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Hepatocellular carcinoma is a major public health problem with one of the highest overall mortality compared to other cancers. The median overall survival in France in a hospital population with hepatocellular carcinoma is 9.4 months. Several publications reported a positive impact of hepatocellular carcinoma screening on diagnosis at an early-stage, eligibility for curative treatment and overall survival. However, the identification of patients to be included in a hepatocellular carcinoma screening program and the application of screening recommendations are not optimal. Other studies suggest a potentially negative impact of delayed diagnosis or treatment initiation on the patient's prognosis. Finally, marked variations between French regions and departments have been described in terms of access to curative treatment and overall survival. In this review article, we propose a state of play of the hepatocellular carcinoma patient's care pathway in France with the aim of identifying potential breaking points with negative impact on prognosis and of developing proposals for improvement., (Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The treatment of hepatocellular carcinoma (HCC) is difficult due to the underlying cirrhosis which has its own influence on therapeutic issues. An inquiry was performed in centres with specialized multidisciplinary team meetings dedicated to HCC (HCC-MTM) or in centres with non-specialized (digestive oncology or general oncology) multidisciplinary team meetings (NS-MTM). The number of cases of HCCs taken in charge yearly was significantly higher in HCC-MTM than in NS-MTM (p=0,0014). Interventional radiologists and transplant surgeons were more frequently implied in HCC-MTM than in NS-MTM (respectively p=0,009 and p=0,02). On site availability of every treatment of HCC was higher in RCP-MTM than in NS-MTM (p=0,015). There were no inclusion in clinical trials in 40.5 % of NS-MTM versus only 17.6 % of HCC-MTM (p=0,0086). In three clinical cases out of seven there were discrepancies between the therapeutic options of HCC-MTM and NS-MTM. In all three cases, the treatment offered to the patient by HCC-MTM was more consistent with clinical standards. These results prompt to perform more studies on the quality of management of patients with HCCs by MTMs.

With 6,000 new cases per year in France and nearly 700,000 new cases per year worldwide, HCC is a frequent cancer occurring in more than 90% of cases on underlying liver disease. Both diseases (cirrhosis and HCC) are involved in patients morbidity and mortality. The prognosis of HCC on cirrhosis is thus generally poor, but mainly varies depending on the stage of the tumor. Despite this poor prognosis, many therapeutic options are available for HCC patients. The curative treatments include orthotopic liver transplantation, surgical resection and radiofrequency thermal ablation. The palliative treatments include transcatheter arterial chemoembolization and more recently a systemic treatment with a new multikinase inhibitor: the sorafenib. However, many questions still need to be address to optimize the therapeutic management of this disease. This review analyses the state of the art in HCC treatment and raises the main questions that clinical trials will have to answer in the future.

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.

Selective inhibitors of cyclooxygenase-2 have less gastroduodenal toxicity than non selective anti-inflammatory drugs. However, there is little information on their effect on the distal gut. A 91 year old woman presented with acute diarrhoea 5 weeks after beginning celecoxib treatment. Laboratory results showed an inflammatory syndrome and increased alanine aminotransferase (ALT) to 13 N. Endoscopic examination of the colon showed diffuse erythematous lesions of the sigmoid and of part of the right colon. No aetiology has been found for colitis or hepatitis. Diarrhea and blood test anomalies disappeared one week after celecoxib was stopped. The role of celecoxib in the etiology of colitis was considered plausible but not for liver damage. This report and a few other cases in the literature suggest that cyclooxygenase-2 selective non-steroidal anti-inflammatory drug inhibitor toxicity should be investigated in case of unexplained acute colitis.

