Pugh A, OMS 0-2 patients in whom a potentially curative treatment is contraindicated.

[How to improve patients and investigators' information on clinical trials: the example of French registry for clinical trials in oncology]. / Comment améliorer l'information des patients et des professionnels sur la recherche clinique : le registre français des essais cliniques en cancérologie.

Cancer patients' willingness to be informed about clinical trials (CT) is rapidly increasing. Health professionals are also interested on being informed on CT in order to provide their patients the best access to innovative treatments. The French cancer plan (2003-2007) launched the creation of a national registry for clinical trials in oncology. The primary objective was to guarantee patients and investigators comprehensive, high quality and updated information about ongoing CT in France, accessed at www.e-cancer.fr. A second objective was to establish a single channel for registration of French CT in conformity with the requirements of the International Committee of Medical Journal Editors. A unique Web access for patients and investigators was created. Information important for patients is presented in the first pages. Scientific information is accessible under further clicks. An information page about clinical research, intended for patients and their relatives, was also prepared in collaboration with patients' advocacy and healthcare professionals. Achieving comprehensiveness is one of the founding principles of the RECF. Over 600 CT were registered as of end of July 2008. All French academic sponsors have registered their CT; the publication of the industrial trials has begun in early 2008.

Prognosis of advanced hepatocellular carcinoma: comparison of three staging systems in two French clinical trials.

OBJECTIVE: The objective of this study was to assess the performance of three staging systems [Okuda, Cancer of the Liver Italian Program (CLIP) and Barcelona Clinic Liver Cancer group (BCLC)], for predicting survival in patients with hepatocellular carcinoma (HCC) and to explore how to improve prognostic classification among French patients with HCC whose main etiology is alcoholic cirrhosis. METHODS: We have pooled two randomized clinical trials in palliative condition from the Fédération Francophone de Cancerologie Digestive. They had included 416 and 122 patients. Performances of Okuda, CLIP and BCLC scores have been compared using Akaike information criterion, discriminatory ability (Harrell's C and the Royston's D statistics), monotonicity of gradients and predictive accuracy (Schemper statistics Vs). To explore how to improve classifications, univariate and multivariate Cox model analyses were carried out. RESULTS: The pooled database included 538 patients. The median survival was 5.3 months (95% confidence interval 4.6-6.2). For all statistics CLIP staging system had a better prognostic ability. Performances of all staging systems were rather disappointing. World Health Organization performance status (WHO PS) for CLIP or alpha-fetoprotein for BCLC allowed a significant improvement of prognostic information. CONCLUSION: Our results indicate that CLIP staging seems to be most adapted to palliative setting and that it could be better by associating WHO PS.

[Hepatotoxicity of medications]. / Du nouveau dans l'hépatotoxicité des médicaments.

A TIMELY TOPIC: Liver toxicity remains a common problem despite adequate information for physicians and drug watch programs. The number of recent publications reporting severe drug-induced liver disease emphasizes the need for prudence. ACUTE AND CHRONIC HEPATOTOXICITY: Cases of acute drug-induced liver disease have been described for nearly all drug classes: a few examples concern hepatitis subsequent to administration of fluoxetin, acarbose, riluzole, coumarin, or orlistat. Fulminant hepatitis is fortunately an exceptional event but has been described after administration of ketoprofene, nimesulid, and clarithyromycin. Chronic liver disease has also resulted from the use of mesalazine, minocyclin or fibrates. Nevirapin prescribed for HIV infection can cause severe liver disease. OTHER AGENTS: Certain herbal agents, such as chelidoin for example, can cause cholestasis. Certain excipients can also be toxic for the liver. Ecstasy appears to be a frequent cause of sometimes severe liver disease in younger subjects.

[Endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography performed during the same anesthesia session]. / Echo-endoscopie et cholangio-pancréatographie rétrograde endoscopique dans un même temps anesthésique.

OBJECTIVES: To evaluate the feasibility, results and importance of a diagnostic and therapeutic biliary and pancreatic exploration associating endoscopic ultrasonography and endoscopic retrograde cholangio-pancreatography during the same anaesthesia session. METHODS: From November 1997 to October 1998, 179 patients (83 males, 96 females), mean age 62 years (range 22 to 95 years), were investigated in our gastroenterology unit for biliary or pancreatic disorders. Two hundred and sixty two examinations were performed by a single physician for patients under general anaesthesia. In 87 cases (42%), endoscopic retrograde cholangio-pancreatography was performed immediately without prior endoscopic ultrasonography; these patients were not included. When endoscopic retrograde cholangio-pancreatography followed endoscopic ultrasonography, it was performed during the same anaesthesia session. RESULTS: In 118 cases, endoscopic ultrasonography was performed first, followed by endoscopic retrograde cholangio-pancreatography 57 times (48%). The sensitivity of endoscopic ultrasonography was 96.5% and the success of therapeutic endoscopic retrograde cholangio-pancreatography was 100%. Endoscopic retrograde cholangio-pancreatography was necessary for 83% of patients with angiocholitis, 60% with cholestasis, 45% with acute biliary pancreatitis and only 28% with common bile duct stone migration. CONCLUSION: To decrease the number of anaesthesia sessions, endoscopic ultrasonography--endoscopic retrograde cholangio-pancreatography during same anaesthesia session appears to be particularly interesting for the diagnosis and treatment of biliary and pancreatic disorders, in terms of cost, accuracy, morbidity and patient comfort.