Aim: To describe French practices for screening hepatocellular carcinoma., Methods: A standardized questionnaire was mailed to all French hospital hepato-gastroenterologists in June 1999., Results: 411 out of 623 practitioners responded (66%). 394 (96%) routinely screen hepatocellular carcinoma, mainly with ultrasound (98%) and mainly at 6-month intervals (77%). Screening was performed in cirrhosis (100%) or extensive fibrosis (54%), independent of the etiology (21%) or the Child-Pugh score of the chronic liver disease (41%), but based on age and treatment feasibility. If of a small hypoechogenic nodule was detected in a young patient with compensated HCV-cirrhosis, 59% of practitioners performed a histological examination. In case of non biopsy-proven hepatocellular carcinoma, a second biopsy (49%), treatment (either percutaneous alcohol injection, resection or transplantation) (24%) or an ultrasonographic follow-up (23%) was proposed. In case of biopsy-proven hepatocellular carcinoma, resection (49%), transplantation (30%) or percutaneous alcohol injection (16%) was proposed., Conclusion: Almost all French specialists routinely screen cirrhotic patients for hepatocellular carcinoma, but use somewhat different modalities. In case of small HCC without contraindications to curative treatment, surgical resection is performed in half the patients.

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.

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.

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.

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.

This study was designed to determine whether the size of esophageal varices were of prognostic value in patients with alcoholic cirrhosis. Esophageal varices were classified into 2 groups according to whether their size was larger or smaller than 4 mm. There was a total of 99 patients; 56 had small varices and 43 had large varices. Of the clinical and biological data collected at the time of determination of the size of the esophageal varices, only the duration of cirrhosis and the prevalence of gastrointestinal bleeding were significantly greater in patients with large esophageal varices. The one- and two-year cumulative rates of patients with large esophageal varices were 63 +/- 7 p. 100 and 42 +/- 8 p. 100, respectively; these results were not significantly different from those in patients with small esophageal varices, i.e. 68 +/- 6 p. 100 and 61 p. 100 respectively (p less than 0.5 for one-year survival; p less than 0.08 for two-year survival). Serum bilirubin and albumin as well as the presence of ascite were of significant prognostic value concerning death at two years while the presence of esophageal varices did not significantly increase the prognostic value of the above-mentioned variables (using Cox's regression model). In conclusion, the results of our study suggest that large esophageal varices, in spite of their association with a high incidence of gastrointestinal bleeding, do not influence prognosis at two years for patients with alcoholic liver cirrhosis.

The cefotiam (CFT) penetration in infected ascitic fluid was investigated in 12 cirrhotic patients. CFT (1 g every 8 h) was given intravenously and measured by HPLC in plasmatic and ascitic samples. The mean ascitic concentrations (+/- SEM), 1 h, 3 h and 8 h after the first injection (J1) were 14.6 +/- 4.6, 11.8 +/- 3 and 8.4 +/- 2.9 micrograms/ml respectively. These values were 38, 62 and 88% of the corresponding mean plasmatic concentrations and higher than the MIC's for the organisms most commonly involved. The mean plasmatic and ascitic concentrations, a few days later (4.5 or 6 days) (Jn) were not significantly different from the corresponding values at J1. A significant decrease of polymorphonuclear cell count was observed between J1 and Jn. These results suggest that CFT diffusion into ascitic fluid is independent of inflammation and CFT is an adequate antibiotic in cirrhotic patients with infected ascitic fluid.

Twelve patients with unresectable hepatocellular carcinoma associated with cirrhosis were treated with Doxorubicin which was given intravenously (30 to 50 mg/m2) every three weeks. Six patients were given only one dose of Doxorubicin. No clinical response was observed. Five patients has serum alphafoetoprotein (AFP) determination during the treatment. AFP concentration rose in 4 patients and fell in 1 patient. Survival rate after 3 and 8 months of treatment was 58 and 33 per cent. These results suggest that Doxorubicin is not an effective treatment for hepatocellular carcinoma.

The ofloxacin diffusion was investigated in 13 cirrhotic patients with spontaneous bacterial peritonitis. Plasma and ascitic samples were collected at times H1, H31 and H8 after a first dose of 200 mg per os, in these 13 patients, after 4.5 or 6 days of 200 mg per os each 8 hours in 9 out of them. After the first dose, the plasmatic and ascitic concentrations, measured by High Performance Liquid Chromatography (HPLC), were between 0 and 3.62 mg/l, 0 and 1.95 mg/l respectively. The steady state concentrations are higher than the MIC'S for the organisms most commonly involved, comparable in the plasma and the ascitic fluid is good and suggest the interest of its use in this indication.