Prevalence and risk factors of bacteriuria in cirrhotic patients: a prospective case-control multicenter study in 244 patients.

BACKGROUND/AIMS: The prevalence and risks factors of bacteriuria in cirrhotics have not been assessed by case-control study, and there are conflicting data concerning the role of liver failure and of ascites. The aims of this study were: i) to evaluate the prevalence of bacteriuria in cirrhotics, ii) to search for associated factors, iii) to evaluate the role of bladder post-void residual volume, and iv) to test the sensitivity of isolated bacteria to norfloxacin. METHODS: The prevalence and risk factors of bacteriuria on admission were determined by a multicenter prospective case-control study. RESULTS: Two hundred and forty-four cirrhotic patients and 240 controls were studied. Bacteriuria was present in 38 patients (15.6%; IC 5%: 11%-20%) and 18 controls (7.5%; IC 5%: 4.2%-11%; p<0.001). By univariate analysis, female sex and ongoing diuretic treatment were associated with bacteriuria (p<0.0001 and p<0.04, respectively). Pugh's grade, ascites and bladder residual volume were not associated with bacteriuria. By multivariate analysis, female sex (p<0.0001) and Child-Pugh score (p<0.03) were predictors of bacteriuria. Sensitivity of bacteria to norfloxacin was observed in 94.7%; sterile urine cultures were noted in 95.2% of patients treated with this antibiotic. CONCLUSION: Bacteriuria is twice as frequent in cirrhotic patients as in matched controls, and there is a trend to association with female sex and liver insufficiency.

Hepatitis C virus infection risk factors in patients admitted in hospital emergency departments in Picardy. Value of oriented screening based on recommendations of the 'Direction Générale de la Santé'.

OBJECTIVE AND DESIGN: Oriented hepatitis C virus (HCV) screening on the basis of transfusion, previous or current parenteral drug addiction, invasive procedures, and in family members of patients with hepatitis C, was recommended in France by the 'Direction Générale de la Santé' (DGS). The aim of this study was to estimate the frequency of these risk factors in patients admitted in hospital emergency departments in Picardy. METHODS: Between 1 June and 31 July 1996, physicians of the emergency units of seven hospitals in Picardy were asked to question admitted patients about risk factors mentioned in the DGS recommendations, and to suggest a screening test when at least one of these risk factors was present. RESULTS: Among 1648 patients, 68.7% had at least one of these risk factors. Screening was accepted by 723 patients, 58.7% of those with at least one risk factor, and more than 70% of those with history of transfusion and/or drug addiction. It was immediately performed in 451, and 2.4% had anti-HCV antibodies. The prevalence of anti-HCV antibodies was 1.5% in patients without history of transfusion or drug addiction and 7.9% in those with at least one of these two risk factors. CONCLUSION: Oriented screening based on transfusion or drug addiction history seems to have better efficiency than the screening policy recommended by the DGS. Poor reliability of answers about medical history was observed probably because of stress related to emergency circumstances. A screening test proposed to patients with these major risk factors by their usual physician would be probably more efficient.

[Hepatotoxicity caused by therapeutic doses of paracetamol in alcoholics. Report of 2 cases of fatal hepatitis in cirrhosis]. / Toxicité hépatique du paracétamol à dose thérapeutique chez le sujet éthylique chronique. A propos de 2 cas d'hépatite mortelle chez des patients cirrhotiques.

Paracetamol is a widely used medication as it is an effective analgesic and antipyretic. Because of the absence of gastro-intestinal side effects, it has been used as the analgesic of choice for alcoholic patients. Hepatotoxicity is dose-related and generally occurs in patients who absorb more than 125 mg/kg/j. However, cases of severe liver damage have been reported after absorption of therapeutic doses of paracetamol in alcoholics. We report 2 cases with a fatal outcome and discuss the mechanisms of toxicity, the prognostic factors and treatment of such event.

[Portal hypertension and neutrocytic ascites in POEMS syndrome]. / Hypertension portale et ascite neutrocytique au cours du syndrome POEMS.

We report a case of portal hypertension and neutrocytic ascites in a 52 year old man with POEMS syndrome. POEMS syndrome is an association of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammapathy and skin changes. Portal hypertension is rare in POEMS syndrome and this is the first time that culture negative neutrocytic ascites has been described with this syndrome.